TY  - BOOK
T1  - Dacie & Lewis Practical Haematology
A1  - Lewis, SM
A1  - Bain , BJ
A1  - Bates, I
ED  - SM Lewis, BJ Bain, I Bates
Y1  - 2006///
VL  - 10th
PB  - Elsevier
CY  - Philadelphia
SN  - 0-443-06660-4
SP  - 1
EP  - 722
N2  - -
ER  - 

TY  - BOOK
T1  - Haemopoietic Stem Cell Transplantation
A1  - Apperley JF
ED  - Apperley JF; Carreras E; Gluckman E; Gratwohl A; Masszi T
Y1  - 2004/05//
PB  - European School of Hematology
N2  - -
ER  - 

TY  - BOOK
T1  - Malaria: a hematological perspective
A1  - Abdalla SH
ED  - Abdalla SH; Pasvol G
Y1  - 2004///
PB  - Imperial College Press
CY  - 57 Shelton Street, Covent Garden, London WC2H 9HE
SN  - 1-86094-357-8
N2  - -
ER  - 

TY  - BOOK
T1  - Management of Chronic Viral Hepatitis
A1  - Foster
A1  - Goldin RD
ED  - Foster; Goldin
Y1  - 2004///
PB  - Dunitz
N2  - -
ER  - 

TY  - BOOK
T1  - Celulas Sanguineas: um Guia Pratico, 3a Edicao
A1  - Bain BJ
Y1  - 2004///
PB  - Artmed
CY  - Porto Alegre
N2  - -
ER  - 

TY  - BOOK
T1  - Infection and Immunity
A1  - Friedland JS
A1  - Lightstone L
Y1  - 2003///
PB  - Martin Dunitz
CY  - London, UK
SN  - 1 84184 373 3
N2  - -
ER  - 

TY  - BOOK
T1  - Chronic Myeloproliferative disorders: Cytogenetic and Molecular genetic abnormailites
A1  - Bain BJ
Y1  - 2003///
PB  - Karger
CY  - Basel
N2  - -
ER  - 

TY  - BOOK
T1  - Aging of Organs and Systems
A1  - Aspinall R
ED  - Aspinall R
Y1  - 2003///
IS  - 3
PB  - Kluwer Academic Publishers
CY  - Dordrecht/Boston/London
SN  - 1-4020-1743-X
N2  - -
ER  - 

TY  - BOOK
T1  - The importance of skin nutrition for wound healing
A1  - Lansdown ABG
Y1  - 2003///
PB  - Campden Publishing Limited
CY  - London
N2  - -
ER  - 

TY  - BOOK
T1  - Diagnostico em Leucemias, 20 Edicao
A1  - Bain BJ
Y1  - 2003///
PB  - Revinter
CY  - Rio de Janeiro
N2  - -
ER  - 

TY  - BOOK
T1  - Leukaemia Diagnosis, 3rd edition
A1  - Bain BJ
Y1  - 2003///
PB  - Blackwell Science
N2  - -
ER  - 

TY  - BOOK
T1  - Silver in wound care and management. Educational Booklet
A1  - Lansdown ABG
Y1  - 2003///
IS  - vo1, no. 3
PB  - Wound Care Society
CY  - UK
N2  - -
ER  - 

TY  - BOOK
T1  - A - Z of Haematology
A1  - Bain BJ
A1  - Gupta R
Y1  - 2003///
PB  - Blackwell Science
N2  - -
ER  - 

TY  - BOOK
T1  - Gut Ecology
A1  - Stagg AJ
ED  - AL Hart; AJ Stagg; H Graffner; H Glise; P Falk; MA Kamm
Y1  - 2002///
PB  - Martin Dunitz
CY  - London
N2  - -
ER  - 

TY  - BOOK
T1  - Genetics of Apoptosis
A1  - Grimm SW
ED  - Grimm S
Y1  - 2002///
PB  - BIOS Scientific Publishers
CY  - Oxford UK
N2  - -
ER  - 

TY  - BOOK
T1  - Evaluation of certain veterinary drug residues in food: 58th Report of the Joint FAO/WHO Expert Committee on Food
A1  - Anadon A
A1  - Arnold D
A1  - Boisseau J
A1  - Boobis AR
A1  - Ellis R
A1  - Greenlees K
A1  - McLean JG
A1  - MacNeil J
A1  - Rojas Martinez JL
A1  - Miterna ES
A1  - Palerm-Neta J
A1  - Soback S
A1  - Stephany RW
Y1  - 2002///
SN  - 9-2412-0911-9
N2  - -
ER  - 

TY  - BOOK
T1  - Toxicological evaluation of certain veterinary drug residues in food
A1  - Anadon A
A1  - Arnold D
A1  - Boisseau J
A1  - Boobis AR
A1  - Ellis R
A1  - Greenlees K
A1  - McLean JG
A1  - MacNeil J
A1  - Rojas Martinez JL
A1  - Miterna ES
A1  - Palerm-Neta J
A1  - Soback S
A1  - Stephany RW
Y1  - 2002///
SN  - 9-2416-6049-x
N2  - -
ER  - 

TY  - BOOK
T1  - Pesticide Residues in Food:2001: toxicological evaluations
A1  - Boobis AR
A1  - Chen BH
A1  - Moretto A
A1  - Priestly BG
A1  - Banasiak U
A1  - Dutra Caldas E
A1  - Funk S
A1  - Hamilton DJ
A1  - Ossendorp BC
Y1  - 2002///
SN  - 9-2416-6517-3
N2  - -
ER  - 

TY  - BOOK
T1  - Future Strategies for Tissue and Organ Replacement
A1  - Polak JM
A1  - Hench LL
A1  - Kemp P
Y1  - 2002///
SN  - 1-8609-4310-1
N2  - -
ER  - 

TY  - BOOK
T1  - Haemoglobinopathy Diagnosis
A1  - Bain BJ
Y1  - 2001///
SN  - 0-6320-5577-4
N2  - -
ER  - 

TY  - BOOK
T1  - Evaluation of certain veterinary drug residues in food: fifty-fourth report of the Joint FAO/WHO expert Committee on Food Additives
A1  - Anadon A
A1  - Appelgren L
A1  - Arnold D
A1  - Boisseau J
A1  - Boobis AR
A1  - Kinabo LDB
A1  - McLean JG
A1  - MacNeil JD
A1  - Miller MA
A1  - Palermo-Neto J
A1  - Rojas Martinez JL
A1  - Soback S
A1  - Stephany RW
Y1  - 2001///
SN  - 9-2412-0900-3
N2  - -
ER  - 

TY  - BOOK
T1  - Bench Aids for the morphological diagnosis of anaemia
A1  - Lewis, SM
A1  - Bain, BJ
A1  - Swirsky , DM
Y1  - 2001///
VL  - 1
PB  - WHO
CY  - Geneva
SN  - 92 4 154532 1
N2  - -
ER  - 

TY  - BOOK
T1  - Dendritic Cell Protocols
A1  - Stagg AJ
ED  - Robinson S; Stagg AJ
Y1  - 2001///
PB  - Humana Press
CY  - Totawa
N2  - -
ER  - 

TY  - BOOK
T1  - Dacies and Lewis Practical Haematology
A1  - Lewis SM
A1  - Bain BJ
A1  - Bates I
Y1  - 2001///
PB  - Churchill Livingstone
CY  - London, UK
N2  - -
ER  - 

TY  - BOOK
T1  - Bone marrow pathology
A1  - Bain BJ
Y1  - 2001///
SN  - 0-6320-5578-2
N2  - -
ER  - 

TY  - BOOK
T1  - Blood Cells, 3rd Edition
A1  - Bain BJ
Y1  - 2001///
PB  - Blackwell Science
CY  - Oxford, UK
N2  - -
ER  - 

TY  - BOOK
T1  - Pesticides Residues in Food - 2000: toxicological evaluations
A1  - Banasiak U
A1  - Calumpang SMF
A1  - Boobis AR
A1  - Borzelleca JF
A1  - Caldas ED
A1  - Fenner-Crisp P
A1  - Funk S
A1  - Hajslova J
A1  - Hakansson H
A1  - Hamilton DJ
A1  - Moretto A
A1  - Ogura A
A1  - Ossendorp BC
A1  - Priestly BG
A1  - Soliman SA
Y1  - 2001///
SN  - 9-2416-6516-5
N2  - -
ER  - 

TY  - BOOK
T1  - Bench aids for the morphological diagnosis of anaemia
A1  - Lewis SM
A1  - Bain BJ
A1  - Swirsky DM
Y1  - 2001///
PB  - World Health Organization
CY  - Geneva
N2  - -
ER  - 

TY  - BOOK
T1  - Pesticides Residues in Food - 2000
A1  - Banasiak U
A1  - Boobis AR
A1  - Borzelleca JF
A1  - Caldas ED
A1  - Calumpang SMF
A1  - Fenner-Crisp P
A1  - Funk S
A1  - Hakansson H
A1  - Hajslova J
A1  - Hamilton DJ
A1  - Moretto A
A1  - Ogura A
A1  - Ossendorp BC
A1  - Priestly BG
A1  - Soliman SA
Y1  - 2001///
SN  - 9-2510-4547-X
N2  - -
ER  - 

TY  - BOOK
T1  - Nutrition and the healing of skin wounds. Educational Booklet
A1  - Lansdown ABG
Y1  - 2001///
PB  - The Wound Care Society
CY  - UK
N2  - -
ER  - 

TY  - BOOK
T1  - Pesticide Residues in Food - 2001
A1  - Banasiak U
A1  - Boobis AR
A1  - Caldas ED
A1  - Chen B
A1  - Funk S
A1  - Hamilton DJ
A1  - Moretto A
A1  - Ossendorp BC
A1  - Priestly BG
Y1  - 2001///
SN  - 9-2510-4662-X
N2  - -
ER  - 

TY  - BOOK
T1  - New challenges to health: the threat of virus infection
A1  - Smith GL
Y1  - 2001///
SN  - 0-5218-0614-3
EP  - 4
N2  - -
ER  - 

TY  - CHAP
T1  - Clinical Prospects of NF-?B Inhibitors to Further Target Therapies in Rheumatology
A1  - Drexler, S
A1  - Turner, JJO
A1  - Foxwell, BMJ
T2  - Further Targeted Therapy in Rheumatology.
Y1  - 2007///
N2  - -
ER  - 

TY  - CHAP
T1  - DNA REPAIR IN MYCOBACTERIA
A1  - Davis, EO
A1  - Rand, L
ED  - Frank Columbus
T2  - DNA Research Trends
Y1  - 2007///
PB  - Nova Science publisher
CY  - New York
N2  - -
ER  - 

TY  - CHAP
T1  - Hodgkin's Lymphoma
A1  - Terpos, E
A1  - Rahemtulla, A
ED  - BMJ Publishing Group
T2  - BMJ Clinical Evidence
Y1  - 2006/11/02/
VL  - BMJ Clinical Evidence
M2  - 15
PB  - BMJ Publishing Group Ltd
SP  - 1
EP  - 21
N2  - -
ER  - 

TY  - CHAP
T1  - Introduction to diabetes mellitus
A1  - Baynes, KCR
ED  - Soumyanath, A
T2  - Traditional medicines for modern times: Antidiabetic plants
Y1  - 2006///
PB  - CRC Press
CY  - Florida, US
N2  - -
ER  - 

TY  - CHAP
T1  - Multidimensional fluorescence imaging applied to biological tissue.
A1  - Elson, DS
A1  - Galletly, N
A1  - Talbot, C
A1  - Requejo-Isidro, J
A1  - McGinty, J
A1  - Dunsby, C
A1  - Lanigan, PMP
A1  - Munro, I
A1  - Benninger, RKP
A1  - de Beule, P
A1  - Auksorius, E
A1  - Hegyi, L
A1  - Sandison, A
A1  - Wallace, A
A1  - Soutter, P
A1  - Neil, MAA
A1  - Lever, J
A1  - Stamp, GW
A1  - French, PMW
ED  - Geddes, CD
Lakowicz, JR
T2  - Reviews in Fluorescence 2006
Y1  - 2006///
M2  - 3
PB  - Springer Science
CY  - New York, USA
SN  - 0-3872-9342-6
SP  - 477
EP  - 524
N2  - -
ER  - 

TY  - CHAP
T1  - Pathophysiology and management of bone metastases in lung cancer
A1  - Terpos, E
A1  - Syrigos,KN
ED  - Syrigos, KN; Nutting CM; Roussos, C
T2  - Tumors of the Chest
Y1  - 2006///
PB  - SRINGER
CY  - Berlin, Heidelberg, New York
SN  - 3-540-31039-8
SP  - 551
EP  - 562
N2  - -
ER  - 

TY  - CHAP
T1  - Impact of genome sequences on mutational analysis of fungal and bacterial pathogens
A1  - Pelicic V
A1  - Nassif X
ED  - Hacker J, Dobrindt U
T2  - Pathogenomics: genome analysis of pathogenic microbes
Y1  - 2006///
PB  - John Wiley & Sons
SN  - 3-527-31265-X
SP  - 1
EP  - 568
N2  - -
ER  - 

TY  - CHAP
T1  - Macrophages and macrophage death in human atherosclerosis
A1  - Hegyi, L
A1  - Siow, RCM
A1  - Skepper, JN
ED  - Schoenhagen M
T2  - Current developments in atherosclerosis research
Y1  - 2006///
PB  - Nova Science Publishers, Inc.
CY  - Hauppauge, NY 11788, USA
SP  - 1
EP  - 32
N2  - -
ER  - 

TY  - CHAP
T1  - Haematology
A1  - Abdalla, S
ED  - Eddleston, M
Davidson, R
Wilkinson, R
Pierini, S
T2  - Oxford Book of Tropical Medicine
Y1  - 2005///
VL  - Second Edition
PB  - Oxford University Press
CY  - Oxford
SN  - 0 19 852509 5
SP  - 549
EP  - 590
N2  - -
UR  - http://www.oup.com/uk/catalogue/?ci=9780198525097
ER  - 

TY  - CHAP
T1  - Carcinoid Syndrome
A1  - Jayasena, C N
A1  - Dhillo, W S
ED  - Dhillo WS & Meeran K
T2  - MEDICINE
Y1  - 2005///
VL  - 12
M2  - 33
SP  - 47
EP  - 48
N2  - -
ER  - 

TY  - CHAP
T1  - Detection and Quantitation of HIV-1-Specific T Lymphocytes in HIV-1 Infected Individuals and Vaccine Recipients
A1  - Nesrina Imami
A1  - Antonio Pires
ED  - Liberman, A. P.
T2  - Progress in AIDS Research
Y1  - 2005///
PB  - Nova Science Publishers
CY  - New York
SN  - 1-59454-181-7
SP  - 109
EP  - 137
N2  - -
UR  - http://www.novapublishers.com
ER  - 

TY  - CHAP
T1  - Peptide vaccines
A1  - Mike M. Putz
A1  - Claude P. Muller
ED  - Stefan H.E. Kaufmann & Michael W. Steward
T2  - Topley & Wilson's Microbiology and Microbial Infections
Y1  - 2005///
VL  - 10th Edition
M2  - Immunology
PB  - Hodder Arnold
CY  - London
SN  - 0 340 80912 4
SP  - 853
EP  - 895
N2  - -
ER  - 

TY  - CHAP
T1  - BCL-6: rearrangement and mutation in lymphoma.
A1  - Wagner, S D
A1  - Kaeda, J S
T2  - Methods Mol Med.
Y1  - 2005///
M2  - 115
SP  - 251
EP  - 270
N2  - -
ER  - 

TY  - CHAP
T1  - Myeloma
A1  - Terpos E
A1  - Rahemtulla A
ED  - Hoffbrand V; Tuddenham E; Catovsky D
T2  - Postgraduate Haematology
Y1  - 2005///
M2  - Fifth Edition
PB  - Blackwell Publishing
SP  - 681
EP  - 702
N2  - -
ER  - 

TY  - CHAP
T1  - Inflammation imaging in the lungs
A1  - Jones, H A
ED  - Daniel P Schuster
Timothy S Blackwell
T2  - Molecular Imaging of the Lungs
Y1  - 2005///
M2  - 203
PB  - Taylor and Francis
SN  - 1-57444-854-4
SP  - 237
EP  - 258
N2  - -
ER  - 

TY  - CHAP
T1  - Mixed leukocyte reactions
A1  - Knight, S.C.
A1  - Bedford, P.A.
A1  - Stagg, A.J.
ED  - Lotze, M.T.
Thomson, A.W.
T2  - Measuring Immunity
Y1  - 2005///
SP  - 350
EP  - 360
N2  - -
ER  - 

TY  - CHAP
T1  - Carcinoid Syndrome
A1  - Jayasena C
A1  - Dhillo WS
ED  - Dhillo WS & Meeran K
T2  - MEDICINE
Y1  - 2005///
VL  - 12
M2  - 33
SP  - 47
EP  - 48
N2  - -
ER  - 

TY  - CHAP
T1  - Hematopoietic culture systems
A1  - Laleh Safinia
A1  - Nicki Panoskaltsis
A1  - Athanasios Mantalaris
ED  - Al-Rubeai M and Chaudhuri J
T2  - Bioreactors for Tissue Engineering: Principles, Design and Operation
Y1  - 2005///
PB  - Kluwer Academic Publishers
N2  - -
ER  - 

TY  - CHAP
T1  - Laboratory Practice
A1  - Lewis, SM
ED  - AV Hoffbrand, D Catovsky, EGD Tuddenham
T2  - Postgraduate Haematology
Y1  - 2005///
VL  - 5th
PB  - Blackwell
CY  - Oxford
SN  - 1 4051 0821 5
SP  - 1007
EP  - 1021
N2  - -
ER  - 

TY  - CHAP
T1  - Rubella virus
A1  - Best J
A1  - Cooray S
A1  - Banatvala J
ED  - Mahy BWJ and Ter Meulen V
T2  - Topley & Wilson’s Microbiology and Microbial Infections
Y1  - 2005///
VL  - 10
M2  - Virology: Volume 1
PB  - Hodder Arnold
CY  - London
SN  - 0-340-88562-9
SP  - 959
EP  - 992
N2  - -
ER  - 

TY  - CHAP
T1  - The spleen
A1  - Lewis, SM
ED  - AV Hoffbrand, D Catovsky, EGD Tuddenhamd
T2  - Postgraduate Haematology
Y1  - 2005///
VL  - 5th
PB  - Blackwell
CY  - Oxford
SN  - 1 4051 0821 5
SP  - 358
EP  - 369
N2  - -
ER  - 

TY  - CHAP
T1  - Regulation of gene expression by ambient pH
A1  - Arst HN Jr
A1  - Tilburn J
ED  - Brambl R, Marzluf GA
T2  - The Mycota: Biochemistry and Molecular Biology, 2nd ed
Y1  - 2004///
M2  - III
PB  - Springer-Verlag
CY  - Berlin
SP  - 121
EP  - 128
N2  - -
ER  - 

TY  - CHAP
T1  - Tissue Engineering of Bone Marrow
A1  - Mantalaris A
A1  - Panoskaltsis N
A1  - Wu JHD
ED  - Wnek, G. and Bowlin, G.
T2  - Encyclopaedia of Biomaterials and Bioengineering
Y1  - 2004///
PB  - Marcel Dekker Inc.
CY  - New York, U.S.A.
N2  - -
ER  - 

TY  - CHAP
T1  - Stem Cell Sources and Assays
A1  - Mantalaris A
A1  - Panoskaltsis N
A1  - Wu JHD
ED  - Wnek, G. and Bowlin G.
T2  - Encyclopaedia of Biomaterials and Bioengineering
Y1  - 2004///
PB  - Marcel Dekker Inc.
CY  - New York, U.S.A.
N2  - -
ER  - 

TY  - CHAP
T1  - Host recognition by fungal pathogens
A1  - Bignell, E.
A1  - Rogers, T.
ED  - Giaconda Sans-Blas and Richard A. Calderone
T2  - Pathogenic fungi: Host interactions and emerging strategies for control
Y1  - 2004///
PB  - Caister Academic Press
CY  - Norfolk
SN  - 0-9542464-8-9
SP  - 3
EP  - 48
N2  - -
ER  - 

TY  - CHAP
T1  - Tissue Engineering of Bone Marrow, Culture Systems
A1  - Mantalaris A
A1  - Panoskaltsis N
A1  - Wu JHD
ED  - Wnek, G. and Bowlin, G.
T2  - Encyclopaedia of Biomaterials and Bioengineering
Y1  - 2004///
PB  - Marcell Dekker Inc.
CY  - New York, U.S.A.
N2  - -
ER  - 

TY  - CHAP
T1  - The Calcitonin Receptor
A1  - Girgis SI
A1  - Moradi-Binhendi N
A1  - Mancini L
A1  - MacIntyre I
ED  - W. J. Lennarz and M. D. Lane
T2  - Encyclopedia of Biological Chemistry
Y1  - 2004///
PB  - Elsevier
CY  - Oxford
SN  - 0-12-443710-9
SP  - 217
EP  - 220
N2  - -
ER  - 

TY  - CHAP
T1  - Diabetes mellitus, lipoprotein disorders and other metabolic diseases
A1  - Baynes, KCR
A1  - Betteridge, DJ
ED  - Axford & O'Callaghan
T2  - Medicine
Y1  - 2004///
VL  - 2
PB  - Blackwells Science
CY  - Oxford
N2  - -
ER  - 

TY  - CHAP
T1  - Regulation of Gene Expression by ambient pH
A1  - Arst HN JR, Tilburn J.
ED  - Brambl R, Marzluf GA
T2  - the Mycota: Biochemistry and Molecular Biology
Y1  - 2004///
VL  - 2nd Ed
M2  - III
PB  - Springer-Verlag Berlin Heidelberg New York
CY  - Germany
SN  - 3-540-42630-2
SP  - 121
EP  - 128
N2  - -
ER  - 

TY  - CHAP
T1  - B-Myb: a highly regulated member of the the Myb transcription factor family.
A1  - Watson, RJ
ED  - Frampton, J
T2  - Myb transcription factors: their role in growth, differentiation and disease
Y1  - 2004///
VL  - 1st
M2  - Proteins and Cell Regulation V
PB  - Kluwer Academic Publishers
CY  - Dordrecht, Netherlands
SN  - 1-4020-2779-6
SP  - 181
EP  - 199
N2  - -
ER  - 

TY  - CHAP
T1  - Regulation of gene expression by ambient pH.
A1  - Arst HN Jr
A1  - Tilburn J
ED  - Brambl R and Marzluf GA
T2  - The Mycota Vol. III.  Biochemistry and Molecular Biology.
Y1  - 2004///
VL  - 2nd
M2  - 3
PB  - Springer-Verlag
CY  - Berlin
SP  - 121
EP  - 128
N2  - -
ER  - 

TY  - CHAP
T1  - Dendrimer drugs prevent scar tissue formation
A1  - Shaunak S
ED  - Noel R. Rose
T2  - Discovery Medicine
Y1  - 2004///
PB  - Peter H. Rheinstein
SP  - 464
EP  - 469
N2  - -
ER  - 

TY  - CHAP
T1  - Synthetic and recombinant vaccines based on peptides, mimotopes and permutational polyepitopes
A1  - Putz MM
A1  - Jung G
A1  - Muller CP
ED  - Epton R
T2  - Innovations and perspectives in Solid Phase Synthesis & Combinatorial Libraries
Y1  - 2004///
VL  - 2004
PB  - Mayflower Worldwide Ltd
CY  - Kingswinford, UK
SP  - 59
EP  - 62
N2  - -
ER  - 

TY  - CHAP
T1  - Ageing and the Immune Response
A1  - S.M. Henson
A1  - R. Aspinall
ED  - R. Aspinall
T2  - Ageing of the Organs and Systems
Y1  - 2003///
M2  - 3
PB  - Kluwer Academic Publishers
N2  - -
ER  - 

TY  - CHAP
T1  - Pathology pf Pulmonary Hypertension
A1  - Bishop AE
A1  - Polak JM
ED  - N. Banner, M.H. Yacoub
T2  - Lung Transplantation
Y1  - 2003///
PB  - Cambridge University Press
CY  - Cambridge, U.K.
SP  - 20
EP  - 28
N2  - -
ER  - 

TY  - CHAP
T1  - Premalignant disease of the genital tract
A1  - Maclean, A
A1  - Dina, R
ED  - Robert W. Shaw,  W.Patrick Soutter,  Stuart L.Stanton
T2  - Gynaecology
Y1  - 2003///
VL  - 3rd
PB  - Churchill Livingstone
N2  - -
ER  - 

TY  - CHAP
T1  - Endocrine Tumors of the Gastrointestinal Tract
A1  - Barakat MT
A1  - Lynn JA
A1  - Bloom SR
ED  - AE Schwartz, D Pertsemlidis & M Gagner
T2  - Endocrine Surgery
Y1  - 2003///
PB  - Marcel Dekker
CY  - New York
SP  - 643
EP  - 658
N2  - -
ER  - 

TY  - CHAP
T1  - Premalignant disease of the genital tract
A1  - Soutter, P
A1  - Dina, R
ED  - Edited by Robert W. Shaw,  W.Patrick Soutter,  Stuart L.Stanton  - Churchill Livingstone 2003
T2  - Gynaecology, 3rd Edition,
Y1  - 2003///
VL  - 3rd Edition,
PB  - Churchill Livingstone
N2  - -
ER  - 

TY  - CHAP
T1  - The chronic lymphoid and myeloid leukemias and systemic mastocytosis
A1  - Clark DM
A1  - Bain BJ
ED  - Wickramasinghe SN and McCullough J
T2  - Blood and Bone Marrow Pathology
Y1  - 2003///
PB  - Churchill Livingstone
CY  - Edinburgh
N2  - -
ER  - 

TY  - CHAP
T1  - Silver
A1  - Lansdown ABG
ED  - J Lagowski
T2  - MacMillan's Encyclopedia "Chemistry: foundations and applications"
Y1  - 2003///
PB  - Gale Group
CY  - Farmington, USA
N2  - -
ER  - 

TY  - CHAP
T1  - An overview of transrelocation-related oncogenesis in the chronic myeloid leukaemias
A1  - Bain BJ
ED  - Bain BJ
T2  - Chronic Myeloproliferative disorders: Cytogenetic and Molecular genetic abnormailites
Y1  - 2003///
PB  - Karger
CY  - Basel
SP  - 1
EP  - 8
N2  - -
ER  - 

TY  - CHAP
T1  - Tuberculosis
A1  - Friedland JS
ED  - Cohen J & Powderly W
T2  - Infectious Diseases
Y1  - 2003///
PB  - Mosby
CY  - London, UK
SP  - 401
EP  - 418
N2  - -
ER  - 

TY  - CHAP
T1  - HIV and its manipulation of chemokine receptors
A1  - Shaunak S
ED  - Friedland JS & Lightstone LB
T2  - Postgraduate Medical Sciences Series. Infection and Immunity
Y1  - 2003///
PB  - Martin Dunitz Publishers
SP  - 177
EP  - 190
N2  - -
ER  - 

TY  - CHAP
T1  - The classification of Interstitial Pneumonias
A1  - A.J Rice
A1  - A.U. Wells
A1  - A.G Nicholson
ED  - Nigel Kirkham, Neil Shepherd
T2  - Progress in Pathology Vol. 6
Y1  - 2003///
M2  - 6
PB  - Greenwich Medical Media
CY  - UK
SN  - 1841101486
SP  - 51
EP  - 77
N2  - -
ER  - 

TY  - CHAP
T1  - Malignant disease of the vulva and vagina
A1  - Dina, R
A1  - Thomas,CH
ED  - Robert W. Shaw,  W.Patrick Soutter,  Stuart L.Stanton
T2  - Gynaecology
Y1  - 2003///
VL  - 3rd
PB  - Churchill Livingstone
N2  - -
ER  - 

TY  - CHAP
T1  - Nutritional Management of the Elderly Person with Diabetes.
A1  - Hickson M
A1  - Wright L.
ED  - Frost G; Dornhorst A; Moses R.
T2  - Nutritional Management of Diabetes Mellitus
Y1  - 2003///
PB  - John Wiley & Sons
CY  - Chichester, UK.
N2  - -
ER  - 

TY  - CHAP
T1  - Cytogenic and molecular genetic abnormalites in systemic mastocytosis
A1  - Gupta R
A1  - Bain BJ
A1  - Knight CL
ED  - Bain BJ
T2  - Chronic Myeloproliferative disorders: Cytogenetic and Molecular genetic abnormailites
Y1  - 2003///
PB  - Karger
CY  - Basel
SP  - 120
EP  - 126
N2  - -
ER  - 

TY  - CHAP
T1  - Malignant disease of the uterus
A1  - Quinn,M
A1  - Jones, B
A1  - Dina, R
ED  - Robert W. Shaw,  W.Patrick Soutter,  Stuart L.Stanton
T2  - Gynaecology
Y1  - 2003///
VL  - 3rd
PB  - Churchill Livingstone
N2  - -
ER  - 

TY  - CHAP
T1  - Hormones and the gastrointestinal tract.
A1  - Hammond PJ
A1  - Bloom SR
A1  - Bishop AE
A1  - Polak JM
ED  - D.A. Warrell, T.M. Cox, J.D. Firth, E.J. Benz
T2  - Oxford Textbook of Medicine
Y1  - 2003///
M2  - 4th
PB  - Oxford University Press
CY  - Oxford, U.K.
SN  - 0-19-262922-0
SP  - 569
EP  - 576
N2  - -
ER  - 

TY  - CHAP
T1  - Genetics and dynamics of the immune response to HTLV-I
A1  - Bangham CRM
T2  - Gann Monograph on Cancer Research
Y1  - 2003///
PB  - Karger
CY  - Basel
SP  - 149
EP  - 170
N2  - -
ER  - 

TY  - CHAP
T1  - IL-4 Knock-out mice
A1  - Kropf P
A1  - Muller I
ED  - Fantuzzi G
T2  - Cytokine Knockouts, 2nd Edition
Y1  - 2003///
PB  - Humana Press
CY  - Totowa, New Jersey, USA
SP  - 187
EP  - 202
N2  - -
ER  - 

TY  - CHAP
T1  - Pathology of pulmonary hypertension
A1  - Bishop AE
A1  - Polak JM
ED  - Banner N R, Polak J M, Yacoub M
T2  - Lung Transplantation
Y1  - 2003///
PB  - Cambridge University Press
CY  - Cambridge
SP  - 19
EP  - 28
N2  - -
ER  - 

TY  - CHAP
T1  - Carcinoma of the ovary and fallopian tube
A1  - Dina, R
A1  - Rustin,GJ
A1  - Soutter, P
ED  - Robert W. Shaw,  W.Patrick Soutter,  Stuart L.Stanton
T2  - Gynaecology
Y1  - 2003///
VL  - 3rd
PB  - Churchill Livingstone
N2  - -
ER  - 

TY  - CHAP
T1  - Insulinomas and hypoglycaemia
A1  - Todd JF
A1  - Bloom SR
T2  - Oxford Textbook of Endocrinology and Diabetes
Y1  - 2002///
SN  - 0-1926-3045-8
SP  - 883
EP  - 888
N2  - -
ER  - 

TY  - CHAP
T1  - Nitric oxide and other vasoactive agents
A1  - Buttery LDK
A1  - Mancini L
A1  - Moradi-Bidhendi N
A1  - O'Shaughnessy MC
A1  - Polak JM
A1  - MacIntyre I
T2  - Principles of Bone Biology
Y1  - 2002///
SN  - 0-1209-8652-3
SP  - 995
EP  - 1013
N2  - -
ER  - 

TY  - CHAP
T1  - Secretin
A1  - Seal LJ
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 2871
EP  - 2874
N2  - -
ER  - 

TY  - CHAP
T1  - Calcitonin gene-related peptide
A1  - Girgis SI
A1  - MacIntyre I
ED  - Thomas Creighton
T2  - Encyclopedia of Molecular Medicine
Y1  - 2002///
PB  - John Wiley & Sons
SN  - 0-4713-7494-6
SP  - 416
EP  - 417
N2  - -
ER  - 

TY  - CHAP
T1  - Pancreatic polypeptide
A1  - Stanley SA
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 2381
EP  - 2384
N2  - -
ER  - 

TY  - CHAP
T1  - The Leishmaniasis Model
A1  - Kropf P
A1  - Brunson K
A1  - Muller I
ED  - Kaufmann SHE & Kabelitz D
T2  - Immunology of Infection, part of Methods in Microbiology Series, 2nd Edition
Y1  - 2002///
PB  - Academic Press Ltd
CY  - London
SP  - 463
EP  - 492
N2  - -
ER  - 

TY  - CHAP
T1  - Endocrinology of the gastrointestinal tract
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
T2  - Comprehensive Clinical Endocrinology
Y1  - 2002///
M2  - 3rd
SN  - 0-7234-3185-X
SP  - 453
EP  - 469
N2  - -
ER  - 

TY  - CHAP
T1  - Secretin
A1  - Seal LJ
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 2871
EP  - 2874
N2  - -
ER  - 

TY  - CHAP
T1  - Pancreatic polypeptide
A1  - Stanley SA
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 2381
EP  - 2384
N2  - -
ER  - 

TY  - CHAP
T1  - Vasoactive intestinal peptide (VIP)
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 3344
EP  - 3346
N2  - -
ER  - 

TY  - CHAP
T1  - Orexins (Hypocretins)
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 2328
EP  - 2331
N2  - -
ER  - 

TY  - CHAP
T1  - Bcl-6 uncouples B lymphocyte proliferation from differentiation.
A1  - Fearon, D T
A1  - Manders, P M
A1  - Wagner, S D
T2  - Adv Exp Med Biol.
Y1  - 2002///
M2  - 512
SP  - 21
EP  - 28
N2  - -
ER  - 

TY  - CHAP
T1  - Glucagon- and proglucagon-derived peptides
A1  - Bloom SR
A1  - Ghatei MA
A1  - Taheri S
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 1430
EP  - 1434
N2  - -
ER  - 

TY  - CHAP
T1  - Modification of host cell function bt normal flora: a molecular perspective
A1  - Stagg AJ
ED  - AL Hart, AJ Stagg, H Graffner, H Glise, P Falk, MA Kamm
T2  - Gut Ecology
Y1  - 2002///
PB  - Martin Dunitz
CY  - London
SP  - 51
EP  - 56
N2  - -
ER  - 

TY  - CHAP
T1  - Glucagon- and proglucagon-derived peptides
A1  - Bloom SR
A1  - Ghatei MA
A1  - Taheri S
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 1430
EP  - 1434
N2  - -
ER  - 

TY  - CHAP
T1  - Bombesin
A1  - Howard JK
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 381
EP  - 383
N2  - -
ER  - 

TY  - CHAP
T1  - Anaemia in newborns, infants and children
A1  - Roberts I
A1  - Vassilou G
T2  - Essential Paediatric Haematology
Y1  - 2002///
SN  - 9-0582-3179-8
SP  - 65
EP  - 91
N2  - -
ER  - 

TY  - CHAP
T1  - The anatomy, organization and ultrastructure of the Islets of Langerhans
A1  - Bishop AE
A1  - Polak JM
ED  - J. Pickup and G. Williams
T2  - Textbook of Diabetes
Y1  - 2002///
PB  - Blackwell Scientific Ltd
CY  - Oxford, U.K.
SN  - 0-6320-5915-X
SP  - 10.1
EP  - 10.6
N2  - -
ER  - 

TY  - CHAP
T1  - Stem Cells: sources and applications
A1  - Buttery LDK
A1  - Polak JM
T2  - Future Strategies for Tissue and Organ Replacement
Y1  - 2002///
SN  - 1-8609-4310-1
SP  - 351
EP  - 368
N2  - -
ER  - 

TY  - CHAP
T1  - Orexins (Hypocretins)
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 2328
EP  - 2331
N2  - -
ER  - 

TY  - CHAP
T1  - Cell culture systems in apoptosis
A1  - Grimm S
ED  - Grimm, S
T2  - Genetics of Apoptosis
Y1  - 2002///
PB  - BIOS Scientific Publishers
CY  - Oxford, UK
N2  - -
ER  - 

TY  - CHAP
T1  - VIPomas
A1  - Howard JK
A1  - Bloom SR
T2  - Oxford Textbook of Endocrinology and Diabetes
Y1  - 2002///
SN  - 0-1926-3045-8
SP  - 895
EP  - 899
N2  - -
ER  - 

TY  - CHAP
T1  - Glucagonoma
A1  - Frankton S
A1  - Bloom SR
T2  - Oxford Textbook of Endocrinology and Diabetes
Y1  - 2002///
SN  - 0-1926-3045-8
SP  - 889
EP  - 894
N2  - -
ER  - 

TY  - CHAP
T1  - Mastocytosis
A1  - O'Shea D
A1  - Dhillo WS
T2  - Oxford Textbook of Endocrinology and Diabetes
Y1  - 2002///
SN  - 0-1926-3045-8
SP  - 937
EP  - 940
N2  - -
ER  - 

TY  - CHAP
T1  - Insulinomas and hypoglycaemia
A1  - Todd JF
A1  - Bloom SR
T2  - Oxford Textbook of Endocrinology and Diabetes
Y1  - 2002///
SN  - 0-1926-3045-8
SP  - 883
EP  - 888
N2  - -
ER  - 

TY  - CHAP
T1  - Ischemic colitis
A1  - Stansby G
A1  - Thomas.H.
A1  - Goldin R
T2  - Diseases of the Visceral Circulation
Y1  - 2002///
SN  - 0-3408-0722-9
SP  - 145
EP  - 157
N2  - -
ER  - 

TY  - CHAP
T1  - Bombesin
A1  - Howard JK
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 381
EP  - 383
N2  - -
ER  - 

TY  - CHAP
T1  - The anatomy, organization and ultrastructure of the Islets of Langerhans
A1  - Bishop AE
A1  - Polak JM
T2  - Textbook of Diabetes
Y1  - 2002///
SN  - 0-6320-5915-X
SP  - 10
EP  - 10
N2  - -
ER  - 

TY  - CHAP
T1  - Gastrinoma
A1  - Calam J
A1  - Taheri S
A1  - Bloom SR
T2  - Oxford Textbook of Endocrinology and Diabetes
Y1  - 2002///
SN  - 0-1926-3045-8
SP  - 877
EP  - 882
N2  - -
ER  - 

TY  - CHAP
T1  - Calcitonin
A1  - MacIntyre I
A1  - Girgis SI
ED  - Thomas Creighton
T2  - Encyclopedia of Molecular Medicine
Y1  - 2002///
PB  - John Wiley & Sons
SN  - 0-4713-7494-6
SP  - 414
EP  - 415
N2  - -
ER  - 

TY  - CHAP
T1  - Infections in multiple myeloma
A1  - Kelleher P
A1  - Chapel H
T2  - Multiple Myeloma
Y1  - 2002///
SN  - 1-9018-6550-9
SP  - 223
EP  - 239
N2  - -
ER  - 

TY  - CHAP
T1  - Cholecystokinin (CCK)
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encylopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 752
EP  - 754
N2  - -
ER  - 

TY  - CHAP
T1  - Cholecystokinin (CCK)
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encylopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 752
EP  - 754
N2  - -
ER  - 

TY  - CHAP
T1  - Immune intervention in tuberculosis
A1  - Young DB
A1  - Robertson BD
T2  - Immunology of Infectious Diseases
Y1  - 2002///
SN  - 1-5558-1214-7
SP  - 439
EP  - 451
N2  - -
ER  - 

TY  - CHAP
T1  - Thrombocytopenia in the newborn
A1  - Roberts IAG
A1  - Murray NA
T2  - Platelets
Y1  - 2002///
SN  - 0-1249-3951-1
SP  - 635
EP  - 658
N2  - -
ER  - 

TY  - CHAP
T1  - Pancreatic polypeptide
A1  - Stanley SA
A1  - Ghatei MA
A1  - Bloom SR
T2  - Wiley Encyclopedia of Molecular Medicine
Y1  - 2002///
SN  - 0-4713-7494-6
SP  - 2381
EP  - 2384
N2  - -
UR  - NULL
ER  - 

TY  - CHAP
T1  - Endocrinology of the gastrointestinal tract
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
T2  - Comprehensive Clinical Endocrinology
Y1  - 2002///
M2  - 3rd
SN  - 0-7234-3185-X
SP  - 453
EP  - 469
N2  - -
ER  - 

TY  - CHAP
T1  - The orexins/hypocretins - novel hypothalamic neuropeptides with multiple functions
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
Y1  - 2001///
SP  - 121
EP  - 133
N2  - -
ER  - 

TY  - CHAP
T1  - Pathology of vascular disease
A1  - Cook HT
A1  - Pusey CD
Y1  - 2001///
SN  - 0-8493-1335-X
SP  - 3
EP  - 21
N2  - -
ER  - 

TY  - CHAP
T1  - Obstetrics, fetal and paediatric
A1  - Roberts I
A1  - McCloy M
Y1  - 2001///
SN  - 0-6320-5114-0
SP  - 87
EP  - 107
N2  - -
ER  - 

TY  - CHAP
T1  - Interactions between dendritic cells
A1  - Knight, S.C.
A1  - Burke, F.
A1  - Bedford, P.A.
T2  - Advances in Experimental Medicine and Biology
Y1  - 2001///
M2  - 495
SP  - 103
EP  - 109
N2  - -
ER  - 

TY  - CHAP
T1  - White blood cells
A1  - Bain BJ
ED  - Jones SL
T2  - Clinical Laboratory Pearls
Y1  - 2001///
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
SN  - 0-7817-2579-8
SP  - 97
EP  - 138
N2  - -
ER  - 

TY  - CHAP
T1  - Dendritic cell/dendritic cell interaction
A1  - Knight SC
A1  - Bedford PA
ED  - Thompson, A.W.
Lotze, M.T.
T2  - Dendritic Cells: Biology and Clinical Applications
Y1  - 2001///
VL  - 2nd
PB  - Academic Press
CY  - London
SN  - 0-1245-5851-8
SP  - 333
EP  - 343
N2  - -
ER  - 

TY  - CHAP
T1  - Isolation of dendritic cells from animal tissues: Isolation of mouse spleen dendritic cells
A1  - Stagg, A.J.
A1  - Burke, F.
A1  - Hill, S.
A1  - Knight, S.C.
ED  - Robinson, S.P.
Stagg, A.J.
T2  - Methods in Molecular Medicine
Y1  - 2001///
PB  - Humana Press
CY  - New Jersey, USA
SP  - 9
EP  - 22
N2  - -
ER  - 

TY  - CHAP
T1  - Fetal somatic gene therapy - a preventive approach to the treatment of genetic disease: the case for
A1  - Coutelle C
A1  - Themis M
A1  - Schneider H
A1  - Cook HT
Y1  - 2001///
SN  - 3-5406-7701-1
SP  - 99
EP  - 114
N2  - -
ER  - 

TY  - CHAP
T1  - Chronic neutrophilic leukaemia
A1  - Imbert M
A1  - Bain B
A1  - Pierre R
A1  - Vardiman JW
A1  - Brunning RD
A1  - Flandrin G
ED  - Jaffe ES, Harris NL, Stein H and Vardiman JW
T2  - World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lumphoid Tissues
Y1  - 2001///
PB  - IARC Press
CY  - Lyon, France
SP  - 27
EP  - 28
N2  - -
ER  - 

TY  - CHAP
T1  - Polyoma virus middle T-antigen: growth factor receptor mimic
A1  - Nicholson PR
A1  - Dilworth SM
Y1  - 2001///
SN  - 0-4445-0496-6
SP  - 85
EP  - 128
N2  - -
ER  - 

TY  - CHAP
T1  - Acquired haemolytic anaemias
A1  - Regan F
A1  - Newlands M
A1  - Bain BJ
Y1  - 2001///
M2  - 9th
SN  - 0-4430-6377-X
SP  - 199
EP  - 230
N2  - -
ER  - 

TY  - CHAP
T1  - The gut and the autonomic nervous system
A1  - Bishop AE
A1  - Polak JM
ED  - Sir Roger Bannister, C.J. Mathias
T2  - Autonomic Failure
Y1  - 2001///
PB  - Oxford University Press
CY  - Oxford, U.K.
SN  - 0-1926-2850-X
SP  - 117
EP  - 125
N2  - -
ER  - 

TY  - CHAP
T1  - The role of cytogenetics in the diagnosis and classification of haematological neoplasms
A1  - Bain BJ
Y1  - 2001///
M2  - 3rd
SN  - 0-1996-3842-X
SP  - 111
EP  - 128
N2  - -
ER  - 

TY  - CHAP
T1  - Isolation of mouse spleen dendritic cells
A1  - Stagg AJ
A1  - Burke F
A1  - Hill S
A1  - Knight SC
ED  - S Robinson & AJ Stagg
T2  - Dendritic Cell Protocols
Y1  - 2001///
PB  - Humana Press
CY  - Totawa
N2  - -
ER  - 

TY  - CHAP
T1  - Chronic myelomonocytic leukaemia
A1  - Vardiman JW
A1  - Pierre R
A1  - Bain B
A1  - Bennett JM
A1  - Imbert M
A1  - Brunning RD
A1  - Flandrin G
ED  - Jaffe ES, Harris NL, Stein H & Vardiman JW
T2  - World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues
Y1  - 2001///
PB  - IARC Press
CY  - Lyon, France
SP  - 49
EP  - 52
N2  - -
ER  - 

TY  - CHAP
T1  - Introduction to laboratory testing
A1  - Jones SL
A1  - Bain BJ
Y1  - 2001///
SN  - 0-7817-2579-8
SP  - 1
EP  - 5
N2  - -
ER  - 

TY  - CHAP
T1  - Investigation of abnormal haemoglobins and thalassaemia
A1  - Wild BJ
A1  - Bain BJ
Y1  - 2001///
M2  - 9th
SN  - 0-4430-6377-X
SP  - 231
EP  - 268
N2  - -
ER  - 

TY  - CHAP
T1  - Preparation and staining methods for blood and bone marrow films
A1  - Bain BJ
A1  - Mitchell SM
Y1  - 2001///
M2  - 9th
SN  - 0-4430-6377-X
SP  - 47
EP  - 64
N2  - -
ER  - 

TY  - CHAP
T1  - Antigen-presenting cells
A1  - Stagg AJ
A1  - Knight SC
T2  - Encyclopaedia of Life Sciences
Y1  - 2001///
PB  - Nature Publishing Group
N2  - -
ER  - 

TY  - CHAP
T1  - Basic haematological techniques
A1  - Bain BJ
A1  - Bates I
Y1  - 2001///
M2  - 9th
SN  - 0-4430-6377-X
SP  - 19
EP  - 46
N2  - -
ER  - 

TY  - CHAP
T1  - Atypical chronic myeloid leukaemia
A1  - Vardiman JW
A1  - Imbert M
A1  - Pierre R
A1  - Bain B
A1  - Brunning RD
A1  - Flandrin G
ED  - Jaffe ES, Harris NL, Stein H & Vardiman JW
T2  - World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haemapoietic and Lymphoid Tissues
Y1  - 2001///
PB  - IARC Press
CY  - Lyon, France
N2  - -
ER  - 

TY  - CHAP
T1  - Blood cell morphology in health and disease
A1  - Bain BJ
Y1  - 2001///
M2  - 9th
SN  - 0-443-06377-X
SP  - 65
EP  - 100
N2  - -
ER  - 

TY  - CHAP
T1  - Chronic eosinophilic leukaemia and the hypersosinophilix syndrome
A1  - Bain B
A1  - Pierre R
A1  - Imbert M
A1  - Vardiman JW
A1  - Brunning RD
A1  - Flandrin G
ED  - Jaffe ES, Harris NL, Stein H & Vardiman JW
T2  - World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues
Y1  - 2001///
PB  - IARC Press
CY  - Lyon, France
SP  - 29
EP  - 31
N2  - -
ER  - 

TY  - CHAP
T1  - The orexins/hypocretins - novel hypothalamic neuropeptides with multiple functions
A1  - Taheri S
A1  - Ghatei MA
A1  - Bloom SR
Y1  - 2001///
SP  - 121
EP  - 133
N2  - -
ER  - 

TY  - CHAP
T1  - Myelodysplastic/myeloproliferative disease, unclassifiable
A1  - Bain B
A1  - Vardiman JW
A1  - Imbert M
A1  - Pierre R
ED  - Jaffes ES, Harris NL, Stein H and Vardiman JW
T2  - World Health Organization Classification of Tumors: Pathology and Genetics of Tumors and Haematopoetic and Lymphoid Tissues
Y1  - 2001///
PB  - IARC Press
CY  - Lyon
SP  - 58
EP  - 59
N2  - -
ER  - 

TY  - CHAP
T1  - Erythrocyte and leucocyte cytochemistry - leukaemia classification
A1  - Swirsky D
A1  - Bain BJ
Y1  - 2001///
M2  - 9th
SN  - 0-4430-6377-X
SP  - 269
EP  - 296
N2  - -
ER  - 

TY  - CHAP
T1  - Interindividual variation of P450 enzymes in vitro and its causes
A1  - Pelkonen O
A1  - Boobis AR
A1  - Kremers P
Y1  - 2001///
M2  - 10
SN  - 0-7484-0864-9
SP  - 269
EP  - 332
N2  - -
ER  - 

TY  - CHAP
T1  - Metallothionein, calmodulin and trace elements in healing skin wounds
A1  - Sampson B
A1  - Lansdown ABG
A1  - Rowe AM
ED  - AM Roussel, RA Anderson, AE Favier
T2  - Trace Elements in Man and Animals
Y1  - 1999///
M2  - 10
SP  - 1038
N2  - -
ER  - 

TY  - CHAP
T1  - Anemia
A1  - Pasvol G
A1  - Abdalla SH
ED  - Geurrant, Walker and Weller
T2  - Tropical Infectious Disease. Principles, Pathogens and Practice
Y1  - 1999///
PB  - Churchill Livingstone
CY  - Philadelphia, Pensylvania
SN  - 0-443-07908-0
N2  - -
ER  - 

TY  - CHAP
T1  - The toxicity of cartilage and bone
A1  - Lansdown ABG
ED  - B Ballantyne, TC Marrs & T Syversen
T2  - General and Applied Toxicology
Y1  - 1999///
VL  - 2nd Edition
PB  - MacMillan
CY  - London
SP  - 965
EP  - 978
N2  - -
ER  - 

TY  - CHAP
T1  - Hormonal mechanisms in the toxicology of the skin
A1  - Lansdown ABG
ED  - PW Harvey, K Rush & A Cockburn
T2  - Hormonal Mechanisms in Toxicology
Y1  - 1998///
PB  - John Wiley
CY  - Chichester
N2  - -
ER  - 

TY  - CHAP
T1  - Hemoglobinometers
A1  - Lewis, SM
A1  - Lewis, SM
ED  - R Bud, DJ Warnerr
T2  - Instruments of Science: An historical encyclopedia
Y1  - 1998///
VL  - 1
PB  - Garland Publishing
CY  - New York
SN  - 0 8153 1561 9
SP  - 310
EP  - 311
N2  - -
ER  - 

TY  - CHAP
T1  - Overview of the Immune system
A1  - R. Aspinall
ED  - J. C. Buckingham, G.E. Giles and A.M. Cowell
T2  - Stress, Stress Hormones and the Immune System
Y1  - 1997///
N2  - -
ER  - 

TY  - CHAP
T1  - Methods for monitoring immune function
A1  - R. Aspinall
ED  - J. C. Buckingham, G.E. Giles and A.M. Cowell
T2  - Stress, Stress Hormones and the Immune System
Y1  - 1997///
PB  - J.Wiley and sons
N2  - -
ER  - 

TY  - CONF
T1  - The central role of thrombin in hemostasis
A1  - Crawley, JTB
A1  - Zanardelli, S
A1  - Chion, CKNK
A1  - Lane, DA
U1  - 22nd Congress of the International-Society-on Thrombosis-and-Haemostasis
Y1  - 2007/07//
Y2  - //
VL  - 5
SP  - 95
EP  - 101
N2  - -
ER  - 

TY  - CONF
T1  - Mouse embryonic stem cell engrafment in healthy and injured mouse lung
A1  - Lane, S
A1  - Rippon, H
A1  - Takata, M
A1  - Mahadeva, R
A1  - Bishop, AE
U1  - Conference of the Tissue-Engineering-and-Regenerative-Medicine-International-Society (TERMIS-EU)
Y1  - 2007/07//
Y2  - //
VL  - 13
SP  - 1731
EP  - 1731
N2  - -
ER  - 

TY  - CONF
T1  - HOX genes are a major target for epigenetic mis-regulation in adult and childhood leukaemia
A1  - Strathdee, G
A1  - Holyoake, TL
A1  - Sim, A
A1  - Parker, A
A1  - Oscier, DG
A1  - Melo, JV
A1  - Meyer, S
A1  - Eden, T
A1  - Dickinson, AM
A1  - Soutar, R
A1  - Brown, R
Y1  - 2007/04//
Y2  - //
VL  - 137
SN  - 0007-1048
SP  - 81
EP  - 81
N2  - -
ER  - 

TY  - CONF
T1  - Development of a hyperspectral fluorescence lifetime imaging microscope and its application to tissue imaging - art. no. 64411K
A1  - Owen, DM
A1  - Manning, HB
A1  - de Beule, P
A1  - Talbot, C
A1  - Requejo-Isidro, J
A1  - Dunsby, C
A1  - McGinty, J
A1  - Benninger, RKP
A1  - Elson, DS
A1  - Munro, I
A1  - Galletly, NP
A1  - Lever, MJ
A1  - Stamp, GW
A1  - Anand, P
A1  - Neil, MAA
A1  - French, PMW
U1  - Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V
Y1  - 2007///
Y2  - //
VL  - 6441
SP  - K4411
EP  - K4411
N2  - -
ER  - 

TY  - CONF
T1  - A novel hyperspectral lifetime probe for autofluorescence - art. no. 643303
A1  - De Beule, PAA
A1  - Dunsby, C
A1  - Owen, DM
A1  - Galletly, NP
A1  - Anand, U
A1  - Benham, CD
A1  - Naylor, A
A1  - Stamp, GW
A1  - Anand, P
A1  - French, PMW
U1  - Conference on Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications VII
Y1  - 2007///
Y2  - //
VL  - 6433
SP  - 43303
EP  - 43303
N2  - -
ER  - 

TY  - CONF
T1  - Osteonecrosis of the jaw in patients with multiple myeloma who receive bisphosphonates
A1  - Terpos, E
U1  - VIth International Meeting on Cancer Induced Bone Disease
AD  - San Antonio, TX, USA
Y1  - 2006/12//
Y2  - 2006/12/10/
VL  - 32 (Supplement 3)
PB  - CANCER TREATMENT REVIEWS
SN  - 0305-7372
SP  - S8
N2  - -
ER  - 

TY  - CONF
T1  - Pathogenesis of bone disease in multiple myeloma: clinical implications
A1  - Terpos, E
A2  - Boulikas T
U1  - 9th International Conference on Drug & Gene-based Therapeutics
AD  - Agia Pelagia, Crete, Greece
J1  - Proceedings of the 9th International Conference on Drug & Gene-based Therapeutics
Y1  - 2006/09//
Y2  - 2006/09/02/
PB  - Proceedings of the 9th International Conference on Drug & Gene-based Therapeutics
SP  - 85
EP  - 87
N2  - -
ER  - 

TY  - CONF
T1  - Preliminary results from a phase 2 trial of AG-858, an autologous heat shock protein-peptide vaccine, in combination with imatinib in patients with chronic phase chronic myeloid leukemia (CML) resistant to prior imatinib monotherapy.
A1  - Marin, D
A1  - Mauro, M
A1  - Goldman, J
A1  - Druker, B
A1  - Devine, S
A1  - Clark, RE
A1  - Paquette, R
A1  - Bashey, A
A1  - Tallman, MS
A1  - Dovholuk, A
A1  - Hoos, A
A1  - Srivastava, P
U1  - 47th Annual Meeting of the American-Society-of-Hematology
Y1  - 2005/11/16/
Y2  - //
VL  - 106
SP  - 318A
EP  - 319A
N2  - -
ER  - 

TY  - CONF
T1  - Use of direct sequence PCR for ABI kinase mutations in patients with CML blast crisis, treated prior to the availability of imatinib therapy
A1  - Ghorashian, S
A1  - Babb, A
A1  - Khorasan, J
A1  - Kaeda, J
A1  - Marin, D
A1  - Apperley, L
U1  - 47th Annual Meeting of the American-Society-of-Hematology
Y1  - 2005/11/16/
Y2  - //
VL  - 106
SP  - 567A
EP  - 567A
N2  - -
ER  - 

TY  - CONF
T1  - Poly(ADP-ribose) polymerase-1 regulates Bcl-6 transcription
A1  - Ambrose, HE
A1  - Beswick, RW
A1  - Wagner, SD
A2  - Nicola Curtin
U1  - PARP2005
AD  - Newcastle
J1  - Medical Science Monitor
Y1  - 2005/10//
Y2  - 2005/10/04/
VL  - 11S1
PB  - Medical Science International Ltd.
CY  - Warsaw
SN  - 1234-1010
N2  - -
UR  - http://www.MedSciMonit.com
ER  - 

TY  - CONF
T1  - Novel treatments of multiple myeloma
A1  - Dimopoulos MA
A1  - Anagnostopoulos A
A1  - Terpos E
U1  - XXXth World Congress of the International Society of Hematology
AD  - Istanbul, Turkey
Y1  - 2005/09//
Y2  - 2005/09/28/
VL  - 10 (Supplement 1)
PB  - HEMATOLOGY
SN  - 1024-5332
SP  - 25
N2  - -
ER  - 

TY  - CONF
T1  - Novel drugs in the treatment of multiple myeloma
A1  - Dimopoulos MA
A1  - Anagnostopoulos A
A1  - Terpos E
U1  - 10th Congress of the European Hematology Association
AD  - Stockholm, Sweden
Y1  - 2005/06//
Y2  - 2005/06/02/
VL  - 1
PB  - HEMATOLOGY (EHA Education Program)
SP  - 211
EP  - 215
N2  - -
ER  - 

TY  - CONF
T1  - RANKL and Macrophage Inflammatory Protein-1 alpha in Multiple Myeloma: Clinical Implications
A1  - Terpos E
A1  - Rahemtulla A
U1  - 10th International Myeloma Workshop
AD  - Sydney, Australia
Y1  - 2005/04//
Y2  - 2005/04/10/
VL  - 90 (Supplement 1)
PB  - HAEMATOLOGICA/THE HEMATOLOGY JOURNAL
SN  - 0390-6078
SP  - 43
EP  - 44
N2  - -
ER  - 

TY  - CONF
T1  - The structural basis for nif gene activation
A1  - Wigneshweraraj, SR
A1  - Burrows, PC
A1  - Bordes, P
A1  - Schumacher, J
A1  - Rappas, M
A1  - Finn, RD
A1  - Cannon, WV
A1  - Zhang, X
A1  - Buck, M
U1  - 14th International Nitrogen Fixation Congress
Y1  - 2005///
Y2  - //
VL  - 41
SP  - 59
EP  - 63
N2  - -
ER  - 

TY  - CONF
T1  - Eating together is important: using a dining room increases energy intake
A1  - Wright L
A1  - Hickson M
A1  - FrostG
U1  - British Dietetic Association National Conference
AD  - Cardiff, Wales
Y1  - 2005///
Y2  - //
N2  - -
ER  - 

TY  - CONF
T1  - Frequency of blast crisis after achieving complete cytogenetic remission in first chronic phase CML patients who recieved imatinib therapy within six months of diagnosis.
A1  - Laurence, A
A1  - Marin, D
A1  - Clark, R
A1  - Shepherd, P
A1  - Mackinnon, S
U1  - 46th Annual Meeting of the American-Society-of-Hematology
Y1  - 2004/11/16/
Y2  - //
VL  - 104
SP  - 292A
EP  - 292A
N2  - -
ER  - 

TY  - CONF
T1  - Improved thymic function in exclusively breast-fed babies is associated with higher breast milk IL-7
A1  - Ngom, PT
A1  - Collinson, AC
A1  - Lopez, JP
A1  - Henson, SM
A1  - Prentice, AM
A1  - Aspinall, R
U1  - 12th Annual International Congress of Immunology and 4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS)
Y1  - 2004///
Y2  - //
SP  - 309
EP  - 313
N2  - -
ER  - 

TY  - CONF
T1  - Stem cells and bioactive materials
A1  - Bielby, RC
A1  - Polak, JM
U1  - Conference of the NATO-Advanced-Study-Institute on Learning from Nature How to Design New Implantable Biomaterials
Y1  - 2004///
Y2  - //
VL  - 171
SP  - 181
EP  - 198
N2  - -
ER  - 

TY  - CONF
T1  - Embryonic stem cells for the engineering and regeneration of mineralized tissues
A1  - Buttery, LDK
A1  - Polak, JM
U1  - Conference of the NATO-Advanced-Study-Institute on Learning from Nature How to Design New Implantable Biomaterials
Y1  - 2004///
Y2  - //
VL  - 171
SP  - 199
EP  - 204
N2  - -
ER  - 

TY  - CONF
T1  - Attenuating mutations in the influenza virus genome which may increase the safety of vaccine production
A1  - Whiteley, A
A1  - Trikic, MZ
A1  - Barclay, WS
U1  - 5th International Conference on Options for the Control of Influenza
Y1  - 2004///
Y2  - //
VL  - 1263
SP  - 687
EP  - 690
N2  - -
ER  - 

TY  - CONF
T1  - A pilot survey to investigate the nutritional status of patients with a fractured neck of femur and level of nutritional support provided during treatment.
A1  - Nematy M
A1  - Hickson M
A1  - Brynes A
A1  - Ruxton C
A1  - Frost G
U1  - Nutrition Society
AD  - Dublin, Ireland
Y1  - 2004///
Y2  - //
VL  - 63
PB  - Proceedings of the Nutrition Society
N2  - -
ER  - 

TY  - CONF
T1  - Toll-like receptor 4 contributes to the efficient control of infection with the protozoan parasite Leishmania major
A1  - Kropf P
A1  - Freudenberg M
A1  - Modolell M
A1  - Price H
A1  - Herath S
A1  - Antoniazi S
A1  - Galanos C
A1  - Smith I
A1  - Muller I
U1  - International Cytokine Society
AD  - Dublin, Ireland
Y1  - 2003///
Y2  - 2003/09/20/
N2  - -
ER  - 

TY  - CONF
T1  - Bone marrow macrophages from TLR4-deficient mice display an impaired capacity to control the replication of Leishmania major parasites
A1  - Kropf P
A1  - Freudenberg M
A1  - Modolell M
A1  - Price H
A1  - Herath S
A1  - Antoniazi S
A1  - Galanos C
A1  - Smith S
A1  - Muller I
U1  - 17th Meeting of the EMDS
AD  - Leicester, UK
Y1  - 2003///
N2  - -
ER  - 

TY  - CONF
T1  - Endothelial nitric oxide synthase is an important regulator of osteoblast growth and differentiation.
A1  - Afzal, F
A1  - Nohadani, M
A1  - Huang, PL
A1  - Polak, JM
A1  - Buttery, LDK
U1  - 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research
Y1  - 2002/09//
Y2  - //
VL  - 17
SP  - S149
EP  - S149
N2  - -
ER  - 

TY  - CONF
T1  - Ageing alters the course of nonhealing Leishmania major infections in IL-4 deficient BALB/c mice
A1  - Muller I
A1  - Herath S
A1  - Kropf P
U1  - Immunoparasitology Meeting
AD  - Woods Hole, MA, USA
Y1  - 2002///
Y2  - 2002/04/26/
N2  - -
ER  - 

TY  - CONF
T1  - Signalling through the T1/ST2 molecule is not necessary for Th2 differentiation, but is important for the regulation of type 1 responses in nonhealing Lesmania major infection
A1  - Kropf P
A1  - Herath S
A1  - Klemenz R
A1  - Muller I
U1  - British Society for Parasitology, Trypanosomiasis and Leishmaniasis seminar
AD  - Edinburgh, UK
Y1  - 2002///
Y2  - 2002/09/08/
N2  - -
ER  - 

TY  - CONF
T1  - The effects of immunotherapy with cytokines and/or vaccines in HAART treated patients
A1  - Gotch, F
A1  - Hardy, G
A1  - Imami, N
A1  - Sullivan, A
A1  - Nelson, M
A1  - Burton, C
A1  - Pido-Lopez, J
A1  - Pires, A
A1  - Moss, R
U1  - 14th International AIDS Conference
Y1  - 2002///
Y2  - //
SP  - 279
EP  - 284
N2  - -
ER  - 

TY  - CONF
T1  - Cross-talk between CD8* and cells in experimental cutaneous leishmaniasis
A1  - Herath S
A1  - Kropf P
A1  - Muller I
U1  - Immunoparasitology Meeting
AD  - Woods Hole, MA, USA
Y1  - 2002///
Y2  - 2002/04/26/
N2  - -
ER  - 

TY  - CONF
T1  - Materials in medicine
A1  - Bielby, RC
A1  - Buttery, LDK
A1  - Polak, JM
U1  - Conference on Materials Science and Engineering
Y1  - 2002///
Y2  - //
SP  - 135
EP  - 151
N2  - -
ER  - 

TY  - CONF
T1  - Study of osteoblast differentiation and proliferation on the surface of binary bioactive gel-glasses
A1  - Bielby, RC
A1  - Saravanapavan, P
A1  - Polak, JM
A1  - Hench, LL
U1  - 14th International Symposium on Ceramics in Medicine (BIOCERAMICS-14)
Y1  - 2002///
Y2  - //
VL  - 218-2
SP  - 269
EP  - 272
N2  - -
ER  - 

TY  - CONF
T1  - Organ-specific distribution and cytokine production of CD4* T 1/ST2+ T cells in Leishmania major infected mice
A1  - Kropf P
A1  - Herath S
A1  - Bickle Q
A1  - Tewari R
A1  - Syed N
A1  - Klemenz R
A1  - Muller I
U1  - Immunoparasitology Meeting
AD  - Woods Hole, MA, USA
Y1  - 2002///
Y2  - 2002/04/26/
N2  - -
ER  - 

TY  - CONF
T1  - A genetic basis for biomedical materials
A1  - Hench, LL
A1  - Xynos, ID
A1  - Edgar, AJ
A1  - Buttery, LDK
A1  - Polak, JM
U1  - Conference on Materials Science and Engineering
Y1  - 2002///
Y2  - //
SP  - 283
EP  - 296
N2  - -
ER  - 

TY  - CONF
T1  - TGF-beta and mycobacterial infection
A1  - Roe T
A1  - Lukey P
A1  - Muller I
A1  - Young D
U1  - 5th International Congress on the Pathogenesis of Mycobacterial infections
AD  - Stockholm, Sweden
Y1  - 2002///
Y2  - 2002/06/27/
N2  - -
ER  - 

TY  - CONF
T1  - Does intensive feeding support improve nutritional status and outcome in acutely ill older in-patients?
A1  - Hickson M
A1  - Nicholl CG
A1  - Bulpitt CJ
A1  - Nunes M
A1  - Peters R
A1  - Cooke J
A1  - Frost G
U1  - Nutrition Society
AD  - London
Y1  - 2002///
Y2  - //
VL  - 61
PB  - Proc.Nut.Soc.
N2  - -
ER  - 

TY  - CONF
T1  - Pelvic nerve plexus trauma at radical hysterectomy and simple hysterectomy - The nerve content of the uterine supporting ligaments
A1  - Butler-Manuel, SA
A1  - Buttery, LDK
A1  - A'Hern, RP
A1  - Polak, JM
A1  - Barton, DPJ
U1  - 46th Annual Meeting of the Society-for-Gynecologic-Investigation
Y1  - 2000/08/15/
Y2  - //
VL  - 89
SP  - 834
EP  - 841
N2  - -
ER  - 

TY  - CONF
T1  - Vaccinia virus entry and exit
A1  - Smith, GL
A1  - Vanderplasschen, A
U1  - 2nd ICGEB-UCI Virology Symposium
Y1  - 2000///
Y2  - //
SP  - 25
EP  - 42
N2  - -
ER  - 

TY  - CONF
T1  - Leptin, starvation and the mouse gut
A1  - Chaudhary, M
A1  - FitzGerald, AJ
A1  - Mandir, N
A1  - Howard, JK
A1  - Lord, GM
A1  - Ghatei, MA
A1  - Bloom, SR
A1  - Goodlad, RA
U1  - 3rd Conference on Food and Cancer Prevention
Y1  - 2000///
Y2  - //
SP  - 314
EP  - 319
N2  - -
ER  - 

TY  - CONF
T1  - Identification of the zinc binding protein in a child with hyperzincaemia as calprotectin (MRP8/MRP14)
A1  - Sampson, B
A1  - Richmond, P
A1  - Golden, BE
A1  - Fagerhol, MK
A1  - Beattie, JH
A1  - Kovar, IZ
U1  - 10th International Symposium on Trace Elements in Man and Animals
Y1  - 2000///
Y2  - //
SP  - 1031
EP  - 1034
N2  - -
ER  - 

TY  - CONF
T1  - Metallothionein, calmodulin, and trace elements in healing skin wounds
A1  - Sampson, B
A1  - Lansdown, A
A1  - Rowe, A
U1  - 10th International Symposium on Trace Elements in Man and Animals
Y1  - 2000///
Y2  - //
SP  - 1038
EP  - 1038
N2  - -
ER  - 

TY  - CONF
T1  - Co-convenor Joint meeting of RSTMH/Wellcome Trust/UK MRC/DFID
A1  - Moore DA
U1  - Working in the tropics - how to do it
Y1  - 2000///
Y2  - 2000/05/09/
N2  - -
ER  - 

TY  - CONF
T1  - Action and interaction of metal ions in intact and wounded skin
A1  - Lansdown ABG
AD  - Bangkok, Thailand
J1  - Proceedings of the 4th Princess Chulabhorn International Science Congress, "Chemicals in the 21st Century"
Y1  - 1999///
N2  - -
ER  - 

TY  - CONF
T1  - High-dose melphalan and stem cell rescue for AL amyloidosis
A1  - Gillmore, JD
A1  - Apperley, JF
A1  - Craddock, C
A1  - Madhoo, S
A1  - Pepys, MB
A1  - Hawkins, PN
U1  - VIIIth International Symposium on Amyloidosis
Y1  - 1999///
Y2  - //
SP  - 102
EP  - 104
N2  - -
ER  - 

TY  - CONF
T1  - Immunoglobulin gene rearrangement in AL amyloidosis
A1  - Abusedra, A
A1  - Vulliamy, T
A1  - Gilmore, JD
A1  - Bybee, A
A1  - Hawkins, PN
A1  - Laffan, M
A1  - Apperley, JF
U1  - VIIIth International Symposium on Amyloidosis
Y1  - 1999///
Y2  - //
SP  - 124
EP  - 126
N2  - -
ER  - 

TY  - CONF
T1  - Macrophage cell cultures continue to produce infectious HIV-1 long after acute cytopathic infection has subsided
A1  - Teo, I
A1  - Choi, JW
A1  - Shaunak, S
U1  - 4th European Conference on Experimental AIDS Research
Y1  - 1999///
Y2  - //
SP  - 177
EP  - 181
N2  - -
ER  - 

TY  - CONF
T1  - Targeting HIV-1 replication in gut-associated lymphoid tissue
A1  - Shaunak, S
A1  - Waterworth, C
A1  - Lynn, WA
U1  - 4th European Conference on Experimental AIDS Research
Y1  - 1999///
Y2  - //
SP  - 163
EP  - 166
N2  - -
ER  - 

TY  - CONF
T1  - Tissue macrophages release MIP-1 alpha and MIP-1 beta but not TNF-alpha, IL-4, IL-6 or IFN-gamma after the internalisation of dextrin 2-sulphate
A1  - Thornton, M
A1  - Krausz, T
A1  - Shaunak, S
U1  - 4th European Conference on Experimental AIDS Research
Y1  - 1999///
Y2  - //
SP  - 183
EP  - 188
N2  - -
ER  - 

TY  - CONF
T1  - Glucagon like peptide-1 (GLP-1), Neuropeptide Y (NPY) and Melanin Concentrating Hormone (MCH) in the hypothalamic regulation of food intake
A1  - Small, CJ
A1  - Rossi, M
A1  - Bloom, SR
U1  - 8th International Congress on Obesity
Y1  - 1999///
Y2  - //
SP  - 279
EP  - 288
N2  - -
ER  - 

TY  - CONF
T1  - Metabolism and genotoxicity of food-derived heterocyclic amines
A1  - Gooderham, NJ
A1  - Lynch, AM
A1  - Yadollahi-Farsani, M
A1  - Murray, S
A1  - Boobis, AR
A1  - Davies, DS
U1  - Symposium on Drug Metabolism - Towards the Next Millennium
Y1  - 1998///
Y2  - //
VL  - 25
SP  - 127
EP  - 136
N2  - -
ER  - 

TY  - CONF
T1  - Development of a CTL inducing vaccine against Plasmodium falciparum using a combination of delivery systems
A1  - Gilbert, SC
A1  - Schneider, J
A1  - Hannan, CM
A1  - Plebanski, M
A1  - Neuman, V
A1  - Degano, P
A1  - Blanchard, TJ
A1  - Becker, M
A1  - Smith, GL
A1  - Hill, AVS
U1  - 9th International Congress of Parasitology (ICOPA IX)
Y1  - 1998///
Y2  - //
SP  - 439
EP  - 444
N2  - -
ER  - 

TY  - CONF
T1  - Investigations in a child with hyperzincaemia: Partial characterisation of an abnormal zinc binding protein, kinetics and studies of liver pathology
A1  - Sampson, B
A1  - Kovar, IZ
A1  - Beattie, JH
A1  - McArdle, HJ
A1  - Rauscher, A
A1  - Fairweather-Tait, SJ
A1  - Jasani, B
U1  - 9th International Symposium on Trace Elements in Man and Animals (TEMA 9)
Y1  - 1997///
Y2  - //
SP  - 484
EP  - 486
N2  - -
ER  - 

TY  - CONF
T1  - Mammalian in vitro systems: predictive value in drug metabolism
A1  - Boobis, AR
U1  - 2nd World Congress on Alternatives and Animal Use in the Life Sciences
Y1  - 1997///
Y2  - //
VL  - 27
SP  - 825
EP  - 833
N2  - -
ER  - 

TY  - JFULL
T1  - Incidence of hyperthyroidism after unrelated donor allogeneic stem cell transplantation.
A1  - Perz, JB
A1  - Marin, D
A1  - Szydlo, RM
A1  - Giles, C
A1  - Olavarria, E
A1  - Williams, G
A1  - Apperley, JF
J1  - Leuk Res
Y1  - 2007/10//
VL  - 31
SN  - 0145-2126
SP  - 1433
EP  - 1436
N2  - We report on three patients who developed overt thyrotoxicosis after volunteer unrelated donor bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia shortly after the onset of chronic graft versus host disease. In all three cases, the etiology of hyperthyroidism is likely to be a combination of toxic factors and an immune process. Systematic evaluation of thyroid function tests in 97 unrelated allograft recipients from our center who survived at least 100 days from stem cell or bone marrow transplantation for hematological diseases gave a rate of overt thyrotoxicosis at 3.1% in this cohort.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17433437&query_hl=1
ER  - 

TY  - JFULL
T1  - Structure of CrmE, a Virus-encoded Tumour Necrosis Factor Receptor.
A1  - Graham, SC
A1  - Bahar, MW
A1  - Abrescia, NG
A1  - Smith, GL
A1  - Stuart, DI
A1  - Grimes, JM
J1  - J Mol Biol
Y1  - 2007/09/21/
VL  - 372
SN  - 0022-2836
SP  - 660
EP  - 671
N2  - Vaccinia virus (VACV), the smallpox vaccine, encodes many proteins that subvert the host immune response. One of these, cytokine response modifier E (CrmE), is secreted by infected cells and protects these cells from apoptotic challenge by tumour necrosis factor alpha (TNFalpha). We have expressed recombinant CrmE from VACV strain Lister in Escherichia coli, shown that the purified protein is monomeric in solution and competent to bind TNFalpha, and solved the structure to 2.0 A resolution. This is the first structure of a virus-encoded tumour necrosis factor receptor (TNFR). CrmE shares significant sequence similarity with mammalian type 2 TNF receptors (TNFSFR1B, p75; TNFR type 2). The structure confirms that CrmE adopts the canonical TNFR fold but only one of the two "ligand-binding" loops of TNFRSF1A is conserved in CrmE, suggesting a mechanism for the higher affinity of poxvirus TNFRs for TNFalpha over lymphotoxin-alpha. The roles of dimerisation and pre-ligand-assembly domains (PLADs) in poxvirus and mammalian TNFR activity are discussed.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17681535&query_hl=1
ER  - 

TY  - JFULL
T1  - Alternative Neisseria spp. type IV pilin glycosylation with a glyceramido acetamido trideoxyhexose residue.
A1  - Chamot-Rooke, J
A1  - Rousseau, B
A1  - Lanternier, F
A1  - Mikaty, G
A1  - Mairey, E
A1  - Malosse, C
A1  - Bouchoux, G
A1  - Pelicic, V
A1  - Camoin, L
A1  - Nassif, X
A1  - Duménil, G
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/09/05/
SN  - 0027-8424
N2  - The importance of protein glycosylation in the interaction of pathogenic bacteria with their host is becoming increasingly clear. Neisseria meningitidis, the etiological agent of cerebrospinal meningitis, crosses cellular barriers after adhering to host cells through type IV pili. Pilin glycosylation genes (pgl) are responsible for the glycosylation of PilE, the major subunit of type IV pili, with the 2,4-diacetamido-2,4,6-trideoxyhexose residue. Nearly half of the clinical isolates, however, display an insertion in the pglBCD operon, which is anticipated to lead to a different, unidentified glycosylation. Here the structure of pilin glycosylation was determined in such a strain by "top-down" MS approaches. MALDI-TOF, nanoelectrospray ionization Fourier transform ion cyclotron resonance, and nanoelectrospray ionization quadrupole TOF MS analysis of purified pili preparations originating from N. meningitidis strains, either wild type or deficient for pilin glycosylation, revealed a glycan mass inconsistent with 2,4-diacetamido-2,4,6-trideoxyhexose or any sugar in the databases. This unusual modification was determined by in-source dissociation of the sugar from the protein followed by tandem MS analysis with collision-induced fragmentation to be a hexose modified with a glyceramido and an acetamido group. We further show genetically that the nature of the sugar present on the pilin is determined by the carboxyl-terminal region of the pglB gene modified by the insertion in the pglBCD locus. We thus report a previously undiscovered monosaccharide involved in posttranslational modification of type IV pilin subunits by a MS-based approach and determine the molecular basis of its biosynthesis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17804791&query_hl=1
ER  - 

TY  - JFULL
T1  - Structural insights into the transcriptional and translational roles of Ebp1.
A1  - Monie, TP
A1  - Perrin, AJ
A1  - Birtley, JR
A1  - Sweeney, TR
A1  - Karakasiliotis, I
A1  - Chaudhry, Y
A1  - Roberts, LO
A1  - Matthews, S
A1  - Goodfellow, IG
A1  - Curry, S
J1  - EMBO J
Y1  - 2007/09/05/
VL  - 26
SN  - 0261-4189
SP  - 3936
EP  - 3944
N2  - The ErbB3-binding protein 1 (Ebp1) is an important regulator of transcription, affecting eukaryotic cell growth, proliferation, differentiation and survival. Ebp1 can also affect translation and cooperates with the polypyrimidine tract-binding protein (PTB) to stimulate the activity of the internal ribosome entry site (IRES) of foot-and-mouth disease virus (FMDV). We report here the crystal structure of murine Ebp1 (p48 isoform), providing the first glimpse of the architecture of this versatile regulator. The structure reveals a core domain that is homologous to methionine aminopeptidases, coupled to a C-terminal extension that contains important motifs for binding proteins and RNA. It sheds new light on the conformational differences between the p42 and p48 isoforms of Ebp1, the disposition of the key protein-interacting motif ((354)LKALL(358)) and the RNA-binding activity of Ebp1. We show that the primary RNA-binding site is formed by a Lys-rich motif in the C terminus and mediates the interaction with the FMDV IRES. We also demonstrate a specific functional requirement for Ebp1 in FMDV IRES-directed translation that is independent of a direct interaction with PTB.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17690690&query_hl=1
ER  - 

TY  - JFULL
T1  - A protein kinase Cepsilon /anti-apoptotic kinase signalling complex protects human vascular endothelial cells against apoptosis through induction of Bcl-2.
A1  - Steinberg, R
A1  - Harari, OA
A1  - Lidington, EA
A1  - Boyle, JJ
A1  - Nohadani, M
A1  - Samarel, AM
A1  - Ohba, M
A1  - Haskard, DO
A1  - Mason, JC
J1  - J Biol Chem
Y1  - 2007/09/04/
SN  - 0021-9258
N2  - Endothelial cell apoptosis is associated with vascular injury and predisposes to atherogenesis. EC express anti-apoptotic genes including Bcl-2, Bcl-X(L) and survivin, which also contribute to angiogenesis and vascular remodelling. We report a central role for PKCepsilon in the regulation of Bcl-2 expression and cytoprotection of human vascular endothelium against apoptosis. Using myristoylated inhibitory peptides, a predominant role for PKCepsilon in VEGF-mediated endothelial resistance to apoptosis was revealed. Immunoblotting of endothelial cells infected with an adenovirus expressing a constitutively-active form of PKCepsilon (Adv-PKCepsilon-CA) or control Adv-beta-gal demonstrated a 3-fold, PKCepsilon-dependent increase in Bcl-2 expression, with no significant change in Bcl-X(L), Bad, Bak or Bax. The induction of Bcl-2 inhibited apoptosis induced by serum starvation or etoposide, and PKCepsilon activation attenuated etoposide-induced caspase-3 cleavage. The functional role of Bcl-2 was confirmed with Bcl-2 antagonist HA-14-1. Inhibition of PI-3K attenuated VEGF-induced protection against apoptosis and this was rescued by over-expression of CA-PKCepsilon, suggesting PKCepsilon acts downstream of PI-3K. Co-immunoprecipitation studies demonstrated a physical interaction between PKCepsilon and Akt, which resulted in formation of a signaling complex, leading to optimal induction of Bcl-2. This study reveals a pivotal role for PKCepsilon in endothelial cell cytoprotection against apoptosis. We demonstrate that PKCepsilon forms a signalling complex and acts co-operatively with Akt to protect human vascular endothelial cells against apoptosis, through induction of the anti-apoptotic protein Bcl-2 and inhibition of caspase-3 cleavage.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17785460&query_hl=1
ER  - 

TY  - JFULL
T1  - Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graft-versus-host disease.
A1  - Tisato, V
A1  - Naresh, K
A1  - Girdlestone, J
A1  - Navarrete, C
A1  - Dazzi, F
J1  - Leukemia
Y1  - 2007/09//
VL  - 21
SN  - 0887-6924
SP  - 1992
EP  - 1999
N2  - The immunosuppressive properties of mesenchymal stem cells (MSC) make them particularly attractive to manipulate graft-versus-host disease (GVHD). So far, the experience of using MSC to treat GVHD is limited to a few cases, controversial results come from preclinical models and several issues remain to be clarified. The present studies were designed to address these questions in a xenogenic model testing the ability of umbilical cord blood-derived MSC (UCB-MSC) to prevent and/or treat GVHD. Sublethally irradiatiated non-obese diabetic/severe combined immunodeficiency NOD/SCID mice transplanted with human peripheral blood mononuclear cells (huPBMC) showed extensive human T-cell proliferation in the peripheral blood, lymphoid and non-lymphoid tissues, which evolved in extensive GVHD (wasting, ruffled hair and hunched back). The mice treated with a single dose of UCB-MSC did not behave differently form the controls. However, when UCB-MSC were given at weekly intervals, there was a marked decrease in human T-cell proliferation and none of the mice developed GVHD. No therapeutic effect was obtained if UCB-MSC were administered at onset of GVHD. This work supports the clinical use of MSC in stem cell transplantation as a prophylaxis rather than treatment of GVHD.Leukemia (2007) 21, 1992-1999; doi:10.1038/sj.leu.2404847; published online 12 July 2007.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17625609&query_hl=1
ER  - 

TY  - JFULL
T1  - Sexual Dimorphism in Superantigen Shock Involves Elevated TNF-{alpha} and TNF-{alpha} induced Hepatic Apoptosis.
A1  - Faulkner, L
A1  - Altmann, DM
A1  - Ellmerich, S
A1  - Huhtaniemi, I
A1  - Stamp, G
A1  - Sriskandan, S
J1  - Am J Respir Crit Care Med
Y1  - 2007/09/01/
VL  - 176
SN  - 1073-449X
SP  - 473
EP  - 482
N2  - Rationale: There is conflicting evidence regarding sex differences in the outcome from severe sepsis and toxic shock. Superantigen-mediated toxic shock affects a higher proportion of female patients. Objectives: The objective of the current study was to investigate sexual dimorphism in superantigen-associated sepsis and in superantigen-mediated shock and to identify the key mechanisms responsible for this sex difference. Methods: We measured mortality and serum cytokines after induction of sepsis with isogenic superantigen-positive and superantigen-negative Streptococcus pyogenes in HLA class II transgenics. During superantigen-mediated toxic shock, we measured mortality, T-cell responses, systemic tumor necrosis factor (TNF)-alpha and TNF receptors, TNF-alpha-induced hepatocyte apoptosis, and conditioning of these responses by tamoxifen treatment. Measurements and Main Results: In both superantigen-associated sepsis and in superantigen-mediated shock, serum TNF-alpha was increased in females compared with males. This was not attributable to a detectable difference in splenic TNF-alpha transcription; rather, serum soluble TNF receptors were higher in males. Pretreatment of females with the estrogen receptor modulator tamoxifen increased serum soluble TNF receptors, reduced the early serum TNF-alpha response, and improved mortality in females challenged with staphylococcal enterotoxin B. Lethal superantigen shock was characterized by hepatocyte apoptosis, and was reproduced by injection of TNF-alpha. Females had enhanced susceptibility to TNF-alpha-mediated lethality. TNF-alpha-induced hepatocyte apoptosis was greater in females, and was reduced by tamoxifen pretreatment. Conclusions: Sexual dimorphism in experimental superantigen toxic shock results from increased systemic TNF-alpha in females, coupled with an increased susceptibility to TNF-alpha-induced hepatocyte apoptosis. Both processes are abrogated by estrogen receptor modulators.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17575097&query_hl=1
ER  - 

TY  - JFULL
T1  - Somatostatin receptor PET imaging with Gallium-68 labeled peptides.
A1  - Win, Z
A1  - Al-Nahhas, A
A1  - Rubello, D
A1  - Gross, MD
J1  - Q J Nucl Med Mol Imaging
Y1  - 2007/09//
VL  - 51
SN  - 1824-4785
SP  - 244
EP  - 250
N2  - Imaging somatostatin receptor status with(68)Ga labeled peptides has progressed rapidly over the last several years. It has generated great interest, and stimulated further research into the development of DOTA-derivative peptides. It has expanded our knowledge of receptor imaging and enhanced our appreciation of the difference between receptor-based and metabolic imaging, as well as more in-depth evaluation of tumor biology. The availability of the (68)Ge/(68)Ga generator provides an attractive alternative to cyclotron-based positron-emitters, especially if kit-based radiopharmaceutical formulations based upon (68)Ga are developed in the future.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17464267&query_hl=1
ER  - 

TY  - JFULL
T1  - CD154 induces a switch in pro-survival Bcl-2 family members in chronic lymphocytic leukaemia.
A1  - Willimott, S
A1  - Baou, M
A1  - Naresh, K
A1  - Wagner, SD
J1  - Br J Haematol
Y1  - 2007/09//
VL  - 138
SN  - 0007-1048
SP  - 721
EP  - 732
N2  - Chronic lymphocytic leukaemia cells survive and proliferate in patients but rapidly die in culture. The microenvironment that sustains leukaemic cells in vivo contains both stromal cell elements and T cells. We defined changes in Bcl-2 family protein expression on culture with CD40 ligand (CD154) expressed on mouse fibroblast L cells, and interleukin-4 (IL-4; CD154/IL-4 system): conditions that support survival and proliferation. Unexpectedly, Bcl-2 protein expression decreased whilst pro-survival Bcl-x(L) (as well as A1 and Mcl-1) increased. However, the CD154-L cell/IL-4 system also increased the pro-apoptotic proteins, Bid and Noxa, suggesting that an increased pool of pro-survival factors and not the effects of a single protein mediate survival. Most pro-apoptotic proteins were not induced in drug or spontaneous apoptosis, but expression of Bcl-x(S), a pro-apoptotic BCL2L1 isoform, was associated with cell death. This was post-transcriptionally controlled, and, therefore, alternative splicing at the Bcl-x locus appears to have a role in the regulation of chronic lymphocytic leukaemia (CLL) cell survival. This study demonstrated a switch in pro-survival proteins associated with the transition from quiescence to CD154-driven proliferation. CLL therapies targeting Bcl-2 may need to be modified to antagonize proliferation centre-specific pro-survival proteins.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17760804&query_hl=1
ER  - 

TY  - JFULL
T1  - New approaches to the treatment of dense deposit disease.
A1  - Smith, RJ
A1  - Alexander, J
A1  - Barlow, PN
A1  - Botto, M
A1  - Cassavant, TL
A1  - Cook, HT
A1  - de Córdoba, SR
A1  - Hageman, GS
A1  - Jokiranta, TS
A1  - Kimberling, WJ
A1  - Lambris, JD
A1  - Lanning, LD
A1  - Levidiotis, V
A1  - Licht, C
A1  - Lutz, HU
A1  - Meri, S
A1  - Pickering, MC
A1  - Quigg, RJ
A1  - Rops, AL
A1  - Salant, DJ
A1  - Sethi, S
A1  - Thurman, JM
A1  - Tully, HF
A1  - Tully, SP
A1  - van der Vlag, J
A1  - Walker, PD
A1  - Würzner, R
A1  - Zipfel, PF
A1  - Dense Deposit Disease Focus Group
J1  - J Am Soc Nephrol
Y1  - 2007/09//
VL  - 18
SN  - 1046-6673
SP  - 2447
EP  - 2456
N2  - The development of clinical treatment protocols usually relies on evidence-based guidelines that focus on randomized, controlled trials. For rare renal diseases, such stringent requirements can represent a significant challenge. Dense deposit disease (DDD; also known as membranoproliferative glomerulonephritis type II) is a prototypical rare disease. It affects only two to three people per million and leads to renal failure within 10 yr in 50% of affected children. On the basis of pathophysiology, this article presents a diagnostic and treatment algorithm for patients with DDD. Diagnostic tests should assess the alternative pathway of complement for abnormalities. Treatment options include aggressive BP control and reduction of proteinuria, and on the basis of pathophysiology, animal data, and human studies, plasma infusion or exchange, rituximab, sulodexide, and eculizumab are additional options. Criteria for treatment success should be prevention of progression as determined by maintenance or improvement in renal function. A secondary criterion should be normalization of activity levels of the alternative complement pathway as measured by C3/C3d ratios and C3NeF levels. Outcomes should be reported to a central repository that is now accessible to all clinicians. As the understanding of DDD increases, novel therapies should be integrated into existing protocols for DDD and evaluated using an open-label Bayesian study design.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17675665&query_hl=1
ER  - 

TY  - JFULL
T1  - Anatomic and functional imaging in the management of lymphoma.
A1  - Al-Nahhas, A
A1  - Win, Z
A1  - Al-Sayed, Y
A1  - Khan, S
A1  - Singh, A
A1  - Rubello, D
A1  - Gishen, P
J1  - Q J Nucl Med Mol Imaging
Y1  - 2007/09//
VL  - 51
SN  - 1824-4785
SP  - 251
EP  - 259
N2  - Lymphoma has become one of the most successfully treated malignancies. The success of treatment and long-term prognosis depend on accurate staging in which imaging plays a pivotal role. In addition to staging, imaging assists in the evaluation of early and late response to therapy, detecting disease activity in a residual mass and locating sites of recurrence. The mainstay of imaging remains computed tomography (CT), which has replaced lymphangiography, and staging laparotomy. Magnetic resonance imaging (MRI) has additional value in detecting disease in bone marrow, the musculoskeletal and central nervous system. Recent technical developments in CT and MRI have improved acquisition times and resolution, but the main drawback of cross-sectional imaging techniques is their reliance on size criteria to define disease, with consequent failure to detect disease in small lymph nodes and exclude disease in large, but treated, masses. Diffuse visceral involvement is likewise difficult to detect by both modalities. Functional imaging with nuclear medicine techniques offers an answer to these problems. Imaging with the fluorinated glucose analogue, [(18)F]FDG positron emission tomography (PET), can detect metabolically active disease by its increased glycolysis that is proportional to mitotic activity. It can separate high from low-grade tumors and aid in prognostication. Recent publications suggest that imaging with [(18)F]FDG PET should be an important component in staging; assessment of response to therapy and restaging. Like other imaging modalities, it has its own drawbacks including inability to detect very small lesions (<5 mm) and reduced specificity due to increased uptake in metabolically active inflammatory and infective tissues. The new generation of hybrid PET-CT combines anatomical and functional imaging and is considered the state-of-the-art imaging technique for the assessment of lymphoma and other malignancies.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17538524&query_hl=1
ER  - 

TY  - JFULL
T1  - The fraction 1 and V protein antigens of Yersinia pestis activate dendritic cells to induce primary T cell responses.
A1  - Kingston, R
A1  - Burke, F
A1  - Robinson, JH
A1  - Bedford, PA
A1  - Jones, SM
A1  - Knight, SC
A1  - Williamson, ED
J1  - Clin Exp Immunol
Y1  - 2007/09//
VL  - 149
SN  - 0009-9104
SP  - 561
EP  - 569
N2  - The F1 and V antigens of Yersinia pestis, despite acting as virulence factors secreted by the organism during infection, also combine to produce an effective recombinant vaccine against plague, currently in clinical trial. The protective mechanisms induced by rF1 + rV probably involve interactions with dendritic cells (DC) as antigen uptake, processing and presenting cells. To study such interactions, naive ex vivo DC from bone marrow, spleen and lymph node were cultured with rF1, rV or combined antigens and demonstrated to secrete interleukin (IL)-4 and IL-12 into the culture supernatant. Cytokine production in response to pulsing was dependent on the maturity of the bone marrow-derived DC culture, so that pulsed 8-day-old cultures had accumulated significantly more intracellular IL-4 and IL-12 than unpulsed cells. DC, pulsed with rF1 + rV for 2-24 h, were able to prime naive autologous lymph node T cells to proliferate in an antigen dose-dependent manner, with an order of potency of 3d bone marrow-derived DC (BMDC) > 7d BMDC > splenic DC. Significantly, cell-free supernatants from rF1 + rV-pulsed BMDC and splenic DC were also able to induce specific primary responses effectively in naive T cells, suggesting that these supernatants contained stimulatory factor(s). This study suggests an important role for DC, or factors secreted by them, in the induction of protective immunity to plague by the rF1 and rV antigens.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17645768&query_hl=1
ER  - 

TY  - JFULL
T1  - Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3'-deoxy-3'-[(18)F]fluorothymidine positron emission tomography.
A1  - Kenny, L
A1  - Coombes, RC
A1  - Vigushin, DM
A1  - Al-Nahhas, A
A1  - Shousha, S
A1  - Aboagye, EO
J1  - Eur J Nucl Med Mol Imaging
Y1  - 2007/09//
VL  - 34
SN  - 1619-7070
SP  - 1339
EP  - 1347
N2  - PURPOSE: 3'-Deoxy-3'-[(18)F]fluorothymidine positron emission tomography ([(18)F]FLT-PET) has been developed for imaging cell proliferation and findings correlate strongly with the Ki-67 labelling index in breast cancer. The aims of this pilot study were to define objective criteria for [(18)F]FLT response and to examine whether [(18)F]FLT-PET can be used to quantify early response of breast cancer to chemotherapy. METHODS: Seventeen discrete lesions in 13 patients with stage II-IV breast cancer were scanned prior to and at 1 week after treatment with combination 5-fluorouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. The uptake at 90 min (SUV(90)) and irreversible trapping (K (i)) of [(18)F]FLT were calculated for each tumour. The reproducibility of [(18)F]FLT-PET was determined in nine discrete lesions from eight patients who were scanned twice before chemotherapy. Clinical response was assessed at 60 days after commencing FEC. RESULTS: All tumours showed [(18)F]FLT uptake and this was reproducible in serial measurements (SD of mean % difference = 10.5% and 15.1%, for SUV(90) and K (i), respectively; test-retest correlation coefficient >/=0.97). Six patients had a significant clinical response (complete or partial) at day 60; these patients also had a significant reduction in [(18)F]FLT uptake at 1 week. Decreases in K (i) and SUV(90) at 1 week discriminated between clinical response and stable disease (p = 0.022 for both parameters). In three patients with multiple lesions there was a mixed [(18)F]FLT response in primary tumours and metastases. [(18)F]FLT response generally preceded tumour size changes. CONCLUSION: [(18)F]FLT-PET can detect changes in breast cancer proliferation at 1 week after FEC chemotherapy.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17333178&query_hl=1
ER  - 

TY  - JFULL
T1  - Recent advances in the expression, evolution, and dynamics of prokaryotic genomes.
A1  - Arraiano, CM
A1  - Bamford, J
A1  - Brüssow, H
A1  - Carpousis, AJ
A1  - Pelicic, V
A1  - Pflüger, K
A1  - Polard, P
A1  - Vogel, J
J1  - J Bacteriol
Y1  - 2007/09//
VL  - 189
SN  - 0021-9193
SP  - 6093
EP  - 6100
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17601780&query_hl=1
ER  - 

TY  - JFULL
T1  - Could a virus contribute to weight gain?
A1  - Vasilakopoulou, A
A1  - le Roux, CW
J1  - Int J Obes (Lond)
Y1  - 2007/09//
VL  - 31
SN  - 0307-0565
SP  - 1350
EP  - 1356
N2  - Objective:Obesity is a serious public health problem associated with increased morbidity and mortality. Although the causes for obesity are unclear, it seems that environmental, genetic, neural and endocrine factors contribute to its development. However, the rapid global spread of obesity resembles epidemiologically the spread of an infectious disease. Thus far, little consideration has been given to the possibility that the epidemic of obesity could be due to an infectious agent. Seven viruses and a scrapie agent have been implicated in obesity.Design:This review evaluates the infectious pathogens and the evidence that these viruses are associated with obesity and concludes that a strong evidence base is emerging that associates certain viruses with obesity.Conclusion:More work is however required to elucidate the mechanisms of weight gain after viral infection. In the mean time, discounting viruses as a contributing factor to obesity would deprive us of a potential new avenue of investigating and treating the ever increasing epidemic of obesity.International Journal of Obesity (2007) 31, 1350-1356; doi:10.1038/sj.ijo.0803623; published online 10 April 2007.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17420782&query_hl=1
ER  - 

TY  - JFULL
T1  - Effect of host lactate on gonococci and meningococci: new concepts on the role of metabolites in pathogenicity.
A1  - Smith, H
A1  - Tang, CM
A1  - Exley, RM
J1  - Infect Immun
Y1  - 2007/09//
VL  - 75
SN  - 0019-9567
SP  - 4190
EP  - 4198
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17562766&query_hl=1
ER  - 

TY  - JFULL
T1  - Multiple myeloma with bone marrow extracellular crystal deposition.
A1  - Brodie, C
A1  - Agrawal, S
A1  - Rahemtulla, A
A1  - O'shea, D
A1  - Lampert, I
A1  - Naresh, KN
J1  - J Clin Pathol
Y1  - 2007/09//
VL  - 60
SN  - 0021-9746
SP  - 1064
EP  - 1065
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17496192&query_hl=1
ER  - 

TY  - JFULL
T1  - The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma.
A1  - Terpos, E
A1  - Dimopoulos, MA
A1  - Sezer, O
J1  - Leukemia
Y1  - 2007/09//
VL  - 21
SN  - 0887-6924
SP  - 1875
EP  - 1884
N2  - Immunomodulatory drugs (IMiDs) and bortezomib have been recently used in the management of patients with both newly diagnosed and relapsed/refractory multiple myeloma. Except of their direct anti-myeloma effect, these agents also alter the interactions between myeloma cells and marrow microenvironment. Several recent studies have investigated their potential effect on myeloma bone disease. Preclinical studies have demonstrated that IMiDs reduce osteoclast formation and function in vitro. Clinical studies have confirmed that thalidomide reduces markers of bone resorption, while lenalidomide induces osteoclast arrest in myeloma patients. However, IMiDs seem to have no effect on osteoblast exhaustion present in myeloma. The proteasome inhibitor bortezomib restores abnormal bone remodeling through the inhibition of osteoclast function and the increase in osteoblast differentiation and activity in vitro. In myeloma patients, bortezomib reduces biochemical markers of bone resorption and normalizes the RANKL/osteoprotegerin ratio, while at the same time increases bone formation markers reducing levels of dickkopf-1 protein. Whether these effects are direct and not only a consequence of the agents' antimyeloma activity is not totally clear. This review summarizes all available data for these attractive agents that combine potent anti-myeloma activity with beneficial effects on bone and may alter the way of management of myeloma-related bone disease.Leukemia (2007) 21, 1875-1884; doi:10.1038/sj.leu.2404843; published online 5 July 2007.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17611556&query_hl=1
ER  - 

TY  - JFULL
T1  - Multiple roles of the endothelial cell protein C receptor.
A1  - Crawley, JT
J1  - J Thromb Haemost
Y1  - 2007/09//
VL  - 5
SN  - 1538-7933
SP  - 1813
EP  - 1816
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17723118&query_hl=1
ER  - 

TY  - JFULL
T1  - The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo-Cushing's states.
A1  - Martin, NM
A1  - Dhillo, WS
A1  - Meeran, K
J1  - Clin Endocrinol (Oxf)
Y1  - 2007/09//
VL  - 67
SN  - 0300-0664
SP  - 476
EP  - 476
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17581261&query_hl=1
ER  - 

TY  - JFULL
T1  - The Transcriptional Corepressor RIP140 Regulates Oxidative Metabolism in Skeletal Muscle.
A1  - Seth, A
A1  - Steel, JH
A1  - Nichol, D
A1  - Pocock, V
A1  - Kumaran, MK
A1  - Fritah, A
A1  - Mobberley, M
A1  - Ryder, TA
A1  - Rowlerson, A
A1  - Scott, J
A1  - Poutanen, M
A1  - White, R
A1  - Parker, M
J1  - Cell Metab
Y1  - 2007/09//
VL  - 6
SN  - 1550-4131
SP  - 236
EP  - 245
N2  - Nuclear receptor signaling plays an important role in energy metabolism. In this study we demonstrate that the nuclear receptor corepressor RIP140 is a key regulator of metabolism in skeletal muscle. RIP140 is expressed in a fiber type-specific manner, and manipulation of its levels in null, heterozygous, and transgenic mice demonstrate that low levels promote while increased expression suppresses the formation of oxidative fibers. Expression profiling reveals global changes in the expression of genes implicated in both myofiber phenotype and metabolic functions. Genes involved in fatty-acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis are upregulated in the absence of RIP140. Analysis of cultured myofibers demonstrates that the changes in expression are intrinsic to muscle cells and that nuclear receptor-regulated genes are direct targets for repression by RIP140. Therefore RIP140 is an important signaling factor in the regulation of skeletal muscle function and physiology.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17767910&query_hl=1
ER  - 

TY  - JFULL
T1  - Histone deacetylase mediated transcriptional activation reduces proviral loads in HTLV-1-associated myelopathy/tropical spastic paraparesis patients.
A1  - Lezin, A
A1  - Gillet, N
A1  - Olindo, S
A1  - Signate, A
A1  - Grandvaux, N
A1  - Verlaeten, O
A1  - Belrose, G
A1  - Carvalho Bittencourt, M
A1  - Hiscott, J
A1  - Asquith, B
A1  - Burny, A
A1  - Smadja, D
A1  - Cesaire, R
A1  - Willems, L
J1  - Blood
Y1  - 2007/08/23/
SN  - 0006-4971
N2  - Epigenetic modifications of chromatin may play a role in maintaining viral latency and thus persistence of the Human T-lymphotropic virus type 1 which is responsible for HTLV-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). A major determinant of disease progression is increased peripheral blood proviral load (PVL), possibly via the accumulation of infected cells in the central nervous system (CNS) creating a damaging inflammatory response. Current therapeutic approaches which focus on reducing either cell proliferation, viral replication or tissue invasion, are still unsatisfactory. Contrasting with these inhibitory strategies, we evaluated the efficacy of a novel approach aimed, paradoxically, at activating viral gene expression in order to expose virus-positive cells to the host immune response. We used valproate (VPA), a histone deacetylase inhibitor which has been used for decades as a chronic, safe treatment for epileptic disorders. Based on in vitro and in vivo data, we provide evidence that transient activation of the latent viral reservoir causes its collapse, a process that may alleviate the condition of HAM/TSP. This represents the first such approach to treating HAM/TSP, using gene activation therapy to tilt the host-pathogen balance in favor of an existing antiviral response. This trial is registered at http://clinicaltrials.gov/ as #NCT00519181.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17717136&query_hl=1
ER  - 

TY  - JFULL
T1  - What can gallium-68 PET add to receptor and molecular imaging?
A1  - Al-Nahhas, A
A1  - Win, Z
A1  - Szyszko, T
A1  - Singh, A
A1  - Khan, S
A1  - Rubello, D
J1  - Eur J Nucl Med Mol Imaging
Y1  - 2007/08/23/
SN  - 1619-7070
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17713764&query_hl=1
ER  - 

TY  - JFULL
T1  - Genomic profile of chronic myelogenous leukemia: Imbalances associated with disease progression.
A1  - Brazma, D
A1  - Grace, C
A1  - Howard, J
A1  - Melo, JV
A1  - Holyoke, T
A1  - Apperley, JF
A1  - Nacheva, EP
J1  - Genes Chromosomes Cancer
Y1  - 2007/08/15/
VL  - 46
SN  - 1045-2257
SP  - 1039
EP  - 1050
N2  - The expression of the chimeric BCR/ABL1 fusion gene resulting from t(9;22)(q34;q11) in chronic myelogenous leukemia (CML) is necessary for malignant transformation, but not sufficient to maintain disease progression. The appearance of various chromosomal and molecular alterations in the accelerated and terminal phase of CML is well documented, but evidence for causal relationship is largely lacking. We carried out a genome wide screening at a resolution of 1 Mb of 54 samples at different stages of CML together with 12 CML cell lines and found that disease progression is accompanied by a spectrum of recurrent genome imbalances. Among the most frequent are losses at 1p36, 5q21, 9p21, and 9q34 and gains at 1q, 8q24, 9q34, 16p, and 22q11, all of which were located with higher precision within the genome than previously possible. These genome imbalances are unique to CML cases with clinically manifested or suspected accelerated/blast stage alike, but not seen in chronic phase samples. Previously unrecognized cryptic imbalances occurring within the Ph-chromosome were also detected, although further scrutiny is required to pin-point gene involvement and seek association with disease features. Importantly, some of these imbalances were seen in the CD34(+) cells but not in the whole BM samples of patients in accelerated phase. Taken together, these findings highlight the potential of screening CD34(+) cells for genome wide imbalances associated with disease progression. Finally, the numerous single copy number variations recorded, many unique to this cohort of patients, raise the possible association of genome polymorphism and CML. (c) 2007 Wiley-Liss, Inc.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17696194&query_hl=1
ER  - 

TY  - JFULL
T1  - Abnormal Preantral Folliculogenesis in Polycystic Ovaries is Associated with Increased Granulosa Cell Division.
A1  - Stubbs, SA
A1  - Stark, J
A1  - Dilworth, SM
A1  - Franks, S
A1  - Hardy, K
J1  - J Clin Endocrinol Metab
Y1  - 2007/08/14/
SN  - 0021-972X
N2  - Context: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women but its etiology remains obscure. Recent data suggest that an intrinsic abnormality of early follicle development in the ovary is key to the pathogenesis of PCOS. We have recently found that in PCOS the proportion of primordial follicles is decreased with a reciprocal increase in the proportion of primary follicles. Objective: To examine whether the accelerated transition of follicles from primordial to primary stages in polycystic ovaries is due to increased granulosa cell (GC) division. Design: Comparison of expression of minichromosome maintenance protein 2 (MCM2; present in the nuclei of cells which are licensed to divide) in archive tissue from normal and polycystic ovaries. Setting: Laboratory-based study. Patients: 16 women with regular cycles (6 with normal and 10 with polycystic ovaries) and 5 anovulatory women with polycystic ovaries (anovPCO), classified histologically, with reference to menstrual history and ultrasound. Main outcome measure: Presence of MCM2 expression in GCs of 1371 follicles. Results: GC proliferation was increased in anovPCO compared with both normal and ovPCO, with an increased proportion of preantral follicles with MCM2-positive GCs (P </= 0.015). The number of GCs differed significantly between the three types of ovary at the transitional (P = 0.013) and primary (P = 0.0096) stages. This was accompanied by an altered relationship (P < 0.0001) between oocyte growth and GC division/cuboidalization. Conclusions: These findings provide evidence for increased GC proliferation in early growing follicles in PCOS. This offers an explanation for the increased proportion of primary follicles in PCOS.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17698906&query_hl=1
ER  - 

TY  - JFULL
T1  - PalC, One of Two Bro1 Domain Proteins in the Fungal pH Signalling Pathway, Localizes to Cortical Structures and Binds Vps32.
A1  - Galindo, A
A1  - Hervás-Aguilar, A
A1  - Rodríguez-Galán, O
A1  - Vincent, O
A1  - Arst, HN
A1  - Tilburn, J
A1  - Peñalva, MA
J1  - Traffic
Y1  - 2007/08/13/
SN  - 1398-9219
N2  - PalC, distantly related to Saccharomyces cerevisiae peripheral endosomal sorting complexes required for transport III (ESCRT-III) component Bro1p and one of six Aspergillus nidulans pH signalling proteins, contains a Bro1 domain. Green fluorescent protein (GFP)-tagged PalC is recruited to plasma membrane-associated punctate structures upon alkalinization, when pH signalling is active. PalC recruitment to these structures is dependent on the seven transmembrane domain (7-TMD) receptor and likely pH sensor PalH. PalC is a two-hybrid interactor of the ESCRT-III Vps20/Vps32 subcomplex and binds Vps32 directly. This binding is largely impaired by Pro439Phe, Arg442Ala and Arg442His substitutions in a conserved region mediating interaction of Bro1p with Vps32p, but these substitutions do not prevent cortical punctate localization, indicating Vps32 independence. In contrast, Arg442Delta impairs Vps32 binding and prevents PalC-GFP recruitment to cortical structures. pH signalling involves a plasma membrane complex including the 7-TMD receptor PalH and the arrestin-like PalF and an endosomal membrane complex involving the PalB protease, the transcription factor PacC and the Vps32 binding, Bro1-domain-containing protein PalA. PalC, which localizes to cortical structures and can additionally bind a component of ESCRT-III, has the features required to bridge these two entities. A likely S. cerevisiae orthologue of PalC has been identified, providing the basis for a unifying hypothesis of gene regulation by ambient pH in ascomycetes.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17696968&query_hl=1
ER  - 

TY  - JFULL
T1  - Tuberculosis antigen-specific immune responses can be detected using enzyme-linked immunospot technology in human immunodeficiency virus (HIV)-1 patients with advanced disease.
A1  - Clark, SA
A1  - Martin, SL
A1  - Pozniak, A
A1  - Steel, A
A1  - Ward, B
A1  - Dunning, J
A1  - Henderson, DC
A1  - Nelson, M
A1  - Gazzard, B
A1  - Kelleher, P
J1  - Clin Exp Immunol
Y1  - 2007/08/02/
SN  - 0009-9104
N2  - There are limited data on the efficacy of T cell-based assays to detect tuberculosis (TB) antigen-specific responses in immune-deficient human immunodeficiency virus (HIV) patients. The aim of this study is to determine whether TB antigen-specific immune responses can be detected in patients with HIV-1 infection, especially in those with advanced disease (CD4 T cell count < 300 cells/microl). An enzyme-linked immunospot (ELISPOT) assay, which detects interferon (IFN)-gamma secreted by T cells exposed to TB antigens, was used to assess specific immune responses in a prospective study of 201 HIV-1-infected patients with risk factors for TB infection, attending a single HIV unit. The performance of the ELISPOT assay to detect TB antigen-specific immune responses is independent of CD4 T cell counts in HIV-1 patients. The sensitivity and specificity of this assay for the diagnosis of active tuberculosis does not differ significantly from values obtained in immunocompetent subjects. The negative predictive value of the TB ELISPOT test is 98.2%. A positive predictive value of 86% for the diagnosis of active tuberculosis was found when the combined number of early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) IFN-gamma spots to CD4 T cell count ratio was > 1.5. TB antigen-specific immune responses can be detected in HIV patients with low CD4 T cell counts using ELISPOT technology in a routine diagnostic laboratory and is a useful test to exclude TB infection in immune-deficient HIV-1 patients. A combination of TB antigen-specific IFN-gamma responses and CD4 T cell counts has the potential to distinguish active tuberculosis from latent infection.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17672869&query_hl=1
ER  - 

TY  - JFULL
T1  - In vivo evidence for apoptosis in the bone marrow in systemic lupus erythematosus.
A1  - Hepburn, AL
A1  - Lampert, IA
A1  - Boyle, JJ
A1  - Horncastle, D
A1  - Ng, WF
A1  - Layton, M
A1  - Vyse, TJ
A1  - Botto, M
A1  - Mason, JC
J1  - Ann Rheum Dis
Y1  - 2007/08//
VL  - 66
SN  - 0003-4967
SP  - 1106
EP  - 1109
N2  - An increase in leucocyte apoptosis and impaired clearance of apoptotic cells has been observed in patients with systemic lupus erythematosus (SLE). Apoptotic cells are likely to be a key source of autoantigens in SLE as they express many of the nuclear autoantigens (in surface blebs and apoptotic bodies) that are relevant to this disease. The clearance of apoptotic cells is usually a rapid process, such that few cells are usually seen in the extracellular environment in vivo. We report a case in which multiple apoptotic bodies were observed in the bone marrow of a patient with SLE that was complicated by an immune-mediated pancytopenia. We have subsequently examined the frequency of apoptotic cells, identified morphologically, and by caspase-3 staining in bone-marrow trephine samples taken from patients with SLE over a 10-year period of follow-up. A high proportion of bone marrows contained apoptotic debris. The novel demonstration of apoptotic bodies in vivo in patients with SLE is unusual and supports the notion that the marrow may be a target organ in the disease. Their abundance is also consistent with the hypothesis that normal clearance mechanisms are defective and/or overwhelmed in SLE.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17277002&query_hl=1
ER  - 

TY  - JFULL
T1  - Leucocyte common antigen (CD45) and CD5 positivity in an "undifferentiated" carcinoma: a potential diagnostic pitfall.
A1  - Ngo, N
A1  - Patel, K
A1  - Isaacson, PG
A1  - Naresh, KN
J1  - J Clin Pathol
Y1  - 2007/08//
VL  - 60
SN  - 0021-9746
SP  - 936
EP  - 938
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17660336&query_hl=1
ER  - 

TY  - JFULL
T1  - Increased detection of Clostridium difficile during a norovirus outbreak.
A1  - Barrett, SP
A1  - Holmes, AH
A1  - Newsholme, WA
A1  - Richards, M
J1  - J Hosp Infect
Y1  - 2007/08//
VL  - 66
SN  - 0195-6701
SP  - 394
EP  - 395
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17669553&query_hl=1
ER  - 

TY  - JFULL
T1  - Assessment of a chemically induced model of lung squamous cell carcinoma in mice by 18F-FDG small-animal PET.
A1  - Ambrosini, V
A1  - Nanni, C
A1  - Pettinato, C
A1  - Fini, M
A1  - D'Errico, A
A1  - Trepidi, S
A1  - Spinelli, A
A1  - Al-Nahhas, A
A1  - Rubello, D
A1  - Zompatori, M
A1  - Fabbri, M
A1  - Franchi, R
A1  - Fanti, S
J1  - Nucl Med Commun
Y1  - 2007/08//
VL  - 28
SN  - 0143-3636
SP  - 647
EP  - 652
N2  - BACKGROUND: Small-animal imaging has become a relevant research field in pre-clinical oncology. In particular, metabolic information provided by small-animal positron emission tomography (PET) is very useful to closely monitor tumour growth and assess therapy response in murine models of human disease. There are various murine models for human lung adenocarcinoma, but those for squamous cell lung carcinoma, the most common form of human cancer, are lacking. AIM: To assess the feasibility of 18F-FDG small-animal PET to monitor tumour growth in a chemically induced model of squamous cell carcinoma of the lung. MATERIALS AND METHODS: Nineteen NIH Swiss mice were skin painted by N-nitroso-tris-chloroethylurea (NTCU) twice a week, with a 3 day interval, for 8 months and 10 NIH Swiss mice skin painted with NTCU solvent (acetone) were used as controls. 18F-FDG PET was performed under sevofluorane anaesthesia and oxygen supplementation at 2, 4, 6 and 8 months from initial treatment. Images were assessed by visual analysis and semi-quantitatively. When a diffuse distribution of tumour was noted, the mean of the counts/pixel measured at three lung levels, corrected for the effective dose injected and for decay, was used for comparison between mutagen-painted and control mice. Pathological evaluation was carried out from the time of the first positive PET results in a subgroup of the whole population to assess correlation with PET findings. Small animal CT was performed at 8 months in another subgroup. RESULTS: In both terms of visual analysis and measurement of total lung activity, 18F-FDG PET at 2 and 4 months from initial treatment were comparable in mutagen-painted and controls. At 6 months, PET images showed a faint and diffuse uptake over both lung fields in mutagen-painted mice with multiple focal areas of increased tracer uptake that merged into confluent masses at 8 months and seriously subverting lung architecture on computed tomography. Total lung activity was significantly higher in mutagen-painted versus control mice at 6 (P=0.00000668) and 8 months (P=0.00000043) from initial treatment and paralleled the progressive lung involvement and histological severity. CONCLUSIONS: 18F-FDG PET may be useful in the assessment of this chemically induced murine model of lung squamous cells carcinoma. The total lung activity may be used as a measure of tumour metabolic activity of the tumour-bearing animals and may be useful in new drug testing studies.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17625387&query_hl=1
ER  - 

TY  - JFULL
T1  - Astrocyte-leucocyte interactions and the mechanisms regulating matrix degradation in CNS tuberculosis.
A1  - Green, JA
A1  - Friedland, JS
J1  - Biochem Soc Trans
Y1  - 2007/08//
VL  - 35
SN  - 0300-5127
SP  - 686
EP  - 688
N2  - The CNS (central nervous system) has a unique pattern of immune response to infection. TB (tuberculosis) of the CNS is devastating with widespread tissue destruction. In TB, astrocyte-leucocyte interactions are key in regulating MMP (matrix metalloproteinase) activity and are regulated by complex signalling pathways. A synergistic interaction between interferon gamma and monocyte-derived mediators drives high-level astrocyte MMP-9 secretion; this and other networking effects are inhibited by steroids. Better understanding of regulatory mechanisms may identify potential switch points that could be future therapeutic targets.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635122&query_hl=1
ER  - 

TY  - JFULL
T1  - Graft versus lymphoma effect after early relapse following reduced-intensity sibling allogeneic stem cell transplantation for relapsed cytotoxic variant of mycosis fungoides.
A1  - Gabriel, IH
A1  - Olavarria, E
A1  - Jones, RR
A1  - Whittaker, S
A1  - Chaidos, A
A1  - Apperley, JF
J1  - Bone Marrow Transplant
Y1  - 2007/08//
VL  - 40
SN  - 0268-3369
SP  - 401
EP  - 403
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17589536&query_hl=1
ER  - 

TY  - JFULL
T1  - Separate cell culture conditions to promote proliferation or quiescent cell survival in chronic lymphocytic leukemia.
A1  - Willimott, S
A1  - Baou, M
A1  - Huf, S
A1  - Wagner, SD
J1  - Leuk Lymphoma
Y1  - 2007/08//
VL  - 48
SN  - 1042-8194
SP  - 1647
EP  - 1650
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17701602&query_hl=1
ER  - 

TY  - JFULL
T1  - Streptococcus pyogenes under pressure.
A1  - Turner, C
A1  - Sriskandan, S
J1  - Nat Med
Y1  - 2007/08//
VL  - 13
SN  - 1078-8956
SP  - 909
EP  - 910
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17680004&query_hl=1
ER  - 

TY  - JFULL
T1  - Bcl-6 and c-Myc are rarely co-expressed in adult diffuse large B-cell lymphoma.
A1  - Wagner, SD
A1  - Amen, F
A1  - Trivedi, PS
A1  - Horncastle, D
A1  - Elderfield, K
A1  - Naresh, KN
J1  - Leuk Lymphoma
Y1  - 2007/08//
VL  - 48
SP  - 1510
EP  - 1513
ER  - 

TY  - JFULL
T1  - Human health and endocrine disruption: a simple multicriteria framework for the qualitative assessment of end point specific risks in a context of scientific uncertainty.
A1  - Martin, OV
A1  - Lester, JN
A1  - Voulvoulis, N
A1  - Boobis, AR
J1  - Toxicol Sci
Y1  - 2007/08//
VL  - 98
SN  - 1096-6080
SP  - 332
EP  - 347
N2  - Endocrine disruption remains one of the most controversial contemporary environmental issues. While the desired level of protection is ultimately a societal choice, endocrine toxicity could result in a wide spectrum of adverse health effects. Although the application of the causal framework of weight-of-evidence approaches to complex toxicological issues has incited much interest, no international criteria or guidance have yet been developed. In this context, the evidence on end point-specific risks to human health contained in the International Program on Chemical Safety Global assessment of the State-of-Science on Endocrine Disruptors report was updated and assessed qualitatively using three simple criteria relevant to the practical application of the precautionary principle (PP): incidence trends, association, and consequence. The current degree of knowledge was then ranked according to ignorance, uncertainty, and risk. The main sources of scientific uncertainty in relation to incidence trends were associated with the evolution of diagnostic criteria or diagnostic tests, while genetic susceptibility is often proposed as an explanation for the wide geographic variations in the incidence of some diseases. Such genetic polymorphisms are also offered as a potential explanation for some of the inconsistent findings or lack of clear dose-response gradients described under the association criterion. The methodology yielded a relative paucity of data addressing directly the impact for adverse human health effect from both individual and public health perspectives. Results are discussed within the context of the application of the PP. Within a participatory context, this simple framework could provide a useful decision-making tool to both communicate scientific uncertainty to the wider public and manage uncertain risks.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17255114&query_hl=1
ER  - 

TY  - JFULL
T1  - ESR or CRP? A comparison of their clinical utility.
A1  - Osei-Bimpong, A
A1  - Meek, JH
A1  - Lewis, SM
J1  - Hematology
Y1  - 2007/08//
VL  - 12
SN  - 1607-8454
SP  - 353
EP  - 357
N2  - OBJECTIVE: To review the normal reference values for erythrocyte sedimentation rate (ESR) and the significance of high values in the elderly, to re-examine the correlation, if any, between ESR and C-reactive protein (CRP) and to compare their utility and limitations for both health screening and clinical management of patients. METHODS: CRP and ESR were measured in 295 blood samples from male and female subjects in whom their family doctors had found no clinically significant symptoms nor abnormal physical sign and in whom all other pathology tests gave normal results. None had been hospitalised during at least a six-week period prior to the study. RESULTS: The results showed a mean ESR of 10 mm/1 h (range 0-25) in both males and females below the age of 40 yrs; this increased with age, to a mean of 18 mm (range 0-35) by 60 yrs in both men and women. In the CRP test, 95% of the samples in the >40 yrs group had CRP range of 0-18 mg/l compared with 0-10 mg/l in the younger subjects. The distribution plot of CRP results showed a left skew with mode at about 2 mg/l, whereas the equivalent ESR distribution shows a broad plateau with less skew. Thus, there was more overlapping of the numerical values for ESR and CRP in subjects younger than 40 yrs, as compared with those over 40 yrs old in whom the two sets of measurements were well separated. The relative utility of the two tests in clinical management of patients was also discussed. Different rates of increase and subsequent fall in the test results were shown over several weeks on a patient with an acute infection. Initially, both tests were increased, but after antibiotic therapy the CRP returned to normal indicating that remission had occurred, whereas the ESR remained high, indicating persistence of the infection. A subsequent dramatic increase in CRP to 180 mg/l confirmed the re-infection that had been indicated earlier by the ESR. After further antibiotic therapy CRP fell to normal, followed later by a slower reduction in ESR to a normal value for the patient's age. CONCLUSION: This study confirms that after the age of 40, there is an age-related elevation of ESR, increasing steadily, especially after age 60 yrs. CRP is also affected by age, but to a much less extent. ESR and CRP appear to be equally useful and reliable as a screening test. Accordingly, in deciding which test should be carried out account must be taken of their relative convenience and cost. However, when required as a clinical test in the management of patients with specific diseases both tests should be carried out in tandem.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17654065&query_hl=1
ER  - 

TY  - JFULL
T1  - Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications.
A1  - Pradat, P
A1  - Tillmann, HL
A1  - Sauleda, S
A1  - Braconier, JH
A1  - Saracco, G
A1  - Thursz, M
A1  - Goldin, R
A1  - Winkler, R
A1  - Alberti, A
A1  - Esteban, JI
A1  - Hadziyannis, S
A1  - Rizzetto, M
A1  - Thomas, H
A1  - Manns, MP
A1  - Trepo, C
A1  - HENCORE Group
J1  - J Viral Hepat
Y1  - 2007/08//
VL  - 14
SN  - 1352-0504
SP  - 556
EP  - 563
N2  - The aims of the study were to verify the long-term effect of time on viral clearance in hepatitis C virus (HCV) patients and to find out factors possibly associated with disease progression. A total of 1641 patients recruited from eight European centres in 1996-1997 were re-analysed 5-7 years after inclusion. The occurrence of decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation was analysed in relation to different host and viral factors. Ninety-three per cent of the HCV patients who had cleared the virus (spontaneously or after antiviral therapy) remained HCV-RNA-negative during follow up and may be considered as 'cured'. Among patients who were sustained responders at inclusion, 2.3% developed liver complications during follow up, and 31% of non-responders did. Advanced age at infection and presence of the human leucocyte antigen (HLA) DRB1*1201-3 allele were possibly associated with a higher rate of progression to decompensated cirrhosis or HCC. Decompensated cirrhosis might be further associated with male gender, non-response to previous therapy, and lack of HLA DRB1*1301 allele, whereas HCC seems to be associated with the presence of the HLA DQ02 allele. Long-term follow up of HCV patients indicates that virological response persists over time and is associated with a very low incidence of liver complications. Advanced age at inclusion, advanced age at infection, viral genotype 1, non-response to previous therapy and possibly some specific HLA alleles are factors independently associated with a faster rate of progression towards liver complications. The large proportion of patients lost to follow up stresses the need for a strengthened and optimized management of HCV patients.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17650289&query_hl=1
ER  - 

TY  - JFULL
T1  - Parathyroid hormone assay predicts hypocalcaemia after total thyroidectomy.
A1  - Sywak, MS
A1  - Palazzo, FF
A1  - Yeh, M
A1  - Wilkinson, M
A1  - Snook, K
A1  - Sidhu, SB
A1  - Delbridge, LW
J1  - ANZ J Surg
Y1  - 2007/08//
VL  - 77
SN  - 1445-1433
SP  - 667
EP  - 670
N2  - BACKGROUND: Postoperative parathyroid gland function after total thyroidectomy (TT) has traditionally been monitored by the measurement of serum calcium concentrations. The purpose of this study is to determine whether measurement of parathyroid hormone (PTH) concentrations in the early postoperative period accurately predicts patients at risk of developing hypocalcaemia. METHODS: A prospective cohort study of patients undergoing TT was carried out. PTH concentrations were measured preoperatively and at 4 and 23 h postoperatively. Serum calcium concentration was measured preoperatively and twice daily for 48 h after surgery. RESULTS: One hundred patients undergoing TT were recruited into the study in the period June 2004 to July 2005. Benign multinodular goitre was the most common indication for surgery (77%). The incidence of temporary hypocalcaemia (Ca < 2.0 mmol/L) was 18%. The mean PTH concentration at 4 h after surgery was 22.3 ng/L and was not significantly different from the 23-h concentration of 23.2 ng/L (P = 0.18). A PTH concentration of < or = 3 ng/L measured at 4 h after surgery had a sensitivity, specificity and likelihood ratio of 0.71, 0.94 and 11.3, respectively, for predicting postoperative hypocalcaemia. The accuracy of a single PTH concentration at 4 h was good for predicting hypocalcaemia (area under receiver-operator characteristic curve 0.90; confidence interval 0.81-0.96). There was no significant difference in accuracy between the 4- and 24-h PTH concentrations (P = 0.14). CONCLUSIONS: A single measurement of PTH concentration in the early postoperative period after TT reliably predicts patients who are likely to develop hypocalcaemia. This approach facilitates early discharge and may decrease the need for multiple postoperative blood tests.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635281&query_hl=1
ER  - 

TY  - JFULL
T1  - Thyroid status during skeletal development determines adult bone structure and mineralization.
A1  - Bassett, JH
A1  - Nordström, K
A1  - Boyde, A
A1  - Howell, PG
A1  - Kelly, S
A1  - Vennström, B
A1  - Williams, GR
J1  - Mol Endocrinol
Y1  - 2007/08//
VL  - 21
SN  - 0888-8809
SP  - 1893
EP  - 1904
N2  - Childhood hypothyroidism delays ossification and bone mineralization, whereas adult thyrotoxicosis causes osteoporosis. To determine how effects of thyroid hormone (T3) during development manifest in adult bone, we characterized TRalpha1(+/m)beta(+/-) mice, which express a mutant T3 receptor (TR) alpha1 with dominant-negative properties due to reduced ligand-binding affinity. Remarkably, adult TRalpha1(+/m)beta(+/-) mice had osteosclerosis with increased bone mineralization even though juveniles had delayed ossification. This phenotype was partially normalized by transient T3 treatment of juveniles and fully reversed in compound TRalpha1(+/m)beta(-/-) mutant mice due to 10-fold elevated hormone levels that allow the mutant TRalpha1 to bind T3. By contrast, deletion of TRbeta in TRalpha1(+/+)beta(-/ -) mice, which causes a 3-fold increase of hormone levels, led to osteoporosis in adults but advanced ossification in juveniles. T3-target gene analysis revealed skeletal hypothyroidism in TRalpha1(m/+)beta(+/-) mice, thyrotoxicosis in TRalpha1(+/+)beta(-/-) mice, and euthyroidism in TRalpha1(+/)beta(-/-) double mutants. Thus, TRalpha1 regulates both skeletal development and adult bone maintenance, with euthyroid status during development being essential to establish normal adult bone structure and mineralization.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17488972&query_hl=1
ER  - 

TY  - JFULL
T1  - Diagnostic accuracy of 18F-FDG PET/CT in characterizing ovarian lesions and staging ovarian cancer: correlation with transvaginal ultrasonography, computed tomography, and histology.
A1  - Castellucci, P
A1  - Perrone, AM
A1  - Picchio, M
A1  - Ghi, T
A1  - Farsad, M
A1  - Nanni, C
A1  - Messa, C
A1  - Meriggiola, MC
A1  - Pelusi, G
A1  - Al-Nahhas, A
A1  - Rubello, D
A1  - Fazio, F
A1  - Fanti, S
J1  - Nucl Med Commun
Y1  - 2007/08//
VL  - 28
SN  - 0143-3636
SP  - 589
EP  - 595
N2  - AIMS: To (a) assess the accuracy of 18F-FDG PET/CT in distinguishing malignant from benign pelvic lesions, compared to transvaginal ultrasonography (TVUS) and (b) to establish the role of whole-body 18F-FDG PET/CT, compared to contrast enhanced computed tomography (CT), in staging patients with ovarian cancer. PATIENTS: Fifty consecutive patients with a pelvic lesion, already scheduled for surgery on the basis of physical examination, TVUS, and serum Ca125 levels, were enrolled in the study. Patients' age ranged between 23 and 89 years (mean 64). All patients underwent TVUS including a colour Doppler study followed by a thorax and abdominal CT scan, and whole-body 18F-FDG PET/CT within 2 weeks prior to surgery. Histological findings obtained at surgery were taken as the 'gold standard' to compare 18F-FDG PET/CT and TVUS, and 18F-FDG PET/CT vs. CT. When tissue analysis showed ovarian cancer, the accuracy of 18F-FDG PET/CT and CT were compared for the purpose of obtaining a precise staging. RESULTS: At surgery, the ovarian lesions were malignant in 32/50 patients (64%) and benign in the remaining 18/50 patients (36%). The sensitivity, specificity, NPV, PPV and accuracy of 18F-FDG PET/CT were 87%, 100%, 81%, 100% and 92%, respectively, compared with 90%, 61%, 78%, 80% and 80%, respectively, for TVUS. In staging ovarian cancer, 18F-FDG PET/CT results were concordant with final pathological staging in 22/32 (69%) patients while CT results were concordant in 17/32 (53%) patients. CT incorrectly down-staged four out of six stage IV patients by missing distant metastasis in the liver, pleura, mediastinum, and in left supraclavicular lymph nodes, which were correctly detected by 18F-FDG PET/CT. CONCLUSION: PET/CT with 18F-FDG provides additional value to TVUS for the differential diagnosis of benign from malignant pelvic lesions, and to CT for the staging of ovarian cancer patients.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17625380&query_hl=1
ER  - 

TY  - JFULL
T1  - Recovery of genetically defined murine norovirus in tissue culture by using a fowlpox virus expressing T7 RNA polymerase.
A1  - Chaudhry, Y
A1  - Skinner, MA
A1  - Goodfellow, IG
J1  - J Gen Virol
Y1  - 2007/08//
VL  - 88
SN  - 0022-1317
SP  - 2091
EP  - 2100
N2  - Despite the significant disease burden caused by human norovirus infection, an efficient tissue-culture system for these viruses remains elusive. Murine norovirus (MNV) is an ideal surrogate for the study of norovirus biology, as the virus replicates efficiently in tissue culture and a low-cost animal model is readily available. In this report, a reverse-genetics system for MNV is described, using a fowlpox virus (FWPV) recombinant expressing T7 RNA polymerase to recover genetically defined MNV in tissue culture for the first time. These studies demonstrated that approaches that have proved successful for other members of the family Caliciviridae failed to lead to recovery of MNV. This was due to our observation that vaccinia virus infection had a negative effect on MNV replication. In contrast, FWPV infection had no deleterious effect and allowed the recovery of infectious MNV from cells previously transfected with MNV cDNA constructs. These studies also indicated that the nature of the 3'-terminal nucleotide is critical for efficient virus recovery and that inclusion of a hepatitis delta virus ribozyme at the 3' end can increase the efficiency with which virus is recovered. This system now allows the recovery of genetically defined noroviruses and will facilitate the analysis of the effects of genetic variation on norovirus pathogenesis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17622609&query_hl=1
ER  - 

TY  - JFULL
T1  - C1q deficiency promotes the production of transgenic-derived IgM and IgG3 autoantibodies in anti-DNA knock-in transgenic mice.
A1  - Fossati-Jimack, L
A1  - Cortes-Hernandez, J
A1  - Norsworthy, PJ
A1  - Walport, MJ
A1  - Cook, HT
A1  - Botto, M
J1  - Mol Immunol
Y1  - 2007/07/31/
SN  - 0161-5890
N2  - C1q-deficient mice have been shown to develop a lupus-like disease and to display an impaired clearance of apoptotic cells that are enriched in lupus autoantigens. However, the role of C1q in the regulation of autoreactive B cells remains debatable. To explore this we crossed MRL/Mp C1q-deficient mice with knock-in transgenic (Tg) mice expressing an anti-ssDNA antibody (V(H)3H9R and V(H)3H9R/V(L)kappa8R). Analysis of the V(H)3H9R mice showed that in the absence of C1q higher titres of Tg-derived IgM and IgG(3) anti-ssDNA antibodies were detectable. In contrast, in the V(H)3H9R/V(L)kappa8R C1q-deficient animals no increase in Tg antibody levels was observed. In both models the lack of C1q induced a marked reduction of marginal zone B cells and this was paralleled by a significant increase in the percentage of plasmocytes. Thus, one could postulate that in the absence of C1q the failure to clear efficiently dying cells provides an additional stimulus to the autoreactive Tg B cells resulting in their emigration from the marginal zone B cell compartment with subsequent increase in plasmocytes. However, the lack of C1q led to an increased production of Tg IgM and IgG(3) antibodies only in V(H)3H9R mice indicating that additional genetic susceptibility factors are required to break self-tolerance.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17675234&query_hl=1
ER  - 

TY  - JFULL
T1  - Two Epstein-Barr virus (EBV) oncoproteins cooperate to repress expression of the proapoptotic tumour-suppressor Bim: clues to the pathogenesis of Burkitt's lymphoma.
A1  - Anderton, E
A1  - Yee, J
A1  - Smith, P
A1  - Crook, T
A1  - White, RE
A1  - Allday, MJ
J1  - Oncogene
Y1  - 2007/07/23/
SN  - 0950-9232
N2  - Epstein-Barr virus (EBV) contributes to the development of several human cancers including the endemic form of Burkitt's lymphoma (BL). In culture, EBV induces the continuous proliferation of primary B cells as lymphoblastoid cell lines (LCLs) and if EBV-negative BL-derived cells are infected with EBV, latency-associated viral factors confer resistance to various inducers of apoptosis. Nuclear proteins EBNA3A and EBNA3C (but not EBNA3B) are necessary to establish LCLs and their expression may be involved in the resistance of BL cells to cytotoxic agents. We have therefore created recombinant EBVs from which each of the EBNA3 genes has been independently deleted, and revertant viruses in which the genes have been re-introduced into the viral genome. Infection of EBV-negative BL cells with this panel of EBVs and challenge with various cytotoxic drugs showed that EBNA3A and EBNA3C cooperate as the main determinants of both drug resistance and the downregulation of the proapoptotic Bcl-2-family member Bcl-2-interacting mediator of cell death (Bim). The regulation of Bim is predominantly at the level of RNA, with little evidence of post-translational Bim stabilization by EBV. In the absence of Bim, EBNA3A and EBNA3C appear to provide no survival advantage. The level of Bim is a critical regulator of B cell survival and reduced expression is a major determinant of lymphoproliferative disease in mice and humans; moreover, Bim is uniquely important in the pathogenesis of BL. By targeting this tumour-suppressor for repression, EBV significantly increases the likelihood of B lymphomagenesis in general, and BL in particular. Our results may also explain the selection pressure that gives rise to a subset of BL that retain expression of the EBNA3 proteins.Oncogene advance online publication, 23 July 2007; doi:10.1038/sj.onc.1210668.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17653091&query_hl=1
ER  - 

TY  - JFULL
T1  - Kisspeptin-54 Stimulates Gonadotrophin Release Most Potently During The Preovulatory Phase Of The Menstrual Cycle In Women.
A1  - Dhillo, WS
A1  - Chaudhri, OB
A1  - Thompson, EL
A1  - Murphy, KG
A1  - Patterson, M
A1  - Ramachandran, R
A1  - Nijher, GK
A1  - Amber, V
A1  - Kokkinos, A
A1  - Donaldson, M
A1  - Ghatei, MA
A1  - Bloom, SR
J1  - J Clin Endocrinol Metab
Y1  - 2007/07/17/
SN  - 0021-972X
N2  - Context: Kisspeptin, the endogenous ligand of the GPR54 receptor, is a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. GPR54-null mice exhibit reproductive dysfunction and exogenous kisspeptin potently stimulates the HPG axis in rodents, primates and human males. The effects of kisspeptin administration to human females are unknown. Objective: To investigate the effects of kisspeptin on LH release during the menstrual cycle in female volunteers. Design: Bolus subcutaneous (sc) kisspeptin-54 to female volunteers and measurement of plasma gonadotrophins. Setting: Hospital clinical research facility. Volunteers: Healthy female volunteers with regular menstrual cycles. Intervention: (i) Volunteers received a sc bolus injection of kisspeptin-54 (0, 0.2, 0.4, 0.8, 1.6, 3.2 and 6.4 nmol/kg, n=3-4 per dose) in the follicular phase. (ii) Volunteers (n=8) received a sc bolus injection of either kisspeptin-54 (0.4 nmol/kg) or saline in random order during each phase of the menstrual cycle. Main outcome measures: plasma gonadotrophins. Results: (i) Kisspeptin-54 caused a dose-dependent increase in mean LH over time at doses from 0.2-6.4 nmol/kg. (ii) Kisspeptin-54 increased plasma LH compared to saline injection in all phases of the cycle. The effect of kisspeptin was greatest in the preovulatory phase and least in the follicular phase of the cycle [mean increase in LH over baseline (IU/L)+/-S.E.M.: follicular phase: 0.12+/-0.17; preovulatory phase: 20.64+/-2.91 (P<0.001 vs follicular phase); luteal phase: 2.17+/-0.79 (P<0.01 vs follicular phase)]. Conclusion: Elevation of plasma kisspeptin in human females potently stimulates LH release in the preovulatory phase and provides a novel mechanism for manipulation of the HPG axis in women.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635940&query_hl=1
ER  - 

TY  - JFULL
T1  - Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases.
A1  - Barrett, A
A1  - Santangelo, S
A1  - Tan, K
A1  - Catchpole, S
A1  - Roberts, K
A1  - Spencer-Dene, B
A1  - Hall, D
A1  - Scibetta, A
A1  - Burchell, J
A1  - Verdin, E
A1  - Freemont, P
A1  - Taylor-Papadimitriou, J
J1  - Int J Cancer
Y1  - 2007/07/15/
VL  - 121
SN  - 0020-7136
SP  - 265
EP  - 275
N2  - The PLU-1/JARID1B nuclear protein, which is expressed in a high proportion of breast cancers, but shows restricted expression elsewhere, belongs to the ARID family of proteins, known to play important roles in development, differentiation, transcriptional regulation and chromatin remodeling. PLU-1/JARID1B is a strong transcriptional repressor, and here we show that the protein localizes in MAD bodies when cotransfected with class IIa histone deacetylases (HDACs) or N-CoR. Direct binding to class I and class IIa HDACs is demonstrated, while the interaction with N-CoR appears to be indirect. The domains involved in the HDAC4-PLU-1/JARID1B interaction were investigated in detail, and the data show that 2 PHD domains in PLU-1/JARID1B, which are involved in transcriptional repression, are also crucial for binding to a domain in the 5' region of HDAC4, overlapping the MEF-2 binding region. Physiological relevance of this interaction in the mammary gland is suggested from the observation that HDAC4 and PLU-1/JARID1B are coexpressed in the pregnant and involuting mouse mammary gland and are both silenced at lactation. Significantly, the expression of both proteins is seen in breast cancers.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17373667&query_hl=1
ER  - 

TY  - JFULL
T1  - How I treat chronic myeloid leukemia in the imatinib era.
A1  - Goldman, JM
J1  - Blood
Y1  - 2007/07/12/
SN  - 0006-4971
N2  - Though it is now generally accepted that imatinib is the best initial treatment for patients newly diagnosed with CML in chronic phase, a number of questions remain unanswered. For example, (1) Is imatinib the best initial treatment for every patient? (2) At what dose should imatinib be started? (3) How should response to treatment be monitored? (4) For how long should the drug be continued in patients who have achieved and maintained a complete molecular response? (5) How does one handle a patient who achieves a 2-log but not a 3-log reduction in BCR-ABL transcripts? (6) How should response or failure be defined? (7) For the patient deemed to have failed imatinib, should one offer dasatinib or nilotinib? (8) For the patient who has failed imatinib but has a possible allogeneic transplant donor, should one offer dasatinib or nilotinib before recommending a transplant? (9) Should the transplant be myeloablative or reduced intensity conditioning? and (10) How should one treat the patient who relapses after allografting? This paper will address these issues, many of which cannot yet be answered definitively.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17626839&query_hl=1
ER  - 

TY  - JFULL
T1  - Response to Mallet et al., 'Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients'.
A1  - Garvey, LJ
A1  - Thomson, EC
A1  - Lloyd, J
A1  - Cooke, GS
A1  - Goldin, RD
A1  - Main, J
J1  - AIDS
Y1  - 2007/07/11/
VL  - 21
SN  - 0269-9370
SP  - 1494
EP  - 1495
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17589202&query_hl=1
ER  - 

TY  - JFULL
T1  - Images in cardiovascular medicine. An unusual site for a common disease.
A1  - Alzetani, M
A1  - Boyle, JJ
A1  - Lefroy, D
A1  - Nihoyannopoulos, P
J1  - Circulation
Y1  - 2007/07/03/
VL  - 116
SN  - 1524-4539
SP  - e1
EP  - e1
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17606848&query_hl=1
ER  - 

TY  - JFULL
T1  - The missing care bundle: antibiotic prescribing in hospitals.
A1  - Cooke, FJ
A1  - Holmes, AH
J1  - Int J Antimicrob Agents
Y1  - 2007/07//
VL  - 30
SN  - 0924-8579
SP  - 25
EP  - 29
N2  - The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes. In short, care bundles aim to ensure that all patients consistently receive the best care or treatment, all of the time. This approach has been successfully applied to the management of various conditions, particularly in the critical care setting. The Institute for Healthcare Improvement's '100K lives campaign' consisted of six care bundles, three of which have addressed preventing hospital-acquired infection. The UK Department of Health's delivery programme to reduce healthcare-associated infections (HCAIs), including methicillin-resistant Staphylococcus aureus (MRSA), includes six 'high-impact interventions', which are care bundles to reduce HCAIs. However, we suggest that one key intervention is missing, and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile, to tackle antibiotic resistance and to improve patient care. The missing intervention addresses the process of antibiotic prescribing. We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics, both for treatment and prophylaxis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17499482&query_hl=1
ER  - 

TY  - JFULL
T1  - Economic factors affecting head and neck reconstructive microsurgery: the surgeons' and hospital's perspective.
A1  - Deleyiannis, FW
A1  - Porter, AC
J1  - Plast Reconstr Surg
Y1  - 2007/07//
VL  - 120
SN  - 1529-4242
SP  - 157
EP  - 165
N2  - BACKGROUND: The purpose of this study was to determine the relative financial value of providing the service of free-tissue transfer for head and neck reconstruction from the surgeons' and hospital's perspective. METHODS: Medical and hospital accounting records of 58 consecutive patients undergoing head and neck resections and simultaneous free-flap reconstruction were reviewed. Software from the Center for Medicare and Medicaid Services was used to calculate anticipated Medicare payments to the surgeon based on current procedural terminology codes and to the hospital based on diagnosis-related group codes. RESULTS: The mean actual payment to the surgeon for a free flap was $2300.60. This payment was 91.6 percent ($2300 out of $2510) of the calculated payment if all payments had been reimbursed by Medicare. Total charges and total payment to the hospital for the 58 patients were $19,148,852 and $2,765,552, respectively. After covering direct costs, total hospital revenue (i.e., margin) was $1,056,886. The mostly commonly assigned diagnosis-related group code was 482 (n = 35). According to the fee schedule for that code, if Medicare had been the insurance plan for these 35 patients, the mean payment to the hospital would have been $45,840. The actual mean hospital payment was $44,133. This actual hospital payment represents 96 percent of the calculated Medicare hospital payment ($44,133 of $45,840). CONCLUSIONS: Free-flap reconstruction of the head and neck generates substantial revenue for the hospital. For their mutual benefit, hospitals should join with physicians in contract negotiations of physician reimbursement with insurance companies. Bolstered reimbursement figures would better attract and retain skilled surgeons dedicated to microvascular reconstruction.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17572558&query_hl=1
ER  - 

TY  - JFULL
T1  - Retro-orbital injection is an effective route for radiopharmaceutical administration in mice during small-animal PET studies.
A1  - Nanni, C
A1  - Pettinato, C
A1  - Ambrosini, V
A1  - Spinelli, A
A1  - Trespidi, S
A1  - Rubello, D
A1  - Al-Nahhas, A
A1  - Franchi, R
A1  - Alavi, A
A1  - Fanti, S
J1  - Nucl Med Commun
Y1  - 2007/07//
VL  - 28
SN  - 0143-3636
SP  - 547
EP  - 553
N2  - BACKGROUND AND AIM: Small-animal PET is acquiring importance for pre-clinical studies. In rodents, radiotracers are usually administrated via the tail vein. This procedure can be very difficult and time-consuming as soft tissue extravasations are very frequent and tail scars can prevent repeated injections after initial failure. The aim of our study was to compare the retro-orbital (RO) versus tail vein intravenous (i.v.) administration of (18)F-FDG and (11)C-choline in mice for small-animal PET studies. METHODS: We evaluated four healthy female ICR CD1 mice according to the following protocol. Day 1: each animal underwent an i.v. injection of 28 MBq of (11)C-choline. PET scan was performed after 10 min and 40 min. Day 2: each animal received an RO injection of 28 MBq of (11)C-choline. A PET scan was performed after 10 min and 40 min. Day 3: each animal received an i.v. injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Day 4: each animal received an RO injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Administration and image acquisition were performed under gas anaesthesia. For FDG studies the animals fasted for 2 h and were kept asleep for 20-30 min after injection, to avoid muscular uptake. Images were reconstructed with 2-D OSEM. For each scan ROIs were drawn on liver, kidneys, lung, brain, heart brown fat and muscles, and the SUV was calculated. We finally compared choline i.v. standard acquisition to choline RO standard acquisition; choline i.v. delayed acquisition to choline RO delayed acquisition; FDG i.v. standard acquisition to FDG RO standard acquisition; FDG i.v. delayed acquisition to FDG RO delayed acquisition. RESULTS: The RO injections for both (18)F-FDG and (11)C-choline were comparable to the intravenous injection of F-FDG for the standard and delayed acquisitions. CONCLUSION: The RO administration in mice represents a technical advantage over intravenous administration in being an easier and faster procedure. However, its use requires high specific activity while its value in peptides and other receptor-specific radiopharmaceuticals needs further assessment.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17538396&query_hl=1
ER  - 

TY  - JFULL
T1  - Vaccinia virus gene F3L encodes an intracellular protein that affects the innate immune response.
A1  - Froggatt, GC
A1  - Smith, GL
A1  - Beard, PM
J1  - J Gen Virol
Y1  - 2007/07//
VL  - 88
SN  - 0022-1317
SP  - 1917
EP  - 1921
N2  - The Vaccinia virus BTB/kelch protein F3 has been characterized and its effects on virus replication in vitro and virus virulence in vivo have been determined. The loss of the F3L gene had no effect on virus growth, plaque phenotype or cytopathic effect in cell culture under the conditions tested. However, the virulence of a virus lacking F3L in an intradermal model was reduced compared with controls, and this was demonstrated by a significantly smaller lesion and alterations to the innate immune response to infection. The predicted molecular mass of the F3 protein is 56 kDa; however, immunoblotting of infected cell lysates using an antibody directed against recombinant F3 revealed two proteins of estimated sizes 37 and 25 kDa.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17554022&query_hl=1
ER  - 

TY  - JFULL
T1  - Antibodies against the CUB1-2 domains of ADAMTS13 in a patient with benign monoclonal gammopathy: no causal relationship.
A1  - Riksen, NP
A1  - Luken, BM
A1  - Klasen, IS
A1  - Voorberg, J
A1  - Crama, N
A1  - van Deuren, M
J1  - Haematologica
Y1  - 2007/07//
VL  - 92
SN  - 1592-8721
SP  - e74
EP  - e76
N2  - We present a patient with a history of benign monoclonal gammopathy, who developed thrombotic thrombocytopenic purpura (TTP), initially presenting as bilateral serous retinal detachment. Plasma of the patient contained high titers of anti ADAMTS13 antibodies that were directed towards the disintegrin/TSR1/cysteine-rich/spacer and CUB1-2 domains. ADAMTS13 activity was undetectable. Total IgG purified from plasma of the patient partially inhibited ADAMTS13 activity. In contrast, the isolated M-protein did neither bind to, nor inhibit activity of ADAMTS13. We conclude that in this patient the monoclonal gammopathy and TTP co-existed as distinct pathological entities.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17650455&query_hl=1
ER  - 

TY  - JFULL
T1  - Effects of high-intensity interval walking training on physical fitness and blood pressure in middle-aged and older people.
A1  - Nemoto, K
A1  - Gen-no, H
A1  - Masuki, S
A1  - Okazaki, K
A1  - Nose, H
J1  - Mayo Clin Proc
Y1  - 2007/07//
VL  - 82
SN  - 0025-6196
SP  - 803
EP  - 811
N2  - OBJECTIVE: To examine whether high-intensity interval walking training increased thigh muscle strength and peak aerobic capacity and reduced blood pressure more than moderate-intensity continuous walking training. PARTICIPANTS AND METHODS: From May 18, 2004, to October 15, 2004 (5-month study period), 60 men and 186 women with a mean +/- SD age of 63 +/- 6 years were randomly divided into 3 groups: no walking training, moderate-intensity continuous walking training, and high-intensity interval walking training. Participants in the moderate-intensity continuous walking training group were instructed to walk at approximately 50% of their peak aerobic capacity for walking, using a pedometer to verify that they took 8000 steps or more per day for 4 or more days per week. Those in the high-intensity interval walking training group, who were monitored by accelerometry, were instructed to repeat 5 or more sets of 3-minute low-intensity walking at 40% of peak aerobic capacity for walking followed by a 3-minute high-intensity walking above 70% of peak aerobic capacity for walking per day for 4 or more days per week. Isometric knee extension and flexion forces, peak aerobic capacity for cycling, and peak aerobic capacity for walking were all measured both before and after training. RESULTS: The targets were met by 9 of 25 men and 37 of 59 women in the no walking training group, by 8 of 16 men and 43 of 59 women in the moderate-intensity continuous walking training group, and by 11 of 19 men and 31 of 68 women in the high-intensity interval walking training group. In the high-intensity interval walking training group, isometric knee extension increased by 13%, isometric knee flexion by 17%, peak aerobic capacity for cycling by 8%, and peak aerobic capacity for walking by 9% (all, P<.001), all of which were significantly greater than the increases observed in the moderate-intensity continuous walking training group (all, P<.01). Moreover, the reduction in resting systolic blood pressure was higher for the high-intensity interval walking training group (P=.01). CONCLUSION: High-intensity interval walking may protect against age-associated increases in blood pressure and decreases in thigh muscle strength and peak aerobic capacity.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17605959&query_hl=1
ER  - 

TY  - JFULL
T1  - Absence of cyclin-D2 and Bcl-2 expression within the germinal centre type of diffuse large B-cell lymphoma identifies a very good prognostic subgroup of patients.
A1  - Amen, F
A1  - Horncastle, D
A1  - Elderfield, K
A1  - Banham, AH
A1  - Bower, M
A1  - Macdonald, D
A1  - Kanfer, E
A1  - Naresh, KN
J1  - Histopathology
Y1  - 2007/07//
VL  - 51
SN  - 0309-0167
SP  - 70
EP  - 79
N2  - AIMS: To validate and improve the existing algorithm (proposed by Hans et al.) to classify diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: Tissue microarrays constructed from 81 patients with DLBCL were studied by immunohistochemistry for expression of CD10, Bcl-6, MUM1, Bcl-2, cyclin-D2, FOXP1 and PKC-gamma proteins. Cases were classified as either germinal centre B-like (GCB) or non-GC according to Hans et al. An alternative classification was also employed, in which cases positive for either CD10 or Bcl-6 were considered as a GC subgroup and cases negative for both CD10 and Bcl-6 were considered as a non-GC subgroup. GC was further subdivided into favourable GC (negative for both Bcl-2 and cyclin-D2) and unfavourable GC (positive for either Bcl-2 or cyclin-D2). The 5-year event-free survival (EFS) amongst patients classified as favourable GC versus 'others' was 49.5% and 7.3%, respectively (log rank P < 0.0001). Similarly, the 5-year overall survival (OS) amongst patients classified as favourable GC versus 'others' was 58.6% and 13.7%, respectively (log rank P = 0.0001). The difference in survival was independent of the international prognostic index. CONCLUSIONS: In this group of patients the risk stratification based on the new algorithm was better than that proposed by Hans et al.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17593082&query_hl=1
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TY  - JFULL
T1  - The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia.
A1  - Mohty, M
A1  - Yong, AS
A1  - Szydlo, RM
A1  - Apperley, JF
A1  - Melo, JV
J1  - Blood
Y1  - 2007/07/01/
VL  - 110
SN  - 0006-4971
SP  - 380
EP  - 383
N2  - Because the polycomb group gene BMI1 regulates the proliferation of both normal and leukemic stem cells, we examined whether BMI1 expression was associated with disease progression in chronic myeloid leukemia (CML). Levels of BMI1 RNA were significantly higher in patients with advanced-phase than in patients with chronic-phase CML in both CD34(+) cells (P = .006) and total peripheral-blood mononuclear cells (P < .001). E2F1, a transcription factor regulating BMI1, was up-regulated in CML compared with controls (P = .001). In a cohort of 64 CML patients, the level of BMI1 at diagnosis correlated with time to transformation to blast crisis, and the combination of low BMI1 and high proteinase-3 expression was associated in multivariate analysis with an improved overall survival (P = .001). We conclude that BMI1 may be a biomarker for the intrinsic heterogeneity of CML, and its measurement at diagnosis can help predict overall survival and thus contribute to better therapeutic decisions.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17360938&query_hl=1
ER  - 

TY  - JFULL
T1  - Mouse embryonic stem cell engrafment in healthy and injured mouse lung
A1  - Lane, S
A1  - Rippon, H
A1  - Takata, M
A1  - Mahadeva, R
A1  - Bishop, AE
J1  - TISSUE ENG
Y1  - 2007/07//
VL  - 13
SN  - 1076-3279
SP  - 1731
EP  - 1731
ER  - 

TY  - JFULL
T1  - Chronic myeloid leukemia - some topical issues
A1  - Mughal, T
A1  - Cortes, J
A1  - Cross, NCP
A1  - Donato, N
A1  - Hantschel, O
A1  - Jabbour, E
A1  - Kantarjian, H
A1  - Melo, JV
A1  - Skorski, T
A1  - Silver, RT
A1  - Goldman, JM
J1  - LEUKEMIA
Y1  - 2007/07//
VL  - 21
SN  - 0887-6924
SP  - 1347
EP  - 1352
ER  - 

TY  - JFULL
T1  - Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1.
A1  - Bausch, B
A1  - Borozdin, W
A1  - Mautner, VF
A1  - Hoffmann, MM
A1  - Boehm, D
A1  - Robledo, M
A1  - Cascon, A
A1  - Harenberg, T
A1  - Schiavi, F
A1  - Pawlu, C
A1  - Peczkowska, M
A1  - Letizia, C
A1  - Calvieri, S
A1  - Arnaldi, G
A1  - Klingenberg-Noftz, RD
A1  - Reisch, N
A1  - Fassina, A
A1  - Brunaud, L
A1  - Walter, MA
A1  - Mannelli, M
A1  - MacGregor, G
A1  - Palazzo, FF
A1  - Barontini, M
A1  - Walz, MK
A1  - Kremens, B
A1  - Brabant, G
A1  - Pfäffle, R
A1  - Koschker, AC
A1  - Lohoefner, F
A1  - Mohaupt, M
A1  - Gimm, O
A1  - Jarzab, B
A1  - McWhinney, SR
A1  - Opocher, G
A1  - Januszewicz, A
A1  - Kohlhase, J
A1  - Eng, C
A1  - Neumann, HP
A1  - European-American Phaeochromocytoma Registry Study Group
J1  - J Clin Endocrinol Metab
Y1  - 2007/07//
VL  - 92
SN  - 0021-972X
SP  - 2784
EP  - 2792
N2  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma. MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed. RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype. CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17426081&query_hl=1
ER  - 

TY  - JFULL
T1  - Intelligent bioprocessing for haemotopoietic cell cultures using monitoring and design of experiments.
A1  - Lim, M
A1  - Ye, H
A1  - Panoskaltsis, N
A1  - Drakakis, EM
A1  - Yue, X
A1  - Cass, AE
A1  - Radomska, A
A1  - Mantalaris, A
J1  - Biotechnol Adv
Y1  - 2007/07//
VL  - 25
SN  - 0734-9750
SP  - 353
EP  - 368
N2  - The need for successful ex-vivo expansion and directed differentiation of haematopoietic stem cells (HSCs) for therapeutic applications has increased over the past decade. Haematopoietic cell cultures are complex and full characterisation of the process environment has yet to be achieved. The complexity and transient nature of HSC cultures make the identification, maintenance and control of optimal operating conditions challenging. Application of real-time, on-line monitoring techniques and process control strategies enhances the ability to operate bioprocesses of desired reproducibility and high product quality. In this review, we discussed the methods by which in vitro culture information necessary for bioprocess control may be obtained, including process considerations, monitoring and analytical tools, and design of experiments (DOE). The successful application of these tools may result in time- and cost-effective cultures for directed differentiation and expansion of haematopoietic components intended for clinical use.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428632&query_hl=1
ER  - 

TY  - JFULL
T1  - Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease.
A1  - Boyton, RJ
A1  - Altmann, DM
J1  - Clin Exp Immunol
Y1  - 2007/07//
VL  - 149
SN  - 0009-9104
SP  - 1
EP  - 8
N2  - Natural killer cells constitute a potent, rapid part of the innate immune response to infection or transformation, and also generate a link to priming of adaptive immunity. Their function can encompass direct cytotoxicity as well as the release of cytokines and chemokines. In humans, a major component of natural killer (NK) cell target recognition depends mainly on the surveillance of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIR). Different KIR can transmit inhibitory or activatory signals to the cell, and effector function is considered to result from the balance of these contributing signals. The regulation of NK cell responses depends on a number of variables: KIR genotype, HLA genotype, heterozygosity versus homozygosity for these, whether there is cognate recognition between the HLA and KIR products carried by an individual, clonal variation between individual NK cells in KIR expression, and the specific modulation of HLA expression by infection, transformation or peptide binding. Different HLA/KIR genotypes can impart different thresholds of activation to the NK cell repertoire and such genotypic variation has been found to confer altered risk in a number of diseases including human immunodeficiency virus (HIV) susceptibility and progression, hepatitis C virus clearance, idiopathic bronchiectasis, autoimmunity and cancer.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17521317&query_hl=1
ER  - 

TY  - JFULL
T1  - Zinc Cream and Reliability of Tuberculosis Skin Testing
A1  - Rao, VB
A1  - Pelly, TF
A1  - Gilman, RH
A1  - Cabrera, L
A1  - Delgado, J
A1  - Soto, G
A1  - Friedland, JS
A1  - Escombe, AR
A1  - Black, RE
A1  - Evans, CA
J1  - Emerging Infectious Diseases
Y1  - 2007/07//
VL  - 13
SP  - 1101
EP  - 1104
N2  - In 50 healthy Peruvian shantytown residents, zinc  cream applied to tuberculosis skin-test sites caused a 32%  increase in induration compared with placebo cream. Persons  with lower plasma zinc had smaller skin-test reactions  and greater augmentation with zinc cream. Zinc defi ciency  caused false-negative skin-test results, and topical zinc  supplementation augmented antimycobacterial immune responses  enough to improve diagnosis.
ER  - 

TY  - JFULL
T1  - Case 36: a difficult diagnosis in a patient with fever and progressive multi-organ failure.
A1  - Gabriel, IH
A1  - Chong, N
A1  - Rice, A
A1  - Negus, R
A1  - Bain, BJ
J1  - Leuk Lymphoma
Y1  - 2007/07//
VL  - 48
SN  - 1042-8194
SP  - 1407
EP  - 1409
N2  - A man in late middle age presented with fever, systemic symptoms, raised inflammatory markers and anaemia of chronic disease. Despite two months of investigation, the diagnosis of a haematological malignancy was made only at autopsy.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17613770&query_hl=1
ER  - 

TY  - JFULL
T1  - Sickle cell disease as a paradigm of immigration hematology: new challenges for hematologists in Europe.
A1  - Roberts, I
A1  - de Montalembert, M
J1  - Haematologica
Y1  - 2007/07//
VL  - 92
SN  - 1592-8721
SP  - 865
EP  - 871
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17606434&query_hl=1
ER  - 

TY  - JFULL
T1  - The central role of thrombin in hemostasis.
A1  - Crawley, JT
A1  - Zanardelli, S
A1  - Chion, CK
A1  - Lane, DA
J1  - J Thromb Haemost
Y1  - 2007/07//
VL  - 5 Suppl 1
SN  - 1538-7933
SP  - 95
EP  - 101
N2  - Following vascular injury, blood loss is controlled by the mechanisms of hemostasis. During this process, the serine proteinase, thrombin, is generated both locally and rapidly at sites of vessel damage. It plays a pivotal role in clot promotion and inhibition, and cell signaling, as well as additional processes that influence fibrinolysis and inflammation. These functions involve numerous cleavage reactions, which must be tightly coordinated. Failure to do so can lead to either bleeding or thrombosis. The crystal structures of thrombin, in combination with biochemical analyses of thrombin mutants, have provided insight into the ways in which thrombin functions, and how its different activities are modulated. Many of the interactions of thrombin are facilitated by exosites on its surface that bind to its substrates and/or cofactors. The use of cofactors not only extends the range of thrombin specificity, but also enhances its catalytic efficiency for different substrates. This explains a paradox (i.e. thrombin is a specific proteinase, and yet one that has multiple, and sometimes opposing, substrate reactions). In this review, we describe the context in which thrombin acts during hemostasis and explain the roles that its exosites and cofactors play in directing thrombin function. Thereafter, we develop the concept of cofactor competition as a means by which the activities of thrombin are controlled.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635715&query_hl=1
ER  - 

TY  - JFULL
T1  - Stem cells in lung repair and regeneration.
A1  - Lane, S
A1  - Rippon, HJ
A1  - Bishop, AE
J1  - Regen Med
Y1  - 2007/07//
VL  - 2
SN  - 1746-076X
SP  - 407
EP  - 415
N2  - Repair or regeneration of defective lung tissue would be of great clinical use. Potential cellular sources for the regeneration of lung tissue in vivo or lung tissue engineering in vitro include endogenous pulmonary stem cells, extrapulmonary circulating stem cells and embryonic stem cells. This review summarizes the recent research on each of these stem cell types and their potential for use in the treatment of lung injury and disease.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635048&query_hl=1
ER  - 

TY  - JFULL
T1  - Evaluation of the utility of the HemoCue 301 haemoglobinometer for blood donor screening.
A1  - Morris, LD
A1  - Osei-Bimpong, A
A1  - McKeown, D
A1  - Roper, D
A1  - Lewis, SM
J1  - Vox Sang
Y1  - 2007/07//
VL  - 93
SN  - 0042-9007
SP  - 64
EP  - 69
N2  - BACKGROUND AND OBJECTIVES: Reliable blood donor screening requires more accurate measure of haemoglobin (Hb) than by either copper sulphate or the haemoglobin colour scale. The HemoCue haemoglobinometer has established a method for this, but it is considerably more expensive; a modified version (HemoCue 301) has now been developed with a cheaper reagent-free cuvette for use in budget-restricted situations. This report describes evaluation of the performance, the assessment of reproducibility and accuracy of this modified analyser against the reference technique for Hb measurement. MATERIALS AND METHODS: Over 300 routine blood samples from specimens received routinely in a hospital laboratory were tested in accordance with the International Committee for Standardization in Haematology (ICSH) protocol. Accuracy and linearity were confirmed by the reference method with the WHO international haemoglobincyanide reference standard. Tests were also performed on selected samples for checking interference by biochemical abnormalities and leucocytosis. The effects of various sample storage conditions prior to testing were also tested. RESULTS: Ninety per cent of results were within 4% of true values, 96% within 6% and in only three cases was the deviation > 10%, due to interference by bilirubinaemia and/or C-reactive protein. At an Hb value of 120 g/l for donor selection, there were no cases where the method would have been misleading. CONCLUSION: HemoCue 301 provides a simple and reliable anaemia screen method, conforming to the requirements of CLIA'88 regulations; it is reliable for discriminating Hb values for donor acceptance. The main advantage is that the cuvettes are significantly cheaper than the previous models, and will not deteriorate in adverse climatic conditions.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17547567&query_hl=1
ER  - 

TY  - JFULL
T1  - A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis.
A1  - Thuong, NT
A1  - Hawn, TR
A1  - Thwaites, GE
A1  - Chau, TT
A1  - Lan, NT
A1  - Quy, HT
A1  - Hieu, NT
A1  - Aderem, A
A1  - Hien, TT
A1  - Farrar, JJ
A1  - Dunstan, SJ
J1  - Genes Immun
Y1  - 2007/07//
VL  - 8
SN  - 1466-4879
SP  - 422
EP  - 428
N2  - Tuberculous meningitis (TBM) results from the haematogenous dissemination of Mycobacterium tuberculosis from the lung to the brain. Dissemination is believed to occur early during infection, before the development of adaptive immunity. Toll-like receptor 2 (TLR2) mediates recognition of M. tuberculosis and initiates the innate immune response to infection. We hypothesized that polymorphisms in the TLR2 gene influence bacterial dissemination and the development of TBM. A case-control study was designed to test the hypothesis. Cases of bacteriologically confirmed pulmonary tuberculosis (TB) (n=183) and TBM (n=175), and cord blood controls (n=389) were enrolled in Vietnam. TLR2 genotype 597CC was associated with susceptibility to TB (odds ratio (OR)=2.22, 95% confidence interval (CI): 1.23-3.99). The association was found with meningeal rather than pulmonary TB (TBM vs control, OR=3.26, 95% CI: 1.72-6.18), and was strongest when miliary TB was found on chest radiography (controls vs TBM with miliary TB, OR=5.28, 95% CI: 2.20-12.65). Furthermore, the association increased with the severity of neurologic symptoms (grade I TBM, OR=1.93, 95% CI: 0.54-6.92; grade II, OR=3.32, 95% CI: 0.84-13.2; and grade III, OR=5.70, 95% CI: 1.81-18.0). These results demonstrate a strong association of TLR2 SNP T597C with the development of TBM and miliary TB and indicate that TLR2 influences the dissemination of M. tuberculosis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17554342&query_hl=1
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TY  - JFULL
T1  - Continuity in clinical education.
A1  - Noimark, DJ
A1  - Meeran, K
J1  - N Engl J Med
Y1  - 2007/06/21/
VL  - 356
SN  - 1533-4406
SP  - 2650
EP  - 2650
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17600894&query_hl=1
ER  - 

TY  - JFULL
T1  - Expression of PD-L1, a marker of disease status, is not reduced by HAART in aviraemic patients.
A1  - Rosignoli, G
A1  - Cranage, A
A1  - Burton, C
A1  - Nelson, M
A1  - Steel, A
A1  - Gazzard, B
A1  - Gotch, F
A1  - Imami, N
J1  - AIDS
Y1  - 2007/06/19/
VL  - 21
SN  - 0269-9370
SP  - 1379
EP  - 1381
N2  - Anergy and defective immune responses are characteristic of chronic HIV-1 infection. The programmed death 1 (PD-1)/PD-1 ligand (PD-L1) pathway appears to be involved in downregulating T-cell functionality. We found raised levels of PD-L1 in aviraemic chronically infected HIV-1-positive patients, which may contribute to incomplete immune reconstitution after treatment with HAART.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17545722&query_hl=1
ER  - 

TY  - JFULL
T1  - Synergistic Up-regulation of Epithelial Cell Matrix Metalloproteinase-9 Secretion in Tuberculosis.
A1  - Elkington, PT
A1  - Green, JA
A1  - Emerson, JE
A1  - Lopez-Pascua, LD
A1  - Boyle, JJ
A1  - O'kane, CM
A1  - Friedland, JS
J1  - Am J Respir Cell Mol Biol
Y1  - 2007/06/15/
SN  - 1044-1549
N2  - Mycobacterium tuberculosis (MTb) kills approximately 2 million people each year. MTb must drive host tissue destruction to disseminate and also to cause pulmonary cavitation. Matrix metalloproteinase-9 (MMP-9, gelatinase B) is implicated in this Tb-related immunopathology. We demonstrate that conditioned media from MTb-infected monocytes (CoMTb) but not direct infection with MTb up-regulates MMP-9 gene expression and secretion from primary human bronchial epithelial cells (NHBE). MMP-9 secretion was increased 8.7-fold by CoMTb (p<0.05) as assayed by gelatin zymography. A549 and 16HBE14o epithelial cell MMP secretion was significantly less than primary NHBE secretion. MMP-9 secretion was decreased 53.2% by inhibition of the p38 MAPK by SB203580 (p<0.01) and 48.3% by inhibition of ERK with PD98059 (p<0.05). MMP-9 secretion was prostaglandin-independent. TNF-alpha was necessary but not sufficient for MMP-9 up-regulation by the monocyte-epithelial cell network. Soluble factors derived from Tb culture synergized with TNF-alpha to increase MMP-9 secretion by NHBE 6-fold (p<0.01 compared to either stimulus alone). Together these data reveal a new mechanism by which host- and pathogen-derived factors act together in MTb infection to drive MAPK-dependent MMP-9 secretion from respiratory epithelial cells.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17575075&query_hl=1
ER  - 

TY  - JFULL
T1  - Probing the receptor interactions of an H5 avian influenza virus using a baculovirus expression system and functionalised poly(acrylic acid) ligands.
A1  - Barclay, WS
A1  - Jones, IM
A1  - Osborn, HM
A1  - Phillipson, L
A1  - Ren, J
A1  - Talevera, GA
A1  - Thompson, CI
J1  - Bioorg Med Chem
Y1  - 2007/06/15/
VL  - 15
SN  - 0968-0896
SP  - 4038
EP  - 4047
N2  - Influenza viruses attach to host cells by binding to terminal sialic acid (Neu5Ac) on glycoproteins or glycolipids. Both the linkage of Neu5Ac and the identity of other carbohydrates within the oligosaccharide are thought to play roles in restricting the host range of the virus. In this study, the receptor specificity of an H5 avian influenza virus haemagglutinin protein that has recently infected man (influenza strain A/Vietnam/1194/04) has been probed using carbohydrate functionalised poly(acrylic acid) polymers. A baculovirus expression system that allows facile and safe analysis of the Neu5Ac binding specificity of mutants of H5 HA engineered at sites that are predicted to effect a switch in host range has also been developed.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17451959&query_hl=1
ER  - 

TY  - JFULL
T1  - Loss of discrete memory B cell subsets is associated with impaired immunization responses in HIV-1 infection and may be a risk factor for invasive pneumococcal disease.
A1  - Hart, M
A1  - Steel, A
A1  - Clark, SA
A1  - Moyle, G
A1  - Nelson, M
A1  - Henderson, DC
A1  - Wilson, R
A1  - Gotch, F
A1  - Gazzard, B
A1  - Kelleher, P
J1  - J Immunol
Y1  - 2007/06/15/
VL  - 178
SN  - 0022-1767
SP  - 8212
EP  - 8220
N2  - Invasive pneumococcal infection is an important cause of morbidity and mortality in HIV-1-infected individuals. B cells play an important role in maintaining serologic memory after infection. IgM memory B cells are significantly reduced in HIV-1-infected patients and their frequency is similar to that observed in other patient groups (splenectomized individuals and patients with primary Ab deficiency) who are also known to have an increased risk of invasive pneumococcal infection. Antiretroviral therapy does not restore marginal zone B cell percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal vaccines compared with healthy controls. Loss of switched memory B cells was associated with impaired tetanus toxoid IgG vaccine responses. Results of this study demonstrate that defects in B cell memory subsets are associated with impaired humoral immune responses in HIV-1 patients who are receiving antiretroviral therapy and may be a contributory factor to the increased risk of invasive pneumococcal infection observed in HIV-1 infection.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17548660&query_hl=1
ER  - 

TY  - JFULL
T1  - Bone marrow trephine combined with immunohistochemistry is superior to bone marrow aspirate in follow-up of myeloma patients.
A1  - Joshi, R
A1  - Horncastle, D
A1  - Elderfield, K
A1  - Lampert, I
A1  - Rahemtulla, A
A1  - Naresh, KN
J1  - J Clin Pathol
Y1  - 2007/06/13/
SN  - 0021-9746
N2  - AIMS: Multiple myeloma (MM) guidelines in the United Kingdom do not advocate performing bone marrow trephine biopsy (BMTB) during follow-up. In a recent study, we found that the plasma cell (PC) % in BMTB performed at the time of autologous stem cell transplant strongly correlated with survival (O'Shea et al, 2006). The current study addresses if BMTB is superior to bone marrow aspiration (BMA) in documenting presence of disease and its volume at follow-up. METHODS: The study involves 106 samples. A conventional 500-cell differential count had been performed on the BMAs to document the PC%. The PC% on BMTB had been estimated on CD138 immunostain. Furthermore, BMTBs had also been immunostained for CD56, cyclin D1 and light chains. RESULTS: The mean PC% in BMAs and BMTBs was 13.1+/-2.6% and 31.8+/-5.8% respectively. Based on BMA, BMTB and serum / urine paraprotein or light chain estimation, on 92 occasions (89%), there was detectable disease. The positive predictive value of both BMA and BMTB was 100%, and the negative predictive value for BMTB and BMA was 57% and 22% respectively. Among 98 secretory MM cases, the BMTB-PC% showed significant correlation with paraprotein levels, whereas BMA-PC% did not. CONCLUSIONS: We strongly recommend performing BMTB and adequately investigating them with immunohistochemistry during follow-up of MM.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17526802&query_hl=1
ER  - 

TY  - JFULL
T1  - Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains.
A1  - Pickering, MC
A1  - de Jorge, EG
A1  - Martinez-Barricarte, R
A1  - Recalde, S
A1  - Garcia-Layana, A
A1  - Rose, KL
A1  - Moss, J
A1  - Walport, MJ
A1  - Cook, HT
A1  - de Córdoba, SR
A1  - Botto, M
J1  - J Exp Med
Y1  - 2007/06/11/
VL  - 204
SN  - 0022-1007
SP  - 1249
EP  - 1256
N2  - Factor H (FH) is an abundant serum glycoprotein that regulates the alternative pathway of complement-preventing uncontrolled plasma C3 activation and nonspecific damage to host tissues. Age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and membranoproliferative glomerulonephritis type II (MPGN2) are associated with polymorphisms or mutations in the FH gene (Cfh), suggesting the existence of a genotype-phenotype relationship. Although AMD and MPGN2 share pathological similarities with the accumulation of complement-containing debris within the eye and kidney, respectively, aHUS is characterized by renal endothelial injury. This pathological distinction was reflected in our Cfh association analysis, which demonstrated that although AMD and MPGN2 share a Cfh at-risk haplotype, the haplotype for aHUS was unique. FH-deficient mice have uncontrolled plasma C3 activation and spontaneously develop MPGN2 but not aHUS. We show that these mice, transgenically expressing a mouse FH protein functionally equivalent to aHUS-associated human FH mutants, regulate C3 activation in plasma and spontaneously develop aHUS but not MPGN2. These animals represent the first model of aHUS and provide in vivo evidence that effective plasma C3 regulation and the defective control of complement activation on renal endothelium are the critical events in the molecular pathogenesis of FH-associated aHUS.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17517971&query_hl=1
ER  - 

TY  - JFULL
T1  - Kenneth Anthony ("Tony") Kalanyi Kebba - Obituary
A1  - Gotch, F
J1  - BRIT MED J
Y1  - 2007/06/09/
VL  - 334
SN  - 0959-8146
SP  - 1227
EP  - 1227
ER  - 

TY  - JFULL
T1  - The SPI-2 type III secretion system restricts motility of Salmonella-containing vacuoles.
A1  - Ramsden, AE
A1  - Mota, LJ
A1  - Münter, S
A1  - Shorte, SL
A1  - Holden, DW
J1  - Cell Microbiol
Y1  - 2007/06/07/
SN  - 1462-5814
N2  - Intracellular replication of Salmonella enterica occurs in membrane-bound compartments, called Salmonella-containing vacuoles (SCVs). Following invasion of epithelial cells, most SCVs migrate to a perinuclear region and replicate in close association with the Golgi network. The association of SCVs with the Golgi is dependent on the Salmonella-pathogenicity island-2 (SPI-2) type III secretion system (T3SS) effectors SseG, SseF and SifA. However, little is known about the dynamics of SCV movement. Here, we show that in epithelial cells, 2 h were required for migration of the majority of SCVs to within 5 mum from the microtubule organizing centre (MTOC), which is located in the same subcellular region as the Golgi network. This initial SCV migration was saltatory, bidirectional and microtubule-dependent. An intact Golgi, SseG and SPI-2 T3SS were dispensable for SCV migration to the MTOC, but were essential for maintenance of SCVs in that region. Live-cell imaging between 4 and 8 h post invasion revealed that the majority of wild-type SCVs displaced less than 2 mum in 20 min from their initial starting positions. In contrast, between 6 and 8 h post invasion the majority of vacuoles containing sseG, sseF or ssaV mutant bacteria displaced more than 2 mum in 20 min from their initial starting positions, with some undergoing large and dramatic movements. Further analysis of the movement of SCVs revealed that large displacements were a result of increased SCV speed rather than a change in their directionality, and that SseG influences SCV motility by restricting vacuole speed within the MTOC/Golgi region. SseG might function by tethering SCVs to Golgi-associated molecules, or by controlling microtubule motors, for example by inhibiting kinesin recruitment or promoting dynein recruitment.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17578517&query_hl=1
ER  - 

TY  - JFULL
T1  - Inhibition of type I and type III interferons by a secreted glycoprotein from Yaba-like disease virus.
A1  - Huang, J
A1  - Smirnov, SV
A1  - Lewis-Antes, A
A1  - Balan, M
A1  - Li, W
A1  - Tang, S
A1  - Silke, GV
A1  - Pütz, MM
A1  - Smith, GL
A1  - Kotenko, SV
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/06/05/
VL  - 104
SN  - 0027-8424
SP  - 9822
EP  - 9827
N2  - Type I (IFN-alpha/beta) and type III (IFN-lambdas) IFNs are important components of the host antiviral response. Although type III IFNs possess intrinsic antiviral activity similar to that of type I IFNs, they signal through a specific unique receptor complex, and their functional importance for antiviral resistance is largely uncharacterized. Here, we report the first virus defense mechanism that directly targets type III IFNs. Y136 from Yaba-like disease virus, a yatapoxvirus, is a secreted glycoprotein related to protein B18 from Vaccinia virus, a known type I IFN-binding protein and a member of the Ig superfamily. Surprisingly, whereas B18 inhibits only type I IFNs, Y136 inhibits both type I and type III IFNs. Y136 inhibits IFN-induced signaling and suppresses IFN-mediated biological activities including up-regulation of MHC class I antigen expression and induction of the antiviral state. These data demonstrate that poxviruses have developed unique strategies to counteract IFN-mediated antiviral protection and highlight the importance of type III IFNs in antiviral defense. These results suggest that type III IFNs may be an effective treatment for some poxviral infections.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17517620&query_hl=1
ER  - 

TY  - JFULL
T1  - TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: results from a genome-wide scan.
A1  - Anderson, AE
A1  - Worku, ML
A1  - Khamri, W
A1  - Bamford, KB
A1  - Walker, MM
A1  - Thursz, MR
J1  - Eur J Immunol
Y1  - 2007/06//
VL  - 37
SN  - 0014-2980
SP  - 1548
EP  - 1561
N2  - Immune responses to microorganisms in the gastrointestinal tract must be carefully controlled to avoid disease. Helicobacter are Gram-negative bacteria which cause persistent infection and, in a minority of hosts, peptic ulceration or gastric cancer. Lymphocyte responses are important determinants of the outcome of infection. Therefore, it is important to identify the genetic determinants of lymphocyte responses to this mucosal pathogen. Using a (C57BL/6xBALB/c) F2 mouse model of Helicobacter infection, we mapped a region of linkage for lymphoproliferation to chromosome 9. Analysis of candidate genes in this region revealed variation of DNA sequence and gene expression in the TLR9 gene between C57BL/6 and BALB/c mouse strains. Reporter assays demonstrated higher levels of TLR9 transcriptional activity and increased NF-kappaB activation associated with the C57BL/6 TLR9 promoter and coding sequences. The importance of TLR9 in the control of lymphocyte responses was confirmed by demonstrating that lymphoproliferation and IFN-gamma secretion was diminished in the TLR9-/- mouse. Furthermore, neutrophil infiltration of the gastric epithelium is reduced in the absence of TLR9. Regulation of TLR9 expression and signalling therefore appears to play an important role in the control of lymphocyte responses to Helicobacter and potentially other luminal microorganisms.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17474149&query_hl=1
ER  - 

TY  - JFULL
T1  - Abnormalities of spinal magnetic resonance images implicate clinical variability in human T-cell lymphotropic virus type I-associated myelopathy.
A1  - Umehara, F
A1  - Nose, H
A1  - Saito, M
A1  - Fukuda, M
A1  - Ogino, M
A1  - Toyota, T
A1  - Yuhi, T
A1  - Arimura, K
A1  - Osame, M
J1  - J Neurovirol
Y1  - 2007/06//
VL  - 13
SN  - 1355-0284
SP  - 260
EP  - 267
N2  - This study investigated the role of human T-cell lymphotropic virus type I HTLV-I infection in 11 patients who developed slowly progressive myelopathy with abnormal spinal cord lesions. The authors performed clinical and neuroradiological examinations and calculated the odds that an HTLV-I-infected individual of a specific genotype, age, and provirus load has HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Anti-HTLV-I antibodies were present in both the serum and cerebrospinal fluid in all of the patients. Abnormal magnetic resonance imaging (MRI) lesions were classified as cervical to thoracic type (CT type), cervical type (C type), and thoracic type (T type). In each type, there was swelling of the spinal cords with high-intensity lesions, which were located mainly in bilateral posterior columns, posterior horns, or lateral columns. Virological and immunological analyses revealed that all patients showed a high risk of developing HAM/TSP. These 11 patients may have developed HAM/TSP, as manifested by spinal cord abnormalities shown on MRI. These MRIs implicate clinical variability of HAM/TSP, which may indicate active-early stages of HAM/TSP lesions.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17613716&query_hl=1
ER  - 

TY  - JFULL
T1  - Dual inhibition of ras and bcr-abl signalling pathways in chronic myeloid leukaemia: a phase I/II study in patients in complete haematological remission.
A1  - Pavlu, J
A1  - Andreasson, C
A1  - Chuah, C
A1  - Kaeda, J
A1  - Goldman, JM
A1  - Apperley, JF
A1  - Marin, D
J1  - Br J Haematol
Y1  - 2007/06//
VL  - 137
SN  - 0007-1048
SP  - 423
EP  - 428
N2  - Zoledronic acid inhibits the prenylation of ras-related proteins downstream of bcr-abl and preclinical studies have shown augmentation of the inhibitory effects of imatinib in BCR-ABL expressing cells. A Phase I/II study was designed to assess the safety and efficacy of the addition of zoledronic acid to imatinib in patients with chronic myeloid leukaemia (CML) with a suboptimal response to imatinib alone. Ten patients with CML who had been treated with imatinib for at least 2 years and had achieved and maintained a complete haematological response were included. Zoledronic acid was administered intravenously on one occasion every 28 d. The initial dose of 4 mg was given for three consecutive months; in the absence of significant toxicity and/or response the dose was escalated to 8 mg for an additional 3 months. Efficacy was assessed by serial monitoring of blood levels of BCR-ABL transcripts and bone marrow cytogenetics. Addition of zoledronic acid to imatinib caused no haematological toxicity. There were no grade III or IV non-haematological adverse effects. Grade I fatigue, hypocalcaemia and fever were common side effects. No responses were demonstrated after 6 months on the combination.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428238&query_hl=1
ER  - 

TY  - JFULL
T1  - Scintigraphic techniques in primary hyperparathyroidism: from pre-operative localisation to intra-operative imaging
A1  - Rubello, D
A1  - Gross, MD
A1  - Mariani, G
A1  - Al-Nahhas, A
J1  - EUR J NUCL MED MOL I
Y1  - 2007/06//
VL  - 34
SN  - 1619-7070
SP  - 926
EP  - 933
N2  - Introduction Primary hyperparathyroidism (PHPT) is an increasingly diagnosed disease worldwide. In most cases, PHPT is related to the presence of a solitary parathyroid adenoma (PA). Fifty percent or more of newly diagnosed PHPT patients are asymptomatic, and there is debate among endocrinologists and endocrine surgeons about whether or not such patients should be treated.Localization Usually, in a PHPT patient with a solitary PA that is well localised pre-operatively, a parathyroidectomy with limited or minimally invasive neck exploration is offered. The diffusion of minimally invasive neck exploration procedures is a consequence of the significant improvement in the accuracy of pre-operative imaging (mainly scintigraphic) techniques; these techniques have changed the surgical strategy to PHPT, from the wide traditional bilateral neck exploration to limited neck exploration.Review The present review considers developments during the past 10-15 years with regard to both the accuracy of pre-operative localising imaging techniques and intra-operative minimally invasive procedures in order to provide endocrinologists and endocrine surgeons with further information about the newly available diagnostic and therapeutic tools for use in PHPT patients with a solitary PA.
ER  - 

TY  - JFULL
T1  - Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung.
A1  - Aguilar, S
A1  - Nye, E
A1  - Chan, J
A1  - Loebinger, M
A1  - Spencer-Dene, B
A1  - Fisk, N
A1  - Stamp, G
A1  - Bonnet, D
A1  - Janes, SM
J1  - Stem Cells
Y1  - 2007/06//
VL  - 25
SN  - 1066-5099
SP  - 1586
EP  - 1594
N2  - Murine mesenchymal stem cells are capable of differentiation into multiple cell types both in vitro and in vivo and may be good candidates to use as cell therapy for diseased or damaged organs. We have previously reported a method of enriching a population of murine MSCs that demonstrated a diverse differentiation potential both in vitro and in vivo. In this study, we show that this enriched population of murine mesenchymal stem cells embolize within lung capillaries following systemic injection and then rapidly expand within, and invade into, the lung parenchyma, forming tumor nodules. These lesions rarely contain cells bearing the immunohistochemical characteristics of lung epithelium, but they do show the characteristics of immature bone and cartilage that resembles exuberant fracture callus or well-differentiated osteosarcoma. Our findings indicate that murine mesenchymal stem cells can behave in a manner similar to tumor cells, with dysregulated growth and aberrant differentiation within the alveolar microenvironment after four passages. We demonstrate that unlike human MSCs, MSCs from different mouse strains can acquire chromosomal abnormalities after only a few in vitro passages. Moreover, other parameters, such as mouse strain used, might also play a role in the induction of these tumors. These findings might be clinically relevant for future stem cell therapy studies. Disclosure of potential conflicts of interest is found at the end of this article.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17363552&query_hl=1
ER  - 

TY  - JFULL
T1  - Mutagenesis of the herpesvirus saimiri terminal repeat region reveals important elements for virus production.
A1  - White, RE
A1  - Carline, L
A1  - Allday, MJ
J1  - J Virol
Y1  - 2007/06//
VL  - 81
SN  - 0022-538X
SP  - 6765
EP  - 6770
N2  - Deletion of the terminal repeats (TR) from herpesvirus saimiri (HVS) renders it unable to produce infectious virus or generate plaques. However, a TR-deleted HVS bacterial artificial chromosome can form replication compartments. Complementation of this mutant shows that one copy of the TR, plus the right junction of the genome with the TR, is sufficient for efficient plaque formation and generation of infectious virus. Within the TR unit, the region around the cleavage site of the genome appears both necessary and sufficient for virus production. Analysis of episomes from productive cells indicates a propensity to amplify TR numbers during the lytic cycle.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428860&query_hl=1
ER  - 

TY  - JFULL
T1  - The price for survival are all patients equal?
A1  - Gabriel, I
A1  - Schenk, M
A1  - Foster, J
A1  - Chaidos, A
A1  - Kanfer, F
A1  - Marin, D
A1  - Milojkovic, D
A1  - Rahemtulla, A
A1  - Olavarria, E
A1  - Apperley, J
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 223
EP  - 223
ER  - 

TY  - JFULL
T1  - CTD treatment of myeloma-a single institution's experience
A1  - Mangles, SE
A1  - Abdalla, SH
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 169
EP  - 169
ER  - 

TY  - JFULL
T1  - A new pathologic scoring system for renal calcineurin-inhibitor toxicity correlates with future graft function.
A1  - Cook, T
J1  - Nat Clin Pract Nephrol
Y1  - 2007/06//
VL  - 3
SN  - 1745-8331
SP  - 316
EP  - 317
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17471278&query_hl=1
ER  - 

TY  - JFULL
T1  - Aberrant positivity for CD79a in erythroid lineage cells - a finding observed in a subset of re-staging bone marrow trephine biopsies after treatment
A1  - Flora, RS
A1  - Brito-Babapulle, F
A1  - Naresh, KN
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 855
EP  - 856
N2  - Aberrant expression of CD79a has been reported in neoplastic cells in peripheral T cell lymphoma, T-cell acute lymphoblastic leukemia and acute myeloid leukemia (especially those with t(8;21)). In this report, we document the first report of CD79a positivity in erythroid precursor cells in bone marrow. In all, we document this finding in five of 18 re-staging bone marrow trephine samples in patients of lymphoma treated with chemotherapy (one index case and 17 additional validation cases). It is important to appreciate this finding especially in rituximab treated patients where one tends to rely on CD79a to identify minimal marrow disease.
ER  - 

TY  - JFULL
T1  - Entrepreneurial experiences
A1  - Shaunak, S
A1  - Brocchini, S
J1  - NAT REV DRUG DISCOV
Y1  - 2007/06//
VL  - 6
SN  - 1474-1776
SP  - 499
EP  - 499
ER  - 

TY  - JFULL
T1  - When is a double Philadelphia not a double Philadelphia
A1  - Brazma, D
A1  - Grace, C
A1  - Virgili, A
A1  - Howard, J
A1  - Chanalaris, A
A1  - Melo, JV
A1  - Apperley, JF
A1  - Nacheva, EP
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 202
EP  - 202
ER  - 

TY  - JFULL
T1  - FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity.
A1  - Fanciulli, M
A1  - Norsworthy, PJ
A1  - Petretto, E
A1  - Dong, R
A1  - Harper, L
A1  - Kamesh, L
A1  - Heward, JM
A1  - Gough, SC
A1  - de Smith, A
A1  - Blakemore, AI
A1  - Froguel, P
A1  - Owen, CJ
A1  - Pearce, SH
A1  - Teixeira, L
A1  - Guillevin, L
A1  - Graham, DS
A1  - Pusey, CD
A1  - Cook, HT
A1  - Vyse, TJ
A1  - Aitman, TJ
J1  - Nat Genet
Y1  - 2007/06//
VL  - 39
SN  - 1061-4036
SP  - 721
EP  - 723
N2  - Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17529978&query_hl=1
ER  - 

TY  - JFULL
T1  - Novel pathway in BCR-ABL signal transduction involves Akt-independent activation of PLC-gamma/mTOR/P70-S6 kinase
A1  - Markova, B
A1  - Breitenbuecher, F
A1  - Melo, JV
A1  - Duyster, J
A1  - Huber, C
A1  - Fischer, T
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 338
EP  - 338
ER  - 

TY  - JFULL
T1  - Further characterization of the signaling proteolysis step in the Aspergillus nidulans pH signal transduction pathway.
A1  - Peñas, MM
A1  - Hervás-Aguilar, A
A1  - Múnera-Huertas, T
A1  - Reoyo, E
A1  - Peñalva, MA
A1  - Arst, HN
A1  - Tilburn, J
J1  - Eukaryot Cell
Y1  - 2007/06//
VL  - 6
SN  - 1535-9778
SP  - 960
EP  - 970
N2  - The Aspergillus nidulans pH-responsive transcription factor PacC is modulated by limited, two-step proteolysis. The first, pH-regulated cleavage occurs in the 24-residue highly conserved "signaling protease box" in response to the alkaline pH signal. This is transduced by the Pal signaling pathway, containing the predicted calpain-like cysteine protease and likely signaling protease, PalB. In this work, we carried out classical mutational analysis of the putative signaling protease PalB, and we describe 9 missense and 18 truncating loss-of-function (including null) mutations. Mutations in the region of and affecting directly the predicted catalytic cysteine strongly support the deduction that PalB is a cysteine protease. Truncating and missense mutations affecting the C terminus highlight the importance of this region. Analysis of three-hemagglutinin-tagged PalB in Western blots demonstrates that PalB levels are independent of pH and Pal signal transduction. We have followed the processing of MYC(3)-tagged PacC in Western blots. We show unequivocally that PalB is essential for signaling proteolysis and is definitely not the processing protease. In addition, we have replaced 15 residues of the signaling protease box of MYC(3)-tagged PacC (pacC900) with alanine. The majority of these substitutions are silent. Leu481Ala, Tyr493Ala, and Gln499Ala result in delayed PacC processing in response to shifting from acidic to alkaline medium, as determined by Western blot analysis. Leu498Ala reduces function much more markedly, as determined by plate tests and processing recalcitrance. Excepting Leu498, this demonstrates that PacC signaling proteolysis is largely independent of sequence in the cleavage region.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17416893&query_hl=1
ER  - 

TY  - JFULL
T1  - Multiple molecular mechanism may account for resistanceto imatinib in resistant cell lines
A1  - Pane, F
A1  - Esposito, N
A1  - Izzo, B
A1  - Quarantelli, F
A1  - Colavita, I
A1  - Buonomo, T
A1  - Roberti, V
A1  - Soverini, S
A1  - Melo, JV
A1  - Martinelli, G
A1  - Martinelli, R
A1  - Ruoppolo, M
A1  - Pane, F
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 418
EP  - 418
ER  - 

TY  - JFULL
T1  - Protein-protein interactions and membrane localization of the human organic solute transporter.
A1  - Sun AQ, Balasubramaniyan N, Xu K, Liu CJ, Ponamgi VM, Liu H, Suchy FJ.
J1  - Am J Physiol Gastrointest Liver Physiol
Y1  - 2007/06//
VL  - 292
SP  - G1586
EP  - G1593
ER  - 

TY  - JFULL
T1  - Papillary thyroid carcinoma: 35-year outcome and prognostic factors in 1858 patients.
A1  - Pelizzo, MR
A1  - Boschin, IM
A1  - Toniato, A
A1  - Piotto, A
A1  - Pagetta, C
A1  - Gross, MD
A1  - Al-Nahhas, A
A1  - Rubello, D
J1  - Clin Nucl Med
Y1  - 2007/06//
VL  - 32
SN  - 0363-9762
SP  - 440
EP  - 444
N2  - BACKGROUND AND AIM: Papillary thyroid carcinoma (PTC) is universally regarded as a curable malignancy with a favorable prognosis. However, a minority of patients may present, or subsequently develop, locoregional and distant metastases that may adversely affect survival. The value of the various staging methods is complicated by different approaches to diagnostic, therapeutic and follow-up strategies. We aimed at assessing the prognostic factors and survival rate in a large cohort of patients treated and followed up in the same center. MATERIALS AND METHODS: A total of 1858 patients with PTC operated on by the same surgeon, and followed in the same center over a period of 35 years, were included. Total thyroidectomy was performed in the majority of patients after I-131 diagnostic scans and thyroglobulin assays. When the latter 2 were positive, therapy with I-131 was given. Follow-up was performed periodically and further therapy doses were administered when necessary. All patients were maintained on life-long thyroxine. RESULTS: Ninety-three patients (5%) developed evidence of locoregional or distant metastases after an average follow-up period of 7.9 years (range 1.53-30.5 years). Univariate analysis showed all variables (except for gender) to be significantly correlated with disease recurrence and survival. Multivariate analysis showed 4 variables to be significant and independent prognostic factors: patient age at first treatment, extent of disease, extent of surgery, and the presence of I-131 positive metastases. DISCUSSION AND CONCLUSION: Our data agree with other scoring systems in that patient age at first treatment and the extent of disease are significant and independent prognostic factors. However, and at variance with other methods, we found that the extent of primary surgery and the presence of I-131 positive or negative metastases have similar prognostic significance. In high risk patients, total thyroidectomy and lymphadenectomy followed by I-131 treatment and TSH-suppressive hormonal therapy are recommended.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17515749&query_hl=1
ER  - 

TY  - JFULL
T1  - In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection.
A1  - Zhang, Y
A1  - Wallace, DL
A1  - de Lara, CM
A1  - Ghattas, H
A1  - Asquith, B
A1  - Worth, A
A1  - Griffin, GE
A1  - Taylor, GP
A1  - Tough, DF
A1  - Beverley, PC
A1  - Macallan, DC
J1  - Immunology
Y1  - 2007/06//
VL  - 121
SN  - 0019-2805
SP  - 258
EP  - 265
N2  - Human natural killer (NK) cells form a circulating population in a state of dynamic homeostasis. We investigated NK cell homeostasis by labelling dividing cells in vivo using deuterium-enriched glucose in young and elderly healthy subjects and patients with viral infection. Following a 24-hr intravenous infusion of 6,6-D(2)-glucose, CD3(-) CD16(+) NK cells sorted from peripheral blood mononuclear cells (PBMC) by fluorescence-activated cell sorter (FACS) were analysed for DNA deuterium content by gas chromatography mass spectrometry to yield minimum estimates for proliferation rate (p). In healthy young adults (n=5), deuterium enrichment was maximal approximately 10 days after labelling, consistent with postmitotic maturation preceding circulation. The mean (+/- standard deviation) proliferation rate was 4 x 3 +/- 2 x 4%/day (equivalent to a doubling time of 16 days) and the total production rate was 15 +/- (7 x 6) x 10(6) cells/l/day. Labelled cells disappeared from the circulation at a similar rate [6 x 9 +/- 4 x 0%/day; half-life (T((1/2))) < 10 days]. Healthy elderly subjects (n=8) had lower proliferation and production rates (P=2 x 5 +/- 1 x 0%/day and 7 x 3 +/- (3 x 7) x 10(6) cells/l/day, respectively; P=0 x 04). Similar rates were seen in patients chronically infected with human T-cell lymphotropic virus type I (HTLV-I) (P=3 x 2 +/- 1 x 9%/day). In acute infectious mononucleosis (n=5), NK cell numbers were increased but kinetics were unaffected (P=2 x 8 +/- 1 x 0%/day) a mean of 12 days after symptom onset. Human NK cells have a turnover time in blood of about 2 weeks. Proliferation rates appear to fall with ageing, remain unperturbed by chronic HTLV-I infection and normalize rapidly following acute Epstein-Barr virus infection.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17346281&query_hl=1
ER  - 

TY  - JFULL
T1  - Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein.
A1  - Cooray, S
A1  - Bahar, MW
A1  - Abrescia, NG
A1  - McVey, CE
A1  - Bartlett, NW
A1  - Chen, RA
A1  - Stuart, DI
A1  - Grimes, JM
A1  - Smith, GL
J1  - J Gen Virol
Y1  - 2007/06//
VL  - 88
SN  - 0022-1317
SP  - 1656
EP  - 1666
N2  - Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators of innate immune signalling. VACV protein N1 is an intracellular homodimer that contributes to virus virulence and was reported to inhibit nuclear factor (NF)-kappaB signalling. However, analysis of NF-kappaB signalling in cells infected with recombinant viruses with or without the N1L gene showed no difference in NF-kappaB-dependent gene expression. Given that N1 promotes virus virulence, other possible functions of N1 were investigated and this revealed that N1 is an inhibitor of apoptosis in cells transfected with the N1L gene and in the context of VACV infection. In support of this finding virally expressed N1 co-precipitated with endogenous pro-apoptotic Bcl-2 proteins Bid, Bad and Bax as well as with Bad and Bax expressed by transfection. In addition, the crystal structure of N1 was solved to 2.9 A resolution (0.29 nm). Remarkably, although N1 shows no sequence similarity to cellular proteins, its three-dimensional structure closely resembles Bcl-x(L) and other members of the Bcl-2 protein family. The structure also reveals that N1 has a constitutively open surface groove similar to the grooves of other anti-apoptotic Bcl-2 proteins, which bind the BH3 motifs of pro-apoptotic Bcl-2 family members. Molecular modelling of BH3 peptides into the N1 surface groove, together with analysis of their physico-chemical properties, suggests a mechanism for the specificity of peptide recognition. This study illustrates the importance of the evolutionary conservation of structure, rather than sequence, in protein function and reveals a novel anti-apoptotic protein from orthopoxviruses.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17485524&query_hl=1
ER  - 

TY  - JFULL
T1  - The use of isobaric tag peptide labeling (iTRAQ) and mass spectrometry to examine rare, primitive hematopoietic cells from patients with chronic myeloid leukemia
A1  - Griffiths, SD
A1  - Burthem, J
A1  - Unwin, RD
A1  - Holyoake, TL
A1  - Melo, JV
A1  - Lucas, GS
A1  - Whetton, AD
J1  - MOL BIOTECHNOL
Y1  - 2007/06//
VL  - 36
SN  - 1073-6085
SP  - 81
EP  - 89
N2  - Chronic Myeloid Leukemia (CML) is a hematopoietic stem cell disease, associated with a t(9, 22) chromosomal translocation leading to formation of the BCR/ABL chimeric protein, which has an intrinsic tyrosine kinase activity. Recently, the BCR/ABL tyrosine kinase inhibitor imatinib mesylate (imatinib) has been successfully used clinically, although, disease relapse can still occur. The precise detail of the mechanism by which CML cells respond to imatinib is still unclear. We therefore systematically examined the effects of imatinib on the primitive CML cell proteome, having first established that the drug inhibits proliferation and induces increased apoptosis and differentiation. To define imatinib-induced effects on the CML proteome, we employed isobaric tag peptide labeling (iTRAQ) coupled to two-dimensional liquid chromatography/tandem mass spectrometry. Given the limited clinical material available, the isobaric tag approach identified a large population of proteins and provided relative quantification on four samples at once. Novel consequences of the action of imatinib were identified using this mass spectrometric approach. DEAD-box protein 3, heat shock protein 105 kDa, and peroxiredoxin-3 were identified as potential protein markers for response to imatinib.
ER  - 

TY  - JFULL
T1  - Use of freelite assay to monitor myeloma with renal failure
A1  - Abdalla, SH
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 205
EP  - 205
ER  - 

TY  - JFULL
T1  - Nondestructive mechanical release of ordered polymer microfiber arrays from porous templates.
A1  - Grimm, S
A1  - Schwirn, K
A1  - Göring, P
A1  - Knoll, H
A1  - Miclea, PT
A1  - Greiner, A
A1  - Wendorff, JH
A1  - Wehrspohn, RB
A1  - Gösele, U
A1  - Steinhart, M
J1  - Small
Y1  - 2007/06//
VL  - 3
SN  - 1613-6829
SP  - 993
EP  - 1000
N2  - The fabrication of one-dimensional (1D) nanostructures and microstructures inside the pores of porous templates is intensively investigated. The release of these structures is commonly accomplished by etching and destroying the templates. The 1D nanostructures and microstructures tend to condense because of the occurrence of capillary forces during drying of the specimens. It is shown that highly ordered arrays of polymer microfibers can be easily detached from silanized porous templates by mechanical lift-off. This procedure leaves the templates intact, thus allowing their recycling, and does not involve the use of solutions or solvents, thus circumventing condensation. Therefore, mechanical lift-off may enable the up-scaling of template-based approaches to the fabrication of highly ordered assemblies of 1D nanostructures and microstructures.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17352430&query_hl=1
ER  - 

TY  - JFULL
T1  - Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research
A1  - Panepinto, JA
A1  - Walters, MC
A1  - Carreras, J
A1  - Marsh, J
A1  - Bredeson, CN
A1  - Gale, RP
A1  - Hale, GA
A1  - Horan, J
A1  - Hows, JM
A1  - Klein, JP
A1  - Pasquini, R
A1  - Roberts, I
A1  - Sullivan, K
A1  - Eapen, M
A1  - Ferster, A
A1  - Non Malignant Marrow Disorders
J1  - BRIT J HAEMATOL
Y1  - 2007/06//
VL  - 137
SN  - 0007-1048
SP  - 479
EP  - 485
N2  - We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received > 10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy.
ER  - 

TY  - JFULL
T1  - Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours.
A1  - Jiao, LR
A1  - Szyszko, T
A1  - Al-Nahhas, A
A1  - Tait, P
A1  - Canelo, R
A1  - Stamp, G
A1  - Wasan, H
A1  - Lowdell, C
A1  - Philips, R
A1  - Thillainayagam, A
A1  - Bansi, D
A1  - Rubello, D
A1  - Limongelli, P
A1  - Woo, K
A1  - Habib, NA
J1  - Eur J Surg Oncol
Y1  - 2007/06//
VL  - 33
SN  - 0748-7983
SP  - 597
EP  - 602
N2  - INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours (n=3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and duodenal ulceration (n=1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17433608&query_hl=1
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TY  - JFULL
T1  - An unusual case of a solitary pulmonary nodule associated with an abscess correctly distinguished by Pet/Ct fusion imaging
A1  - Rossi, FD
A1  - Cracco, E
A1  - Rampin, L
A1  - Al-Nahhas, A
A1  - Muzzio, R
A1  - Rubello, D
J1  - J EXP CLIN CANC RES
Y1  - 2007/06//
VL  - 26
SN  - 0392-9078
SP  - 287
EP  - 289
N2  - The case of a male patient affected by concomitant solitary pulmonary nodule and chest abscess located on the same side and each close to the other is reported. The importance in differential diagnosis of these two lesions obtained by the 18F-FDG PET/CT fusion imaging examination is discussed..
ER  - 

TY  - JFULL
T1  - Relation of fasting plasma peptide YY to glucose metabolism and cardiovascular risk factors after restrictive bariatric surgery.
A1  - Hanusch-Enserer, U
A1  - Ghatei, MA
A1  - Cauza, E
A1  - Bloom, SR
A1  - Prager, R
A1  - Roden, M
J1  - Wien Klin Wochenschr
Y1  - 2007/06//
VL  - 119
SN  - 0043-5325
SP  - 291
EP  - 296
N2  - INTRODUCTION: Surgically induced weight loss results in reduction of comorbidities in severely obese humans. Reversal of abnormal secretion of appetite-regulating gut hormones such as peptide YY (PYY) could be contributing to the improvement of cardiovascular risk factors. METHODS: Severely obese patients (n = 42, BMI = 45.7 +/- 5.3 kg/m(2)) underwent clinical examination and blood sampling for measurement of PYY, plasma lipids, oral glucose tolerance testing and assessment of insulin secretion (HOMA-%B) and action (HOMA-R, QUICKI) before and during 12 months following gastric banding. Comparisons were made at each time point of the study as well as across the total study period. RESULTS: Weight loss after bariatric surgery resulted in improvement of insulin resistance by 54% (p < 0.03) and plasma triglycerides by 26% (p < 0.01) without changes in fasting PYY (16.2 +/- 8.7 pmol/l at baseline, 15.1 +/- 6.3 pmol/l at 12 months). Fasting PYY correlated negatively with plasma total cholesterol at baseline (p = 0.02) but was not associated with body weight, body mass or abdominal diameter. Individual changes in PYY (DeltaPYY) related to changes in insulin (Deltafasting insulin) at 12 months (r = -0.582, p = 0.02) and HOMA-B at 6 months (r = -0.677, p = 0.006) and 12 months (r = -0.660, p = 0.007). Diabetic status had no impact on these correlations. DISCUSSION: PYY correlates with a major cardiovascular risk factor and surrogate parameters of insulin secretion but not to weight loss or body mass in severe obesity.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17571233&query_hl=1
ER  - 

TY  - JFULL
T1  - Efficacy of thalidomide based therapy in the treatment of primary plasma cell leukaemia
A1  - Tso, A
A1  - Terpos, E
A1  - Abdalla, SH
A1  - Luckit, J
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 178
EP  - 178
ER  - 

TY  - JFULL
T1  - Case 35: an unusual haematological neoplasm characterized by cells with cytoplasmic tails.
A1  - Kassam, S
A1  - Rice, A
A1  - Morilla, R
A1  - Bain, BJ
J1  - Leuk Lymphoma
Y1  - 2007/06//
VL  - 48
SN  - 1042-8194
SP  - 1208
EP  - 1210
N2  - A middle aged Northern European man presented with a submental lymph node and was found on imaging to have generalized lymphadenopathy. There was bone marrow infiltration by small apparently lymphoid cells, many with cytoplasmic tails; these cells were CD56(+) and weakly CD4(+). A provisional diagnosis was confirmed by further immunophenotyping.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17577785&query_hl=1
ER  - 

TY  - JFULL
T1  - Fishing injury resulting in Mycobacterium fortuitum palmar abscess.
A1  - Patel, B
A1  - Nanchalal, J
A1  - Friedland, JS
J1  - Eur J Clin Microbiol Infect Dis
Y1  - 2007/06//
VL  - 26
SN  - 0934-9723
SP  - 427
EP  - 429
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17458567&query_hl=1
ER  - 

TY  - JFULL
T1  - Chemokines and their receptors in respiratory disease: a therapeutic target for respiratory syncytial virus infection.
A1  - Thomas, LH
A1  - Friedland, JS
A1  - Sharland, M
J1  - Expert Rev Anti Infect Ther
Y1  - 2007/06//
VL  - 5
SN  - 1744-8336
SP  - 415
EP  - 425
N2  - Cell recruitment is a multistep process orchestrated by chemokines and their receptors. The chemokine/receptor system is central to many inflammatory diseases, making it a key target for therapeutic intervention. Despite complexity and redundancy within the system, effective antagonists are in development and undergoing clinical trials, for example, maraviroc, for use in HIV treatment. Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, with global annual infection estimated at 64 million people. Current treatment is purely supportive, with no effective vaccine available. RSV pathology is partly due to excessive airway inflammation. Evidence is growing for a key role for chemokine receptors. Receptor blockade may therefore provide a feasible therapeutic option to inhibit RSV-induced inflammation and thereby reduce disease severity.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17547506&query_hl=1
ER  - 

TY  - JFULL
T1  - Pyderma gangrenosa with MGUS responding to thalidomide
A1  - Chan, I
A1  - Leonard, J
A1  - Abdalla, SH
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 198
EP  - 199
ER  - 

TY  - JFULL
T1  - Role of small animal PET in stimulating the development of new radiopharmaceuticals in oncology.
A1  - Nanni, C
A1  - Rubello, D
A1  - Khan, S
A1  - Al-Nahhas, A
A1  - Fanti, S
J1  - Nucl Med Commun
Y1  - 2007/06//
VL  - 28
SN  - 0143-3636
SP  - 427
EP  - 429
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17460532&query_hl=1
ER  - 

TY  - JFULL
T1  - Second autologous stem cell transplantation for multiple myeloma in first relapse
A1  - Chaidos, A
A1  - Giles, C
A1  - Gabriel, I
A1  - Apperley, JF
A1  - Kanfer, E
A1  - Olavarria, E
A1  - Bua, M
A1  - Samson, D
A1  - Rahemtulla, A
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 256
EP  - 256
ER  - 

TY  - JFULL
T1  - Longterm follow up of T-VAD for untreated multiple myeloma
A1  - Oakervee, H
A1  - Popat, R
A1  - Hamblin, M
A1  - Rule, S
A1  - Rahemtulla, A
A1  - Cavenagh, J
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 177
EP  - 178
ER  - 

TY  - JFULL
T1  - Role of central nervous system and ovarian insulin receptor substrate 2 signaling in female reproductive function in the mouse.
A1  - Neganova, I
A1  - Al-Qassab, H
A1  - Heffron, H
A1  - Selman, C
A1  - Choudhury, AI
A1  - Lingard, SJ
A1  - Diakonov, I
A1  - Patterson, M
A1  - Ghatei, M
A1  - Bloom, SR
A1  - Franks, S
A1  - Huhtaniemi, I
A1  - Hardy, K
A1  - Withers, DJ
J1  - Biol Reprod
Y1  - 2007/06//
VL  - 76
SN  - 0006-3363
SP  - 1045
EP  - 1053
N2  - Insulin receptor signaling regulates female reproductive function acting in the central nervous system and ovary. Female mice that globally lack insulin receptor substrate (IRS) 2, which is a key mediator of insulin receptor action, are infertile with defects in hypothalamic and ovarian functions. To unravel the tissue-specific roles of IRS2, we examined reproductive function in female mice that lack Irs2 only in the neurons. Surprisingly, these animals had minimal defects in pituitary and ovarian hormone levels, ovarian anatomy and function, and breeding performance, which indicates that the central nervous system IRS2 is not an obligatory signaling component for the regulation of reproductive function. Therefore, we undertook a detailed analysis of ovarian function in a novel Irs2 global null mouse line. Comparative morphometric analysis showed reduced follicle size, increased numbers of atretic follicles, as well as impaired oocyte growth and antral cavity development in Irs2 null ovaries. Granulosa cell proliferation was also defective in the Irs2 null ovaries. Furthermore, the insulin- and eCG-stimulated phosphoinositide-3-OH kinase signaling events, which included phosphorylation of Akt/protein kinase B and glycogen synthase kinase 3-beta, were impaired, whereas mitogen-activated protein kinase signaling was preserved in Irs2 null ovaries. These abnormalities were associated with reduced expression of cyclin D2 and increased CDKN1B levels, which indicates dysregulation of key components of the cell cycle apparatus implicated in ovarian function. Our data suggest that ovarian rather than central nervous system IRS2 signaling is important in the regulation of female reproductive function.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17329594&query_hl=1
ER  - 

TY  - JFULL
T1  - Role of 18F-dopa PET/CT imaging in the management of patients with 111In-pentetreotide negative GEP tumours.
A1  - Ambrosini, V
A1  - Tomassetti, P
A1  - Rubello, D
A1  - Campana, D
A1  - Nanni, C
A1  - Castellucci, P
A1  - Farsad, M
A1  - Montini, G
A1  - Al-Nahhas, A
A1  - Franchi, R
A1  - Fanti, S
J1  - Nucl Med Commun
Y1  - 2007/06//
VL  - 28
SN  - 0143-3636
SP  - 473
EP  - 477
N2  - PURPOSE: To assess whether 18F-dopa PET/CT is able to provide information relevant in changing the clinical management of patients with gastro-enteropancreatic (GEP) tumours where there is negative or inconclusive conventional radiological imaging (ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) and 111In-pentetreotide scintigraphy. MATERIALS AND METHODS: From January 2005 to October 2006, 84 patients with clinical and biochemical suspicion of GEP tumours were investigated by US and CT scans, MRI and 111In-pentetreotide scintigraphy. In 13/84 (15.4%) both conventional radiological imaging and 111In-pentetreotide scintigraphy provided negative or inconclusive findings, and patients were referred for 18F-dopa PET/CT imaging. Each patient received 5.3 MBq x kg(-1) 18F-dopa intravenously, and imaged 60 min later using a hybrid PET/CT scanner. RESULTS: 18F-dopa PET/CT detected the primary tumour in all 13 patients (size range, 7-26 mm, mean, 18 mm; SUVmax range, 2.3-16.3, mean, 5.7) and further 12 unsuspected lesions (size range, 12-23 mm, mean 17; SUVmax range 2.8-12.7, mean 4.6). Confirmation of the PET/CT findings was obtained in all patients from histopathological analysis of tissue obtained after surgery and/or biopsy. All the 18F-dopa-positive primary lesions were confirmed as being the primary tumour at histology, whereas of the other 12 unsuspected 18F-dopa-positive lesions, 11 were found to be metastatic deposits and one due to unspecific inflammation (one false positive result). Notably, the results of 18F-dopa PET/CT imaging changed the clinical management in 11/13 patients (84%). CONCLUSIONS: Our preliminary results suggest that 18F-dopa PET/CT has a promising role in GEP patients with negative or inconclusive findings at conventional radiological imaging and 111In-pentetreotide scintigraphy. The findings were helpful in biopsy guidance and played a major role in changing the management of those patients.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17460538&query_hl=1
ER  - 

TY  - JFULL
T1  - The role of high dose chemotherapy and peripheral blood stem cell support in refractory trophoblastic disease and non-gestational choriocarcinoma: A review of eight patients
A1  - Gabriel, I
A1  - Chaidos, A
A1  - Giles, C
A1  - Apperley, J
A1  - Seckl, M
A1  - Bower, M
A1  - Kanfer, E
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 185
EP  - 185
ER  - 

TY  - JFULL
T1  - Risk assessment in haemotopoietic stem cell transplantation: disease and disease stage.
A1  - Chaidos, A
A1  - Kanfer, E
A1  - Apperley, JF
J1  - Best Pract Res Clin Haematol
Y1  - 2007/06//
VL  - 20
SN  - 1521-6926
SP  - 125
EP  - 154
N2  - This chapter addresses the impact of the disease and disease status on the outcome of stem-cell transplantation. In consideration of the other topics addressed within this volume we have elected to focus on allogeneic rather than autologous transplantation. Furthermore we have not tried to be comprehensive and discuss the role of disease status in all conditions amenable to allografting, but rather to review the evidence that exists for selected haematological malignancies. Where possible we have made some clear recommendations, but where evidence is less clear we have indicated the ongoing controversies.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17448953&query_hl=1
ER  - 

TY  - JFULL
T1  - The retinoblastoma protein is an essential mediator of osteogenesis that links the p204 protein to the Cbfa1 transcription factor thereby increasing its activity.
A1  - Luan Y, Yu XP, Xu K, Ding B, Yu J, Huang Y, Yang N, Lengyel P, Di Cesare PE, Liu CJ.
J1  - J Biol Chem
Y1  - 2007/06//
VL  - 282
SP  - 16860
EP  - 16870
ER  - 

TY  - JFULL
T1  - Enhanced Bcr-Abl-specific antileukemic activity of arsenic trioxide through glutathione-depletion in imatinib-resistant cells
A1  - Konig, H
A1  - Hartel, N
A1  - Schultheis, B
A1  - Schatz, M
A1  - Lorentz, C
A1  - Melo, JV
A1  - Hehlmann, R
A1  - Hochhaus, A
A1  - La Rosee, P
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 838
EP  - 841
N2  - The development of resistance to imatinib mesylate may partly depend on high Bc-Abl-expression levels. Arsenic trioxide (ATO) has Bcr-Abl suppressing activity in vitro. Here we investigated means to improve ATO activity in CML by modulating cellular glutathione (GSH), a key regulator of ATO-activity in malignant disease. Our studies demonstrate that depletion of cellular glutathione using dl-buthionine-[S,R]-sulfoximine (BSO) enhances ATO activity against CML cells. GSH-depletion promotes enhanced Bcr-Abl specific activity of ATO through avid repression of Bcr-Abl protein levels and total cellular Bcr-Abl activity. These data provide a rationale for the clinical development of optimized ATO-based regimens through incorporation of GSH-modulators in CML treatment.
ER  - 

TY  - JFULL
T1  - The polycomb group BMI-1 gene is a molecular marker for predicting prognosis of chronic myeloid leukaemia
A1  - Mohty, M
A1  - Yong, ASM
A1  - Szydlo, RM
A1  - Apperley, JF
A1  - Melo, JV
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 196
EP  - 197
ER  - 

TY  - JFULL
T1  - Genes expressed by both mesangial cells and bone marrow-derived cells underlie genetic susceptibility to crescentic glomerulonephritis in the rat.
A1  - Smith, J
A1  - Lai, PC
A1  - Behmoaras, J
A1  - Roufosse, C
A1  - Bhangal, G
A1  - McDaid, JP
A1  - Aitman, T
A1  - Tam, FW
A1  - Pusey, CD
A1  - Cook, HT
J1  - J Am Soc Nephrol
Y1  - 2007/06//
VL  - 18
SN  - 1046-6673
SP  - 1816
EP  - 1823
N2  - The Wistar-Kyoto (WKY) rat shows marked susceptibility to crescentic glomerulonephritis. In the model of nephrotoxic nephritis (NTN) that is induced by a small dose of nephrotoxic globulin, WKY rats developed crescents in 80 +/- 2% of glomeruli at day 10, whereas no crescents were seen in Lewis rats. This was associated with marked increase in monocyte chemoattractant protein-1 synthesis in WKY glomeruli. It was posited whether susceptibility depended on circulating cells or intrinsic renal cells. Bone marrow (BM) isografts from WKY to WKY or Lewis to Lewis did not affect susceptibility to NTN. When BM was transferred from WKY to Lewis rats, crescents developed in 35 +/- 9% of glomeruli 10 d after induction of NTN, indicating that susceptibility could be transferred by BM cells. However, crescents were also seen in WKY rats that were given Lewis marrow. For assessment of the contribution of intrinsic renal cells, kidneys from WKY or Lewis rats were transplanted into F1 animals. In NTN, the ratio of crescents in the transplanted kidney to the native kidney was significantly higher for WKY-to-F1 than for Lewis-to-F1 transplants, demonstrating that the kidney itself also influences susceptibility. Mesangial cell responses were then examined in the two strains. Mesangial cells that were derived from WKY rats synthesized significantly more monocyte chemoattractant protein-1 basally and after stimulation with heat-aggregated rabbit IgG or TNF-alpha. These results show that susceptibility to NTN in the WKY rat depends on both circulating and intrinsic renal cells and that there are genetic differences between the strains in mesangial responses to inflammatory stimuli.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17475818&query_hl=1
ER  - 

TY  - JFULL
T1  - Cord blood derived mesenchymal stem cells are effective at preventing graft-versus-host disease
A1  - Tisato, V
A1  - Naresh, K
A1  - Girdlestone, J
A1  - Navarrete, C
A1  - Dazzi, F
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 317
EP  - 317
ER  - 

TY  - JFULL
T1  - Value of appropriate histology in follow-up of myeloma
A1  - Joshi, R
A1  - Horncastle, D
A1  - Elderfield, K
A1  - Lampert, I
A1  - Rahemtulla, A
A1  - Naresh, KN
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 120
EP  - 120
ER  - 

TY  - JFULL
T1  - Survival in myeloma-possible impact of thalidomide
A1  - Abdalla, SH
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 209
EP  - 209
ER  - 

TY  - JFULL
T1  - Chronic myeloid leukaemia as a model of disease evolution in human cancer.
A1  - Melo, JV
A1  - Barnes, DJ
J1  - Nat Rev Cancer
Y1  - 2007/06//
VL  - 7
SN  - 1474-175X
SP  - 441
EP  - 453
N2  - Chronic myeloid leukaemia (CML) can be considered as a paradigm for neoplasias that evolve through a multi-step process. CML is also one of the best examples of a disease that can be targeted by molecular therapy; however, the success of new 'designer drugs' is largely restricted to the chronic phase of the disease. If not cured at this stage, CML invariably progresses and transforms into an acute-type leukaemia undergoing a 'blast crisis'. The causes of this transformation are still poorly understood. What mechanisms underlie this progression, and are they shared by other common cancers?
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17522713&query_hl=1
ER  - 

TY  - JFULL
T1  - Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence.
A1  - Gubser, C
A1  - Goodbody, R
A1  - Ecker, A
A1  - Brady, G
A1  - O'Neill, LA
A1  - Jacobs, N
A1  - Smith, GL
J1  - J Gen Virol
Y1  - 2007/06//
VL  - 88
SN  - 0022-1317
SP  - 1667
EP  - 1676
N2  - Camelpox virus (CMLV) gene 176R encodes a protein with sequence similarity to murine schlafen (m-slfn) proteins. In vivo, short and long members of the m-slfn family inhibited T-cell development, whereas in vitro, only short m-slfns caused arrest of fibroblast growth. CMLV 176 protein (v-slfn) is most closely related to short m-slfns; however, when expressed stably in mammalian cells, v-slfn did not inhibit cell growth. v-slfn is a predominantly cytoplasmic 57 kDa protein that is expressed throughout infection. Several other orthopoxviruses encode v-slfn proteins, but the v-slfn gene is fragmented in all sequenced variola virus and vaccinia virus (VACV) strains. Consistent with this, all 16 VACV strains tested do not express a v-slfn detected by polyclonal serum raised against the CMLV protein. In the absence of a small animal model to study CMLV pathogenesis, the contribution of CMLV v-slfn to orthopoxvirus virulence was studied via its expression in an attenuated strain of VACV. Recombinant viruses expressing wild-type v-slfn or v-slfn tagged at its C terminus with a haemagglutinin (HA) epitope were less virulent than control viruses. However, a virus expressing v-slfn tagged with the HA epitope at its N terminus had similar virulence to controls, implying that the N terminus has an important function. A greater recruitment of lymphocytes into infected lung tissue was observed in the presence of wild-type v-slfn but, interestingly, these cells were less activated. Thus, v-slfn is an orthopoxvirus virulence factor that affects the host immune response to infection.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17485525&query_hl=1
ER  - 

TY  - JFULL
T1  - Mechanical and cold hypersensitivity in nerve-injured C57BL/6J mice is not associated with fear-avoidance- and depression-related behaviour.
A1  - Hasnie, FS
A1  - Wallace, VC
A1  - Hefner, K
A1  - Holmes, A
A1  - Rice, AS
J1  - Br J Anaesth
Y1  - 2007/06//
VL  - 98
SN  - 0007-0912
SP  - 816
EP  - 822
N2  - BACKGROUND: Neuropathic pain is associated with significant co-morbidity, including anxiety and depression, which impact considerably on the overall patient experience. However, pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. To improve the clinical validity of a widely used rodent model of traumatic peripheral neuropathy, we have investigated fear-avoidance- and depression-related behaviours in nerve-injured and sham-operated mice over a 4 week period. METHODS: Male C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) or sham surgery and were assessed on days 7, 14, and 28 after operation. Withdrawal thresholds to punctate mechanical and cooling stimuli were measured. Mice were tested on the novel open-field and elevated plus-maze tests for fear-avoidance behaviour, and on the tail suspension test for depression-related behaviour. RESULTS: Hypersensitivity to punctate mechanical and cool stimuli was evident up to day 28 after PSNL. However, there was no change in fear-avoidance- or depression-related behaviours regardless of interval after-surgery. CONCLUSION: These data demonstrate that pain behaviour in nerve-injured C57BL/6J mice was not associated with alterations in emotion-related behaviours.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17478455&query_hl=1
ER  - 

TY  - JFULL
T1  - Can organisational change reduce hospital acquired infections?
A1  - Holmes, AH
J1  - J Hosp Infect
Y1  - 2007/06//
VL  - 65 Suppl 2
SN  - 0195-6701
SP  - 191
EP  - 192
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17540269&query_hl=1
ER  - 

TY  - JFULL
T1  - Antimicrobial prophylaxis for endocarditis: emotion or science? Reply
A1  - Bogle, RG
A1  - Ashrafian, H
J1  - HEART
Y1  - 2007/06//
VL  - 93
SN  - 1355-6037
SP  - 753
EP  - 754
ER  - 

TY  - JFULL
T1  - BCR-ABL kinase mutations in response to dasatinib
A1  - Khorashad, JS
A1  - Mehta, P
A1  - Milojkovic, D
A1  - Marin, DC
A1  - Kaeda, JS
A1  - Swale, B
A1  - Stevens, D
A1  - Goldman, JM
A1  - Apperley, JF
J1  - HAEMATOL-HEMATOL J
Y1  - 2007/06//
VL  - 92
SN  - 0390-6078
SP  - 202
EP  - 202
ER  - 

TY  - JFULL
T1  - Quantifying HTLV-I dynamics.
A1  - Asquith, B
A1  - Bangham, CR
J1  - Immunol Cell Biol
Y1  - 2007/06//
VL  - 85
SN  - 0818-9641
SP  - 280
EP  - 286
N2  - Despite significant advances in our understanding of the immune response to persistent viruses like human T-cell lymphotropic virus type I (HTLV-I), many important questions remain unanswered. Mathematical modelling enables us to interpret and synthesise diverse experimental data in new ways and thus can contribute to our understanding. Here, we review recent advances in mathematical modelling of HTLV-I infection and illustrate how mathematics has enabled us to identify factors that determine an individual's viral burden and risk of developing HTLV-I-associated diseases.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17372609&query_hl=1
ER  - 

TY  - JFULL
T1  - RSV-infected airway epithelial cells cause biphasic up-regulation of CCR1 expression on human monocytes.
A1  - Morrison, PT
A1  - Thomas, LH
A1  - Sharland, M
A1  - Friedland, JS
J1  - J Leukoc Biol
Y1  - 2007/06//
VL  - 81
SN  - 0741-5400
SP  - 1487
EP  - 1495
N2  - Respiratory syncytial virus (RSV) infection can cause extensive airway inflammation, which is orchestrated by chemokines and their receptors. RSV-infected epithelial cells secrete many cytokines and chemokines, but little is known about regulation of chemokine receptors on target cells. We investigated the effects of conditioned media (CM) from RSV-infected epithelial cells on monocyte CCR1, CCR2, and CCR5 expression. RSV-CM but not control-CM stimulated a biphasic increase in cell-surface CCR1, and levels peaked at 36 h and 96 h poststimulation. Similar CCR1 up-regulation occurred on monocyte-derived macrophages. Cytochlasin D and colchicine blocked both peaks of expression, demonstrating requirement of a functional cytoskeleton. Intracellular staining revealed little internal sequestration of CCR1 protein, and CCR1 up-regulation was inhibited by actinomycin D and cycloheximide, indicating that both waves of RSV-CM-induced surface CCR1 expression were dependent on de novo transcription and protein synthesis. Cytokine-neutralizing experiments showed that the effects of RSV-CM were decreased by blocking TNF-alpha (percent inhibition=51+/-2.3% at 36 h peak and 42+/-7.7% at 96 h peak) and to a lesser extent, IL-1 (percent inhibition=32+/-7.2% at 36 h and 23+/-2.9% at 96 h). In summary, RSV-CM causes a biphasic up-regulation of surface CCR1 on monocytes, which is dependent on an intact cytoskeleton, requires new gene transcription and protein synthesis, and is mediated in part by the proinflammatory cytokines TNF-alpha and IL-1.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17389578&query_hl=1
ER  - 

TY  - JFULL
T1  - Increased haemoglobin A2 percentage in HIV infection: disease or treatment?
A1  - Wilkinson, MJ
A1  - Bain, BJ
A1  - Phelan, L
A1  - Benzie, A
J1  - AIDS
Y1  - 2007/05/31/
VL  - 21
SN  - 0269-9370
SP  - 1207
EP  - 1208
N2  - An elevated haemoglobin A2 percentage has been reported in HIV-infected patients, possibly attributable to therapy. In cross-sectional and cohort studies we have established that A2 is often elevated in untreated patients; a further rise during treatment is attributable specifically to zidovudine. The haemoglobin A2 may be high enough to lead to a misdiagnosis of beta thalassemia trait if there is a lack of awareness of this unexpected effect of HIV infection and its treatment.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17502732&query_hl=1
ER  - 

TY  - JFULL
T1  - Natural Ventilation for Prevention of Airborne Contagion: Authors' Reply.
A1  - Escombe, AR
A1  - Moore, DA
A1  - Friedland, JS
A1  - Evans, CA
A1  - Gilman, RH
J1  - PLoS Med
Y1  - 2007/05/29/
VL  - 4
SN  - 1549-1676
SP  - e195
N2  - 
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17535109&query_hl=1
ER  - 

TY  - JFULL
T1  - Searching for novel biomarkers of centrally and peripehrally-acting neurotoxicants, using surface-enhanced laser desorption/ionisation-time-of-flight mass spectrometry (SELDI-TOF MS).
A1  - Fang, M
A1  - Boobis, AR
A1  - Edwards, RJ
J1  - Food Chem Toxicol
Y1  - 2007/05/24/
SN  - 0278-6915
N2  - The neurotoxicity of chemicals to humans is difficult to monitor as there are no suitable methods of detecting early neuronal dysfunction. Here, a proof of principle study was designed to assess the potential of identifying protein biomarkers in accessible biofluids for this purpose. Groups of rats were treated with a range of doses of the model neurotoxicants, acrylamide (0, 2, 10, 50mg/kg) and methylmercury (0, 0.2, 1, 5mg/kg) for up to 3 weeks and samples of serum, urine, and cerebral spinal fluid analysed by surface-enhanced laser desorption/ionisation-time-of-flight mass spectrometry. There was no neuropathology up to the highest dose tested. Protein profiles were obtained from all samples and changes in the levels of many proteins were detected in both serum and urine, although not cerebral spinal fluid. In serum, the combination of three protein ion levels with m/z values of 4968, 9402 and 12,948 was able to correctly classify the treatment groups thus: 88% control, 100% acrylamide, 92% methylmercury. In urine, three protein ions with m/z values of 4944, 12,966 and 21,992 classified correctly the groups: 67% control, 94% acrylamide, 97% methylmercury. Similar classifications using other serum and urinary protein ions were also possible. This indicates the potential of serum and urine protein biomarkers for the assessment of sub-clinical neurotoxicity.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17602814&query_hl=1
ER  - 

TY  - JFULL
T1  - Synthesis of glycerol phosphate lipoteichoic acid in Staphylococcus aureus.
A1  - Gründling, A
A1  - Schneewind, O
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/05/15/
VL  - 104
SN  - 0027-8424
SP  - 8478
EP  - 8483
N2  - Lipoteichoic acid (LTA), a glycerol phosphate surface polymer, is a component of the envelope of Gram-positive bacteria. However, the molecular basis for its synthesis or function is not known. Here we report that Staphylococcus aureus LtaS synthesizes glycerol phosphate LTA. Construction of a mutant S. aureus strain with inducible ltaS expression revealed that LTA synthesis is required for bacterial growth and cell division. An ltaS homologue of Bacillus subtilis restored LTA synthesis and the growth of ltaS mutant staphylococci. Thus, LtaS inhibition can be used as a target to treat human infections caused by antibiotic-resistant S. aureus or other bacterial pathogens.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17483484&query_hl=1
ER  - 

TY  - JFULL
T1  - The detection of airborne transmission of tuberculosis from HIV-infected patients, using an in vivo air sampling model.
A1  - Escombe, AR
A1  - Oeser, C
A1  - Gilman, RH
A1  - Navincopa, M
A1  - Ticona, E
A1  - Martínez, C
A1  - Caviedes, L
A1  - Sheen, P
A1  - Gonzalez, A
A1  - Noakes, C
A1  - Moore, DA
A1  - Friedland, JS
A1  - Evans, CA
J1  - Clin Infect Dis
Y1  - 2007/05/15/
VL  - 44
SN  - 1537-6591
SP  - 1349
EP  - 1357
N2  - BACKGROUND: Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures. METHODS: An animal facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima, Peru. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air for 16 months. Animals had tuberculin skin tests performed at monthly intervals, and those with positive reactions were removed for autopsy and culture for tuberculosis. RESULTS: Over 505 consecutive days, there were 118 ward admissions by 97 patients with pulmonary tuberculosis, with a median duration of hospitalization of 11 days. All patients were infected with HIV and constituted a heterogeneous group with both new and existing diagnoses of tuberculosis. There was a wide variation in monthly rates of guinea pigs developing positive tuberculin test results (0%-53%). Of 292 animals exposed to ward air, 159 developed positive tuberculin skin test results, of which 129 had laboratory confirmation of tuberculosis. The HIV-positive patients with pulmonary tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with 1.25 for HIV-negative patients with tuberculosis in similar studies from the 1950s. The mean monthly patient infectiousness varied greatly, from production of 0-44 infectious quanta per hour, as did the theoretical risk for a health care worker to acquire tuberculosis by breathing ward air. CONCLUSIONS: HIV-positive patients with tuberculosis varied greatly in their infectiousness, and some were highly infectious. Use of environmental control strategies for nosocomial tuberculosis is therefore a priority, especially in areas with a high prevalence of both tuberculosis and HIV infection.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17443474&query_hl=1
ER  - 

TY  - JFULL
T1  - Resistance to imatinib mesylate in chronic myeloid leukaemia.
A1  - Melo, JV
A1  - Chuah, C
J1  - Cancer Lett
Y1  - 2007/05/08/
VL  - 249
SN  - 0304-3835
SP  - 121
EP  - 132
N2  - Despite the remarkable results achieved with imatinib for the treatment of chronic myeloid leukaemia, the emergence of resistance to this tyrosine kinase inhibitor has become a significant problem. Much progress has been recently made in elucidating the mechanisms which underlie imatinib resistance. The most common cause of such drug resistance is the selection of leukaemic clones with point mutations in the Abl kinase domain leading to amino acid substitutions which prevent the appropriate binding of the drug. Other mechanisms include genomic amplification of BCR-ABL and modulation of drug efflux or influx transporters. There is a pressing need, therefore, to develop and test novel drugs and strategies. Two such compounds are now being explored in clinical trials. This review will describe the molecular basis of imatinib-resistance and strategies to overcome resistance.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16949736&query_hl=1
ER  - 

TY  - JFULL
T1  - In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection.
A1  - Asquith, B
A1  - Zhang, Y
A1  - Mosley, AJ
A1  - de Lara, CM
A1  - Wallace, DL
A1  - Worth, A
A1  - Kaftantzi, L
A1  - Meekings, K
A1  - Griffin, GE
A1  - Tanaka, Y
A1  - Tough, DF
A1  - Beverley, PC
A1  - Taylor, GP
A1  - Macallan, DC
A1  - Bangham, CR
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/05/08/
VL  - 104
SN  - 0027-8424
SP  - 8035
EP  - 8040
N2  - Human T-lymphotropic virus type 1 (HTLV-1) is a persistent CD4+ T-lymphotropic retrovirus. Most HTLV-1-infected individuals remain asymptomatic, but a proportion develop adult T cell leukemia or inflammatory disease. It is not fully understood how HTLV-1 persists despite a strong immune response or what determines the risk of HTLV-1-associated diseases. Until recently, it has been difficult to quantify lymphocyte kinetics in humans in vivo. Here, we used deuterated glucose labeling to quantify in vivo lymphocyte dynamics in HTLV-1-infected individuals. We then used these results to address four questions. (i) What is the impact of HTLV-1 infection on lymphocyte dynamics? (ii) How does HTLV-1 persist? (iii) What is the extent of HTLV-1 expression in vivo? (iv) What features of lymphocyte kinetics are associated with HTLV-1-associated myelopathy/tropical spastic paraparesis? We found that CD4+CD45RO+ and CD8+CD45RO+ T lymphocyte proliferation was elevated in HTLV-1-infected subjects compared with controls, with an extra 10(12) lymphocytes produced per year in an HTLV-1-infected subject. The in vivo proliferation rate of CD4+CD45RO+ cells also correlated with ex vivo viral expression. Finally, the inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis was associated with significantly increased CD4+CD45RO+ cell proliferation. We suggest that there is persistent viral gene expression in vivo, which is necessary for the maintenance of the proviral load and determines HTLV-1-associated myelopathy/tropical spastic paraparesis risk.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17483473&query_hl=1
ER  - 

TY  - JFULL
T1  - The interferon inducing pathways and the hepatitis C virus.
A1  - Meurs, EF
A1  - Breiman, A
J1  - World J Gastroenterol
Y1  - 2007/05/07/
VL  - 13
SN  - 1007-9327
SP  - 2446
EP  - 2454
N2  - The innate immune response is triggered by a variety of pathogens, including viruses, and requires rapid induction of type I interferons (IFN), such as IFNbeta and IFNalpha. IFN induction occurs when specific pathogen motifs bind to specific cellular receptors. In non-professional immune, virally-infected cells, IFN induction is essentially initiated after the binding of dsRNA structures to TLR3 receptors or to intracytosolic RNA helicases, such as RIG-I/MDA5. This leads to the recruitment of specific adaptors, such as TRIF for TLR3 and the mitochondrial-associated IPS-1/VISA/MAVS/CARDIF adapter protein for the RNA helicases, and the ultimate recruitment of kinases, such as MAPKs, the canonical IKK complex and the TBK1/IKKepsilon kinases, which activate the transcription factors ATF-2/c-jun, NF-kappaB and IRF3, respectively. The coordinated action of these transcription factors leads to induction of IFN and of pro-inflammatory cytokines and to the establishment of the innate immune response. HCV can cleave both the adapters TRIF and IPS-1/VISA/MAVS/CARDIF through the action of its NS3/4A protease. This provokes abrogation of the induction of the IFN and cytokine pathways and favours viral propagation and presumably HCV chronic infection.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17552028&query_hl=1
ER  - 

TY  - JFULL
T1  - Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3.
A1  - Villegas-Mendez, A
A1  - Montes, R
A1  - Ambrose, LR
A1  - Warrens, AN
A1  - Laffan, M
A1  - Lane, DA
J1  - J Thromb Haemost
Y1  - 2007/05//
VL  - 5
SN  - 1538-7933
SP  - 980
EP  - 988
N2  - BACKGROUND: The endothelial cell protein C receptor (EPCR) presents protein C to the thrombin:thrombomodulin complex on the endothelium of large vessels, and enhances the generation of activated protein C (APC) and activation of protease-activated receptor-1. A previous report has demonstrated binding of soluble (s) EPCR to activated neutrophils via surface proteinase 3 (PR3). METHODS: We now report further characterization of this interaction. Activated neutrophils and purified PR3 both decrease endothelial cell (EC) surface EPCR, suggestive of its proteolysis. RESULTS: When added to purified recombinant sEPCR, PR3 produced multiple cleavages, with early products including 20 kDa N-terminal and C-terminal (after Lys(176)) fragments. The binding of active site blocked PR3 to sEPCR was studied by surface plasmon resonance. Estimates of the K(D) of 18.5-102 nM were obtained with heterogeneous binding, suggestive of more than a single interaction site. CONCLUSIONS: This work demonstrates PR3 binding to and proteolysis of EPCR and suggests a mechanism by which anticoagulant and cell protective pathways can be down-regulated during inflammation.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17459006&query_hl=1
ER  - 

TY  - JFULL
T1  - Definition of a minimal region of deletion of chromosome 7 in uterine leiomyomas by tiling-path microarray CGH and mutation analysis of known genes in this region.
A1  - Vanharanta, S
A1  - Wortham, NC
A1  - Langford, C
A1  - El-Bahrawy, M
A1  - van der Spuy, Z
A1  - Sjöberg, J
A1  - Lehtonen, R
A1  - Karhu, A
A1  - Tomlinson, IP
A1  - Aaltonen, LA
J1  - Genes Chromosomes Cancer
Y1  - 2007/05//
VL  - 46
SN  - 1045-2257
SP  - 451
EP  - 458
N2  - Somatic interstitial deletions of chromosome segment 7q22-q31 in uterine leiomyomas are a frequent event, thought to be indicative of a tumor suppressor gene in the region. Previous LOH and CGH studies have refined this region to 7q22.3-q31, although the target gene has not been identified. Here, we have used tiling-path resolution microarray CGH to further refine the region and to identify homozygous deletions in fibroids. Furthermore, we have screened all manually annotated genes in the region for mutations. We have refined the minimum deleted region at 7q22.3-q31 to 2.79 Mbp and identified a second region of deletion at 7q34. However, we identified no pathogenic coding variation.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17285575&query_hl=1
ER  - 

TY  - JFULL
T1  - Interactions between Neisseria meningitidis and the complement system.
A1  - Schneider, MC
A1  - Exley, RM
A1  - Ram, S
A1  - Sim, RB
A1  - Tang, CM
J1  - Trends Microbiol
Y1  - 2007/05//
VL  - 15
SN  - 0966-842X
SP  - 233
EP  - 240
N2  - Meningococcal infection remains a worldwide health problem, and understanding the mechanisms by which Neisseria meningitidis evades host innate and acquired immunity is crucial. The complement system is vital for protecting individuals against N. meningitidis. However, this pathogen has evolved several mechanisms to avoid killing by human complement. Bacterial structures such as polysaccharide capsule and those which mimic or bind host molecules function to prevent complement-mediated lysis and phagocytosis. This review provides an update on the recent findings on the diverse mechanisms by which N. meningitidis avoids complement-mediated killing, and how polymorphisms in genes encoding human complement proteins affect susceptibility to this important human pathogen.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17398100&query_hl=1
ER  - 

TY  - JFULL
T1  - Glandular Paget's disease of the nipple.
A1  - Shousha, S
J1  - Histopathology
Y1  - 2007/05//
VL  - 50
SN  - 0309-0167
SP  - 812
EP  - 814
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17376174&query_hl=1
ER  - 

TY  - JFULL
T1  - Effects of exercise on gut peptides, energy intake and appetite
A1  - Martins, C
A1  - Morgan, LM
A1  - Bloom, SR
A1  - Robertson, MD
J1  - J ENDOCRINOL
Y1  - 2007/05//
VL  - 193
SN  - 0022-0795
SP  - 251
EP  - 258
N2  - This study investigated the acute effects of exercise on the postprandial levels of appetite-related hormones and metabolites, energy intake (EI) and subjective measures of appetite. Ghrelin, polypeptide YY (PYY), glucagon-like peptide-1 (GLP-1) and pancreatic polypeptide (PP) were measured in the fasting state and postprandially in 12 healthy, normal-weight volunteers (six males and six females) using a randomised crossover design. One hour after a standardised breakfast, subjects either cycled for 60 min at 65% of their maximal heart rate or rested. Subjective appetite was assessed throughout the study using visual analogue scales and subsequent El at a buffet meal was measured at the end (3-h post-breakfast and I-h post-exercise). Exercise significantly increased mean PYY, GLP-1 and PP levels, and this effect was maintained during the post-exercise period for GLP-1 and PP. No significant effect of exercise was observed on postprandial levels of ghrehn. During the exercise period, hunger scores were significantly decreased; however, this effect disappeared in the post-exercise period. Exercise significantly increased subsequent absolute El, but produced a significant decrease in relative El after accounting for the energy expended during exercise. Hunger scores and PYY, GLP-1 and PP levels showed an inverse temporal pattern during the 1-h exercise/control intervention. In conclusion, acute exercise, of moderate intensity, temporarily decreased hunger sensations and was able to produce a short-term negative energy balance. This impact on appetite and subsequent energy homeostasis was not explained by changes in postprandial levels of ghrelin; however, 'exercise-induced anorexia' may potentially be linked to increased PYY, GLP-1 and PP levels.
ER  - 

TY  - JFULL
T1  - Physiological blockade of gut hormones increases food intake.
A1  - Vincent, R
A1  - le Roux, C
A1  - Kokkinos, A
A1  - Ghatei, M
A1  - Bloom, S
J1  - INT J OBESITY
Y1  - 2007/05//
VL  - 31
SN  - 0307-0565
SP  - S21
EP  - S21
ER  - 

TY  - JFULL
T1  - Reversal of refractory c4d chronic allograft nephropathy with ritximab.
A1  - Galliford, J
A1  - Cook, T
A1  - Brookes, P
A1  - Chan, K
A1  - Taube, D
A1  - Dorling, A
J1  - AM J TRANSPLANT
Y1  - 2007/05//
VL  - 7
SN  - 1600-6135
SP  - 526
EP  - 526
ER  - 

TY  - JFULL
T1  - Further characterization of ADAMTS-13 inactivation by thrombin.
A1  - Lam, JK
A1  - Chion, CK
A1  - Zanardelli, S
A1  - Lane, DA
A1  - Crawley, JT
J1  - J Thromb Haemost
Y1  - 2007/05//
VL  - 5
SN  - 1538-7933
SP  - 1010
EP  - 1018
N2  - BACKGROUND: The multimeric size and platelet-tethering function of von Willebrand factor (VWF) are modulated by the plasma metalloprotease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13). In vitro ADAMTS-13 is susceptible to proteolytic inactivation by thrombin. OBJECTIVES: In this study, we aimed to characterize the inactivation of ADAMTS-13 by thrombin and to assess its physiological significance. METHODS AND RESULTS: By N-terminal sequencing of cleavage products, and by mutagenesis, we identified the principal thrombin cleavage sites in ADAMTS-13 as R257 and R1176. Using a library of 76 thrombin mutants, we highlighted the functional importance of exosite I on thrombin in the proteolysis of ADAMTS-13. Proteolysis of ADAMTS-13 by thrombin caused an 8-fold reduction in its affinity for VWF that contributed to its loss of VWF-cleaving function. Intriguingly, thrombin-cleaved ADAMTS-13 both bound and proteolyzed a short recombinant VWF A2 domain substrate (VWF115) normally. Following activation of coagulation in normal plasma, endogenous ADAMTS-13, but not added ADAMTS-13, appeared resistant to coagulation-induced fragmentation. An estimation of the K(m) for ADAMTS-13 proteolysis by thrombin was appreciably higher than the physiological concentration of ADAMTS-13. This was corroborated by the comparatively low affinity of ADAMTS-13 for thrombin (K(D) 95 nM). CONCLUSIONS: Together, our data suggest that ADAMTS-13 is protected from rapid proteolytic inactivation by thrombin in normal plasma. Whether this remains the case under pathological situations involving elevated/sustained generation of thrombin remains unclear.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17355572&query_hl=1
ER  - 

TY  - JFULL
T1  - Ventilation-perfusion scintigraphy is more sensitive than multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause of pulmonary hypertension.
A1  - Tunariu, N
A1  - Gibbs, SJ
A1  - Win, Z
A1  - Gin-Sing, W
A1  - Graham, A
A1  - Gishen, P
A1  - Al-Nahhas, A
J1  - J Nucl Med
Y1  - 2007/05//
VL  - 48
SN  - 0161-5505
SP  - 680
EP  - 684
N2  - Pulmonary hypertension (PH) is a progressive disease with a poor prognosis. Identifying chronic thromboembolic pulmonary disease as a cause of PH has major clinical implications as these patients could be potentially offered a surgical cure. Ventilation-perfusion (V/Q) scintigraphy has a high sensitivity to detect embolic disease but its value has been challenged with the emergence of multidetector CT pulmonary angiography (CTPA). We compared the value of V/Q scintigraphy with CTPA in detecting chronic thromboembolic pulmonary disease. METHODS: We retrospectively reviewed the results of V/Q scintigraphy and CTPA performed on patients who had been referred to the Pulmonary Hypertension Service at Hammersmith Hospital between 2000 and 2005. A total of 227 patients (85 males, 142 females; age range, 18-81 y; mean age, 42 y) had all tests done at Hammersmith Hospital and were included in the study. Interpretation of scans was according to the modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) criteria. CTPA was considered as suggestive of chronic thromboembolic pulmonary disease if it showed visualization of the thrombus or webs, recanalization, perfusion abnormalities, stenosis, or strictures. Standard pulmonary angiography was performed via femoral approach. In 90% of the cases, CTPA and V/Q scintigraphy were performed within 10 d. RESULTS: Seventy-eight patients (group A) had a final diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) and 149 (group B) had non-CTEPH etiology. Among group A, V/Q scintigraphy was reported as high probability in 75 patients, intermediate probability in 1 patient, and low probability in 2 patients. CTPA was positive in 40 patients and negative in 38 patients. Among group B, V/Q scintigraphy was reported as low probability in 134, intermediate probability in 7, and high probability in 8 patients. CTPA was negative in 148 patients and false-positive in 1 patient. Statistical analysis showed V/Q scintigraphy to have a sensitivity of 96%-97.4% and a specificity of 90%-95%. CTPA showed a sensitivity of 51% and a specificity of 99%. CONCLUSION: Our results demonstrate that V/Q scintigraphy has a higher sensitivity than CTPA in detecting CTEPH as a potential curable cause of PH.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17475953&query_hl=1
ER  - 

TY  - JFULL
T1  - 68Ga-DOTATATE PET in neuroectodermal tumours: first experience.
A1  - Win, Z
A1  - Al-Nahhas, A
A1  - Towey, D
A1  - Todd, JF
A1  - Rubello, D
A1  - Lewington, V
A1  - Gishen, P
J1  - Nucl Med Commun
Y1  - 2007/05//
VL  - 28
SN  - 0143-3636
SP  - 359
EP  - 363
N2  - BACKGROUND AND AIM: Phaeochromocytoma is initially imaged with computed tomography (CT) or magnetic resonance imaging (MRI) but functional imaging is commonly needed to assess disease activity, the presence of metastasis and response to therapy. Traditionally, this is done with 123I -MIBG with good sensitivity and specificity. However, spatial resolution remains limited even with SPECT. We aimed to assess the utility of a new somatostatin analogue PET tracer, 68Ga-DOTATATE in the management of phaeochromocytoma. METHODS: We retrospectively reviewed five patients with malignant phaeochromocytoma who underwent imaging with CT and 123I-MIBG and compared the results with those of PET imaging using 68Ga-DOTATATE. Blinded analysis of the numbers and extent of lesions were done for all imaging modality. RESULTS: Two patients had negative 123I-MIBG and positive 68Ga-DOTATATE scans. One had a weakly positive 123I-MIBG and a strongly positive 68Ga-DOTATATE scan. One had a positive 123I-MIBG and positive 68Ga-DOTATATE scans. The fifth patient was negative to all imaging including CT. 68Ga-DOTATATE showed more lesions with higher uptake and better resolution compared to 123I-MIBG. CONCLUSION: The findings in our small group of patients demonstrate the value of somatostatin receptor PET imaging in malignant phaeochromocytoma. In lesions with no or low MIBG uptake, the next investigation of choice should be PET imaging with 68Ga-DOTATATE, in view to therapy with Y-labelled DOTATATE.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17414885&query_hl=1
ER  - 

TY  - JFULL
T1  - T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice.
A1  - von Delwig, A
A1  - Altmann, DM
A1  - Charlton, FG
A1  - McKie, N
A1  - Isaacs, JD
A1  - Holmdahl, R
A1  - Robinson, JH
J1  - Ann Rheum Dis
Y1  - 2007/05//
VL  - 66
SN  - 0003-4967
SP  - 599
EP  - 604
N2  - AIM: To study collagen-induced arthritis in human leucocyte antigen (HLA)-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules (MHC-II) and to determine T cell specificity against the arthritogenic CII(259-273) epitope of type II collagen either unmodified or post-translationally glycosylated at Lys(264). METHODS: Arthritis was induced by immunisation with human type II collagen in complete Freund's adjuvant and measured by footpad swelling, clinical score and histology. T cell responses were assessed by proliferation of spleen and lymph node cells and in antigen presentation assays, using T cell hybridomas specific for the glycosylated and non-glycosylated CII(259-273) epitope. RESULTS: The incidence of arthritis was 50% in DR1-transgenic mice lacking endogenous MHC-II molecules. Recall T cell responses in draining lymph nodes and spleen were consistently greater against the non-glycosylated epitope than to the glycosylated CII(259-273). Most of the T cell hybridomas generated from CII-immunised mice recognised the non-glycosylated CII epitope and this form of the epitope was also presented with 100-fold higher efficiency and 1 h faster kinetics by both macrophages and dendritic cells. CONCLUSION: This study shows that T cell responses to the non-glycosylated epitope of heterologous (human) CII are dominant in HLA-DR1 transgenic mice lacking MHC-II, which could contribute to the pathogenicity of autoimmune arthritis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17114189&query_hl=1
ER  - 

TY  - JFULL
T1  - Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study.
A1  - Ronkainen, J
A1  - Talley, NJ
A1  - Aro, P
A1  - Storskrubb, T
A1  - Johansson, SE
A1  - Lind, T
A1  - Bolling-Sternevald, E
A1  - Vieth, M
A1  - Stolte, M
A1  - Walker, MM
A1  - Agréus, L
J1  - Gut
Y1  - 2007/05//
VL  - 56
SN  - 0017-5749
SP  - 615
EP  - 620
N2  - BACKGROUND: Eosinophilic oesophagitis may be increasing but the prevalence in the general population remains unknown. Our aim was to assess this and the presence of eosinophils in the distal oesophageal epithelium in the community. METHODS: Oesophagogastroduodenoscopy was performed in a random sample (n = 1000) of the adult Swedish population (mean age 54 years, 49% men). Oesophageal biopsy samples were obtained from 2 cm above, and at, the Z-line. Any eosinophil infiltration of the epithelium was defined as "eosinophils present". Definite eosinophilic oesophagitis was defined as > or =20, probable as 15-19, and possible as 5-14 eosinophils/high-power field (HPF, at magnification x 40) in oesophageal biopsy specimens. RESULTS: Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1%, mean age 54 years, 63% men), in 54% without troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95% CI 0.01 to 0.8%, mean age 51 years, 75% men) and probable eosinophilic oesophagitis in seven subjects (0.7%, 95% CI 0.2 to 1.2%, mean age 58 years, 43% men). Erosive oesophagitis (OR = 2.99, 95% CI 1.58 to 5.66) and absence of dyspepsia (OR = 0.23, 95% CI 0.07 to 0.75) and Helicobacter pylori infection (OR = 0.41, 95% CI 0.19 to 0.92) were independent predictors for "eosinophils present". Definite eosinophilic oesophagitis was associated with dysphagia (2/66 vs 2/926, p = 0.025), and probable eosinophilic oesophagitis with narrowing of the oesophageal lumen (2/15 vs 5/978, p = 0.005). CONCLUSIONS: Oesophageal eosinophils were present in nearly 5% of the general population; approximately 1% had definite or probable eosinophilic oesophagitis. Oesophageal eosinophils may be a manifestation of reflux disease in adults, but the condition is as likely to be asymptomatic and go unrecognised.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17135307&query_hl=1
ER  - 

TY  - JFULL
T1  - Appetite regulation: an overview.
A1  - Dhillo, WS
J1  - Thyroid
Y1  - 2007/05//
VL  - 17
SN  - 1050-7256
SP  - 433
EP  - 445
N2  - Obesity is a major public health problem associated with morbidity and mortality and continues to increase worldwide. This review focuses on the regions of the brain that are important in appetite regulation and the circulating factors implicated in the control of food intake. The hypothalamus is critical in the regulation of food intake containing neural circuits, which produce a number of peptides that influence food intake. The arcuate nucleus of the hypothalamus produces both orexigenic peptides (agouti-related protein and neuropeptide Y) and anorectic peptides (alpha-melanocyte-stimulating hormone and cocaine- and amphetamine-related transcript). The lateral hypothalamus produces the orexigenic peptides (melanin-concentrating hormone and orexins). Other hypothalamic factors recently implicated in appetite regulation include the endocannabinoids, brain-derived neurotrophic factor, nesfatin-1, AMP-activated protein kinase, mammalian target of rapamycin protein, and protein tyrosine phosphatase. Circulating factors that affect food intake mediate their effects by signaling to the hypothalamus and/or brainstem. A number of circulating factors are produced by peripheral organs, for example, leptin by adipose tissue, insulin and pancreatic polypeptide by the pancreas, gut hormones (e.g., ghrelin, obestatin, glucagon-like peptide-1, oxyntomodulin, peptide YY), and triiodothyronine by the thyroid gland. Circulating carbohydrates, lipids, and amino acids also affect appetite regulation. Knowledge regarding appetite regulation has vastly expanded in recent years providing targets for antiobesity drug design.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17542673&query_hl=1
ER  - 

TY  - JFULL
T1  - Gastrostomy placement in paediatric patients with neuromuscular disorders: indications and outcome.
A1  - Ramelli, GP
A1  - Aloysius, A
A1  - King, C
A1  - Davis, T
A1  - Muntoni, F
J1  - Dev Med Child Neurol
Y1  - 2007/05//
VL  - 49
SN  - 0012-1622
SP  - 367
EP  - 371
N2  - Studies of children with neurodevelopmental disorders have shown that receiving nutrition through a gastrostomy can improve clinical outcomes and quality of life. However, there is little information on gastrostomy and its effect in patients with neuromuscular disorders. A retrospective casenote review of all patients with a gastrostomy, followed-up at the Hammersmith Hospital, London, was undertaken to assess the indications for, and outcomes of, gastrostomy placement. Notes for 32 patients (17 males, 15 females) were reviewed (age range 32mo-31y; median age 12y 5mo). We found three main groups of diagnoses: congenital muscular dystrophy (n=15), structural congenital myopathies (n=11), and other neuromuscular disorders (n=6). Two main patterns of feeding problems were identified before gastrostomy: swallowing difficulties, and nutrition and growth problems. The follow-up period after gastrostomy was from 12 months to 19 years (mean 5y). Weight faltering was reversed in 17 out of 22 patients, and height faltering in 9 out of 14, where data were available. Twenty-six patients had a reduced frequency of chest infections. No significant complication of gastrostomy placement was documented. Twenty-eight patients or their families were happy with the results of the gastrostomy. Gastrostomy seems to have a substantial positive impact in patients with neuromuscular disease and feeding difficulties.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17489811&query_hl=1
ER  - 

TY  - JFULL
T1  - Carbon monoxide-releasing molecules modulate leukocyte-endothelial interactions under flow.
A1  - Urquhart, P
A1  - Rosignoli, G
A1  - Cooper, D
A1  - Motterlini, R
A1  - Perretti, M
J1  - J Pharmacol Exp Ther
Y1  - 2007/05//
VL  - 321
SN  - 0022-3565
SP  - 656
EP  - 662
N2  - Carbon monoxide (CO) generated by the enzyme heme oxygenase during the breakdown of heme is known to mediate a number of biological effects. Here, we investigated whether CO liberated from a water-soluble CO-releasing molecule (CO-RM) is capable of modulating leukocyte-endothelial interactions. Tricarbonylchoro(glycinato)ruthenium (II) (CORM-3), a fast CO releaser, proved to be anti-inflammatory in two distinct models of acute inflammation in vivo. In both cases, a significant reduction in neutrophil extravasation was observed. Subsequent in vitro static experiments showed that CORM-3 produced a direct effect on neutrophil (polymorphonuclear neutrophil; PMN) adhesion molecule expression; dose-dependently inhibiting platelet-activating factor stimulated CD11b up-regulation and L-selectin shedding, whereas no effect was observed on up-regulation of human umbilical vein endothelial cell (HUVEC) adhesion molecules intercellular adhesion molecule-1 or E-selectin nor on interleukin-8 chemokine production. In addition, when PMN interaction with HUVECs was studied, an inhibitory effect of CORM-3 on cell capture and rolling was observed. The effect of CORM-3 on PMN CD11b expression was mimicked by the incubation of PMN with the selective large potassium channel opener 1,3-dihydro-1-(2-hydroxy-5-(trifluoromethyl)-phenyl)-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS-1619), which suggests that CORM-3 actions in this instance are mediated, at least in part, via opening of this channel. In conclusion, we have reported that CORM-3 possesses acute anti-inflammatory effects in vivo and that these are probably the result of targeting PMN activation and rolling upon the endothelium.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17289832&query_hl=1
ER  - 

TY  - JFULL
T1  - Gut hormones and appetite control.
A1  - Wren, AM
A1  - Bloom, SR
J1  - Gastroenterology
Y1  - 2007/05//
VL  - 132
SN  - 0016-5085
SP  - 2116
EP  - 2130
N2  - Many peptides are synthesized and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that they also physiologically influence eating behavior. Our understanding of how neurohormonal gut-brain signaling regulates energy homeostasis has advanced significantly in recent years. Ghrelin is an orexigenic peptide produced by the stomach, which appears to act as a meal initiator. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin. Recent research suggests that gut hormones can be manipulated to regulate energy balance in humans, and that obese subjects retain sensitivity to the actions of gut hormones. Gut hormone-based therapies may thus provide an effective and well-tolerated treatment for obesity.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17498507&query_hl=1
ER  - 

TY  - JFULL
T1  - Invasive group A streptococcal infection in injecting drug users and non-drug users in a single UK city.
A1  - Curtis, SJ
A1  - Tanna, A
A1  - Russell, HH
A1  - Efstratiou, A
A1  - Paul, J
A1  - Cubbon, M
A1  - Sriskandan, S
J1  - J Infect
Y1  - 2007/05//
VL  - 54
SN  - 0163-4453
SP  - 422
EP  - 426
N2  - OBJECTIVES: Injecting drug users (IDU) represent an increasing proportion of patients with invasive group A streptococcal (GAS) disease. Our aims were to characterise the clinical presentation and strains causing GAS bacteremia in IDU from a single UK city (Brighton and Hove), and to compare this patient group with non-drug users (non-DU) with GAS bacteremia. METHODS: Consecutive GAS blood culture isolates from twenty-two IDU and twenty-two non-DU presenting to the city hospital were studied. Clinical features, strain emm typing and superantigen toxin genotyping were investigated. RESULTS: GAS invasive disease presented differently in IDU compared to non-DU with a predominance of injection site abscesses and lower mortality in IDU. GAS strains from IDU were predominantly emm82 and emm83 types, which are uncommon in the UK and emm82 strains appeared clonal. The non-DU GAS strains demonstrated a broader range of emm types including most frequently emm1 and emm89. There was no major difference in superantigen gene profile between the isolate groups. CONCLUSION: The distinct presentation of invasive GAS disease in IDU compared with non-DU was associated with distinct emm types, a predominance of abscesses, and low mortality, although the small numbers preclude definitive conclusions. Further study is required to establish if these findings reflect strain differences or epidemiological differences in colonisation patterns and injecting practice.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17116332&query_hl=1
ER  - 

TY  - JFULL
T1  - Low-dose oral tri-iodothyronine does not directly increase food intake in man.
A1  - Martin, NM
A1  - Small, CJ
A1  - Lee, JL
A1  - Ellis, S
A1  - Dhillo, WS
A1  - Smith, KL
A1  - Kong, WM
A1  - Frost, GS
A1  - Bloom, SR
J1  - Diabetes Obes Metab
Y1  - 2007/05//
VL  - 9
SN  - 1462-8902
SP  - 435
EP  - 437
N2  - Previously, we have shown that low-dose tri-iodothyronine (T3) increases food intake in rodents. This randomised, double-blind, placebo-controlled study aimed to investigate the effects of low-dose T3 on food intake in normal body weight individuals. However, despite an elevation in fT3 comparable to our earlier studies, administration of low-dose T3 in the fasted state did not stimulate food intake in man.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17391172&query_hl=1
ER  - 

TY  - JFULL
T1  - Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D: results from a rural Ugandan cohort.
A1  - Kaleebu, P
A1  - Nankya, IL
A1  - Yirrell, DL
A1  - Shafer, LA
A1  - Kyosiimire-Lugemwa, J
A1  - Lule, DB
A1  - Morgan, D
A1  - Beddows, S
A1  - Weber, J
A1  - Whitworth, JA
J1  - J Acquir Immune Defic Syndr
Y1  - 2007/05/01/
VL  - 45
SN  - 1525-4135
SP  - 28
EP  - 33
N2  - OBJECTIVES: To determine whether there are differences in coreceptor use in subjects infected with HIV-1 envelope subtypes A and D that could explain the differences in progression rates between these subtypes in a rural Ugandan cohort. METHODS: HIV-1 was subtyped in env by V3 sequencing or heteroduplex mobility assay. Coreceptor use was determined by the ability of the isolates to replicate in U87 CD4 cells expressing different coreceptors. The Fisher exact test was used to examine the relation between coreceptor use and subtype, clinical stage, and V3 charge. The Kruskall-Wallis nonparametric test was used to examine the association between median CD4 cell counts, coreceptor use, and subtype. Logistic regression was used to examine predicted coreceptor use at different CD4 groupings. RESULTS: Isolates from 66 participants were analyzed. Thirty-one were infected with subtype A, and 35 were infected with subtype D. Although this work was based on a small sample size, we found statistically significant differences. The probability of having an X4 virus was higher in subtype D infections than in subtype A infections among those with a non-AIDS clinical status (Fisher exact test, P = 0.040). Logistic regression analysis, in which we predicted X4 use by subtype and stratified by CD4 group, confirmed these findings among those with a CD4 count >200 cells/microL (likelihood ratio test, P = 0.003). R5 viruses were associated with higher median CD4 cell counts than X4 or X4/R5 (Kruskall-Wallis test, P = 0.0045). A V3 charge of +5 and greater was highly associated with X4 virus (Fisher exact test, P = 0.006). CONCLUSIONS: These subtype differences in coreceptor use may partially explain the faster progression rates we have previously reported in individuals infected with subtype D compared with subtype A. Our observations may have implications for the future use of coreceptor inhibitors in this population.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17310935&query_hl=1
ER  - 

TY  - JFULL
T1  - Characterization of androgen-regulated expression of CYP3A5 in human prostate
A1  - Moilanen, AM
A1  - Hakkola, J
A1  - Vaarala, MH
A1  - Kauppila, S
A1  - Hirvikoski, P
A1  - Vuoristo, JT
A1  - Edwards, RJ
A1  - Paavonen, TK
J1  - CARCINOGENESIS
Y1  - 2007/05//
VL  - 28
SN  - 0143-3334
SP  - 916
EP  - 921
N2  - Testosterone is needed for the growth and development of the prostate. Androgen deprivation therapy is used for the treatment of prostate cancer. CYP3A5 is a human drug-metabolizing cytochrome P450 enzyme that metabolizes testosterone to the inactive 6 beta-hydroxylated metabolite. We identified CYP3A5 as a novel androgen-regulated gene in human prostate by GeneChip analysis of human prostate tissues obtained from patients 3 days after therapeutic castration and from control patients. We further showed androgen induction of CYP3A5 messenger RNA (mRNA) in LNCaP prostate cancer cell line. Immunoblotting studies revealed CYP3A5 protein expression in all prostate samples studied. Immunohistochemistry and in situ hybridization was used for localization of CYP3A5 expression in prostate tissue. CYP3A5 was detected both in luminal and in basal epithelial cells of human prostate. Androgen response element was identified in the CYP3A5 proximal promoter and in electrophoretic mobility shift assay androgen receptor was found to bind this element. Androgen induction was abolished by mutation of the response element. We suggest that CYP3A5 is a part of an autoregulatory feedback loop controlling prostate cell exposure to androgens.
ER  - 

TY  - JFULL
T1  - Unusual features of the cell cycle in mycobacteria: polar-restricted growth and the snapping-model of cell division.
A1  - Thanky, NR
A1  - Young, DB
A1  - Robertson, BD
J1  - Tuberculosis (Edinb)
Y1  - 2007/05//
VL  - 87
SN  - 1472-9792
SP  - 231
EP  - 236
N2  - Cell division patterns in mycobacteria have been examined in order to further our understanding of how these important organisms grow in the apparent absence of key systems required for the growth of rod-shaped bacteria. Analysis of the distribution of cell lengths in the population during different phases of growth showed that the modal cell length decreases during later phases of growth, declining from 3.5 to 2.5 microm for Mycobacterium bovis BCG cells sampled in log phase and stationary phase, respectively. The population also became more homogeneous, as indicated by the proportion of cells in the most common class increasing from 15% to 28%. Similar patterns were observed for Mycobacterium smegmatis and Mycobacterium tuberculosis. Consistent with other actinomycetes, and in contrast to most rod-shaped bacteria, the deposition of newly synthesised peptidoglycan in mycobacteria is restricted to the poles of the cell, as evidenced by staining with fluorescently labelled vancomycin. A "V-form" of bacteria was observed in cultures at all stages of growth, but the proportion decreased in older cultures. The V-shape appears to be a result of the uneven splitting of the exterior cell envelope at the new septum; this exposes the new peptidoglycan which is illustrated by spots of fluorescent vancomycin staining associated with the exterior side of the "V", and supports the 'snapping division model'. The restriction of growth to the poles of the cell differs from the pattern observed in other rod-shaped bacteria, in which the cell poles are inert and lateral growth occurs by deposition of peptidoglycan along the body of the cylinder. The mechanisms that maintain the shape of mycobacteria and that identify the mid-point for cell division remain to be determined.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17287144&query_hl=1
ER  - 

TY  - JFULL
T1  - Total CD34+ cells per 10 HPF in bone marrow trephines of patients with chronic myeloid leukaemia correlates with probability of complete cytogenetic response following imatinib treatment.
A1  - Elliot, V
A1  - Marin, D
A1  - Horncastle, D
A1  - Elderfield, K
A1  - Howard, J
A1  - Apperley, JF
A1  - Lampert, IA
A1  - Naresh, KN
J1  - Histopathology
Y1  - 2007/05//
VL  - 50
SN  - 0309-0167
SP  - 810
EP  - 812
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17376172&query_hl=1
ER  - 

TY  - JFULL
T1  - Metformin prolongs the postprandial fall in plasma ghrelin concentrations in type 2 diabetes.
A1  - English, PJ
A1  - Ashcroft, A
A1  - Patterson, M
A1  - Dovey, TM
A1  - Halford, JC
A1  - Harrison, J
A1  - Eccleston, D
A1  - Bloom, SR
A1  - Ghatei, MA
A1  - Wilding, JP
J1  - Diabetes Metab Res Rev
Y1  - 2007/05//
VL  - 23
SN  - 1520-7552
SP  - 299
EP  - 303
N2  - BACKGROUND: Weight loss is difficult to achieve in type 2 diabetes and many therapies are associated with weight gain, an effect attenuated by metformin. We studied the effects of metformin on energy expenditure, appetite and the regulation of PYY and ghrelin in type 2 diabetes. METHODS: Plasma peptide YY (PYY), ghrelin, resting metabolic rate (RMR), postprandial thermogenesis (PPTG), and appetite ratings were measured at baseline and following a mixed meal in 11 type 2 diabetic subjects treated with diet alone (T2D) and 10 treated with metformin monotherapy (T2MF). The groups were similar in age, gender and adiposity. RESULTS: There were no differences in baseline anthropometric, or metabolic variables between the groups. Postprandially, plasma ghrelin fell equally in both groups (23% versus 24.5%, p < 0.05 versus baseline, p = NS between groups) but were reduced for longer in T2MF (below baseline 60-240 min T2MF versus 60-180 min T2D) coincidentally with a prolonged sensation of fullness and suppression of hunger in the metformin-treated group. There were no differences in PYY concentrations, RMR or PPTG. CONCLUSIONS: Metformin prolongs the postprandial fall in ghrelin concentrations. These effects may prolong the inter-meal interval, thereby decreasing snack intake and daily energy intake, promoting weight loss.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16952199&query_hl=1
ER  - 

TY  - JFULL
T1  - Monitoring peripheral blood regulatory T cells on clinically defined groups of kidney transplant recipients.
A1  - Sagoo, P
A1  - Sawitzki, B
A1  - Hernandez-Fuentes, M
A1  - Perucha, E
A1  - Craciun, L
A1  - Brouard, S
A1  - Chaprnan, S
A1  - Bradeau, C
A1  - Peters, B
A1  - Roberts, I
A1  - Janssen, U
A1  - Soulillou, JP
A1  - Warrens, AN
A1  - Wood, K
A1  - Goldman, M
A1  - Volk, HD
A1  - Lechler, RI
J1  - AM J TRANSPLANT
Y1  - 2007/05//
VL  - 7
SN  - 1600-6135
SP  - 340
EP  - 340
ER  - 

TY  - JFULL
T1  - Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8(+) T-cell responses in HLA-A2.1/Kb transgenic mice
A1  - Zhang, YX
A1  - Li, S
A1  - Shan, M
A1  - Pan, XW
A1  - Zhuang, K
A1  - He, LH
A1  - Gould, K
A1  - Tien, P
J1  - IMMUNOLOGY
Y1  - 2007/05//
VL  - 121
SN  - 0019-2805
SP  - 105
EP  - 112
N2  - The potency of CD8(+) cytotoxic T lymphocyte (CTL) responses toward core antigen has been shown to affect the outcomes of hepatitis B virus (HBV) infection. Since single-chain trimers (SCT) composed of peptide epitope beta(2)-microglobulin (beta(2)m) and major histocompatiblity complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses, we investigated the properties of human leucocyte antigen (HLA)-A2 SCTs encoding the HBV core antigen (HBcAg) epitopes C18-27 and C107-115. Transfection of NIH-3T3 cells with pcDNA3.0-SCT-C18-27 and SCT-C107-115 leads to stable presentation of HBcAg epitopes at the cell surface. HLA-A2.1/Kb transgenic mice vaccinated with the SCT constructs, either as a DNA vaccine alone or followed by a boost with recombinant vaccinia virus, were shown to generate HBcAg-specific CTL responses by enzyme-linked immunospot assay (ELISPOT) and in vitro interferon-gamma release experiments. HBcAg-specific CTLs from vaccinated HLA-A2.1/Kb transgenic mice were able to inhibit HBV surface and e antigen expression as indicated by HepG2.2.15 cells. Our data indicate that a DNA vaccine encoding a human HLA-A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA-A2-positive HBV carriers.
ER  - 

TY  - JFULL
T1  - Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma.
A1  - Ippolito, G
A1  - Palazzo, FF
A1  - Sebag, F
A1  - De Micco, C
A1  - Henry, JF
J1  - Br J Surg
Y1  - 2007/05//
VL  - 94
SN  - 0007-1323
SP  - 566
EP  - 570
N2  - BACKGROUND: Distinction of parathyroid cancer from atypical parathyroid adenoma (APA) at operation is difficult. The aim of this study was to determine whether parathyroid cancer and APA have different operative findings and long-term outcomes. METHODS: A retrospective review was undertaken of patients with suspicious or malignant parathyroid tumours treated between 1974 and 2005. Parathyroid cancer was defined as a lesion with vascular or tissue invasion, and APA as a neoplasm with broad fibrous bands, trabecular growth, mitosis and nuclear atypia. RESULTS: Twenty-seven patients with suspicious or malignant parathyroid tumours were identified. After histological review, parathyroid cancer was confirmed in 11 patients (group 1) and 16 tumours were classified as APA (group 2). The clinical presentation and operative findings of the two types of tumour were indistinguishable. At initial surgery, seven patients in group 1 underwent en bloc resection, and four had parathyroidectomy. Four of the seven patients who had en bloc resection had recurrences. No recurrences were observed in the other seven patients in group 1 at a median follow-up of 65 months. In group 2, eight patients had en bloc resection and eight had parathyroidectomy; no patient had recurrence at a median follow-up of 91 months. CONCLUSION: Operative findings cannot distinguish APA from parathyroid cancer reliably. Without evidence of macroscopic local invasion, the value of en bloc resection at initial surgery remains debatable.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17380564&query_hl=1
ER  - 

TY  - JFULL
T1  - Brain-gut axis and food intake
A1  - Bloom, S
J1  - INT J OBESITY
Y1  - 2007/05//
VL  - 31
SN  - 0307-0565
SP  - S6
EP  - S6
ER  - 

TY  - JFULL
T1  - Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy.
A1  - Simula, MP
A1  - Marktel, S
A1  - Fozza, C
A1  - Kaeda, J
A1  - Szydlo, RM
A1  - Nadal, E
A1  - Bua, M
A1  - Rahemtulla, A
A1  - Kanfer, E
A1  - Marin, D
A1  - Olavarria, E
A1  - Goldman, JM
A1  - Apperley, JF
A1  - Dazzi, F
J1  - Leukemia
Y1  - 2007/05//
VL  - 21
SN  - 0887-6924
SP  - 943
EP  - 948
N2  - Donor lymphocyte infusions (DLI) are an effective treatment for patients with chronic myeloid leukemia (CML) in relapse after allografting but the optimal cell dose has yet to be identified. To address this question, we investigated the factors affecting the dose required to achieve remission (effective cell dose, (ECD)) in 81 patients treated with an escalating dose regimen. The overall proportion of patients who achieved a molecular remission was 88%. The cumulative proportion of remitters increased significantly at each dose level. With a CD3(+) cell dose < or =10(7)/kg, 56% of patients in molecular/cytogenetic relapse obtained molecular remission, whereas only 20% of those in hematologic relapse did so. At the same cell dose, 58% of patients who received lymphocytes from volunteer unrelated donors achieved remission, as compared to 29% of those who received DLI from sibling donors. We conclude that the response to DLI is dose-dependent and that the ECD is influenced by the quantity and phase of CML at relapse and degree of donor/recipient histocompatibility.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17361226&query_hl=1
ER  - 

TY  - JFULL
T1  - The permeability transition pore in cell death.
A1  - Grimm, S
A1  - Brdiczka, D
J1  - Apoptosis
Y1  - 2007/05//
VL  - 12
SN  - 1360-8185
SP  - 841
EP  - 855
N2  - The permeability transition pore (PT-pore) is a multi-component protein aggregate in mitochondria that comprises factors in the inner as well as in the outer mitochondrial membrane. This complex has two functions: firstly, it regulates the integration of oxidative phosphorylation into the cellular energy household and secondly, it induces cell death when converted into an unspecific channel. The latter causes a collapse of the mitochondrial membrane potential and activates a chain of events that culminate in the demise of the cell. It has been controversial for some time whether the PT-pore is causative for or only amplifies a signal of cell death but novel results confirm a central role of this protein complex for cell death induction. While a considerable body of data exist on its subunit composition, recent genetic knock-out experiments suggest that the identity of the core factors of the PT-pore is still unresolved. Moreover, accumulating evidence point to a much more complex composition of this protein complex than anticipated. Here, we review the current knowledge of its subunit composition, the evidence of a role in cell death, and we propose a model for the activation of the PT-pore for cell death.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17453156&query_hl=1
ER  - 

TY  - JFULL
T1  - Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism.
A1  - Bassett, JH
A1  - O'Shea, PJ
A1  - Sriskantharajah, S
A1  - Rabier, B
A1  - Boyde, A
A1  - Howell, PG
A1  - Weiss, RE
A1  - Roux, JP
A1  - Malaval, L
A1  - Clement-Lacroix, P
A1  - Samarut, J
A1  - Chassande, O
A1  - Williams, GR
J1  - Mol Endocrinol
Y1  - 2007/05//
VL  - 21
SN  - 0888-8809
SP  - 1095
EP  - 1107
N2  - Thyrotoxicosis is an important but under recognized cause of osteoporosis. Recently, TSH deficiency, rather than thyroid hormone excess, has been suggested as the underlying cause. To investigate the molecular mechanism of osteoporosis in thyroid disease, we characterized the skeleton in mice lacking either thyroid hormone receptor alpha or beta (TRalpha(0/0), TRbeta-/-). Remarkably, in the presence of normal circulating thyroid hormone and TSH concentrations, adult TRalpha(0/0) mice had osteosclerosis accompanied by reduced osteoclastic bone resorption, whereas juveniles had delayed endochondral ossification with reduced bone mineral deposition. By contrast, adult TRbeta-/- mice with elevated TSH and thyroid hormone levels were osteoporotic with evidence of increased bone resorption, whereas juveniles had advanced ossification with increased bone mineral deposition. Analysis of T3 target gene expression revealed skeletal hypothyroidism in TRalpha(0/0) mice, but skeletal thyrotoxicosis in TRbeta-/- mice. These studies demonstrate that bone loss in thyrotoxicosis is independent of circulating TSH levels and mediated predominantly by TRalpha, thus identifying TRalpha as a novel drug target in the prevention and treatment of osteoporosis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17327419&query_hl=1
ER  - 

TY  - JFULL
T1  - Current strategies for identifying and validating targets for new treatment-shortening drugs for TB.
A1  - Williams, KJ
A1  - Duncan, K
J1  - Curr Mol Med
Y1  - 2007/05//
VL  - 7
SN  - 1566-5240
SP  - 297
EP  - 307
N2  - There is an urgent need for new drugs to treat tuberculosis. During the last forty years the only drugs to have been developed are variations on existing ones, but new drug candidates must offer improvements over existing agents. In particular, we require new drugs having novel mechanisms of action that are active against drug-resistant strains and also kill persistent bacilli, thus shortening the length of chemotherapy. Recent advances in our understanding of the biology of Mycobacterium tuberculosis, in particularly the availability of the genome sequence coupled with development of new genetic tools, have greatly contributed to the discovery of potential drug targets for new antituberculars. However, although many potential new drug targets have been identified, greater effort is required in target validation to show properly that they are essential for bacterial growth and survival. In this review, the current drug development pipeline and the strategies employed to identify and validate novel tuberculosis drug targets are presented.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17504114&query_hl=1
ER  - 

TY  - JFULL
T1  - Concordant F-18 FDG PET and Y-90 Bremsstrahlung scans depict selective delivery of Y-90-microspheres to liver tumors: confirmation with histopathology.
A1  - Tehranipour, N
A1  - AL-Nahhas, A
A1  - Canelo, R
A1  - Stamp, G
A1  - Woo, K
A1  - Tait, P
A1  - Gishen, P
J1  - Clin Nucl Med
Y1  - 2007/05//
VL  - 32
SN  - 0363-9762
SP  - 371
EP  - 374
N2  - Selective Internal Radiation Therapy using yttrium-90 (Y-90) microspheres is a novel method for the treatment of advanced liver cancer. The procedure involves intrahepatic arterial delivery of the Y-90 microspheres. Since hepatic tumors derive their blood supply mainly from the hepatic arteries, it is assumed that the microspheres will be preferentially delivered to tumor cells. However, this has not been confirmed at histology. We report a case of hepatic metastasis from an unknown primary, where treatment with Y-90 microspheres was the only available option due to inoperability and low tolerance to chemotherapy. Pretherapy F-18 FDG-PET scan defined the distribution of the active tumor within the liver. Following the injection of Y-90 microspheres, Bremsstrahlung imaging showed uptake only in the F-18 FDG-PET-defined tumor area. Post therapy debulking surgery was performed and histopathology of tumor samples confirmed the preferential distribution of the injected microspheres in the hepatic tumor circulation with very little in the healthy liver tissue. The case confirms the preferential blood flow to hepatic tumors as depicted by the distribution of Y-90 microspheres injected directly in the hepatic arteries. It also demonstrates that concordance between F-18 FDG-PET and Y-90 Bremsstrahlung scans can be a useful clue to the in vivo distribution of microspheres.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17452865&query_hl=1
ER  - 

TY  - JFULL
T1  - Transcriptional activation of cartilage oligomeric matrix protein by Sox9, Sox5, and Sox6 transcription factors and CBP/p300 coactivators.
A1  - Liu CJ, Zhang Y, Xu K, Parsons D, Alfonso D, Di Cesare PE.
J1  - Front Biosci
Y1  - 2007/05//
VL  - 12
SP  - 3899
EP  - 3910
ER  - 

TY  - JFULL
T1  - C-terminal antibodies (CTAbs): a simple and broadly applicable approach for the rapid generation of protein-specific antibodies with predefined specificity.
A1  - Edwards, RJ
A1  - Wrigley, A
A1  - Bai, Z
A1  - Bateman, M
A1  - Russell, H
A1  - Murray, S
A1  - Lu, H
A1  - Taylor, GW
A1  - Boobis, AR
A1  - Sriskandan, S
J1  - Proteomics
Y1  - 2007/05//
VL  - 7
SN  - 1615-9853
SP  - 1364
EP  - 1372
N2  - Recent advances in proteomic techniques have resulted in an ever-increasing need to produce antibodies. Here, to address this problem, a technically simple approach of targeting the extreme C-termini of proteins with antibodies (CTAbs) was investigated in proteins secreted by the human pathogen Streptococcus pyogenes. Target proteins were identified by a conventional proteomic approach and CTAbs produced against synthetic five amino acid peptides representing the C-terminus of each target protein. In every case where protein secretion was demonstrated (n = 20), CTAbs were successfully produced and bound specifically to the target protein (100% success rate). The apparent specificity was consistent with the structural heterogeneity of the C-termini of S. pyogenes proteins. The global specificity of CTAb binding was defined using a combinatorial library of synthetic peptides representing structural variants of the original synthetic immunogen. This is a systematic and comprehensive approach for the development of antibodies with defined specificity that can be used in a range of applications.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17407178&query_hl=1
ER  - 

TY  - JFULL
T1  - Targeting an E2F site in the mouse genome prevents promoter silencing in quiescent and post-mitotic cells.
A1  - Tavner, F
A1  - Frampton, J
A1  - Watson, RJ
J1  - Oncogene
Y1  - 2007/04/26/
VL  - 26
SN  - 0950-9232
SP  - 2727
EP  - 2735
N2  - Previous studies have shown that the cell cycle-regulated B-myb promoter contains a conserved E2F binding site that is critical for repressing transcription in quiescent cells. To investigate its significance for permanent promoter silencing, we have inactivated this binding site in the mouse genome. Mice homozygous for the mutant B-mybmE2F allele were fully viable, however, B-myb transcription was derepressed during quiescence in mouse embryo fibroblasts (MEFs) derived from mutant animals. Moreover, it was found that mutation of the E2F site resulted in abnormal maintenance of B-myb expression in senescent MEFs and in differentiated brain tissue. These findings therefore reveal a direct and primary role for repressive E2F complexes in silencing gene expression in post-mitotic cells. Analysis of histone modifications at the promoter showed that histone H3 lysine 9 was constitutively acetylated throughout the cell cycle in homozygous mutant MEFs. This mouse system is the first description of an E2F site mutation in situ and will facilitate the study of E2F function in vivo.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17072340&query_hl=1
ER  - 

TY  - JFULL
T1  - Brief report: Targeted therapy for inherited GPI deficiency.
A1  - Almeida, AM
A1  - Murakami, Y
A1  - Baker, A
A1  - Maeda, Y
A1  - Roberts, IAG
A1  - Kinoshita, T
A1  - Layton, DM
A1  - Karadimitris, A
J1  - NEW ENGL J MED
Y1  - 2007/04/19/
VL  - 356
SN  - 0028-4793
SP  - 1641
EP  - 1647
N2  - Disrupted binding of the transcription factor Sp1 to the mutated promoter region of the mannosyl transferase-encoding gene PIGM causes inherited glycosylphosphatidylinositol (GPI) deficiency characterized by splanchnic vein thrombosis and epilepsy. We show that this results in histone hypoacetylation at the promoter of PIGM. The histone deacetylase inhibitor butyrate increases PIGM transcription and surface GPI expression in vitro as well as in vivo through enhanced histone acetylation in an Sp1-dependent manner. More important, the drug caused complete cessation of intractable seizures in a child with inherited GPI deficiency.
ER  - 

TY  - JFULL
T1  - Targeted therapy for inherited GPI deficiency.
A1  - Almeida, AM
A1  - Murakami, Y
A1  - Baker, A
A1  - Maeda, Y
A1  - Roberts, IA
A1  - Kinoshita, T
A1  - Layton, DM
A1  - Karadimitris, A
J1  - N Engl J Med
Y1  - 2007/04/19/
VL  - 356
SN  - 1533-4406
SP  - 1641
EP  - 1647
N2  - Disrupted binding of the transcription factor Sp1 to the mutated promoter region of the mannosyl transferase-encoding gene PIGM causes inherited glycosylphosphatidylinositol (GPI) deficiency characterized by splanchnic vein thrombosis and epilepsy. We show that this results in histone hypoacetylation at the promoter of PIGM. The histone deacetylase inhibitor butyrate increases PIGM transcription and surface GPI expression in vitro as well as in vivo through enhanced histone acetylation in an Sp1-dependent manner. More important, the drug caused complete cessation of intractable seizures in a child with inherited GPI deficiency.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17442906&query_hl=1
ER  - 

TY  - JFULL
T1  - Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning.
A1  - Crawley, C
A1  - Iacobelli, S
A1  - Björkstrand, B
A1  - Apperley, JF
A1  - Niederwieser, D
A1  - Gahrton, G
J1  - Blood
Y1  - 2007/04/15/
VL  - 109
SN  - 0006-4971
SP  - 3588
EP  - 3594
N2  - Despite the widespread adoption of reduced-intensity conditioning (RIC) for myeloma, there are few data comparing outcomes with RIC with myeloablative conditioning (MAC). We report the outcomes of patients undergoing allogeneic transplantations for myeloma and reported to the EBMT. A minimum data set was available on 320 RIC and 196 MAC allografts performed between 1998 and 2002. The RIC patients were older (51 vs 45 years) with more progressive disease (28% vs 21%) and more had received a prior transplant (76% vs 11%). In addition, there was a longer time to transplantation and an increased use of peripheral blood and T-cell depletion. For RIC and MAC, respectively, the nonrelapse mortality (NRM) at 2 years was 24% and 37% (P = .002); overall survival, 38.1% and 50.8% (not significant [ns]); and progression-free survival (PFS), 18.9% and 34.5% (P = .001). On multivariate analysis, RIC was associated with a reduction in NRM (HR, 0.5), but this was offset by an increase in relapse risk (HR, 2.0), and the conditioning intensity did not impact on overall survival or retain significance for PFS. These data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158231&query_hl=1
ER  - 

TY  - JFULL
T1  - Cowpox virus pneumonia in a domestic cat in Great Britain
A1  - Schoniger, S
A1  - Chan, DL
A1  - Hollinshead, M
A1  - Humm, K
A1  - Smith, GL
A1  - Beard, PM
J1  - VET REC
Y1  - 2007/04/14/
VL  - 160
SN  - 0042-4900
SP  - 522
EP  - 523
ER  - 

TY  - JFULL
T1  - In vivo CD8+ T cell control of immunodeficiency virus infection in humans and macaques.
A1  - Asquith, B
A1  - McLean, AR
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/04/10/
VL  - 104
SN  - 0027-8424
SP  - 6365
EP  - 6370
N2  - Forty million people are estimated to be infected with HIV-1, and only a small fraction of those have access to life-prolonging antiretroviral treatment. As the epidemic grows there is an urgent need for effective therapeutic and prophylactic vaccines. Nonhuman primate models of immunodeficiency virus infection are essential for the preclinical evaluation of candidate vaccines. To interpret the results of these trials, comparative studies of the human and macaque immune responses are needed. Despite the widespread use of macaques to evaluate vaccines designed to elicit a CD8(+) cytotoxic T lymphocyte (CTL) response, the efficiency with which CTL control immunodeficiency virus infections has not been compared between humans and macaques, largely because of difficulties in assaying the functional CTL response. We recently developed a method for estimating the rate at which CTLs kill cells productively infected with HIV-1 in humans in vivo. Here, using the same technique, we quantify the rate at which CTLs kill infected cells in macaque models of HIV infection. We show that CTLs kill productively infected cells significantly faster (P = 0.004) and that escape variants have significantly higher fitness costs (P = 0.003) in macaques compared with humans. These results suggest that it may be easier to elicit a protective CTL response in macaques than in humans and that vaccine studies conducted in macaques need to be interpreted accordingly.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17404226&query_hl=1
ER  - 

TY  - JFULL
T1  - Statins audit: wrong question, wrong conclusions (vol 369, pg 640, 2007)
A1  - Moon, JC
A1  - Bogle, RG
A1  - Minas, R
J1  - LANCET
Y1  - 2007/04/07/
VL  - 369
SN  - 0140-6736
SP  - 1168
EP  - 1168
ER  - 

TY  - JFULL
T1  - Upregulation of the TGF beta signalling pathway by Bcr-Abl: Implications for haemopoietic cell growth and chronic myeloid leukaemia
A1  - Moller, GMO
A1  - Frost, V
A1  - Melo, JV
A1  - Chantry, A
J1  - FEBS LETT
Y1  - 2007/04/03/
VL  - 581
SN  - 0014-5793
SP  - 1329
EP  - 1334
N2  - Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by uncontrolled growth of progenitor cells expressing the tyrosine kinase fusion gene product, Bcr-Abl. At present, little is known regarding how TGF beta, and downstream Smad transcription factors, influence CML cell proliferation in the context of Bcr-Abl expression. Here we show that ectopic Bcr-Abl expression dramatically increases TGF beta/Smad-dependent transcriptional activity in Cosl cells, and that this may be due to enhancement of Smad promoter activity. Bcr-Abl expressing TF-1 myeloid cells are more potently growth arrested by TGF beta compared to the parental TF-1 cell line. Additionally, growth of Bcr-Abl-expressing CD34+ cells from chronic phase CML patients is inhibited by TGF beta and, interestingly, treatment of a non-proliferating CD34+ CML cell subpopulation with the TGF beta kinase inhibitor SB431542 enhanced cell death mediated by the Bcr-Abl inhibitor imatinib. Our data suggest that the expression of Bcr-Abl leads to hyper-responsiveness of myeloid cells to TGF beta, and we hypothesise that this novel cross-regulatory mechanism might play an important role in maintaining the transformed progenitor cell population in CML. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
ER  - 

TY  - JFULL
T1  - Poly-(ADP-ribose) polymerase-1 (Parp-1) binds in a sequence-specific manner at the Bcl-6 locus and contributes to the regulation of Bcl-6 transcription.
A1  - Ambrose, HE
A1  - Papadopoulou, V
A1  - Beswick, RW
A1  - Wagner, SD
J1  - Oncogene
Y1  - 2007/04/02/
SN  - 0950-9232
N2  - Bcl-6 is a transcription factor that is normally expressed in germinal centre B cells. It is essential for the formation of germinal centres and the production of high-affinity antibodies. Transcriptional downregulation of Bcl-6 occurs on terminal differentiation to plasma cells. Bcl-6 is highly expressed in B-cell non-Hodgkin's lymphoma and, in a subset of cases of diffuse large cell lymphoma, the mechanism of Bcl-6 overexpression involves interruption of normal transcriptional controls. Transcriptional control of Bcl-6 is, therefore, important for normal antibody responses and lymphomagenesis, but little is known of the cis-acting control elements. This report focuses on a region of mouse/human sequence homology in the first intron of Bcl-6, which is a candidate site for such a control element. We demonstrate that poly-(ADP-ribose) polymerase-1 (Parp-1) binds in vitro and in vivo to specific sequences in this region. We further show that PARP inhibitors, and Parp-1 knockdown by siRNA induce Bcl-6 mRNA expression in Bcl-6 expressing cell lines. We speculate that Parp-1 activation plays a role in switching off Bcl-6 transcription and subsequent B-cell exit from the germinal centre.Oncogene advance online publication, 2 April 2007; doi:10.1038/sj.onc.1210434.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17404575&query_hl=1
ER  - 

TY  - JFULL
T1  - Expression of cytochromes P450 3A and P-glycoprotein in human large intestine in paired tumour and normal samples.
A1  - Canaparo, R
A1  - Nordmark, A
A1  - Finnström, N
A1  - Lundgren, S
A1  - Seidegård, J
A1  - Jeppsson, B
A1  - Edwards, RJ
A1  - Boobis, AR
A1  - Rane, A
J1  - Basic Clin Pharmacol Toxicol
Y1  - 2007/04//
VL  - 100
SN  - 1742-7835
SP  - 240
EP  - 248
N2  - Our objective was to investigate the expression of different cytochromes P450 3A (CYP3A4, CYP3A5, and CYP3A7) and P-glycoprotein (ABCB1) genes along the human large intestine in paired tumour and normal samples. Real-time reverse transcriptase-polymerase chain reaction was used to measure CYP3A4-, CYP3A5-, CYP3A7- and ABCB1-specific mRNA expression, and Western blot analysis was used to measure membrane protein levels of CYP3A4/7, CYP3A5 and P-glycoprotein. Levels of mRNA and membrane protein fractions in the large intestine were compared with those of normal human liver. The mRNA expressions of CYP3A4, CYP3A5, CYP3A7 and ABCB1 in the large intestine were found to be highly variable, but overall the levels were significantly lower than those measured in liver (P < 0.0001, P < 0.001, P < 0.0001 and P < 0.01, respectively). At the membrane protein level, CYP3A4/7 was detected in all large intestine samples examined and the levels were substantially higher than those of the liver (P < 0.01). Although expression of CYP3A5 was detected in all large intestine samples, in most the levels were too low to allow quantification. P-glycoprotein was readily detected at levels slightly higher than those of liver (P < 0.05). Comparison between paired samples of normal and tumour in large intestine showed no significant differences in either the mRNA or membrane protein levels of these genes. In conclusion, this work suggests a potential role of the large intestine in the absorption and metabolism of xenobiotics and nutrients and no difference in the CYP3A and P-glycoprotein membrane protein fractions and mRNA expression between normal and tumour tissues.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17371528&query_hl=1
ER  - 

TY  - JFULL
T1  - Missed upper gastrointestinal cancer within 3 years of previous endoscopy
A1  - Milestone, AN
A1  - Kent, AJ
A1  - Goldin, RD
A1  - Hoare, JM
J1  - GASTROENTEROLOGY
Y1  - 2007/04//
VL  - 132
SN  - 0016-5085
SP  - A312
EP  - A313
ER  - 

TY  - JFULL
T1  - Cell dynamics and immune response to BLV infection: A unifying model
A1  - Florins, A
A1  - Gillet, N
A1  - Asquith, B
A1  - Mortreux, F
A1  - Wattel, E
A1  - Burny, A
A1  - Kettmann, R
A1  - Bangham, C
A1  - Willems, L
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 589
EP  - 589
ER  - 

TY  - JFULL
T1  - The first case of optic neuritis preceding progressive outer retinal necrosis (PORN) after bone marrow transplantation (BMT): a severe manifestation of varicella-zoster virus (VZV) infection
A1  - Patel A
A1  - Narat S
A1  - Graham E
A1  - Olavarria E
J1  - British Journal of Haematology
Y1  - 2007/04//
IS  - Suppl 1
VL  - 137
SP  - 78
ER  - 

TY  - JFULL
T1  - Recent HIV-1 infection in a high-risk Ugandan cohort: implications for Phase IIB test-of-concept HIV vaccine trials.
A1  - Kebba, A
A1  - Imami, N
A1  - Bugembe-Lule, D
A1  - Senkaali, D
A1  - Kaleebu, P
A1  - Grosskurth, H
A1  - Gotch, F
J1  - Pharmacogenomics
Y1  - 2007/04//
VL  - 8
SN  - 1462-2416
SP  - 409
EP  - 414
N2  - Assessment of vaccine efficacy on end points used in Phase IIB test-of-concept trials will require taking into consideration the effect of variables correlated with the end points and distribution of the variables within subgroups of the trial population. Here we report that evaluation of sexual activity in vaccinees and longitudinal collection of plasma viral load data from putative transmitters prior to transmission will contribute to the plausible assessment of efficacy against acquisition of infection. Data also suggest that efficacy on post-infection end points may depend on whether transmission pairs are matched or mismatched for HLA class I alleles.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17391079&query_hl=1
ER  - 

TY  - JFULL
T1  - The cellular origin and proliferative status of regenerating renal parenchyma after mercuric chloride damage and erythropoietin treatment
A1  - Yen, TH
A1  - Alison, MR
A1  - Cook, HT
A1  - Jeffery, R
A1  - Otto, WR
A1  - Wright, NA
A1  - Poulsom, R
J1  - CELL PROLIFERAT
Y1  - 2007/04//
VL  - 40
SN  - 0960-7722
SP  - 143
EP  - 156
N2  - Objectives: In this study, we have sought to establish the cellular origin and proliferative status of the renal parenchyma as it regenerates after damage induced by mercuric chloride, with or without erythropoietin treatments, that might alter the response. Materials and methods: Female mice were irradiated and male whole bone marrow was transplanted into them. Six weeks later recipient mice were assigned to one of four groups: control, mercuric chloride treated, erythropoietin treated and treated with mercuric chloride plus erythropoietin. Results: Tubular injury scores were high 3 days after mercuric chloride and had recovered partially after 14 days, in line with serum urea nitrogen levels. Confocal microscopy confirmed the tubular location of bone marrow-derived cells. A 'four-in-one' analytical technique (identifying cell origin, tubular phenotype, tubular basement membranes and S-phase status) revealed that tubular necrosis increased bone marrow derivation of renal tubular epithelium from a baseline of similar to 1.3% to similar to 4.0%. Erythropoietin increased the haematocrit, but no other effects were detected. Conclusion: As 1 in 12 proximal tubular cells in S-phase was derived from bone marrow, we conclude that in the kidney, the presence of bone marrow-derived cells makes a minor but important regenerative contribution after tubular necrosis.
ER  - 

TY  - JFULL
T1  - Long-term safety of filgrastim (rhG-CSF) administration: response to Confer & Miller and Bacher & Zander
A1  - Tigue, CC
A1  - Trifilio, SM
A1  - Tallman, MS
A1  - Goldman, JM
A1  - Bennett, CL
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 79
EP  - 80
ER  - 

TY  - JFULL
T1  - HTLV-1 can infect human lung epithelial cells and induce gene expression of cytokines, chemokines, and cell adhesion molecules
A1  - Gillet, N
A1  - Lezin, A
A1  - Mosley, A
A1  - Defoiche, J
A1  - Belrose, G
A1  - Verlaten, O
A1  - Olindo, S
A1  - Smadja, D
A1  - Cesaire, R
A1  - Macallan, D
A1  - Asquith, B
A1  - Bangham, C
A1  - Burny, A
A1  - Willems, L
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 618
EP  - 619
ER  - 

TY  - JFULL
T1  - Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy.
A1  - Kropf, P
A1  - Baud, D
A1  - Marshall, SE
A1  - Munder, M
A1  - Mosley, A
A1  - Fuentes, JM
A1  - Bangham, CR
A1  - Taylor, GP
A1  - Herath, S
A1  - Choi, BS
A1  - Soler, G
A1  - Teoh, T
A1  - Modolell, M
A1  - Müller, I
J1  - Eur J Immunol
Y1  - 2007/04//
VL  - 37
SN  - 0014-2980
SP  - 935
EP  - 945
N2  - Complex regulation of T cell functions during pregnancy is required to ensure materno-fetal tolerance. Here we reveal a novel pathway for the temporary suppression of maternal T cell responses in uncomplicated human pregnancies. Our results show that arginase activity is significantly increased in the peripheral blood of pregnant women and remarkably high arginase activities are expressed in term placentae. High enzymatic activity results in high turnover of its substrate L-arginine and concomitant reduction of this amino acid in the microenvironment. Amino acid deprivation is emerging as a regulatory pathway of lymphocyte responses and we assessed the consequences of this enhanced arginase activity on T cell responses. Arginase-mediated L-arginine depletion induces down-regulation of CD3 zeta, the main signalling chain of the TCR, and functional T cell hyporesponsiveness. Importantly, this arginase-mediated T cell suppression was reversible, as inhibition of arginase activity or addition of exogenous L-arginine restored CD3 zeta chain expression and T cell proliferation. Thus, L-arginine metabolism constitutes a novel physiological mechanism contributing to the temporary suppression of the maternal immune response during human pregnancy.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17330821&query_hl=1
ER  - 

TY  - JFULL
T1  - Accumulation of plasmacytoid dendritic cells in the intestine of acute ulcerative colitis
A1  - Ng, SC
A1  - Plamondon, S
A1  - Knight, SC
A1  - Kamm, MA
A1  - Stagg, AJ
J1  - GUT
Y1  - 2007/04//
VL  - 56
SN  - 0017-5749
SP  - A116
EP  - A116
ER  - 

TY  - JFULL
T1  - Myocardial infarction (MI) in a 28 year old woman following treatment with DDAVP and tranexamic acid
A1  - Patel, A
A1  - Laffan, M
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 52
EP  - 53
ER  - 

TY  - JFULL
T1  - Marginal zone B-cell lymphoma with prominent follicular colonisation - difficulties in diagnosis; a study of 15 cases
A1  - Naresh, K
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 58
EP  - 58
ER  - 

TY  - JFULL
T1  - Management of paraproteinaemia.
A1  - Cook, L
A1  - Macdonald, DH
J1  - Postgrad Med J
Y1  - 2007/04//
VL  - 83
SN  - 1469-0756
SP  - 217
EP  - 223
N2  - A paraprotein is a monoclonal immunoglobulin or light chain present in the blood or urine; it is produced by a clonal population of mature B cells, most commonly plasma cells. In individuals aged >50 years the incidence of a paraprotein is 3.2%. Plasma cell disorders can be considered as a spectrum of conditions ranging from monoclonal gammopathy of undetermined significance (MGUS), through asymptomatic, to symptomatic myeloma. MGUS is defined by a low level of paraprotein <30 g/l, bone marrow plasma cells <10% and the absence of myeloma related organ or tissue damage (predominantly renal, skeletal or bone marrow impairment.) MGUS requires no therapy and the overall risk of progression to myeloma is 1% per year. Myeloma remains incurable with a median survival of 3-4 years; autologous stem cell transplant can prolong survival, if appropriate. Thalidomide in combination with dexamethasone has an emerging role in the treatment of myeloma.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17403946&query_hl=1
ER  - 

TY  - JFULL
T1  - Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway.
A1  - Pollard, PJ
A1  - Spencer-Dene, B
A1  - Shukla, D
A1  - Howarth, K
A1  - Nye, E
A1  - El-Bahrawy, M
A1  - Deheragoda, M
A1  - Joannou, M
A1  - McDonald, S
A1  - Martin, A
A1  - Igarashi, P
A1  - Varsani-Brown, S
A1  - Rosewell, I
A1  - Poulsom, R
A1  - Maxwell, P
A1  - Stamp, GW
A1  - Tomlinson, IP
J1  - Cancer Cell
Y1  - 2007/04//
VL  - 11
SN  - 1535-6108
SP  - 311
EP  - 319
N2  - Germline mutations in the fumarate hydratase (FH) tumor suppressor gene predispose to leiomyomatosis, renal cysts, and renal cell cancer (HLRCC). HLRCC tumors overexpress HIF1alpha and hypoxia pathway genes. We conditionally inactivated mouse Fh1 in the kidney. Fh1 mutants developed multiple clonal renal cysts that overexpressed Hif1alpha and Hif2alpha. Hif targets, such as Glut1 and Vegf, were upregulated. We found that Fh1-deficient murine embryonic stem cells and renal carcinomas from HLRCC showed similar overexpression of HIF and hypoxia pathway components to the mouse cysts. Our data have shown in vivo that pseudohypoxic drive, resulting from HIF1alpha (and HIF2alpha) overexpression, is a direct consequence of Fh1 inactivation. Our mouse may be useful for testing therapeutic interventions that target angiogenesis and HIF-prolyl hydroxylation.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17418408&query_hl=1
ER  - 

TY  - JFULL
T1  - CD4+ CD25+ regulatory T-cells exhibit a higher T-cell receptor diversity than CD4+ CD25- conventional T-cells after allogeneic stem cell transplantation
A1  - Fozza, C
A1  - Nadal, E
A1  - Longinotti, M
A1  - Dazzi, F
J1  - BONE MARROW TRANSPL
Y1  - 2007/04//
VL  - 39
SN  - 0268-3369
SP  - S46
EP  - S46
ER  - 

TY  - JFULL
T1  - Cartilage oligomeric matrix protein associates with granulin-epithelin precursor (GEP) and potentiates GEP-stimulated chondrocyte proliferation.
A1  - Xu K, Zhang Y, Ilalov K, Carlson CS, Feng JQ, Di Cesare PE, Liu CJ.
J1  - J Biol Chem
Y1  - 2007/04//
VL  - 282
SP  - 11347
EP  - 11355
ER  - 

TY  - JFULL
T1  - Helicobacter infection in the surfactant protein D-deficient mouse.
A1  - Khamri, W
A1  - Worku, ML
A1  - Anderson, AE
A1  - Walker, MM
A1  - Hawgood, S
A1  - Reid, KB
A1  - Clark, HW
A1  - Thursz, MR
J1  - Helicobacter
Y1  - 2007/04//
VL  - 12
SN  - 1083-4389
SP  - 112
EP  - 123
N2  - BACKGROUND: Surfactant protein D (SP-D), a component of innate immunity, is expressed in the gastric mucosa and is up-regulated in the presence of Helicobacter infection. SP-D binds to Helicobacter in vitro, suggesting the involvement of SP-D in Helicobacter-induced immune responses. The aim of this study was to determine the role of SP-D in gastric epithelial defense in vivo. METHODS: Specific pathogen-free SP-D-deficient mice (SP-D(-/-)) and C57BL/6 wild-type controls were challenged by gavage with different doses of Helicobacter felis, a mouse-adapted Helicobacter strain. Mice were assessed for colonization rates and density of infection. Inflammatory responses were measured by neutrophil counting and T-cell responses by proliferation assays on spleen cells stimulated with H. felis sonicate. The in vitro effect of SP-D on Helicobacter uptake by monocyte-derived dendritic cells was assessed by confocal microscopy and FACS analyses. RESULTS: SP-D(-/-) mice were more susceptible to low-dose infectious challenge than C57BL/6 controls (p = .02). The density of colonization was higher in the SP-D(-/-) infected mice. Neutrophil infiltrates were lower in the SP-D(-/-) mice, particularly in the acid-secreting regions of the stomach. T-cell proliferative responses to Helicobacter antigen were reduced in SP-D(-/-) mice (p = .001) after 12 weeks infection. In vitro uptake of Helicobacter by dendritic cells was significantly enhanced in the presence of SP-D (p = .001). CONCLUSION: In the absence of SP-D, Helicobacter uptake by dendritic cells is impaired. This provides an explanation for the diminished inflammation and immune responses in the SP-D(-/-) mice.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17309747&query_hl=1
ER  - 

TY  - JFULL
T1  - Liver dysfunction in long-term survivors of stem cell transplantation
A1  - Nathwani, R
A1  - Olavarria, E
A1  - Kanfer, E
A1  - Rahemtulla, A
A1  - Marin, D
A1  - Todd, J
A1  - Apperley, J
A1  - Salooja, N
J1  - BONE MARROW TRANSPL
Y1  - 2007/04//
VL  - 39
SN  - 0268-3369
SP  - S205
EP  - S206
ER  - 

TY  - JFULL
T1  - The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions.
A1  - Harvey, CB
A1  - Bassett, JH
A1  - Maruvada, P
A1  - Yen, PM
A1  - Williams, GR
J1  - Endocrinology
Y1  - 2007/04//
VL  - 148
SN  - 0013-7227
SP  - 1764
EP  - 1773
N2  - The THRB gene encodes the well-described thyroid hormone (T3) receptor (TR) isoforms TRbeta1 and TRbeta2 and two additional variants, TRbeta3 and TRDeltabeta3, of unknown physiological significance. TRbeta1, TRbeta2, and TRbeta3 are bona fide T3 receptors that bind DNA and T3 and regulate expression of T3-responsive target genes. TRDeltabeta3 retains T3 binding activity but lacks a DNA binding domain and does not activate target gene transcription. TRDeltabeta3 can be translated from a specific TRDeltabeta3 mRNA or is coexpressed with TRbeta3 from a single transcript that contains an internal TRDeltabeta3 translation start site. In these studies, we provide evidence that the TRbeta3/Deltabeta3 locus is present in rat but not in other vertebrates, including humans. We compared the activity of TRbeta3 with other TR isoforms and investigated mechanisms of action of TRDeltabeta3 at specific thyroid hormone response elements (TREs) in two cell types. TRbeta3 was the most potent isoform, but TR potency was TRE dependent. TRDeltabeta3 acted as a cell-specific and TRE-dependent modulator of TRbeta3 when coexpressed at low concentrations. At higher concentrations, TRDeltabeta3 was a TRE-selective and cell-specific antagonist of TRalpha1, -beta1, and -beta3. Both TRbeta3 and TRDeltabeta3 were expressed in the nucleus in the absence and presence of hormone, and their actions were determined by cell type and TRE structure, whereas TRDeltabeta3 actions were also dependent on the TR isoform with which it interacted. Analysis of these complex responses implicates a range of nuclear corepressors and coactivators as cell-, TR isoform-, and TRE-specific modulators of T3 action.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17218414&query_hl=1
ER  - 

TY  - JFULL
T1  - A multi-centre prospective observational study of platelet transfusion practice in neonates with severe thrombocytopenia
A1  - Stanworth, S
A1  - Ballard, S
A1  - Casbard, A
A1  - Murphy, M
A1  - Roberts, I
A1  - Murray, N
A1  - PlaNet Study Grp
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 35
EP  - 36
ER  - 

TY  - JFULL
T1  - Tissue samples involved by multicentric Castleman's disease among HIV-positive individuals is often involved by microscopic foci of Kaposi's sarcoma
A1  - Naresh, K
A1  - Rice, A
A1  - Bower, M
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 58
EP  - 58
ER  - 

TY  - JFULL
T1  - In vivo selection of HTLV-1 specific CD4(+) cells by disease susceptive class II allele and immunodominant peptide complex in HTLV-1-associated neurological disease
A1  - Nose, H
A1  - Usuku, K
A1  - Seth, N
A1  - Kubota, R
A1  - Goon, P
A1  - Tanaka, Y
A1  - Izumo, S
A1  - Arimura, K
A1  - Ohara, Y
A1  - Wucherpfennig, K
A1  - Bangham, C
A1  - Osame, M
A1  - Saito, M
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 643
EP  - 643
ER  - 

TY  - JFULL
T1  - Inhibition of p38 mitogen-activated protein kinase is effective in the treatment of experimental crescentic glomerulonephritis and suppresses monocyte chemoattractant protein-1 but not IL-1beta or IL-6.
A1  - Sheryanna, A
A1  - Bhangal, G
A1  - McDaid, J
A1  - Smith, J
A1  - Manning, A
A1  - Foxwell, BM
A1  - Feldmann, M
A1  - Cook, HT
A1  - Pusey, CD
A1  - Tam, FW
J1  - J Am Soc Nephrol
Y1  - 2007/04//
VL  - 18
SN  - 1046-6673
SP  - 1167
EP  - 1179
N2  - Activation of p38 mitogen-activated protein kinase (MAPK) is known to be important in cytokine production and cell survival in inflammation. This study examined the effect of inhibiting p38 MAPK after onset of renal injury in an experimental model of crescentic glomerulonephritis. Furthermore, this study investigated whether p38 MAPK inhibition would cause widespread suppression of the cytokine network in vivo or uncontrolled apoptosis. In the in vivo studies, daily treatment with a p38 MAPKalpha/beta inhibitor was started 1 h (early treatment study) or 4 d (late treatment study) after induction of nephrotoxic nephritis in Wistar Kyoto rats. The treated rats remained healthy with normal weight gain during the study. Both early and late treatment with p38 MAPK inhibitor reduced renal monocyte chemoattractant protein-1 (MCP-1) levels, the number of glomerular macrophages, the severity of tissue injury, and proteinuria compared with the vehicle group. Unexpected, treatment with p38 MAPK inhibitor did not suppress renal levels of IL-1beta or IL-6. In the in vitro study, the p38 MAPKalpha/beta inhibitor reduced production of MCP-1 and IL-6 by TNF-alpha-or IL-1beta-stimulated mesangial cells without any effect on cell viability or apoptosis. In conclusion, p38 MAPK inhibition is effective in reducing the severity of crescentic glomerulonephritis even when treatment is started after onset of disease. The therapeutic effect is associated with selective suppression of MCP-1, without widespread suppression of cytokine production or increased apoptosis. Therefore, p38 MAPK therapeutic blockade is a promising strategy in the treatment of antibody-mediated glomerulonephritis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17314328&query_hl=1
ER  - 

TY  - JFULL
T1  - Increased CMV-specific CTL associated with decreased expression of Foxp3 in HAM/TSP
A1  - Hayashi, D
A1  - Kubota, R
A1  - Nose, H
A1  - Arimura, K
A1  - Izumo, S
A1  - Osame, M
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 615
EP  - 615
ER  - 

TY  - JFULL
T1  - Is JAK2 V617F negative ET due to clonal lymphoid proliferations? A report of three cases of JAK2 negative sustained thrombocytosis in lyrnhoproliferative disorders mimicking co-existing essential thrombocythaemia
A1  - Brito-Babapulle, F
A1  - Clarke, I
A1  - Naresh, K
A1  - Gabriel, I
A1  - Taylor, K
A1  - Kanfer, E
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 62
EP  - 62
ER  - 

TY  - JFULL
T1  - Future prospects for the MODS assay in multidrug-resistant tuberculosis diagnosis.
A1  - Moore, DA
J1  - Future Microbiol
Y1  - 2007/04//
VL  - 2
SN  - 1746-0921
SP  - 97
EP  - 101
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17661646&query_hl=1
ER  - 

TY  - JFULL
T1  - Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity
A1  - Fuselli, S
A1  - Gilman, RH
A1  - Chanock, SJ
A1  - Bonatto, SL
A1  - De Stefano, G
A1  - Evans, CA
A1  - Labuda, D
A1  - Luiselli, D
A1  - Salzano, FM
A1  - Soto, G
A1  - Vallejo, G
A1  - Sajantila, A
A1  - Pettener, D
A1  - Tarazona-Santos, E
J1  - PHARMACOGENOMICS J
Y1  - 2007/04//
VL  - 7
SN  - 1470-269X
SP  - 144
EP  - 152
N2  - N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.
ER  - 

TY  - JFULL
T1  - Echocardiographic findings in long term survivors of allogeneic stem cell transplantation for chronic myeloid leukemia
A1  - Ayto, R
A1  - Garfield, B
A1  - Todd, J
A1  - Kanfer, E
A1  - Olavaria, E
A1  - Rahemtulla, A
A1  - Marin, D
A1  - Apperley, J
A1  - Salooja, N
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 77
EP  - 78
ER  - 

TY  - JFULL
T1  - A novel Pro92His, and previously described, Glu255-, double mutation of NADH-cytochrome b5 reductase associated with apparent type I RCM
A1  - Percy, MJ
A1  - Crowley, LJ
A1  - Layton, M
A1  - Lappin, T
A1  - Barber, M
J1  - FASEB J
Y1  - 2007/04//
VL  - 21
SN  - 0892-6638
SP  - A1044
EP  - A1044
ER  - 

TY  - JFULL
T1  - Activation of latent provirus: nEw therapy for HTLV-1-associated myelopathy/tropical spastic paraparesis? (a proof-of-concept study)
A1  - Lezin, A
A1  - Gillet, N
A1  - Olindo, S
A1  - Belrose, G
A1  - Verlaeten, O
A1  - Asquith, B
A1  - Grandvaux, N
A1  - Burny, A
A1  - Smadja, D
A1  - Cesaire, R
A1  - Willems, L
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 643
EP  - 644
ER  - 

TY  - JFULL
T1  - Bone marrow trephine findings in CMML
A1  - Ngo, N
A1  - Lampert, I
A1  - Naresh, K
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 24
EP  - 24
ER  - 

TY  - JFULL
T1  - Impaired maturation and function of HTLV-1-specific CTLs in HAM/TSP
A1  - Saito, M
A1  - Sabouri, A
A1  - Nose, H
A1  - Usuku, K
A1  - Izumo, S
A1  - Arimura, K
A1  - Osame, M
A1  - Ohara, Y
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 584
EP  - 584
ER  - 

TY  - JFULL
T1  - In vivo selection of human T cell lymphotropic virus type-1-specific CD4(+) cells by disease susceptive class II allele and immunodominant peptide complex in HTLV-1-associated neurological disease
A1  - Nose, H
A1  - Usuku, K
A1  - Kubota, R
A1  - Izumo, S
A1  - Arimura, K
A1  - Bangham, C
A1  - Osame, M
A1  - Saito, M
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 634
EP  - 634
ER  - 

TY  - JFULL
T1  - Exaggerated postprandial GLP-2 response after Roux-en-Y gastric bypass might be causative for post surgical intestinal adaptation
A1  - Wallis, K
A1  - Le Roux, CW
A1  - Aylwin, SJ
A1  - Patel, AG
A1  - Welbourn, R
A1  - Bloom, SR
A1  - Forbes, A
A1  - Ghatei, MA
A1  - Walters, JR
J1  - GASTROENTEROLOGY
Y1  - 2007/04//
VL  - 132
SN  - 0016-5085
SP  - A71
EP  - A71
ER  - 

TY  - JFULL
T1  - Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin.
A1  - Germain, N
A1  - Galusca, B
A1  - Le Roux, CW
A1  - Bossu, C
A1  - Ghatei, MA
A1  - Lang, F
A1  - Bloom, SR
A1  - Estour, B
J1  - Am J Clin Nutr
Y1  - 2007/04//
VL  - 85
SN  - 0002-9165
SP  - 967
EP  - 971
N2  - BACKGROUND: Food intake is controlled by the arcuate nucleus through integration of peripheral hormonal signals such as leptin, ghrelin, peptide YY (PYY), and glucagon-like peptide 1 (GLP-1). The most common condition resulting in underweight young women in the developed world is restrictive anorexia nervosa (AN). However, constitutional thinness (CT) is also known to exist in the same low-weight range. Women with CT have normal menstrual periods and do not have the psychological or hormonal features of AN. Little is currently known about regulation of food intake in subjects with CT. OBJECTIVE: We tested the hypothesis that concentrations of leptin, ghrelin, PYY, and GLP-1 in persons with AN are significantly different from those in persons with CT. DESIGN: Concentrations of PYY, GLP-1, ghrelin, and leptin were measured in 3 groups of young women: normal weight (n = 7), CT (n = 10), and AN (n = 12). Samples were collected every 4 h for 24 h. RESULTS: PYY concentrations were significantly higher in CT subjects than in AN or control subjects. GLP-1 concentrations were significantly higher in AN than in CT subjects, whereas ghrelin was significantly higher in AN subjects than in control and CT subjects. CT subjects had the lowest ghrelin concentrations. Leptin concentrations were significantly lower in AN subjects. PYY and leptin circadian variations were not significantly different between CT and control subjects, whereas these profiles were blunted in AN subjects. CONCLUSIONS: Orexigenic and anorexigenic hormones in CT contrast with an adaptative profile characterizing AN. The hormones appear to be valuable biomarkers for distinguishing these 2 categories of severely underweight subjects.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17413094&query_hl=1
ER  - 

TY  - JFULL
T1  - Myocardial infarction (MI) in a 28 year old woman following treatment with DDAVP and tranexamic acid
A1  - Patel A
A1  - Laffan M
J1  - British Journal of Haematology
Y1  - 2007/04//
IS  - Suppl 1
VL  - 137
SP  - 52
EP  - 53
ER  - 

TY  - JFULL
T1  - The Bxs6 locus of BXSB mice is sufficient for high-level expression of gp70 and the production of gp70 immune complexes.
A1  - Rankin, J
A1  - Boyle, JJ
A1  - Rose, SJ
A1  - Gabriel, L
A1  - Lewis, M
A1  - Thiruudaian, V
A1  - Rogers, NJ
A1  - Izui, S
A1  - Morley, BJ
J1  - J Immunol
Y1  - 2007/04/01/
VL  - 178
SN  - 0022-1767
SP  - 4395
EP  - 4401
N2  - High levels of the retroviral envelope protein gp70 and gp70 immune complexes have been linked to a single locus on chromosome 13 (Bxs6) in the BXSB model, to which linkage of nephritis was also seen. Congenic lines containing the BXSB Bxs6 interval on a non-autoimmune C57BL/10 background were bred in the presence or absence of the BXSB Y chromosome autoimmune accelerator gene (Yaa), which accelerates disease in male mice. In these mice, we have shown that Bxs6 is sufficient to cause high-level expression of gp70 and the production of gp70 autoantibodies, independently of Yaa, with gp70 immune complex levels enhanced by Yaa. In the presence of Yaa, Bxs6 also causes mild nephritis, and interestingly the sporadic production of high levels of anti-DNA Abs in some mice. Fine mapping using rare recombinant mice suggested that Bxs6 lies between 59.7 and 74.8 megabases (Mb), although the interval of 0.6 Mb between 73.6 and 78.6 Mb on chromosome 13 cannot be excluded in this study.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17371996&query_hl=1
ER  - 

TY  - JFULL
T1  - Control of CTL response to HTLV-1 virus by regulatory T cells in asymptomatic carriers, HAM/TSP patients, and ATL patients
A1  - Toulza, F
A1  - Nosaka, K
A1  - Takiguchi, M
A1  - Mitsuya, H
A1  - Taylor, GP
A1  - Bangham, CRM
J1  - AIDS RES HUM RETROV
Y1  - 2007/04//
VL  - 23
SN  - 0889-2229
SP  - 583
EP  - 583
ER  - 

TY  - JFULL
T1  - Bone marrow trephine findings in AML with multi-lineage dysplasia
A1  - Ngo, N
A1  - Lampert, I
A1  - Naresh, K
J1  - BRIT J HAEMATOL
Y1  - 2007/04//
VL  - 137
SN  - 0007-1048
SP  - 24
EP  - 24
ER  - 

TY  - JFULL
T1  - Peritoneal mesothelioma: an unusual cause of an acute phase response presenting to the rheumatologist.
A1  - Hamdulay, SS
A1  - Cook, HT
A1  - Strickland, N
A1  - Davies, KA
A1  - Mason, JC
J1  - Clin Rheumatol
Y1  - 2007/04//
VL  - 26
SN  - 0770-3198
SP  - 584
EP  - 586
N2  - The presence of an acute phase response may pre-date the eventual diagnosis of malignant disease by months or even years. We describe two patients referred to the rheumatology clinic, in which extensive investigation failed to identify an underlying cause to account for the presenting symptoms and an associated acute phase response. Several months later, repeated abdominal CT scans revealed an abnormality and subsequent laparoscopic biopsy confirmed a diagnosis of peritoneal mesothelioma.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16416032&query_hl=1
ER  - 

TY  - JFULL
T1  - Potential of CD34 in the regulation of symmetrical and asymmetrical divisions by hematopoietic progenitor cells.
A1  - Bullock, TE
A1  - Wen, B
A1  - Marley, SB
A1  - Gordon, MY
J1  - Stem Cells
Y1  - 2007/04//
VL  - 25
SN  - 1066-5099
SP  - 844
EP  - 851
N2  - The control of symmetric and asymmetric division in the hematopoietic stem/progenitor cell population is critically important for the regulation of blood cell production. Asymmetric divisions depend on cell polarization, which may be conferred by location and/or interaction with neighboring cells. In this study, we sought evidence for polarization in CD34+ cells, which interact by binding to one another. In these cells, surface molecules became redistributed by mechanisms that included transport by lipid rafts, and the interacting cells were able to communicate via gap junctions. These changes were accompanied by modulation of cell cycle regulating proteins (p16(Ink4a), p27(kip1), cyclins D, and the retinoblastoma pathway proteins) and a reduction in progenitor cell proliferation in vitro. These results are consistent with an increase in asymmetric cell division kinetics. Accordingly, we found that interaction between CD34+ cells influenced the plane of cell division in a way that suggests unequal sharing of Notch-1 between daughter cell progeny. We conclude that interaction between CD34+ cells may coordinate cell function and participate in the control of hematopoietic stem/progenitor cell division kinetics.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17185613&query_hl=1
ER  - 

TY  - JFULL
T1  - Sensor I threonine of the AAA+ ATPase transcriptional activator PspF is involved in coupling nucleotide triphosphate hydrolysis to the restructuring of sigma 54-RNA polymerase.
A1  - Schumacher, J
A1  - Joly, N
A1  - Rappas, M
A1  - Bradley, D
A1  - Wigneshweraraj, SR
A1  - Zhang, X
A1  - Buck, M
J1  - J Biol Chem
Y1  - 2007/03/30/
VL  - 282
SN  - 0021-9258
SP  - 9825
EP  - 9833
N2  - Transcriptional initiation invariably involves the transition from a closed RNA polymerase (RNAP) promoter complex to a transcriptional competent open complex. Activators of the bacterial sigma(54)-RNAP are AAA+ proteins that couple ATP hydrolysis to restructure the sigma(54)-RNAP promoter complex. Structures of the sigma(54) activator PspF AAA+ domain (PspF(1-275)) bound to sigma(54) show two loop structures proximal to sigma(54) as follows: the sigma(54) contacting the GAFTGA loop 1 structure and loop 2 that classifies sigma(54) activators as pre-sensor 1 beta-hairpin AAA+ proteins. We report activities for PspF(1-275) mutated in the AAA+ conserved sensor I threonine/asparagine motif (PspF(1-275)(T148A), PspF(1-275)(N149A), and PspF(1-275)(N149S)) within the second region of homology. We show that sensor I asparagine plays a direct role in ATP hydrolysis. However, low hydrolysis rates are sufficient for functional output in vitro. In contrast, PspF(1-275)(T148A) has severe defects at the distinct step of sigma(54) promoter restructuring. This defect is not because of the failure of PspF(1-275)(T148A) to stably engage with the closed sigma(54) promoter, indicating (i) an important role in ATP hydrolysis-associated motions during energy coupling for remodeling and (ii) distinguishing PspF(1-275)(T148A) from PspF(1-275) variants involved in signaling to the GAFTGA loop 1, which fail to stably engage with the promoter. Activities of loop 2 PspF(1-275) variants are similar to those of PspF(1-275)(T148A) suggesting a functional signaling link between Thr(148) and loop 2. In PspF(1-275) this link relies on the conserved nucleotide state-dependent interaction between the Walker B residue Glu(108) and Thr(148). We propose that hydrolysis is relayed via Thr(148) to loop 2 creating motions that provide mechanical force to the GAFTGA loop 1 that contacts sigma(54).
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17242399&query_hl=1
ER  - 

TY  - JFULL
T1  - Enhanced differentiation and mineralization of human fetal osteoblasts on PDLLA containing Bioglass composite films in the absence of osteogenic supplements.
A1  - Tsigkou, O
A1  - Hench, LL
A1  - Boccaccini, AR
A1  - Polak, JM
A1  - Stevens, MM
J1  - J Biomed Mater Res A
Y1  - 2007/03/15/
VL  - 80
SN  - 1549-3296
SP  - 837
EP  - 851
N2  - This study investigates the cellular response of fetal osteoblasts to bioactive resorbable composite films consisting of a poly-D,L-lactide (PDLLA) matrix and bioactive glass 45S5 Bioglass (BG) particles at three different concentrations (0% (PDLLA), 5% (P/BG5), and 40% (P/BG40)). Using scanning electron microscopy (SEM) we observed that cells were less spread and elongated on PDLLA and P/BG5, whereas cells on P/BG40 were elongated but with multiple protrusions spreading over the BG particles. Vinculin immunostaining revealed similar distribution of focal adhesion contacts on all cells independent of substratum, indicating that all materials permitted cell adhesion. However, when differentiation and maturation of fetal osteoblasts was examined, incorporation of 45S5 BG within the PDLLA matrix was found to significantly (p < 0.05) enhance alkaline phosphatase enzymatic activity and osteocalcin protein synthesis compared to tissue culture polystyrene controls and PDLLA alone. Alizarin red staining indicated extracellular matrix mineralization on both P/BG5 and P/BG40, with significantly more bone nodules formed than on PDLLA. Real time RT-PCR revealed that expression of bone sialoprotein was also affected by the BG containing films compared to controls, whereas expression of Collagen Type I was not influenced. By performing these investigations in the absence of osteogenic factors it appears that the incorporation of BG stimulates osteoblast differentiation and mineralization of the extracellular matrix, demonstrating the osteoinductive capacity of the composite.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17072851&query_hl=1
ER  - 

TY  - JFULL
T1  - Monocyte-dependent fibroblast CXCL8 secretion occurs in tuberculosis and limits survival of mycobacteria within macrophages.
A1  - O'Kane, CM
A1  - Boyle, JJ
A1  - Horncastle, DE
A1  - Elkington, PT
A1  - Friedland, JS
J1  - J Immunol
Y1  - 2007/03/15/
VL  - 178
SN  - 0022-1767
SP  - 3767
EP  - 3776
N2  - CXCL8 is a chemokine that is implicated in the formation of tuberculous (TB) granulomas and in immunity to Mycobacterium tuberculosis (Mtb). Fibroblast chemokine secretion is important for modulating inflammatory responses in chronic lung disease and inflammatory arthritis but has not been investigated in the pathophysiology of TB. In this study, we used a cellular model to examine monocyte/macrophage-dependent stimulation of fibroblasts by Mtb in the regulation of chemokine secretion, particularly that of CXCL8. Human lung fibroblasts grown in collagen were stimulated with conditioned medium from Mtb-infected monocytes (CoMTb). CoMTb-induced prolonged dose-dependent, p38-mediated expression of stable CXCL8 mRNA by fibroblasts accompanied by a >10-fold increase in CXCL8 secretion (487 +/- 88 ng/ml vs 48.6 +/- 34 ng/ml in controls) at 120 h. Fibroblasts strongly expressed CXCL8 in vivo in human TB granulomas. Inhibition of TNF-alpha or IL-1 in CoMTb abrogated the induction of CXCL8 at a pretranscriptional level. CXCL8 secretion was NF-kappaB, C/EBP, and JNK dependent. Sustained NF-kappaB activation was demonstrated beyond 24 h in response to CoMTb. Exogenous CXCL8 reduced the survival of Mtb within macrophages, and inhibition of CXCL8 was associated with intracellular mycobacterial proliferation. These data show that fibroblasts have a previously unrecognized role in modulating inflammation in TB by their CXCL8-dependent contribution to cell recruitment and mycobacterial killing within the granuloma.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17339475&query_hl=1
ER  - 

TY  - JFULL
T1  - Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy.
A1  - Hochhaus, A
A1  - Kantarjian, HM
A1  - Baccarani, M
A1  - Lipton, JH
A1  - Apperley, JF
A1  - Druker, BJ
A1  - Facon, T
A1  - Goldberg, SL
A1  - Cervantes, F
A1  - Niederwieser, D
A1  - Silver, RT
A1  - Stone, RM
A1  - Hughes, TP
A1  - Muller, MC
A1  - Ezzeddine, R
A1  - Countouriotis, AM
A1  - Shah, NP
J1  - Blood
Y1  - 2007/03/15/
VL  - 109
SN  - 0006-4971
SP  - 2303
EP  - 2309
N2  - Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17138817&query_hl=1
ER  - 

TY  - JFULL
T1  - AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis.
A1  - Carpenter, EP
A1  - Corbett, A
A1  - Thomson, H
A1  - Adacha, J
A1  - Jensen, K
A1  - Bergeron, J
A1  - Kasampalidis, I
A1  - Exley, R
A1  - Winterbotham, M
A1  - Tang, C
A1  - Baldwin, GS
A1  - Freemont, P
J1  - EMBO J
Y1  - 2007/03/07/
VL  - 26
SN  - 0261-4189
SP  - 1363
EP  - 1372
N2  - Oxidative stress is a principal cause of DNA damage, and mechanisms to repair this damage are among the most highly conserved of biological processes. Oxidative stress is also used by phagocytes to attack bacterial pathogens in defence of the host. We have identified and characterised two apurinic/apyrimidinic (AP) endonuclease paralogues in the human pathogen Neisseria meningitidis. The presence of multiple versions of DNA repair enzymes in a single organism is usually thought to reflect redundancy in activities that are essential for cellular viability. We demonstrate here that these two AP endonuclease paralogues have distinct activities in DNA repair: one is a typical Neisserial AP endonuclease (NApe), whereas the other is a specialised 3'-phosphodiesterase Neisserial exonuclease (NExo). The lack of AP endonuclease activity of NExo is shown to be attributable to the presence of a histidine side chain, blocking the abasic ribose-binding site. Both enzymes are necessary for survival of N. meningitidis under oxidative stress and during bloodstream infection. The novel functional pairing of NExo and NApe is widespread among bacteria and appears to have evolved independently on several occasions.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17318183&query_hl=1
ER  - 

TY  - JFULL
T1  - Endothelial progenitor cells in patients with eisenmenger syndrome or idiopathic pulmonary arterial hypertension
A1  - Diller, GP
A1  - Okonko, DO
A1  - Wort, JS
A1  - Wilkins, MR
A1  - Wharton, J
A1  - Gatzoulis, MA
J1  - J AM COLL CARDIOL
Y1  - 2007/03/06/
VL  - 49
SN  - 0735-1097
SP  - 269A
EP  - 269A
ER  - 

TY  - JFULL
T1  - Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study.
A1  - Thwaites, GE
A1  - Macmullen-Price, J
A1  - Tran, TH
A1  - Pham, PM
A1  - Nguyen, TD
A1  - Simmons, CP
A1  - White, NJ
A1  - Tran, TH
A1  - Summers, D
A1  - Farrar, JJ
J1  - Lancet Neurol
Y1  - 2007/03//
VL  - 6
SN  - 1474-4422
SP  - 230
EP  - 236
N2  - BACKGROUND: Adjunctive dexamethasone increases survival from tuberculous meningitis, but the underlying mechanism is unclear. We aimed to determine the effect of dexamethasone on cerebral MRI changes and their association with intracerebral inflammatory responses and clinical outcome in adults treated for tuberculous meningitis. METHODS: Cerebral MRI was undertaken, when possible, at diagnosis and after 60 days and 270 days of treatment in adults with tuberculous meningitis admitted to two hospitals in Vietnam. Patients were randomly assigned either dexamethasone (n=24) or placebo (n=19) and received 9 months of treatment with standard first-line antituberculosis drugs. We assessed associations between MRI findings, treatment allocation, and resolution of fever, coma, cerebrospinal fluid inflammation, and neurological outcome. FINDINGS: 83 scans were done for 43 patients: 19 given placebo, 24 given dexamethasone. Basal meningeal enhancement (82%) and hydrocephalus (77%) were the most common presenting findings. Fewer patients had hydrocephalus after 60 days of treatment with dexamethasone than after placebo treatment (p=0.217). Tuberculomas developed in 74% of patients during treatment and in equal proportions in the treatment groups; they were associated with long-term fever, but not relapse or poor clinical outcome. The basal ganglia were the most common site of infarction; the proportion with infarction after 60 days was halved in the dexamethasone group (27%vs 58%, p=0.130). INTERPRETATION: Dexamethasone may affect outcome from tuberculous meningitis by reducing hydrocephalus and preventing infarction. The effect may have been under-estimated because the most severe patients could not be scanned.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17303529&query_hl=1
ER  - 

TY  - JFULL
T1  - Impact of L-arginine deprivation on macrophage effector functions
A1  - Choi, BS
A1  - Clara-Martinez-Fal, I
A1  - Corset, C
A1  - Muller, I
A1  - Kropf, P
J1  - IMMUNOLOGY
Y1  - 2007/03//
VL  - 120
SN  - 0019-2805
SP  - 83
EP  - 83
ER  - 

TY  - JFULL
T1  - Extracellular matrix formation and mineralization on a phosphate-free porous bioactive glass scaffold using primary human osteoblast (HOB) cells.
A1  - Jones, JR
A1  - Tsigkou, O
A1  - Coates, EE
A1  - Stevens, MM
A1  - Polak, JM
A1  - Hench, LL
J1  - Biomaterials
Y1  - 2007/03//
VL  - 28
SN  - 0142-9612
SP  - 1653
EP  - 1663
N2  - Sol-gel derived bioactive glasses of the 70S30C (70mol% SiO2, 30mol% CaO) composition have been foamed to produce 3D bioactive scaffolds with hierarchical interconnected pore morphologies similar to trabecular bone. The aim of this study was to investigate primary human osteoblast response to porous bioactive glass scaffolds. The scaffolds supported osteoblast growth and induced differentiation, within the 3-week culture period, as depicted by enhanced ALPase enzymatic activity, without the addition of supplementary factors such as ascorbic acid, beta-glycerophosphate and dexamethasone. This is the first time this has been observed on a bioactive glass that does not contain phosphate. Deposition of extracellular matrix was also confirmed by enhanced production of the extracellular matrix protein collagen type I. SEM showed indications of mineralized bone nodule formation without the addition of growth factors. The 70S30C bioactive glass scaffolds therefore fulfil many of the criteria for an ideal scaffold for bone tissue engineering applications.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17175022&query_hl=1
ER  - 

TY  - JFULL
T1  - Critical observations on the neurotoxicity of silver.
A1  - Lansdown, AB
J1  - Crit Rev Toxicol
Y1  - 2007/03//
VL  - 37
SN  - 1040-8444
SP  - 237
EP  - 250
N2  - Silver is a xenobiotic element with no recognized trace metal value in the human body. It is absorbed into the body through the lungs, gastrointestinal tract, mucus membranes of the urinogenital tract, and through the skin, mainly in the form of silver protein complexes. Although silver is metabolized throughout the soft tissues, available evidence from experimental animal studies and human clinical reports has failed to unequivocally establish that it enters tissues of the central nervous system or is a cause of neurotoxic damage. Argyria characterized by deposition of particles of silver sulfide or silver selenide is the principle contraindication for using silver in medical devices or occupationally. This presents discoloration of the skin but is not regarded as a health risk or manifestation of toxicity. No evidence is available to demonstrate the toxic risk of silver to the peripheral nervous system, although silver sulfide deposits have been identified in the region of cutaneous nerves. Transitory silver sulfide deposits seen in the tissues of the blood-brain and blood-CSF barriers are mostly lysosomally bound or deposited on basement membranes or collagen without toxic effect. Silver is mostly excreted from the body in the urine and feces. Further research is indicated to evaluate the role of metal binding proteins including metallothioneins as cytoprotectants for neurological tissue.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17453933&query_hl=1
ER  - 

TY  - JFULL
T1  - ADAMTS13 and von Willebrand factor and the risk of myocardial infarction in men.
A1  - Chion, CK
A1  - Doggen, CJ
A1  - Crawley, JT
A1  - Lane, DA
A1  - Rosendaal, FR
J1  - Blood
Y1  - 2007/03/01/
VL  - 109
SN  - 0006-4971
SP  - 1998
EP  - 2000
N2  - Von Willebrand factor (VWF) mediates the tethering/adhesion of platelets at sites of vascular injury. This function depends on its multimeric size, which is controlled by ADAMTS13. We measured plasma ADAMTS13 and VWF antigen levels by enzyme-linked immunosorbent assay (ELISA) in a large population-based case-control study (Study of Myocardial Infarctions Leiden [SMILE]), consisting of 560 men with a first myocardial infarction (MI) and 646 control subjects. Although ABO blood groups influenced VWF levels, they had no influence on ADAMTS13. Furthermore, there was no relationship between plasma ADAMTS13 and VWF levels. Similar to VWF, the estimated risk of MI was increased for every quartile of ADAMTS13 when compared to the lowest quartile (odds ratio, 1.5-1.6). If confirmed, the association of ADAMTS13 with MI may suggest an unexpected mechanistic action of ADAMTS13.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17053057&query_hl=1
ER  - 

TY  - JFULL
T1  - RNA binding by the herpes simplex virus type 1 nucleocytoplasmic shuttling protein UL47 is mediated by an N-terminal arginine-rich domain that also functions as its nuclear localization signal.
A1  - Donnelly, M
A1  - Verhagen, J
A1  - Elliott, G
J1  - J Virol
Y1  - 2007/03//
VL  - 81
SN  - 0022-538X
SP  - 2283
EP  - 2296
N2  - The function of the alphaherpesvirus UL47 tegument protein has not yet been defined. Nonetheless, previous studies with transfected cells have shown that both the herpes simplex virus type 1 homologue (hUL47, or VP13/14) and the bovine herpesvirus type 1 (BHV-1) homologue (bUL47, or VP8) have the capacity to shuttle between the nucleus and the cytoplasm. Furthermore, hUL47 packaged into the virion has also been shown to bind several individual virus-specific RNA transcripts. Here, we extend these observations and show that hUL47 binds a wide range of RNA species in vitro. It has a high affinity for polyadenylated transcripts but has no apparent selectivity for virus-encoded RNA over cellular RNA. We also show that the virion population of bUL47 binds RNA in vitro. However, while purified recombinant hUL47 retains its RNA binding activity, recombinant bUL47 does not, suggesting that the BHV-1 homologue may require virus-induced modification for its activity. We identify the minimal RNA binding domain in hUL47 as a 26-residue N-terminal peptide containing an arginine-rich motif that is essential but not sufficient for optimal RNA binding, and we demonstrate that this RNA binding domain incorporates the hUL47 minimal nuclear localization signal. In addition, we show that soon after hUL47 is expressed during infection, it colocalizes in the infected cell nucleus with ICP4, the major virus transcriptional activator. Using RNA immunoprecipitations, we demonstrate that hUL47 is also bound in vivo to at least one viral transcript, the ICP0 mRNA. Taken together, these results suggest that hUL47 may play a role in RNA biogenesis in the infected cell.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17166902&query_hl=1
ER  - 

TY  - JFULL
T1  - NS1 proteins of avian influenza A viruses can act as antagonists of the human alpha/beta interferon response.
A1  - Hayman, A
A1  - Comely, S
A1  - Lackenby, A
A1  - Hartgroves, LC
A1  - Goodbourn, S
A1  - McCauley, JW
A1  - Barclay, WS
J1  - J Virol
Y1  - 2007/03//
VL  - 81
SN  - 0022-538X
SP  - 2318
EP  - 2327
N2  - Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-beta promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-beta induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-beta induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17182679&query_hl=1
ER  - 

TY  - JFULL
T1  - The V beta specific response to bacterial superantigens is determined by concentration and HLA class II
A1  - Llewelyn, M
A1  - Sriskandan, S
A1  - Terrazzini, N
A1  - Cohen, J
A1  - Altmann, DM
J1  - IMMUNOLOGY
Y1  - 2007/03//
VL  - 120
SN  - 0019-2805
SP  - 77
EP  - 77
ER  - 

TY  - JFULL
T1  - Dissecting signalling pathways regulating tissue destruction in pulmonary tuberculosis
A1  - Rand, L
A1  - Green, JA
A1  - Elkington, PTG
A1  - Friedland, JS
J1  - IMMUNOLOGY
Y1  - 2007/03//
VL  - 120
SN  - 0019-2805
SP  - 48
EP  - 48
ER  - 

TY  - JFULL
T1  - Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.
A1  - Nadal, E
A1  - Garin, M
A1  - Kaeda, J
A1  - Apperley, J
A1  - Lechler, R
A1  - Dazzi, F
J1  - Leukemia
Y1  - 2007/03//
VL  - 21
SN  - 0887-6924
SP  - 472
EP  - 479
N2  - The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus-leukemia (GvL) effect exerted by donor T cells. CD4(+)CD25(high) regulatory T cells (T(regs)) have been shown to downregulate antitumor responses but their role on GvL has not been evaluated. We performed a cross-sectional study in which we enumerated and characterized CD4(+)CD25(high) T(regs) in the peripheral blood of CML patients undergoing allogeneic SCT. We documented higher frequencies of T(regs) in patients after transplant as compared to normal controls and newly diagnosed patients. The increment was particularly evident in patients who had received their SCT 18 months before. In vitro functional studies demonstrated that the T(regs) purified from SCT patients exhibited a more potent suppressive activity than T(regs) isolated from healthy volunteers. Patients in whom T(regs) numbers were higher than controls more than 18 months after SCT showed evidence of disease relapse. Although the increment in T(regs) might have an advantageous effect on graft rejection in the early phase post-transplant, our data suggest that T(regs) exert an inhibitory effect on GvL.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17215853&query_hl=1
ER  - 

TY  - JFULL
T1  - The neuroendocrine physiology of kisspeptin in the human.
A1  - Dhillo, WS
A1  - Murphy, KG
A1  - Bloom, SR
J1  - Rev Endocr Metab Disord
Y1  - 2007/03//
VL  - 8
SN  - 1389-9155
SP  - 41
EP  - 46
N2  - Kisspeptin is a 54-amino acid peptide, encoded by the KiSS-1 gene, which activates the G protein-coupled receptor GPR54. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of reproduction. GPR54-deficient mice have abnormal sexual development. Central or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG) axis in animal models. This review discusses the evidence that kisspeptin also plays a key role in human reproduction. Inactivating GPR54 mutations cause normosmic hypogonadotrophic hypogonadism in humans. Mutations which increase GPR54 signaling are associated with gonadotrophin-dependent premature puberty. Acute intravenous administration of kisspeptin to healthy human male volunteers potently increased plasma LH levels and significantly increased plasma FSH and testosterone without side effects. Plasma kisspeptin is found at low concentrations in the circulation of men and non-pregnant women, but is markedly increased in pregnancy. The placenta is believed to be the source of these high levels of circulating kisspeptin. The kisspeptin-GPR54 system is also implicated in tumour biology. Consistent with this role, plasma kisspeptin concentrations are elevated in patients with abnormal proliferation of placental tissue (gestational trophoblastic neoplasia or GTN) at presentation and fall after treatment with chemotherapy. The kisspeptin/GPR54 system therefore appears to play an important role in the regulation of reproduction in humans. Kisspeptin represents a novel tool for the manipulation of the HPG axis in humans and plasma kisspeptin may be a novel tumour marker in patients with GTN.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17323132&query_hl=1
ER  - 

TY  - JFULL
T1  - Lactate acquisition promotes successful colonization of the murine genital tract by Neisseria gonorrhoeae.
A1  - Exley, RM
A1  - Wu, H
A1  - Shaw, J
A1  - Schneider, MC
A1  - Smith, H
A1  - Jerse, AE
A1  - Tang, CM
J1  - Infect Immun
Y1  - 2007/03//
VL  - 75
SN  - 0019-9567
SP  - 1318
EP  - 1324
N2  - Previous studies on Neisseria gonorrhoeae have demonstrated that metabolism of lactate in the presence of glucose increases the growth rate of the bacterium and enhances its resistance to complement-mediated killing. Although these findings in vitro suggest that the acquisition of lactate promotes gonococcal colonization, the significance of this carbon source to the survival of the gonococcus in vivo remains unknown. To investigate the importance of lactate utilization during Neisseria gonorrhoeae genital tract infection, we identified the gene lctP, which encodes the gonococcal lactate permease. A mutant that lacks a functional copy of lctP was unable to take up exogenous lactate and did not grow in defined medium with lactate as the sole carbon source, in contrast to the wild-type and complemented strains; the mutant strain exhibited no growth defect in defined medium containing glucose. In defined medium containing physiological concentrations of lactate and glucose, the lctP mutant demonstrated reduced early growth and increased sensitivity to complement-mediated killing compared with the wild-type strain; the enhanced susceptibility to complement was associated with a reduction in lipopolysaccharide sialylation of the lctP mutant. The importance of lactate utilization during colonization was evaluated in the murine model of lower genital tract infection. The lctP mutant was significantly attenuated in its ability to colonize and survive in the genital tract, while the complemented mutant exhibited no defect for colonization. Lactate is a micronutrient in the genital tract that contributes to the survival of the gonococcus.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158905&query_hl=1
ER  - 

TY  - JFULL
T1  - Optimal management of patients with newly diagnosed chronic phase chronic myeloid leukemia in 2007
A1  - Mughal, T
A1  - Goldman, JM
J1  - SPAN J PSYCHOL
Y1  - 2007/03//
VL  - 7
SP  - S95
EP  - S101
N2  - <p>Chronic myeloid leukemia cells contain a Bcr-Abl oncoprotein with an enhanced tyrosine kinase activity, which is considered to be the principal cause of the leukemia. The use of the first-generation tyrosine kinase inhibitor imatinib to inhibit the dysregulated kinase activity has proved remarkably successful, and imatinib as a single-agent is now considered to be the best initial treatment for the majority of adult patients in chronic phase. For patients who develop resistance to imatinib, the Bcr-Abl signaling pathway is often re-activated, second generation tyrosine kinase inhibitors, such as dasatinib or nilotinib, might restore the kinase inhibition. Allogeneic stem cell transplantation is now generally offered to older patients in whom imatinib therapy, and perhaps dasatinib or nilotinib also, have failed; efforts to establish firm criteria for the selection of second-line therapies after imatinib failure continue. At this time, children and younger adults should probably be considered for transplantation as first-line treatment.</p>
ER  - 

TY  - JFULL
T1  - Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats.
A1  - McGowan, BM
A1  - Stanley, SA
A1  - White, NE
A1  - Spangeus, A
A1  - Patterson, M
A1  - Thompson, EL
A1  - Smith, KL
A1  - Donovan, J
A1  - Gardiner, JV
A1  - Ghatei, MA
A1  - Bloom, SR
J1  - Am J Physiol Endocrinol Metab
Y1  - 2007/03//
VL  - 292
SN  - 0193-1849
SP  - E913
EP  - E919
N2  - The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4+/-0.2 (vehicle) vs. 2.9+/-0.5 g (H3), P<0.001; ARC 0.7+/-0.3 (vehicle) vs. 2.7+/-0.2 g (H3), P<0.05; and APOA 0.8+/-0.1 (vehicle) vs. 2.2+/-0.2 g (H3), P<0.05]. Cumulative food intake was significantly increased<or=8 h following administration into the SON and 4 h into the APOA. A significant increase in Fos-like immunoreactivity was seen in the SON following central relaxin-3 administration. Relaxin-3 stimulates feeding in several hypothalamic nuclei, and these studies provide additional support for relaxin-3 as an important peptide in appetite regulation.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17132825&query_hl=1
ER  - 

TY  - JFULL
T1  - Hormonal regulation of appetite.
A1  - Bloom, S
J1  - Obes Rev
Y1  - 2007/03//
VL  - 8 Suppl 1
SN  - 1467-7881
SP  - 63
EP  - 65
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17316304&query_hl=1
ER  - 

TY  - JFULL
T1  - Genes required for glycolipid synthesis and lipoteichoic acid anchoring in Staphylococcus aureus.
A1  - Gründling, A
A1  - Schneewind, O
J1  - J Bacteriol
Y1  - 2007/03//
VL  - 189
SN  - 0021-9193
SP  - 2521
EP  - 2530
N2  - Staphylococcus aureus lipoteichoic acid (LTA) is composed of a linear 1,3-linked polyglycerolphosphate chain and is tethered to the bacterial membrane by a glycolipid (diglucosyl-diacylglycerol [Glc2-DAG]). Glc2-DAG is synthesized in the bacterial cytoplasm by YpfP, a processive enzyme that transfers glucose to diacylglycerol (DAG), using UDP-glucose as its substrate. Here we present evidence that the S. aureus alpha-phosphoglucomutase (PgcA) and UTP:alpha-glucose 1-phosphate uridyltransferase (GtaB) homologs are required for the synthesis of Glc2-DAG. LtaA (lipoteichoic acid protein A), a predicted membrane permease whose structural gene is located in an operon with ypfP, is not involved in Glc2-DAG synthesis but is required for synthesis of glycolipid-anchored LTA. Our data suggest a model in which LtaA facilitates the transport of Glc2-DAG from the inner (cytoplasmic) leaflet to the outer leaflet of the plasma membrane, delivering Glc2-DAG as a substrate for LTA synthesis, thereby generating glycolipid-anchored LTA. Glycolipid anchoring of LTA appears to play an important role during infection, as S. aureus variants lacking ltaA display defects in the pathogenesis of animal infections.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17209021&query_hl=1
ER  - 

TY  - JFULL
T1  - Testimony and new challenges
A1  - Greaves, M
A1  - Lane, DA
J1  - J THROMB HAEMOST
Y1  - 2007/03//
VL  - 5
SN  - 1538-7933
SP  - 448
EP  - 449
ER  - 

TY  - JFULL
T1  - Low-dose pancreatic polypeptide inhibits food intake in man.
A1  - Jesudason, DR
A1  - Monteiro, MP
A1  - McGowan, BM
A1  - Neary, NM
A1  - Park, AJ
A1  - Philippou, E
A1  - Small, CJ
A1  - Frost, GS
A1  - Ghatei, MA
A1  - Bloom, SR
J1  - Br J Nutr
Y1  - 2007/03//
VL  - 97
SN  - 0007-1145
SP  - 426
EP  - 429
N2  - Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to food ingestion and remains elevated for up to 6 h postprandially. Plasma levels are elevated in patients with pancreatic tumours. An intravenous infusion of PP has been reported to reduce food intake in man, suggesting that PP is a satiety hormone. We investigated whether a lower infusion rate of PP would induce significant alterations in energy intake. The study was randomised and double-blinded. Fourteen lean fasted volunteers (five men and nine women) received 90 min infusions of PP (5 pmol/kg per min) and saline on two separate days. The dose chosen was half that used in a previous human study which reported a decrease in appetite but at supra-physiological levels of PP. One hour after the end of the infusion, a buffet lunch was served and energy intake measured. PP infusion was associated with a significant 11 % reduction in energy intake compared with saline (2440 (se 200) v. 2730 (se 180) kJ; P<0 x 05). Preprandial hunger as assessed by a visual analogue score was decreased in the PP-treated group compared to saline. These effects were achieved with plasma levels of PP within the pathophysiological range of pancreatic tumours.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17313701&query_hl=1
ER  - 

TY  - JFULL
T1  - Mapping of citrullinated alpha-enolase antibodies to an immunodominant epitope with high sequence similarity to bacterial enolase
A1  - Lundberg, K
A1  - Kinloch, A
A1  - Allison, H
A1  - Sriskandan, S
A1  - Moyes, D
A1  - Venables, P
J1  - ANN RHEUM DIS
Y1  - 2007/03/01/
VL  - 66
SN  - 0003-4967
SP  - A18
EP  - A19
ER  - 

TY  - JFULL
T1  - AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis
A1  - Carpenter E
A1  - Corbett A
A1  - Thomson H
A1  - Adacha J
A1  - Jensen K
A1  - Bergeron J
A1  - Kasampalidis I
A1  - Exley R
A1  - Winterbotham M
A1  - Tang C
A1  - Baldwin GS
A1  - Freemont P
J1  - EMBO Journal
Y1  - 2007/03//
IS  - 5
VL  - 26
SN  - 0261-4189
SP  - 1363
EP  - 1372
ER  - 

TY  - JFULL
T1  - Emerging strategies for the treatment of mutant Bcr-Abl T-315I myeloid leukemia
A1  - Mughal, TI
A1  - Goldman, JM
J1  - CLIN LYMPHOMA MYELOM
Y1  - 2007/03//
VL  - 7
SP  - S81
EP  - S84
N2  - The lessons learned from the remarkably successful use of the first-generation tyrosine kinase inhibitor (TKI) imatinib in patients with chronic myeloid leukemia resulted in a major paradigm shift in the treatment of many human cancers, and now further lessons are being learned from our enhanced understanding of the molecular mechanisms of resistance to imatinib and second-generation TKIs, particularly dasatinib and nilotinib. Although diverse mechanisms seem to be involved, the principal cause appears to be the emergence of point mutations in the AN kinase domain that affect drug affinity and some of which impair the efficacy with which the drugs bind. Currently, > 50 different mutations have been identified, and the extent to which they confer resistance varies considerably. One of the more common mutations results from the substitution of isoleucine for threonine at AN amino acid position 351, known as the T-315I mutation. It appears that the precise position of the substitution within the kinase domain dictates the degree of resistance to TKIs, and patients with the T-315I mutation develop almost complete resistance to imatinib, dasatinib, and nilotinib. Herein, we discuss the emerging strategies for circumventing resistance associated with the Bcr-Abl T-315I mutation.
ER  - 

TY  - JFULL
T1  - Laboratory development and assay standardization for the evaluation of HIV vaccines in Africa and India
A1  - Gilmour, J
A1  - Stevens, G
A1  - Gill, D
A1  - Tarragona, T
A1  - Seamons, L
A1  - Birungi, J
A1  - Kato, PK
A1  - Semaganda, A
A1  - Anzala, O
A1  - Farah, B
A1  - Ogola, S
A1  - Indangasi, J
A1  - Mhlanga, P
A1  - Ndzamela, N
A1  - Thakar, M
A1  - Pujari, A
A1  - Purandare, B
A1  - Mishra, S
A1  - Goonetilleke, N
A1  - Moore, S
A1  - Mahmoud, A
A1  - Gotch, F
A1  - Styles, T
A1  - Stout, J
A1  - Dally, L
A1  - Boaz, MJ
A1  - Hayes, P
J1  - CYTOM PART B-CLIN CY
Y1  - 2007/03//
VL  - 72B
SN  - 1552-4949
SP  - 120
EP  - 120
ER  - 

TY  - JFULL
T1  - Factors for graft-versus-host disease after donor lymphocyte infusions with an escalating dose regimen: lack of association with cell dose.
A1  - Fozza, C
A1  - Szydlo, RM
A1  - Abdel-Rehim, MM
A1  - Nadal, E
A1  - Goldman, JM
A1  - Apperley, JF
A1  - Dazzi, F
J1  - Br J Haematol
Y1  - 2007/03//
VL  - 136
SN  - 0007-1048
SP  - 833
EP  - 836
N2  - We investigated the risk factors for graft-versus-host disease (GVHD) in 82 patients treated with donor lymphocyte infusions (DLI) using an escalating dose regimen for chronic myeloid leukaemia in relapse following conventional allografting. Two factors emerged as predictors of both acute and chronic GVHD: the infusion of male recipients with lymphocytes from a female donor and the interval between transplant and last DLI, but only the first remained significant at multivariate analysis. Surprisingly, lymphocyte dose did not influence the incidence of GVHD. Our results suggest that DLI can be given in large cell doses without increasing the risk of GVHD.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17341269&query_hl=1
ER  - 

TY  - JFULL
T1  - Development of a reverse genetics system enabling the rescue of recombinant avian influenza virus A/Turkey/England/50-92/91 (H5N1).
A1  - Howard, W
A1  - Hayman, A
A1  - Lackenby, A
A1  - Whiteley, A
A1  - Londt, B
A1  - Banks, J
A1  - McCauley, J
A1  - Barclay, W
J1  - Avian Dis
Y1  - 2007/03//
VL  - 51
SN  - 0005-2086
SP  - 393
EP  - 395
N2  - We previously described the use of an established reverse genetics system for the generation of recombinant human influenza A viruses from cloned cDNAs. Here, we have assembled a set of plasmids to allow recovery of the avian H5N1 influenza virus A/Turkey/England/50-92/91 entirely from cDNA. This system enables us to introduce mutations or truncations into the cDNAs to create mutant viruses altered specifically in a chosen gene. These mutant viruses can then be used in future pathogenesis studies in chickens and in studies to understand the host range restrictions of avian influenza viruses in humans.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17494592&query_hl=1
ER  - 

TY  - JFULL
T1  - Incretins and other peptides in the treatment of diabetes.
A1  - Todd, JF
A1  - Bloom, SR
J1  - Diabet Med
Y1  - 2007/03//
VL  - 24
SN  - 0742-3071
SP  - 223
EP  - 232
N2  - Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone, released postprandially,which stimulates insulin secretion and insulin gene expression as well as pancreatic B-cell growth. Together with glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect which is the augmentation of insulin secretion following oral administration of glucose. Patients with Type 2 diabetes have greatly impaired or absent incretin-mediated insulin secretion which is mainly as a result of decreased secretion of GLP-1. However,the insulinotropic action of GLP-1 is preserved in patients with Type 2 diabetes,and this has encouraged attempts to treat Type 2 diabetic patients with GLP-1.GLP-1 also possesses a number of potential advantages over existing agents for the treatment of Type 2 diabetes. In addition to stimulating insulin secretion and promoting pancreatic B-cell mass, GLP-1 suppresses glucagon secretion,delays gastric emptying and inhibits food intake. Continuous intravenous and subcutaneous administration significantly improves glycaemic control and causes reductions in both HbA1c and body weight. However, GLP-1 is metabolized extremely rapidly in the circulation by the enzyme dipeptidyl peptidase IV(DPP-IV). This is the probable explanation for the short-lived effect of single doses of native GLP-1, making it an unlikely glucose-lowering agent. The DPP-IV resistant analogue, exenatide, has Food and Drug Administration (FDA) approval for the treatment of Type 2 diabetes and selective DPP-IV inhibitors are underdevelopment. Both approaches have demonstrated remarkable efficacy in animal models and human clinical studies. Both are well tolerated and appear to have advantages over current therapies for Type 2 diabetes, particularly in terms of the effects on pancreatic B-cell restoration and potential weight loss.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17263764&query_hl=1
ER  - 

TY  - JFULL
T1  - Old rhesus macaques treated with interleukin-7 show increased TREC levels and respond well to influenza vaccination.
A1  - Aspinall, R
A1  - Pido-Lopez, J
A1  - Imami, N
A1  - Henson, SM
A1  - Ngom, PT
A1  - Morre, M
A1  - Niphuis, H
A1  - Remarque, E
A1  - Rosenwirth, B
A1  - Heeney, JL
J1  - Rejuvenation Res
Y1  - 2007/03//
VL  - 10
SN  - 1549-1684
SP  - 5
EP  - 17
N2  - Old age is accompanied by an increased incidence of infection and poorer responses to vaccination. In this proof of principle study, old female rhesus macaques (aged 18.5 to 23.9 years) were treated with recombinant simian interleukin-7 (IL-7) or saline, according to a two-phase regime. Treatment was not associated with bone loss as judged by plasma carboxy terminal telopeptide of type I collagen (ICTP) levels, nor with neutropenia. IL-7-treated animals showed an increase in the number of blood CD4(+) CD3(+) and CD8(+) CD3(+) T cells after both phases of treatment and a transient increase in the number of naïve (CD62L(+) CD45RA(+)) T cells for both CD4(+) and CD8(+) subsets after only the first treatment. Increases in TREC levels per T cell followed both phases of treatment, but were more prolonged after the second phase. Following vaccination with inactivated influenza strain A/PR/8/34, hemagglutination inhibition assays showed that half of the IL-7-treated animals showed a greater than eight-fold increase in antibody titer following the first challenge with the vaccine. In addition IL-7-treated animals showed higher numbers of central memory CD8(+) T cells compared to pretreatment levels with numbers greater than in the saline-treated group. Animals with the highest hemagglutination inhibition titers and the best proliferation against flu antigen were among those with the highest TREC per T cell levels after the second phase of treatment. Treatment of the elderly with IL-7 may provide an effective therapy to improve the immune system.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17378748&query_hl=1
ER  - 

TY  - JFULL
T1  - Leishmania transmission from the sand fly vector: parasite secretory gel
A1  - Rogers, M
A1  - Ilg, T
A1  - Sizova, O
A1  - Nikolaev, A
A1  - Ferguson, M
A1  - Muller, I
A1  - Bates, P
J1  - IMMUNOLOGY
Y1  - 2007/03//
VL  - 120
SN  - 0019-2805
SP  - 63
EP  - 63
ER  - 

TY  - JFULL
T1  - Calcitonin and prednisolone display antagonistic actions on bone and have synergistic effects in experimental arthritis.
A1  - Mancini, L
A1  - Paul-Clark, MJ
A1  - Rosignoli, G
A1  - Hannon, R
A1  - Martin, JE
A1  - Macintyre, I
A1  - Perretti, M
J1  - Am J Pathol
Y1  - 2007/03//
VL  - 170
SN  - 0002-9440
SP  - 1018
EP  - 1027
N2  - We tested here the hypothesis that calcitonin and glucocorticoids, known to modulate bone metabolism, could have opposite actions on bone cells regulating expression of cytokine receptor activator of nuclear factor-kappaBeta ligand (RANKL) and osteoprotegerin (OPG). In the U2OS osteosarcoma cell line, calcitonin (10(-11) to 10(-9) mol/L) reduced RANKL and augmented OPG both at the mRNA and protein levels. Cell incubation with prednisolone (10(-8) to 10(-6) mol/L), the glucocorticoid chosen for this study, produced opposite results. These molecular studies prompted more functional analyses whereby osteoclast bone resorptive activity was determined. Calcitonin (10(-10) mol/L) abrogated the stimulating effect of 10 ng/ml RANKL or 10(-9) mol/L prednisolone; similar results were obtained with OPG. Assessment of calcitonin and prednisolone effects in an in vivo model of rheumatoid arthritis revealed partially surprising results. In fact, calcitonin not only preserved bone morphology (as assessed on day 18) in rats subjected to arthritis and treated with prednisolone (0.8 to 4 mg/kg daily from day 13) but also synergized with the steroid to elicit its antiarthritic effects. These results suggest that calcitonin could be used as a novel cotreatment to augment efficacy and reduce side effects associated with the prolonged use of steroids.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17322385&query_hl=1
ER  - 

TY  - JFULL
T1  - Different target range and cytotoxic specificity of adaphostin and 17-allylamino-17-demethoxygeldanamycin in imatinib-resistant and sensitive cell lines.
A1  - Barnes, DJ
A1  - De, S
A1  - van Hensbergen, P
A1  - Moravcsik, E
A1  - Melo, JV
J1  - Leukemia
Y1  - 2007/03//
VL  - 21
SN  - 0887-6924
SP  - 421
EP  - 426
N2  - Imatinib mesylate is a selective inhibitor of the oncogenic tyrosine kinase, Bcr-Abl, and is widely used as a first-line treatment for chronic myeloid leukaemia (CML). Prolonged monotherapy is frequently associated with patients becoming refractory to imatinib. Therefore, there is considerable interest in small molecule inhibitors which may be used either as replacements or as adjuncts to existing imatinib therapy. For this purpose, it is most likely that drugs which do not share imatinib's mechanism of action will be most valuable. We compared two such compounds with different modes of action, adaphostin and 17-allylamino-17-demethoxygeldanamycin (17-AAG), for their cytotoxic effect and ability to induce the downregulation of cellular proteins in a murine haemopoietic cell line transformed with human p210(Bcr-Abl), and two subclones resistant to imatinib owing to an Abl-kinase domain mutation (E255K) or amplification of the BCR-ABL gene, respectively. We found that, whereas 17-AAG selectively killed Bcr-Abl-positive cells and inhibited proteins dependent on heat-shock protein 90 for their stability (p210(Bcr-Abl) and Akt), adaphostin induced the downregulation of multiple cell-signalling proteins (p210(Bcr-Abl), Akt, Bcr, Abl and STAT5a) and was cytotoxic to both Bcr-Abl-positive and -negative cells. We suggest that both compounds may prove useful in the treatment of CML but caution that undesirable side-effects may result from the inhibition of multiple cell signalling proteins.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17252018&query_hl=1
ER  - 

TY  - JFULL
T1  - mda-5, but not RIG-I, is a common target for paramyxovirus V proteins
A1  - Childs, K
A1  - Stock, N
A1  - Ross, C
A1  - Andrejeva, J
A1  - Hilton, L
A1  - Skinner, M
A1  - Randall, R
A1  - Goodbourn, S
J1  - VIROLOGY
Y1  - 2007/03/01/
VL  - 359
SN  - 0042-6822
SP  - 190
EP  - 200
N2  - The induction of IFN-beta by the paramyxovirus PIV5 (formerly known as SV5) is limited by the action of the viral V protein that targets the cellular RNA helicase mda-5. Here we show that 12 other paramyxoviruses also target mda-5 by a direct interaction between the conserved cysteine-rich C-terminus of their V proteins and the helicase domain of mda-5. The inhibition of IFN-beta induction is not species-restricted, being observed in a range of mammalian cells as well as in avian cells, and we show that the inhibition of mda-5 function is also not restricted to mammalian cells. In contrast, the V proteins do not bind to the related RNA helicase RIG-I and do not inhibit its activity. The relative contributions of mda-5 and RIG-I to IFN-beta induction are discussed. (c) 2006 Elsevier Inc. All rights reserved.
ER  - 

TY  - JFULL
T1  - Networks regulate differential microglial MMP and TIMP expression in CNS tuberculosis
A1  - Green, JA
A1  - Elkington, PTG
A1  - Rand, L
A1  - Fry, J
A1  - Dholakia, S
A1  - Graeber, M
A1  - Friedland, JS
J1  - IMMUNOLOGY
Y1  - 2007/03//
VL  - 120
SN  - 0019-2805
SP  - 31
EP  - 31
ER  - 

TY  - JFULL
T1  - Optimal management of patients with newly diagnosed chronic phase chronic myeloid leukemia in 2007
A1  - Mughal, T
A1  - Goldman, JM
J1  - CLIN LYMPHOMA MYELOM
Y1  - 2007/03//
VL  - 7
SP  - S95
EP  - S101
N2  - Chronic myeloid leukemia cells contain a Bcr-Abl oncoprotein with an enhanced tyrosine kinase activity, which is considered to be the principal cause of the leukemia. The use of the first-generation tyrosine kinase inhibitor imatinib to inhibit the dysregulated kinase activity has proved remarkably successful, and imatinib as a single-agent is now considered to be the best initial treatment for the majority of adult patients in chronic phase. For patients who develop resistance to imatinib, the Bcr-Abl signaling pathway is often re-activated, second generation tyrosine kinase inhibitors, such as dasatinib or nilotinib, might restore the kinase inhibition. Allogeneic stem cell transplantation is now generally offered to older patients in whom imatinib therapy, and perhaps dasatinib or nilotinib also, have failed; efforts to establish firm criteria for the selection of second-line therapies after imatinib failure continue. At this time, children and younger adults should probably be considered for transplantation as first-line treatment.
ER  - 

TY  - JFULL
T1  - White blood cell scan in the follow-up of infectious diseases: is the withdrawal of antibiotic therapy necessary?
A1  - Liberatore, M
A1  - Al-Nahhas, A
A1  - Rubello, D
J1  - Nucl Med Commun
Y1  - 2007/03//
VL  - 28
SN  - 0143-3636
SP  - 151
EP  - 153
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17264771&query_hl=1
ER  - 

TY  - JFULL
T1  - SseL, a Salmonella deubiquitinase required for macrophage killing and virulence.
A1  - Rytkönen, A
A1  - Poh, J
A1  - Garmendia, J
A1  - Boyle, C
A1  - Thompson, A
A1  - Liu, M
A1  - Freemont, P
A1  - Hinton, JC
A1  - Holden, DW
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/02/27/
VL  - 104
SN  - 0027-8424
SP  - 3502
EP  - 3507
N2  - Expression of the Salmonella enterica serovar Typhimurium pathogenicity island 2 (SPI-2) type III secretion system is controlled by the two-component regulatory system SsrA-SsrB. We used a transcriptomic approach to help define the SsrA-SsrB regulon. We identified a gene encoding an uncharacterized effector (SseL) whose translocation into host cells depends on the SPI-2 secretion system. SseL has similarities to cysteine proteases with deubiquitinating activity. A GST-SseL fusion protein specifically hydrolyzed mono- and polyubiquitin substrates in vitro with a preference for K63-linked ubiquitin chains. Ubiquitin-modified proteins accumulated in macrophages infected with Salmonella sseL mutant strains but to a lesser extent when infected with bacteria expressing active protein, demonstrating that SseL functions as a deubiquitinase in vivo. Salmonella sseL mutant strains did not show a replication defect or induce altered levels of cytokine production upon infection of macrophages but were defective for a delayed cytotoxic effect and were attenuated for virulence in mice.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17360673&query_hl=1
ER  - 

TY  - JFULL
T1  - Bacterial resistance to silver-based antibiotics.
A1  - Lansdown, A
A1  - Williams, A
J1  - Nurs Times
Y1  - 2007/02/27/
VL  - 103
SN  - 0954-7762
SP  - 48
EP  - 49
N2  - Alan Lansdown and Angela Williams discuss the potential problem of silver resistance in wound care and suggest that on the basis of present knowledge, true bacterial resistance to silver is rare.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17375724&query_hl=1
ER  - 

TY  - JFULL
T1  - Statins audit: wrong question, wrong conclusions.
A1  - Moon, JC
A1  - Bogle, RG
A1  - Minhas, R
A1  - Minas, R
J1  - Lancet
Y1  - 2007/02/24/
VL  - 369
SN  - 1474-547X
SP  - 640
EP  - 640
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17321305&query_hl=1
ER  - 

TY  - JFULL
T1  - The effect of a 12-week low glycaemic index diet on heart disease risk factors and 24 h glycaemic response in healthy middle-aged volunteers at risk of heart disease: a pilot study.
A1  - Philippou, E
A1  - McGowan, BM
A1  - Brynes, AE
A1  - Dornhorst, A
A1  - Leeds, AR
A1  - Frost, GS
J1  - Eur J Clin Nutr
Y1  - 2007/02/21/
SN  - 0954-3007
N2  - Objective:To compare the effects of two energy-restricted healthy diets, one with a low GI and one with a high GI, on heart disease risk factors and weight loss in subjects at risk of heart disease.Design:A 12-week randomized parallel study of low and high GI, healthy eating diets was carried out.Setting:The study was carried out at the Hammersmith Hospital.Subjects:Eighteen subjects were recruited by advertisement and randomized to one of the two diets. Fourteen completed the study but one was excluded from the final analysis.Methods:At randomization, subjects were advised to follow the intervention diet for 12 weeks. Before randomization and on completion of the study, anthropometrics, fasting cholesterol and glucose blood tests and 24-h glucose measurements were taken using a continuous glucose monitoring system (CGMS). Statistical analysis was carried out using non-parametric tests. Median (IQR) are presented.Results:A significantly different dietary GI was achieved in the low GI (median: 51.3 (IQR: 51.0-52.0) compared to the high GI (59.3 (59.2-64.0) (P=0.032) group. By week 12, both groups reduced their energy intake by: low GI group: (-)167 ((-)312-(-)123) kcal/day (P=0018) vs high GI group: (-)596 ((-)625-(-)516) (P=0.018) kcal/day, the difference between the groups being significant (P=0.010). However, only the low GI group lost weight ((-)4.0 ((-)4.4-(-)2.4) kg (P=0.018) whereas the high GI group did not significantly change in weight ((-)1.5 ((-)3.6-0.8) kg (P=0.463). By week 12, the low GI group also had a significantly lower 24-h area under the curve (AUC) (7556 (7315-8434) vs 8841 (8424-8846) mmol-h/l (P=0.045) and overnight AUC (2429 (2423-2714) vs 3000 (2805-3072) mmol-h/l (P=0.006) glucose as measured by CGMS. There were no differences in the other heart disease risk factors assessed.Conclusions:This pilot study provides some evidence that consuming a low GI diet in addition to weight loss and healthy eating may reduce cardiovascular risk. Other potential benefits of GI might have been masked by weight loss in the low GI group. Larger-scale studies need to follow.Sponsorship:The study was funded by the British Heart Foundation.European Journal of Clinical Nutrition advance online publication, 21 February 2007; doi:10.1038/sj.ejcn.1602688.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17311054&query_hl=1
ER  - 

TY  - JFULL
T1  - Drying a tuberculosis vaccine without freezing.
A1  - Wong, YL
A1  - Sampson, S
A1  - Germishuizen, WA
A1  - Goonesekera, S
A1  - Caponetti, G
A1  - Sadoff, J
A1  - Bloom, BR
A1  - Edwards, D
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/02/20/
VL  - 104
SN  - 0027-8424
SP  - 2591
EP  - 2595
N2  - With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, "vial-fillable" powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4 degrees C and 25 degrees C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17299039&query_hl=1
ER  - 

TY  - JFULL
T1  - Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.
A1  - Coombes, RC
A1  - Kilburn, LS
A1  - Snowdon, CF
A1  - Paridaens, R
A1  - Coleman, RE
A1  - Jones, SE
A1  - Jassem, J
A1  - Van de Velde, CJ
A1  - Delozier, T
A1  - Alvarez, I
A1  - Del Mastro, L
A1  - Ortmann, O
A1  - Diedrich, K
A1  - Coates, AS
A1  - Bajetta, E
A1  - Holmberg, SB
A1  - Dodwell, D
A1  - Mickiewicz, E
A1  - Andersen, J
A1  - Lønning, PE
A1  - Cocconi, G
A1  - Forbes, J
A1  - Castiglione, M
A1  - Stuart, N
A1  - Stewart, A
A1  - Fallowfield, LJ
A1  - Bertelli, G
A1  - Hall, E
A1  - Bogle, RG
A1  - Carpentieri, M
A1  - Colajori, E
A1  - Subar, M
A1  - Ireland, E
A1  - Bliss, JM
A1  - Intergroup Exemestane Study
J1  - Lancet
Y1  - 2007/02/17/
VL  - 369
SN  - 1474-547X
SP  - 559
EP  - 570
N2  - BACKGROUND: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS: After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17307102&query_hl=1
ER  - 

TY  - JFULL
T1  - Rescue of a human cell line from endogenous Cdk1 depletion by Cdk1 lacking inhibitory phosphorylation sites.
A1  - Gupta, M
A1  - Trott, D
A1  - Porter, AC
J1  - J Biol Chem
Y1  - 2007/02/16/
VL  - 282
SN  - 0021-9258
SP  - 4301
EP  - 4309
N2  - Cells that transiently overexpress cyclin-dependent kinase 1 lacking inhibitory phosphorylation sites (Cdk1-AF) undergo premature and catastrophic mitosis, reflecting the key role for Cdk1 in promoting a timely transit from G(2) into mitosis. Conversely, cells depleted of Cdk1 undergo repeated S phases without intervening mitoses (endoreduplication), reflecting a role for Cdk1 in preventing premature S phases. It is not known how Cdk1 prevents entry into S phase at times in G(2) when it does not promote mitosis. Also uncertain is the extent of redundancy between inhibitory phosphorylation and other mechanisms for controlling Cdk1 activity. We describe here human cells that not only tolerate stable Cdk1-AF expression but also rely on it for survival when endogenous Cdk1 is depleted. When residual endogenous Cdk1 expression is further depleted, however, proliferation of Cdk1-AF-rescued cells is inhibited. Interestingly, this inhibition is not accompanied by endoreduplication. These results are consistent with a two-threshold model for Cdk1 kinase activity, one for suppressing endoreduplication and one for promoting mitosis. They also indicate that inhibitory phosphorylation is indispensable for only a fraction of the total cellular complement of Cdk1.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17164242&query_hl=1
ER  - 

TY  - JFULL
T1  - Kaposi sarcoma herpesvirus-encoded vFLIP and vIRF1 regulate antigen presentation in lymphatic endothelial cells.
A1  - Lagos, D
A1  - Trotter, MW
A1  - Vart, RJ
A1  - Wang, HW
A1  - Matthews, NC
A1  - Hansen, A
A1  - Flore, O
A1  - Gotch, F
A1  - Boshoff, C
J1  - Blood
Y1  - 2007/02/15/
VL  - 109
SN  - 0006-4971
SP  - 1550
EP  - 1558
N2  - Kaposi sarcoma-associated herpesvirus (KSHV) is etiologically linked to Kaposi sarcoma (KS), a tumor genetically akin to lymphatic endothelial cells (LECs). We obtained the immune transcriptional signature of KS and used KSHV-infected LECs (KLECs) as an in vitro model to determine the effects of KSHV on transcription and expression of genes involved in immunity. The antigen presentation, interferon (IFN) response, and cytokine transcriptomes of KLECs resemble those of KS. Transcription of genes involved in class I presentation is increased in KS and after infection of LECs, but MHC-I and ICAM-1 surface expression are down-regulated in KLECs. Inhibition of IFN induction of MHC-I transcription indicates that KSHV regulates MHC-I transcription. We show that MHC-I transcription is regulated by the KSHV-encoded viral FLICE inhibitory protein (vFLIP) and by viral IFN regulatory factor 1 (vIRF1). vFLIP up-regulates MHC-I and ICAM-1 through activation of NF-kappaB and stimulates T-cell proliferation, revealing a mechanism to prevent uncontrolled viral dissemination. In contrast, vIRF1 inhibits basal and IFN- and vFLIP-induced MHC-I transcription and surface expression through its interaction with the transcriptional coactivator p300, contributing to immune evasion. We propose that regulation of MHC-I by vFLIP and vIRF1 plays a crucial role in the host-pathogen equilibrium.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17047149&query_hl=1
ER  - 

TY  - JFULL
T1  - Genetic dissection of spontaneous autoimmunity driven by 129-derived chromosome 1 Loci when expressed on C57BL/6 mice.
A1  - Carlucci, F
A1  - Cortes-Hernandez, J
A1  - Fossati-Jimack, L
A1  - Bygrave, AE
A1  - Walport, MJ
A1  - Vyse, TJ
A1  - Cook, HT
A1  - Botto, M
J1  - J Immunol
Y1  - 2007/02/15/
VL  - 178
SN  - 0022-1767
SP  - 2352
EP  - 2360
N2  - Extensive evidence indicates that genetic predisposition is a central element in susceptibility to systemic lupus erythematosus both in humans and animals. We have previously shown that a congenic line carrying a 129-derived chromosome 1 interval on the C57BL/6 background developed humoral autoimmunity. To further dissect the contribution to autoimmunity of this 129 interval, we have created six subcongenic strains carrying fractions of the original 129 region and analyzed their serological and cellular phenotypes. At 1 year of age the congenic strain carrying a 129 interval between the microsatellites D1Mit15 (87.9 cM) and D1Mit115 (99.7 cM) (B6.129chr1b) had high levels of autoantibodies, while all the other congenic lines were not significantly different from the C57BL/6 controls. The B6.129chr1b strain displayed only mild proliferative glomerulonephritis despite high levels of IgG and C3 deposited in the kidneys. FACS analysis of the spleens revealed that the B6.129chr1b mice had a marked increase in the percentage of activated T cells associated with a significant reduction in the proportion of CD4(+)CD25(high) regulatory T cells. Moreover, this analysis showed a significantly reduced percentage of marginal zone B cells that preceded autoantibody production. Interestingly the 129chr1b-expressing bone marrow-derived macrophages displayed an impaired uptake of apoptotic cells in vitro. Collectively, our data indicate that the 129chr1b segment when recombined on the C57BL/6 genomic background is sufficient to induce loss of tolerance to nuclear Ags. These findings have important implication for the interpretation of the autoimmune phenotype associated with gene-targeted models.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17277141&query_hl=1
ER  - 

TY  - JFULL
T1  - Glucagon-like peptide-1 (7-36) amide response to low versus high glycaemic index preloads in overweight subjects with and without type II diabetes mellitus.
A1  - Milton, JE
A1  - Sananthanan, CS
A1  - Patterson, M
A1  - Ghatei, MA
A1  - Bloom, SR
A1  - Frost, GS
J1  - Eur J Clin Nutr
Y1  - 2007/02/14/
SN  - 0954-3007
N2  - Background and objective:Glucagon-like-peptide-1 (7-36) amide (GLP-1) is an insulin secretagogue and potential treatment for type II diabetes mellitus. An alternative to GLP-1 administration is endogenous dietary stimulation. We described a greater GLP-1 release following ingestion of liquids versus solids. We add to this work studying the effect of fluid preloads with differing glycaemic indices (GI) on the metabolic response to a meal.Subjects and design:GLP-1, insulin and glucose responses were measured in six overweight individuals and six subjects with type II diabetes on three occasions, after preload (milk, low GI; Ovaltine Light, high GI; or water, non-nutritive control) and meal ingestion.Results:In people with and without diabetes, the high GI preload produced the greatest glucose incremental area under the curve (IAUC)(0-20), followed by the low GI preload, and water (P<0.001). In both groups, insulin IAUC(0-20) was higher following high and low GI preloads compared with water (NS). In people without diabetes, the GLP-1 response was higher when high and low GI preloads were consumed compared with water (P=0.041), with no significant difference between nutritive preloads. GLP-1 response did not differ between preloads in people with diabetes. Despite initial differences, total IAUCs(0-200) for biochemical variables did not differ by preload.Conclusion:We confirm that nutritive liquids stimulate GLP-1 to a greater extent than water in subjects without diabetes; however, this does not influence subsequent meal-induced response. The GI of preloads does not influence the degree of GLP-1 stimulation.European Journal of Clinical Nutrition advance online publication, 14 February 2007; doi:10.1038/sj.ejcn.1602654.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17299480&query_hl=1
ER  - 

TY  - JFULL
T1  - Swine cysticercosis hotspots surrounding Taenia solium tapeworm carriers.
A1  - Lescano, AG
A1  - Garcia, HH
A1  - Gilman, RH
A1  - Guezala, MC
A1  - Tsang, VC
A1  - Gavidia, CM
A1  - Rodriguez, S
A1  - Moulton, LH
A1  - Green, JA
A1  - Gonzalez, AE
A1  - Cysticercosis Working Group in Peru
J1  - Am J Trop Med Hyg
Y1  - 2007/02//
VL  - 76
SN  - 0002-9637
SP  - 376
EP  - 383
N2  - We estimated the Taenia solium swine cysticercosis risk gradient surrounding tapeworm carriers in seven rural communities in Peru. At baseline, the prevalences of taeniasis by microscopy and swine cysticercosis by serology were 1.2% (11 of 898) and 30.8% (280 of 908), respectively. The four-month cumulative seroincidence was 9.8% (30 of 307). The unadjusted swine seroprevalence and seroincidence rates increased exponentially by 12.0% (95% confidence [CI] = 9.7-14.3%) and 32.8% (95% CI = 25.0-41.0%), respectively when distance to carriers decreased by half. Swine seroprevalence was 18.4% at > 500 meters from a carrier, 36.5% between 51 and 500 meters, and 68.9% within 50 meters (P < 0.001). Swine seroincidence also displayed a strong gradient near tapeworm carriers (3.8%, 12.2%, and 44.0%; P < 0.001). Within 50 meters, swine seroprevalence appeared unaffected if the owners harbored tapeworms, although pigs owned by a tapeworm carrier had a four times higher seroincidence compared with other pigs (P = 0.005). In rural areas, swine cysticercosis occurs in high-risk hotspots around carriers where control interventions could be delivered.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17297051&query_hl=1
ER  - 

TY  - JFULL
T1  - Conventional Western blotting techniques will not reliably quantify p210(BCR-ABL1) levels in CML mononuclear cells
A1  - Patel, H
A1  - Marley, SB
A1  - Gordon, MY
J1  - BLOOD
Y1  - 2007/02/01/
VL  - 109
SN  - 0006-4971
SP  - 1335
EP  - 1335
ER  - 

TY  - JFULL
T1  - Molecular analysis of Mycobacterium tuberculosis causing multidrug-resistant tuberculosis meningitis.
A1  - Caws, M
A1  - Thwaites, GE
A1  - Duy, PM
A1  - Tho, DQ
A1  - Lan, NT
A1  - Hoa, DV
A1  - Chau, TT
A1  - Huyen, MN
A1  - Anh, PT
A1  - Chau, NV
A1  - Chinh, TN
A1  - Stepniewska, K
A1  - Farrar, J
J1  - Int J Tuberc Lung Dis
Y1  - 2007/02//
VL  - 11
SN  - 1027-3719
SP  - 202
EP  - 208
N2  - SETTING: Tertiary referral hospitals in southern Vietnam. OBJECTIVE: Molecular characterisation of multidrug-resistant (MDR) tuberculous meningitis (TBM). DESIGN: Mycobacterium tuberculosis isolates from the cerebrospinal fluid (CSF) of 198 Vietnamese adults were compared with 237 isolates from patients with pulmonary tuberculosis (PTB) matched for age, sex and residential district. Isolates resistant to isoniazid or rifampicin (RMP) were sequenced in the rpoB and katG genes, inhA promoter and oxyR-ahpC intergenic regions. RESULTS: While drug resistance rates were lower in the CSF (2.5% MDR) than pulmonary isolates (5.9% MDR), the difference was not significant. The most commonly mutated codons were 531, 526 and 516 in rpoB and 315 in katG. Four novel triple mutants in rpoB were identified. CONCLUSION: RMP resistance is a good surrogate marker for MDR-TBM in this setting. However, probes directed against these three codons would have a maximum sensitivity of only 65%. A rapid phenotypic detection test may be more applicable for the diagnosis of MDR-TBM.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17263292&query_hl=1
ER  - 

TY  - JFULL
T1  - T-cell receptor repertoire usage after allografting differs between CD4+CD25+ regulatory T cells and their CD4+CD25- counterpart.
A1  - Fozza, C
A1  - Nadal, E
A1  - Longinotti, M
A1  - Dazzi, F
J1  - Haematologica
Y1  - 2007/02//
VL  - 92
SN  - 1592-8721
SP  - 206
EP  - 214
N2  - BACKGROUND AND OBJECTIVES: After allogeneic haematopoietic stem cell transplantation (SCT) the whole T-cell receptor (TCR) repertoire shows a markedly skewed pattern for 2-3 years. A small fraction of CD4+ T cells is represented by CD25+ regulatory lymphocytes (Treg), which play a crucial role in modulating peripheral tolerance. To investigate their ability to react to the massive antigenic stimulation generated in an allogeneic host, which could significantly affect their pattern of reconstitution, we analyzed the TCR repertoire of Treg after SCT, focusing on the degree of similarity to CD4+CD25- conventional T cells (Tconv). DESIGN AND METHODS: We assessed the TCR Vbeta repertoire of Treg in ten patients who had received allogeneic SCT, by using complementarity determining region 3 (CDR3) spectratyping. We developed a new similarity score for the analysis. This score expresses the proportion of Vbeta with similar profile between Treg and Tconv. RESULTS: For up to 3 years after SCT the repertoires of Treg and Tconv were characterized by several Vbeta with different profiles between the two cell subsets, while they were extremely similar in patients more than 3 years post-allografting (similarity score= 0.90 vs. 0.61). The differences observed early after SCT were mainly ascribable to Vbeta expressing an oligoclonal profile in Tconv but not in Treg. INTERPRETATION AND CONCLUSIONS: Our data show that the TCR repertoires of Treg and Tconv are significantly different early post-SCT, while they tend to become identical with full reconstitution. This difference could reflect either a discrepancy in the in vivo reactivity against common antigenic stimulations or be the result of different post-transplant ontogeny.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17296570&query_hl=1
ER  - 

TY  - JFULL
T1  - Recent progress in PYY research--an update report for 8th NPY meeting.
A1  - Ashby, D
A1  - Bloom, SR
J1  - Peptides
Y1  - 2007/02//
VL  - 28
SN  - 0196-9781
SP  - 198
EP  - 202
N2  - PYY(3-36) is a gut regulatory peptide which has recently been found to reduce appetite. Variability of this effect across different experimental conditions has led to confusion and polarization of opinion on its potential as an anti-obesity treatment. This review summarizes recent progress in this area. The basic anorexigenic effect leading to weight loss in rodents has now been confirmed by several groups. Anorexia has also been confirmed in human studies although optimal route and dosing remain to be defined. Gastric bypass causes PYY levels to rise, which may in part mediate the weight loss occurring after this surgery, and levels have been found to be normal or low in obese people. The straightforward ARC model of mechanism, involving inhibition and activation, respectively, of NPY and POMC neurons, is giving way to a more complicated system involving vagal afferent signals. Conclusion: It works, but not how we thought it did.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354277&query_hl=1
ER  - 

TY  - JFULL
T1  - Altered monocyte cyclooxygenase response to lipopolysaccharlde in type 1 diabetes.(vol 55, pg 3439, 2006)
A1  - Beyan, H
A1  - Goodier, MR
A1  - Nawroly, NS
A1  - Hawa, MI
A1  - Bustin, SA
A1  - Ogunkolade, WB
A1  - Londei, M
A1  - Yousaf, N
A1  - Leslie, RDG
J1  - DIABETES
Y1  - 2007/02//
VL  - 56
SN  - 0012-1797
SP  - 549
EP  - 549
ER  - 

TY  - JFULL
T1  - Inaccuracy of high-performance liquid chromatography estimation of haemoglobin F in the presence of increased haemoglobin A1c.
A1  - Grey, V
A1  - Wilkinson, M
A1  - Phelan, L
A1  - Hughes, C
A1  - Bain, BJ
J1  - Int J Lab Hematol
Y1  - 2007/02//
VL  - 29
SN  - 1751-5521
SP  - 42
EP  - 44
N2  - Increasingly high-performance liquid chromatography is being used for identification and quantification of normal and variant haemoglobins. In many laboratories, the Beta Thal Short programme of the Bio-Rad Variant II instrument is used for this purpose. We noted that a factitious elevation of haemoglobin F was sometimes observed in diabetic patients and therefore carried out a systematic study of this phenomenon. We found discrepant results in 41% of samples from diabetic patients but in no normal volunteers. This factitious elevation could be predicted from a retention time for haemoglobin F of more than 1.15 min, the normal retention time being 1.08-1.15 min. Haemoglobinopathy laboratories need to be alert to the possibility of this erroneous result.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17224006&query_hl=1
ER  - 

TY  - JFULL
T1  - Molecular dynamics simulations of proteins with chemically modified disulfide bonds
A1  - Godwin, A
A1  - Choi, JW
A1  - Pedone, E
A1  - Balan, S
A1  - Jumnah, R
A1  - Shaunak, S
A1  - Brocchini, S
A1  - Zloh, M
J1  - THEOR CHEM ACC
Y1  - 2007/02//
VL  - 117
SN  - 1432-881X
SP  - 259
EP  - 265
N2  - Proteins that are used as therapeutic drugs act in the extracellular microenvironment. They usually have a small number of intramolecular disulfide bonds to help maintain their tertiary structure in the vascular circulation. In general, most cysteine residues are part of a disulfide bond with free sulfhydrals being uncommon. We have studied whether the site-specific chemical reduction of disulfides and the incorporation of a 3-carbon methylene bridge between the cysteines in interferon-alpha 2a would change the structure of this protein. Bridging of both of the disulfide bonds of interferon-alpha 2a was studied using two different molecular simulation protocols: (1) molecular dynamics, and (2) stochastic dynamics. We have shown that the disulfide bonds in interferon-alpha 2a can be reduced and chemically modified without significantly altering the tertiary structure of the protein. This offers the novel possibility of chemically modifying therapeutically important proteins without affecting their biological properties.
ER  - 

TY  - JFULL
T1  - Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review.
A1  - Jindal, P
A1  - Regan, L
A1  - Fourkala, EO
A1  - Rai, R
A1  - Moore, G
A1  - Goldin, RD
A1  - Sebire, NJ
J1  - Hum Reprod
Y1  - 2007/02//
VL  - 22
SN  - 0268-1161
SP  - 313
EP  - 316
N2  - BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17008326&query_hl=1
ER  - 

TY  - JFULL
T1  - Long-term effects of perinatal nutrition on T lymphocyte kinetics in young Gambian men
A1  - Ghattas, H
A1  - Wallace, DL
A1  - Solon, JA
A1  - Henson, SM
A1  - Zhang, Y
A1  - Ngom, PT
A1  - Aspinall, R
A1  - Morgan, G
A1  - Griffin, GE
A1  - Prentice, AM
A1  - Macallan, DC
J1  - AM J CLIN NUTR
Y1  - 2007/02//
VL  - 85
SN  - 0002-9165
SP  - 480
EP  - 487
N2  - Background: Nutritional status is highly dependent on season in countries such as The Gambia. In a rural Gambian setting, individuals born during periods of seasonal nutritional deprivation ("hungry seasons") are susceptible to mortality from infectious diseases in adult life.Objective: We investigated the hypothesis that impaired immunocompetence in those born in the hungry season results from an underlying defect in immunologic memory, similar to the immunosenescence of old age, which is likely to be reflected in the phenotype and kinetics of T lymphocytes in young adults.Design: T cell phenotype in terms of CD3, CD4, CD8, CD45RA, and CD45R0 expression and in vivo dynamics measured by stable isotope labeling of T cell subsets combined with gas chromatography-mass spectrometry and frequency of T cell receptor excision circles were measured in 25 young (18-24-y-old) Gambian men. Thirteen of these 25 men were exposed to perinatal malnutrition as defined by birth season and birth weight.Results: In persons born in the hungry season with low birth weight, no differences in the proportions of memory or naive T cells were found. Kinetic analysis showed higher proliferation rates in memory (CD45R0(+)) subsets of T cells than in nalve (CD45R0(-)) cells, which is consistent with previous studies, but no evidence was found for an effect of birth weight or season on T lymphocyte proliferation and disappearance rates. No significant correlations were found between in vivo T cell kinetics and frequency of T cell receptor excision circles. Only absolute numbers of granulocytes were elevated in those born in the nutritionally deprived season.Conclusion: In healthy young Gambian men, T lymphocyte homeostasis is extremely robust regardless of perinatal nutritional compromise.
ER  - 

TY  - JFULL
T1  - Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1.
A1  - Yoshida, C
A1  - Yoshida, F
A1  - Sears, DE
A1  - Hart, SM
A1  - Ikebe, D
A1  - Muto, A
A1  - Basu, S
A1  - Igarashi, K
A1  - Melo, JV
J1  - Blood
Y1  - 2007/02/01/
VL  - 109
SN  - 0006-4971
SP  - 1211
EP  - 1219
N2  - The malignant phenotype of chronic myeloid leukemia (CML) is due to the abnormal tyrosine kinase activity of the Bcr-Abl oncoprotein. We have previously reported that expression of the Bach2 transcription factor, which induces apoptosis in response to oxidative stress, is greatly reduced in CML cells. Because these cells are resistant to apoptosis, we tested whether Bach2 could also be regulated through posttranslational mechanisms that promote inhibition of the apoptotic response to mutagenic stimuli in CML. We found that Bach2 is phosphorylated on S521 via the phosphatidylinositol-3/S6 kinase pathway, and substitution of this site to alanine leads to nuclear accumulation of the protein, indicating that this phosphorylation is important for its subcellular localization. Ectopic expression of the S521 mutant imparts greater impairment to CML cell growth than the wild-type factor. Furthermore, we showed that Bach2 transcriptionally represses heme oxygenase-1, an antiapoptotic factor up-regulated in CML. Because CML cells are known to produce high levels of intracellular reactive oxygen species, overexpression of heme oxygenase-1 resulting from inhibition of Bach2 activity may contribute to their genomic instability and leukemic phenotype.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17018862&query_hl=1
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TY  - JFULL
T1  - MUM1 expression dichotomises follicular lymphoma into predominantly, MUM1-negative low-grade and MUM1-positive high-grade subtypes.
A1  - Naresh KN
J1  - Haematologica
Y1  - 2007/02//
PB  - 92
SP  - 267
EP  - 268
ER  - 

TY  - JFULL
T1  - The use of adjunctive leukemia specific therapy to improve outcome in patients with chronic myeloid leukemia transplanted using a reduced intensity conditioning (RIC) regimen
A1  - Craddock, CF
A1  - Griffiths, MJ
A1  - Arrazi, JM
A1  - Siddique, S
A1  - Pallan, L
A1  - Lennard, AL
A1  - Byrne, JL
A1  - Olavarria, E
J1  - BIOL BLOOD MARROW TR
Y1  - 2007/02//
VL  - 13
SN  - 1083-8791
SP  - 129
EP  - 129
ER  - 

TY  - JFULL
T1  - CD59 protects against lesion formation in LDL receptor deficient mice: Evidence for complement activation in atherogenesis
A1  - Yun, S
A1  - Leung, V
A1  - Botto, M
A1  - Haskard, DO
A1  - Boyle, JJ
J1  - HEART
Y1  - 2007/02//
VL  - 93
SN  - 1355-6037
ER  - 

TY  - JFULL
T1  - Dynamin is required for F-actin assembly and pedestal formation by enteropathogenic Escherichia coli (EPEC).
A1  - Unsworth, KE
A1  - Mazurkiewicz, P
A1  - Senf, F
A1  - Zettl, M
A1  - McNiven, M
A1  - Way, M
A1  - Holden, DW
J1  - Cell Microbiol
Y1  - 2007/02//
VL  - 9
SN  - 1462-5814
SP  - 438
EP  - 449
N2  - After attaching to human intestinal epithelial cells, enteropathogenic Escherichia coli (EPEC) induces the formation of an actin-rich pedestal-like structure. The signalling pathway leading to pedestal formation is initiated by the bacterial protein Tir, which is inserted into the host cell plasma membrane. The domain exposed on the cell surface binds to another bacterial protein, intimin, while one of the cytoplasmic domains binds the adaptor protein Nck. This leads to recruitment of other cytoskeletal proteins including neural Wiskott-Aldrich syndrome protein (N-WASP) and Arp2/3, resulting in focused actin polymerization at the site of bacterial attachment. In this study we investigated the role of the large GTPase dynamin 2 (Dyn2) in pedestal formation. We found that in HeLa cells, both endogenous and overexpressed Dyn2 were recruited to sites of EPEC attachment. Recruitment of endogenous Dyn2 required the presence of Tir, Nck and N-WASP but was independent of cortactin and Arp2/3. Knock-down of Dyn2 expression by RNA interference reduced actin polymerization and pedestal formation. Overexpression of dominant-negative mutants of Dyn2 also reduced pedestal formation and prevented recruitment of N-WASP, Arp3 and cortactin, but not Nck. Together, our results indicate that Dyn2 is an integral component of the signalling cascade leading to actin polymerization in EPEC pedestals.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16965516&query_hl=1
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TY  - JFULL
T1  - Natural ventilation for the prevention of airborne contagion.
A1  - Escombe, AR
A1  - Oeser, CC
A1  - Gilman, RH
A1  - Navincopa, M
A1  - Ticona, E
A1  - Pan, W
A1  - Martínez, C
A1  - Chacaltana, J
A1  - Rodríguez, R
A1  - Moore, DA
A1  - Friedland, JS
A1  - Evans, CA
J1  - PLoS Med
Y1  - 2007/02//
VL  - 4
SN  - 1549-1676
SP  - e68
EP  - e68
N2  - BACKGROUND: Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. METHODS AND FINDINGS: The study was carried out in eight hospitals in Lima, Peru; five were hospitals of "old-fashioned" design built pre-1950, and three of "modern" design, built 1970-1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. CONCLUSIONS: Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17326709&query_hl=1
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TY  - JFULL
T1  - Reply to "Dr D Dhasmana and Dr R Davidson: Multi-drug resistant tuberculous meningitis"
A1  - Thwaites, GE
A1  - Hien, TT
A1  - Farrar, JJ
J1  - J Infect
Y1  - 2007/02//
VL  - 54
SN  - 0163-4453
SP  - 206
N2  - 
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16857263&query_hl=1
ER  - 

TY  - JFULL
T1  - Monocytes infected with Mycobacterium tuberculosis regulate MAP kinase-dependent astrocyte MMP-9 secretion.
A1  - Harris, JE
A1  - Green, JA
A1  - Elkington, PT
A1  - Friedland, JS
J1  - J Leukoc Biol
Y1  - 2007/02//
VL  - 81
SN  - 0741-5400
SP  - 548
EP  - 556
N2  - Tuberculosis (TB) of the CNS (CNS-TB) carries a high mortality. Disease pathology is characterized by widespread destruction of CNS tissues. Matrix metalloproteinase-9 (MMP-9) is able to catabolyze specific components of the CNS tissue matrix and blood-brain barrier. Increased cerebrospinal fluid MMP-9 concentrations are associated with tissue damage, leukocyte infiltration, and death in CNS-TB. Using zymography, Western analysis, and transcription factor assays, we investigated mechanisms regulating MMP-9 activity in CNS-TB. We demonstrate that conditioned media from monocytes infected with Mycobacterium tuberculosis (CoMTB) induce MMP-9 secretion from astrocytes (U373-MG). IL-1beta and TNF-alpha are necessary but not sufficient for such induction of astrocyte MMP-9 secretion. CoMTB up-regulates AP-1 DNA-binding activity, and the c-Jun, FosB, and JunB subunits are particularly increased. MMP-9 secretion from CoMTB-stimulated astrocytes is dependent on the activity of p38, Erk, and Jnk MAPKs. Phosphorylation of p38, Erk, and Jnk is activated rapidly, peaking 30 min poststimulation with CoMTB. Inhibition of IL-1beta but not TNF-alpha in CoMTB decreases p38, Erk, and Jnk activity in astrocytes. Consistently, IL-1beta signals through the MAPK cascade at physiological levels, whereas TNF-alpha, IL-6, IL-10, CCL-2, CCL-5, and CXCL-8 (all present in CoMTB) do not. In summary, the data suggest that monocyte-dependent cytokine networks may play a key role in the development of a matrix-degrading environment during CNS-TB.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17079649&query_hl=1
ER  - 

TY  - JFULL
T1  - Case 34: acute leukemia in a patient with a previous history of breast cancer.
A1  - Gabriel, IH
A1  - Abdalla, SH
A1  - Ryley, S
A1  - Bain, BJ
J1  - Leuk Lymphoma
Y1  - 2007/02//
VL  - 48
SN  - 1042-8194
SP  - 403
EP  - 405
N2  - A 56-year-old woman presented with acute myeloid leukemia 3 years after presenting with carcinoma of the breast. Detailed investigations led to a precise diagnosis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17325903&query_hl=1
ER  - 

TY  - JFULL
T1  - Annexin-1 modulates T-cell activation and differentiation.
A1  - D'Acquisto, F
A1  - Merghani, A
A1  - Lecona, E
A1  - Rosignoli, G
A1  - Raza, K
A1  - Buckley, CD
A1  - Flower, RJ
A1  - Perretti, M
J1  - Blood
Y1  - 2007/02/01/
VL  - 109
SN  - 0006-4971
SP  - 1095
EP  - 1102
N2  - Annexin-1 is an anti-inflammatory protein that plays an important homeostatic role in innate immunity; however, its potential actions in the modulation of adaptive immunity have never been explored. Although inactive by itself, addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation. This effect was paralleled by increased nuclear factor-kappaB (NF-kappaB), nuclear factor of activated T cells (NFATs), and activator protein-1 (AP-1) activation and preceded by a rapid T-cell receptor (TCR)-induced externalization of the annexin-1 receptor. Interestingly, differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells; in the collagen-induced arthritis model, treatment of mice with annexin-1 during the immunization phase exacerbated signs and symptoms at disease onset. Consistent with these findings, blood CD4+ cells from patients with rheumatoid arthritis showed a marked up-regulation of annexin-1 expression. Together these results demonstrate that annexin-1 is a molecular "tuner" of TCR signaling and suggest this protein might represent a new target for the development of drugs directed to pathologies where an unbalanced Th1/Th2 response or an aberrant activation of T cells is the major etiologic factor.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17008549&query_hl=1
ER  - 

TY  - JFULL
T1  - IL-1 beta stimulates divergent upper and lower airway epithelial cell CCL5 secretion.
A1  - Thomas, LH
A1  - Wickremasinghe, MI
A1  - Friedland, JS
J1  - Clin Immunol
Y1  - 2007/02//
VL  - 122
SN  - 1521-6616
SP  - 229
EP  - 238
N2  - Direct infection of respiratory epithelium induces chemokine secretion and upregulates cytokine networks, which are central in regulating inflammation. IL-1beta may have a pivotal role in such networks. Differential control of chemokine secretion within specific airway regions, which have distinct roles in immunity, is not well characterized. We investigated IL-1beta-induced CXCL8 and CCL5 secretion from primary normal human bronchial and small airway epithelial cells, and the alveolar cell line A549. CXCL8 was secreted by all cells, but only lower airway cells secreted CCL5. IL-1beta induced nuclear translocation of NF-kappaB (p50, p65 and c-Rel subunits), NF-IL-6 and AP-1, each with distinct kinetics. This was associated with high level CCL5 promoter activation, via transcription factor binding to multiple regions, including NF-kappaB, AP-1 and NF-IL-6 sites. The IL-1-related cytokine IL-18 did not drive or modulate IL-1beta-induced CXCL8 or CCL5 secretion. In summary, IL-1beta, but not IL-18, induces transcription-dependent lower airway epithelial cell-specific CCL5 secretion. Differential chemokine secretion may have profound effects on local leukocyte influx within upper or lower airways exposed to airway infection or environmental stimuli, which might then require different anti-inflammatory strategies.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17126080&query_hl=1
ER  - 

TY  - JFULL
T1  - Fluorescence lifetime imaging of unstained human atherosclerotic plaques
A1  - Hegyi, L
A1  - Talbot, C
A1  - Monaco, C
A1  - Sandison, A
A1  - Davies, AH
A1  - Peston, D
A1  - Requejo-Isidro, J
A1  - Elson, DS
A1  - Dunsby, C
A1  - Munro, I
A1  - Neil, MA
A1  - French, PM
A1  - Stamp, GW
A1  - Lever, MJ
J1  - HEART
Y1  - 2007/02//
VL  - 93
SN  - 1355-6037
ER  - 

TY  - JFULL
T1  - IFNgamma synergizes with IL-1beta to up-regulate MMP-9 secretion in a cellular model of central nervous system tuberculosis.
A1  - Harris, JE
A1  - Fernandez-Vilaseca, M
A1  - Elkington, PT
A1  - Horncastle, DE
A1  - Graeber, MB
A1  - Friedland, JS
J1  - FASEB J
Y1  - 2007/02//
VL  - 21
SN  - 1530-6860
SP  - 356
EP  - 365
N2  - Matrix metalloproteinase-9 (MMP-9) activity is implicated in pathogenesis of central nervous system tuberculosis (CNS-TB). IFNgamma, a key cytokine in TB, usually inhibits MMP-9 secretion. Addition of IFNgamma to conditioned media from M. tb-infected monocytes (CoMTB) resulted in a 7-fold increase in MMP-9 activity detected by gelatin zymography (P<0.01). In contrast, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 secretion, measured by ELISA, was suppressed. Dexamethasone abolished the synergistic increase in MMP-9 activity. Interleukin (IL)-1beta in CoMTB is a critical mediator of synergy with IFNgamma, and IL-1beta alone synergizes with IFNgamma to increase MMP-9 secretion from 51 +/- 31 to 762 +/- 136 U. IL-1beta activity is dependent on p38 mitogen-activated protein (MAPK) kinase, which was found to be phosphorylated in tissue specimens from patients with CNS-TB. Extracellular signal regulated kinase (Erk) and p38 MAPK activation did not affect IFNgamma signaling pathways. Inhibition of janus-activated kinase (JAK)-2 by 50 microM AG540 decreased MMP-9 secretion to 124 +/- 11.1 from 651 +/- 229 U of activity (P<0.01). However, signal transducer and activator of transcription (STAT)-3 but not STAT-1 phosphorylation was synergistically up-regulated by IFNgamma and CoMTB. In summary, synergy between IL-1beta and STAT-3 dependent IFNgamma signaling is key in control of up-regulation of MMP-9 activity in CNS-TB and may be a significant mechanism of brain tissue destruction.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158965&query_hl=1
ER  - 

TY  - JFULL
T1  - Increased expression of the pro-apoptotic ATP-sensitive P2X7 receptor in experimental and human glomerulonephritis.
A1  - Turner, CM
A1  - Tam, FW
A1  - Lai, PC
A1  - Tarzi, RM
A1  - Burnstock, G
A1  - Pusey, CD
A1  - Cook, HT
A1  - Unwin, RJ
J1  - Nephrol Dial Transplant
Y1  - 2007/02//
VL  - 22
SN  - 0931-0509
SP  - 386
EP  - 395
N2  - BACKGROUND: The involvement of IL-1beta and other pro-inflammatory cytokines in most forms of glomerulonephritis is now well established. The P2X(7) receptor, an ATP-sensitive P2X receptor, functions not only as a non-selective cation channel, but it is also involved in the rapid processing and release of IL-1beta, apoptosis and necrotic cell death. Therefore, we wanted to investigate if expression of this receptor is altered in the glomeruli of rodent models of glomerulonephritis. METHODS: P2X(7) receptor protein expression was investigated using immunohistochemistry, and apoptosis was assessed using the TUNEL assay and caspase-3 immunostaining. Real-time PCR with gene-specific primers was used to detect P2X(7), IL-1beta, p53, bax and bcl-2 mRNA expression. RESULTS: Although the levels of the P2X(7) receptor protein in mouse kidney are normally very low, or undetectable, we detected an increase in glomerular expression of this receptor and an increase in glomerular apoptotic cells in a mouse model of accelerated nephrotoxic nephritis. We also observed increased glomerular and tubular expression of the P2X(7) receptor protein in renal biopsy tissue of patients with autoimmune-related glomerulonephritis. Furthermore, P2X(7) receptor mRNA increased in the kidneys of a rat model of proliferative glomerulonephritis and this coincided with the onset of proteinuria. We also observed increased mRNA expression of Il-1beta and the pro-apoptotic markers p53 and bax, but not of anti-apoptotic bcl-2. CONCLUSION: Although there is an association between expression of the pro-inflammatory and pro-apoptotic P2X(7) receptor and glomerulonephritis in these rodent models, and in at least one form of human glomerulonephritis, the underlying relationship and its functional significance remain to be explored.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17040997&query_hl=1
ER  - 

TY  - JFULL
T1  - A new inhibitor of apoptosis from vaccinia virus and eukaryotes.
A1  - Gubser, C
A1  - Bergamaschi, D
A1  - Hollinshead, M
A1  - Lu, X
A1  - van Kuppeveld, FJ
A1  - Smith, GL
J1  - PLoS Pathog
Y1  - 2007/02//
VL  - 3
SN  - 1553-7374
SP  - e17
EP  - e17
N2  - A new apoptosis inhibitor is described from vaccinia virus, camelpox virus, and eukaryotic cells. The inhibitor is a hydrophobic, multiple transmembrane protein that is resident in the Golgi and is named GAAP (Golgi anti-apoptotic protein). Stable expression of both viral GAAP (v-GAAP) and human GAAP (h-GAAP), which is expressed in all human tissues tested, inhibited apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Conversely, knockout of h-GAAP by siRNA induced cell death by apoptosis. v-GAAP and h-GAAP display overlapping functions as shown by the ability of v-GAAP to complement for the loss of h-GAAP. Lastly, deletion of the v-GAAP gene from vaccinia virus did not affect virus replication in cell culture, but affected virus virulence in a murine infection model. This study identifies a new regulator of cell death that is highly conserved in evolution from plants to insects, amphibians, mammals, and poxviruses.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17319741&query_hl=1
ER  - 

TY  - JFULL
T1  - Novel compounds with antiproliferative activity against imatinib-resistant cell lines.
A1  - Lerma, EI
A1  - Nguyen, VA
A1  - Wang, T
A1  - Tipping, A
A1  - Melo, JV
A1  - Kufe, D
A1  - Austin, DJ
A1  - Deisseroth, A
J1  - Mol Cancer Ther
Y1  - 2007/02//
VL  - 6
SN  - 1535-7163
SP  - 655
EP  - 666
N2  - Chronic myelogenous leukemia is caused by the Bcr-Abl hybrid gene that encodes the p210Bcr-Abl chimeric oncoprotein. Although it reduces the total body burden of leukemia cells, the use of imatinib mesylate as a single agent may be accompanied by the evolution of resistance due mainly to the acquisition of point mutations. Imatinib has been combined with drugs that inhibit both the active and the inactive states of the p210Bcr-Abl kinase. These combinations have reduced but not completely eliminated the rate at which point mutations are acquired in the p210Bcr-Abl kinase. Thus, it is important to identify additional new inhibitors of the p210Bcr-Abl kinase. One possible method to prevent evolution of resistance is to simultaneously use multiple kinase inhibitors each with a different mechanism of action. To identify such a new class of inhibitors that could suppress the growth of chronic myelogenous leukemia cells and prevent the evolution of cells that are resistant to imatinib, we screened two low-complexity libraries of compounds based on planar and linear scaffolds. These libraries were screened using a cell-based assay for molecules that suppress p210Bcr-Abl-dependent cell growth. The application of this method resulted in the isolation of two new classes of drugs, both of which inhibited imatinib-resistant cells in the low micromolar range. Some of these drugs were potent inhibitors not only of Abl tyrosine kinase but also of the Src, Lyn, and Fyn tyrosine kinases.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17267662&query_hl=1
ER  - 

TY  - JFULL
T1  - Mesenchymal stem cells are effective at preventing but not at treating GvJD
A1  - Tisato, V
A1  - Naresh, K
A1  - Navarrete, C
A1  - Dazzi, F
J1  - BIOL BLOOD MARROW TR
Y1  - 2007/02//
VL  - 13
SN  - 1083-8791
SP  - 44
EP  - 45
ER  - 

TY  - JFULL
T1  - Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.
A1  - Chiu, C
A1  - Heaps, AG
A1  - Cerundolo, V
A1  - McMichael, AJ
A1  - Bangham, CR
A1  - Callan, MF
J1  - Blood
Y1  - 2007/02/01/
VL  - 109
SN  - 0006-4971
SP  - 1086
EP  - 1094
N2  - Functional studies show that programming of CD8+ T cells occurs early after initial antigen encounter within as little as 2 hours. To define the molecular basis of these events, we transferred TCR transgenic T cells from F5 Rag-/- mice into naive recipients and stimulated them with recombinant vaccinia expressing the immunodominant influenza epitope NP366-374. Transcription in epitope-specific cytotoxic T lymphocytes (CTLs) was analyzed using Affymetrix 430 2.0 GeneChips and quantitative polymerase chain reaction (PCR). We demonstrated an early transcriptional burst with the greatest number of genes reaching peak expression 12 hours after stimulation. Using in vivo cytotoxicity assays we demonstrated that early up-regulation of cytolytic genes was accompanied by acquisition of killing capacity within 24 hours of stimulation. However, T-cell proliferation was not observed until 48 hours. We therefore conclude that clonal expansion rather than acquisition of effector function is the rate-limiting step in the development of a primary CTL response.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16990607&query_hl=1
ER  - 

TY  - JFULL
T1  - Noninvasive and invasive evaluation of pulmonary arterial pressure in highlanders.
A1  - Kojonazarov, BK
A1  - Imanov, BZ
A1  - Amatov, TA
A1  - Mirrakhimov, MM
A1  - Naeije, R
A1  - Wilkins, MR
A1  - Aldashev, AA
J1  - Eur Respir J
Y1  - 2007/02//
VL  - 29
SN  - 0903-1936
SP  - 352
EP  - 356
N2  - The purpose of the present study was to evaluate Doppler echocardiography for the detection of pulmonary hypertension in high-altitude inhabitants. In total, 60 (55 male) patients aged 18-71 yrs were recruited from an ECG screening programme applied to 1,430 inhabitants living at an altitude of 2,500-3,600 m in Kyrgyzstan. Of these, 44 met ECG criteria for right ventricular hypertrophy. All underwent Doppler echocardiography followed by a cardiac catheterisation within 7 days of arrival in Bishkek (Kyrgyzstan; altitude 760 m). Pulmonary flow acceleration time and the maximum velocity of tricuspid regurgitation were measured. Sufficient quality tricuspid regurgitant jets were recovered in only 28% of the patients. Therefore, pulmonary artery pressure was estimated from the pulmonary flow acceleration time, which was recovered in 100% of the patients. It was found that 37 (62%) of the patients had pulmonary hypertension on echocardiography. Pulmonary hypertension was confirmed in 29 patients on catheterisation. Pulmonary hypertension was detected with 70% sensitivity and 88% specificity by echocardiography, as compared to 59% sensitivity and 81 % specificity by ECG. The correlation coefficient between echocardiography and catheterisation studies was r(2) = 0.78. It is concluded that a combination of ECG and echocardiography may be useful for screening high-altitude pulmonary hypertension.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17079253&query_hl=1
ER  - 

TY  - JFULL
T1  - Increased CD4+CD25high+regulatory T-cell are associated with disease relapse after allogeneic stem cell transplantation (SCT) for chronic myeloid leukaemia (CML)
A1  - Nadal, E
A1  - Kaeda, J
A1  - Apperley, JF
A1  - Lechler, R
A1  - Dazzi, F
J1  - BIOL BLOOD MARROW TR
Y1  - 2007/02//
VL  - 13
SN  - 1083-8791
SP  - 15
EP  - 15
ER  - 

TY  - JFULL
T1  - Specificity of anti-human leukocyte antigen antibody responses after immunization with Remune, an inactivated HIV-1 vaccine.
A1  - Page, M
A1  - Ojugo, A
A1  - Imami, N
A1  - Hardy, G
A1  - Gotch, F
A1  - Almond, N
J1  - AIDS
Y1  - 2007/01/30/
VL  - 21
SN  - 0269-9370
SP  - 375
EP  - 377
N2  - Antibody responses against human leukocyte antigen (HLA) classes I and II were detected in HIV-1 infected individuals who received a fixed inactivated HIV-1 (Remune) immunotherapy. The response was specific for HLA-B62 and HLA-DR4 concordant with the host cell line, HUT-78, used in vaccine production. These responses were not detected in HLA-B62 and HLA-DR4-positive individuals indicating that immunotherapy did not break tolerance to self-antigens.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17255748&query_hl=1
ER  - 

TY  - JFULL
T1  - Myocardial infarction in sickle-cell disease.
A1  - Pavlu, J
A1  - Ahmed, RE
A1  - O'Regan, DP
A1  - Partridge, J
A1  - Lefroy, DC
A1  - Layton, DM
J1  - Lancet
Y1  - 2007/01/20/
VL  - 369
SN  - 1474-547X
SP  - 246
EP  - 246
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17240292&query_hl=1
ER  - 

TY  - JFULL
T1  - Nonpeptidic glucagon-like peptide 1 receptor agonists: a magic bullet for diabetes?
A1  - Murphy, KG
A1  - Bloom, SR
J1  - Proc Natl Acad Sci U S A
Y1  - 2007/01/16/
VL  - 104
SN  - 0027-8424
SP  - 689
EP  - 690
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17213306&query_hl=1
ER  - 

TY  - JFULL
T1  - Monocyte-astrocyte networks regulate matrix metalloproteinase gene expression and secretion in central nervous system tuberculosis in vitro and in vivo.
A1  - Harris, JE
A1  - Nuttall, RK
A1  - Elkington, PT
A1  - Green, JA
A1  - Horncastle, DE
A1  - Graeber, MB
A1  - Edwards, DR
A1  - Friedland, JS
J1  - J Immunol
Y1  - 2007/01/15/
VL  - 178
SN  - 0022-1767
SP  - 1199
EP  - 1207
N2  - CNS tuberculosis (CNS-TB) is the most deadly form of tuberculous disease accounting for 10% of clinical cases. CNS-TB is characterized by extensive tissue destruction, in which matrix metalloproteinases (MMPs) may play a critical role. We investigated the hypothesis that Mycobacterium tuberculosis activates monocyte-astrocyte networks increasing the activity of key MMPs. We examined the expression of all human MMPs and the tissue inhibitors of metalloproteinases (TIMPs) in human astrocytes stimulated by conditioned medium from M. tuberculosis-infected monocytes (CoMTB). Real-time RT-PCR showed that gene expression of MMP-1, -2, -3, -7, and -9 was increased (p < 0.05). MMP-9 secretion was significantly up-regulated at 24 h and increased over 120 h (p < 0.01). MMP-1, -3, and -7 secretion was not detected. Secretion of MMP-2 was constitutive and unaffected by CoMTB. Astrocyte gene expression and secretion of TIMP-1 was not affected by CoMTB although TIMP-2 secretion increased 3-fold at 120 h. Immunohistochemical analysis of human brain biopsies confirmed that astrocyte MMP-9 secretion is a predominant feature in CNS-TB in vivo. Dexamethasone inhibited astrocyte MMP-9, but not TIMP-1/2 secretion in response to CoMTB. CoMTB stimulated the nuclear translocation of NF-kappaB, inducing a 6-fold increase in nuclear p65 and a 2-fold increase in nuclear p50. This was associated with degradation of IkappaBalpha and beta within 30 min, persisting for 24 h. In summary, networks active between monocytes and astrocytes regulate MMP-9 activity in tuberculosis and astrocytes are a major source of MMP-9 in CNS-TB. Astrocytes may contribute to a matrix degrading environment within the CNS and subsequent morbidity and mortality.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17202385&query_hl=1
ER  - 

TY  - JFULL
T1  - A role for the conserved GAFTGA motif of AAA+ transcription activators in sensing promoter DNA conformation.
A1  - Dago, AE
A1  - Wigneshweraraj, SR
A1  - Buck, M
A1  - Morett, E
J1  - J Biol Chem
Y1  - 2007/01/12/
VL  - 282
SN  - 0021-9258
SP  - 1087
EP  - 1097
N2  - Transcription from sigma54-dependent bacterial promoters can be regarded as a second paradigm for bacterial gene transcription. The initial sigma54-RNA polymerase (RNAP).promoter complex, the closed complex, is transcriptionally silent. The transcriptionally proficient sigma54-RNAP.promoter complex, the open complex, is formed upon remodeling of the closed complex by actions of a specialized activator protein that belongs to the AAA (ATPases associated with various cellular activities) protein family in an ATP hydrolysis-dependent reaction. The integrity of a highly conserved signature motif in the AAA activator (known as the GAFTGA motif) is important for the remodeling activity of the AAA activator and for open complex formation. We now provide evidence that the invariant threo-nine residue of the GAFTGA motif plays a role in sensing the DNA downstream of the sigma54-RNAP-binding site and in coupling this information to sigma54-RNAP via the conserved regulatory Region I domain of sigma54 during open complex formation.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17090527&query_hl=1
ER  - 

TY  - JFULL
T1  - MODS assay for the diagnosis of TB - Reply
A1  - Moore, DAJ
A1  - Gilman, RH
A1  - Friedland, JS
J1  - NEW ENGL J MED
Y1  - 2007/01/11/
VL  - 356
SN  - 0028-4793
SP  - 189
EP  - 189
ER  - 

TY  - JFULL
T1  - MODS assay for the diagnosis of TB.
A1  - Palomino, JC
A1  - Martin, A
A1  - Portaels, F
J1  - N Engl J Med
Y1  - 2007/01/11/
VL  - 356
SN  - 1533-4406
SP  - 188; author reply 189
EP  - 188; author reply 189
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17215539&query_hl=1
ER  - 

TY  - JFULL
T1  - Stringent and reproducible tetracycline-regulated transgene expression by site-specific insertion at chromosomal loci with pre-characterised induction characteristics.
A1  - Brough, R
A1  - Papanastasiou, AM
A1  - Porter, AC
J1  - BMC Mol Biol
Y1  - 2007///
VL  - 8
SN  - 1471-2199
SP  - 30
EP  - 30
N2  - BACKGROUND: The ability to regulate transgene expression has many applications, mostly concerning the analysis of gene function. Desirable induction characteristics, such as low un-induced expression, high induced expression and limited cellular heterogeneity, can be seriously impaired by chromosomal position effects at the site of transgene integration. Many clones may therefore need to be screened before one with optimal induction characteristics is identified. Furthermore, such screens must be repeated for each new transgene investigated, and comparisons between clones with different transgenes is complicated by their different integration sites. RESULTS: To circumvent these problems we have developed a "screen and insert" strategy in which clones carrying a transgene for a fluorescent reporter are first screened for those with optimal induction characteristics. Site-specific recombination (SSR) is then be used repeatedly to insert any new transgene at the reporter transgene locus of such clones so that optimal induction characteristics are conferred upon it. Here we have tested in a human fibrosarcoma cell line (HT1080) two of many possible implementations of this approach. Clones (e.g. Rht14-10) in which a GFP reporter gene is very stringently regulated by the tetracycline (tet) transactivator (tTA) protein were first identified flow-cytometrically. Transgenes encoding luciferase, I-SceI endonuclease or Rad52 were then inserted by SSR at a LoxP site adjacent to the GFP gene resulting stringent tet-regulated transgene expression. In clone Rht14-10, increases in expression from essentially background levels (+tet) to more than 104-fold above background (-tet) were reproducibly detected after Cre-mediated insertion of either the luciferase or the I-SceI transgenes. CONCLUSION: Although previous methods have made use of SSR to integrate transgenes at defined sites, none has effectively combined this with a pre-selection step to identify integration sites that support optimal regulatory characteristics. Rht14-10 and similar HT1080-derived clones can now be used in conjunction with a convenient delivery vector (pIN2-neoMCS), in a simple 3-step protocol leading to stringent and reproducible transgene regulation. This approach will be particularly useful for transgenes whose products are very active at low concentrations and/or for comparisons of multiple related transgenes.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17493262&query_hl=1
ER  - 

TY  - JFULL
T1  - How to lose a billion pounds.
A1  - Moon, JC
A1  - Bogle, RG
J1  - Int J Clin Pract
Y1  - 2007/01//
VL  - 61
SN  - 1368-5031
SP  - 2
EP  - 3
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17229170&query_hl=1
ER  - 

TY  - JFULL
T1  - C-terminal regions of topoisomerase IIalpha and IIbeta determine isoform-specific functioning of the enzymes in vivo.
A1  - Linka, RM
A1  - Porter, AC
A1  - Volkov, A
A1  - Mielke, C
A1  - Boege, F
A1  - Christensen, MO
J1  - Nucleic Acids Res
Y1  - 2007///
VL  - 35
SN  - 1362-4962
SP  - 3810
EP  - 3822
N2  - Topoisomerase II removes supercoils and catenanes generated during DNA metabolic processes such as transcription and replication. Vertebrate cells express two genetically distinct isoforms (alpha and beta) with similar structures and biochemical activities but different biological roles. Topoisomerase IIalpha is essential for cell proliferation, whereas topoisomerase IIbeta is required only for aspects of nerve growth and brain development. To identify the structural features responsible for these differences, we exchanged the divergent C-terminal regions (CTRs) of the two human isoforms (alpha 1173-1531 and beta 1186-1621) and tested the resulting hybrids for complementation of a conditional topoisomerase IIalpha knockout in human cells. Proliferation was fully supported by all enzymes bearing the alpha CTR. The alpha CTR also promoted chromosome binding of both enzyme cores, and was by itself chromosome-bound, suggesting a role in enzyme targeting during mitosis. In contrast, enzymes bearing the beta CTR supported proliferation only rarely and when expressed at unusually high levels. A similar analysis of the divergent N-terminal regions (alpha 1-27 and beta 1-43) revealed no role in isoform-specific functions. Our results show that it is the CTRs of human topoisomerase II that determine their isoform-specific functions in proliferating cells. They also indicate persistence of some functional redundancy between the two isoforms.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17526531&query_hl=1
ER  - 

TY  - JFULL
T1  - Complement C1q reduces early atherosclerosis in low-density lipoprotein receptor-deficient mice.
A1  - Bhatia, VK
A1  - Yun, S
A1  - Leung, V
A1  - Grimsditch, DC
A1  - Benson, GM
A1  - Botto, MB
A1  - Boyle, JJ
A1  - Haskard, DO
J1  - Am J Pathol
Y1  - 2007/01//
VL  - 170
SN  - 0002-9440
SP  - 416
EP  - 426
N2  - We explored the role of the classic complement pathway in atherogenesis by intercrossing C1q-deficient mice (C1qa-/-) with low-density lipoprotein receptor knockout mice (Ldlr-/-). Mice were fed a normal rodent diet until 22 weeks of age. Aortic root lesions were threefold larger in C1qa-/-/Ldlr-/- mice compared with Ldlr-/- mice (3.72 +/- 1.0% aortic root versus 1.1 +/- 0.4%; mean +/- SEM, P < 0.001). Furthermore, the cellular composition of lesions in C1qa-/-/Ldlr-/- was more complex, with an increase in vascular smooth muscle cells. The greater aortic root lesion size in C1qa-/-/Ldlr-/- mice occurred despite a significant reduction in C5b-9 deposition per lesion unit area, suggesting the critical importance of proximal pathway activity. Apoptotic cells were readily detectable by cleaved caspase-3 staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and electron microscopy in C1qa-/-/Ldlr-/-, whereas apoptotic cells were not detected in Ldlr-/- mice. This is the first direct demonstration of a role for the classic complement pathway in atherogenesis. The greater lesion size in C1qa-/-/Ldlr-/- mice is consistent with the emerging homeostatic role for C1q in the disposal of dying cells. This study suggests the importance of effective apoptotic cell removal for containing the size and complexity of early lesions in atherosclerosis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17200212&query_hl=1
ER  - 

TY  - JFULL
T1  - Increased susceptibility of heterozygous factor H deficient mice to accelerated serum nephrotoxic nephritis
A1  - Pickering, MC
A1  - Rose, KL
A1  - Carlucci, F
A1  - Howard, J
A1  - Cook, HT
A1  - Botto, M
J1  - MOL IMMUNOL
Y1  - 2007/01//
VL  - 44
SN  - 0161-5890
SP  - 228
EP  - 228
ER  - 

TY  - JFULL
T1  - Use of recombinant activated factor VII in massive obstetric haemorrhage.
A1  - Haynes, J
A1  - Laffan, M
A1  - Plaat, F
J1  - Int J Obstet Anesth
Y1  - 2007/01//
VL  - 16
SN  - 0959-289X
SP  - 40
EP  - 49
N2  - Massive obstetric haemorrhage is a life-threatening emergency that remains a major cause of maternal mortality. Conventional management is aimed at optimising uterine tone, replacing circulating volume and blood products, and surgery to achieve haemostasis. Recently there have been numerous reports of the (unlicensed) use of recombinant activated factor VII in the management of major obstetric haemorrhage. We report our experience of using it in the treatment of major post-partum haemorrhage in four previously healthy parturients. The published reports of recombinant activated factor VII use in post-partum haemorrhage (unrelated to pre-existing coagulopathies) are compared.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17126006&query_hl=1
ER  - 

TY  - JFULL
T1  - Natural killer T cells in families of patients with systemic lupus erythematosus: their possible role in regulation of IGG production.
A1  - Green, MR
A1  - Kennell, AS
A1  - Larche, MJ
A1  - Seifert, MH
A1  - Isenberg, DA
A1  - Salaman, MR
J1  - Arthritis Rheum
Y1  - 2007/01//
VL  - 56
SN  - 0004-3591
SP  - 303
EP  - 310
N2  - OBJECTIVE: To determine whether there is a link between the frequency of natural killer T (NKT) cells and high levels of IgG in patients with systemic lupus erythematosus (SLE) and their relatives. METHODS: Blood samples were obtained from patients with SLE, their first-degree relatives, patients with rheumatoid arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined as CD56+ T cells) was expressed as a percentage of total blood lymphocytes. Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA (dsDNA) were determined. RESULTS: The frequency of NKT cells was lower in patients with SLE than in control subjects. No such decrease was observed in the relatives of patients with SLE or in patients with RA. High levels of IgG were observed in both patients with SLE and their relatives, while low levels of IgM were observed in these same groups. In relatives of patients with SLE, an inverse correlation between the frequency of NKT cells and IgG levels was observed. Moreover, raised levels of IgG in patients with SLE and their relatives and high levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT cells. CONCLUSION: These results suggest that NKT cells have an important role in the regulation of IgG production, although NKT cells with invariant T cell receptors may not necessarily be involved. NKT cells in the setting of SLE could lack the cytokine stimulus from NK or other cells that is needed to exert control on IgG production. Enhancement of NKT cell activity may provide a novel basis for therapy in SLE.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17195234&query_hl=1
ER  - 

TY  - JFULL
T1  - Bacterial resistance to silver in wound care and medical devices
A1  - Lansdown ABG
A1  - Williams A
J1  - Journal of Wound Care
Y1  - 2007///
VL  - 16
SP  - 15
EP  - 19
ER  - 

TY  - JFULL
T1  - Cell dynamics and immune response to BLV infection: a unifying model.
A1  - Florins, A
A1  - Gillet, N
A1  - Asquith, B
A1  - Boxus, M
A1  - Burteau, C
A1  - Twizere, JC
A1  - Urbain, P
A1  - Vandermeers, F
A1  - Debacq, C
A1  - Sanchez-Alcaraz, MT
A1  - Schwartz-Cornil, I
A1  - Kerkhofs, P
A1  - Jean, G
A1  - Théwis, A
A1  - Hay, J
A1  - Mortreux, F
A1  - Wattel, E
A1  - Reichert, M
A1  - Burny, A
A1  - Kettmann, R
A1  - Bangham, C
A1  - Willems, L
J1  - Front Biosci
Y1  - 2007///
VL  - 12
SN  - 1093-4715
SP  - 1520
EP  - 1531
N2  - Bovine Leukemia virus (BLV) is the natural etiological agent of a lymphoproliferative disease in cattle. BLV can also be transmitted experimentally to a related ruminant species, sheep, in which the pathogenesis is more acute. Although both susceptible species develop a strong anti-viral immune response, the virus persists indefinitely throughout life, apparently at a transcriptionally silent stage, at least in a proportion of infected cells. Soon after infection, these humoral and cytotoxic activities very efficiently abolish the viral replicative cycle, permitting only mitotic expansion of provirus-carrying cells. Short term cultures of these infected cells initially indicated that viral expression protects against spontaneous apoptosis, suggesting that leukemia is a process of accumulation of long-lived cells. This conclusion was recently reconsidered following in vivo dynamic studies based on perfusions of nucleoside (bromodeoxyuridine) or fluorescent protein markers (CFSE). In sheep, the turnover rate of infected cells is increased, suggesting that a permanent clearance process is exerted by the immune system. Lymphocyte trafficking from and to the secondary lymphoid organs is a key component in the maintenance of cell homeostasis. The net outcome of the immune selective pressure is that only cells in which the virus is transcriptionally silenced survive and accumulate, ultimately leading to lymphocytosis. Activation of viral and/or cellular expression in this silent reservoir with deacetylase inhibitors causes the collapse of the proviral loads. In other words, modulation of viral expression appears to be curative in lymphocytic sheep, an approach that might also be efficient in patients infected with the related Human T-lymphotropic virus type 1. In summary, a dynamic interplay between BLV and the host immune response modulates a complex equilibrium between (i) viral expression driving (or) favoring proliferation and (ii) viral silencing preventing apoptosis. As conclusion, we propose a hypothetical model unifying all these mechanisms.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17127399&query_hl=1
ER  - 

TY  - JFULL
T1  - Three-year immune reconstitution in PI-sparing and PI-containing antiretroviral regimens in advanced HIV-1 disease.
A1  - Samri, A
A1  - Goodall, R
A1  - Burton, C
A1  - Imami, N
A1  - Pantaleo, G
A1  - Kelleher, A
A1  - Poli, G
A1  - Gotch, F
A1  - Autran, B
J1  - Antivir Ther
Y1  - 2007///
VL  - 12
SN  - 1359-6535
SP  - 553
EP  - 558
N2  - BACKGROUND: The long-term immunological benefit of protease inhibitor (PI)-sparing antiretroviral therapy (ART) using non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains poorly investigated. METHODS: A total of 120 ART-naive, HIV-1-infected participants were included in the immunology substudy of INITIO, an international randomized trial comparing two NRTIs (didanosine + stavudine) combined with either: one NNRTI (efavirenz; EFV), one non-boosted PI (nelfinavir; NFV), or one NNRTI + one PI (EFV/NFV). CD4+ T-cell counts, HIV-1 plasma RNA load (VL), T-cell phenotype, T-cell proliferation and IFN-gamma production against opportunistic/recall and HIV-1 antigens/peptides were compared at baseline and at week (W) 96 and W156. RESULTS: Participants (37 EFV, 44 NFV, 39 EFV/NFV) had similar baseline VL; median CD4+ T-cell counts/mm3 were: 144 (64-303) EFV, 212 (42-313) NFV and 257 (86-331) EFV/NFV. At W156, the proportion of patients with VL < or =50 copies/ml was not different between the arms (P=0.3). From baseline to W156 there was a significant increase in CD4+ T-cell counts (P<0.001) and in naive CD4+ T cells (P<0.001), with no difference between arms and percentages of total and activated CD8+ T cells decreased significantly (P<0.001) in all arms. The decrease in activated memory CD4+ T-cells was significantly greater in the EFV arm at W96 (P=0.03) and W156 (P=0.01), but did not persist after adjusting for baseline CD4+ T-cell counts. During follow-up, responses to opportunistic pathogens increased in all patients while specific T-cell responses to HIV-1-p24 and gp160 recombinant proteins or to Gag and Nef peptides were not restored. CONCLUSION: Regimens using/sparing PIs provide similar levels of long-term immune reconstitution even in patients with low CD4+ T-cell counts.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17668564&query_hl=1
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TY  - JFULL
T1  - Size matters: body composition and outcomes in maintenance hemodialysis patients.
A1  - Kotanko, P
A1  - Thijssen, S
A1  - Kitzler, T
A1  - Wystrychowski, G
A1  - Sarkar, SR
A1  - Zhu, F
A1  - Gotch, F
A1  - Levin, NW
J1  - Blood Purif
Y1  - 2007///
VL  - 25
SN  - 0253-5068
SP  - 27
EP  - 30
N2  - In hemodialysis patients a low body mass index (BMI) is correlated with an unfavorable clinical outcome, a phenomenon known as "reverse epidemiology". Mechanisms underlying this observation are unclear. We propose the following: uremic toxin generation occurs predominantly in visceral organs and the mass of key uremiogenic viscera (gut, liver) relative to body weight is higher in small people. Consequently, the rate of uremic toxin generation per unit of BMI is higher in patients with a low BMI. Body water, mainly determined by muscle mass, serves as a dilution compartment for uremic toxins. Therefore, the concentration of uremic toxins is higher in small subjects. Uremic toxins are taken up by adipose and muscle tissues, subsequently metabolized and stored. Thus, the larger the ratio of fat and muscle mass to visceral mass, the lower the concentration of uremic toxins and the better the survival. To test this hypothesis, studies on uremic toxin kinetics in relation to body composition are needed.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17170533&query_hl=1
ER  - 

TY  - JFULL
T1  - Interpretation of renal biopsies in IgA nephropathy.
A1  - Cook, HT
J1  - Contrib Nephrol
Y1  - 2007///
VL  - 157
SN  - 0302-5144
SP  - 44
EP  - 49
N2  - The renal biopsy is essential for the diagnosis of IgA nephropathy. It should also be possible to derive important information from the biopsy about prognosis and likely response to treatment. Biopsy features that are associated with progression to end-stage renal disease are glomerulosclerosis and tubulointerstitial scarring, marked crescent formation and marked arteriolar hyalinosis. However, with our present classification systems the renal biopsy adds little over and above clinical features in predicting outcome. It may be possible to improve the predictive value of the renal biopsy by adopting the following recommendations in developing new classifications: (1) looking at the ability of the biopsy to predict changes in renal function in the short term after biopsy rather than prediction of progression to end stage renal disease; (2) examining subgroups of patients where the biopsy is likely to be most informative; (3) distinguishing the effects of reversible and irreversible changes particularly with regard to response to treatment; (4) ensuring uniformity of definitions between pathologists, and (5) paying attention to small lesions and considering including additional biopsy features. The most important role for the renal biopsy in the future is likely to be in predicting response to therapy rather than predicting progression to end-stage renal disease.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17495436&query_hl=1
ER  - 

TY  - JFULL
T1  - Assessment of response to treatment of unresectable liver tumours with 90Y microspheres: value of FDG PET versus computed tomography.
A1  - Szyszko, T
A1  - Al-Nahhas, A
A1  - Canelo, R
A1  - Habib, N
A1  - Jiao, L
A1  - Wasan, H
A1  - Pagou, M
A1  - Tait, P
J1  - Nucl Med Commun
Y1  - 2007/01//
VL  - 28
SN  - 0143-3636
SP  - 15
EP  - 20
N2  - INTRODUCTION: Selective internal radiation therapy (SIRT) with SIR spheres (90Y microspheres) is a treatment option for liver tumours in patients in whom other therapies are inappropriate or have failed. This study aims to assess the value of FDG PET in assessing the response to SIRT as compared to computed tomography (CT). MATERIAL AND METHODS: Twenty-one patients (11 F, 10 M; age range 40-75 years, mean, 58 years) received SIR spheres at the Hammersmith Hospital. One patient received two treatments. Most patients had colorectal metastases (n=10), while the others (n=11) had liver metastasis from different primaries. The mean administered dose was 1.9 GBq (range, 1.2-2.5 GBq). Follow-up was done with FDG PET and CT at 6 weeks, and 6-monthly thereafter. Pre-therapy and post-therapy CT and PET scans were assessed visually (RECIST criteria for CT) and semi-quantitative for PET using the standardized uptake value (SUV). RESULT: Eighty-six percent of patients showed decreased PET activity at 6 weeks while only 13% showed a partial response in the size of tumour on CT scan. The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7 (P=0.01). CT imaging showed progressive disease in 27% patients and stable liver disease in 60% patients. Based on FDG PET results one patient had surgery for down-staged tumour. CONCLUSION: FDG PET imaging is more sensitive than CT in the assessment of early response to SIR spheres, allowing clinicians to proceed with further therapeutic options.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17159544&query_hl=1
ER  - 

TY  - JFULL
T1  - Abnormal bone remodeling process is due to an imbalance in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) axis in patients with solid tumors metastatic to the skeleton
A1  - Mountzios, G
A1  - Dimopoulos, MA
A1  - Bamias, A
A1  - Papadopoulos, G
A1  - Kastritis, E
A1  - Syrigos, K
A1  - Pavlakis, G
A1  - Terpos, E
J1  - ACTA ONCOL
Y1  - 2007///
VL  - 46
SN  - 0284-186X
SP  - 221
EP  - 229
N2  - The role of receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, and osteopontin (OPN) was studied in patients with solid tumors metastatic to the bone in relation to the type of malignancy and the neoplastic burden to the skeleton. Levels of soluble RANKL (sRANKL), OPG and OPN were assessed in 61 patients with breast, lung and prostate cancer with newly-diagnosed metastasis to the bone, in parallel with bone resorption [C-telopeptide of type-I collagen (CTX), tartrate-resistant acid phosphatase-5b (TRACP-5b)] and bone formation markers [bone-alkaline phosphatase (bALP), osteocalcin (OC), and C-terminal propeptide of collagen type-I (CICP)]. Patients had elevated serum levels of sRANKL, OPG, OPN, TRACP-5b, and bALP, and reduced OC levels compared to controls. OPG correlated with the extent of metastatic bone burden. Patients with breast and lung cancer shared increased levels of sRANKL, OPG, and OPN whereas prostate cancer patients had elevated values of OPG and bALP only. These results suggest that patients with solid tumors metastatic to the bone have severe disruption of the sRANKL/OPG axis. Breast and lung cancer seem to exert their osteolytic action through upregulation of the sRANKL/OPG system and OPN, whereas prostate cancer seems to provoke profound elevation of OPG levels only, thus leading to increased osteoblastic activity.
ER  - 

TY  - JFULL
T1  - Metastatic ductal eccrine adenocarcinoma masquerading as an invasive ductal carcinoma of the male breast.
A1  - Mclean, SR
A1  - Shousha, S
A1  - Francis, N
A1  - Lim, A
A1  - Eccles, S
A1  - Brock, CS
A1  - Palmieri, C
J1  - J INVEST MED
Y1  - 2007/01//
VL  - 55
SN  - 1081-5589
SP  - S93
EP  - S93
ER  - 

TY  - JFULL
T1  - Minimally invasive parathyroidectomy without intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism.
A1  - Mihai, R
A1  - Palazzo, FF
A1  - Gleeson, FV
A1  - Sadler, GP
J1  - Br J Surg
Y1  - 2007/01//
VL  - 94
SN  - 0007-1323
SP  - 42
EP  - 47
N2  - BACKGROUND: Minimally invasive parathyroidectomy (MIP) is the preferred operation for patients with primary hyperparathyroidism (HPT) and positive preoperative imaging. This non-randomized case series assessed the long-term results of MIP performed without the use of intraoperative parathyroid hormone (ioPTH) monitoring. METHODS: The study involved prospective collection of demographic, biochemical and operative details on a consecutive, unselected cohort of 298 patients who underwent surgery for non-familial primary HPT during a 5-year interval. The mean preoperative serum calcium level was 3.00 mmol/l with a mean parathyroid hormone concentration of 25.8 pmol/l. (99m)Tc-labelled sestamibi scanning and neck ultrasonography were performed in 262 patients. RESULTS: Sestamibi scan showed unilateral uptake in 182 patients and a single parathyroid adenoma was confirmed on ultrasonography in 161 patients. MIP was performed in 150 patients. The mean duration of operation was 25 (range 8-65) min. Four patients needed conversion to conventional neck exploration. There was one postoperative haematoma and three cases of temporary recurrent laryngeal nerve neuropraxia. All but four patients were normocalcaemic after MIP. All the parathyroid tumours removed were adenomas, with a mean weight of 1.3 (range 0.1-17.4) g. No patient developed recurrent HPT after a median follow-up of 16 (range 3-48) months. CONCLUSION: The outcome of MIP without ioPTH monitoring was comparable to that reported in series that used ioPTH monitoring.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17083106&query_hl=1
ER  - 

TY  - JFULL
T1  - C1q can alter the levels of IgM autoantibody production in anti-DNA transgenic models
A1  - Fossati-Jimack, L
A1  - Cortes-Hernandez, J
A1  - Norsworthy, P
A1  - Cook, HT
A1  - Botto, M
J1  - MOL IMMUNOL
Y1  - 2007/01//
VL  - 44
SN  - 0161-5890
SP  - 171
EP  - 171
ER  - 

TY  - JFULL
T1  - Case 32. Eosinophilia: reactive or neoplastic?
A1  - Fletcher, S
A1  - Abdalla, S
A1  - Edwards, M
A1  - Bain, BJ
J1  - Leuk Lymphoma
Y1  - 2007/01//
VL  - 48
SN  - 1042-8194
SP  - 174
EP  - 176
N2  - A diagnosis of eosinophilic leukemia was suspected in a patient who presented with eosinophilia and a mild macrocytic anemia and was found to have trisomy 8. Further tests and the subsequent clinical course permitted an accurate diagnosis.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17325861&query_hl=1
ER  - 

TY  - JFULL
T1  - Systems biology and its impact on anti-infective drug development.
A1  - Stumpf, MP
A1  - Robertson, BD
A1  - Duncan, K
A1  - Young, DB
J1  - Prog Drug Res
Y1  - 2007///
VL  - 64
SN  - 0071-786X
SP  - 1, 3
EP  - 20, 3
N2  - Systems biology offers the potential for more effective selection of novel targets for anti-infective drugs. In contrast to conventional reductionist biology, a systems approach allows targets to be viewed in a wider context of the entire physiology of the cell, with the potential to identify key susceptible nodes and to predict synergistic effects of blocking multiple pathways. In addition to the holistic perspective provided by systems biology, the emphasis on quantitative analysis is likely to add further rigour to the process of target selection. Systems biology also offers the potential to incorporate different levels of information into the selection process. Consideration of data from microbial population biology may be important in the context of predicting future drug-resistance profiles associated with targeting a particular pathway, for example. This chapter provides an overview of major themes in the developing field of systems biology, summarising the core technologies and the strategies used to translate datasets into useful quantitative models capable of predicting complex biological behaviour.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17195469&query_hl=1
ER  - 

TY  - JFULL
T1  - A point mutation in an Sp1 binding motif in the promoter of the mannosyltransferase-encoding PIG-M gene causes inherited glycosylphosphatidylinositol deficiency
A1  - Murakarni, Y
A1  - Almeida, A
A1  - Layton, M
A1  - Hillmen, P
A1  - Maeda, Y
A1  - Karadimitris, A
A1  - Kinoshita, T
J1  - MOL IMMUNOL
Y1  - 2007/01//
VL  - 44
SN  - 0161-5890
SP  - 218
EP  - 218
ER  - 

TY  - JFULL
T1  - The basic, quantifiable parameter of dialysis prescription is Kt/V urea; treatment time is determined by the ultrafiltration requirement; all three parameters are of equal importance.
A1  - Gotch, F
J1  - Blood Purif
Y1  - 2007///
VL  - 25
SN  - 0253-5068
SP  - 18
EP  - 26
N2  - There have only been two randomized controlled trials studying outcome as a function of dose in hemodialysis (HD). The first was the National Cooperative Dialysis Study which showed that adequate dialysis was achieved with spKt/V >1.00. The second study was HEMO which was originally designed to study spKt/V 1.2 compared to spKt/V 1.45. Unfortunately by the time HEMO was started, observational studies (OS) had convinced the nephrology community that the minimum adequate dose of spKt/V was 1.40, so the lower target was increased to 1.4 and the upper target to 1.7. The study showed no difference in outcome, although OS have now demonstrated that outcome improves up to spKt/v 2.00. Analysis of HEMO as treated showed that there is a fundamental flaw in dose-targeted OS in that the optimal dose always, but spuriously, increases as the studied dose increases due to dose-targeting bias. Similar flaws exist in the association of treatment time to outcome.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17170532&query_hl=1
ER  - 

TY  - JFULL
T1  - The protein C anticoagulant pathway: new insights
A1  - Lane, DA
J1  - THROMB RES
Y1  - 2007/01//
VL  - 119
SN  - 0049-3848
SP  - S6
EP  - S7
ER  - 

TY  - JFULL
T1  - LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre.
A1  - Perz, JB
A1  - Giles, C
A1  - Szydlo, R
A1  - O'Shea, D
A1  - Sanz, J
A1  - Chaidos, A
A1  - Wagner, S
A1  - Davis, J
A1  - Loaiza, S
A1  - Marin, D
A1  - Apperley, J
A1  - Olavarria, E
A1  - Rahemtulla, A
A1  - Lampert, I
A1  - Naresh, K
A1  - Samson, D
A1  - MacDonald, D
A1  - Kanfer, EJ
J1  - Bone Marrow Transplant
Y1  - 2007/01//
VL  - 39
SN  - 0268-3369
SP  - 41
EP  - 47
N2  - High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3-161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17115062&query_hl=1
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TY  - JFULL
T1  - Site-specific PEGylation of protein disulfide bonds using a three-carbon bridge.
A1  - Balan, S
A1  - Choi, JW
A1  - Godwin, A
A1  - Teo, I
A1  - Laborde, CM
A1  - Heidelberger, S
A1  - Zloh, M
A1  - Shaunak, S
A1  - Brocchini, S
J1  - Bioconjug Chem
Y1  - 2007/01//
VL  - 18
SN  - 1043-1802
SP  - 61
EP  - 76
N2  - The covalent conjugation of a functionalized poly(ethylene glycol) (PEG) to multiple nucleophilic amine residues results in a heterogeneous mixture of PEG positional isomers. Their physicochemical, biological, and pharmaceutical properties vary with the site of conjugation of PEG. Yields are low because of inefficient conjugation chemistry and production costs high because of complex purification procedures. Our solution to these fundamental problems in PEGylating proteins has been to exploit the latent conjugation selectivity of the two sulfur atoms that are derived from the ubiquitous disulfide bonds of proteins. This approach to PEGylation involves two steps: (1) disulfide reduction to release the two cysteine thiols and (2) re-forming the disulfide by bis-alkylation via a three-carbon bridge to which PEG was covalently attached. During this process, irreversible denaturation of the protein did not occur. Mechanistically, the conjugation is conducted by a sequential, interactive bis-alkylation using alpha,beta-unsaturated beta'-monosulfone functionalized PEG reagents. The combination of (a) maintaining the protein's tertiary structure after disulfide reduction, (b) the mechanism for bis-thiol selectivity of the PEG reagent, and (c) the steric shielding of PEG ensure that only one PEG molecule is conjugated at each disulfide bond. PEG was site-specifically conjugated via a three-carbon bridge to 2 equiv of the tripeptide glutathione, the cyclic peptide hormone somatostatin, the tetrameric protein l-asparaginase, and to the disulfides in interferon alpha-2b (IFN). SDS-PAGE, mass spectral, and NMR analyses were used to confirm conjugation, thiol selectivity, and connectivity. The biological activity of the l-asparaginase did not change after the attachment of four PEG molecules. In the case of IFN, a small reduction in biological activity was seen with the single-bridged IFN (without PEG attached). A significantly larger reduction in biological activity was seen with the three-carbon disulfide single-bridged PEG-IFNs and with the double-bridged IFN (without PEG attached). The reduction of the PEG-IFN's in vitro biological activity was a consequence of the steric shielding caused by PEG, and it was comparable to that seen with all other forms of PEG-IFNs reported. However, when a three-carbon bridge was used to attach PEG, our PEG-IFN's biological activity was found to be independent of the length of the PEG. This property has not previously been described for PEG-IFNs. Our studies therefore suggest that peptides, proteins, enzymes, and antibody fragments can be site-specifically PEGylated across a native disulfide bond using three-carbon bridges without destroying their tertiary structure or abolishing their biological activity. The stoichiometric efficiency of this approach also enables recycling of any unreacted protein. It therefore offers the potential to make PEGylated biopharmaceuticals as cost-effective medicines for global use.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17226958&query_hl=1
ER  - 

TY  - JFULL
T1  - Acrometastasis to the foot: an unusual presentation of transitional cell carcinoma of the bladder.
A1  - Khan, S
A1  - Win, Z
A1  - Lloyd, CR
A1  - Neriman, D
A1  - Szyszko, TA
A1  - Svensson, WE
A1  - Al-Nahhas, A
J1  - Nucl Med Rev Cent East Eur
Y1  - 2007///
VL  - 10
SN  - 1506-9680
SP  - 26
EP  - 28
N2  - Metastases from bladder cancer to the bones of the hands or feet are rare and usually present after the diagnosis of the primary lesion has been made. This case report describes a 76-year-old man presenting with initial signs of infection of the right foot. Subsequent bone scan revealed multiple bony metastases and hydronephrosis raising the possibility of a primary bladder tumour that was later confirmed by urine cytology and fine needle aspiration of the foot.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17694499&query_hl=1
ER  - 

TY  - JFULL
T1  - Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma.
A1  - McCarthy, NE
A1  - Jones, HA
A1  - Marks, NA
A1  - Shiner, RJ
A1  - Ind, PW
A1  - Al-Hassi, HO
A1  - English, NR
A1  - Murray, CM
A1  - Lambert, JR
A1  - Knight, SC
A1  - Stagg, AJ
J1  - Clin Exp Allergy
Y1  - 2007/01//
VL  - 37
SN  - 0954-7894
SP  - 72
EP  - 82
N2  - BACKGROUND: Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory-tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. OBJECTIVE: To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. METHODS: Sputum cells were induced from steroid-naïve, allergen-challenged and allergen-naïve subjects (atopic asthmatics, atopic non-asthmatics and non-atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. RESULTS: hRTDC stained HLA-DR(+) (negative for markers of other cell lineages) were predominantly myeloid and comprised approximately 0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4(+) naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC-dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05-P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c(-)CD123(high) hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. CONCLUSION: Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17210044&query_hl=1
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TY  - JFULL
T1  - Chronic myeloproliferative disorders: the role of tyrosine kinases in pathogenesis, diagnosis and therapy.
A1  - Macdonald, D
A1  - Cross, NC
J1  - Pathobiology
Y1  - 2007///
VL  - 74
SN  - 1015-2008
SP  - 81
EP  - 88
N2  - The term chronic myeloproliferative disorders was originally used by Damashek to describe the link amongst a group of acquired blood diseases. Recent molecular genetic analysis has provided a scientific basis for this observation. Underlying myeloproliferative disorders are acquired abnormalities of tyrosine kinase genes. These may be chromosomal translocations resulting in the creation of a fusion kinase gene, examples of which include ABL, FGFR, and PDGFR as seen in disorders CML, 8p11 myeloproliferative syndrome, atypical CML and chronic eosinophilic leukaemia. The second group of tyrosine kinase abnormalities are point mutations in JAK2, a cytosolic TK. This abnormality is seen in 30-97% of cases of MPD with the phenotype PV, ET or CIMF.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17587879&query_hl=1
ER  - 

TY  - JFULL
T1  - Early risk assessment for viral haemorrhagic fever: experience at the Hospital for Tropical Diseases, London, UK.
A1  - Woodrow, CJ
A1  - Eziefula, AC
A1  - Agranoff, D
A1  - Scott, GM
A1  - Watson, J
A1  - Chiodini, PL
A1  - Lockwood, DN
A1  - Grant, AD
J1  - J Infect
Y1  - 2007/01//
VL  - 54
SN  - 0163-4453
SP  - 6
EP  - 11
N2  - OBJECTIVES: To implement a policy of systematic screening for viral haemorrhagic fever (VHF) among travellers returning from African countries with fever, commencing at initial clinical contact. METHODS: A protocol based on UK Advisory Committee on Dangerous Pathogens guidance was developed collaboratively by medical, nursing and laboratory staff. Audit was carried out to quantify resource demands and effects on time to diagnose malaria, the main differential diagnosis. RESULTS: A protocol is now implemented for all patients presenting to HTD with fever, with clear guidelines for interaction with clinical and laboratory staff at each stage. The protocol required moderate amounts of clinical and laboratory staff time and resulted in some additional hospital admissions. The time to a diagnosis of malaria increased from a median of 90 (range 50-125) min in patients without VHF risk to a median of 140 (range 101-225) min (p=0.0025) in those assessed as at risk. CONCLUSIONS: Although all acute medical services need to have robust procedures for early detection of patients with serious transmissible conditions, few implement such a policy. Our protocol requires increased human and other resources but has no important impact on the rapidity of diagnosis of malaria, and is now embedded in local practice.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16549203&query_hl=1
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TY  - JFULL
T1  - Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver.
A1  - Barter, ZE
A1  - Bayliss, MK
A1  - Beaune, PH
A1  - Boobis, AR
A1  - Carlile, DJ
A1  - Edwards, RJ
A1  - Houston, JB
A1  - Lake, BG
A1  - Lipscomb, JC
A1  - Pelkonen, OR
A1  - Tucker, GT
A1  - Rostami-Hodjegan, A
J1  - Curr Drug Metab
Y1  - 2007/01//
VL  - 8
SN  - 1389-2002
SP  - 33
EP  - 45
N2  - Reported predictions of human in vivo hepatic clearance from in vitro data have used a variety of values for the scaling factors human microsomal protein (MPPGL) and hepatocellularity (HPGL) per gram of liver, generally with no consideration of the extent of their inter-individual variability. We have collated and analysed data from a number of sources, to provide weighted meangeo values of human MPPGL and HPGL of 32 mg g-1 (95% Confidence Interval (CI); 29-34 mg.g-1) and 99x10(6) cells.g-1 (95% CI; 74-131 mg.g-1), respectively. Although inter-individual variability in values of MPPGL and HPGL was statistically significant, gender, smoking or alcohol consumption could not be detected as significant covariates by multiple linear regression. However, there was a weak but statistically significant inverse relationship between age and both MPPGL and HPGL. These findings indicate the importance of considering differences between study populations when forecasting in vivo pharmacokinetic behaviour. Typical clinical pharmacology studies, particularly in early drug development, use young, fit, healthy male subjects of around 30 years of age. In contrast, the average age of patients for many diseases is about 60 years of age. The relationship between age and MPPGL observed in this study estimates values of 40 mg.g-1 for a 30 year old individual and 31 mg.g-1 for a 60 year old individual. Investigators may wish to consider the reported covariates in the selection of scaling factors appropriate for the population in which estimates of clearance are being predicted. Further studies are required to clarify the influence of age (especially in paediatric subjects), donor source and ethnicity on values of MPPGL and HPGL. In the meantime, we recommend that the estimates (and their variances) from the current meta-analysis be used when predicting in vivo kinetic parameters from in vitro data.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17266522&query_hl=1
ER  - 

TY  - JFULL
T1  - Novel zinc-based fixative for high quality DNA, RNA and protein analysis.
A1  - Lykidis, D
A1  - Van Noorden, S
A1  - Armstrong, A
A1  - Spencer-Dene, B
A1  - Li, J
A1  - Zhuang, Z
A1  - Stamp, GW
J1  - Nucleic Acids Res
Y1  - 2007///
VL  - 35
SN  - 1362-4962
SP  - e85
EP  - e85
N2  - We have developed a reliable, cost-effective and non-toxic fixative to meet the needs of contemporary molecular pathobiology research, particularly in respect of RNA and DNA integrity. The effects of 25 different fixative recipes on the fixed quality of tissues from C57BL/6 mice were investigated. Results from IHC, PCR, RT-PCR, RNA Agilent Bioanalyser and Real-Time PCR showed that a novel zinc-based fixative (Z7) containing zinc trifluoroacetate, zinc chloride and calcium acetate was significantly better than the standard zinc-based fixative (Z2) and neutral buffered formalin (NBF) for DNA, RNA and protein preservation. DNA sequences up to 2.4 kb in length and RNA fragments up to 361 bp in length were successfully amplified from Z7 fixed tissues, as demonstrated by PCR, RT-PCR and Real-Time PCR. Total protein analysis was achieved using 2-D gel electrophoresis. In addition, nucleic acids and proteins were very stable over a 6-14-month period. This improved, non-toxic and economical tissue fixative could be applied for routine use in pathology laboratories to permit subsequent genomic/proteomic studies.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17576663&query_hl=1
ER  - 

TY  - JFULL
T1  - Epstein-barr virus-induced resistance to drugs that activate the mitotic spindle assembly checkpoint in Burkitt's lymphoma cells.
A1  - Leao, M
A1  - Anderton, E
A1  - Wade, M
A1  - Meekings, K
A1  - Allday, MJ
J1  - J Virol
Y1  - 2007/01//
VL  - 81
SN  - 0022-538X
SP  - 248
EP  - 260
N2  - Epstein-Barr virus (EBV) is associated with a number of human cancers, and latent EBV gene expression has been reported to interfere with cell cycle checkpoints and cell death pathways. Here we show that latent EBV can compromise the mitotic spindle assembly checkpoint and rescue Burkitt's lymphoma (BL)-derived cells from caspase-dependent cell death initiated in aberrant mitosis. This leads to unscheduled mitotic progression, resulting in polyploidy and multi- and/or micronucleation. The EBV latent genes responsible for this phenotype are expressed from the P3HR1 strain of virus and several viruses with similar genomic deletions that remove the EBNA2 gene. Although EBNA2 and the latent membrane proteins are not expressed, the EBNA3 proteins are present in these BL cells. Survival of the EBV-positive cells is not consistently associated with EBV lytic gene expression or with the genes that are expressed in EBV latency I BL cells (i.e., EBNA1, EBERs, and BARTs) but correlates with reduced expression of the cellular proapoptotic BH3-only protein Bim. These data suggest that a subset of latent EBV gene products may increase the likelihood of damaged DNA being inherited because of the impaired checkpoint and enhanced survival capacity. This could lead to greater genetic diversity in progeny cells and contribute to tumorigenesis. Furthermore, since it appears that this restricted latent EBV expression interferes with the responses of Burkitt's lymphoma-derived cells to cytotoxic drugs, the results of this study may have important therapeutic implications in the treatment of some BL.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17035311&query_hl=1
ER  - 

TY  - JFULL
T1  - Antimicrobial prophylaxis for endocarditis: emotion or science?
A1  - Ashrafian, H
A1  - Bogle, RG
J1  - Heart
Y1  - 2007/01//
VL  - 93
SN  - 1468-201X
SP  - 5
EP  - 6
N2  - Yet another guideline on the prevention of infective endocarditis has been published, this time limiting prophylaxis to high-risk patients.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16914480&query_hl=1
ER  - 

TY  - JFULL
T1  - Zinc in wound healing: theoretical, experimental, and clinical aspects.
A1  - Lansdown, AB
A1  - Mirastschijski, U
A1  - Stubbs, N
A1  - Scanlon, E
A1  - Agren, MS
J1  - Wound Repair Regen
Y1  - 2007/01//
VL  - 15
SN  - 1067-1927
SP  - 2
EP  - 16
N2  - Zinc is an essential trace element in the human body and its importance in health and disease is appreciated. It serves as a cofactor in numerous transcription factors and enzyme systems including zinc-dependent matrix metalloproteinases that augment autodebridement and keratinocyte migration during wound repair. Zinc confers resistance to epithelial apoptosis through cytoprotection against reactive oxygen species and bacterial toxins possibly through antioxidant activity of the cysteine-rich metallothioneins. Zinc deficiency of hereditary or dietary cause can lead to pathological changes and delayed wound healing. Oral zinc supplementation may be beneficial in treating zinc-deficient leg ulcer patients, but its therapeutic place in surgical patients needs further clarification. Topical administration of zinc appears to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, and the sustained release of zinc ions that stimulates epithelialization of wounds in normozincemic individuals. Zinc oxide in paste bandages (Unna boot) protects and soothes inflamed peri-ulcer skin. Zinc is transported through the skin from these formulations, although the systemic effects seem insignificant. We present here the first comprehensive account of zinc in wound management in relation to current concepts of wound bed preparation and the wound-healing cascade. This review article suggests that topical zinc therapy is underappreciated even though clinical evidence emphasizes its importance in autodebridement, anti-infective action, and promotion of epithelialization.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17244314&query_hl=1
ER  - 

TY  - JFULL
T1  - Selection of protein phosphatase 2A regulatory subunits is mediated by the C-terminus of the catalytic subunit.
A1  - Longin, S
A1  - Zwaenepoel , K
A1  - Louis, JV
A1  - Dilworth, S
A1  - Goris, J
J1  - J. Biol. Chem.
Y1  - 2007///
ER  - 

TY  - JFULL
T1  - The contribution of cytomegalovirus to changes in NK cell receptor expression in HIV-1-infected individuals.
A1  - Mela, CM
A1  - Goodier, MR
J1  - J Infect Dis
Y1  - 2007/01/01/
VL  - 195
SN  - 0022-1899
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17152020&query_hl=1
ER  - 

TY  - JFULL
T1  - Critical observations on the neurotoxicity of silver
A1  - Lansdown ABG
J1  - Critical Reviews in Toxicology
Y1  - 2007///
IS  - 1
VL  - 37
SP  - 1
EP  - 14
ER  - 

TY  - JFULL
T1  - Stem cells as a treatment for chronic liver disease and diabetes.
A1  - Levicar, N
A1  - Dimarakis, I
A1  - Flores, C
A1  - Tracey, J
A1  - Gordon, MY
A1  - Habib, NA
J1  - Handb Exp Pharmacol
Y1  - 2007///
SN  - 0171-2004
SP  - 243
EP  - 262
N2  - Advances in stem cell biology and the discovery of pluripotent stem cells have made the prospect of cell therapy and tissue regeneration a clinical reality. Cell therapies hold great promise to repair, restore, replace or regenerate affected organs and may perform better than any pharmacological or mechanical device. There is an accumulating body of evidence supporting the contribution of adult stem cells, in particular those of bone marrow origin, to liver and pancreatic islet cell regeneration. In this review, we will focus on the cell therapy for the diseased liver and pancreas by adult haematopoietic stem cells, as well as their possible contribution and application to tissue regeneration. Furthermore, recent progress in the generation, culture and targeted differentiation of human haematopoietic stem cells to hepatic and pancreatic lineages will be discussed. We will also explore the possibility that stem cell technology may lead to the development of clinical modalities for human liver disease and diabetes.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17554512&query_hl=1
ER  - 

TY  - JFULL
T1  - A phase I, randomized study of combined IL-2 and therapeutic immunisation with antiretroviral therapy.
A1  - Hardy, GA
A1  - Imami, N
A1  - Nelson, MR
A1  - Sullivan, AK
A1  - Moss, R
A1  - Aasa-Chapman, MM
A1  - Gazzard, B
A1  - Gotch, FM
J1  - J Immune Based Ther Vaccines
Y1  - 2007///
VL  - 5
SN  - 1476-8518
SP  - 6
EP  - 6
N2  - BACKGROUND: Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection. DESIGN: Chronically infected patients with low CD4 counts T-cell counts who commenced antiretroviral therapy (ART) were subsequently treated with combined interleukin-2 and therapeutic vaccination. METHODS: Thirty six anti-retroviral naive patients were recruited and initiated on combination ART for 17 weeks before randomization to: A) ongoing ART alone; B) ART with IL-2 twice daily for 5 days every four weeks starting at week 17 for 3 cycles; C) ART with IL-2 as in group B and Remune HIV-1 vaccine administered once every 3 months, starting at week 17; and D) ART with Remune vaccine as in group C. Patients were studied for 65 weeks following commencement of ART, with an additional prior 6 week lead-in observation period. CD4 and CD8 T-cell counts, evaluations of HIV-1 RNA levels and proliferative responses to recall and HIV-1 antigens were complemented with assessment of IL-4-secretion alongside quantification of anti-HIV-1 CD8 T-cell responses and neutralizing antibody titres. RESULTS: Neither IL-2 nor Remune vaccination induced sustained HIV-1-specific T-cell responses. However, we report an inverse relationship between HIV-1-specific proliferative responses and IL-4 production which continuously increased in patients receiving immunotherapy, but not patients receiving ART alone. CONCLUSION: Induction of HIV-1-specific cell-mediated responses is a major challenge in chronically HIV-1-infected patients even when combining immunisation with IL-2 therapy. An antigen-specific IL-4-associated suppressive response may play a role in attenuating HIV-specific responses.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428345&query_hl=1
ER  - 

TY  - JFULL
T1  - Nuclear positioning of the BACH2 gene in BCR-ABL positive leukemic cells
A1  - Ono, A
A1  - Kono, K
A1  - Ikebe, D
A1  - Muto, A
A1  - Sun, JY
A1  - Kobayashi, M
A1  - Ueda, K
A1  - Melo, JV
A1  - Igarashi, K
A1  - Tashiro, S
J1  - GENE CHROMOSOME CANC
Y1  - 2007/01//
VL  - 46
SN  - 1045-2257
SP  - 67
EP  - 74
N2  - BACH2 is a B-cell-specific transcription repressor and is also know as a tumor suppressor in B cell malignancy. Expression of BACH2 is induced in BCR-ABL positive lymphoid cell lines including BV173 by imatinib, a molecular targeting agent for the treatment of chronic myeloid leukemia (CML). Here we show that the activity of the BACH2 gene is related to the nuclear positioning of the gene loci. We examined the spatial association of the BACH2 gene with the centromeric heterochromatin, a transcriptionally repressive subnuclear compartment, by comparing cells with low (BV173 and K562) and high (NAMALWA) levels of BACH2 mRNA. The BACH2 gene was located closer to the centromeric heterochromatin in BV173 and K562 cells as compared to NAMALWA cells. In BV173 cells, the BACH2-centromere distance increased after imatinib treatment to levels similar to those in NAMALWA cells. We also found that diethylmaleate, an oxidative stressor, enhanced the antiproliferative effect of imatinib in only BV173 cells. Since BACH2 induces apoptosis by oxidative stress, these observations suggest that down-regulation of the BACH2 gene through the interaction with centromeric heterochromatin would take part in leukomogenesis of BCR-ABL positive lymphoid leukemia. 2006 Wiley-Liss, Inc.
ER  - 

TY  - JFULL
T1  - Pulmonary infection with Cryptococcus neoformans in the face of underlying sarcoidosis.
A1  - Boyton, RJ
A1  - Altmann, DM
A1  - Wright, A
A1  - Kon, OM
J1  - Respiration
Y1  - 2007///
VL  - 74
SN  - 0025-7931
SP  - 462
EP  - 466
N2  - We present a case of limited pulmonary cryptococcal infection following exposure to pigeon excreta in a patient with sarcoidosis. The pathogenicity of Cryptococcus neoformans depends on the interplay between the immune status of the host and the virulence of the infecting strain. It can range from asymptomatic lung colonization in the immunocompetent host to rapidly progressive meningitis in immunocompromised patients. Immunological models of respiratory disease emphasize a distinction between infections associated with immune suppression on the one hand and diseases such as sarcoidosis believed to involve an excessive Th1-mediated immune response on the other. This case exemplifies the complex nature of immunological responses in the lung and highlights the importance of considering the possibility of co-existent fungal infection in individuals with sarcoidosis. Novel immunotherapeutic options for cryptococcal infection are discussed.
L1  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16106116&query_hl=1
ER  - 

TY  - JFULL
T1  - Overexpression of the heat-shock protein 70 is associated to imatinib resistance in chronic myeloid leukemia
A1  - Pocaly, M
A1  - Lagarde, V
A1  - Etienne, G
A1  - Ribeil, JA
A1  - Claverol, S
A1  - Bonneu, M
A1  - Moreau-Gaudry, F
A1  - Guyonnet-Duperat, V
A1  - Hermine, O
A1  - Melo, JV
A1  - Dupouy, M
A1  - Turcq, B
A1  - Mahon, FX
A1  - Pasquet, JM
J1  - LEUKEMIA
Y1  - 2007/01//
VL  - 21
SN  - 0887-6924
SP  - 93
EP  - 101
N2  - Imatinib is an effective therapy for chronic myeloid leukemia ( CML), a myeloproliferative disorder characterized by the expression of the recombinant oncoprotein Bcr-AbI. In this investigation, we studied an imatinib-resistant cell line ( K562-r) generated from the K562 cell line in which none of the previously described mechanisms of resistance had been detected. A threefold increase in the expression of the heat-shock protein 70 ( Hsp70) was detected in these cells. This increase was not associated to heat-shock transcription factor-1 ( HSF-1) overexpression or activation. RNA silencing of Hsp70 decreased dramatically its expression ( 90%), and was accompanied by a 34% reduction in cell viability. Overexpression of Hsp70 in the imatinib-sensitive K562 line induced resistance to imatinib as detected by a large reduction in cell death in the presence of 1 mu M of imatinib. Hsp70 level was also increased in blast cells of CML patients resistant to imatinib, whereas the level remained low in responding patients. Taken together, the results demonstrate that overexpression of Hsp70 can lead to both in vitro and in vivo resistance to imatinib in CML cells. Moreover, the overexpression of Hsp70 detected in imatinib-resistant CML patients supports this mechanism and identifies potentially a marker and a therapeutic target of CML evolution.
ER  - 

TY  - JFULL
T1  - Successful treatment of extramedullary plasmacytoma of the carvenous sinus using a combination of intermediate dose of thalidomide