TY - BOOK T1 - Chronic Fatigue Syndrome. A1 - Puri BK Y1 - 2005/06/27/ PB - Hammersmith Press CY - London SN - 1-905140-00-2 N2 - - ER - TY - BOOK T1 - Attention-Deficit Hyperactivity Disorder. A1 - Puri BK Y1 - 2005/// PB - Hammersmith Press CY - London SN - 1-905140-01-0 N2 - - ER - TY - BOOK T1 - Mental Health Law: A Practical Guide. A1 - Puri BK A1 - Brown R A1 - McKee HM A1 - Treasaden IH Y1 - 2005/// PB - Hodder Arnold, London and Oxford University Press, New York SN - 0-340-88503-3 N2 - - ER - TY - BOOK T1 - The Natural Way to Beat Depression, Paperback (Revised) Edition A1 - Puri BK A1 - Boyd H Y1 - 2005/// PB - Hodder Mobius CY - London SN - 0-340-82497-2 N2 - - ER - TY - BOOK T1 - Revision Notes in Psychiatry, 2nd edition. A1 - Puri BK A1 - Hall AD Y1 - 2004/// PB - Arnold, London and Oxford University Press, New York. SN - 0-340-76131-8 N2 - - ER - TY - BOOK T1 - MRI from Picture to Proton (Japanese language edition) A1 - McRobbie DW A1 - Moore EA A1 - Graves MJ A1 - Prince MR Y1 - 2004/// PB - Ohmsha Ltd CY - Tokyo N2 - - ER - TY - BOOK T1 - The Natural Way to Beat Depression: The Groundbreaking Discovery of EPA. A1 - Puri B A1 - Boyd H Y1 - 2004/// PB - Hodder Mobius CY - London SN - 0-340-82496-4 N2 - - ER - TY - BOOK T1 - MRI from Picture to Proton A1 - McRobbie DW A1 - Moore EA A1 - Graves MJ A1 - Prince MR Y1 - 2003/// PB - Cambridge University Press CY - Cambridge CB2 2RU, UK SN - 0 521 52319 2 SP - 1 EP - 359 N2 - - ER - TY - BOOK T1 - Textbook of Psychiatry, 2nd edition. A1 - Puri BK A1 - Laking PJ A1 - Treasaden IH Y1 - 2002/// PB - Churchill Livingstone CY - Edinburgh SN - 0-443-07016-4 N2 - - ER - TY - BOOK T1 - ) SPSS in Practice: An Illustrated Guide, 2nd edition. A1 - Puri BK Y1 - 2002/// PB - Arnold, London and Oxford University Press, New York SN - 0-340-76112-1 N2 - - ER - TY - BOOK T1 - SPSS in practice: an illustrated guide A1 - Puri BK Y1 - 2002/// SN - 0-3407-6112-1 N2 - - ER - TY - BOOK T1 - Handbook of Magnetic Stimulation A1 - Puri BK ED - Pascual-Leone A; Davey N; Rothwell J; Wassermann E; Puri BK Y1 - 2002/// PB - Arnold, London and Oxford University Press, New York SN - 0-340-72009-3 N2 - - ER - TY - BOOK T1 - Medical Image Registration A1 - Hajnal JV ED - Hajnal JV; Hawkes DJ; Hill DG Y1 - 2001/// PB - CRC Press CY - Baton Rouge, Florida. SN - 0-8493-0064-9 N2 - - ER - TY - BOOK T1 - Advance imaging - PET. Challenges in acute coronary syndromes A1 - Camici PG A1 - Spinks TJ Y1 - 2001/// SN - 0-6320-5579-0 N2 - - ER - TY - BOOK T1 - Saunders’ Pocket Essentials of Psychiatry, 2nd edition. A1 - Puri BK Y1 - 2000/// PB - W.B. Saunders CY - Edinburgh SN - 0-7020-2575-5 N2 - - ER - TY - BOOK T1 - Complete MCQs in Psychiatry: Self-Assessment for Parts 1 & 2 of the MRCPsych. A1 - Puri BK A1 - Hall AD Y1 - 1999/// PB - Arnold, London and Oxford University Press, New York SN - 0-340-74035-3 N2 - - ER - TY - BOOK T1 - Sciences Basic to Psychiatry, 2nd edition A1 - Puri BK A1 - Tyrer PJ Y1 - 1999/// PB - Churchill Livingstone CY - Edinburgh SN - 0-443-05514-9 N2 - - ER - TY - BOOK T1 - A Psychiatric Vade Mecum A1 - Puri BK A1 - McKee HM Y1 - 1998/// PB - Arnold, London and Oxford University Press, New York SN - 0-340-69171-9 N2 - - ER - TY - BOOK T1 - Revision Notes in Psychiatry A1 - Puri BK A1 - Hall AD Y1 - 1998/// PB - Arnold, London and Oxford University Press, New York SN - 0-340-66227-1 N2 - - ER - TY - CHAP T1 - Microbulles ciblees pour I'imagerie ultrasonore A1 - Sennoga, CA A1 - Yeh, JS A1 - Seddon, JM A1 - Nourshargh, S A1 - Eckersley, RJ A1 - Haskard, DO A1 - Cosgrove , DO A1 - Nihoyannopoulos, P ED - Tranquart F, Correreas J-M, Bouakaz A T2 - Echographie de Contraste Y1 - 2007/// PB - Springer CY - Paris SP - 321 EP - 328 N2 - - ER - TY - CHAP T1 - Chronic ischaemic heart disease A1 - Crea F A1 - Camici PG A1 - De Caterina R A1 - Lanza GA ED - AJ Camm, TF Leuscher & PW Serruys T2 - The ESC Textbook of Cardiovascular Medicine Y1 - 2006/// PB - Blackwell Publishing CY - Oxford SP - 391 EP - 424 N2 - - ER - TY - CHAP T1 - The application of in vivo MRI and MRS in phenomic studies of murine models of disease A1 - Bell, JD ED - G. Webb T2 - Modern Magnetic Resonance Y1 - 2006/// M2 - 2 PB - Springer CY - UK N2 - - ER - TY - CHAP T1 - Application of MRI to Cell Tracking A1 - Bhakoo, K A1 - Chapon, C A1 - Jackson, J A1 - Jones, W ED - G.A. Webb T2 - Handbook of Modern Magnetic Resonance: Biological Sciences Y1 - 2006/// PB - Springer SP - (in press) N2 - - ER - TY - CHAP T1 - Nuclear Cardiology A1 - Kaufmann P A1 - Camici PG ED - AJ Camm, TF Leuscher & PW Serruys T2 - The ESC Textbook of Cardiovascular Medicine Y1 - 2006/// PB - Blackwell Publishing CY - Oxford SP - 141 EP - 158 N2 - - ER - TY - CHAP T1 - Optimization of MRI Contrast for Pre-Clinical Studies at High Magnetic Field A1 - Kuo, Y-T A1 - Herlihy, A H ED - Graham A. Webb T2 - Modern Magnetic Resonance Y1 - 2006/// M2 - 1 PB - Springer SP - 753 EP - 762 N2 - - ER - TY - CHAP T1 - Molecular basis of hemophilia A A1 - Kemball-Cook, G A1 - Tuddenham, EGD ED - Lee, CA; Berntorp, EE; Hoots, WK T2 - Textbook of Hemophilia Y1 - 2005/// PB - Blackwell CY - Oxford SN - 1 405 12769 4 SP - 19 EP - 26 N2 - - ER - TY - CHAP T1 - Nuclear Magnetic Resonance Spectroscopy in the Study of Human Liver A1 - Lim AKP A1 - Khan SA A1 - Cox IJ A1 - Taylor-Robinson SD ED - Tosi, R., Tugnoli, V. T2 - Nuclear Magnetic Resonance Spectroscopy in the Study of Neoplastic Tissue Y1 - 2005/// PB - Nova Science Publishers Inc. CY - New York SN - 1-59454-258-9 SP - 295 EP - 312 N2 - - ER - TY - CHAP T1 - Application of MRI to Stem Cell Imaging A1 - Bhakoo, K A1 - Jones, W A1 - Jackson, J A1 - Chapon, C ED - N.A. Habib, M.Y. Gordon, N. Levicar et al T2 - Stem Cell Repair and Regeneration Y1 - 2005/// PB - Imperial College Press CY - London N2 - - ER - TY - CHAP T1 - Lipids and depression. A1 - B.K. Puri ED - Shlomo Yehuda & David I. Mostofsky T2 - Nutrients, Stress, and Mental Disorders. Y1 - 2005/// VL - First PB - Humana Press CY - Totowa, New Jersey, USA. SN - 1-58829-432-3 SP - 221 EP - 230 N2 - - UR - http://www.humanapress.com ER - TY - CHAP T1 - Magnetic resonance imaging of injury to the preterm brain. A1 - Dyet LE A1 - Cowan F T2 - Recent advances in Paediatrics Y1 - 2005/// M2 - 22 SP - 85 EP - 104 N2 - - ER - TY - CHAP T1 - The internal capsule in neonatal imaging. A1 - Cowan FM A1 - de Vries LS T2 - Seminars in Fetal and Neonatal Medicine Y1 - 2005/// M2 - 10 SP - 461 EP - 474 N2 - - ER - TY - CHAP T1 - Coronary Flow Reserve A1 - Camici PG ED - JA Bianco T2 - Subclinical atherosclerosis; Beyond Framingham Y1 - 2005/// PB - Taylor and Francis Parthenon Publishing Group CY - London, Oxford, New York N2 - - ER - TY - CHAP T1 - Defining outcome in newborns with neurological problems – a state of the art review. A1 - Graça A A1 - Cowan F T2 - Portuguese Paediatric Journal Y1 - 2005/// N2 - - ER - TY - CHAP T1 - Treatment of Huntington's disease with eicosapentaenoic acid. A1 - B.K. Puri ED - Shlomo Yehuda & David I. Mostofsky. T2 - Nutrients, Stress, and Mental Disorders Y1 - 2005/// VL - First PB - Humana Press. CY - Totowa, New Jersey, USA. SN - 1-58829-432-3 SP - 279 EP - 286 N2 - - UR - http://www.humanapress.com ER - TY - CHAP T1 - Central nervous system complications A1 - Forton DM A1 - Taylor-Robinson SD A1 - Cox IJ A1 - Thomas HC ED - Thomas HC, Lemon S, Zuckerman A. T2 - Viral Hepatitis Y1 - 2005/// VL - 3rd M2 - 29 PB - Blackwell Publishing Ltd CY - Oxford SN - 1-4051-3005-9 SP - 482 EP - 495 N2 - - ER - TY - CHAP T1 - Recent trends in the care complications and outcome of prematurity A1 - Azzopardi D A1 - Mallaiah R ED - Hilary Critchley, Phillip Bennett, Steven Thornton T2 - Preterm Birth Y1 - 2004/// PB - RCOG SN - 1-9003-6492-1 N2 - - ER - TY - CHAP T1 - The value of the autopsy in determining the cause of failure to respond to resuscitation at birth. A1 - Cowan F A1 - Squier W T2 - Seminars in Neonatology Y1 - 2004/// M2 - 9 SP - 331 EP - 345 N2 - - ER - TY - CHAP T1 - The application of magnetic resonance imaging and spectroscopy to gene therapy. A1 - Bhakoo KK A1 - Bell JD A1 - Cox IJ A1 - Taylor-Robinson SD ED - Conn MP T2 - Methods Enzymol. Y1 - 2004/// PB - Elsevier Academic Press SN - 0-12-182791-7 SP - 13 EP - 303 N2 - - ER - TY - CHAP T1 - Apoptosis and Necrosis A1 - Mehmet H A1 - BeesleyJ A1 - Edwards AD ED - Polin R, Fox W, Abman S. T2 - Fetal and neonatal physiology Y1 - 2004/// PB - Saunders CY - Philadelphia SP - 72 EP - 87 N2 - - ER - TY - CHAP T1 - Contrast marginalised gradient template matching A1 - Basalamah S A1 - Bharath A A1 - McRobbie D T2 - Computer Vision - ECCV 2004, Pt 3 Lecture Notes in Computer Science 3023 Y1 - 2004/// SP - 417 EP - 429 N2 - - ER - TY - CHAP T1 - The role of diffusion and perfusion weighted brain imaging in neonatology A1 - Rutherford MA A1 - Counsell SJ ED - JH Gillard, AD Waldman, PB Barker T2 - Clinical MR Neuroimaging Y1 - 2004/// PB - Cambridge University Press CY - Cambridge N2 - - ER - TY - CHAP T1 - Normal Haemostasis A1 - Kemball-Cook, G A1 - Tuddenham, EGD A1 - McVey, JH ED - Hoffbrand, Tuddenham and Catovsky T2 - Postgraduate Haematology Y1 - 2004/// VL - 5th PB - Blackwell CY - Oxford SN - 1 405 10821 5 SP - 783 EP - 807 N2 - - ER - TY - CHAP T1 - The Application of Magnetic Resonance Imaging and Spectroscopy to Gene Therapy A1 - Bhakoo, K K A1 - Bell, J D A1 - Cox, I J A1 - Taylor-Robinson, S D T2 - Methods in Enzymology Y1 - 2004/// VL - Imaging in Biological Research M2 - 386 PB - Elsevier Inc. SP - 303 EP - 313 N2 - - UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15120258&query_hl=7&itool=pubmed_DocSum ER - TY - CHAP T1 - Niacin testing in other psychiatric and neurological disorders. A1 - Puri BK ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry and Neurology, 2nd edition. Y1 - 2003/// PB - Marius Press, CY - Carnforth SN - 1-871622-25-5 SP - 353 EP - 356 N2 - - ER - TY - CHAP T1 - Clinical and biochemical fatty acid abnormalities in dyslexia, dyspraxia and schizotypy: an overview. A1 - Richardson AJ A1 - Cyhlarova E A1 - Puri BK ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry and Neurology, 2nd edition. Y1 - 2003/// PB - Marius Press CY - Carnforth SN - 1-871622-25-5 SP - 477 EP - 490 N2 - - ER - TY - CHAP T1 - A possible role for fatty acid treatment in paediatric depression. A1 - Puri BK ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry and Neurology, 2nd edition. Y1 - 2003/// PB - Marius Press CY - Carnforth SN - 1-871622-25-5 SP - 543 EP - 550 N2 - - ER - TY - CHAP T1 - The pathogenesis of Atherosclerosis A1 - Naoumova RP A1 - Scott J ED - Warrell D, Cox T, Firth J T2 - Oxford Textbook of Medicine 4th Edition Y1 - 2003/// PB - Oxford University Press SP - 797 EP - 801 N2 - - ER - TY - CHAP T1 - Positron emission tomography A1 - Camici PG A1 - Rosen SD ED - PJ Ell & SS Gambhir T2 - Nuclear Medicine in Clinical Diagnosis and Treatment Y1 - 2003/// VL - 3rd Edition PB - Churchill-Livingstone CY - London SP - 1075 EP - 1091 N2 - - ER - TY - CHAP T1 - Diagnosis of heart disease in diabetes. New insights into myocardial insulin resistance A1 - Barnes E A1 - Camici PG ED - W Stanley & L Ryden T2 - The Diabetic Coronary Patient Y1 - 2003/// PB - Science Press Ltd CY - London SP - 41 EP - 52 N2 - - ER - TY - CHAP T1 - Long-term follow-up of a single patient with schizophrenia treated with ethyl-EPA alone. A1 - Puri BK A1 - Richardson AJ ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry and Neurology, 2nd edition. Y1 - 2003/// PB - Marius Press CY - Carnforth SN - 1-871622-25-5 SP - 377 EP - 390 N2 - - ER - TY - CHAP T1 - A randomised trial of ethyl eicosapentaenoate in end-stage patients with Huntington’s disease. A1 - Puri BK ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry and Neurology, 2nd edition. Y1 - 2003/// PB - Marius Press CY - Carnforth SN - 1-871622-25-5 SP - 575 EP - 582 N2 - - ER - TY - CHAP T1 - Methodology for imaging time-dependent phenomena A1 - Eckersley RJ A1 - Bamber JC ED - C. R. Hill, J. C. Bamber, and G. R. ter Haar T2 - Physical principles of medical ultrasonics Y1 - 2003/// PB - John Wiley & Sons, Ltd CY - London N2 - - ER - TY - CHAP T1 - Hypothalamic neuropeptides and regulation of fat mass in Prader-Willi syndrome A1 - AP Goldstone A1 - UA Unmehopa A1 - Thomas EL A1 - AE Brynes A1 - JD Bell A1 - G Frost A1 - MA Ghatei A1 - A Holland A1 - SR Bloom A1 - DF Swaab ED - U Eiholzer, D l’Allemand, W Zipf T2 - Prader-Willi Syndrome as a Model for Obesity Y1 - 2003/// PB - Karger CY - Basel SN - 3805575742 SP - 31 EP - 43 N2 - - ER - TY - CHAP T1 - Magnetic resonance spectroscopy in the assessment of brain phospholipid metabolism in dyslexia. A1 - Puri BK A1 - Richardson AJ ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry and Neurology, 2nd edition. Y1 - 2003/// PB - Marius Press CY - Carnforth SN - 1-871622-25-5 SP - 501 EP - 510 N2 - - ER - TY - CHAP T1 - Mood and emotion A1 - Puri BK T2 - Handbook of transcrannial Magnetic Stimulation Y1 - 2002/// SN - 0-3407-2009-3 SP - 335 EP - 338 N2 - - ER - TY - CHAP T1 - Electromagnetic fields A1 - Hand JW T2 - Practical radiation protection in healthcare Y1 - 2002/// SN - 0-1926-3082-2 SP - 369 EP - 391 N2 - - ER - TY - CHAP T1 - The magnetic resonance imaging appearances of the normal infant brain from term to two years. A1 - Cowan FM ED - Rutherford M A T2 - MR of the Neonatal Brain. Y1 - 2002/// PB - Harcourt Health Sciences CY - London N2 - - ER - TY - CHAP T1 - Apoptosis and necrosis in perinatal brain injury A1 - Edwards AD A1 - Mehmet H T2 - Birth asphyxia and the brain: basic science and clinical implications Y1 - 2002/// SN - 0-8799-3499-9 SP - 135 EP - 152 N2 - - ER - TY - CHAP T1 - Hypoxic-ischaemic encephalopathy A1 - Edwards AD A1 - Mehmet H A1 - Hagberg H T2 - The newborn brain;neuroscience and clinical applications Y1 - 2002/// SN - 0-5217-9338-6 SP - 385 EP - 414 N2 - - ER - TY - CHAP T1 - Hypoxic-ischaemic encephalopathy A1 - Edwards AD A1 - Mehmet H A1 - Hagberg H T2 - The newborn brain;neuroscience and clinical applications Y1 - 2002/// SN - 0-5217-9338-6 SP - 385 EP - 414 N2 - - ER - TY - CHAP T1 - Magnetic resonance spectroscopy of the neonatal brain A1 - Robertson NJ A1 - Cox IJ ED - Rutherford MA T2 - Magnetic Resonance Imaging of the Neonatal Brain Y1 - 2002/// PB - WB Saunders SN - 07020 25348 SP - 295 EP - 314 N2 - - ER - TY - CHAP T1 - Hyperthermia in the treatment of cancer A1 - Vernon CC A1 - Hand JW T2 - Treatment of cancer Y1 - 2002/// M2 - 4th SN - 0-3407-5964-X SP - 81 EP - 102 N2 - - ER - TY - CHAP T1 - Transcranial magnetic stimulation in psychiatry:introduction A1 - Puri BK T2 - Handbook of transcranial stimulation Y1 - 2002/// SN - 0-3407-2009-3 SP - 360 N2 - - ER - TY - CHAP T1 - The use of transcranial magnetic stimulation in major psychiatric disorders A1 - Puri BK T2 - Handbook of transcranial stimulation Y1 - 2002/// SN - 0-3407-2009-3 SP - 396 EP - 399 N2 - - ER - TY - CHAP T1 - Cardiac Positron Emission Tomography A1 - Camici PG ED - F Fedele T2 - Incontri di Cardiologia e Pneumologia Y1 - 2002/// PB - CEDIS Editore Roma SP - 44 EP - 48 N2 - - ER - TY - CHAP T1 - Preparation of the iodine-124 derivative of the Bolton-Hunter reagent ([I-124]I-SHPP) and its use for labelling a VEGF antibody a a PET tracer A1 - Glaser M A1 - Carroll VA A1 - Collingridge DR A1 - Aboagye EO A1 - Price P A1 - Bicknell R A1 - Harris AL A1 - Luthra SK A1 - Brady F T2 - Journalof labelled compounds & radiopharmaceuticals Y1 - 2002/// SP - 1077 EP - 1090 N2 - - ER - TY - CHAP T1 - Apoptosis and necrosis in perinatal brain injury A1 - Edwards AD A1 - Mehmet H T2 - Birth asphyxia and the brain: basic science and clinical implications Y1 - 2002/// M2 - 7 SN - 0-8799-3499-9 SP - 135 EP - 152 N2 - - ER - TY - CHAP T1 - Metabolic disorders of the newborn A1 - Patay Z A1 - Robertson NJ A1 - Cox IJ ED - Rutherford MA T2 - Magnetic Resonance Imaging of the Neonatal Brain Y1 - 2002/// PB - WB Saunders SN - 07020 25348 SP - 315 EP - 348 N2 - - ER - TY - CHAP T1 - Advance imaging - PET A1 - Camici PG ED - De Bono and Sobel T2 - Challenges in Acute Coronary Syndromes Y1 - 2001/// PB - Blackwell Science CY - Oxford SP - 148 EP - 172 N2 - - ER - TY - CHAP T1 - Imaging the preterm neonate A1 - Maalouf EF A1 - Counsell SJ ED - Rutherford MA T2 - magnetic resonance imaging of the neonatal brain Y1 - 2001/// PB - WB Saunders CY - London N2 - - ER - TY - CHAP T1 - Liver in vivo magnetic resonance spectroscopy of humans. A1 - Cox IJ ED - Young IR, Grant DM, Harris RK. T2 - Methods in Biomedical Magnetic Resonance Imaging and Spectroscopy Y1 - 2000/10// PB - John Wiley & Sons CY - Chichester SN - 0471-98804-9 N2 - - ER - TY - CHAP T1 - The pathogenesis of atherosclerosis A1 - Naoumova RP A1 - Scott J ED - Weatherall DJ, Lendingham JG, Warrell DA T2 - Concise Oxford Textbook of Medicine Y1 - 2000/// PB - Oxford University Press SP - 48 EP - 50 N2 - - ER - TY - CHAP T1 - Psychiatric disorders and how to spot them. A1 - Puri BK ED - P.J. Tredgold and D. Gray T2 - An Introduction to the Signs and Symptoms of Clinical Medicine Y1 - 2000/// PB - Arnold, London and Oxford University Press, New York SN - 0-340-73207-5 SP - 147 EP - 159 N2 - - ER - TY - CHAP T1 - MRI and MRS in neuropsychiatry. A1 - Puri BK ED - I.R. Young, D.M. Grant and R.K. Harris T2 - Methods in Biomedical Magnetic Resonance Imaging and Spectroscopy Y1 - 2000/// PB - Wiley CY - New York SN - 0-471-98804-9 SP - 1135 EP - 1143 N2 - - ER - TY - CHAP T1 - Outcome after intrapartum asphyxia in term infants. A1 - Cowan F T2 - Seminars in Neonatology Y1 - 2000/// M2 - 5 SP - 127 EP - 140 N2 - - ER - TY - CHAP T1 - Clinical investigation of the microcirculation in patients with cardiovascular disease A1 - Camici PG ED - HAJ Struijker & G Ambrosio T2 - Microcirculation and Cardiovascular Disease Y1 - 2000/// PB - Lippincott, Williams & Wilkins SP - 127 EP - 142 N2 - - ER - TY - CHAP T1 - Insights into the pathophysiology of syndrome X obtained using Positron Emission Tomography 9PET) A1 - Rosen SD A1 - Camici PG ED - JC Kaski T2 - Chest Pain with Normal Coronary Angiograms Y1 - 1999/// PB - Kluwer Academic Publishers CY - London SP - 69 EP - 80 N2 - - ER - TY - CHAP T1 - Sustained remission of symptoms following treatment with eicosapentaenoic acid in a case of schizophrenia with dyslexia. A1 - Richardson AJ A1 - Puri BK ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry Y1 - 1999/// PB - Marius Press, CY - Carnforth SN - 1-871622-10-7 SP - 181 EP - 188 N2 - - ER - TY - CHAP T1 - Diagnosis of heart disease in diabetes. New insights into myocardial insulin resistance A1 - Barnes E A1 - Camici PG ED - W Stanley T2 - The Diabetic Coronary Patient Y1 - 1999/// PB - Science Press Ltd CY - London SP - 39 EP - 50 N2 - - ER - TY - CHAP T1 - La fisiopatologia dell'angina post-prandiale. Conoscere e Curare il Cuore '99 A1 - Camici PG ED - Prati PL T2 - Atti XVI Simposio del centro per la lotta contro l'infarto Y1 - 1999/// PB - Novartis Edizioni SP - 101 EP - 106 N2 - - ER - TY - CHAP T1 - Brain phospholipid metabolism in dyslexia assessed by magnetic resonance spectroscopy. A1 - Puri BK A1 - Richardson AJ ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry Y1 - 1999/// PB - Marius Press CY - Carnforth SN - 1-871622-10-7 SP - 243 EP - 249 N2 - - ER - TY - CHAP T1 - Essential fatty acids in dyslexia: theory, evidence and clinical trials. A1 - Richardson AJ A1 - Easton T A1 - McDaid AM A1 - Hall JA A1 - Montgomery P A1 - Clisby C A1 - Puri BK ED - A.I.M Glen, M. Peet and D.F. Horrobin T2 - Phospholipid Spectrum Disorder in Psychiatry. Y1 - 1999/// PB - Marius Press CY - Carnforth SN - 1-871622-10-7 SP - 225 EP - 241 N2 - - ER - TY - CHAP T1 - The coronary microcirculation and myocardial ischemia A1 - Camici PG A1 - Rimoldi O ED - E Van Der Wall, P Blanska, MG Niemeyer, W Vaalburg, JGMH Crijns T2 - Advanced imaging in coronary artery disease Y1 - 1998/// PB - Kluwer Academic Publishers CY - London N2 - - ER - TY - CHAP T1 - Positron Emission Tomorgraphy A1 - Camici PG ED - IPC Murray & PJ Ell T2 - Nuclear Medicine in Clinical Diagnosis and Treatment Y1 - 1998/// VL - 2nd Edition PB - Churchill-Livingstone CY - London SP - 1353 EP - 1368 N2 - - ER - TY - CHAP T1 - Magnetic resonance imaging of the neonatal brain. A1 - Maalouf E A1 - Counsell S A1 - Battin M A1 - Cowan F T2 - British Journal of Hospital Medicine Y1 - 1998/// M2 - 59 SP - 41 EP - 45 N2 - - ER - TY - CHAP T1 - Diagnosi di vitalita miocardia: ruolo della PET A1 - Camici PG ED - A Maresta, R Casanova, M Dondi T2 - La Cardiologia Nucleare Nel'infarto Miocardico Y1 - 1998/// PB - Centro Scientifico Editore N2 - - ER - TY - CHAP T1 - Sedation for Magnetic Sedation for Magnetic Resonance Scanning of Infants and Young Children. A1 - Cowan FM ED - Whitwam JG & McCloy RF. T2 - Principles and Practice of Sedation. Y1 - 1998/// PB - Blackwell Healthcare CY - London SP - 206 EP - 213 N2 - - ER - TY - CHAP T1 - Detection and clinical consequences of myocardial ischaemia and reduced coronary reserve A1 - Camici PG ED - F Camerini, A Gavazzi & R De Maria T2 - Advances in Cardio-myopathies Y1 - 1997/// PB - Springer-Verlag CY - Berlin SP - 36 EP - 41 N2 - - ER - TY - CHAP T1 - Recent Advances in the management of the premature infant A1 - Mupanemunda R A1 - Azzopardi D ED - MG Elder, R Romero, RF Lamont T2 - Preterm Birth Y1 - 1997/// PB - Churchill Livingstone SN - 0-443-05857-1 N2 - - ER - TY - CHAP T1 - The Molecular Defect in Hemophilia A A1 - Kemball-Cook, G A1 - Tuddenham, EGD ED - Forbes, CD; Aledort, L; Madhok, R T2 - Hemophilia Y1 - 1997/// PB - Chapman & Hall CY - London SN - 0 412 63820 7 SP - 21 EP - 33 N2 - - ER - TY - CONF T1 - Genetic mutations in the ras/raf/mapkinase pathway results in cherubism A1 - Idowu, BD A1 - Mangion, J A1 - Gale, RE A1 - Flanagan, AM U1 - Annual Meeting of the Bone-Research-Society Y1 - 2007/07// Y2 - // VL - 22 SP - 1124 EP - 1124 N2 - - ER - TY - CONF T1 - Quantifying brain development in early childhood using segmentation and registration - art. no. 65120O A1 - Aljabar, P A1 - Bhatia, KK A1 - Murgasova, M A1 - Hajnal, JV A1 - Boardman, JP A1 - Srinivasan, L A1 - Rutherford, MA A1 - Dyet, LE A1 - Edwards, AD A1 - Rueckert, D U1 - Medical Imaging 2007 Conference Y1 - 2007/// Y2 - // VL - 6512 SP - O5120 EP - O5120 N2 - - ER - TY - CONF T1 - STIR: Software for Tomographic Image Reconstruction Release 2 A1 - Thielemans, K A1 - Mustafovic, S A1 - Tsoumpas, C A2 - Philips B. U1 - Nuclear Science Symposium and Medical Imaging Conference AD - San Diego, California, USA J1 - Nuclear Science Symposium Conference Record Y1 - 2006/10// Y2 - 2006/10/20/ VL - 4 PB - IEEE SN - 1082-3654 SP - 2174 EP - 2176 N2 - - L1 - http://www.ieee.org ER - TY - CONF T1 - A variant in the thrombomodulin promoter leads to impaired expression in response to inflammatory cytokines; previous CHD-risk association explained A1 - Konstantoulas, CJ A1 - Cooper, J A1 - Grizenkova, J A1 - Miller, GJ A1 - Humphries, SE A1 - Ireland, H U1 - 14th Meeting of the International-Society-of-Atherosclerosis Y1 - 2006/06// Y2 - // VL - 7 SP - 315 EP - 315 N2 - - ER - TY - CONF T1 - Automatic Extraction and Matching of Neonatal Cerebral Vasculature A1 - Xue H A1 - Malamateniou C A1 - Allsop J A1 - Srinivasan L A1 - Hajnal J A1 - Rueckert D U1 - IEEE International Symposium on Biomedical Imaging Y1 - 2006/04// PB - IEEE SP - 125 EP - 128 N2 - - UR - http://pubs.doc.ic.ac.uk/isbi-06-neonatal-vasculature ER - TY - CONF T1 - Analysis of Growth in the Developing Brain Using Non-Rigid Registration A1 - Aljabar P A1 - Bhatia KK A1 - Hajnal J A1 - Boardman J A1 - Srinivasan L A1 - Rutherford M A1 - Dyet L A1 - Edwards A A1 - Rueckert D U1 - IEEE International Symposium on Biomedical Imaging Y1 - 2006/04// PB - IEEE SP - 201 EP - 204 N2 - - UR - http://pubs.doc.ic.ac.uk/isbi-06-brain-growth ER - TY - CONF T1 - A novel approach to accurate 3D high resolution and high SNR fetal brain imaging A1 - Jiang, SZ A1 - Xue, H A1 - Glover, A A1 - Rutherford, M A1 - Hajnal, JV U1 - 3rd IEEE International Symposium on Biomedical Imaging Y1 - 2006/// Y2 - // SP - 662 EP - 665 N2 - - ER - TY - CONF T1 - Cell-type specific experience-dependent structural plasticity of axonal branches and boutons in the adult neocortex. A1 - De Paola, V. A1 - Song, S. A1 - Holtmaat, A. A1 - Wilbrecht, L. A1 - Knott, G. A1 - Caroni, P. A1 - Svoboda, K. U1 - EMBO Fellows meeting AD - La Jolla, USA Y1 - 2006/// N2 - - ER - TY - CONF T1 - Neuroprotection with hypothermia following birth asphyxia A1 - Azzopardi, D U1 - 20th European Congress of Perinatal Medicine Y1 - 2006/// Y2 - // SP - 221 EP - 229 N2 - - ER - TY - CONF T1 - Effect of random coincidences for quantitative cardiac PET studies using 3D oxygen-15 water scans - art. no. 61424K A1 - Bouchareb, Y A1 - Thielemans, K A1 - Spinks, T A1 - Rimoldi, O A1 - Camici, PG U1 - Medical Imaging 2006 Conference Y1 - 2006/// Y2 - // VL - 6142 SP - K1424 EP - K1424 N2 - - ER - TY - CONF T1 - Two-dimensional ultrasonic phased arrays in an application for noninvasive surgery: Random or regular? A1 - Filonenko, EA A1 - Hand, JW A1 - Gavrilov, LR A1 - Khokhlova, VA U1 - 5th International Symposium on Therapeutic Ultrasound Y1 - 2006/// Y2 - // VL - 829 SP - 385 EP - 389 N2 - - ER - TY - CONF T1 - Whole brain morphometric analysis of changes associated with pre-term birth - art. no. 61445Y A1 - Thomaz, CE A1 - Boardman, JP A1 - Counsell, S A1 - Hill, DLG A1 - Hajnal, JV A1 - Edwards, AD A1 - Rutherford, MA A1 - Gillies, DF A1 - Rueckert, D U1 - Medical Imaging 2006 Conference Y1 - 2006/// Y2 - // VL - 6144 SP - Y1445 EP - Y1445 N2 - - ER - TY - CONF T1 - The Challenges of developing a collaborative data and compute grid for Neurosciences A1 - Geddes, J A1 - Mackay, C A1 - Lloyd, S A1 - Simpson, A A1 - Power, D A1 - Russell, D A1 - Katzarova, M A1 - Rossor, M A1 - Fox, N A1 - Fletcher, J A1 - Hill, D A1 - McLeish, K A1 - Hajnal, JV A1 - Lawrie, S A1 - Job, D A1 - McIntosh, A A1 - Wardlaw, J A1 - Sandercock, P A1 - Palmer, J A1 - Perry, D A1 - Procter, R A1 - Ure, J A1 - Bath, P A1 - Watson, G U1 - 19th IEEE Symposium on Computer-Based Medical Systems Y1 - 2006/// Y2 - // SP - 81 EP - 86 N2 - - ER - TY - CONF T1 - Cell-type specific experience-dependent structural plasticity of axonal branches and boutons in the adult neocortex. A1 - De Paola, V. A1 - Song, S. A1 - Holtmaat, A. A1 - Wilbrecht, L. A1 - Knott, G. A1 - Caroni, P. A1 - Svoboda, K. U1 - FENS 2006 AD - Vienna, Austria Y1 - 2006/// N2 - - ER - TY - CONF T1 - Scatter Simulation Including Double Scatter A1 - Tsoumpas, C A1 - Aguiar, P A1 - Ros, D A1 - Dikaios, N A1 - Thielemans, K A2 - Yu B U1 - Nuclear Science Symposium & Medical Imaging Conference AD - Fajardo, Puerto Rico J1 - IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD Y1 - 2005/10/29/ Y2 - 2005/// VL - 1-5 PB - IEEE CY - 345 E 47TH ST, NEW YORK, NY 10017 USA SN - 1082-3654 SP - 1615 EP - 1619 N2 - - ER - TY - CONF T1 - Novel genetic predisposition to coronary heart disease associated with the protein C pathway A1 - Ireland, H A1 - Konstantoulas, CJ A1 - Humphries, SE A1 - Ohlin, AK A1 - Mather, H A1 - Goodall, AH A1 - Hogwood, J A1 - Stearns-Kurosawa, DJ A1 - Kurosawa, S A1 - Esmon, CT U1 - BSCR Spring Meeting 2005 Y1 - 2005/07// Y2 - // VL - 91 SP - U244 EP - U244 N2 - - ER - TY - CONF T1 - A thrombomodulin haplotype (V/DELTT), associated with risk of coronary heart disease, does not influence plasma levels of soluble thrombomodulin A1 - Konstantoulas, C A1 - Cooper, J A1 - Warnock, G A1 - Miller, GJ U1 - 75th Congress of the European-Atherosclerosis-Society Y1 - 2005/04// Y2 - // VL - 6 SP - 94 EP - 94 N2 - - ER - TY - CONF T1 - EPCR genotype 6936A > G (Ser219Gly): Reduced APC generation in Gly homozygotes with type 2 diabetes A1 - Ireland, H A1 - Konstantoulas, C A1 - Humphries, SE A1 - Mather, H A1 - Goodall, AH A1 - Hogwood, J A1 - Esmon, CT U1 - 75th Congress of the European-Atherosclerosis-Society Y1 - 2005/04// Y2 - // VL - 6 SP - 92 EP - 92 N2 - - ER - TY - CONF T1 - Modeling the nonlinear microbubble response to coded, multi-pulse sequences A1 - Chetty, K A1 - Eckersley, RJ U1 - 2005 IEEE International Ultrasonics Symposium Y1 - 2005/// Y2 - // SP - 2007 EP - 2010 N2 - - ER - TY - CONF T1 - Nonlinear corruption of ultasound transmission by microbubble contrast agents A1 - Eckersley, RJ A1 - Tang, MX U1 - 2005 IEEE International Ultrasonics Symposium Y1 - 2005/// Y2 - // SP - 1691 EP - 1694 N2 - - ER - TY - CONF T1 - Scatter estimation and motion correction in PET A1 - Thielemans, K U1 - Nuclear Science Symposium/Medical Imaging Conference Y1 - 2005/// Y2 - // SP - 1745 EP - 1747 N2 - - ER - TY - CONF T1 - Comparison of analytic and iterative reconstruction methods for quantitative cardiac PET studies in 3D using oxygen-15 water scans A1 - Bouchareb, Y A1 - Thielemans, K A1 - Spinks, T A1 - Rimoldi, O A1 - Camici, PG U1 - Nuclear Science Symposium/Medical Imaging Conference Y1 - 2005/// Y2 - // SP - 2120 EP - 2123 N2 - - ER - TY - CONF T1 - Dendritic spine shape affects membrane-bound protein flux between the spine head and the dendritic shaft. A1 - S.Hugel A1 - V. De Paola A1 - P.Caroni A1 - B.H.Gahwiler A1 - R.A.McKinney U1 - Society for Neuroscience Meeting AD - Washington, DC, USA Y1 - 2005/// N2 - - ER - TY - CONF T1 - Propagating labels of the human brain based on non-rigid MR image registration: an evaluation A1 - Heckemann, RA A1 - Hajnal, JV A1 - Rueckert, D A1 - Hill, DLG A1 - Hammers, A U1 - Medical Imaging 2005 Conference Y1 - 2005/// Y2 - // VL - 5747 SP - 1864 EP - 1871 N2 - - ER - TY - CONF T1 - Long-term 2-photon imaging of cortical axons and their boutons in adult mice. A1 - De Paola, V. A1 - Song, S. A1 - Holtmaat, A. A1 - Wilbrecht, L., A1 - Knott, G. A1 - Caroni, P. U1 - Imaging Neurons and Neural Activity: New Methods, New Results. AD - Cold Spring Harbor Laboratory, NY, USA Y1 - 2005/// N2 - - ER - TY - CONF T1 - NeuroGrid: Using grid technology to advance neuroscience A1 - Geddes, J A1 - Lloyd, S A1 - Simpson, A A1 - Rossor, M A1 - Fox, N A1 - Hill, D A1 - Hajnal, JV A1 - Lawrie, S A1 - McIntosh, A A1 - Johnstone, E A1 - Wardlaw, J A1 - Perry, D A1 - Procter, R A1 - Bath, P A1 - Bullmore, E U1 - 18th IEEE Symposium on Computer-Based Medical Systems Y1 - 2005/// Y2 - // SP - 570 EP - 572 N2 - - ER - TY - CONF T1 - Evaluation of the single scatter simulation algorithm implemented in the STIR library A1 - Tsoumpas, C A1 - Aguiar, P A1 - Nikita, KS A1 - Ros, D A1 - Thielemans, K U1 - Nuclear Science Symposium/Medical Imaging Conference Y1 - 2004/// Y2 - // SP - 3361 EP - 3365 N2 - - ER - TY - CONF T1 - In vivo imaging of cortical axon dynamics during early postnatal development reveals long-range growth and pruning prior to stable bouton formation. A1 - C.Portera-Cailliau A1 - V. De Paola A1 - P.Caroni A1 - R.Yuste A1 - K.Svoboda U1 - Society for Neuroscience Meeting. AD - San Diego, California, USA Y1 - 2004/// N2 - - ER - TY - CONF T1 - Consistent groupwise non-rigid registration for atlas construction A1 - Bhatia K A1 - Hajnal JV A1 - Puri BK A1 - Edwards AD A1 - Rueckert D U1 - MICCAI Conference Y1 - 2004/// Y2 - 2004/// N2 - - ER - TY - CONF T1 - Using a maximum uncertainly LDA-based approach to classify and analyse MR brain images A1 - Thomaz CE A1 - Boardman JP A1 - Hill D A1 - Hajnal JV A1 - Edwards AD A1 - Rutherford M A1 - Rueckert D U1 - MICCAI Conference Y1 - 2004/// Y2 - 2004/// N2 - - ER - TY - CONF T1 - A study of pressure-dependent attenuation in ultrasound contrast imaging A1 - Tang, MX A1 - Eckersley, RJ A1 - Noble, JA U1 - 2nd IEEE International Symposium on Biomedical Imaging Y1 - 2004/// Y2 - // SP - 516 EP - 519 N2 - - ER - TY - CONF T1 - Long-term imaging of pre-synaptic terminals in the adult somatosensory cortex in vivo. A1 - De Paola, V. A1 - Song, S A1 - Holtmaat, A. A1 - Wilbrecht, L. A1 - Caroni, P. A1 - Svoboda, K. U1 - Society for Neuroscience Meeting. AD - San Diego, California, USA Y1 - 2004/// N2 - - ER - TY - CONF T1 - Analysis of serial MR images of joints A1 - Leung, KK A1 - Heckemann, RA A1 - Saeed, N A1 - Brooks, KJ A1 - Buckton, JB A1 - Changani, K A1 - Reid, DG A1 - Rueckert, D A1 - Hajnal, JV A1 - Holden, M A1 - Hill, DLG U1 - 2nd IEEE International Symposium on Biomedical Imaging Y1 - 2004/// Y2 - // SP - 221 EP - 224 N2 - - ER - TY - CONF T1 - The derivation of detector efficiencies in PET from single photon blank scans A1 - Hogg, D A1 - Thielemans, K A1 - Spinks, TJ U1 - IEEE Nuclear Science Symposium/Medical Imaging Conference Y1 - 2004/// Y2 - // SP - 2206 EP - 2209 N2 - - ER - TY - CONF T1 - Characterization of novel microbubble contrast agents A1 - Eckersley, RJ A1 - Sennoga, CA A1 - Campbell, RC A1 - Blomley, MJK U1 - IEEE International Ultrasonics Symposium Y1 - 2003/// Y2 - // SP - 1499 EP - 1502 N2 - - ER - TY - CONF T1 - Comparison of unconventional inter-filtering methods to penalised-likelihood for space-invariant tomographs A1 - Mustafovic, S A1 - Thielemans, K U1 - IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC) Y1 - 2003/// Y2 - // SP - 1691 EP - 1695 N2 - - ER - TY - CONF T1 - Additive and multiplicative versions of the maximum a posteriori algorithm with median root prior A1 - Mustafovic, S A1 - Thielemans, K U1 - IEEE Nuclear Science Symposium Y1 - 2002/// Y2 - // SP - 1783 EP - 1785 N2 - - ER - TY - CONF T1 - Normalisation of listmode data with application to HiDAC data A1 - Thielemans, K A1 - Morel, C A1 - Jacobson, MW A1 - Kaempf, JH A1 - Mustafovic, S U1 - IEEE Nuclear Science Symposium Y1 - 2002/// Y2 - // SP - 1559 EP - 1563 N2 - - ER - TY - CONF T1 - High Resolution Visualization of Synaptic Morphology and Dynamics in Transgenic Mice Expressing GFP-Fusion Proteins In Single Neurons. A1 - De Paola, V. A1 - Sadhu, A. A1 - Pajusola, K. A1 - Pun, S. A1 - Xu, L. A1 - Arber, S. A1 - McKinney, R.A. A1 - Caroni, P. U1 - EMBO/FMI Conference. Organizing the Brain: Genes, Neurons, and Circuits. AD - Ascona, Switzerland Y1 - 2002/// N2 - - ER - TY - CONF T1 - Object dependency of resolution and convergence rate in OSEM with filtering A1 - Mustafovic, S A1 - Thielemans, K A1 - Hogg, D A1 - Bloomfield, P U1 - IEEE Nuclear Science Symposium Y1 - 2002/// Y2 - // SP - 1786 EP - 1790 N2 - - ER - TY - CONF T1 - Glutamate spillover triggers changes in synaptic connectivity. A1 - D. Richards A1 - V. De Paola A1 - P. Caroni A1 - B. Gähwiler A1 - R.A. McKinney U1 - Society for Neuroscience Meeting AD - Orlando, Florida, USA Y1 - 2002/// N2 - - ER - TY - CONF T1 - Presynaptic terminal dynamics in mature hippocampal networks. A1 - De Paola, V. A1 - Caroni, P. U1 - USGEB Young Investigator Meeting AD - Lausanne, Switzerland Y1 - 2001/// N2 - - ER - TY - CONF T1 - Bacterial replication initiator DnaA. Rules for DnaA binding and roles of DnaA in origin unwinding and helicase loading A1 - Messer, W A1 - Blaesing, F A1 - Jakimowicz, D A1 - Krause, M A1 - Majka, J A1 - Nardmann, J A1 - Schaper, S A1 - Seitz, H A1 - Speck, C A1 - Weigel, C A1 - Wegrzyn, G A1 - Welzeck, M A1 - Zakrzewska-Czerwinska, J U1 - EMBO Workshop on the Nucleoid Organisation and the Cell Cycle Y1 - 2001/01// Y2 - // VL - 83 SP - 5 EP - 12 N2 - - ER - TY - CONF T1 - PET image reconstruction by vector norm optimization A1 - Maros,I. A1 - Thielemans,K. U1 - International workshop on medical imaging and augmented reality (MIRA 2001), Hong Kong, Peoples Republic of China Y1 - 2001/// PB - IEEE Computer Soc CY - Los Alamitos SP - 152 EP - 156 N2 - - ER - TY - CONF T1 - Coronary microcirculatory dysfunction in aortic stenosis A1 - Rajappan, K A1 - Rimoldi, O A1 - Pennell, DJ A1 - Camici, PG A1 - Sheridan, DJ U1 - 28th Annual Meeting on Computers in Cardiology Y1 - 2001/// Y2 - // VL - 28 SP - 289 EP - 292 N2 - - ER - TY - CONF T1 - Algorithm for retrieval of deep brain temperature in new-born infant from microwave radiometric data A1 - Mizushina, S A1 - Maruyma, K A1 - Sugiura, T A1 - Van Leeuwen, GMJ A1 - Hand, JW A1 - Marrocco, G A1 - Bardati, F A1 - Edwards, AD A1 - Azzopardi, D A1 - Land, D U1 - IEEE MTT-S International Microwave Symposium (IMS2000) Y1 - 2000/// Y2 - // SP - 1033 EP - 1036 N2 - - ER - TY - CONF T1 - Functional domains of DnaA proteins A1 - Messer, W A1 - Blaesing, F A1 - Majka, J A1 - Nardmann, J A1 - Schaper, S A1 - Schmidt, A A1 - Seitz, H A1 - Speck, C A1 - Tungler, D A1 - Wegrzyn, G A1 - Weigel, C A1 - Welzeck, M A1 - Zakrzewska-Czerwinska, J U1 - Bacterial Cell Cycle Meeting Y1 - 1999/08// Y2 - // VL - 81 SP - 819 EP - 825 N2 - - ER - TY - CONF T1 - Transgenic mice expressing GFP fusion proteins in adult neurons of the central and peripheral nervous system. A1 - De Paola, V. A1 - Caroni, P. U1 - EMBO/FMI Conference. Neuronal Circuits: From Molecules to Organisms. AD - Ascona, Switzerland Y1 - 1999/// N2 - - ER - TY - CONF T1 - Ultrasound hyperthermia and the prediction of heating A1 - Hand, JW U1 - 3rd Mayneord-Phillips Summer School Y1 - 1998/// Y2 - // SP - 151 EP - 176 N2 - - ER - TY - CONF T1 - Functional imaging of tissue response to bolus injection of ultrasound contrast agent A1 - Eckersley, RJ A1 - Cosgrove, DO A1 - Blomley, MJ A1 - Hashimoto, H U1 - 1998 IEEE Ultrasonics Symposium Y1 - 1998/// Y2 - // SP - 1779 EP - 1782 N2 - - ER - TY - CONF T1 - The coronary microcirculation and myocardial ischemia A1 - Camici, PG A1 - Rimoldi, O U1 - 2nd European Conference on Cardiac PET Research Y1 - 1998/// Y2 - // VL - 202 SP - 101 EP - 107 N2 - - ER - TY - CONF T1 - Targeted-GFP expression in adult neurons of transgenic mice. A1 - De Paola, V. A1 - Caroni, P. U1 - 2nd Swiss Meeting on Muscle Research AD - Macolin, Switzerland Y1 - 1998/// N2 - - ER - TY - JFULL T1 - Role of the highly structured 5'-end region of MDR1 mRNA in P-glycoprotein expression. A1 - Randle, RA A1 - Raguz, S A1 - Higgins, CF A1 - Yagüe, E J1 - Biochem J Y1 - 2007/09/15/ VL - 406 SN - 1470-8728 SP - 445 EP - 455 N2 - Overexpression of P-glycoprotein, encoded by the MDR1 (multidrug resistance 1) gene, is often responsible for multidrug resistance in acute myeloid leukaemia. We have shown previously that MDR1 (P-glycoprotein) mRNA levels in K562 leukaemic cells exposed to cytotoxic drugs are up-regulated but P-glycoprotein expression is translationally blocked. In the present study we show that cytotoxic drugs down-regulate the Akt signalling pathway, leading to hypophosphorylation of the translational repressor 4E-BP [eIF (eukaryotic initiation factor) 4E-binding protein] and decreased eIF4E availability. The 5'-end of MDR1 mRNA adopts a highly-structured fold. Fusion of this structured 5'-region upstream of a reporter gene impeded its efficient translation, specifically under cytotoxic stress, by reducing its competitive ability for the translational machinery. The effect of cytotoxic stress could be mimicked in vivo by blocking the phosphorylation of 4E-BP by mTOR (mammalian target of rapamycin) using rapamycin or eIF4E siRNA (small interfering RNA), and relieved by overexpression of either eIF4E or constitutively-active Akt. Upon drug exposure MDR1 mRNA was up-regulated, apparently stochastically, in a small proportion of cells. Only in these cells could MDR1 mRNA compete successfully for the reduced amounts of eIF4E and translate P-glycoprotein. Consequent drug efflux and restoration of eIF4E availability results in a feed-forward relief from stress-induced translational repression and to the acquisition of drug resistance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17573715&query_hl=1 ER - TY - JFULL T1 - Targeting of adenovirus serotype 5 (Ad5) and 5/47 pseudotyped vectors in vivo: fundamental involvement of coagulation factors and redundancy of CAR binding by Ad5. A1 - Waddington, SN A1 - Parker, AL A1 - Havenga, M A1 - Nicklin, SA A1 - Buckley, SM A1 - McVey, JH A1 - Baker, AH J1 - J Virol Y1 - 2007/09// VL - 81 SN - 0022-538X SP - 9568 EP - 9571 N2 - Vitamin K-dependent coagulation factors can promote adenoviral cell transduction in vitro. In vivo, warfarin pretreatment ablates liver targeting of an adenovirus serotype 5 (Ad5) vector deleted of CAR binding capability. Here, we assess in vivo transduction and biodistribution of Ad5 vectors with nonmodified fibers (Ad5) and a serotype 47 fiber-pseudotyped Ad5 (Ad5/47; subgroup D) virus following intravascular injection. Warfarin reduced liver transduction by both viruses. However, no impact on early liver virus accumulation was observed, suggesting no effect on Kupffer cell interactions. Hence, coagulation factors play a pivotal role in selectively mediating liver hepatocyte transduction of Ad5 and Ad5/47 vectors. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17553882&query_hl=1 ER - TY - JFULL T1 - Relationship between white matter apparent diffusion coefficients in preterm infants at term-equivalent age and developmental outcome at 2 years. A1 - Krishnan, ML A1 - Dyet, LE A1 - Boardman, JP A1 - Kapellou, O A1 - Allsop, JM A1 - Cowan, F A1 - Edwards, AD A1 - Rutherford, MA A1 - Counsell, SJ J1 - Pediatrics Y1 - 2007/09// VL - 120 SN - 1098-4275 SP - e604 EP - e609 N2 - OBJECTIVE: The aim of this study was to develop a simple reproducible method for the measurement of apparent diffusion coefficient values in the white matter of preterm infants using diffusion-weighted imaging to test the hypothesis that elevated mean apparent diffusion coefficient values are associated with lower developmental quotient scores at 2 years' corrected age. METHODS: We obtained diffusion-weighted imaging in 38 preterm infants at term-equivalent age who had no evidence of overt cerebral pathology on conventional MRI. Mean apparent diffusion coefficient values at the level of the centrum semiovale were determined. The children were assessed using a standardized neurologic examination, and the Griffiths Mental Development Scales were administered to obtain a developmental quotient at 2 years' corrected age. The relationship between mean apparent diffusion coefficient values and developmental quotient was examined. Clinical data relating to postnatal sepsis, antenatal steroid exposure, supplemental oxygen, gender, patent ductus arteriosus, and inotrope requirement were collected, and the mean apparent diffusion coefficient values for each group were compared. RESULTS: The mean (+/-SD) apparent diffusion coefficient value in the white matter was 1.385 +/- 0.07 x 10(-3) mm2/second, and the mean developmental quotient was 108.9 +/- 11.5. None of the children had a significant neurologic problem. There was a significant negative correlation between mean apparent diffusion coefficient and developmental quotient. CONCLUSION: These findings suggest that higher white matter apparent diffusion coefficient values at term-equivalent age in preterm infants without overt lesions are associated with poorer developmental performance in later childhood. Consequently, apparent diffusion coefficient values at term may be of prognostic value for neurodevelopmental outcome in infants who are born preterm and who have no other imaging indicators of abnormality. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17698966&query_hl=1 ER - TY - JFULL T1 - Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. A1 - Levy, L A1 - Howell, M A1 - Das, D A1 - Harkin, S A1 - Episkopou, V A1 - Hill, CS J1 - Mol Cell Biol Y1 - 2007/09// VL - 27 SN - 0270-7306 SP - 6068 EP - 6083 N2 - E3 ubiquitin ligases play important roles in regulating transforming growth factor beta (TGF-beta)/Smad signaling. Screening of an E3 ubiquitin ligase small interfering RNA library, using TGF-beta induction of a Smad3/Smad4-dependent luciferase reporter as a readout, revealed that Arkadia is an E3 ubiquitin ligase that is absolutely required for this TGF-beta response. Knockdown of Arkadia or overexpression of a dominant-negative mutant completely abolishes transcription from Smad3/Smad4-dependent reporters, but not from Smad1/Smad4-dependent reporters or from reporters driven by Smad2/Smad4/FoxH1 complexes. We show that Arkadia specifically activates transcription via Smad3/Smad4 binding sites by inducing degradation of the transcriptional repressor SnoN. Arkadia is essential for TGF-beta-induced SnoN degradation, but it has little effect on SnoN levels in the absence of signal. Arkadia interacts with SnoN and induces its ubiquitination irrespective of TGF-beta/Activin signaling, but SnoN is efficiently degraded only when it forms a complex with both Arkadia and phosphorylated Smad2 or Smad3. Finally, we describe an esophageal cancer cell line (SEG-1) that we show has lost Arkadia expression and is deficient for SnoN degradation. Reintroduction of wild-type Arkadia restores TGF-beta-induced Smad3/Smad4-dependent transcription and SnoN degradation in these cells, raising the possibility that loss of Arkadia function may be relevant in cancer. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17591695&query_hl=1 ER - TY - JFULL T1 - Negative correlation between cerebral inorganic phosphate and the volumetric niacin response in male patients with schizophrenia who have seriously and dangerously violently offended: A (31)P magnetic resonance spectroscopy study. A1 - Puri, BK A1 - Richardson, AJ A1 - Counsell, SJ A1 - Ward, PE A1 - Bustos, MG A1 - Hamilton, G A1 - Bhakoo, KK A1 - Treasaden, IH J1 - Prostaglandins Leukot Essent Fatty Acids Y1 - 2007/08/30/ SN - 0952-3278 N2 - The aim of the study was to examine the association of arachidonic acid-related signal transduction with cerebral metabolism in patients with schizophrenia who have violently and dangerously offended while psychotic. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 11 male patients with schizophrenia who had violently offended (homicide, attempted murder, or wounding with intent to cause grievous bodily harm) while psychotic. Spectra were obtained from 70x70x70mm(3) voxels using an image-selected in vivo spectroscopy pulse sequence. Niacin flush testing results were quantified as the volumetric niacin response. There was a strong, and negative, correlation between the volumetric niacin response and the metabolite concentration of inorganic phosphate expressed as a ratio of the total 31-phosphorus signal (p<0.005). Our results suggest that patients with schizophrenia who have violently offended and have poor phospholipid-related signal transduction may have higher levels of cerebral energy metabolism. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17765531&query_hl=1 ER - TY - JFULL T1 - The PhenoGen Informatics website: tools for analyses of complex traits. A1 - Bhave, SV A1 - Hornbaker, C A1 - Phang, TL A1 - Saba, L A1 - Lapadat, R A1 - Kechris, K A1 - Gaydos, J A1 - McGoldrick, D A1 - Dolbey, A A1 - Leach, S A1 - Soriano, B A1 - Ellington, A A1 - Ellington, E A1 - Jones, K A1 - Mangion, J A1 - Belknap, JK A1 - Williams, RW A1 - Hunter, LE A1 - Hoffman, PL A1 - Tabakoff, B J1 - BMC Genet Y1 - 2007/08/30/ VL - 8 SN - 1471-2156 SP - 59 EP - 59 N2 - ABSTRACT: BACKGROUND: With the advent of "omics" (e.g. genomics, transcriptomics, proteomics and phenomics), studies can produce enormous amounts of data. Managing this diverse data and integrating with other biological data are major challenges for the bioinformatics community. Comprehensive new tools are needed to store, integrate and analyze the data efficiently. Description: The PhenoGen Informatics website (http://phenogen.uchsc.edu) is a comprehensive toolbox for storing, analyzing and integrating microarray data and related genotype and phenotype data. The site is particularly suited for combining QTL and microarray data to search for "candidate" genes contributing to complex traits. In addition, the site allows, if desired by the investigators, sharing of the data. Investigators can conduct "in-silico" microarray experiments using their own and/or "shared" data. CONCLUSION: The PhenoGen website provides access to tools that can be used for high-throughput data storage, analyses and interpretation of the results. Some of the advantages of the architecture of the website are that, in the future, the present set of tools can be adapted for the analyses of any type of high-throughput "omics" data, and that access to new tools, available in the public domain or developed at PhenoGen, can be easily provided. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17760997&query_hl=1 ER - TY - JFULL T1 - Application of magnetic resonance methods to studies of gene therapy A1 - So, PW A1 - Parkes, HG A1 - Bell, JD J1 - PROG NUCL MAG RES SP Y1 - 2007/08/30/ VL - 51 SN - 0079-6565 SP - 49 EP - 62 ER - TY - JFULL T1 - The safety of evening primrose oil in epilepsy. A1 - Puri, BK J1 - Prostaglandins Leukot Essent Fatty Acids Y1 - 2007/08/29/ SN - 0952-3278 N2 - The concern that evening primrose oil might cause epilepsy or seizures, or reduce the threshold for seizures, originated from two papers published in the early 1980s. These original reports are re-examined, and the association of evening primrose oil with seizures is shown to be spurious. Not only are linoleic acid and gamma-linolenic acid safe in epilepsy, with prolonged oral administration of linoleic acid and alpha-linolenic acid (in a 4:1 mixture) protecting rats from having seizures in four different epilepsy models, but the evening primrose oil-derived omega-6 fatty acid arachidonic acid inhibits sodium ion currents and synaptic transmission, while the evening primrose oil-derived eicosanoid prostaglandin E(1) appears to have anticonvulsant activity. In light of these findings, it is suggested that formularies should now remove seizures or epilepsy as a side-effect of evening primrose oil, and should remove a history of seizures or epilepsy as a contraindication to taking evening primrose oil. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17764919&query_hl=1 ER - TY - JFULL T1 - Should cranial MRI screening of preterm infants become routine? A1 - de Vries, LS A1 - Cowan, FM J1 - Nat Clin Pract Neurol Y1 - 2007/08/28/ SN - 1745-8358 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17724489&query_hl=1 ER - TY - JFULL T1 - A 31-phosphorus neurospectroscopy study of omega-3 long-chain polyunsaturated fatty acid intervention with eicosapentaenoic acid and docosahexaenoic acid in patients with chronic refractory epilepsy. A1 - Puri, BK A1 - Koepp, MJ A1 - Holmes, J A1 - Hamilton, G A1 - Yuen, AW J1 - Prostaglandins Leukot Essent Fatty Acids Y1 - 2007/08/28/ SN - 0952-3278 N2 - The aim of this study was to determine whether supplementation with the n-3 long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid in patients with chronic refractory epilepsy is associated with beneficial changes in cerebral biochemistry. In a 3-month pilot randomized double-blind placebo-controlled study, three patients received eicosapentaenoic acid and docosahexaenoic acid daily and four received a placebo. 31-Phosphorus neurospectroscopy showed a decrease in phosphodiesters, an increase in gammaNTP and an increase in the broadband component in the active group over this period, while the opposite changes occurred in the placebo group. Therefore, in chronic refractory epilepsy, omega-3 supplementation may be associated with reduced membrane phospholipid breakdown in the brain, an improvement in brain energy metabolism, and an increased level of phospholipids in membranes and/or vesicle bilayers in cells in the brain. The unfavourable biochemical changes observed in the placebo group may be a feature of chronic intractable epilepsy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17761409&query_hl=1 ER - TY - JFULL T1 - Early growth in brain volume is preserved in the majority of preterm infants. A1 - Boardman, JP A1 - Counsell, SJ A1 - Rueckert, D A1 - Hajnal, JV A1 - Bhatia, KK A1 - Srinivasan, L A1 - Kapellou, O A1 - Aljabar, P A1 - Dyet, LE A1 - Rutherford, MA A1 - Allsop, JM A1 - Edwards, AD J1 - Ann Neurol Y1 - 2007/08/14/ SN - 0364-5134 N2 - OBJECTIVE: Preterm infants have reduced cerebral tissue volumes in adolescence. This study addresses the question: Is reduced global brain growth in the neonatal period inevitable after premature birth, or is it associated with specific medical risk factors? METHODS: Eighty-nine preterm infants at term equivalent age without focal parenchymal brain lesions were studied with 20 full-term control infants. Using a deformation-based morphometric approach, we transformed images to a reference anatomic space, and we used the transformations to calculate whole-brain volume and ventricular volume for each subject. Patterns of volume difference were correlated with clinical data. RESULTS: Cerebral volume is not reduced compared with term born control infants (p = 0.765). Supplemental oxygen requirement at 28 postnatal days is associated with lower cerebral tissue volume at term (p < 0.001), but there were no significant differences in cerebral volumes attributable to perinatal sepsis (p = 0.515) and quantitatively defined diffuse white matter injury (p = 0.183). As expected, the ventricular system is significantly larger in preterm infants at term equivalent age compared with term control infants (p < 0.001). INTERPRETATION: Cerebral volume is not reduced during intensive care for the majority of preterm infants, but prolonged supplemental oxygen dependence is a risk factor for early attenuation of global brain growth. The reduced cerebral tissue volume seen in adolescents born preterm does not appear to be an inevitable association of prematurity, but rather caused by either specific disease during intensive care or factors operating beyond the neonatal period. Ann Neurol 2007. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17696128&query_hl=1 ER - TY - JFULL T1 - The Nuclear Receptor Cofactor RIP140 is Required for the Regulation of Hepatic Lipid and Glucose Metabolism by LXR. A1 - Herzog, B A1 - Hallberg, M A1 - Seth, A A1 - Woods, A A1 - White, R A1 - Parker, MG J1 - Mol Endocrinol Y1 - 2007/08/07/ SN - 0888-8809 N2 - The liver X receptors (LXRs) are nuclear receptors which play important roles in the regulation of lipid metabolism. In this study, we demonstrate that RIP140 is a cofactor for LXR in liver. Analysis of RIP140 null mice and hepatocytes depleted of RIP140 indicate that the cofactor is essential for the ability of LXR to activate the expression of a set of genes required for lipogenesis. Furthermore we demonstrate that RIP140 is required for the ability of LXR to repress the expression of the PEPCK gene in Fao cells and mice. Thus, we conclude that the function of RIP140 as a cofactor for LXR in liver varies according to the target genes and metabolic process, serving as a coactivator in lipogenesis but as a corepressor in gluconeogenesis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17684114&query_hl=1 ER - TY - JFULL T1 - AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. A1 - Claret, M A1 - Smith, MA A1 - Batterham, RL A1 - Selman, C A1 - Choudhury, AI A1 - Fryer, LG A1 - Clements, M A1 - Al-Qassab, H A1 - Heffron, H A1 - Xu, AW A1 - Speakman, JR A1 - Barsh, GS A1 - Viollet, B A1 - Vaulont, S A1 - Ashford, ML A1 - Carling, D A1 - Withers, DJ J1 - J Clin Invest Y1 - 2007/08// VL - 117 SN - 0021-9738 SP - 2325 EP - 2336 N2 - Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. In contrast, AgRP alpha 2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17671657&query_hl=1 ER - TY - JFULL T1 - Hypothermia. A1 - Azzopardi, D A1 - Edwards, AD J1 - Semin Fetal Neonatal Med Y1 - 2007/08// VL - 12 SN - 1744-165X SP - 303 EP - 310 N2 - Experimental studies show that, following hypoxic ischaemic injury, mild induced hypothermia-a reduction of body temperature by about 3 degrees C -- preserves cerebral energy metabolism, reduces cerebral tissue injury and improves neurological function. Randomized trials in full-term and near-full-term newborns suggest that treatment with mild hypothermia is safe and improves survival without disabilities up to 18 months of age. Although the optimal time of initiation, the depth and duration, and the method of cooling are uncertain, in the absence of specific treatments many clinicians will wish to consider treating asphyxiated infants with hypothermia. Guidance now needs to be provided to promote uniform practice, to avoid inappropriate treatment and to foster continuing collaboration in future studies of neuroprotection following asphyxia. If the promising results of the current trials are confirmed by the findings from other on-going studies, with longer follow-up, the impact of such a treatment on the babies, their families and health resources in the shorter and longer terms will be considerable. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17392043&query_hl=1 ER - TY - JFULL T1 - Cranial Ultrasound in Metabolic Disorders Presenting in the Neonatal Period: Characteristic Features and Comparison with MR Imaging. A1 - Leijser, LM A1 - de Vries, LS A1 - Rutherford, MA A1 - Manzur, AY A1 - Groenendaal, F A1 - de Koning, TJ A1 - van der Heide-Jalving, M A1 - Cowan, FM J1 - AJNR Am J Neuroradiol Y1 - 2007/08// VL - 28 SN - 0195-6108 SP - 1223 EP - 1231 N2 - BACKGROUND AND PURPOSE: Brain imaging is an integral part of the diagnostic work-up for metabolic disorders, and the bedside availability of cranial ultrasonography (cUS) allows very early brain imaging in symptomatic neonates. Our aim was to investigate the role and range of abnormalities seen on cUS in neonates presenting with metabolic disorders. A secondary aim, when possible, was to address the question of whether brain MR imaging is more informative by comparing cUS to MR imaging findings. MATERIALS AND METHODS: Neonates with a metabolic disorder who had at least 1 cUS scan were eligible. cUS images were reviewed for anatomic and maturation features, cysts, calcium, and other abnormalities. When an MR imaging scan had been obtained, both sets of images were compared. RESULTS: Fifty-five infants (35 also had MR imaging) were studied. The most frequent findings were in oxidative phosphorylation disorders (21 cUS and 12 MR imaging): ventricular dilation (11 cUS and 6 MR imaging), germinolytic cysts (GLCs; 7 cUS and 5 MR imaging), and abnormal white matter (7 cUS and 6 MR imaging); in peroxisomal biogenesis disorders (13 cUS and 9 MR imaging): GLCs (10 cUS and 6 MR imaging), ventricular dilation (10 cUS and 5 MR imaging), abnormal cortical folding (8 cUS and 7 MR imaging), and lenticulostriate vasculopathy (8 cUS); in amino acid metabolism and urea cycle disorders (14 cUS and 11 MR imaging): abnormal cortical folding (9 cUS and 4 MR imaging), abnormal white matter (8 cUS and 8 MR imaging), and hypoplasia of the corpus callosum (7 cUS and 6 MR imaging); in organic acid disorders (4 cUS and 2 MR imaging): periventricular white matter echogenicity (2 cUS and 1 MR imaging); and in other disorders (3 cUS and 1 MR imaging): ventricular dilation (2 cUS and 1 MR imaging). cUS findings were consistent with MR imaging findings. cUS was better for visualizing GLCs and calcification. MR imaging was more sensitive for subtle tissue signal intensity changes in the white matter and abnormality in areas difficult to visualize with cUS, though abnormalities of cortical folding suggestive of polymicrogyria were seen on cUS. CONCLUSION: A wide range of abnormalities is seen using cUS in neonatal metabolic disorders. cUS is a reliable bedside tool for early detection of cysts, calcium, structural brain abnormalities, and white matter echogenicity, all suggestive of metabolic disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17698520&query_hl=1 ER - TY - JFULL T1 - Sylvian fissure morphology in Prader-Willi syndrome and early-onset morbid obesity. A1 - Miller, JL A1 - Couch, JA A1 - Leonard, CM A1 - Schwenk, K A1 - Towler, SD A1 - Shuster, J A1 - Goldstone, AP A1 - He, G A1 - Driscoll, DJ A1 - Liu, Y J1 - Genet Med Y1 - 2007/08// VL - 9 SN - 1098-3600 SP - 536 EP - 543 N2 - PURPOSE: Prader-Willi syndrome is a well-defined genetic cause of childhood-onset obesity that can serve as a model for investigating early-onset childhood obesity. Individuals with Prader-Willi syndrome have speech and language impairments, suggesting possible involvement of the perisylvian region of the brain. Clinical observations suggest that many individuals with early-onset morbid obesity have similar speech/language deficits, indicating possible perisylvian involvement in these children as well. We hypothesized that similar perisylvian abnormalities may exist in both disorders. METHODS: Participants included individuals with Prader-Willi syndrome (n = 27), their siblings (n = 16), individuals with early-onset morbid obesity (n = 13), and their siblings (n = 10). Quantitative and qualitative assessments of sylvian fissure conformation, insula closure, and planum temporale length were performed blind to hemisphere and diagnosis. RESULTS: Quantitative measurements verified incomplete closure of the insula in individuals with Prader-Willi syndrome. Planar asymmetry showed its normal bias toward leftward asymmetry in all groups except those with Prader-Willi syndrome maternal uniparental disomy. Individuals with Prader-Willi syndrome and siblings had a normal distribution of sylvian fissure types in both hemispheres, while individuals with early-onset morbid obesity and their siblings had a high proportion of rare sylvian fissures in the right hemisphere. CONCLUSIONS: The contrast between the anatomic findings in individuals with Prader-Willi syndrome and early-onset morbid obesity suggests that the language problems displayed by children with these two conditions may be associated with different neurodevelopmental processes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17700392&query_hl=1 ER - TY - JFULL T1 - Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart. A1 - Mongillo, M A1 - John, AS A1 - Leccisotti, L A1 - Pennell, DJ A1 - Camici, PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2007/08// VL - 34 SN - 1619-7070 SP - 1172 EP - 1177 N2 - PURPOSE: We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic beta-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. METHODS: Eight patients (aged 67 +/- 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 +/- 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [(11)C]meta-hydroxy-ephedrine (HED) volume of distribution (V (d)) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 +/- 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 +/- 6 years, p < 0.01 vs patients) data. RESULTS: MGU in patients was reduced in both normal remote (0.44 +/- 0.14 mumol.min(-1).g(-1)) and dysfunctional (0.49 +/- 0.14 mumol.min(-1).g(-1)) segments compared with controls (0.61 +/- 0.7 mumol.min(-1).g(-1); p < 0.001 vs both). HED V (d) was reduced in dysfunctional segments of patients (38.9 +/- 21.2 ml.g(-1)) compared with normal segments (52.2 +/- 19.6 ml.g(-1)) and compared with controls (62.7 +/- 11.3 ml.g(-1)). In patients, regional MGU was correlated with HED V (d). CONCLUSION: The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17294189&query_hl=1 ER - TY - JFULL T1 - Advances in imaging the interphase nucleus using thin cryosections. A1 - Pombo, A J1 - Histochem Cell Biol Y1 - 2007/08// VL - 128 SN - 0948-6143 SP - 97 EP - 104 N2 - The mammalian genome is partitioned amongst various chromosomes and encodes for approximately 30,000 protein-coding genes. Gene expression occurs after exit from mitosis, when chromosomes partially decondense within the cell nucleus to allow the enzymatic activities that work on chromatin to access each gene in a regulated fashion. Differential patterns of gene expression evolve during cell differentiation to give rise to the over 200 cell types in higher eukaryotes. The architectural organisation of the genome inside the interphase cell nucleus, and associated enzymatic activities, reveals dynamic and functional compartmentalization of the genome. In this review, I highlight the advantages of Tokuyasu cryosectioning on the investigation of nuclear structure and function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17636315&query_hl=1 ER - TY - JFULL T1 - Pre- and post-synaptic sympathetic function in human hibernating myocardium. A1 - John, AS A1 - Mongillo, M A1 - Depre, C A1 - Khan, MT A1 - Rimoldi, OE A1 - Pepper, JR A1 - Dreyfus, GD A1 - Pennell, DJ A1 - Camici, PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2007/07/28/ SN - 1619-7070 N2 - PURPOSE: Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. METHODS: Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([(11)C]meta-hydroxy-ephedrine; HED) and beta-adrenoceptor (beta-AR) density ([(11)C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. RESULTS: The volume of distribution (V(d)) of HED in HM (47.95+/-28.05 ml/g) and infarcted myocardium (42.69+/-25.76 ml/g) was significantly reduced compared with controls (66.09+/-14.48 ml/g). The V(d) of HED in normal myocardium (49.93+/-20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial beta-AR density was significantly lower in HM (5.49+/-2.35 pmol/g), infarcted (4.82+/-2.61 pmol/g) and normal (5.86+/-1.81 pmol/g) segments of patients compared with healthy controls (8.61+/-1.32 pmol/g). CONCLUSION: Noradrenaline uptake-1 mechanism and beta-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17661029&query_hl=1 ER - TY - JFULL T1 - Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses. A1 - Kaufmann, PA A1 - Rimoldi, O A1 - Gnecchi-Ruscone, T A1 - Luscher, TF A1 - Camici, PG J1 - Am J Physiol Heart Circ Physiol Y1 - 2007/07/27/ SN - 0363-6135 N2 - We studied the impact of systemic infusion of the nitric oxide synthase (NOS) inhibitor N(G)-Monomethyl-L-arginine (L-NMMA) on coronary flow reserve (CFR) in patients with coronary artery disease (CAD). We have previously demonstrated that CFR to adenosine was significantly increased after systemic infusion of L-NMMA in normal volunteers but not in freshly transplanted denervated hearts. At baseline, myocardial blood flow (MBF, ml/min/g) was measured at rest and during iv adenosine (140 microg/kg/min) in 10 controls (47+/-5 years) and 10 CAD patients (58+/-8 years; p<0.01 vs. controls) using positron emission tomography and oxygen-15 labeled water. Both MBF measurements were repeated during iv infusion of 10 mg/kg L-NMMA. CFR was calculated as adenosine-MBF/rest-MBF. CFR was significantly higher in healthy volunteers than in CAD patients and increased significantly after L-NMMA in controls (4.00+/-1.10 to 6.15+/-1.35; p<0.0001) and in patients, both in territories subtended by stenotic coronary arteries (>70% luminal diameter) (2.06+/-1.13 to 3.21+/-1.07; p<0.01) and in remote segments (3.20+/-1.23 to 3.92+/-1.62; p<0.05). In conclusion, CFR can be significantly increased in CAD by a systemic infusion of L-NMMA. Similarly to our previous findings in normal volunteers, this suggests that adenosine-induced hyperemia in CAD patients is constrained by neurally-mediated vasoconstriction which can be relieved by systemic NOS inhibition by L-NMMA. Key words: Coronary circulation, autonomic nervous system, nitric oxide, ischemic heart disease, positron emission tomography. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17660388&query_hl=1 ER - TY - JFULL T1 - MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia. A1 - Schmitz, SA A1 - O'regan, DP A1 - Fitzpatrick, J A1 - Neuwirth, C A1 - Potter, E A1 - Tosi, I A1 - Hajnal, JV A1 - Naoumova, RP J1 - Neuroradiology Y1 - 2007/07/21/ SN - 0028-3940 N2 - INTRODUCTION: Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. METHODS: In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 +/- 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 +/- 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. RESULTS: The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 +/- 4.2 vs. 4.5 +/- 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. CONCLUSION: Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17643240&query_hl=1 ER - TY - JFULL T1 - Fluorescence lifetime tomography of live cells expressing enhanced green fluorescent protein embedded in a scattering medium exhibiting background autofluorescence. A1 - Soloviev, VY A1 - McGinty, J A1 - Tahir, KB A1 - Neil, MA A1 - Sardini, A A1 - Hajnal, JV A1 - Arridge, SR A1 - French, PM J1 - Opt Lett Y1 - 2007/07/15/ VL - 32 SN - 0146-9592 SP - 2034 EP - 2036 N2 - We present a novel fluorescence lifetime tomography system applied to a highly scattering autofluorescent phantom containing live cells expressing the fluorophore enhanced green fluorescent protein (EGFP). The fluorescence signal was excited using a fiber-laser-pumped supercontinuum source and detected using wide-field time gating imaging. To facilitate rapid 3D reconstruction of the fluorescence lifetime distribution, the time-resolved data were Fourier-transformed in time to give complex functions that formed a data set for the Fourier domain reconstruction. Initially the presence of an unspecified background autofluorescence signal impeded reconstruction of the lifetime distribution, but we show that this problem can be addressed using a simple iterative technique. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17632634&query_hl=1 ER - TY - JFULL T1 - Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and its Gd(III) complex. A1 - Wardle, NJ A1 - Herlihy, AH A1 - So, PW A1 - Bell, JD A1 - Bligh, SW J1 - Bioorg Med Chem Y1 - 2007/07/15/ VL - 15 SN - 0968-0896 SP - 4714 EP - 4721 N2 - A new synthetic pathway to 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and 1-(2-[beta,D-galactopyranosyloxy]ethyl)-4,7,10-tris(carboxymethyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents was developed involving full hydroxyl- and carboxyl-group protection in precursors to product. Two sequences of cyclen-N-functionalisation were subsequently investigated, one successfully, towards synthesis of the novel 'smart' bifunctional Gal-PA-DO3A-NH2 chelate. The longitudinal proton relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH2)] and [Gd-(Gal-DO3A)] complexes were increased by 28% and 37% in the presence of beta-galactosidase, respectively. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17512738&query_hl=1 ER - TY - JFULL T1 - Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling. A1 - Nagano, Y A1 - Mavrakis, KJ A1 - Lee, KL A1 - Fujii, T A1 - Koinuma, D A1 - Sase, H A1 - Yuki, K A1 - Isogaya, K A1 - Saitoh, M A1 - Imamura, T A1 - Episkopou, V A1 - Miyazono, K A1 - Miyazawa, K J1 - J Biol Chem Y1 - 2007/07/13/ VL - 282 SN - 0021-9258 SP - 20492 EP - 20501 N2 - Transforming growth factor-beta (TGF-beta) signaling is controlled by a variety of regulators that target either signaling receptors or activated Smad complexes. Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress signaling at the transcriptional level through inactivation of Smad complexes. We previously found that Arkadia is a positive regulator of TGF-beta signaling that induces ubiquitin-dependent degradation of Smad7 through its C-terminal RING domain. We report here that Arkadia induces degradation of SnoN and c-Ski in addition to Smad7. Arkadia interacts with SnoN and c-Ski in their free forms as well as in the forms bound to Smad proteins, and constitutively down-regulates levels of their expression. Arkadia thus appears to effectively enhance TGF-beta signaling through simultaneous down-regulation of two distinct types of negative regulators, Smad7 and SnoN/c-Ski, and may play an important role in determining the intensity of TGF-beta family signaling in target cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17510063&query_hl=1 ER - TY - JFULL T1 - MICROBUBBLE CONTRAST AGENT DETECTION USING BINARY CODED PULSES. A1 - Eckersley, RJ A1 - Tang, MX A1 - Chetty, K A1 - Hajnal, JV J1 - Ultrasound Med Biol Y1 - 2007/07/13/ SN - 0301-5629 N2 - Real-time visualization of microbubbles in the microvasculature of deep tissues remains a challenge for existing nonlinear microbubble imaging techniques. A technique with high sensitivity to nonlinear signals is required to compensate for the effects of limited power used to avoid bubble destruction and the high attenuation of the overlying tissues for deeper targets. The use of coded pulses in ultrasound imaging is well established as a means of improving the signal-to-noise ratio (SNR) within B-mode ultrasound imaging, but the feasibility of this approach for detecting microbubbles has not been well studied. In this work we investigate the use of binary phase encoding together with phase and amplitude modulation (PIAM) for the detection of nonlinear signals from microbubbles. A series of simulation experiments were conducted using a modified Rayleigh-Plesset model together with Golay and Barker coding techniques to investigate (i) the ability of binary encoded PIAM to detect nonlinear signals, (ii) the effect of the SNR and insonating pressure on the detection process, (iii) the sensitivity of different pulse encoding approaches and (iv) the effects of bubble resonance behavior on the detection process. The results show that the binary encoding approach combined with PIAM is able to detect nonlinear signals from microbubbles. It was found that nonlinear scattering from the microbubbles degrades the sensitivity of the binary encoded approach such that at high SNR there is no advantage in using these pulses over existing short-pulse PIAM. However, at lower SNR (<20 dB) the increased pulse length provides improved sensitivity without significant loss of spatial resolution, even under conditions in which the detection failed completely for existing approaches. The results also show that both the insonating acoustic pressure and resonance behavior of bubbles have an effect on the detection sensitivity and spatial resolution for the binary encoded approach. (E-mail: r.eckersley@imperial.ac.uk). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17629609&query_hl=1 ER - TY - JFULL T1 - Evidence for a Sav1866-like architecture for the human multidrug transporter P-glycoprotein. A1 - Zolnerciks, JK A1 - Wooding, C A1 - Linton, KJ J1 - FASEB J Y1 - 2007/07/12/ SN - 1530-6860 N2 - The recently reported structures of the bacterial multidrug exporter Sav1866 suggest a domain architecture in which both nucleotide-binding domains (NBDs) of this ATP binding cassette (ABC) transporter contact both transmembrane domains (TMDs). Such a domain arrangement is particularly unexpected because it is not found in the structures of three solute importers BtuCD, HI1470/1, and ModBC from the same protein family. There is also no precedent for such an arrangement from biochemical studies with any ABC transporter. Sav1866 is homologous with the clinically relevant human P-glycoprotein (ABCB1). If the structure proposed for Sav1866 is physiologically relevant, the long intracellular loops of P-glycoprotein TMD2 should contact NBD1. We have tested this by using cysteine mutagenesis and chemical cross-linking to verify proximal relationships of the introduced sulfhydryls across the proposed interdomain interface. We report the first biochemical evidence in support of the domain arrangement proposed for the multidrug resistance class of ABC transporters. With a domain arrangement distinctly different from the three solute importers it seems likely that the TMDs of ABC importers and exporters have evolved different mechanisms to couple to common conformational changes at conserved NBDs.--Zolnerciks, J. K., Wooding, C., Linton, K. J. Evidence for a Sav1866-like architecture for the human multidrug transporter P-glycoprotein. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17627029&query_hl=1 ER - TY - JFULL T1 - MRI of moving subjects using multislice snapshot images with volume reconstruction (SVR): application to fetal, neonatal, and adult brain studies. A1 - Jiang, S A1 - Xue, H A1 - Glover, A A1 - Rutherford, M A1 - Rueckert, D A1 - Hajnal, JV J1 - IEEE Trans Med Imaging Y1 - 2007/07// VL - 26 SN - 0278-0062 SP - 967 EP - 980 N2 - Motion degrades magnetic resonance (MR) images and prevents acquisition of self-consistent and high-quality volume images. A novel methodology, Snapshot magnetic resonance imaging (MRI) with Volume Reconstruction (SVR) has been developed for imaging moving subjects at high resolution and high signal-to-noise ratio (SNR). The method combines registered 2-D slices from sequential dynamic single-shot scans. The SVR approach requires that the anatomy in question is not changing shape or size and is moving at a rate that allows snapshot images to be acquired. After imaging the target volume repeatedly to guarantee sufficient sampling every where, a robust slice-to-volume registration method has been implemented that achieves alignment of each slice within 0.3 mm in the examples tested. Multilevel scattered interpolation has been used to obtain high-fidelity reconstruction with root-mean-square (rms) error that is less than the noise level in the images. The SVR method has been performed successfully for brain studies on subjects that cannot stay still, and in some cases were moving substantially during scanning. For example, awake neonates, deliberately moved adults and, especially, on fetuses, for which no conventional high-resolution 3-D method is currently available. Fine structure of the in-utero fetal brain is clearly revealed for the first time and substantial SNR improvement is realized by having many individually acquired slices contribute to each voxel in the reconstructed image. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17649910&query_hl=1 ER - TY - JFULL T1 - Three-tesla cardiac magnetic resonance imaging for preterm infants. A1 - Foran, AM A1 - Fitzpatrick, JA A1 - Allsop, J A1 - Schmitz, S A1 - Franklin, J A1 - Pamboucas, C A1 - O'Regan, D A1 - Hajnal, JV A1 - Edwards, AD J1 - Pediatrics Y1 - 2007/07// VL - 120 SN - 1098-4275 SP - 78 EP - 83 N2 - OBJECTIVES: We aimed to establish the feasibility of acquiring 3.0-T cardiac MRIs without sedation, anesthesia, or breath-holding for preterm infants and to obtain preliminary quantitative data on left ventricular function in this population. METHODS: Twelve preterm infants underwent 3.0-T cardiac MRI without sedation or breath-holding. The median gestational age was 29 weeks (range: 26-33 weeks), the median birth weight was 1240 g (range: 808-2200 g), and the median postconceptional age at the time of cardiac MRI was 33 weeks (range: 31-40 weeks). Anatomic images were acquired with T2-weighted spin-echo sequences, and ventricular function was assessed with balanced steady-state free precession cine sequences. We assessed left ventricular function by using the area-length ejection fraction method on horizontal long-axis images and the volumetric Sergeant's discs method of analysis on short-axis images. RESULTS: Imaging was successful for 10 of 12 infants. For those 10, the area-length ejection fraction method in the horizontal long-axis plane estimated median stroke volume at 2.9 mL, cardiac output at 0.4 L/minute, end-diastolic volume at 3.8 mL, end-systolic volume at 0.3 mL, and ejection fraction at 74.6%. Short-axis volumetric estimations were made for 4 infants. With this approach, the median stroke volume was 2.4 mL, cardiac output 0.35 L/minute, end-diastolic volume 4.3 mL, end-systolic volume 2.1 mL, and ejection fraction 56%. CONCLUSIONS: Three-tesla cardiac MRI is feasible for preterm infants without sedation, anesthesia, or breath-holding and has the potential to provide a wide range of precise quantitative data that may be of great value for the investigation of cardiac function in preterm infants. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17606564&query_hl=1 ER - TY - JFULL T1 - MR-guided focused ultrasound. A1 - Gedroyc, WM A1 - Anstee, A J1 - Expert Rev Med Devices Y1 - 2007/07// VL - 4 SN - 1743-4440 SP - 539 EP - 547 N2 - The joining of high-intensity focused ultrasound with high-resolution MR guidance has created a system that can produce tissue destruction deep within solid organs without any invasion. Accurate targeting and thermal mapping are provided by MRI and allow very accurate deposition of energy in tissues that can be altered in response to near real-time thermal imaging produced by MR so that the variation in tissue response that is otherwise observed can be overcome. Current areas of successful application of MR-guided focused ultrasound are described in the treatment of uterine fibroids and other areas of emerging applications in additional solid organs are also discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17605689&query_hl=1 ER - TY - JFULL T1 - Effect of arylamine acetyltransferase Nat3 gene knockout on N-acetylation in the mouse. A1 - Sugamori, KS A1 - Brenneman, D A1 - Wong, S A1 - Gaedigk, A A1 - Yu, V A1 - Abramovici, H A1 - Rozmahel, R A1 - Grant, DM J1 - Drug Metab Dispos Y1 - 2007/07// VL - 35 SN - 0090-9556 SP - 1064 EP - 1070 N2 - Arylamine N-acetyltransferases (NAT) catalyze the biotransformation of many important arylamine drugs and procarcinogens. NAT can either detoxify or activate procarcinogens, complicating the manner in which these enzymes may participate in enhancing or preventing toxic responses to particular agents. Mice possess three NAT isoenzymes: Nat1, Nat2, and Nat3. Whereas Nat1 and Nat2 can efficiently acetylate many arylamines, few substrates appear to be appreciably metabolized by Nat3. We generated a Nat3 knockout mouse strain and used it along with our double Nat1/2(-/-) knockout strain to further investigate the functional role of Nat3. Nat3(-/-) mice showed normal viability and reproductive capacity. Nat3 expression was very low in wild-type animals and completely undetectable in Nat3(-/-) mice. In contrast, greatly elevated expression of Nat3 transcript was observed in Nat1/2(-/-) mice. We used a transcribed marker polymorphism approach to establish that the increased expression of Nat3 in Nat1/2(-/-) mice is a positional artifact of insertion of the phosphoglycerate kinase-neomycin resistance cassette in place of the Nat1/Nat2 gene region and upstream of the intact Nat3 gene, rather than a biological compensatory mechanism. Despite the increase in Nat3 transcript, the N-acetylation of p-aminosalicylate, sulfamethazine, 2-aminofluorene, and 4-aminobiphenyl was undetectable either in vivo or in vitro in Nat1/2(-/-) animals. In parallel, no difference was observed in the in vivo clearance or in vitro metabolism of any of these substrates between wild-type and Nat3(-/-) mice. Thus, Nat3 is unlikely to play a significant role in the N-acetylation of arylamines either in wild-type mice or in mice lacking Nat1 and Nat2 activities. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17403913&query_hl=1 ER - TY - JFULL T1 - Is the chest pain in cardiac syndrome X due to subendocardial ischaemia? A1 - Camici, PG J1 - Eur Heart J Y1 - 2007/07// VL - 28 SN - 0195-668X SP - 1539 EP - 1540 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17526504&query_hl=1 ER - TY - JFULL T1 - Genetic mutations in the ras/raf/mapkinase pathway results in cherubism A1 - Idowu, BD A1 - Mangion, J A1 - Gale, RE A1 - Flanagan, AM J1 - J BONE MINER RES Y1 - 2007/07// VL - 22 SN - 0884-0431 SP - 1124 EP - 1124 ER - TY - JFULL T1 - Structural linear measurements in the newborn brain: accuracy of cranial ultrasound compared to MRI. A1 - Leijser, LM A1 - Srinivasan, L A1 - Rutherford, MA A1 - Counsell, SJ A1 - Allsop, JM A1 - Cowan, FM J1 - Pediatr Radiol Y1 - 2007/07// VL - 37 SN - 0301-0449 SP - 640 EP - 648 N2 - BACKGROUND: Structural size in the neonatal brain is of clinical importance. Cranial ultrasonography (cUS) is the primary method used for evaluating the neonatal brain and it is important to know whether linear measurements made using this technique are accurate. OBJECTIVE: To compare linear measurements of different cerebral structures made from neonatal cUS and contemporaneous MRI. MATERIALS AND METHODS: Preterm and term infants studies with cUS and MRI on the same day were studied. Linear measurements made using both techniques from many cerebral structures were compared using a paired t-test. RESULTS: A total of 44 sets of scans from 26 preterm and 8 term infants were assessed. Small but significant differences between the cUS and MRI measurements (P<0.05) were found for the ventricular index, the posterior horn depth of the lateral ventricle, the extracerebral space and interhemispheric fissure, and the cortex of the cingulate gyrus. No significant differences were found for any other measurements. CONCLUSION: Linear measurements from cUS are accurate for most neonatal cerebral structures. Significant differences compared to MRI were found for a few structures, but only for the cortex were the absolute differences marked and possibly of clinical importance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17486330&query_hl=1 ER - TY - JFULL T1 - Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo. A1 - Keramaris-Vrantsis, E A1 - Lu, PJ A1 - Doran, T A1 - Zillmer, A A1 - Ashar, J A1 - Esapa, CT A1 - Benson, MA A1 - Blake, DJ A1 - Rosenfeld, J A1 - Lu, QL J1 - Muscle Nerve Y1 - 2007/06/06/ VL - 36 SN - 0148-639X SP - 455 EP - 465 N2 - Mutations in the fukutin-related protein gene (FKRP) are associated with a spectrum of diseases from mild limb-girdle muscular dystrophy type 2I to severe congenital muscular dystrophy type 1C, muscle-eye-brain disease (MEB), and Walker-Warburg syndrome (WWS). The effect of mutations on the transportation of the mutant proteins may constitute the underlying mechanisms for the pathogenesis of these diseases. Here we examined the subcellular localization of mouse and human normal and mutant FKRP proteins in cells and in muscle in vivo. Both normal human and mouse FKRPs localize in part of the Golgi apparatus in muscle fibers. Mutations in the FKRP gene invariably altered the localization of the protein, leading to endoplasmic reticulum retention within cells and diminished Golgi localization in muscle fibers. Our results therefore suggest that an individual missense point mutation can confer at least two independent effects on the protein, causing (1) reduction or loss of the presumed glycosyltransferase activity directly and (2) mislocalization that could further alter the function of the protein. The complexity of the effect of individual missense point mutations may partly explain the wide variation of the FKRP-related myopathies. Muscle Nerve, 2007. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17554798&query_hl=1 ER - TY - JFULL T1 - A multivariate statistical analysis of the developing human brain in preterm infants A1 - Thomaz, CE A1 - Boardman, JP A1 - Counsell, S A1 - Hill, DLG A1 - Hajnal, JV A1 - Edwards, AD A1 - Rutherford, MA A1 - Gillies, DF A1 - Rueckert, D J1 - IMAGE VISION COMPUT Y1 - 2007/06/01/ VL - 25 SN - 0262-8856 SP - 981 EP - 994 N2 - Preterm delivery accounts for 5% of all deliveries and its consequences contribute to significant individual, medical, and social problems. The neuroanatomical substrates of these disorders are not known, but are essential for understanding mechanisms of causation, and developing strategies for intervention. In the recent years, multivariate pattern recognition methods that analyse all voxels simultaneously have been proposed to characterise the neuroanatomical differences between a reference group of magnetic resonance (MR) images and the population under investigation. Most of these techniques have overcome the difficulty of dealing with the inherent high dimensionality of 3D MR brain image data by using pre-processed segmented images or a small number of specific features. However, an intuitive way of mapping the classification results back into the original image domain for further interpretation remains challenging. In this paper, we propose the idea of using Principal Components Analysis (PCA) plus the maximum uncertainty Linear Discriminant Analysis (MLDA) approach to classify and analyse MR brain images that have been aligned with either affine or non-rigid registration techniques. This approach avoids the computation costs intrinsic to commonly used covariance-based optimisation processes for solving small sample size problems, resulting in a simple and efficient implementation for the maximisation and interpretation of the Fisher's classification results. In order to demonstrate the effectiveness of the approach, we have used a neonatal MR brain data set that contains images of 93 preterm infants at term equivalent age and 20 term controls. Our results indicate that the two-stage linear framework makes clear the statistical differences between the control and preterm samples, showing a classification accuracy of 95.0% and 97.8% for the controls and preterms samples, respectively, using the leave-one-out method. Moreover, it provides a simple and intuitive method of visually analysing the differences between preterm infants at term equivalent age and the control group, such as differences in cerebrospinal fluid spaces, structure of the corpus callosum, and subtle differences in myelination. (C) 2006 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome. A1 - Miller, JL A1 - James, GA A1 - Goldstone, AP A1 - Couch, JA A1 - He, G A1 - Driscoll, DJ A1 - Liu, Y J1 - J Neurol Neurosurg Psychiatry Y1 - 2007/06// VL - 78 SN - 1468-330X SP - 615 EP - 619 N2 - BACKGROUND: Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. METHODS: We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. RESULTS: Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. CONCLUSIONS: Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158560&query_hl=1 ER - TY - JFULL T1 - Analysis of 'candidate genes' for alcohol consumption in HXB/BXH rats A1 - Bhave, SV A1 - Saba, L A1 - Printz, M A1 - Flodman, R A1 - Gaydos, J A1 - Mangion, J A1 - Hubner, N A1 - Hoffman, PL A1 - Tabakoff, B J1 - ALCOHOL CLIN EXP RES Y1 - 2007/06// VL - 31 SN - 0145-6008 SP - 135A EP - 135A 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 - S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase A1 - Aguilar, V A1 - Alliouachene, S A1 - Sotiropoulos, A A1 - Sobering, A A1 - Athea, Y A1 - Djouadi, F A1 - Miraux, S A1 - Thiaudiere, E A1 - Foretz, M A1 - Viollet, B A1 - Diolez, P A1 - Bastin, J A1 - Benit, P A1 - Rustin, P A1 - Carling, D A1 - Sandri, M A1 - Ventuar-Clapier, R A1 - Pende, M J1 - CELL METAB Y1 - 2007/06// VL - 5 SN - 1550-4131 SP - 476 EP - 487 N2 - S6 kinase (S6K) deletion in metazoans causes small cell size, insulin hypersensitivity, and metabolic adaptations; however, the underlying molecular mechanisms are unclear. Here we show that S6K-deficient skeletal muscle cells have increased AMP and inorganic phosphate levels relative to ATP and phosphocreatine, causing AMP-activated protein kinase (AMPK) upregulation. Energy stress and muscle cell atrophy are specifically triggered by the S6K1 deletion, independent of S6K2 activity. Two known AMPK-dependent functions, mitochondrial biogenesis and fatty acid beta-oxidation, are upregulated in S6K-deficient muscle cells, leading to a sharp depletion of lipid content, while glycogen stores are spared. Strikingly, AMPK inhibition in S6K-deficient cells restores cell growth and sensitivity to nutrient signals. These data indicate that S6K1 controls the energy state of the cell and the AMPK-dependent metabolic program, providing a mechanism for cell mass accumulation under high-calorie diet. ER - TY - JFULL T1 - The Colorado INIA informatics weibsite - Analysis of 'candidate genes' for complextraits A1 - Bhave, SV A1 - Hornbaker, C A1 - Phang, T A1 - Saba, L A1 - Lapadat, R A1 - Kechris, K A1 - Gaydos, J A1 - McGoldrick, D A1 - Dolbey, A A1 - Soriano, B A1 - Ellington, A A1 - Ellington, E A1 - Jones, K A1 - Mangion, J A1 - Belknap, J A1 - Williams, RW A1 - Hunter, LE A1 - Hoffman, PL A1 - Talbakoff, B J1 - ALCOHOL CLIN EXP RES Y1 - 2007/06// VL - 31 SN - 0145-6008 SP - 134A EP - 134A ER - TY - JFULL T1 - Functional characterization of point mutations in the LDLR gene found in Portuguese patients with clinical diagnosis of familial hypercholesterolaemia. A1 - Silva, S A1 - Patel, D A1 - Bourbon, M A1 - Soutar, AK J1 - ATHEROSCLEROSIS SUPP Y1 - 2007/06// VL - 8 SN - 1567-5688 SP - 213 EP - 213 ER - TY - JFULL T1 - Involvement of prefrontal cortex in visual search. A1 - Anderson, EJ A1 - Mannan, SK A1 - Husain, M A1 - Rees, G A1 - Sumner, P A1 - Mort, DJ A1 - McRobbie, D A1 - Kennard, C J1 - Exp Brain Res Y1 - 2007/06// VL - 180 SN - 0014-4819 SP - 289 EP - 302 N2 - Visual search for target items embedded within a set of distracting items has consistently been shown to engage regions of occipital and parietal cortex, but the contribution of different regions of prefrontal cortex remains unclear. Here, we used fMRI to compare brain activity in 12 healthy participants performing efficient and inefficient search tasks in which target discriminability and the number of distractor items were manipulated. Matched baseline conditions were incorporated to control for visual and motor components of the tasks, allowing cortical activity associated with each type of search to be isolated. Region of interest analysis was applied to critical regions of prefrontal cortex to determine whether their involvement was common to both efficient and inefficient search, or unique to inefficient search alone. We found regions of the inferior and middle frontal cortex were only active during inefficient search, whereas an area in the superior frontal cortex (in the region of FEF) was active for both efficient and inefficient search. Thus, regions of ventral as well as dorsal prefrontal cortex are recruited during inefficient search, and we propose that this activity is related to processes that guide, control and monitor the allocation of selective attention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17310377&query_hl=1 ER - TY - JFULL T1 - The human mirror system: a motor resonance theory of mind-reading. A1 - Agnew, ZK A1 - Bhakoo, KK A1 - Puri, BK J1 - Brain Res Rev Y1 - 2007/06// VL - 54 SN - 0165-0173 SP - 286 EP - 293 N2 - Electrophysiological data confirm the existence of neurons that respond to both motor and sensory events in the macaque brain. These mirror neurons respond to execution and observation of goal-orientated actions. It has been suggested that they comprise a neural basis for encoding an internal representation of action. In this paper the evidence for a parallel system in humans is reviewed and the implications for human theory of mind processing are discussed. Different components of theory of mind are discussed; the evidence for mirror activity within subtypes is addressed. While there is substantial evidence for a human mirror system, there are weaknesses in the attempts to localize such a system in the brain. Preliminary evidence indicates that mirror neurons may be involved in theory of mind; however, these data by their very nature are reliant on the presence, and precise characterization, of the human mirror system. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17544152&query_hl=1 ER - TY - JFULL T1 - SH3BP2, PTPN11 and NF1 mutations resulting in the cherubism phenotype A1 - Idowu, BD A1 - Mangion, J A1 - Gale, RE A1 - Flanagan, AM J1 - BONE Y1 - 2007/06// VL - 40 SN - 8756-3282 SP - S160 EP - S161 ER - TY - JFULL T1 - A conserved sequence immediately N-terminal to the Bateman domains in AMP-activated protein kinase gamma subunits is required for the interaction with the beta subunits A1 - Viana, R A1 - Towler, MC A1 - Pan, DA A1 - Carling, D A1 - Viollet, B A1 - Hardie, DG A1 - Sanz, P J1 - J BIOL CHEM Y1 - 2007/06/01/ VL - 282 SN - 0021-9258 SP - 16117 EP - 16125 N2 - Mammalian AMP-activated protein kinase is a serine/threonine protein kinase that acts as a sensor of cellular energy status. AMP-activated protein kinase is a heterotrimer of three different subunits, i.e. alpha, beta and gamma, with alpha being the catalytic subunit and beta and gamma having regulatory roles. Although several studies have defined different domains in alpha and beta involved in the interaction with the other subunits of the complex, little is known about the regions of the gamma subunits involved in these interactions. To study this, we have made sequential deletions from the N termini of the gamma subunit isoforms and studied the interactions with alpha and beta subunits, both by two-hybrid analysis and by co-immunoprecipitation. Our results suggest that a conserved region of 20-25 amino acids in gamma 1, gamma 2, and gamma 3, immediately N-terminal to the Bateman domains, is required for the formation of a functional, active alpha beta gamma complex. This region is required for the interaction with the beta subunits. The interaction between the beta and gamma subunits does not require this region and occurs instead within the Bateman domains of the gamma subunit, although the beta-gamma interaction does appear to stabilize the beta-gamma interaction. In addition, sequential deletions from the C termini of the gamma subunits indicate that deletion of any of the CBS (cystathionine beta-synthase) motifs prevents the formation of a functional complex with the alpha and beta subunits. ER - TY - JFULL T1 - Integrated genetic linkage analysis and expression profiling in the rat heart to identify primary drivers of cardiac hypertrophy A1 - Sarwar, R A1 - Petretto, E A1 - Lu, H A1 - Kumaran, M A1 - Schroen, B A1 - Fischer, J A1 - Hubner, N A1 - Mangion, J A1 - Pinto, Y A1 - Pravenec, M A1 - Aitman, T A1 - Cook, S J1 - HEART Y1 - 2007/06// VL - 93 SN - 1355-6037 SP - A6 EP - A6 ER - TY - JFULL T1 - Coronary microvascular dysfunction - Reply A1 - Camici, PG A1 - Crea, F J1 - NEW ENGL J MED Y1 - 2007/05/31/ VL - 356 SN - 0028-4793 SP - 2325 EP - 2325 ER - TY - JFULL T1 - Early assessment of visual function in full term newborns. A1 - Ricci, D A1 - Cesarini, L A1 - Groppo, M A1 - De Carli, A A1 - Gallini, F A1 - Serrao, F A1 - Fumagalli, M A1 - Cowan, F A1 - Ramenghi, LA A1 - Anker, S A1 - Mercuri, E A1 - Mosca, F J1 - Early Hum Dev Y1 - 2007/05/18/ SN - 0378-3782 N2 - BACKGROUND:: The assessment of visual function is part of all the neonatal neurological examination but it is often limited to the evaluation of ocular movements and the ability to fix and follow a target. AIM OF THE STUDY:: To develop a simple battery of test items assessing different aspects of visual function that could be used as early as 48 h after birth. STUDY DESIGN AND SUBJECTS:: The final battery, which has been used in 50 full term low risk neonates, includes 9 items assessing ocular motility, both spontaneous and with focus on a visual target, fixation and tracking (horizontal, vertical and in an arc), the ability to discriminate stripes of different spatial frequency, and attention at distance. RESULTS:: The battery proved easy to perform and did not require long training. The testing did not require a specific setting and was easy to use even for infants in incubators. The equipment is small and cleanable. CONCLUSION:: Our paper suggests that a simple battery, which can be performed in 5/10 min, can be easily applied and provides useful information on various aspects of early neonatal visual function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17513071&query_hl=1 ER - TY - JFULL T1 - Creatine supplements in patients with idiopathic inflammatory myopathies who are clinically weak after conventional pharmacologic treatment: Six-month, double-blind, randomized, placebo-controlled trial. A1 - Chung, YL A1 - Alexanderson, H A1 - Pipitone, N A1 - Morrison, C A1 - Dastmalchi, M A1 - Ståhl-Hallengren, C A1 - Richards, S A1 - Thomas, EL A1 - Hamilton, G A1 - Bell, JD A1 - Lundberg, IE A1 - Scott, DL J1 - Arthritis Rheum Y1 - 2007/05/15/ VL - 57 SN - 0004-3591 SP - 694 EP - 702 N2 - OBJECTIVE: To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable. METHODS: In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ((31)P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids. RESULTS: A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P = 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P = 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine. CONCLUSION: Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17471547&query_hl=1 ER - TY - JFULL T1 - Automatic detection and quantification of hippocampal atrophy on MRI in temporal lobe epilepsy: a proof-of-principle study. A1 - Hammers, A A1 - Heckemann, R A1 - Koepp, MJ A1 - Duncan, JS A1 - Hajnal, JV A1 - Rueckert, D A1 - Aljabar, P J1 - Neuroimage Y1 - 2007/05/15/ VL - 36 SN - 1053-8119 SP - 38 EP - 47 N2 - In temporal lobe epilepsy (TLE), hippocampal atrophy (HA) is a marker of poor prognosis regarding seizure remission, but predicts success of anterior temporal lobe resection. Manual quantification of HA on MRI is time-consuming and limited by investigator availability. Normal ranges of hippocampal volumes, both in absolute terms and relative to intracranial volume, and of hippocampal asymmetry were defined using an automatic label propagation and decision fusion technique based on thirty manually derived atlases of healthy controls. Manual test-retest reliability and overlaps of automatically and manually determined hippocampal volumes were quantified with similarity indices (SIs). Correct clinical identification of ipsilateral HA, and contralaterally normal hippocampal volumes, was determined in nine patients with histologically confirmed hippocampal sclerosis in terms of volumes and asymmetry indices (AIs) for standard statistical thresholds and with receiver operating characteristic (ROC) analysis. Manual test-retest reliability was very high, with SIs between 0.87 and 0.90. Manual and automatic hippocampus labels overlapped with a SI of 0.83 on the unaffected but with 0.76 on the atrophic side. Accuracy was higher for less atrophic hippocampi. The automatic method correctly identified 6/9 HAs in terms of absolute volume, 7/9 in terms of relative volume at a standard 2 SD threshold, and 9/9 for AIs. ROC-determined thresholds allowed clinically desirable correct identification of all HAs (100% sensitivity) with 85-100% specificity for volumes, and 100% specificity for AIs. The method has the potential to automatically detect unilateral HA, but further work is needed to determine its performance in detecting clinically important bilateral disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17428687&query_hl=1 ER - TY - JFULL T1 - Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: Relation to liver, muscle and regional body fat content. A1 - Thomas, EL A1 - Potter, E A1 - Tosi, I A1 - Fitzpatrick, J A1 - Hamilton, G A1 - Amber, V A1 - Hughes, R A1 - North, C A1 - Holvoet, P A1 - Seed, M A1 - Betteridge, DJ A1 - Bell, JD A1 - Naoumova, RP J1 - Atherosclerosis Y1 - 2007/05/04/ SN - 0021-9150 N2 - Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30mg daily for 4 weeks, increasing to 45mg for 12 weeks. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed to measure adipose tissue (AT) body content as well as intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) at baseline and after treatment. Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) -32.3% (p=0.002), plasma glucose -4.4% (p=0.03), alanine-aminotransferase (ALT) -7.7% (p=0.005) and adiponectin 130.1% (p=0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p=0.02) and subcutaneous (7.1%, p=0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p=0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated (r=0.72, p<0.01; r=.0.86, p<0.01, respectively). In patients with FCHL on conventional lipid-lowering therapy, the addition of pioglitazone acts favourably on several metabolic parameters. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17482623&query_hl=1 ER - TY - JFULL T1 - Reconstruction of undersampled dynamic images by modeling the motion of object elements. A1 - Prieto, C A1 - Batchelor, PG A1 - Hill, DL A1 - Hajnal, JV A1 - Guarini, M A1 - Irarrazaval, P J1 - Magn Reson Med Y1 - 2007/05// VL - 57 SN - 0740-3194 SP - 939 EP - 949 N2 - Dynamic MRI is restricted due to the time required to obtain enough data to reconstruct the image sequence. Several undersampled reconstruction techniques have been proposed to reduce the acquisition time. In most of these techniques the nonacquired data are recovered by modeling the temporal information as varying pixel intensities represented in time or in temporal frequencies. Here we propose a new approach that recovers the missing data through a motion estimation of the object elements ("obels," or pieces of tissue) of the image. This method assumes that an obel displacement through the sequence has lower bandwidth than fluctuations in pixel intensities caused by the motion, and thus it can be modeled with fewer parameters. Preliminary results show that this technique can effectively reconstruct (with root mean square (RMS) errors below 4%) cardiac images and joints with undersampling factors of 8 and 4, respectively. Moreover, in the reconstruction process an approximation of the motion vectors is obtained for each obel, which can be used to quantify dynamic information. In this method the motion need not be confined to a part of the field of view (FOV) or to a portion of the temporal frequency. It is appropriate for dynamic studies in which the obels' motion model has fewer parameters than the number of acquired samples. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17457881&query_hl=1 ER - TY - JFULL T1 - Deletion of the c-Jun N-terminal kinase 3 gene protects neonatal mice against cerebral hypoxic-ischaemic injury. A1 - Pirianov, G A1 - Brywe, KG A1 - Mallard, C A1 - Edwards, AD A1 - Flavell, RA A1 - Hagberg, H A1 - Mehmet, H J1 - J Cereb Blood Flow Metab Y1 - 2007/05// VL - 27 SN - 0271-678X SP - 1022 EP - 1032 N2 - c-Jun N-terminal kinase 3 (JNK3) is a member of the stress-activated group of mitogen-activated protein kinases. c-Jun N-terminal kinase 3 is a potent mediator of apoptosis and the use of JNK inhibitors or jnk3 gene deletion each protect against brain injury in adults. However, little is known about the role of JNK3 or its mechanism of action in neonatal brain injury. The aim of the present study was to compare the vulnerability of neonatal JNK3 knockout (JNK3 KO) mice and wild-type (WT) mice to cerebral hypoxic-ischaemic injury (HII) using unilateral-carotid occlusion combined with transient hypoxia. The degree of neural tissue loss in JNK3 KO mice was substantially reduced compared with WT mice (JNK3 KO 27.8%+/-2.8% versus WT 48.3%+/-2.0%, P or =25th or <25th percentile for term, such that larger infants showed a lower frequency of favorable outcomes in the control group but greater improvement with cooling. For larger infants, the number needed to treat was 3.8. Pyrexia (> or =38 degrees C) in control infants was associated with adverse outcomes. Although there was a small correlation with birth weight, the adverse effect of greater birth weight in control infants remained significant after adjustment for pyrexia and severity of encephalopathy. CONCLUSIONS: Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy. The protective effect of hypothermia was greater in larger infants. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17473091&query_hl=1 ER - TY - JFULL T1 - Postmortem brain MRI with selective tissue biopsy as an adjunct to autopsy following neonatal encephalopathy. A1 - Nicholl, RM A1 - Balasubramaniam, VP A1 - Urquhart, DS A1 - Sellathurai, N A1 - Rutherford, MA J1 - Eur J Paediatr Neurol Y1 - 2007/05// VL - 11 SN - 1090-3798 SP - 167 EP - 174 N2 - Following the death of a neonate it is essential that parents are given full and accurate information about the probable cause of death. Perinatal autopsy often adds new information or may even change the presumed diagnosis [Cartlidge PH, Dawson AT, Stewart JH, Vujanic GM. Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths. Br Med J 1995;310(6973):155-8; Khong TY. Falling neonatal autopsy rates. Br Med J 2002;324(7340):749-50] informing decisions regarding the management of any future pregnancy. Autopsy can be considered the "gold standard" for the identification of antecedent events leading to a neonatal death. However, recent events in the UK have added to an already declining rate in neonatal autopsies [Brodlie M, Laing IA. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. Br Med J 2002;324(7340):761-3]. To try and redress this balance the Chief Medical Officer has recommended that research should be commissioned into the use of non-invasive imaging to provide a similar standard of information [The Chief Medical Officer. The removal, retention and use of human organs and tissues from post mortem examination. London, England: The Stationary Office, Department of Health; 2001]. Previous publications on postmortem MRI have focused largely on investigation of the foetus and of still birth [Griffiths PD, Variend D, Evans M, Jones A, Wilkinson ID, Paley MNJ, et al. Postmortem MR imaging of the fetal and stillborn central nervous system. Am J Neuroradiol 2003;24(1):22-7; Whitby EH, Paley MN, Cohen M, GriffithsPD. Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy? Semin Fetal Neonatal Med 2005;10(5):475-83]. We report our experience on the use of postmortem brain MRI combined with selective tissue biopsy, in six neonatal deaths in the setting of a large district general hospital. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17270474&query_hl=1 ER - TY - JFULL T1 - "Click labeling" with 2-[18f]fluoroethylazide for positron emission tomography. A1 - Glaser, M A1 - Arstad, E J1 - Bioconjug Chem Y1 - 2007/05// VL - 18 SN - 1043-1802 SP - 989 EP - 993 N2 - As an effort in the development of more flexible (18)F-labeling chemistry, we report herein on the use of the Cu(I)-catalyzed Huisgen cycloaddition, also known as the "click reaction", to form (18)F-labeled 1,2,3-triazoles. Nucleophilic fluorination of 2-azidoethyl-4-toluenesulfonate followed by distillation provided 2-[(18)F]fluoroethylazide in 55% radiochemical yield (decay-corrected). 2-[(18)F]fluoroethylazide was reacted with a small library of terminal alkynes in the presence of excess Cu(2+)/ascorbate or copper powder. The most reactive alkyne, N-benzylpropynamide provided nearly quantitative incorporation of 2-[(18)F]fluoroethylazide after 15 min at ambient temperature, whereas the majority of the alkyne substrates provided excellent yields of the corresponding (18)F-labeled 1,2,3-triazoles following heating to 80 degrees C. Using the method described, a model peptide was obtained in 92.3 +/- 0.3% (n = 3) radiochemical yield (decay-corrected) after purification by semipreparative HPLC. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17429938&query_hl=1 ER - TY - JFULL T1 - Cdc6 ATPase activity regulates ORC x Cdc6 stability and the selection of specific DNA sequences as origins of DNA replication. A1 - Speck, C A1 - Stillman, B J1 - J Biol Chem Y1 - 2007/04/20/ VL - 282 SN - 0021-9258 SP - 11705 EP - 11714 N2 - DNA replication, as with all macromolecular synthesis steps, is controlled in part at the level of initiation. Although the origin recognition complex (ORC) binds to origins of DNA replication, it does not solely determine their location. To initiate DNA replication ORC requires Cdc6 to target initiation to specific DNA sequences in chromosomes and with Cdt1 loads the ring-shaped mini-chromosome maintenance (MCM) 2-7 DNA helicase component onto DNA. ORC and Cdc6 combine to form a ring-shaped complex that contains six AAA+ subunits. ORC and Cdc6 ATPase mutants are defective in MCM loading, and ORC ATPase mutants have reduced activity in ORC x Cdc6 x DNA complex formation. Here we analyzed the role of the Cdc6 ATPase on ORC x Cdc6 complex stability in the presence or absence of specific DNA sequences. Cdc6 ATPase is activated by ORC, regulates ORC x Cdc6 complex stability, and is suppressed by origin DNA. Mutations in the conserved origin A element, and to a lesser extent mutations in the B1 and B2 elements, induce Cdc6 ATPase activity and prevent stable ORC x Cdc6 formation. By analyzing ORC x Cdc6 complex stability on various DNAs, we demonstrated that specific DNA sequences control the rate of Cdc6 ATPase, which in turn controls the rate of Cdc6 dissociation from the ORC x Cdc6 x DNA complex. We propose a mechanism explaining how Cdc6 ATPase activity promotes origin DNA sequence specificity; on DNA that lacks origin activity, Cdc6 ATPase promotes dissociation of Cdc6, whereas origin DNA down-regulates Cdc6 ATPase resulting in a stable ORC x Cdc6 x DNA complex, which can then promote MCM loading. This model has relevance for origin specificity in higher eukaryotes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17314092&query_hl=1 ER - TY - JFULL T1 - Role of DNA methylation in stable gene repression. A1 - Lande-Diner, L A1 - Zhang, J A1 - Ben-Porath, I A1 - Amariglio, N A1 - Keshet, I A1 - Hecht, M A1 - Azuara, V A1 - Fisher, AG A1 - Rechavi, G A1 - Cedar, H J1 - J Biol Chem Y1 - 2007/04/20/ VL - 282 SN - 0021-9258 SP - 12194 EP - 12200 N2 - A large fraction of the animal genome is maintained in a transcriptionally repressed state throughout development. By generating viable Dnmt1(-)(/)(-) mouse cells we have been able to study the effect of DNA methylation on both gene expression and chromatin structure. Our results confirm that the underlying methylation pattern has a profound effect on histone acetylation and is the major effector of me-H3(K4) in the animal genome. We demonstrate that many methylated genes are subject to additional repression mechanisms that also impact on histone acetylation, and the data suggest that late replication timing may play an important role in this process. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17311920&query_hl=1 ER - TY - JFULL T1 - Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants. A1 - Anjari, M A1 - Srinivasan, L A1 - Allsop, JM A1 - Hajnal, JV A1 - Rutherford, MA A1 - Edwards, AD A1 - Counsell, SJ J1 - Neuroimage Y1 - 2007/04/15/ VL - 35 SN - 1053-8119 SP - 1021 EP - 1027 N2 - Infants born preterm have a high incidence of neurodevelopmental impairment in later childhood, often associated with poorly defined cerebral white matter abnormalities. Diffusion tensor imaging quantifies the diffusion of water within tissues and can assess microstructural abnormalities in the developing preterm brain. Tract-based spatial statistics (TBSS) is an automated observer-independent method of aligning fractional anisotropy (FA) images from multiple subjects to allow groupwise comparisons of diffusion tensor imaging data. We applied TBSS to test the hypothesis that preterm infants have reduced fractional anisotropy in specific regions of white matter compared to term-born controls. We studied 26 preterm infants with no evidence of focal lesions on conventional magnetic resonance imaging (MRI) at term equivalent age and 6 healthy term-born control infants. We found that the centrum semiovale, frontal white matter and the genu of the corpus callosum showed significantly lower FA in the preterm group. Infants born at less than or equal to 28 weeks gestational age (n=11) displayed additional reductions in FA in the external capsule, the posterior aspect of the posterior limb of the internal capsule and the isthmus and middle portion of the body of the corpus callosum. This study demonstrates that TBSS provides an observer-independent method of identifying white matter abnormalities in the preterm brain at term equivalent age in the absence of focal lesions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17344066&query_hl=1 ER - TY - JFULL T1 - Pituitary abnormalities in Prader-Willi syndrome and early onset morbid obesity. A1 - Miller, JL A1 - Goldstone, AP A1 - Couch, JA A1 - Shuster, J A1 - He, G A1 - Driscoll, DJ A1 - Liu, Y A1 - Schmalfuss, IM J1 - Am J Med Genet A Y1 - 2007/04/12/ SN - 1552-4825 N2 - Prader-Willi syndrome (PWS) is a well-defined syndrome of childhood-obesity which can serve as a model for investigating early onset childhood obesity. Many of the clinical features of PWS (e.g., hyperphagia, hypogonadotropic hypogonadism, growth hormone deficiency) are hypothesized to be due to abnormalities of the hypothalamus and/or pituitary gland. Children who become severely obese very early in life (i.e., before age 4 years) may also have a genetic etiology of their obesity, perhaps with associated neuroendocrine and hypothalamo-pituitary defects, as infants and very young children have limited access to environmental factors that contribute to obesity. We hypothesized that morphologic abnormalities of the pituitary gland would be seen in both individuals with PWS and other subjects with early onset morbid obesity (EMO). This case-control study included individuals with PWS (n = 27, age 3 months to 39 years), patients with EMO of unknown etiology (n = 16, age 4-22 years; defined as body mass index greater than the 97th centile for age before age 4 years), and normal weight siblings (n = 25, age 7 months to 43 years) from both groups. Participants had 3-dimensional magnetic resonance imaging to evaluate the pituitary gland, a complete history and physical examination, and measurement of basal pituitary hormones. Subjects with PWS and EMO had a higher prevalence of pituitary morphological abnormalities than did control subjects (74% PWS, 69% EMO, 8% controls; P < 0.001). Anterior pituitary hormone deficiencies were universal in individuals with PWS (low IGF-1 in 100%, P < 0.001 PWS vs. controls; central hypothyroidism in 19%, P = 0.052, and hypoplastic genitalia or hypogonadotropic hypogonadism in 100%, P < 0.001), and was often seen in individuals with EMO (6%, P = 0.89 vs. control, 31%, P = 0.002, and 25%, P = 0.018, respectively). The presence of a hypoplastic pituitary gland appeared to correlate with the presence of anterior pituitary hormone deficiencies in individuals with EMO, but no correlation was apparent in individuals with PWS. In conclusion, the high frequency of both morphological and hormonal abnormalities of the pituitary gland in both individuals with PWS and EMO suggests that abnormalities in the hypothalamo-pituitary axis are features not only of PWS, but also frequently of EMO of unknown etiology. (c) 2007 Wiley-Liss, Inc. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17431897&query_hl=1 ER - TY - JFULL T1 - Parallel magnetic resonance imaging. A1 - Larkman, DJ A1 - Nunes, RG J1 - Phys Med Biol Y1 - 2007/04/07/ VL - 52 SN - 0031-9155 SP - R15 EP - R55 N2 - Parallel imaging has been the single biggest innovation in magnetic resonance imaging in the last decade. The use of multiple receiver coils to augment the time consuming Fourier encoding has reduced acquisition times significantly. This increase in speed comes at a time when other approaches to acquisition time reduction were reaching engineering and human limits. A brief summary of spatial encoding in MRI is followed by an introduction to the problem parallel imaging is designed to solve. There are a large number of parallel reconstruction algorithms; this article reviews a cross-section, SENSE, SMASH, g-SMASH and GRAPPA, selected to demonstrate the different approaches. Theoretical (the g-factor) and practical (coil design) limits to acquisition speed are reviewed. The practical implementation of parallel imaging is also discussed, in particular coil calibration. How to recognize potential failure modes and their associated artefacts are shown. Well-established applications including angiography, cardiac imaging and applications using echo planar imaging are reviewed and we discuss what makes a good application for parallel imaging. Finally, active research areas where parallel imaging is being used to improve data quality by repairing artefacted images are also reviewed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17374908&query_hl=1 ER - TY - JFULL T1 - Structure and function of ABC transporters. A1 - Linton, KJ J1 - Physiology (Bethesda) Y1 - 2007/04// VL - 22 SN - 1548-9213 SP - 122 EP - 130 N2 - ATP binding cassette transporters are ubiquitous integral membrane proteins that actively transport ligands across biological membranes, a process critical for most aspects of cell physiology. These proteins are important clinically and economically. Their dysfunction underlies a number of human genetic diseases, and the ability of some to pump cytotoxic molecules from cells confers resistance to antibiotics, herbicides, and chemotherapeutic drugs. Recent structure analyses interpreted in light of a large body of biochemistry has resulted in the ATP-switch model for function in which the paired nucleotide binding domains switch between an ATP-dependent closed conformation and a nucleotide-free, open conformation to drive the translocation of ligand. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17420303&query_hl=1 ER - TY - JFULL T1 - Epigenetic signatures of stem-cell identity. A1 - Spivakov, M A1 - Fisher, AG J1 - Nat Rev Genet Y1 - 2007/04// VL - 8 SN - 1471-0056 SP - 263 EP - 271 N2 - Pluripotent stem cells, similar to more restricted stem cells, are able to both self-renew and generate differentiated progeny. Although this dual functionality has been much studied, the search for molecular signatures of 'stemness' and pluripotency is only now beginning to gather momentum. While the focus of much of this work has been on the transcriptional features of embryonic stem cells, recent studies have indicated the importance of unique epigenetic profiles that keep key developmental genes 'poised' in a repressed but activatable state. Determining how these epigenetic features relate to the transcriptional signatures of ES cells, and whether they are also important in other types of stem cell, is a key challenge for the future. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17363975&query_hl=1 ER - TY - JFULL T1 - Chromatin organization and differentiation in embryonic stem cell models. A1 - Giadrossi, S A1 - Dvorkina, M A1 - Fisher, AG J1 - Curr Opin Genet Dev Y1 - 2007/04// VL - 17 SN - 0959-437X SP - 132 EP - 138 N2 - Embryonic stem cells derived from mammalian embryos represent indispensable tools for mammalian genetics. Their key features--self-renewal and pluripotency--enable them, on the one hand, to be propagated in culture almost indefinitely and, on the other, to be used to study the molecular details of cell commitment and differentiation. In the past few years, it has become clear that chromatin and epigenetic modifications have a central role in maintaining the gene expression programs that are important for both self-renewal and cell commitment. Therefore, studies focused on the chromatin profiles of embryonic stem cells are likely to be very informative for understanding pluripotency and the process of differentiation, and ultimately for using embryonic stem cells as a tool for cell replacement therapy or as models for the study of genetic diseases, cancer progression or drug testing. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17336511&query_hl=1 ER - TY - JFULL T1 - AMP-activated protein kinase and the regulation of energy metabolism A1 - Carling, D J1 - FASEB J Y1 - 2007/04// VL - 21 SN - 0892-6638 SP - A206 EP - A206 ER - TY - JFULL T1 - Quantification of deep gray matter in preterm infants at term-equivalent age using manual volumetry of 3-tesla magnetic resonance images. A1 - Srinivasan, L A1 - Dutta, R A1 - Counsell, SJ A1 - Allsop, JM A1 - Boardman, JP A1 - Rutherford, MA A1 - Edwards, AD J1 - Pediatrics Y1 - 2007/04// VL - 119 SN - 1098-4275 SP - 759 EP - 765 N2 - OBJECTIVE: Nonhypothesis-based MRI-analysis techniques including deformation-based morphometry and automated tissue segmentation have suggested that preterm infants at term-equivalent age have reduced tissue volume in the basal ganglia and thalami, which is most apparent among infants with supratentorial lesions. The aim of our study was to test this hypothesis by direct measurement of thalamic and lentiform nuclei volumes in preterm infants at term-equivalent age and term-born controls using manual volumetry. DESIGN/METHODS: Forty preterm infants at term-equivalent age (median gestational age: 29.5 weeks; median birth weight: 1.3 kg) and 8 term-born controls were examined using a 3-T Philips (Best, Netherlands) system. T1-weighted volume images and T2-weighted fast-spin echo pseudovolumes were acquired. There was no significant difference in postmenstrual age at image acquisition between the 2 groups. ImageJ 1.34 (National Institutes of Health, Bethesda, MD) was used for manual segmentations. RESULTS: The median thalamic and lentiform nuclei volumes for preterm infants at term-equivalent age were 13.6 and 3.07 cm3, respectively, significantly smaller than term-control volumes of 16.3 and 5.6 cm3, respectively. Ten preterm infants at term-equivalent age had supratentorial lesions (intraventricular hemorrhage, periventricular leukomalacia, or hemorrhagic parenchymal infarction), and the median thalamic and lentiform volumes for this group were 10.4 and 1.7 cm3, respectively. When this group was excluded, the remaining infants who had mild or moderate diffuse excessive high signal intensity in the white matter on T2-weighted images had a smaller, yet significant, volume reduction compared with controls. Tissue volumes were not related to weight and gestational age at birth. CONCLUSIONS: Manual volumetry confirms that preterm infants at term-equivalent age have reduced thalamic and lentiform volumes compared with controls. This was most marked among infants with supratentorial lesions but was also seen among those with nonfocal white matter abnormalities. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17403847&query_hl=1 ER - TY - JFULL T1 - The effect of temperature on the QTc interval in the newborn infant receiving extracorporeal membrane oxygenation (ECMO) A1 - Horan, M A1 - Edwards, AD A1 - Firmin, RK A1 - Ablett, T A1 - Rawson, H A1 - Field, D J1 - EARLY HUM DEV Y1 - 2007/04// VL - 83 SN - 0378-3782 SP - 217 EP - 223 N2 - Objective: To explore the changes in the QTc interval during mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO).Design: Twenty seven neonates (median gestation 40 weeks; range 33-41 weeks) enrolled in a pilot study of mild hypothermia were studied during the first five days of ECMO. The first group (N=7) were maintained at 37 degrees C throughout the study period. Subsequent groups (N=5) were cooled to 36 degrees C, 35 degrees C and 34 degrees C respectively for twenty four hours and the final group to 34 degrees C for forty eight hours before being rewarmed to 37 degrees C.Using a 24 h digital monitor, the QT and QTc intervals were recorded continuously during the cooling and rewarming period and validated using standard 12 lead electrocardiograms. Patients were carefully assessed clinically and routine biochemistry (including magnesium and calcium) laboratory tests measured pre ECMO and at timed intervals during cooling and rewarming.Results: The mean difference between the continuous digital and 12 lead ECG values for QTc was - 13.3 ms. During the first 24 h of cooling, the mean (95th centile) values for the digitally measured QTc interval at 37 degrees C=431(506) milliseconds (ms); 36 degrees C=459(521) ms; 35 degrees C=445(516) ms; 34 degrees C=465(531) ms; 34 degrees C for 48 h=466(521) ms. During this period overall QTc increased by 3.12 ms (95% confidence intervals 6.17 to 0.84; p = 0.04) for each degree fall in body temperature. During rewarming, there was no significant relationship between QTc and temperature change. No serious arrhythmias were during cooling. Using univariate analysis, no relationship was found between QTc and electrolytes, heart rate and blood pressure.Conclusions: QTc shows significant variability in individuals, and only a small proportion of this can be explained by rectal temperature. Mild hypothermia was not associated with serious cardiac arrhythmias. (c) 2006 Elsevier Ireland Ltd. All rights reserved. ER - TY - JFULL T1 - Pax6 is misexpressed in Sox1 null lens fiber cells A1 - Donner, AL A1 - Ko, F A1 - Episkopou, V A1 - Maas, RL J1 - GENE EXPR PATTERNS Y1 - 2007/04// VL - 7 SN - 1567-133X SP - 606 EP - 613 N2 - Sox1 null lens fiber cells fail to elongate and have disrupted expression of gamma-crystallin. We have evaluated the expression of Sox1 and Pax6 proteins during critical stages of lens morphogenesis, with particular focus on fiber cell differentiation. While Pax6 and Sox1 are coexpressed during early stages of fiber cell differentiation, Sox1 up-regulation coincides temporally with the down-regulation of Pax6, and these proteins therefore display a striking inverse expression pattern in the lens fiber cell compartment. Furthermore, Pax6 is inappropriately expressed in the fiber cells of Sox1 null mice and the Pax6 target, alpha 5 integrin, is simultaneously misexpressed. Finally, we demonstrate a genetic interaction between Sox1 and Pax6, as Sox1 heterozygosity partially rescues the diameter of Pax6(Sey) lenses by increasing the number of cells in the fiber cell compartment. (c) 2007 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - Mechanisms of disease: genetic causes of familial hypercholesterolemia. A1 - Soutar, AK A1 - Naoumova, RP J1 - Nat Clin Pract Cardiovasc Med Y1 - 2007/04// VL - 4 SN - 1743-4300 SP - 214 EP - 225 N2 - Familial hypercholesterolemia (FH) is characterized by raised serum LDL cholesterol levels, which result in excess deposition of cholesterol in tissues, leading to accelerated atherosclerosis and increased risk of premature coronary heart disease. FH results from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a loss-of-function mutation in the LDL-receptor gene (LDLR) or by a mutation in the gene encoding apolipoprotein B (APOB). FH is primarily an autosomal dominant disorder with a gene-dosage effect. An autosomal recessive form of FH caused by loss-of-function mutations in LDLRAP1, which encodes a protein required for clathrin-mediated internalization of the LDL receptor by liver cells, has also been documented. The most recent addition to the database of genes in which defects cause FH is one encoding a member of the proprotein convertase family, PCSK9. Rare dominant gain-of-function mutations in PCSK9 cosegregate with hypercholesterolemia, and one mutation is associated with a particularly severe FH phenotype. Expression of PCSK9 normally downregulates the LDL-receptor pathway by indirectly causing degradation of LDL-receptor protein, and loss-of-function mutations in PCSK9 result in low plasma LDL levels. Thus, PCSK9 is an attractive target for new drugs aimed at lowering serum LDL cholesterol, which should have additive lipid-lowering effects to the statins currently used. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17380167&query_hl=1 ER - TY - JFULL T1 - Adenovirus 5 fibers mutated at the putative HSPG-binding site show restricted retargeting with targeting peptides in the HI loop A1 - Kritz, AB A1 - Nicol, CG A1 - Dishart, KL A1 - Nelson, R A1 - Holbeck, S A1 - Von Seggern, DJ A1 - Work, LM A1 - Mcvey, JH A1 - Nicklin, SA A1 - Baker, AH J1 - MOL THER Y1 - 2007/04// VL - 15 SN - 1525-0016 SP - 741 EP - 749 N2 - Adenoviral vectors are commonly used for liver-directed gene therapy following systemic administration owing to their strong propensity for hepatocyte transduction. However, many disease applications would benefit from the delivery of adenoviruses to alternate tissues via this route. Research has thus focused on stripping the virus of native hepatic tropism in conjunction with modifying virus capsid proteins to incorporate novel tropism. Recently, the KO1S* adenovirus serotype 5 fiber mutant, devoid of both coxsackie and adenovirus receptor binding in the fiber knob domain and mutated at the putative heparan sulphate proteoglycan binding site in the fiber shaft, was shown to possess strikingly poor hepatic tropism in mice, rats, and non-human primates. Thus, it is an ideal candidate for retargeting strategies. We therefore assessed the ability of peptide-modified KO1S* fibers to retarget adenovirus. Peptide insertions were well tolerated and virions produced to high titers. However, expected retargeting at the level of transduction was not observed, despite cell-binding studies showing enhanced vector targeting at the cell surface. Cy3 labeling studies showed retarded trafficking of S*-containing fibers. Taken together, our data demonstrates that KO1S* mutant fibers are ineffective for cell retargeting strategies. ER - TY - JFULL T1 - Desmin immunolocalisation in autosomal dominant Emery-Dreifuss muscular dystrophy. A1 - Piercy, RJ A1 - Zhou, H A1 - Feng, L A1 - Pombo, A A1 - Muntoni, F A1 - Brown, SC J1 - Neuromuscul Disord Y1 - 2007/04// VL - 17 SN - 0960-8966 SP - 297 EP - 305 N2 - Autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) is one of a number of allelic disorders caused by mutations in the nuclear lamina proteins, lamins A and C. The disorder is characterised by the early onset of skeletal muscle weakness and joint contractures and later, by dilated cardiomyopathy and cardiac arrythmias. Although the pathophysiology is not understood, one theory suggests that disordered structural organisation at weakened nuclei in contractile cells may underlie the disease. Previous work shows that mice deficient in lamin A/C develop similar skeletal and cardiac muscle signs to patients with AD-EDMD and ultrastructural examination of muscle from these mice shows abnormal localisation of desmin. We hypothesised therefore that desmin localisation may be abnormal in muscle or cells from patients with AD-EDMD and/or in cells expressing mutant lamins. In order to evaluate this, desmin immunolocalisation was determined in skeletal muscle biopsy sections from patients with AD-EDMD and cell lines including MyoD-transfected fibroblast-derived myotubes from AD-EDMD patients and murine embryonic stem cell-derived cardiomyocytes stably transfected with mutant human lamin A. Ultrastructural examination of patient muscle was also performed. Desmin was expressed and localised normally in patient muscle and cell lines and ultrastructural examination was similar to controls. These results fail to provide any evidence that dominant mutations in lamin A/C lead to a disorganisation of the desmin associated cytoskeleton. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17329105&query_hl=1 ER - TY - JFULL T1 - Agonist-dependent internalization of D2 receptors: Imaging quantification by confocal microscopy. A1 - Goggi, JL A1 - Sardini, A A1 - Egerton, A A1 - Strange, PG A1 - Grasby, PM J1 - Synapse Y1 - 2007/04// VL - 61 SN - 0887-4476 SP - 231 EP - 241 N2 - In positron emission tomography and single photon emission computed tomography studies using D2 dopamine (DA) receptor radiotracers, a decrease in radiotracer binding potential (BP) is usually interpreted in terms of increased competition with synaptic DA. However, some data suggest that this signal may also reflect agonist (DA)-induced increases in D2 receptor (D2R) internalization, a process which would presumably also decrease the population of receptors available for binding to hydrophilic radioligands. To advance interpretation of alterations in D2 radiotracer BP, direct methods of assessment of D2R internalization are required. Here, we describe a confocal microscopy-based approach for the quantification of agonist-dependent receptor internalization. The method relies upon double-labeling of the receptors with antibodies directed against intracellular as well as extracellular epitopes. Following agonist stimulation, DA D2R internalization was quantified by differentiating, in optical cell sections, the signal due to the staining of the extracellular from intracellular epitopes of D2Rs. Receptor internalization was increased in the presence of the D2 agonists DA and bromocriptine, but not the D1 agonist SKF38393. Pretreatment with either the D2 antagonist sulpiride, or inhibitors of internalization (phenylarsine oxide and high molarity sucrose), blocked D2-agonist induced receptor internalization, thus validating this method in vitro. This approach therefore provides a direct and streamlined methodology for investigating the pharmacological and mechanistic aspects of D2R internalization, and should inform the interpretation of results from in vivo receptor imaging studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17230553&query_hl=1 ER - TY - JFULL T1 - Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. A1 - Sanders, MJ A1 - Grondin, PO A1 - Hegarty, BD A1 - Snowden, MA A1 - Carling, D J1 - Biochem J Y1 - 2007/04/01/ VL - 403 SN - 1470-8728 SP - 139 EP - 148 N2 - AMPK (AMP-activated protein kinase) is activated allosterically by AMP and by phosphorylation of Thr172 within the catalytic alpha subunit. Here we show that mutations in the regulatory gamma subunit reduce allosteric activation of the kinase by AMP. In addition to its allosteric effect, AMP significantly reduces the dephosphorylation of Thr172 by PP (protein phosphatase)2Calpha. Moreover, a mutation in the gamma subunit almost completely abolishes the inhibitory effect of AMP on dephosphorylation. We were unable to detect any effect of AMP on Thr172 phosphorylation by either LKB1 or CaMKKbeta (Ca2+/calmodulin-dependent protein kinase kinase beta) using recombinant preparations of the proteins. However, using partially purified AMPK from rat liver, there was an apparent AMP-stimulation of Thr172 phosphorylation by LKB1, but this was blocked by the addition of NaF, a PP inhibitor. Western blotting of partially purified rat liver AMPK and LKB1 revealed the presence of PP2Calpha in the preparations. We suggest that previous studies reporting that AMP promotes phosphorylation of Thr172 were misinterpreted. A plausible explanation for this effect of AMP is inhibition of dephosphorylation by PP2Calpha, present in the preparations of the kinases used in the earlier studies. Taken together, our results demonstrate that AMP activates AMPK via two mechanisms: by direct allosteric activation and by protecting Thr172 from dephosphorylation. On the basis of our new findings, we propose a simple model for the regulation of AMPK in mammalian cells by LKB1 and CaMKKbeta. This model accounts for activation of AMPK by two distinct signals: a Ca2+-dependent pathway, mediated by CaMKKbeta and an AMP-dependent pathway, mediated by LKB1. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17147517&query_hl=1 ER - TY - JFULL T1 - Sox2 and Pou2f1 interact to control lens and olfactory placode development A1 - Donner, AL A1 - Episkopou, V A1 - Maas, RL J1 - DEV BIOL Y1 - 2007/03/15/ VL - 303 SN - 0012-1606 SP - 784 EP - 799 N2 - Sox2, which encodes an SRY-like HMG box transcription factor, is critical for vertebrate development. Sox2 mediates its transcriptional effects through the formation of complexes with specific co-factors, many of which are unknown. In this report, we identify Oct-1, encoded by the Pou2f1 gene, as a co-factor for Sox2 in the context of mouse lens and nasal placode induction. Oct-1, Sox2, and Pax6 are co-expressed during lens and nasal placode induction and during subsequent developmental stages. Genetic combination of Sox2 and Pou2f1 mutant alleles results in impaired induction of the lens placode, an ocular phenotype that includes anophthalmia, and a complete failure of nasal placode induction. These ocular and nasal phenotypes closely resemble those observed in Pax6 null embryos. Moreover, we identify DNA-binding sites that support the cooperative formation of a complex between Sox2 and Oct-1 and mediate Sox2/Oct-1-dependent transactivation of the Pax6 lens ectoderm enhancer in vitro. We demonstrate that the same Sox- and Octamer-binding sites are essential for Pax6 enhancer activity in the lens placode and its derivatives in transgenic mouse embryos. Collectively, these results indicate that Pou2f1, Sox2 and Pax6 are interdependent components of a molecular pathway utilized in both lens and nasal placode induction. (c) 2006 Elsevier Inc. All rights reserved. ER - TY - JFULL T1 - Design and development of a prototype endocavitary probe for high-intensity focused ultrasound delivery with integrated magnetic resonance imaging A1 - Wharton, IP A1 - Rivens, IH A1 - ter Haar, GR A1 - Gilderdale, DJ A1 - Collins, DJ A1 - Hand, JW A1 - Abel, PD A1 - Desouza, NM J1 - J MAGN RESON IMAGING Y1 - 2007/03// VL - 25 SN - 1053-1807 SP - 548 EP - 556 N2 - Purpose: To integrate a high intensity focused ultrasound (HIFU) transducer with an MR receiver coil for endocavitary MR-guided thermal ablation of localized pelvic lesions.Materials and Methods: A hollow semicylindrical probe (diameter 3.2 ern) with a rectangular upper surface (7.2 cm X 3.2 cm) was designed to house a HIFU transducer and enable acoustic contact with an intraluminal wall. The probe was distally rounded to ease endocavitary insertion and was proximally tapered to a 1.5-cm diameter cylindrical handle through which the irrigation tubes (for transducer cooling) and electrical connections were passed. MR compatibility of piezoeeramic and piezocomposite transducers was assessed using gradient-echo (GRE) sequences. The radiofrequency (RF) tuning of identical 6.5 cm X 2.5 cm rectangular receiver coils on the upper surface of the probe was adjusted to compensate for the presence of the conductive components of the HIFU transducers. A T1-weighted (T1-W) sliding window dual-echo GRE sequence monitored phase changes in the focal zone of each transducer. High-intensity (2400 W/cm(-2)), short duration (< 1.5 seconds) exposures produced subtherapeutic temperature rises.Results: For T1-W images, signal-to-noise ratio (SNR) improved by 40% as a result of quartering the conductive surface of the piezoceramic transducer. A piezocomposite transducer showed a further 28% improvement. SNRs for an endocavitary coil in the focal plane of the HIFU transducer (4 cm from its face) were three times greater than from a phased body array coil. Local shimming improved uniformity of phase images. Phase changes were detected at subtherapeutic exposures.Conclusion: We combined a HIFU transducer with an MR receiver coil in an endocavitary probe. SNRs were improved by quartering the conductive surface of the piezoceramic. Further improvement was achieved with a piezoeomposite transducer. A phase change was seen on MR images during both subtherapeutic and therapeutic HIFU exposures. ER - TY - JFULL T1 - Relationship between intrahepatocellular lipid content and features of the metabolic syndrome in subjects with known nonalcoholic fatty liver disease and healthy volunteers A1 - Mehta, SR A1 - Godsland, IF A1 - Thomas, EL A1 - Bell, JD A1 - Patel, N A1 - Fitzpatrick, J A1 - Durighel, G A1 - Westerland, O A1 - Anyakou, U A1 - Pavitt, D A1 - Taylor-Robinson, SD A1 - Johnston, DG J1 - DIABETIC MED Y1 - 2007/03// VL - 24 SN - 0742-3071 SP - 45 EP - 46 ER - TY - JFULL T1 - Cognitive and behavioral findings in Prader-Willi syndrome and early-onset morbid obesity A1 - Miller, J A1 - Kranzler, J A1 - Hatfield, A A1 - Mueller, OT A1 - Theriaque, DW A1 - Goldstone, AP A1 - Shuster, JJ A1 - Driscoll, DJ J1 - AM J MED GENET A Y1 - 2007/03/01/ VL - 143A SN - 1552-4825 SP - 496 EP - 497 ER - TY - JFULL T1 - Significant evidence of one or more susceptibility loci for endometriosis with near-Mendelian inheritance on chromosome 7p13-15. A1 - Zondervan, KT A1 - Treloar, SA A1 - Lin, J A1 - Weeks, DE A1 - Nyholt, DR A1 - Mangion, J A1 - MacKay, IJ A1 - Cardon, LR A1 - Martin, NG A1 - Kennedy, SH A1 - Montgomery, GW J1 - Hum Reprod Y1 - 2007/03// VL - 22 SN - 0268-1161 SP - 717 EP - 728 N2 - BACKGROUND: Endometriosis is a common disease with a heritable component. The collaborative International Endogene Study consists of two data sets (Oxford and Australia) comprising 1176 families with multiple affected. The aim was to investigate whether the apparent concentration of cases in a proportion of families could be explained by one or more rare variants with (near-)Mendelian autosomal inheritance. METHODS AND RESULTS: Linkage analyses (aimed at finding chromosomal regions harbouring disease-predisposing genes) were conducted in families with three or more affected (Oxford: n = 52; Australia: n = 196). In the Oxford data set, a non-parametric linkage score (Kong & Cox (K&C) Log of ODds (LOD)) of 3.52 was observed on chromosome 7p (genome-wide significance P = 0.011). A parametric MOD score (equal to maximum LOD maximized over 357 possible inheritance models) of 3.89 was found at 65.72 cM (D7S510) for a dominant model with reduced penetrance. After including the Australian data set, the non-parametric K&C LOD of the combined data set was 1.46 at 57.3 cM; the parametric analysis found an MOD score of 3.30 at D7S484 (empirical significance: P = 0.035) for a recessive model with high penetrance. Critical recombinant analysis narrowed the probable region of linkage down to overlapping 6.4 Mb and 11 Mb intervals containing 48 and 96 genes, respectively. CONCLUSIONS: This is the first report to suggest that there may be one or more high-penetrance susceptibility loci for endometriosis with (near-)Mendelian inheritance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158817&query_hl=1 ER - TY - JFULL T1 - In silico prediction of FVIII epitopes recognised by natural autoantibodies in polyvalent immunoglobulin concentrates. A1 - Di Giambattista, M A1 - Branckaert, T A1 - Hougardy, V A1 - Kemball-Cook, G A1 - Laub, R J1 - Mol Immunol Y1 - 2007/03// VL - 44 SN - 0161-5890 SP - 1903 EP - 1913 N2 - Inhibitory antibodies directed against blood coagulation factor VIII (FVIII) impair FVIII replacement therapy, constituting a serious complication in haemophilic and autoimmune patients. Identifying B-cell FVIII epitopes and mapping them on the molecule remain important challenges. Using a combination of different algorithms, more than 30 hypothetical linear epitopes were predicted on the FVIII molecule surface. We selected several major predicted sequences, spanning all FVIII domains, for specific antibody induction in rabbits. All peptides tested successfully induced production of specific anti-FVIII rabbit antibodies, supporting the relevance of our approach. To investigate the presence of FVIII-reactive antibodies in the healthy donor population, a pooled fraction rich in all IgG subclasses was purified on peptide-Sepharose columns. Substantial amounts of Ig, specific for each FVIII peptide, were purified with yields ranging from 8 to 223 ng/mg immunoglobulins. Our results confirm the diversity of FVIII epitopes recognised by natural human anti-FVIII autoantibodies. All IgG subclasses were found in the affinity-isolated anti-peptide material, with overrepresentation of IgG2 and IgG4. Evidence was also found for new FVIII epitopes. Five human anti-peptide preparations displayed FVIII-neutralising activity, ranging from 1.3 to 5.3 BU/mg. Although the presence of naturally occurring anti-FVIII antibodies in healthy donors has been previously described, our methodology has allowed, for the first time, a fine mapping of several inhibitory and non-inhibitory epitopes. Our observations support the hypothesis that FVIII inhibitors in haemophilia A and autoimmune disease may originate from the proliferation of natural FVIII-specific B-cell clones. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17113150&query_hl=1 ER - TY - JFULL T1 - Chromosome organization: new facts, new models. A1 - Branco, MR A1 - Pombo, A J1 - Trends Cell Biol Y1 - 2007/03// VL - 17 SN - 0962-8924 SP - 127 EP - 134 N2 - The study of nuclear organization has radically changed the way we envision gene regulation, imposing a paradigm shift from a seemingly featureless nucleus to a highly compartmentalized and complex organelle. The positioning of genes, regulatory sequences and transcription factors in relation to each other and to landmarks in the nucleus, such as nuclear bodies and the lamina, is important in determining which genes are transcribed at any one time. Investigating chromatin organization during interphase is therefore essential to the understanding of gene expression. The recent discovery of interactions between distal chromatin segments that occur within the same chromosome or across different chromosomes, and that have a role in transcription regulation, suggests a re-evaluation of current models of chromosome organization and the development of new ones. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17197184&query_hl=1 ER - TY - JFULL T1 - Arkadia enhances Nodal/TGF-beta signaling by coupling phospho-Smad2/3 activity and turnover. A1 - Mavrakis, KJ A1 - Andrew, RL A1 - Lee, KL A1 - Petropoulou, C A1 - Dixon, JE A1 - Navaratnam, N A1 - Norris, DP A1 - Episkopou, V J1 - PLoS Biol Y1 - 2007/03// VL - 5 SN - 1545-7885 SP - e67 EP - e67 N2 - Regulation of transforming growth factor-beta (TGF-beta) signaling is critical in vertebrate development, as several members of the TGF-beta family have been shown to act as morphogens, controlling a variety of cell fate decisions depending on concentration. Little is known about the role of intracellular regulation of the TGF-beta pathway in development. E3 ubiquitin ligases target specific protein substrates for proteasome-mediated degradation, and several are implicated in signaling. We have shown that Arkadia, a nuclear RING-domain E3 ubiquitin ligase, is essential for a subset of Nodal functions in the embryo, but the molecular mechanism of its action in embryonic cells had not been addressed. Here, we find that Arkadia facilitates Nodal signaling broadly in the embryo, and that it is indispensable for cell fates that depend on maximum signaling. Loss of Arkadia in embryonic cells causes nuclear accumulation of phospho-Smad2/3 (P-Smad2/3), the effectors of Nodal signaling; however, these must be repressed or hypoactive as the expression of their direct target genes is reduced or lost. Molecular and functional analysis shows that Arkadia interacts with and ubiquitinates P-Smad2/3 causing their degradation, and that this is via the same domains required for enhancing their activity. Consistent with this dual function, introduction of Arkadia in homozygous null (-/-) embryonic stem cells activates the accumulated and hypoactive P-Smad2/3 at the expense of their abundance. Arkadia-/- cells, like Smad2-/- cells, cannot form foregut and prechordal plate in chimeras, confirming this functional interaction in vivo. As Arkadia overexpression never represses, and in some cells enhances signaling, the degradation of P-Smad2/3 by Arkadia cannot occur prior to their activation in the nucleus. Therefore, Arkadia provides a mechanism for signaling termination at the end of the cascade by coupling degradation of P-Smad2/3 with the activation of target gene transcription. This mechanism can account for achieving efficient and maximum Nodal signaling during embryogenesis and for rapid resetting of target gene promoters allowing cells to respond to dynamic changes in extracellular signals. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17341133&query_hl=1 ER - TY - JFULL T1 - Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits. A1 - Thompson, EC A1 - Cobb, BS A1 - Sabbattini, P A1 - Meixlsperger, S A1 - Parelho, V A1 - Liberg, D A1 - Taylor, B A1 - Dillon, N A1 - Georgopoulos, K A1 - Jumaa, H A1 - Smale, ST A1 - Fisher, AG A1 - Merkenschlager, M J1 - Immunity Y1 - 2007/03// VL - 26 SN - 1074-7613 SP - 335 EP - 344 N2 - Ikaros DNA-binding proteins are critical for the development of lymphocytes and other hematopoietic lineages, but it remains unclear how they cooperate with other regulators of signaling and transcription to achieve ordered gene expression during development. Here, we show that Ikaros proteins regulate the pre-BCR component lambda5 in a stage-specific manner. In pre-BI cells, Ikaros modulated lambda5 expression in competition with the transcriptional activator EBF. This required Ikaros binding to the Igll1 (lambda5) promoter and was abolished either by mutation of the Ikaros DNA-binding domain or by deletion of a single Ikaros site from the Igll1 promoter. At the transition from the pre-BI to pre-BII stage, the expression of the Ikaros family member Aiolos was upregulated and required for the efficient silencing of Igll1. Aiolos expression was controlled by pre-BCR signals via the adaptor protein SLP-65. Thus, pre-BCR signaling regulates Aiolos and the silencing of Igll1 via a developmental-stage-specific feedback loop. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17363301&query_hl=1 ER - TY - JFULL T1 - No contribution of angiotensin-converting enzyme (ACE) gene variants to severe obesity: a model for comprehensive case/control and quantitative cladistic analysis of ACE in human diseases. A1 - Bell, CG A1 - Meyre, D A1 - Petretto, E A1 - Levy-Marchal, C A1 - Hercberg, S A1 - Charles, MA A1 - Boyle, C A1 - Weill, J A1 - Tauber, M A1 - Mein, CA A1 - Aitman, TJ A1 - Froguel, P A1 - Walley, AJ J1 - Eur J Hum Genet Y1 - 2007/03// VL - 15 SN - 1018-4813 SP - 320 EP - 327 N2 - Candidate gene analyses are often inconclusive owing to genetic or phenotypic heterogeneity, low statistical power, selection of nonfunctional SNPs, and inadequate statistical analysis of the genetic architecture. Angiotensin-converting enzyme (ACE) is involved in adipocyte growth and function and the ACE-processed angiotensin II inhibits adipocyte differentiation. Associations between body mass index (BMI) and ACE polymorphisms have been reported in general populations, but the contribution to severe obesity of this gene, which is located under an obesity genome-scan linkage peak on 17q23, is unknown. ACE is one of the most studied genes and markers responsible for variation in circulating ACE enzyme levels have been extensively characterised. Eight of these variants were genotyped in 1054 severely obese cases and 918 nonobese controls, as well as 116 nuclear families from the genome scan (n=447), enabling the known clades to be inferred. Qualitative analysis of individual single-nucleotide polymorphisms (SNPs), haplotypes, clades, and diploclades demonstrated no significant associations (P<0.05) after minimal correction for multiple testing. Quantitative analysis of clades and diploclades for BMI, waist-to-hip ratio, or ZBMI in children were also not significant. This rigorous, large-scale study of common, well-defined, severe polygenic obesity provides strong evidence that functionally relevant sequence variation in ACE, whether it is defined at the level of SNPs, haplotypes, or clades, is not associated with severe obesity in French Caucasians. Such a study design exemplifies the strategy needed to clearly define the contribution of the ACE gene to the plethora of complex genetic diseases where weak associations have been previously reported. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17164796&query_hl=1 ER - TY - JFULL T1 - ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment. A1 - Weylandt, KH A1 - Nebrig, M A1 - Jansen-Rosseck, N A1 - Amey, JS A1 - Carmena, D A1 - Wiedenmann, B A1 - Higgins, CF A1 - Sardini, A J1 - Mol Cancer Ther Y1 - 2007/03// VL - 6 SN - 1535-7163 SP - 979 EP - 986 N2 - Resistance to anticancer drugs and consequent failure of chemotherapy is a complex problem severely limiting therapeutic options in metastatic cancer. Many studies have shown a role for drug efflux pumps of the ATP-binding cassette transporters family in the development of drug resistance. ClC-3, a member of the CLC family of chloride channels and transporters, is expressed in intracellular compartments of neuronal cells and involved in vesicular acidification. It has previously been suggested that acidification of intracellular organelles can promote drug resistance by increasing drug sequestration. Therefore, we hypothesized a role for ClC-3 in drug resistance. Here, we show that ClC-3 is expressed in neuroendocrine tumor cell lines, such as BON, LCC-18, and QGP-1, and localized in intracellular vesicles co-labeled with the late endosomal/lysosomal marker LAMP-1. ClC-3 overexpression increased the acidity of intracellular vesicles, as assessed by acridine orange staining, and enhanced resistance to the chemotherapeutic drug etoposide by almost doubling the IC(50) in either BON or HEK293 cell lines. Prevention of organellar acidification, by inhibition of the vacuolar H(+)-ATPase, reduced etoposide resistance. No expression of common multidrug resistance transporters, such as P-glycoprotein or multidrug-related protein-1, was detected in either the BON parental cell line or the derivative clone overexpressing ClC-3. The probable mechanism of enhanced etoposide resistance can be attributed to the increase of vesicular acidification as consequence of ClC-3 overexpression. This study therefore provides first evidence for a role of intracellular CLC proteins in the modulation of cancer drug resistance. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17363491&query_hl=1 ER - TY - JFULL T1 - Modeling epithelial cell behavior and organization A1 - Maheswaran, S A1 - Speight, PM A1 - Hammond, P J1 - IEEE T NANOBIOSCI Y1 - 2007/03// VL - 6 SN - 1536-1241 SP - 77 EP - 85 N2 - We propose an individual cell based model for epithelial cell interactions. The model includes biological processes such as cell division, differentiation, adhesion, and death. Cell types include stem, transit amplifying, intermediate, mature, and dead. Stem and transit amplifying cells are allowed to divide provided they are on the basement membrane. In particular, the roles of differential adhesion and cell division during the development are discussed. The typical ordered structure of a healthy epithelium is shown to arise provided differential adhesion and cell division are modeled appropriately. ER - TY - JFULL T1 - A rare polymorphism in the low density lipoprotein (LDL) gene that affects mRNA splicing. A1 - Bourbon, M A1 - Sun, XM A1 - Soutar, AK J1 - Atherosclerosis Y1 - 2007/02/27/ SN - 0021-9150 N2 - Familial hypercholesterolaemia (FH) is usually caused by mutations in the low density lipoprotein (LDL) receptor gene (LDLR) that impair clearance of LDL from the circulation. The increased risk of premature coronary heart disease associated with FH can be reduced by dietary advice and treatment with lipid-lowering drug therapy, but it is important to identify affected individuals at an early stage. Several programmes for genetic diagnosis of FH that rely on identifying nucleotide substitutions in genomic DNA have been initiated, but the validity of these is dependent on distinguishing between a silent nucleotide variant and a mutation that affects LDL-receptor function. Here we describe a single nucleotide substitution in the coding region of exon 9 of LDLR that is an apparently silent polymorphism: CGG (Arg406) to AGG (Arg). Analysis of mRNA from the patient's cells showed that the mutation introduces a new splice site that is used to the exclusion of the natural splice site and causes a deletion of 31bp from the mRNA, predicted to introduce premature termination four codons after R406. This finding emphasizes the caution needed in genetic diagnosis of FH based on genomic DNA sequence alone. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17335829&query_hl=1 ER - TY - JFULL T1 - Medical progress - Coronary microvascular dysfunction A1 - Camici, PG A1 - Crea, F J1 - NEW ENGL J MED Y1 - 2007/02/22/ VL - 356 SN - 0028-4793 SP - 830 EP - 840 ER - TY - JFULL T1 - Coronary microvascular dysfunction. A1 - Camici, PG A1 - Crea, F J1 - N Engl J Med Y1 - 2007/02/22/ VL - 356 SN - 1533-4406 SP - 830 EP - 840 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17314342&query_hl=1 ER - TY - JFULL T1 - White matter lesions in term infants with neonatal encephalopathy: Correlation with later scans' and neurodevelopmental outcome A1 - Bregant, T A1 - Rutherford, M A1 - Cowan, F J1 - EARLY HUM DEV Y1 - 2007/02// VL - 83 SN - 0378-3782 SP - 128 EP - 128 ER - TY - JFULL T1 - Patterns of brain injury in neonates exposed to perinatal sentinel events A1 - Okereafor, A A1 - Allsop, J A1 - Counsell, S A1 - Fitzpatrick, J A1 - Azzopardi, D A1 - Rutherford, M A1 - Cowan, F J1 - EARLY HUM DEV Y1 - 2007/02// VL - 83 SN - 0378-3782 SP - 126 EP - 127 ER - TY - JFULL T1 - Structure and function of ABC transporters: the ATP switch provides flexible control. A1 - Linton, KJ A1 - Higgins, CF J1 - Pflugers Arch Y1 - 2007/02// VL - 453 SN - 0031-6768 SP - 555 EP - 567 N2 - ATP-binding cassette (ABC) transporters are ubiquitous integral membrane proteins that facilitate the transbilayer movement of ligands. They comprise, minimally, two transmembrane domains, which impart ligand specificity, and two nucleotide-binding domains (NBDs), which power the transport cycle. Almost 25 years of biochemistry is reviewed in light of the recent structure analyses resulting in the ATP-switch model for function in which the NBDs switch between a dimeric conformation, closed around two molecules of ATP, and a nucleotide-free, dimeric 'open' conformation. The flexibility of this switching mechanism has evolved to provide different kinetic control for different transporters and has also been co-opted to diverse functions other than transmembrane transport. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16937116&query_hl=1 ER - TY - JFULL T1 - Radical scavengers: A practical solution to the reproducibility issue in the fluoridation of diaryliodonium salts A1 - Carroll, MA A1 - Nairne, J A1 - Smith, G A1 - Widdowson, DA J1 - J FLUORINE CHEM Y1 - 2007/02// VL - 128 SN - 0022-1139 SP - 127 EP - 132 N2 - The addition of radical scavengers to the fluoridation of diaryliodonium salts was demonstrated to improve significantly both the reproducibility of the process and the material yield of the desired fluoroarene products. It was also established that the selectivity of the process was not influenced by the presence of the radical scavengers. TEMPO and galvinoxyl were found to be the most suitable radical scavengers in the fluoridation process allowing the methodology to be used routinely for the first time. (c) 2006 Published by Elsevier B.V. ER - TY - JFULL T1 - Assessment of the visual system in preterm infants using diffusion tractography and fMRI A1 - Raafat, RM A1 - Dresner, MA A1 - Counsel, SJ A1 - Srinivasan, L A1 - Hajnal, JV A1 - Edwards, AD J1 - EARLY HUM DEV Y1 - 2007/02// VL - 83 SN - 0378-3782 SP - 127 EP - 128 ER - TY - JFULL T1 - Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography. A1 - Counsell, SJ A1 - Dyet, LE A1 - Larkman, DJ A1 - Nunes, RG A1 - Boardman, JP A1 - Allsop, JM A1 - Fitzpatrick, J A1 - Srinivasan, L A1 - Cowan, FM A1 - Hajnal, JV A1 - Rutherford, MA A1 - Edwards, AD J1 - Neuroimage Y1 - 2007/02/01/ VL - 34 SN - 1053-8119 SP - 896 EP - 904 N2 - Our aim was to investigate the feasibility of studying white matter tracts and connections between the thalamus and the cortex in 2-year-old infants who were born preterm by probabilistic magnetic resonance (MR) tractography. Using this approach, we were able to visualize and quantify connectivity distributions in a number of white matter tracts, including the corticospinal tracts, optic radiations, fibers of the genu and splenium of the corpus callosum, superior longitudinal fasciculus and inferior fronto-occipital fasciculus, and to map the distribution within thalamus of fibers connecting to specific cortical regions. In eleven infants with no MR evidence of focal cerebral lesions and appropriate neurodevelopment as shown by general quotient (GQ) scores above 100, we mapped cortical connections to the thalamus that appeared similar to those reported in adults. However, in a proof-of-principle experiment, we examined one further child with marked white matter abnormalities and found that the volume and pattern of thalamo-cortical connections were severely disrupted. This technique promises to be a useful tool for assessing connectivity in the developing brain and in infants with lesions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17174575&query_hl=1 ER - TY - JFULL T1 - Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism A1 - Shojaee-Moradie, F A1 - Baynes, KCR A1 - Pentecost, C A1 - Bell, JD A1 - Thomas, EL A1 - Jackson, NC A1 - Stolinski, M A1 - Whyte, M A1 - Lovell, D A1 - Bowes, SB A1 - Gibney, J A1 - Jones, RH A1 - Umpleby, AM J1 - DIABETOLOGIA Y1 - 2007/02// VL - 50 SN - 0012-186X SP - 404 EP - 413 N2 - It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables.We randomised 17 sedentary overweight male subjects (age 50 +/- 2.6 years, BMI 27.6 +/- 0.5 kg/m(2)) to a 6-week exercise programme (n=10) or control group (n=7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic-euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg(-1) min(-1)]. In the exercise group subjects were studied > 72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning.After 6 weeks, fasting glycerol, palmitic acid Ra (p=0.003, p=0.042) and NEFA concentration (p=0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p=0.026; p=0.007 and p=0.04). There was no change in muscle triacylglycerol and liver fat in either group.Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise. ER - TY - JFULL T1 - SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. A1 - Esapa, CT A1 - Waite, A A1 - Locke, M A1 - Benson, MA A1 - Kraus, M A1 - McIlhinney, RA A1 - Sillitoe, RV A1 - Beesley, PW A1 - Blake, DJ J1 - Hum Mol Genet Y1 - 2007/02/01/ VL - 16 SN - 0964-6906 SP - 327 EP - 342 N2 - Myoclonus-dystonia syndrome (MDS) is a genetically heterogeneous disorder characterized by myoclonic jerks often seen in combination with dystonia and psychiatric co-morbidities and epilepsy. Mutations in the gene encoding epsilon-sarcoglycan (SGCE) have been found in some patients with MDS. SGCE is a maternally imprinted gene with the disease being inherited in an autosomal dominant pattern with reduced penetrance upon maternal transmission. In the central nervous system, epsilon-sarcoglycan is widely expressed in neurons of the cerebral cortex, basal ganglia, hippocampus, cerebellum and the olfactory bulb. epsilon-Sarcoglycan is located at the plasma membrane in neurons, muscle and transfected cells. To determine the effect of MDS-associated mutations on the function of epsilon-sarcoglycan we examined the biosynthesis and trafficking of wild-type and mutant proteins in cultured cells. In contrast to the wild-type protein, disease-associated epsilon-sarcoglycan missense mutations (H36P, H36R and L172R) produce proteins that are undetectable at the cell surface and are retained intracellularly. These mutant proteins become polyubiquitinated and are rapidly degraded by the proteasome. Furthermore, torsinA, that is mutated in DYT1 dystonia, a rare type of primary dystonia, binds to and promotes the degradation of epsilon-sarcoglycan mutants when both proteins are co-expressed. These data demonstrate that some MDS-associated mutations in SGCE impair trafficking of the mutant protein to the plasma membrane and suggest a role for torsinA and the ubiquitin proteasome system in the recognition and processing of misfolded epsilon-sarcoglycan. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17200151&query_hl=1 ER - TY - JFULL T1 - Ability to acquire drug resistance arises early during the tumorigenesis process. A1 - Yagüe, E A1 - Arance, A A1 - Kubitza, L A1 - O'Hare, M A1 - Jat, P A1 - Ogilvie, CM A1 - Hart, IR A1 - Higgins, CF A1 - Raguz, S J1 - Cancer Res Y1 - 2007/02/01/ VL - 67 SN - 0008-5472 SP - 1130 EP - 1137 N2 - Resistance to chemotherapy is one of the principal causes of cancer mortality and is generally considered a late event in tumor progression. Although cellular models of drug resistance have been useful in identifying the molecules responsible for conferring drug resistance, most of these cellular models are derived from cell lines isolated from patients at a late stage in cancer progression. To ask at which stage in the tumorigenic progression does the cell gain the ability to acquire drug resistance, we generated a series of pre-tumorigenic and tumorigenic cells from human embryonic skin fibroblasts by introducing, sequentially, the catalytic subunit of telomerase, SV40 large T and small T oncoproteins, and an oncogenic form of ras. We show that the ability to acquire multidrug resistance (MDR) can arise before the malignant transformation stage. The minimal set of changes necessary to obtain pre-tumorigenic drug-resistant cells is expression of telomerase and inactivation of p53 and pRb. Thus, the pathways inactivated during tumorigenesis also confer the ability to acquire drug resistance. Microarray and functional studies of drug-resistant pre-tumorigenic cells indicate that the drug efflux pump P-glycoprotein is responsible for the MDR phenotype in this pre-tumorigenic cell model. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17283147&query_hl=1 ER - TY - JFULL T1 - Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography. A1 - Rimoldi, OE A1 - Drake-Holland, AJ A1 - Noble, MI A1 - Camici, PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2007/02// VL - 34 SN - 1619-7070 SP - 197 EP - 205 N2 - PURPOSE: Positron emission tomography (PET) studies in patients with diabetic autonomic neuropathy (DAN) have demonstrated the impact of this disease on cardiac sympathetic innervation and myocardial blood flow (MBF). To investigate the effects of selective partial sympathetic denervation of the left ventricle (LV) on baseline and hyperaemic MBF, we measured myocardial presynaptic catecholamine re-uptake (uptake-1), beta-adrenoceptor (beta-AR) density and MBF non-invasively by means of PET in a canine model of regional sympathetic denervation. METHODS: In 11 anaesthetised dogs, the sympathetic nerves of the free wall and septum of the LV were removed by means of dissection and phenol painting. Three weeks later, the animals were studied with PET. MBF was measured at baseline and following i.v. adenosine (140 microg kg(-1) min(-1)) and dobutamine (20 microg kg(-1) min(-1)) using(15)O-labelled water. Sympathetic denervation was confirmed by an 80+/-12% decrease in the volume of distribution (V(d)) of [(11)C]hydroxyephedrine (HED) compared with innervated regions. Myocardial beta-AR density was measured using [(11)C]CGP12177. RESULTS: Innervated and denervated regions showed no differences in MBF at baseline and during adenosine or dobutamine. [(11)C]HED V(d)was inversely correlated with MBF in both regions at baseline, and the correlation was lost during hyperaemia in denervated regions. However, for any given value of MBF, [(11)C]HED V(d)was significantly lower in the denervated regions. beta-AR density was comparable in denervated and innervated regions (17.9+/-4.2 vs 18.4+/-3.3 pmol g(-1); p=NS). CONCLUSION: In this experimental model, selective, regional sympathetic denervation of the LV, which results in a profound reduction in [(11)C]HED V(d), did not affect baseline or hyperaemic MBF. In addition, we demonstrated that, under baseline conditions, there was a significant inverse correlation between [(11)C]HED V(d)and MBF in both denervated and innervated regions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16951953&query_hl=1 ER - TY - JFULL T1 - Lack of influence of mild hypothermia on amplitude integrated-electroencephalography in neonates receiving extracorporeal membrane oxygenation. A1 - Horan, M A1 - Azzopardi, D A1 - Edwards, AD A1 - Firmin, RK A1 - Field, D J1 - Early Hum Dev Y1 - 2007/02// VL - 83 SN - 0378-3782 SP - 69 EP - 75 N2 - OBJECTIVE: To observe amplitude integrated electroencephalography (aEEG) in neonates receiving ECMO and to determine whether mild hypothermia influenced the aEEG recording. METHODS: Twenty-six consecutive neonates enrolled in a pilot study of mild hypothermia during ECMO were studied. The first group (N=6) was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C (N=4), 35 degrees C (N=5), and finally 34 degrees C (N=6) respectively for 24 h and the final group (N=5) to 34 degrees C for 48 h before being rewarmed to 37 degrees C. The aEEG was recorded continuously during the first 5 days of ECMO. The aEEG was classified as normal, moderately or severely suppressed and examined for the occurrence of seizures. To assess the effect of temperature, the aEEG was compared over 12 h during the final 6 h of cooling and during the first 6 h once infants were rewarmed. RESULTS: No change in aEEG amplitude was noted over the temperature range studied. Of the 26 traces obtained, 16 (62%) were normal throughout, 6 (23%) were intermittently moderately abnormal and 1 (14%) was severely abnormal. Three (11%) traces had periods of frequent seizure activity and these were not associated with clinical manifestations in two neonates. In one infant who suffered a cerebral haemorrhage, the aEEG became abnormal before cranial ultrasound abnormalities were apparent. CONCLUSIONS: Continuous cerebral monitoring with aEEG is feasible during ECMO and may add information to clinical examination. Mild hypothermia to 34 degrees C for up to 48 h does not influence the aEEG suggesting that cerebral monitoring with aEEG is possible during mild hypothermia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16814962&query_hl=1 ER - TY - JFULL T1 - Phospho-dependent functional modulation of GABA(B) receptors by the metabolic sensor AMP-dependent protein kinase A1 - Kuramoto, N A1 - Wilkins, ME A1 - Fairfax, BP A1 - Revilla-Sanchez, R A1 - Terunuma, M A1 - Tamaki, K A1 - Iemata, M A1 - Warren, N A1 - Couve, A A1 - Calver, A A1 - Horvath, Z A1 - Freeman, K A1 - Carling, D A1 - Huang, L A1 - Gonzales, C A1 - Cooper, E A1 - Smart, TG A1 - Pangalos, MN A1 - Moss, SJ J1 - NEURON Y1 - 2007/01/18/ VL - 53 SN - 0896-6273 SP - 233 EP - 247 N2 - GABA(B) receptors are heterodimeric G protein-coupled receptors composed of R1 and R2 subunits that mediate slow synaptic inhibition in the brain by activating inwardly rectifying K+ channels (GIRKs) and inhibiting Ca2+, channels. We demonstrate here that GABAB receptors are intimately associated with 5'AMP-dependent protein kinase (AMPK). AMPK acts as a metabolic sensor that is potently activated by increases in 5'AMP concentration that are caused by enhanced metabolic activity, anoxia, or ischemia. AMPK binds the R1 subunit and directly phosphorylates S783 in the R2 subunit to enhance GABAB receptor activation of GIRKs. Phosphorylation of S783 is evident in many brain regions, and is increased dramatically after ischemic injury. Finally, we also reveal that S783 plays a critical role in enhancing neuronal survival after ischemia. Together our results provide evidence of a neuroprotective mechanism, which, under conditions of metabolic stress or after ischemia, increases GABAB receptor function to reduce excitotoxicity and thereby promotes neuronal survival. ER - TY - JFULL T1 - A revolution in liver ultrasound. A1 - Cosgrove, DO J1 - Eur J Gastroenterol Hepatol Y1 - 2007/01// VL - 19 SN - 0954-691X SP - 1 EP - 2 N2 - Liver ultrasound has been revolutionized by the development of microbubble contrast agents and multipulse software designed to detect their nonlinear resonances. The ability to visualize all parts of the liver's vasculature, including the sinusoids, at high spatial and temporal resolution gives unique insights into the haemodynamics of focal liver lesions. It has enabled ultrasound to detect and, as described by Celli N, et al.Eur J Gastroenterol Hepatol 2007; 3-14, to characterize such lesions with an accuracy comparable to multidetector computed tomography with consequent improvements in patient handling. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17206070&query_hl=1 ER - TY - JFULL T1 - Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5. A1 - Roessler, S A1 - Györy, I A1 - Imhof, S A1 - Spivakov, M A1 - Williams, RR A1 - Busslinger, M A1 - Fisher, AG A1 - Grosschedl, R J1 - Mol Cell Biol Y1 - 2007/01// VL - 27 SN - 0270-7306 SP - 579 EP - 594 N2 - Early differentiation of B lymphocytes requires the function of multiple transcription factors that regulate the specification and commitment of the lineage. Loss- and gain-of-function experiments have provided important insight into the transcriptional control of B lymphopoiesis, whereby E2A was suggested to act upstream of EBF1 and Pax5 downstream of EBF1. However, this simple hierarchy cannot account for all observations, and our understanding of a presumed regulatory network, in which transcription factors and signaling pathways operate, is limited. Here, we show that the expression of the Ebf1 gene involves two promoters that are differentially regulated and generate distinct protein isoforms. We find that interleukin-7 signaling, E2A, and EBF1 activate the distal Ebf1 promoter, whereas Pax5, together with Ets1 and Pu.1, regulates the stronger proximal promoter. In the absence of Pax5, the function of the proximal Ebf1 promoter and accumulation of EBF1 protein are impaired and the replication timing and subcellular localization of the Ebf1 locus are altered. Taken together, these data suggest that the regulation of Ebf1 via distinct promoters allows for the generation of several feedback loops and the coordination of multiple determinants of B lymphopoiesis in a regulatory network. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17101802&query_hl=1 ER - TY - JFULL T1 - Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants. A1 - Biagioni, E A1 - Frisone, MF A1 - Laroche, S A1 - Kapetanakis, BA A1 - Ricci, D A1 - Adeyi-Obe, M A1 - Lewis, H A1 - Kennea, N A1 - Cioni, G A1 - Cowan, F A1 - Rutherford, M A1 - Azzopardi, D A1 - Mercuri, E J1 - Clin Neurophysiol Y1 - 2007/01// VL - 118 SN - 1388-2457 SP - 53 EP - 59 N2 - OBJECTIVE: The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS: We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS: The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION: There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE: Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17095296&query_hl=1 ER - TY - JFULL T1 - Interferon-gamma (IFN-gamma)-inducible intracellular inactivation of hepatitis B virus (HBV): Comparison of APOBEC3 and nitric oxide pathways A1 - Phillips, S A1 - Taylor, JA A1 - Chokshi, S A1 - Navaratnam, N A1 - Naoumov, NV J1 - J HEPATOL Y1 - 2007/01// VL - 46 SN - 0168-8278 SP - S158 EP - S158 ER - TY - JFULL T1 - Automatic cortical segmentation in the developing brain. A1 - Xue, H A1 - Srinivasan, L A1 - Jiang, S A1 - Rutherford, M A1 - Edwards, AD A1 - Rueckert, D A1 - Hajnal, JV J1 - Inf Process Med Imaging Y1 - 2007/// VL - 20 SN - 1011-2499 SP - 257 EP - 269 N2 - The segmentation of neonatal cortex from magnetic resonance (MR) images is much more challenging than the segmentation of cortex in adults. The main reason is the inverted contrast between grey matter (GM) and white matter (WM) that occurs when myelination is incomplete. This causes mislabeled partial volume voxels, especially at the interface between GM and cerebrospinal fluid (CSF). We propose a fully automatic cortical segmentation algorithm, detecting these mislabeled voxels using a knowledge-based approach and correcting errors by adjusting local priors to favor the correct classification. Our results show that the proposed algorithm corrects errors in the segmentation of both GM and WM compared to the classic EM scheme. The segmentation algorithm has been tested on 25 neonates with the gestational ages ranging from approximately 27 to 45 weeks. Quantitative comparison to the manual segmentation demonstrates good performance of the method (mean Dice similarity: 0.758 +/- 0.037 for GM and 0.794 +/- 0.078 for WM). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17633705&query_hl=1 ER - TY - JFULL T1 - Low soluble thrombomodulin activity and antigen is associated with a family history of heart disease while a high level is associated with a personal history of heart disease in type 2 diabetes. A1 - Konstantoulas, CJ A1 - Cooper, JA A1 - Ohlin, AK A1 - Humphries, SE A1 - Goodall, AH A1 - Toh, CH A1 - Mather, H A1 - Ireland, H J1 - Thromb Haemost Y1 - 2007/01// VL - 97 SN - 0340-6245 SP - 161 EP - 164 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17200788&query_hl=1 ER - TY - JFULL T1 - Cardiac troponin I is a potential novel substrate for AMP-activated protein kinase A1 - Oliveira, SM A1 - Davies, J A1 - Carling, D A1 - Watkins, H A1 - Redwood, C J1 - BIOPHYS J Y1 - 2007/01// SN - 0006-3495 SP - 180A EP - 180A ER - TY - JFULL T1 - Rapporteur report: Basics and technology and metrology and standards. A1 - Hand, JW J1 - Prog Biophys Mol Biol Y1 - 2007/01// VL - 93 SN - 0079-6107 SP - 192 EP - 194 N2 - The first and second sessions of the Workshop focussed on the basics of ultrasound and infrasound, their applications in both industry and medicine, and metrology and protection standards for ultrasound applications. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17007912&query_hl=1 ER - TY - JFULL T1 - Synthesis and reactivity of [F-18]-N-fluorobenzenesulfonimide A1 - Teare, H A1 - Robins, EG A1 - Arstad, E A1 - Sajinder, KL A1 - Gouverneur, V J1 - CHEM COMMUN Y1 - 2007/// SN - 1359-7345 SP - 2330 EP - 2332 N2 - A novel [F-18]NF reagent and two novel radiochemical transformations have been developed: [F-18]NFSi has been prepared from sodium dibenzenesulfonimide and reacted in the presence of silyl enol ethers and allylsilanes to deliver labelled fluorinated ketones and allylic fluorides respectively; the radiosynthesis of the fluorinated A ring of vitamin D-3 has also been completed with success. ER - TY - JFULL T1 - Diagnostic and clinical perspectives of fusion imaging in cardiology: is the total greater than the sum of its parts? A1 - Bax, JJ A1 - Beanlands, RS A1 - Klocke, FJ A1 - Knuuti, J A1 - Lammertsma, AA A1 - Schaefers, MA A1 - Schelbert, HR A1 - Von Schulthess, GK A1 - Shaw, LJ A1 - Yang, GZ A1 - Camici, PG J1 - Heart Y1 - 2007/01// VL - 93 SN - 1468-201X SP - 16 EP - 22 N2 - Positron emission tomography, cardiovascular magnetic resonance and multislice computed tomography have contributed to changing our pathophysiological understanding of many conditions. Clinically, they have provided new tools for the identification of preclinical disease and a better understanding of how disease progresses. The application of these imaging modalities to preclinical disease and the use of these techniques in patients with overt cardiovascular disease are reviewed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16387827&query_hl=1 ER - TY - JFULL T1 - Frequency and pressure dependent attenuation and scattering by microbubbles. A1 - Tang, MX A1 - Eckersley, RJ J1 - Ultrasound Med Biol Y1 - 2007/01// VL - 33 SN - 0301-5629 SP - 164 EP - 168 N2 - The aim of this study was to evaluate experimentally the degree of pressure dependence of attenuation and scattering by microbubbles at low acoustic pressures with an empirical nonlinear model. In addition, the pressure dependency over a range of frequencies (1 to 5 MHz) has been studied. A series of transmission and scattering measurements were made with the microbubble SonoVue, using an automated system. Results show that, within the pressure range studied, attenuation as a result of the microbubble is pressure-dependent, whereas no such dependence of scattering was detectable. The pressure dependence of attenuation for SonoVue was found to be most significant at 1.5 MHz. The scattering is shown to be the highest at the lowest insonation frequency, around 1 approximately 1.25 MHz, and then decreases with frequency. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17189060&query_hl=1 ER - TY - JFULL T1 - Can disease progression in non-alcoholic fatty liver disease be predicted by metabolic biomarkers of lipid accumulation and peroxidation? A1 - Cobbold, JF A1 - Anstee, QM A1 - Goldin, RD A1 - Cox, RD A1 - Thursz, MR A1 - Thomas, HC A1 - Taylor-Robinson, SD A1 - Cox, IJ J1 - J HEPATOL Y1 - 2007/01// VL - 46 SN - 0168-8278 SP - S265 EP - S265 ER - TY - JFULL T1 - Impact of multiple treatment interruptions on virus-host interactions in HBeAg-positive chronic hepatitis B (CHB) A1 - Chokshi, S A1 - Petretto, E A1 - Cooksley, H A1 - Mangion, J A1 - Hill, J A1 - Naoumov, N J1 - J HEPATOL Y1 - 2007/01// VL - 46 SN - 0168-8278 SP - S154 EP - S154 ER - TY - JFULL T1 - The proteasome restricts permissive transcription at tissue-specific gene loci in embryonic stem cells. A1 - Szutorisz, H A1 - Georgiou, A A1 - Tora, L A1 - Dillon, N J1 - Cell Y1 - 2006/12/29/ VL - 127 SN - 0092-8674 SP - 1375 EP - 1388 N2 - The ability of stem cells to activate different gene expression programs requires the choreographed assembly of trans-acting factors at enhancers and promoters during cell differentiation. In this study, we show that the proteasome acts on specific regulatory regions in embryonic stem (ES) cells to prevent incorrect transcriptional initiation. Chemical or siRNA-mediated inhibition of proteasome activity results in increased transcription factor and RNA polymerase II binding and leads to activation of cryptic promoters. Analysis of the binding profiles of different proteasome subunits in normal ES cells and following RNAi knockdown of individual subunits provides evidence for a targeted assembly of the 26S proteasome at specific regulatory elements. Our results suggest that the proteasome promotes a dynamic turnover of transcription factor and Pol II binding at tissue-specific gene domains in ES cells, thereby restricting permissive transcriptional activity and keeping the genes in a potentiated state, ready for activation at later stages. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17190601&query_hl=1 ER - TY - JFULL T1 - Processing of transmission data from an uncollimated single photon source A1 - Dikaios, N A1 - Dinelle, K A1 - Spinks, T A1 - Nikita, K A1 - Thielemans, K J1 - NUCL INSTRUM METH A Y1 - 2006/12/20/ VL - 569 SN - 0168-9002 SP - 416 EP - 420 N2 - The EXACT 3D PET scanner uses a Cs-137 single photon rotating point source for the transmission scan. As the source is uncollimated, the transmission data are contaminated by scatter. It has been suggested that segmentation of the reconstructed image can restore the quantitative information in the image. We study here if the results can be further improved by the application of a scale factor for every transaxial plane. (c) 2006 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - Myocardial glucose transport and utilization in patients with type 2 diabetes mellitus, left ventricular dysfunction, and coronary artery disease. A1 - Dutka, DP A1 - Pitt, M A1 - Pagano, D A1 - Mongillo, M A1 - Gathercole, D A1 - Bonser, RS A1 - Camici, PG J1 - J Am Coll Cardiol Y1 - 2006/12/05/ VL - 48 SN - 1558-3597 SP - 2225 EP - 2231 N2 - OBJECTIVES: This research was designed to assess the effect of type 2 diabetes mellitus (T2DM) on myocardial glucose utilization in patients with heart failure secondary to coronary artery disease. BACKGROUND: Patients with T2DM and coronary artery disease have an increased morbidity and mortality compared with patients with coronary artery disease without diabetes that may relate to a reduction in the ability of the myocardium to utilize glucose. METHODS: Myocardial blood flow and glucose utilization were assessed during a hyperinsulinemic clamp by 18F-flurodeoxyglucose and positron emission tomography in 54 patients (19 with T2DM) with multivessel coronary artery disease and heart failure. In a subgroup of 18 patients, myocardial biopsies were obtained during coronary bypass surgery to assess glucose transporter (GLUT4) distribution and protein concentration, and compared with myocardium from transplant donor hearts. RESULTS: Myocardial blood flow was similar in patients without diabetes and those with T2DM. Myocardial glucose utilization was lower in patients with T2DM (0.34 +/- 0.16 vs. 0.47 +/- 0.24 micromol x min(-1) x g(-1), p = 0.0002) despite comparable plasma insulin concentrations and a higher blood glucose concentration. Extraction of glucose by the myocardium was reduced in patients with T2DM (7.1 +/- 3.1% vs. 13.5 +/- 5.2%, p < 0.01). Myocardial GLUT4 protein was similar in patients with and without T2DM (p = 0.75). CONCLUSIONS: Patients with coronary artery disease and heart failure exhibit myocardial insulin resistance, and this is greater in those with T2DM. This may limit the ability of the myocardium in patients with T2DM to withstand ischemia and may contribute to the increased cardiovascular morbidity and mortality in such patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17161251&query_hl=1 ER - TY - JFULL T1 - Correction of head movement on PET studies: comparison of methods. A1 - Montgomery, AJ A1 - Thielemans, K A1 - Mehta, MA A1 - Turkheimer, F A1 - Mustafovic, S A1 - Grasby, PM J1 - J Nucl Med Y1 - 2006/12// VL - 47 SN - 0161-5505 SP - 1936 EP - 1944 N2 - Head movement presents a continuing problem in PET studies. Head restraint minimizes movement but is unreliable, resulting in the need to develop alternative strategies. These include frame-by-frame (FBF) realignment or use of motion tracking (MT) during the scan to realign PET acquisition data. Here we present a comparative analysis of these 2 methods of motion correction. METHODS: Eight volunteers were examined at rest using (11)C-raclopride PET with the radioligand administered as a bolus followed by constant infusion to achieve steady state. Binding potential (BP) was estimated using the ratio method during 2 periods of the scan at steady state. Head movement was compensated by using coregistration between frames (FBF) and 3 methods using MT measurements of head position acquired with a commercially available optical tracking system. RESULTS: All methods of realignment improved test-retest reliability and noise characteristics of the raw data, with important consequences for the power to detect small changes in radiotracer binding, and the potential to reduce false-positive and false-negative results. MT methods were superior to FBF realignment using coregistration on some indices. CONCLUSION: Such methods have considerable potential to improve the reliability of PET data with important implications for the numbers of volunteers required to test hypotheses. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17138736&query_hl=1 ER - TY - JFULL T1 - Using cerebral ultrasound effectively in the newborn infant. A1 - Leijser, LM A1 - de Vries, LS A1 - Cowan, FM J1 - Early Hum Dev Y1 - 2006/12// VL - 82 SN - 0378-3782 SP - 827 EP - 835 N2 - Cranial ultrasound is the most available and easily repeatable technique for imaging the neonatal brain. Its quality and diagnostic accuracy depend on various factors; the suitability of the ultrasound machine for neonatal cranial work, the use of optimal settings and probes, appropriate scanning protocols, the use of a variety of acoustic windows and, not least, the scanning experience of the examiner. Knowledge of normal anatomy and the echogenicities of different tissues in normal and pathological situations as well as familiarity with the physiological and pathological processes likely to be encountered is vital. This paper assesses the value and appropriate use, safety and diagnostic accuracy of modern, high-quality ultrasound in evaluating the brain of the preterm and term born infant. Issues of concern regarding teaching, supervision and experience of the examiner are also addressed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17074450&query_hl=1 ER - TY - JFULL T1 - Nonlinear propagation of ultrasound through microbubble contrast agents and implications for imaging. A1 - Tang, MX A1 - Eckersley, RJ J1 - IEEE Trans Ultrason Ferroelectr Freq Control Y1 - 2006/12// VL - 53 SN - 0885-3010 SP - 2406 EP - 2415 N2 - Microbubble contrast agents produce nonlinear echoes under ultrasound insonation, and current imaging techniques detect these nonlinear echoes to generate contrast agent images accordingly. For these techniques, there is a potential problem in that bubbles along the ultrasound transmission path between transducer and target can alter the ultrasound transmission nonlinearly and contribute to the nonlinear echoes. This can lead to imaging artefacts, especially in regions at depth. In this paper we provide insight, through both simulation and experimental measurement, into the nonlinear propagation caused by microbubbles and the implications for current imaging techniques. A series of investigations at frequencies below, at, and above the resonance frequency of microbubbles were performed. Three specific effects on the pulse propagation (i.e., amplitude attenuation, phase changes, and harmonic generation) were studied. It was found that all these effects are dependent on the initial pulse amplitude, and their dependence on the initial phase of the pulse is shown to be insignificant. Two types of imaging errors are shown to result from this nonlinear propagation: first, that tissue can be misclassified as microbubbles; second, the concentration of microbubbles in the image can be misrepresented. It is found that these imaging errors are significant for all three pulse frequencies when the pulses transmit through a microbubble suspension of 6 cm in path length. It also is found that the first type of error is larger at the bubble resonance frequency. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17186923&query_hl=1 ER - TY - JFULL T1 - Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. A1 - Humphries, SE A1 - Whittall, RA A1 - Hubbart, CS A1 - Maplebeck, S A1 - Cooper, JA A1 - Soutar, AK A1 - Naoumova, R A1 - Thompson, GR A1 - Seed, M A1 - Durrington, PN A1 - Miller, JP A1 - Betteridge, DJ A1 - Neil, HA A1 - Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee J1 - J Med Genet Y1 - 2006/12// VL - 43 SN - 1468-6244 SP - 943 EP - 949 N2 - AIMS: To determine the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9), and to examine their effect in development of coronary heart disease (CHD) in patients with clinically defined definite familial hypercholesterolaemia in UK. Patients and METHODS: 409 patients with familial hypercholesterolaemia patients (158 with CHD) were studied. The LDLR was partially screened by single-strand conformational polymorphism (SSCP) (exons 3, 4, 6-10 and 14) and by using a commercial kit for gross deletions or rearrangements. APOB (p.R3500Q) and PCSK9 (p.D374Y) were detected by specific assays. Coding exons of PCSK9 were screened by SSCP. RESULTS: Mutations were detected in 253 (61.9%) PATIENTS: 236 (57.7%) carried LDLR, 10 (2.4%) carried APOB p.Q3500 and 7 (1.7%) PCSK9 p.Y374. No additional mutations were identified in PCSK9. After adjusting for age, sex, smoking and systolic blood pressure, compared to those with no detectable mutation, the odds ratio of having CHD in those with an LDLR mutation was 1.84 (95% CI 1.10 to 3.06), for APOB 3.40 (0.71 to 16.36), and for PCSK9 19.96 (1.88 to 211.5; p = 0.001 overall). The high risk in patients carrying LDLR and PCSK9 p.Y374 was partly explained by their higher pretreatment cholesterol levels (LDLR, PCSK9 and no mutation, 10.29 (1.85), 13.12 and 9.85 (1.90) mmol/l, respectively, p = 0.001). The post-statin treatment lipid profile in PCSK9 p.Y374 carriers was worse than in patients with no identified mutation (LDL-C, 6.77 (1.82) mmol/l v 4.19 (1.26) mmol/l, p = 0.001, HDL-C 1.09 (0.27) mmol/l v 1.36 (0.36) mmol/l, p = 0.03). CONCLUSIONS: The higher CHD risk in patients carrying PCSK9 p.Y347 or a detected LDLR mutation supports the usefulness of DNA testing in the diagnosis and management of patients with familial hypercholesterolaemia. Mutations in PCSK9 appear uncommon in patients with familial hypercholesterolaemia in UK. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17142622&query_hl=1 ER - TY - JFULL T1 - Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling A1 - Steinberg, GR A1 - Michell, BJ A1 - van Denderen, BJW A1 - Watt, MJ A1 - Carey, AL A1 - Fam, BC A1 - Andrikopoulos, S A1 - Proietto, J A1 - Gorgun, CZ A1 - Carling, D A1 - Hotamisligil, GS A1 - Febbraio, MA A1 - Kay, TW A1 - Kemp, BE J1 - CELL METAB Y1 - 2006/12// VL - 4 SN - 1550-4131 SP - 465 EP - 474 N2 - Elevated levels of tumor necrosis factor (TNF alpha) are implicated in the development of insulin resistance, but the mechanisms mediating these chronic effects are not completely understood. We demonstrate that TNF alpha signaling through TNF receptor (TNFR) 1 suppresses AMPK activity via transcriptional upregulation of protein phosphatase 2C (PP2C). This in turn reduces ACC phosphorylation, suppressing fatty-acid oxidation, increasing intramuscular diacylglycerol accumulation, and causing insulin resistance in skeletal muscle, effects observed both in vitro and in vivo. Importantly even at pathologically elevated levels of TNF alpha observed in obesity, the suppressive effects of TNF alpha on AMPK signaling are reversed in mice null for both TNFR1 and 2 or following treatment with a TNF alpha neutralizing antibody. Our data demonstrate that AMPK is an important TNF alpha signaling target and is a contributing factor to the suppression of fatty-acid oxidation and the development of lipid-induced insulin resistance in obesity. ER - TY - JFULL T1 - Manganese-enhanced magnetic resonance imaging (MEMRI) without compromise of the blood-brain barrier detects hypothalamic neuronal activity in vivo. A1 - Kuo, YT A1 - Herlihy, AH A1 - So, PW A1 - Bell, JD J1 - NMR Biomed Y1 - 2006/12// VL - 19 SN - 0952-3480 SP - 1028 EP - 1034 N2 - There is growing interest in the use of manganese-enhanced MRI (MEMRI) to detect neuronal activity and architecture in animal models. The MEMRI neuronal activity studies have been generally performed either by stereotactic brain injection or by systemic administration of Mn(2+) in conjunction with the disruption of the blood-brain barrier (BBB). These approaches, however, have limited the use of MEMRI because of the procedure-related morbidity/mortality or because brain activity measured by these methods can diverge from genuine physiological responses. In this study, the hypothesis that MEMRI, performed with systemic administration of Mn(2+) without compromising the BBB integrity, is able to detect hypothalamic function associated with feeding was tested. This procedure was tested on a simple physiological condition, fasting, and with this method temporal and regional differences in Mn(2+) enhancement could be detected. It is concluded that MEMRI can be used to study hypothalamic function in the murine brain without compromising the BBB. It was also shown that region-specific Mn(2+) enhancement in the mouse brain can be modulated by fasting. More importantly, this non-invasive in vivo imaging technique is able to demonstrate differences in brain activities, previously possible only by in vitro studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16845705&query_hl=1 ER - TY - JFULL T1 - Investigating the nonlinear microbubble response to chirp encoded, multipulse sequences. A1 - Chetty, K A1 - Hajnal, JV A1 - Eckersley, RJ J1 - Ultrasound Med Biol Y1 - 2006/12// VL - 32 SN - 0301-5629 SP - 1887 EP - 1895 N2 - A modified Rayleigh-Plesset model was used to investigate the nonlinear acoustic response of ultrasound contrast microbubbles to multipulse phase and amplitude modulated, chirp encoded sequences. Trade-offs between the signal-to-noise ratio (SNR) and axial resolution were quantified for differing chirp time-bandwidth products and methods for minimising the artifacts formed in the postprocessing stages were developed. It was found that the chirp length can be increased and bandwidth reduced to improve SNR, though resolution is sacrificed. Results from the simulated chirp, pulse inverted, amplitude modulated (chirp PIAM) sequences were also compared with equivalent short pulse PIAM sequences and it was found that the chirp sequences preserve their extra energy after scattering, which translates to an improved SNR after processing. Compression artifacts were reduced by using chirps with a centre frequency and bandwidth tuned to the frequency response of the microbubble and reversing the frequency sweep of one chirp in the sequence. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17169700&query_hl=1 ER - TY - JFULL T1 - Artifacts on electroencephalograms may influence the amplitude-integrated EEG classification: a qualitative analysis in neonatal encephalopathy. A1 - Hagmann, CF A1 - Robertson, NJ A1 - Azzopardi, D J1 - Pediatrics Y1 - 2006/12// VL - 118 SN - 1098-4275 SP - 2552 EP - 2554 N2 - This is a case report and a descriptive study demonstrating that artifacts are common during long-term recording of amplitude-integrated electroencephalograms and may lead to erroneous classification of the amplitude-integrated electroencephalogram trace. Artifacts occurred in 12% of 200 hours of recording time sampled from a representative sample of 20 infants with neonatal encephalopathy. Artifacts derived from electrical or movement interference occurred with similar frequency; both types of artifacts influenced the voltage and width of the amplitude-integrated electroencephalogram band. This is important knowledge especially if amplitude-integrated electroencephalogram is used as a selection tool for neuroprotection intervention studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17142543&query_hl=1 ER - TY - JFULL T1 - The role of cranial ultrasound and magnetic resonance imaging in the diagnosis of infections of the central nervous system. A1 - de Vries, LS A1 - Verboon-Maciolek, MA A1 - Cowan, FM A1 - Groenendaal, F J1 - Early Hum Dev Y1 - 2006/12// VL - 82 SN - 0378-3782 SP - 819 EP - 825 N2 - Imaging data concerning infection of the central nervous system (CNS) in neonates are usually confined to small groups of infants. We have reviewed the imaging findings in 96 preterm and full-term infants admitted to our neonatal intensive care unit over a 15 year period. Neuro-imaging, especially cranial ultrasound (CUS) and magnetic resonance imaging (MRI) provided useful information; CUS allows the early and later detection of calcification, germinolytic and parenchymal cysts, ventricular dilatation and strands and ependymal abnormality; diffusion weighted imaging (DWI) is especially useful in the acute stage of bacterial and viral infections, while conventional MRI helps in the detection of neocortical dysplasia in CMV infection and defining cerebellar abnormality. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17059873&query_hl=1 ER - TY - JFULL T1 - Automatic quantification of changes in bone in serial MR images of joints. A1 - Leung, KK A1 - Holden, M A1 - Saeed, N A1 - Brooks, KJ A1 - Buckton, JB A1 - Williams, AA A1 - Campbell, SP A1 - Changani, K A1 - Reid, DG A1 - Zhao, Y A1 - Wilde, M A1 - Rueckert, D A1 - Hajnal, JV A1 - Hill, DL J1 - IEEE Trans Med Imaging Y1 - 2006/12// VL - 25 SN - 0278-0062 SP - 1617 EP - 1626 N2 - Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17167996&query_hl=1 ER - TY - JFULL T1 - Cardiac nociception. A1 - Camici, PG A1 - Pagani, M J1 - Circulation Y1 - 2006/11/28/ VL - 114 SN - 1524-4539 SP - 2309 EP - 2312 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17130354&query_hl=1 ER - TY - JFULL T1 - Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging. A1 - Chaudhri, OB A1 - Parkinson, JR A1 - Kuo, YT A1 - Druce, MR A1 - Herlihy, AH A1 - Bell, JD A1 - Dhillo, WS A1 - Stanley, SA A1 - Ghatei, MA A1 - Bloom, SR J1 - Biochem Biophys Res Commun Y1 - 2006/11/17/ VL - 350 SN - 0006-291X SP - 298 EP - 306 N2 - The anorexigenic gut hormones oxyntomodulin (OXM) and glucagon-like peptide-1 (GLP-1) are thought to physiologically regulate appetite and food intake. Using manganese-enhanced magnetic resonance imaging, we have shown distinct patterns of neuronal activation in the hypothalamus in response to intraperitoneal injections into fasted mice of 900 and 5400 nmol/kg OXM or 900 nmol/kg GLP-1. Administration of OXM at either dose resulted in a reduced rate of signal enhancement, reflecting a reduction in neuronal activity, in the arcuate, paraventricular, and supraoptic nuclei of the hypothalamus. Conversely, GLP-1 caused a reduction in signal enhancement in the paraventricular nucleus only and an increase in the ventromedial hypothalamic nucleus. Our data show that these two apparently similar peptides generate distinct patterns of activation within the hypothalamus, suggesting that GLP-1 and OXM may act via different hypothalamic pathways. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17007819&query_hl=1 ER - TY - JFULL T1 - Imaging molecular and cellular events in transplantation. A1 - George, AJ A1 - Bhakoo, KK A1 - Haskard, DO A1 - Larkman, DJ A1 - Reynolds, PR J1 - Transplantation Y1 - 2006/11/15/ VL - 82 SN - 0041-1337 SP - 1124 EP - 1129 N2 - Imaging methods such as nuclear medicine (including positron emission tomography), magnetic resonance imaging, ultrasound, and optical imaging can be used to provide information about the expression of genes, and the location of molecules and cells in intact animals or patients. In the setting of transplantation, this will allow monitoring of inflammatory responses, as well as the state of the graft. In this review, the advantages and disadvantages of different approaches to imaging will be discussed, as well as their potential application to transplantation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17102760&query_hl=1 ER - TY - JFULL T1 - Genetic defects causing familial hypercholesterolaemia: Identification of deletions and duplications in the LDL-receptor gene and summary of all mutations found in patients attending the Hammersmith Hospital Lipid Clinic. A1 - Tosi, I A1 - Toledo-Leiva, P A1 - Neuwirth, C A1 - Naoumova, RP A1 - Soutar, AK J1 - Atherosclerosis Y1 - 2006/11/07/ SN - 0021-9150 N2 - Familial hypercholesterolaemia (FH) results from defective catabolism of low density lipoproteins (LDL), leading to premature atherosclerosis and early coronary heart disease. It is commonly caused by mutations in LDLR, encoding the LDL receptor that mediates hepatic uptake of LDL, or in APOB, encoding its major ligand. More rarely, dominant mutations in PCSK9 or recessive mutations in LDLRAP1 (ARH) cause FH, gene defects that also affect the LDL-receptor pathway. We have used multiplex ligation-dependent probe amplification (MLPA) to identify deletions and rearrangements in LDLR, some not detectable by Southern blotting, thus completing our screening for mutations causing FH in a group of FH patients referred to a Lipid Clinic in London. To summarise, mutations in LDLR were found in 153 unrelated heterozygous FH patients and 24 homozygotes/compound heterozygotes, and in over 200 relatives of 80 index patients. LDLR mutations included 85 different point mutations (7 not previously described) and 13 different large rearrangements. The APOB R3500Q mutation was present in 14 heterozygous patients and a mutation in PCSK9 in another 4; LDLRAP1 mutations were found in 4 "homozygous" FH patients. Our data confirm that DNA-based diagnosis provides information that is important for management of FH in a considerable number of families. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17094996&query_hl=1 ER - TY - JFULL T1 - Sustainable use of continuous positive airway pressure in extremely preterm infants during the first week after delivery. A1 - Booth, C A1 - Premkumar, MH A1 - Yannoulis, A A1 - Thomson, M A1 - Harrison, M A1 - Edwards, AD J1 - Arch Dis Child Fetal Neonatal Ed Y1 - 2006/11// VL - 91 SN - 1359-2998 SP - F398 EP - F402 N2 - BACKGROUND: Early use of nasal continuous positive airway pressure (nCPAP) may reduce lung damage, but it is not clear how many extremely preterm infants can be cared for without mechanical ventilation on the first days after delivery. OBJECTIVES: To describe our experience of nCPAP in infants born at <27 weeks' gestation and to determine the chance of reintubation of this group of extremely preterm infants. METHODS: A retrospective, observational study examined the period from November 2002 to October 2003, when efforts were made to extubate infants to nCPAP at the earliest opportunity. Data were collected on all infants born at <27 weeks' and gestation admitted to The Neonatal Intensive Care Unit, Queen Charlotte's and Chelsea Hospital, London, UK. The chance of an individual infant requiring reintubation within 48 h of delivery was estimated, calculating the predictive probability using a Bayesian approach, and oxygen requirements at 36 weeks' postmenstrual age were examined. RESULTS: 60 infants, 34 inborn and 26 ex utero transfers, were admitted; 7 infants admitted 24 h after birth were excluded and 5 died within 48 h. The mean birth weight was 788 g and the gestational age was 25.3 weeks. Extubation was attempted on day 1 in 21 of 52 infants on ventilators and was successful in 14; and on day 2 in 14 of 35 and successful in 10 of infants extubated within 48 h of delivery survived to discharge. 5 of 23 infants on mechanical ventilation at 48 h of age were on air at 36 weeks postmenstrual age, and 12 of 26 of those were on nCPAP at 48 h of age. The probability of an individual baby remaining on nCPAP was 66% (95% CI 46% to 86%) on day 1 and 80% (95% CI 60% to 99%) on day 2. The smallest infant to be successfully extubated was 660 g and the youngest gestational age was 23.8 weeks. CONCLUSIONS: Extremely preterm infants can be extubated to nCPAP soon after delivery, with a reasonable probability of not requiring immediate reintubation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16820391&query_hl=1 ER - TY - JFULL T1 - The human ClC-4 protein, a member of the CLC chloride channel/transporter family, is localized to the endoplasmic reticulum by its N-terminus. A1 - Okkenhaug, H A1 - Weylandt, KH A1 - Carmena, D A1 - Wells, DJ A1 - Higgins, CF A1 - Sardini, A J1 - FASEB J Y1 - 2006/11// VL - 20 SN - 1530-6860 SP - 2390 EP - 2392 N2 - Despite considerable similarity in their amino acid sequences and structural features, the mammalian members of the CLC chloride channel/transporter family have different subcellular locations. The subcellular location and function of one of these members, hClC-4, is controversial. To characterize its cellular function, we investigated its tissue distribution and subcellular location. Expression was high in excitable tissues such as the nervous system and skeletal muscle. When heterologously expressed in HEK293 cells and in skeletal muscle fibers, hClC-4 localizes to the endoplasmic/sarcoplasmic reticulum (ER/SR) membranes, in contrast to hClC-3, which localizes to vesicular structures. This location was confirmed by identification of endogenous ClC-4 in membrane fractions from mouse brain homogenate enriched for the sarco-endoplasmic reticulum ATPase SERCA2, an ER/SR marker. To identify the motif responsible for ER localization of hClC-4, we generated hClC-4 truncations and chimeras between hClC-4 and hClC-3 or the unrelated plasma membrane protein Ly49E. A stretch of amino acids, residues 14-63, at the N-terminus constitutes a novel motif both necessary and sufficient for targeting hClC-4 and other membrane proteins to the ER. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17023393&query_hl=1 ER - TY - JFULL T1 - Dopamine D1 receptors in the anterior cingulate cortex regulate effort-based decision making. A1 - Schweimer, J A1 - Hauber, W J1 - Learn Mem Y1 - 2006/11// VL - 13 SN - 1072-0502 SP - 777 EP - 782 N2 - The anterior cingulate cortex (ACC) has been implicated in encoding whether or not an action is worth performing in view of the expected benefit and the cost of performing the action. Dopamine input to the ACC may be critical for this form of effort-based decision making; however, the role of distinct ACC dopamine receptors is yet unknown. Therefore, we examined in rats the effects of an intra-ACC D1 and D2 receptor blockade on effort-based decision making tested in a T-maze cost-benefit task. In this task, subjects could either choose to climb a barrier to obtain a high reward in one arm or a low reward in the other arm without a barrier. Unlike vehicle-treated rats, rats with intra-ACC infusion of the D1 receptor antagonist SCH23390 exhibited a reduced preference for the high-cost- high-reward response option when having the choice to obtain a low reward with little effort. In contrast, in rats with intra-ACC infusion of the D2 receptor antagonist eticlopride, the preference for the high-cost-high-reward response option was not altered relative to vehicle-treated rats. These data provide the first evidence that D1 receptors in the ACC regulate effort-based decision making. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17142306&query_hl=1 ER - TY - JFULL T1 - Re: Palliation bias is being overlooked in neonatal hypothermia trials. A1 - Edwards, AD A1 - Azzopardi, DV J1 - Arch Dis Child Fetal Neonatal Ed Y1 - 2006/11// VL - 91 SN - 1359-2998 SP - F465 N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17056853&query_hl=1 ER - TY - JFULL T1 - Nonlinear phase correction of navigated multi-coil diffusion images. A1 - Atkinson, D A1 - Counsell, S A1 - Hajnal, JV A1 - Batchelor, PG A1 - Hill, DL A1 - Larkman, DJ J1 - Magn Reson Med Y1 - 2006/11// VL - 56 SN - 0740-3194 SP - 1135 EP - 1139 N2 - Cardiac pulsatility causes a nonrigid motion of the brain. In multi-shot diffusion imaging this leads to spatially varying phase changes that must be corrected. A conjugate gradient based reconstruction is presented that includes phase changes measured using two-dimensional navigator echoes, coil sensitivity information, navigator-determined weightings, and data from multiple coils and averages.A multi-shot echo planar sequence was used to image brain regions where pulsatile motion is not uniform. Reduced susceptibility artifacts were observed compared to a clinical single-shot sequence. In a higher slice, fiber directions derived from single-shot data show distortions from anatomical scans by as much as 7 mm compared to less than 2 mm for our multi-shot reconstructions. The reduced distortions imply that phase encoding can be applied in the shorter left-right direction, enabling time savings through the use of a rectangular field of view. Higher resolution diffusion imaging in the spine permits visualization of a nerve root. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16986111&query_hl=1 ER - TY - JFULL T1 - Detection of vascular expression of E-selectin in vivo with MR imaging. A1 - Reynolds, PR A1 - Larkman, DJ A1 - Haskard, DO A1 - Hajnal, JV A1 - Kennea, NL A1 - George, AJ A1 - Edwards, AD J1 - Radiology Y1 - 2006/11// VL - 241 SN - 0033-8419 SP - 469 EP - 476 N2 - PURPOSE: To develop a contrast agent for targeting E-selectin expressed on activated vascular endothelium and to evaluate detection of the agent with magnetic resonance (MR) imaging in an in vivo mouse model of inflammation. MATERIALS AND METHODS: All animal experiments were approved according to animal welfare and local ethics committee regulations. An anti-murine E-selectin F(ab')2 monoclonal antibody, MES-1, was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Flow cytometry, Perl Prussian blue staining for iron, and MR imaging were performed by using Chinese hamster ovary (CHO) cells expressing mouse E-selectin to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO. Serial imaging was performed by using a 9.4-T MR imaging system with a custom receive-only coil. Tissue slices were stained to define distribution of E-selectin expression and localization of the MES-1-USPIO conjugate. RESULTS: MES-1-USPIO was shown to bind to CHO cells expressing mouse E-selectin in vitro. After injection of MES-1-USPIO in vivo, distinct changes in R2 relaxation rate (1/T2) characteristics were detected in inflamed ears when they were compared with control ears. Histologic analysis confirmed the vascular endothelial distribution of MES-1-USPIO. CONCLUSION: E-selectin expression in vivo can be selectively and directly imaged noninvasively with MR. This has the potential to be useful in the study of inflammatory disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17005768&query_hl=1 ER - TY - JFULL T1 - Non-invasive evaluation of hepatic fibrosis using magnetic resonance and ultrasound techniques. A1 - Cobbold, JF A1 - Wylezinska, M A1 - Cunningham, C A1 - Crossey, ME A1 - Thomas, HC A1 - Cox, IJ A1 - Patel, N A1 - Taylor-Robinson, SD J1 - Gut Y1 - 2006/11// VL - 55 SN - 0017-5749 SP - 1670; author reply 1670 EP - 1670; author reply 1670 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17047120&query_hl=1 ER - TY - JFULL T1 - Curvature and tortuosity of the superficial femoral artery: a possible risk factor for peripheral arterial disease. A1 - Wood, NB A1 - Zhao, SZ A1 - Zambanini, A A1 - Jackson, M A1 - Gedroyc, W A1 - Thom, SA A1 - Hughes, AD A1 - Xu, XY J1 - J Appl Physiol Y1 - 2006/11// VL - 101 SN - 8750-7587 SP - 1412 EP - 1418 N2 - Atherosclerosis in the superficial femoral artery (SFA) resulting in peripheral arterial disease is more common in men than women and shows a predilection for the region of the adductor canal. Blood flow patterns are related to development of atherosclerosis, and we investigated if curvature and tortuosity of the femoral artery differed between young men and women and if differences resulted in adverse flow patterns. Magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) were combined in 18 young adult volunteers (9 men) to assess the relationship of flow features to likely sites of future atherosclerosis formation. Subjects underwent MRI of the right SFA, three-dimensional vascular geometry was reconstructed, and measures of tortuosity and curvature were calculated. Tortuosity and curvature were significantly greater for men than women, and this was related to increased body surface area, body mass index, or weight in men. In both sexes, "tortuosity" increased from the midthigh to the popliteal fossa. The greatest curvature was found within the distal quarter of the SFA. CFD modeling was undertaken on MRI-based reconstructions of the SFA. Wall shear stresses (WSS) were extracted from the computations. WSS showed greater spatial variation in the men than in the women, and the men exhibited lower mean WSS. These data indicate that sex differences related to body size and anatomical course of the femoral artery may contribute to the enhanced risk of focal atherosclerosis in the adductor canal. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16825527&query_hl=1 ER - TY - JFULL T1 - The mechanistic classification of addictive drugs. A1 - Lüscher, C A1 - Ungless, MA J1 - PLoS Med Y1 - 2006/11// VL - 3 SN - 1549-1676 SP - e437 EP - e437 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17105338&query_hl=1 ER - TY - JFULL T1 - Myocardial insulin sensitivity correlates with sympathetic drive in patients with left ventricular dysfunction A1 - Mongillo, M A1 - John, A A1 - Rimoldi, O A1 - Pennell, D A1 - Camici, PG J1 - CIRCULATION Y1 - 2006/10/31/ VL - 114 SN - 0009-7322 SP - 804 EP - 804 ER - TY - JFULL T1 - A role for Dicer in immune regulation. A1 - Cobb, BS A1 - Hertweck, A A1 - Smith, J A1 - O'Connor, E A1 - Graf, D A1 - Cook, T A1 - Smale, ST A1 - Sakaguchi, S A1 - Livesey, FJ A1 - Fisher, AG A1 - Merkenschlager, M J1 - J Exp Med Y1 - 2006/10/30/ VL - 203 SN - 0022-1007 SP - 2519 EP - 2527 N2 - Micro RNAs (miRNAs) regulate gene expression at the posttranscriptional level. Here we show that regulatory T (T reg) cells have a miRNA profile distinct from conventional CD4 T cells. A partial T reg cell-like miRNA profile is conferred by the enforced expression of Foxp3 and, surprisingly, by the activation of conventional CD4 T cells. Depleting miRNAs by eliminating Dicer, the RNAse III enzyme that generates functional miRNAs, reduces T reg cell numbers and results in immune pathology. Dicer facilitates, in a cell-autonomous fashion, the development of T reg cells in the thymus and the efficient induction of Foxp3 by transforming growth factor beta. These results suggest that T reg cell development involves Dicer-generated RNAs. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17060477&query_hl=1 ER - TY - JFULL T1 - Heritability and tissue specificity of expression quantitative trait loci. A1 - Petretto, E A1 - Mangion, J A1 - Dickens, NJ A1 - Cook, SA A1 - Kumaran, MK A1 - Lu, H A1 - Fischer, J A1 - Maatz, H A1 - Kren, V A1 - Pravenec, M A1 - Hubner, N A1 - Aitman, TJ J1 - PLoS Genet Y1 - 2006/10/20/ VL - 2 SN - 1553-7404 SP - e172 EP - e172 N2 - Variation in gene expression is heritable and has been mapped to the genome in humans and model organisms as expression quantitative trait loci (eQTLs). We applied integrated genome-wide expression profiling and linkage analysis to the regulation of gene expression in fat, kidney, adrenal, and heart tissues using the BXH/HXB panel of rat recombinant inbred strains. Here, we report the influence of heritability and allelic effect of the quantitative trait locus on detection of cis- and trans-acting eQTLs and discuss how these factors operate in a tissue-specific context. We identified several hundred major eQTLs in each tissue and found that cis-acting eQTLs are highly heritable and easier to detect than trans-eQTLs. The proportion of heritable expression traits was similar in all tissues; however, heritability alone was not a reliable predictor of whether an eQTL will be detected. We empirically show how the use of heritability as a filter reduces the ability to discover trans-eQTLs, particularly for eQTLs with small effects. Only 3% of cis- and trans-eQTLs exhibited large allelic effects, explaining more than 40% of the phenotypic variance, suggestive of a highly polygenic control of gene expression. Power calculations indicated that, across tissues, minor differences in genetic effects are expected to have a significant impact on detection of trans-eQTLs. Trans-eQTLs generally show smaller effects than cis-eQTLs and have a higher false discovery rate, particularly in more heterogeneous tissues, suggesting that small biological variability, likely relating to tissue composition, may influence detection of trans-eQTLs in this system. We delineate the effects of genetic architecture on variation in gene expression and show the sensitivity of this experimental design to tissue sampling variability in large-scale eQTL studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17054398&query_hl=1 ER - TY - JFULL T1 - Automatic anatomical brain MRI segmentation combining label propagation and decision fusion. A1 - Heckemann, RA A1 - Hajnal, JV A1 - Aljabar, P A1 - Rueckert, D A1 - Hammers, A J1 - Neuroimage Y1 - 2006/10/15/ VL - 33 SN - 1053-8119 SP - 115 EP - 126 N2 - Regions in three-dimensional magnetic resonance (MR) brain images can be classified using protocols for manually segmenting and labeling structures. For large cohorts, time and expertise requirements make this approach impractical. To achieve automation, an individual segmentation can be propagated to another individual using an anatomical correspondence estimate relating the atlas image to the target image. The accuracy of the resulting target labeling has been limited but can potentially be improved by combining multiple segmentations using decision fusion. We studied segmentation propagation and decision fusion on 30 normal brain MR images, which had been manually segmented into 67 structures. Correspondence estimates were established by nonrigid registration using free-form deformations. Both direct label propagation and an indirect approach were tested. Individual propagations showed an average similarity index (SI) of 0.754+/-0.016 against manual segmentations. Decision fusion using 29 input segmentations increased SI to 0.836+/-0.009. For indirect propagation of a single source via 27 intermediate images, SI was 0.779+/-0.013. We also studied the effect of the decision fusion procedure using a numerical simulation with synthetic input data. The results helped to formulate a model that predicts the quality improvement of fused brain segmentations based on the number of individual propagated segmentations combined. We demonstrate a practicable procedure that exceeds the accuracy of previous automatic methods and can compete with manual delineations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860573&query_hl=1 ER - TY - JFULL T1 - Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. A1 - Parker, AL A1 - Waddington, SN A1 - Nicol, CG A1 - Shayakhmetov, DM A1 - Buckley, SM A1 - Denby, L A1 - Kemball-Cook, G A1 - Ni, S A1 - Lieber, A A1 - McVey, JH A1 - Nicklin, SA A1 - Baker, AH J1 - Blood Y1 - 2006/10/15/ VL - 108 SN - 0006-4971 SP - 2554 EP - 2561 N2 - Upon local delivery, adenovirus (Ad) serotype 5 viruses use the coxsackie and Ad receptor (CAR) for cell binding and alpha(v) integrins for internalization. When administered systemically, however, their role in liver tropism is limited because CAR-permissive and mutated viruses show similar biodistribution, a finding recently attributed to blood coagulation factor (F) IX or complement protein C4BP binding to the adenovirus fiber and "bridging" to either low-density lipoprotein receptor-related protein or heparan sulfate proteoglycans. Here, we show that hepatocyte transduction in vitro can be enhanced by the vitamin K-dependent factors FX, protein C, and FVII in addition to FIX but not by prothrombin (FII), FXI, and FXII. This phenomenon was not dependent on proteolytic activation or cell signaling activity and for FX was mediated by direct virus-factor binding. Human FX substantially enhanced hepatocyte transduction by CAR-permissive and mutated viruses in an ex vivo liver perfusion model. In vivo, global down-regulation of vitamin K-dependent zymogens by warfarin significantly diminished liver uptake of CAR-deleted Ads; however, this phenomenon was fully rescued by acute infusion of human FX. Our results indicate a common and pivotal role for distinct vitamin K-dependent coagulation factors in mediating hepatocyte transduction by adenoviruses in vitro and in vivo. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16788098&query_hl=1 ER - TY - JFULL T1 - Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin A1 - Talbot, K A1 - Cho, DS A1 - Ong, WY A1 - Benson, MA A1 - Han, LY A1 - Kazi, HA A1 - Kamins, J A1 - Hahn, CG A1 - Blake, DJ A1 - Arnold, SE J1 - HUM MOL GENET Y1 - 2006/10/15/ VL - 15 SN - 0964-6906 SP - 3041 EP - 3054 N2 - Variations in the gene encoding the novel protein dysbindin-1 (DTNBP1) are among the most commonly reported genetic variations associated with schizophrenia. Recent studies show that those variations are also associated with cognitive functioning in carriers with and without psychiatric diagnoses, suggesting a general role for dysbindin-1 in cognition. Such a role could stem from the protein's known ability to affect neuronal glutamate release. How dysbindin-1 might affect glutamate release nevertheless remains unknown without the discovery of the protein's neuronal binding partners and its subcellular locus of action. We demonstrate here that snapin is a binding partner of dysbindin-1 in vitro and in the brain. Tissue fractionation of whole mouse brains and human hippocampal formations revealed that both dysbindin-1 and snapin are concentrated in tissue enriched in synaptic vesicle membranes and less commonly in postsynaptic densities. It is not detected in presynaptic tissue fractions lacking synaptic vesicles. Consistent with that finding, immunoelectron microscopy showed that dysbindin-1 is located in (i) synaptic vesicles of axospinous terminals in the dentate gyrus inner molecular layer and CA1 stratum radiatum and in (ii) postsynaptic densities and microtubules of dentate hilus neurons and CA1 pyramidal cells. The labeled synapses are often asymmetric with thick postsynaptic densities suggestive of glutamatergic synapses, which are likely to be derived from dentate mossy cells and CA3 pyramidal cells. The function of dysbindin-1 in presynaptic, postsynaptic and microtubule locations may all be related to known functions of snapin. ER - TY - JFULL T1 - Postinjury vascular intimal hyperplasia in mice is completely inhibited by CD34+ bone marrow-derived progenitor cells expressing membrane-tethered anticoagulant fusion proteins. A1 - Chen, D A1 - Weber, M A1 - Shiels, PG A1 - Dong, R A1 - Webster, Z A1 - McVey, JH A1 - Kemball-Cook, G A1 - Tuddenham, EG A1 - Lechler, RI A1 - Dorling, A J1 - J Thromb Haemost Y1 - 2006/10// VL - 4 SN - 1538-7933 SP - 2191 EP - 2198 N2 - BACKGROUND: Coagulation proteins promote neointimal hyperplasia and vascular remodelling after vessel injury, but the precise mechanisms by which they act in vivo remain undetermined. OBJECTIVES: This study, using an injury model in which the neointima is derived from bone marrow (BM)-derived cells, compared inhibition of tissue factor or thrombin on either BM-derived or existing vascular smooth muscle cells. METHODS: Two transgenic (Tg) mouse strains expressing membrane-tethered tissue factor pathway inhibitor (TFPI) or hirudin (Hir) fusion proteins driven by an alpha smooth muscle actin (SMA) promoter were generated (alpha-TFPI-Tg and alpha-Hir-Tg) and the phenotype after wire-induced endovascular injury was compared with that in wild-type (WT) controls. Results: WT mice developed progressive neointimal expansion, whereas injury in either Tg was followed by repair back to a preinjured state. This was also seen when WT mice were reconstituted with BM from Tg mice but not when Tgs were reconstituted with WT BM, in which injury was followed by slowly progressive neointimal expansion. Injection of CD34+ cells from Tg mice into injured WT mice resulted in the accumulation of fusion protein-expressing cells from day 3 onwards and an absence of neointimal hyperplasia in those areas. CONCLUSIONS: Neointimal development after wire-induced endovascular injury in mice was completely inhibited when BM-derived cells infiltrating the damaged artery expressed membrane tethered anticoagulant fusion proteins under an alpha-SMA promoter. These findings enhance our understanding of the pathological role that coagulation proteins play in vascular inflammation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16803463&query_hl=1 ER - TY - JFULL T1 - x-f Choice: reconstruction of undersampled dynamic MRI by data-driven alias rejection applied to contrast-enhanced angiography. A1 - Malik, SJ A1 - Schmitz, S A1 - O'Regan, D A1 - Larkman, DJ A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2006/10// VL - 56 SN - 0740-3194 SP - 811 EP - 823 N2 - A technique for reconstructing dynamic undersampled MRI data, termed "x-f choice," was developed and applied to dynamic contrast-enhanced MR angiography (DCE-MRA). Regular undersampling in k-t space (a hybrid of k-space and time) creates aliasing in the conjugate x-f space that must be resolved. When regions in the object containing fast dynamic change are sparse, as in DCE-MRA, signal overlap caused by aliasing is often much less than the undersample factor would imply. x-f Choice reconstruction identifies overlapping signals using a model of the full non-aliased x-f space that is automatically generated from the undersampled data, and applies parallel imaging (PI) to separate them. No extra reference scans are required to generate either the model or the coil sensitivity maps. At each location in the reconstructed images, g-factor noise amplification is compared with predicted reconstruction errors to obtain an optimized solution. Acceleration factors greater than the number of receiver coils are possible, but are limited by the sparseness of the dynamic content and the signal-to-noise ratio (SNR) (in DCE-MRA the latter is dominant). Temporal fidelity was validated for up to a factor 10 speed-up using retrospectively undersampled data from a six-coil array. The method was tested on volunteers using fivefold prospective undersampling. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16897770&query_hl=1 ER - TY - JFULL T1 - Activation of AMPK alpha- and gamma-isoform complexes in the intact ischemic rat heart A1 - Li, J A1 - Coven, DL A1 - Miller, EJ A1 - Hu, XY A1 - Young, ME A1 - Carling, D A1 - Sinusas, AJ A1 - Young, LH J1 - AM J PHYSIOL-HEART C Y1 - 2006/10// VL - 291 SN - 0363-6135 SP - H1927 EP - H1934 N2 - AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic alpha-subunits and regulatory beta- and gamma-subunits with multiple isoforms. Mutations in the cardiac gamma(2)-isoform have been associated with hypertrophic cardiomyopathy and pre-excitation syndromes. However, physiological regulation of AMPK complexes containing different subunit isoforms is not well defined and is important for an understanding of the function of this signaling pathway in the intact heart. We evaluated the kinase activity associated with heart AMPK complexes containing specific alpha- and gamma-subunit isoforms of AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion activated the immunoprecipitated alpha(1)-isoform (6-fold, P < 0.01) and alpha(2)-isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham controls. The degree of alpha-subunit activation depended on the extent of ischemia and paralleled echocardiographic contractile dysfunction. The regulatory gamma(1)- and gamma(2)-isoforms were expressed in the heart. The gamma(1)- and gamma(2)-isoforms coimmunoprecipitated with alpha(1)- and alpha(2)-isoforms in proportion to gamma(2)-subunit content. gamma(1)-Isoform immunocomplexes accounted for 70% of AMPK activity and AMPK phosphorylation (Thr(172)) in hearts. Ischemia similarly increased AMPK activity associated with the gamma(1)- and gamma(2)-isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic alpha 1- and alpha(2)-isoforms are activated by regional ischemia in vivo in the heart, irrespective of the regulatory gamma(1)-or gamma(2)-isoforms to which they are complexed. Despite the pathophysiological importance of gamma(2)-isoform mutations, gamma(1)-isoform complexes account for most of the AMPK activity in the ischemic heart. ER - TY - JFULL T1 - Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization. A1 - Kajihara, T A1 - Jones, M A1 - Fusi, L A1 - Takano, M A1 - Feroze-Zaidi, F A1 - Pirianov, G A1 - Mehmet, H A1 - Ishihara, O A1 - Higham, JM A1 - Lam, EW A1 - Brosens, JJ J1 - Mol Endocrinol Y1 - 2006/10// VL - 20 SN - 0888-8809 SP - 2444 EP - 2455 N2 - The integrity of the feto-maternal interface is critical for survival of the conceptus. This interface, consisting of the maternal decidua and the invading placental trophoblast, is exposed to profound changes in oxygen tension during pregnancy. We demonstrate that human endometrial stromal cells become extraordinarily resistant to oxidative stress-induced apoptosis upon decidualization in response to cAMP and progesterone signaling. This differentiation process is associated with the induction of the forkhead transcription factor FOXO1, which in turn increases the expression of the mitochondrial antioxidant manganese superoxide dismutase. However, silencing of FOXO1 did not increase the susceptibility of decidualized cells to oxidative cell death. Comparative analysis demonstrated that hydrogen peroxide, a source of free radicals, strongly induces FOXO3a mRNA and protein expression in undifferentiated human endometrial stromal cells but not in decidualized cells. Expression of a constitutively active FOXO3a mutant elicited apoptosis in decidualized cells. Furthermore, silencing of endogenous FOXO3a in undifferentiated cells abrogated apoptosis induced by hydrogen peroxide. These results suggest that the induction of FOXO1 may enhance the ability of decidualized cells to prevent oxidative damage while the simultaneous repression of FOXO3a expression disables the signaling pathway responsible for oxidative cell death. The differential regulation of FOXO expression provides the decidua with a robust system capable of coping with prolonged episodes of oxidative stress during pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16709600&query_hl=1 ER - TY - JFULL T1 - Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease. A1 - Thomas, EL A1 - Brynes, AE A1 - Hamilton, G A1 - Patel, N A1 - Spong, A A1 - Goldin, RD A1 - Frost, G A1 - Bell, JD A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/09/28/ VL - 12 SN - 1007-9327 SP - 5813 EP - 5819 N2 - AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL). METHODS: Whole body MRI and (1)H MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD). RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT) depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17007047&query_hl=1 ER - TY - JFULL T1 - MAGfect: a novel liposome formulation for MRI labelling and visualization of cells. A1 - Oliver, M A1 - Ahmad, A A1 - Kamaly, N A1 - Perouzel, E A1 - Caussin, A A1 - Keller, M A1 - Herlihy, A A1 - Bell, J A1 - Miller, AD A1 - Jorgensen, MR J1 - Org Biomol Chem Y1 - 2006/09/21/ VL - 4 SN - 1477-0520 SP - 3489 EP - 3497 N2 - Cellular entry of imaging probes, such as contrast agents for magnetic resonance imaging (MRI), is a key requirement for many molecular imaging studies, particularly imaging intracellular events and cell tracking. Here, we describe the successful development and in vitro analysis of MAGfect, a novel liposome formulation containing a lipidic gadolinium contrast agent for MRI, Gd-DOTA-Chol , designed to enter and label cells. Liposome formulation and cell incubation time were optimised for maximum cellular uptake of the imaging probe in a variety of cell lines. MRI analysis of cells incubated with MAGfect showed them to be highly MRI active. This formulation was examined further for cytotoxicity, cell viability and mechanism of cell labelling. One of the key advantages of using MAGfect as a labelling vehicle arises from its potential for additional functions, such as concomitant drug or gene delivery and fluorescent labelling. The gadolinium liposome was found to be an effective vehicle for transport of plasmid DNA (pDNA) into cells and expression levels were comparable to the commercial transfection agent Trojene. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17036144&query_hl=1 ER - TY - JFULL T1 - Towards NR2B receptor selective imaging agents for PET - synthesis and evaluation of N-[C-11]-(2-methoxy)benzyl (E)-styrene-, 2-naphthyl- and 4-trifluoromethoxyphenylamidine A1 - Arstad, E A1 - Platzer, S A1 - Berthele, A A1 - Pilowsky, LS A1 - Luthra, SK A1 - Wester, HJ A1 - Henriksen, G J1 - BIOORGAN MED CHEM Y1 - 2006/09/15/ VL - 14 SN - 0968-0896 SP - 6307 EP - 6313 N2 - Three potent and selective C-11-labelled NR2B antagonists have been synthesized and evaluated as PET ligands. The brain uptake of the compounds in mice varied substantially and was dominated by metabolism. One compound was found to have favourable uptake and retention in the brain, as well as a binding pattern consistent with the expression of the target receptor as measured by in vitro autoradiography. However, the metabolism of the compounds tested was too rapid to allow for in vivo imaging. (c) 2006 Elsevier Ltd. All rights reserved. ER - TY - JFULL T1 - Quantifying the activity of adenoviral E1A CR2 deletion mutants using renilla luciferase bioluminescence and 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography imaging. A1 - Leyton, J A1 - Lockley, M A1 - Aerts, JL A1 - Baird, SK A1 - Aboagye, EO A1 - Lemoine, NR A1 - McNeish, IA J1 - Cancer Res Y1 - 2006/09/15/ VL - 66 SN - 0008-5472 SP - 9178 EP - 9185 N2 - The adenoviral E1A CR2 mutant dl922-947 has potent activity in ovarian cancer. We have used Renilla luciferase bioluminescence imaging to monitor viral E1A expression and replication and [18F]fluorothymidine positron emission tomography ([18F]FLT-PET) to quantify the activity of dl922-947 in vivo. We created dlCR2 Ren, with the same E1A CR2 deletion as dl922-947 and the luciferase gene from Renilla reniformis downstream of E1. Light emitted from s.c. and i.p. IGROV1 ovarian carcinoma xenografts was measured following treatment with dlCR2 Ren. Mice bearing s.c. IGROV1 xenografts were injected with 2.96 to 3.7 MBq of [18F]FLT 48 and 168 hours following i.t. injection of dl922-947 or control virus Ad LM-X. The presence of Renilla luciferase in dlCR2 Ren did not reduce in vitro nor in vivo potency compared with dl922-947. Light emission correlated closely with E1A expression in vitro and peaked 48 hours after dlCR2 Ren injection in both s.c. and i.p. IGROV1 xenografts. It diminished by 168 hours in s.c. tumors but persisted for at least 2 weeks in i.p. models. Normalized tumor [18F]FLT uptake at 60 minutes (NUV60), fractional retention, and area under radioactivity curve all decreased marginally 48 hours after dl922-947 treatment and significantly at 168 hours compared with controls. There was a close linear correlation between NUV60 and both tumor proliferation (Ki67 labeling index) and thymidine kinase 1 expression. Renilla luciferase bioluminescence and [18F]FLT-PET imaging are capable of quantifying the activity and effectiveness of E1A CR2-deleted adenoviral mutants in ovarian cancer. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16982761&query_hl=1 ER - TY - JFULL T1 - Dobutamine-induced hyperaemia inversely correlates with coronary artery stenosis severity and highlights dissociation between myocardial blood flow and oxygen consumption. A1 - Jagathesan, R A1 - Barnes, E A1 - Rosen, SD A1 - Foale, R A1 - Camici, PG J1 - Heart Y1 - 2006/09// VL - 92 SN - 1468-201X SP - 1230 EP - 1237 N2 - OBJECTIVES: To compare the relationship between dobutamine myocardial blood flow (MBF), rate-pressure product (RPP) and stenosis severity in patients with coronary artery disease (CAD). METHODS: 27 patients with single-vessel CAD were allocated to three groups based on stenosis severity: group 1, 50-69% (n = 9); group 2, 70-89% (n = 9); and group 3, >or= 90% (n = 9). Nine normal volunteers served as controls. Resting and dobutamine MBF were measured by positron emission tomography in the territory subtended by the stenosis (Isc) and remote myocardium (Rem). Mean left ventricular MBF was used for controls. RESULTS: In group 1, mean dobutamine MBF-Isc (2.48 (SD 0.48 ml/min/g)) and dobutamine MBF-Rem (2.70 (0.50) ml/min/g, NS) were comparable. In groups 2 and 3, dobutamine MBF-Isc (1.91 (0.44) and 1.22 (0.21) ml/min/g) was significantly lower than dobutamine MBF-Rem (2.27 (0.28) and 1.98 (0.25) ml/min/g, p < 0.02 and p < 0.005, respectively). An inverse relation between dobutamine MBF and stenosis severity existed both in Isc (r = 0.79, p < 0.001) and in Rem territories (r = 0.71, p < 0.001). For any given RPP, dobutamine MBF was greater in controls than in Rem (p < 0.05), which in turn was greater than in Isc (p < 0.05). CONCLUSION: Dobutamine MBF inversely correlated with stenosis severity and achieved significant flow heterogeneity for coronary stenoses > 70%. Dobutamine MBF and RPP were dissociated in both Isc and Rem segments in patients compared with controls. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16547210&query_hl=1 ER - TY - JFULL T1 - Phosphatidylserine exposure in B lymphocytes: a role for lipid packing. A1 - Elliott, JI A1 - Sardini, A A1 - Cooper, JC A1 - Alexander, DR A1 - Davanture, S A1 - Chimini, G A1 - Higgins, CF J1 - Blood Y1 - 2006/09/01/ VL - 108 SN - 0006-4971 SP - 1611 EP - 1617 N2 - Plasma membrane lipids are usually distributed asymmetrically, with phosphatidylserine (PS) confined to the inner leaflet. PS exposure at the outer leaflet occurs early in apoptosis, but it is also constitutive on some nonapoptotic cell populations where it plays a role in cell signaling. How PS is transported ("flopped") to the cell surface is unknown. Contrary to previous reports that normal murine B lymphocytes lack lipid asymmetry, we show that PS is normally restricted to the inner leaflet of these cells. PS exposure on normal B cells did, however, occur spontaneously ex vivo. Consistent with the hypothesis that loss of PS asymmetry is regulated by CD45, PS is constitutively exposed on viable, CD45-deficient B cells. We show that calcium-stimulated PS exposure in B cells is strain variable, ABCA1 independent, and both preceded by and dependent on a decrease in lipid packing. This decrease in lipid packing is concomitant with cell shrinkage and consequent membrane distortion, both of which are potently inhibited by blockers of volume-regulatory K+ and Cl- ion channels. Thus, changes in plasma membrane organization precede PS translocation. The data suggest a model in which PS redistribution may occur by a translocase-independent mechanism at energetically favorable sites of membrane perturbation where lipid packing is decreased. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16684961&query_hl=1 ER - TY - JFULL T1 - Determinants of adiposity during preweaning postnatal growth in appropriately grown and growth-restricted term infants. A1 - Modi, N A1 - Thomas, EL A1 - Harrington, TA A1 - Uthaya, S A1 - Doré, CJ A1 - Bell, JD J1 - Pediatr Res Y1 - 2006/09// VL - 60 SN - 0031-3998 SP - 345 EP - 348 N2 - The distribution and quantity of adipose tissue are markers of morbidity risk in children and adults. Poor intrauterine growth and accelerated postnatal growth are believed to add to these risks. The aim of this study was to assess adipose tissue content and distribution at birth and 6 wk in relation to intrauterine growth restriction, postnatal growth, and infant diet. We measured weight, length, and head circumference and adipose content and distribution using magnetic resonance imaging at 6 wk of age in appropriately grown for gestational age (AGA) and growth-restricted (GR) infants and compared this with birth data. By 6 wk, GR infants showed complete catch-up in comparison to AGA infants in relation to head growth and adiposity. Catch-up in length and weight was not complete. Accelerated linear growth, but not accelerated weight gain, was associated with a highly significant increase in adiposity (r = 0.57, p = 0.001) regardless of AGA/GR status. The highest adiposity at 6 wk, allowing for baseline variables and linear growth, was seen in exclusively breast-fed GR infants (mean, 95% confidence interval: 33.5%, 29.51-37.5). Adipose tissue distribution remained constant and was unrelated to growth and diet. Reduced birth adiposity (B = -0.185, p = 0.003), but not low birth head size (B = 0.32, p = 0.093), was a significant predictor of accelerated postnatal head growth (R(2) = 0.29, adjusted R(2) = 0.23, p = 0.012). Increasing adiposity appears to be an inevitable accompaniment of accelerated linear growth. Low total adipose tissue quantity at birth appears to direct nutrition toward head growth. Adipose tissue may be involved in the signaling of catch-up growth. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16857778&query_hl=1 ER - TY - JFULL T1 - Frequently encountered cranial ultrasound (cUS) features in the preterm infants' brain: Correlation between cUS and MRI A1 - Leijser, LM A1 - Srinivasan, L A1 - Rutherford, MA A1 - Counsell, SJ A1 - Allsop, JM A1 - Cowan, FM J1 - EARLY HUM DEV Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 632 EP - 632 ER - TY - JFULL T1 - Critical role for peptide YY in protein-mediated satiation and body-weight regulation. A1 - Batterham, RL A1 - Heffron, H A1 - Kapoor, S A1 - Chivers, JE A1 - Chandarana, K A1 - Herzog, H A1 - Le Roux, CW A1 - Thomas, EL A1 - Bell, JD A1 - Withers, DJ J1 - Cell Metab Y1 - 2006/09// VL - 4 SN - 1550-4131 SP - 223 EP - 233 N2 - Dietary protein enhances satiety and promotes weight loss, but the mechanisms by which appetite is affected remain unclear. We investigated the role of gut hormones, key regulators of ingestive behavior, in mediating the satiating effects of different macronutrients. In normal-weight and obese human subjects, high-protein intake induced the greatest release of the anorectic hormone peptide YY (PYY) and the most pronounced satiety. Long-term augmentation of dietary protein in mice increased plasma PYY levels, decreased food intake, and reduced adiposity. To directly determine the role of PYY in mediating the satiating effects of protein, we generated Pyy null mice, which were selectively resistant to the satiating and weight-reducing effects of protein and developed marked obesity that was reversed by exogenous PYY treatment. Our findings suggest that modulating the release of endogenous satiety factors, such as PYY, through alteration of specific diet constituents could provide a rational therapy for obesity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16950139&query_hl=1 ER - TY - JFULL T1 - Thalamic atrophy in infants with PVL and cerebral visual impairment. A1 - Ricci, D A1 - Anker, S A1 - Cowan, F A1 - Pane, M A1 - Gallini, F A1 - Luciano, R A1 - Donvito, V A1 - Baranello, G A1 - Cesarini, L A1 - Bianco, F A1 - Rutherford, M A1 - Romagnoli, C A1 - Atkinson, J A1 - Braddick, O A1 - Guzzetta, F A1 - Mercuri, E J1 - Early Hum Dev Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 591 EP - 595 N2 - The aim of this retrospective study was to establish the presence and severity of cerebral visual impairment in preterm infants with PVL. We also wished to establish whether abnormalities of visual function are related to brain MRI findings and more specifically not only to the involvement of optic radiations and occipital cortex but also to changes in the thalami, that are often affected in infants with PVL. Twelve infants with cystic PVL were assessed at 1 year (+2) corrected age with a battery of tests specifically designed to assess various aspects of visual function in infancy, such as ocular movements, visual acuity, visual fields and fixation shift. All infants also had a brain MRI. Eleven of the 12 had involvement of the optic radiations: all had some abnormalities of visual function and visual impairment was more severe in infants with more extensive involvement of the optic radiations. The child with normal optic radiations had normal visual function. Six of the 12 infants also had obvious signs of atrophy of the thalami and all had severe and wide-ranging abnormalities of visual function in all testing domains. Two children had equivocal atrophy of the thalami, both had some abnormalities of visual function. Four children had normal thalami and had normal visual function or only minor abnormalities on one of the visual tests. Our results suggest that the atrophy of the thalami may play an additional role in the abnormal development of visual function in infants with PVL and abnormal optic radiations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16500047&query_hl=1 ER - TY - JFULL T1 - The effect of preterm birth on neonatal cerebral vasculature studied with magnetic resonance angiography at 3 Tesla. A1 - Malamateniou, C A1 - Counsell, SJ A1 - Allsop, JM A1 - Fitzpatrick, JA A1 - Srinivasan, L A1 - Cowan, FM A1 - Hajnal, JV A1 - Rutherford, MA J1 - Neuroimage Y1 - 2006/09// VL - 32 SN - 1053-8119 SP - 1050 EP - 1059 N2 - Preterm birth is associated with a high incidence of neurodevelopmental deficits. Magnetic resonance imaging (MRI) has proved to be a valuable tool for monitoring development in the preterm brain. We used a dedicated time-of-flight (TOF) magnetic resonance angiography (MRA) protocol at 3 Tesla (3T) optimized to assess morphological characteristics of the neonatal cerebral vessels associated with preterm birth in a sample of 37 infants. We found statistically significant decreased tortuosity in all proximal segments of the cerebral vasculature (anterior, middle and posterior cerebral arteries) in the preterm infants imaged at term equivalent age compared to the term born infants, with no differences in vessel diameter between the two groups. This distinct phenotype of decreased tortuosity was shown to persist until 18 months of age in longitudinal MRA studies in infants born preterm, suggesting that this is not a delay in maturation. Biparietal head diameter measurements were significantly smaller in the preterm at term infants and were inversely correlated with middle cerebral artery tortuosity measurements in both the term born and the preterm at term infants. To our knowledge, this is the first systematic MRA study on the effect of preterm delivery on neonatal cerebral vasculature. Our intention is to build on the findings of this study by combining the data with other measurements of brain growth and vascular haemodynamics to understand more about the interdependence of vessel and brain development and their relationship to prematurity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860576&query_hl=1 ER - TY - JFULL T1 - [Guidelines on the management of stable angina pectoris. Executive summary] A1 - Fox, K A1 - García, MA A1 - Ardissino, D A1 - Buszman, P A1 - Camici, PG A1 - Crea, F A1 - Daly, C A1 - de Backer, G A1 - Hjemdahl, P A1 - López-Sendón, J A1 - Morais, J A1 - Pepper, J A1 - Sechtem, U A1 - Simoons, M A1 - Thygesen, K A1 - Grupo de trabajo de la sociedad europea de cardiologia sobre el manejo de la angina estable J1 - Rev Esp Cardiol Y1 - 2006/09// VL - 59 SN - 0300-8932 SP - 919 EP - 970 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17162834&query_hl=1 ER - TY - JFULL T1 - Role of corticotrophin releasing factor (CRF) in NMDAR-mediated responses and firing rate of ventral tegmental neurons A1 - Bonci, A A1 - Ungless, M A1 - Wanat, M J1 - ALCOHOL CLIN EXP RES Y1 - 2006/09// VL - 30 SN - 0145-6008 SP - 93A EP - 93A ER - TY - JFULL T1 - Resting and hyperaemic blood flow in regionally denervated canin myocardium: an in vivo stufy with positron emission tomography A1 - Rimoldi O A1 - Drake-Holland AJ A1 - Noble MIM A1 - Camici PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2006/09// ER - TY - JFULL T1 - Patterns of brain injury seen in neonates presenting with a postnatal collapse A1 - Foran, A A1 - Rutherford, M A1 - Cowan, F J1 - EARLY HUM DEV Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 629 EP - 629 ER - TY - JFULL T1 - The essentiality of eicosapentaenoic acid in breast milk during human lactation: implications to formula milk manufacturers A1 - Puri, BK A1 - Stannard, JP J1 - AGRO FOOD IND HI TEC Y1 - 2006/09// VL - 17 SN - 1722-6996 SP - 7 EP - 8 N2 - The case is described of a European woman in her thirties whose diet contained very little n-3 long-chain polyunsaturated fatty acids apart from an intake of one docosahexaenoic acid-enriched egg daily over the past six years. This enrichment process was carried out by feeding hens a diet close to that of their wild ancestor, the Jungle Fowl. by including a wider range of seeds and green vegetation than is normally the case in modem farming practice. During this period the subject has had two full-term normal pregnancies. Analyses of her breast milk during the postnatal periods have consistently shown that her milk is richer in both eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) than average European human milk from lactating women. This study demonstrates it is ideal for lactating women to consume a dietary source of LCP's from which they can provide both EPA and DHA for their baby The study also demonstrates current average human milk is considerably lower in EPA/DPA than is conditionally optimal and we would recommend further study in this area to define optimal EFA levels for lactating women based on a balanced source of dietary lipids rather than based on a diet lacking in these essential fatty acids which we believe produces inadequate fatty acids in human milk. ER - TY - JFULL T1 - Redistribution of nucleoside transporters to the cell membrane provides a novel approach for imaging thymidylate synthase inhibition by positron emission tomography. A1 - Perumal, M A1 - Pillai, RG A1 - Barthel, H A1 - Leyton, J A1 - Latigo, JR A1 - Forster, M A1 - Mitchell, F A1 - Jackman, AL A1 - Aboagye, EO J1 - Cancer Res Y1 - 2006/09/01/ VL - 66 SN - 0008-5472 SP - 8558 EP - 8564 N2 - Thymidylate synthase (EC 2.1.1.45) is a key enzyme for the de novo synthesis of DNA and as such a target for anticancer drug development. There is a need to develop noninvasive methods for assessing thymidylate synthase inhibition in tumors. The aim of this study was to assess the potential of 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) for early measurement of thymidylate synthase inhibition and to elucidate the cellular mechanisms involved. Radiation-induced fibrosarcoma-1 tumor-bearing mice were injected with a single i.p. dose of the thymidylate synthase inhibitor 5-fluorouracil (5-FU; 165 mg/kg) and imaged by [(18)F]FLT-PET at 1 to 2 hours after treatment. Deoxyuridine, thymidine kinase 1 (cytoplasmic thymidine kinase; EC2.7.1.21), and ATP levels in excised tumors were measured. Cellular assays for membrane transport were also done. There was a 1.8-fold increase in the 60-minute [(18)F]FLT tumor/heart radioactivity ratio in drug-treated mice compared with vehicle controls (P = 0.0016). Plasma and tumor deoxyuridine levels increased significantly but thymidine kinase and ATP levels were unchanged. Whole-cell assays implicated a (low level) functional role for the type-1 equilibrative nucleoside transporter (ENT). There was an increase in type-1 ENT-binding sites per cell from 49,110 in untreated cells to 73,142 (P = 0.03) in cells treated with 10 mug/mL 5-FU for 2 hours, without a change in transporter affinity (P = 0.41). We conclude that [(18)F]FLT-PET can be used to measure thymidylate synthase inhibition as early as 1 to 2 hours after treatment with 5-FU by a mechanism involving redistribution of nucleoside transporters to the plasma membrane. (Cancer Res 2006; 66(17): 8558-64). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16951168&query_hl=1 ER - TY - JFULL T1 - A combined linkage and expression study of rat heart to identify primary drivers of cardiac hypertrophy A1 - Sarwar, R A1 - Petretto, E A1 - Mangion, J A1 - Pravenec, M A1 - Aitman, T A1 - Cook, S J1 - HEART Y1 - 2006/09// VL - 92 SN - 1355-6037 ER - TY - JFULL T1 - Neurological outcome of premature infants following a controlled-trial of skin-to-skin contact A1 - Hickson, A A1 - Rutherford, M A1 - Glover, V A1 - Stevenson, J A1 - Dore, C A1 - Cowan, F A1 - Modi, N J1 - EARLY HUM DEV Y1 - 2006/09// VL - 82 SN - 0378-3782 SP - 631 EP - 632 ER - TY - JFULL T1 - Effects of long-term oral dipyridamole treatment on coronary microcirculatory function in patients with chronic stable angina: A substudy of the persantine in stable angina (PISA) study. A1 - Jagathesan, R A1 - Rosen, SD A1 - Foale, RA A1 - Camici, PG A1 - Picano, E J1 - J Cardiovasc Pharmacol Y1 - 2006/09// VL - 48 SN - 0160-2446 SP - 110 EP - 116 N2 - AIMS: A meta-analysis of 13 randomized placebo-controlled trials demonstrated a benefit for dipyridamole therapy, particularly with longer duration of treatment. Although the mechanism of this effect is not well understood, dipyridamole increases endogenous tissue adenosine, which may have a beneficial effect on myocardial perfusion. Therefore, we measured the effects of dipyridamole on myocardial blood flow (MBF) and coronary flow reserve (CFR) by using positron emission tomography and H2O in patients with coronary artery disease. METHODS: Forty-four patients with angiographically documented coronary artery disease were double-blind randomized to either oral dipyridamole [200 milligrams (mg) twice daily (bd)] or placebo as add-on to conventional antianginal treatment for 24 weeks. MBF was measured at rest and during dobutamine stress at baseline and study completion for the region subtended by the most severe coronary artery stenosis (Isc) and remote myocardium subtended by arteries with minimal or no disease (Rem). CFR was calculated as MBF-peak/MBF-rest. RESULTS: Thirty-five patients completed the study. Isc MBF-rest decreased in patients receiving dipyridamole (0.10 mL/minute/g; P = 0.03) and increased in the placebo group (0.16 mL/minute/g; P = 0.01) during the 24-week study. No significant change in MBF-peak was demonstrated in either group. Consequently, Isc-CFR increased significantly in patients receiving dipyridamole (1.65 +/- 0.47 vs 1.83 +/- 0.67; P < 0.05). By contrast, Isc-CFR decreased significantly in those receiving placebo (1.74 +/- 0.44 versus 1.38 +/- 0.46; P < 0.03). No change was seen in Rem-CFR territories. CONCLUSIONS: At the end of treatment, a reduction in baseline MBF but no significant changes in hyperemic MBF were observed in ischemic myocardial territories, and therefore the significance of the observed improvement in CFR remains unclear. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17031264&query_hl=1 ER - TY - JFULL T1 - Increased expression of the 5-HT transporter confers a low-anxiety phenotype linked to decreased 5-HT transmission. A1 - Jennings, KA A1 - Loder, MK A1 - Sheward, WJ A1 - Pei, Q A1 - Deacon, RM A1 - Benson, MA A1 - Olverman, HJ A1 - Hastie, ND A1 - Harmar, AJ A1 - Shen, S A1 - Sharp, T J1 - J Neurosci Y1 - 2006/08/30/ VL - 26 SN - 1529-2401 SP - 8955 EP - 8964 N2 - A commonly occurring polymorphic variant of the human 5-hydroxytryptamine (5-HT) transporter (5-HTT) gene that increases 5-HTT expression has been associated with reduced anxiety levels in human volunteer and patient populations. However, it is not known whether this linkage between genotype and anxiety relates to variation in 5-HTT expression and consequent changes in 5-HT transmission. Here we test this hypothesis by measuring the neurochemical and behavioral characteristics of a mouse genetically engineered to overexpress the 5-HTT. Transgenic mice overexpressing the human 5-HTT (h5-HTT) were produced from a 500 kb yeast artificial chromosome construct. These transgenic mice showed the presence of h5-HTT mRNA in the midbrain raphe nuclei, as well as a twofold to threefold increase in 5-HTT binding sites in the raphe nuclei and a range of forebrain regions. The transgenic mice had reduced regional brain whole-tissue levels of 5-HT and, in microdialysis experiments, decreased brain extracellular 5-HT, which reversed on administration of the 5-HTT inhibitor paroxetine. Compared with wild-type mice, the transgenic mice exhibited a low-anxiety phenotype in plus maze and hyponeophagia tests. Furthermore, in the plus maze test, the low-anxiety phenotype of the transgenic mice was reversed by acute administration of paroxetine, suggesting a direct link between the behavior, 5-HTT overexpression, and low extracellular 5-HT. In toto, these findings demonstrate that associations between increased 5-HTT expression and anxiety can be modeled in mice and may be specifically mediated by decreases in 5-HT transmission. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16943551&query_hl=1 ER - TY - JFULL T1 - The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. A1 - Uitterlinden, AG A1 - Ralston, SH A1 - Brandi, ML A1 - Carey, AH A1 - Grinberg, D A1 - Langdahl, BL A1 - Lips, P A1 - Lorenc, R A1 - Obermayer-Pietsch, B A1 - Reeve, J A1 - Reid, DM A1 - Amedei, A A1 - Amidei, A A1 - Bassiti, A A1 - Bustamante, M A1 - Husted, LB A1 - Diez-Perez, A A1 - Dobnig, H A1 - Dunning, AM A1 - Enjuanes, A A1 - Fahrleitner-Pammer, A A1 - Fang, Y A1 - Karczmarewicz, E A1 - Kruk, M A1 - van Leeuwen, JP A1 - Mavilia, C A1 - van Meurs, JB A1 - Mangion, J A1 - McGuigan, FE A1 - Pols, HA A1 - Renner, W A1 - Rivadeneira, F A1 - van Schoor, NM A1 - Scollen, S A1 - Sherlock, RE A1 - Ioannidis, JP A1 - APOSS Investigators A1 - EPOS Investigators A1 - EPOLOS Investigators A1 - FAMOS Investigators A1 - LASA Investigators A1 - Rotterdam Study Investigators A1 - GENOMOS Study J1 - Ann Intern Med Y1 - 2006/08/15/ VL - 145 SN - 1539-3704 SP - 255 EP - 264 N2 - BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures. DESIGN: Prospective multicenter large-scale association study. SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. PARTICIPANTS: 26,242 participants (18,405 women). MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16908916&query_hl=1 ER - TY - JFULL T1 - Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease. A1 - Cox, IJ A1 - Sharif, A A1 - Cobbold, JF A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/08/14/ VL - 12 SN - 1007-9327 SP - 4773 EP - 4783 N2 - Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiological processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16937457&query_hl=1 ER - TY - JFULL T1 - Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease A1 - Cox, IJ A1 - Sharif, A A1 - Cobbold, JFL A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - WORLD J GASTROENTERO Y1 - 2006/08/14/ VL - 12 SN - 1007-9327 SP - 4773 EP - 4783 N2 -

Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiological processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response. (C) 2006 The WIG Press. All rights reserved.

ER - TY - JFULL T1 - [Guidelines on the management of stable angina pectoris: executive summary] A1 - Task Force per il Trattamento dell'Angina Pectoris Stabile della Società Europea di Cardiologia A1 - Fox, K A1 - Alonso Garcia, MA A1 - Ardissino, D A1 - Buszman, P A1 - Camici, PG A1 - Crea, F A1 - Daly, C A1 - De Backer, G A1 - Hjemdahl, P A1 - Lopez-Sendon, J A1 - Marco, J A1 - Morais, J A1 - Pepper, J A1 - Sechtem, U A1 - Simoons, M A1 - Thygesen, K A1 - Priori, SG A1 - Blanc, JJ A1 - Budaj, A A1 - Camm, J A1 - Dean, V A1 - Deckers, J A1 - Dickstein, K A1 - Lekakis, J A1 - McGregor, K A1 - Metra, M A1 - Osterspey, A A1 - Tamargo, J A1 - Zamorano, JL A1 - Andreotti, F A1 - Becher, H A1 - Dietz, R A1 - Fraser, A A1 - Gray, H A1 - Hernandez Antolin, RA A1 - Huber, K A1 - Kremastinos, DT A1 - Maseri, A A1 - Nesser, HJ A1 - Pasierski, T A1 - Sigwart, U A1 - Tubaro, M A1 - Weis, M J1 - G Ital Cardiol (Rome) Y1 - 2006/08// VL - 7 SN - 1827-6806 SP - 535 EP - 583 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17089560&query_hl=1 ER - TY - JFULL T1 - Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. A1 - Dyet, LE A1 - Kennea, N A1 - Counsell, SJ A1 - Maalouf, EF A1 - Ajayi-Obe, M A1 - Duggan, PJ A1 - Harrison, M A1 - Allsop, JM A1 - Hajnal, J A1 - Herlihy, AH A1 - Edwards, B A1 - Laroche, S A1 - Cowan, FM A1 - Rutherford, MA A1 - Edwards, AD J1 - Pediatrics Y1 - 2006/08// VL - 118 SN - 1098-4275 SP - 536 EP - 548 N2 - OBJECTIVES: The aim was to survey the range of cerebral injury and abnormalities of cerebral development in infants born between 23 and 30 weeks' gestation using serial MRI scans of the brain from birth, and to correlate those findings with neurodevelopmental outcome after 18 months corrected age. METHODS: Between January 1997 and November 2000, consecutive infants born at < 30 weeks' gestational age underwent serial MRI brain scans from birth until term-equivalent age. Infants were monitored after 18 months of age, corrected for prematurity, with the Griffiths Mental Development Scales and neurologic assessment. RESULTS: A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to 30 weeks of gestation. Four infants had major destructive brain lesions, and tissue loss was seen at term for the 2 survivors. Fifty-one infants had early hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had ventricular dilation. Twenty-six infants had punctate white matter lesions on early scans; these persisted for 33% of infants assessed at term. Early scans showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia abnormalities for 17. At term, 53% of infants without previous hemorrhage had ventricular dilation and 80% of infants had diffuse excessive high signal intensity within the white matter on T2-weighted scans. Complete follow-up data were available for 66% of infants. Adverse outcomes were associated with major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilation after intraventricular hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular dilation without intraventricular hemorrhage. CONCLUSIONS: Diffuse white matter abnormalities and post-hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16882805&query_hl=1 ER - TY - JFULL T1 - In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography. A1 - Leyton, J A1 - Alao, JP A1 - Da Costa, M A1 - Stavropoulou, AV A1 - Latigo, JR A1 - Perumal, M A1 - Pillai, R A1 - He, Q A1 - Atadja, P A1 - Lam, EW A1 - Workman, P A1 - Vigushin, DM A1 - Aboagye, EO J1 - Cancer Res Y1 - 2006/08/01/ VL - 66 SN - 0008-5472 SP - 7621 EP - 7629 N2 - Histone deacetylase inhibitors (HDACI) are emerging as growth inhibitory compounds that modulate gene expression and inhibit tumor cell proliferation. We assessed whether 3'-deoxy-3'-[(18)F]fluorothymidine-positron emission tomography ([18F]FLT-PET) could be used to noninvasively measure the biological activity of a novel HDACI LAQ824 in vivo. We initially showed that thymidine kinase 1 (TK1; EC2.7.1.21), the enzyme responsible for [18F]FLT retention in cells, was regulated by LAQ824 in a drug concentration-dependent manner in vitro. In HCT116 colon carcinoma xenograft-bearing mice, LAQ824 significantly decreased tumor [18F]FLT uptake in a dose-dependent manner. At day 4 of treatment, [18F]FLT tumor-to-heart ratios at 60 minutes (NUV60) were 2.16 +/- 0.15, 1.86 +/- 0.13, and 1.45 +/- 0.20 in vehicle, and 5 and 25 mg/kg LAQ824 treatment groups, respectively (P < or = 0.05). LAQ825 at 5 mg/kg also significantly reduced both TK1 levels and [18F]FLT uptake at day 10 but not at day 2 (P < or = 0.05). [18F]FLT NUV60 correlated significantly with cellular proliferation (r = 0.68; P = 0.0019) and was associated with drug-induced histone H4 hyperacetylation. Of interest to [18F]FLT-PET imaging, both TK1 mRNA copy numbers and protein levels decreased in the order vehicle >5 mg/kg LAQ824 > 25 mg/kg LAQ824, providing a rationale for the use of [18F]FLT-PET in this setting. We also observed increases in Rb hypophosphorylation and p21 levels, factors that could have contributed to the alteration in TK1 transcription in vivo. In conclusion, we have shown the utility of [18F]FLT-PET for monitoring the biological activity of the HDACI, LAQ824. Drug-induced changes in tumor [18F]FLT uptake were due, at least in part, to reductions in TK1 transcription and translation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16885362&query_hl=1 ER - TY - JFULL T1 - Reply to "Normalization procedures and detection of linkage signal in genetical-genomics experiments". A1 - Petretto, E A1 - Mangion, J A1 - Cook, SA A1 - Aitman, TJ A1 - Pravenec, M A1 - Schulz, H A1 - Fischer, J A1 - Hubner, N J1 - Nat Genet Y1 - 2006/08// VL - 38 SN - 1061-4036 SP - 858 EP - 859 N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16874321&query_hl=1 ER - TY - JFULL T1 - Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity. A1 - Miller, J A1 - Kranzler, J A1 - Liu, Y A1 - Schmalfuss, I A1 - Theriaque, DW A1 - Shuster, JJ A1 - Hatfield, A A1 - Mueller, OT A1 - Goldstone, AP A1 - Sahoo, T A1 - Beaudet, AL A1 - Driscoll, DJ J1 - J Pediatr Y1 - 2006/08// VL - 149 SN - 0022-3476 SP - 192 EP - 198 N2 - OBJECTIVES: To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. STUDY DESIGN: This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. RESULTS: The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. CONCLUSIONS: Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16887432&query_hl=1 ER - TY - JFULL T1 - Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth. A1 - Kapellou, O A1 - Counsell, SJ A1 - Kennea, N A1 - Dyet, L A1 - Saeed, N A1 - Stark, J A1 - Maalouf, E A1 - Duggan, P A1 - Ajayi-Obe, M A1 - Hajnal, J A1 - Allsop, JM A1 - Boardman, J A1 - Rutherford, MA A1 - Cowan, F A1 - Edwards, AD J1 - PLoS Med Y1 - 2006/08// VL - 3 SN - 1549-1676 SP - e265 EP - e265 N2 - BACKGROUND: We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. METHODS AND FINDINGS: We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. CONCLUSIONS: Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16866579&query_hl=1 ER - TY - JFULL T1 - [Guidelines on the management of stable angina pectoris; the experts of the European Society of Cardiology on the management of stable angina pectoris] A1 - Fox, K A1 - Garcia, MA A1 - Ardissino, D A1 - Buszman, P A1 - Camici, PG A1 - Crea, F A1 - Daly, C A1 - Backer, G A1 - Hjemdahl, P A1 - Lopez-Sendon, J A1 - Marco, J A1 - Morais, J A1 - Pepper, J A1 - Sechtem, U A1 - Simoons, M A1 - Thygsen, K A1 - European Society of Cardiology J1 - Kardiol Pol Y1 - 2006/08// VL - 64 SN - 0022-9032 SP - 823 EP - 880 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16981057&query_hl=1 ER - TY - JFULL T1 - Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin-dependent protein kinase kinase beta A1 - Stahmann, N A1 - Woods, A A1 - Carling, D A1 - Heller, R J1 - MOL CELL BIOL Y1 - 2006/08// VL - 26 SN - 0270-7306 SP - 5933 EP - 5945 N2 - AMP-activated protein kinase (AMPK) is a sensor of cellular energy state in response to metabolic stress and other regulatory signals. AMPK is controlled by upstream kinases which have recently been identified as LKB1 or Ca2(+)/calmodulin-dependent protein kinase kinase beta (CaMKK beta). Our study of human endothelial cells shows that AMPK is activated by thrombin through a Ca2+-dependent mechanism involving the thrombin receptor protease-activated receptor 1 and G.-protein-mediated phospholipase C activation. Inhibition of CaMKK with STO-609 or downregulation of CaMKK beta using RNA interference decreased thrombin-induced AMPK activation significantly, indicating that CaMKK beta was the responsible AMPK kinase. In contrast, downregulation of LKB1 did not affect thrombin-induced AMPK activation but abolished phosphorylation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside. Thrombin stimulation led to phosphorylation of acetyl coenzyme A carboxylase (ACC) and endothelial nitric oxide synthase (eNOS), two downstream targets of AMPK. Inhibition or downregulation of CaMKK beta or AMPK abolished phosphorylation of ACC in response to thrombin but had no effect on eNOS phosphorylation, indicating that thrombin-stimulated phosphorylation of eNOS is not mediated by AMPK. Our results underline the role of Ca2+ as a regulator of AMPK activation in response to a physiologic stimulation. We also demonstrate that endothelial cells possess two pathways to activate AMPK, one Ca2+/CaMKK beta dependent and one AMP/LKB1 dependent. ER - TY - JFULL T1 - Magnetic resonance guided focused ultrasound surgery of uterine fibroids--the tissue effects of GnRH agonist pre-treatment. A1 - Smart, OC A1 - Hindley, JT A1 - Regan, L A1 - Gedroyc, WM J1 - Eur J Radiol Y1 - 2006/08// VL - 59 SN - 0720-048X SP - 163 EP - 167 N2 - OBJECTIVE: The purpose of this study was to determine the ablative effect of magnetic resonance guided focused ultrasound (MRgFUS) on fibroid tissue following the administration of gonadotrophin releasing hormone (GnRH) agonist. STUDY DESIGN: Fifty women with clinically symptomatic uterine fibroids were treated. Those with uterine diameter of 10 cm or greater were given 3 months pre-treatment with GnRH agonists. Data regarding number of ultrasound sonications, Joules of energy delivered and volume of thermal destruction was recorded. RESULTS: Twenty-seven subjects were given GnRH agonist therapy before MRgFUS and 23 women underwent MRgFUS without pre-treatment. All patients in both study groups completed MR guided FUS as an outpatient procedure with no device related adverse events reported. In the group of women who received GnRH agonists, the volume of ablation was significantly larger than that in the control group (0.06 cm3 versus 0.03 cm3, P<0.05), per Joule of energy applied. CONCLUSION: The use of GnRH agonists potentiates the thermal effects of MRgFUS in women undergoing treatment of uterine fibroids. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16740371&query_hl=1 ER - TY - JFULL T1 - Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. A1 - Crow, YJ A1 - Hayward, BE A1 - Parmar, R A1 - Robins, P A1 - Leitch, A A1 - Ali, M A1 - Black, DN A1 - van Bokhoven, H A1 - Brunner, HG A1 - Hamel, BC A1 - Corry, PC A1 - Cowan, FM A1 - Frints, SG A1 - Klepper, J A1 - Livingston, JH A1 - Lynch, SA A1 - Massey, RF A1 - Meritet, JF A1 - Michaud, JL A1 - Ponsot, G A1 - Voit, T A1 - Lebon, P A1 - Bonthron, DT A1 - Jackson, AP A1 - Barnes, DE A1 - Lindahl, T J1 - Nat Genet Y1 - 2006/08// VL - 38 SN - 1061-4036 SP - 917 EP - 920 N2 - Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3' --> 5' DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1(-/-) mouse leads to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16845398&query_hl=1 ER - TY - JFULL T1 - Galectin-1 induces skeletal muscle differentiation in human fetal mesenchymal stem cells and increases muscle regeneration. A1 - Chan, J A1 - O'Donoghue, K A1 - Gavina, M A1 - Torrente, Y A1 - Kennea, N A1 - Mehmet, H A1 - Stewart, H A1 - Watt, DJ A1 - Morgan, JE A1 - Fisk, NM J1 - Stem Cells Y1 - 2006/08// VL - 24 SN - 1066-5099 SP - 1879 EP - 1891 N2 - Cell therapy for degenerative muscle diseases such as the muscular dystrophies requires a source of cells with the capacity to participate in the formation of new muscle fibers. We investigated the myogenic potential of human fetal mesenchymal stem cells (hfMSCs) using a variety of stimuli. The use of 5-azacytidine or steroids did not produce skeletal muscle differentiation, whereas myoblast-conditioned medium resulted in only 1%-2% of hfMSCs undergoing muscle differentiation. However, in the presence of galectin-1, 66.1% +/- 5.7% of hfMSCs, but not adult bone marrow-derived mesenchymal stem cells, assumed a muscle phenotype, forming long, multinucleated fibers expressing both desmin and sarcomeric myosin via activation of muscle regulatory factors. Continuous exposure to galectin-1 resulted in more efficient muscle differentiation than pulsed exposure (62.3% vs. 39.1%; p < .001). When transplanted into regenerating murine muscle, galectin-1-exposed hfMSCs formed fourfold more human muscle fibers than nonstimulated hfMSCs (p = .008), with similar results obtained in a scid/mdx dystrophic mouse model. These data suggest that hfMSCs readily undergo muscle differentiation in response to galectin-1 through a stepwise progression similar to that which occurs during embryonic myogenesis. The high degree of myogenic conversion achieved by this method has relevance for the development of therapies for muscular dystrophies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16675596&query_hl=1 ER - TY - JFULL T1 - Proton MR spectroscopy in neonates with perinatal cerebral hypoxic-ischemic injury: Metabolite peak-area ratios, relaxation times, and absolute concentrations A1 - Cheong, JLY A1 - Cady, EB A1 - Penrice, J A1 - Wyatt, JS A1 - Cox, IJ A1 - Robertson, NJ J1 - AM J NEURORADIOL Y1 - 2006/08// VL - 27 SN - 0195-6108 SP - 1546 EP - 1554 N2 - BACKGROUND: Results from cerebral proton H-1-MR spectroscopy studies of neonates with perinatal hypoxic-ischemic injury have generally been presented as metabolite peak-area ratios, which are T1 and T2-weighted, rather than absolute metabolite concentrations. We hypothesized that compared with 1H-MR spectroscopy peak-area ratios, calculation of absolute metabolite concentrations and relaxation times measured within the first 4 days after birth (1) would improve prognostic accuracy and (2) enhance the understanding of underlying neurochemical changes in neonates with neonatal encephalopathy.METHODS: Seventeen term infants with neonatal encephalopathy and 10 healthy controls were studied at 2.4T at 1 (1-3) and 2 (2-4) (median [interquartile range]) days afterbirth, respectively. Infants with neonatal encephalopathy were classified into 2 outcome groups (normal/mild and severe/fatal), according to neurodevelopmental assessments at 1 year. The MR spectroscopy peak-area ratios, relaxation times, absolute concentrations, and concentration ratios of lactate (Lac), creatine plus phosphocreatine (Cr), N-acetylaspartate (NAA), and choline-containing compounds (Cho) from a voxel centered on the thalami were analyzed according to outcome group.RESULTS: Comparing the severe/fatal group with the controls (significance assumed with P < 0.05), we found that Lac/NAA, Lac/Cho, and Lac/Cr peak-area ratios increased and NAA/Cr and NAA/Cho decreased; Lac, NAA, and Cr T2s were increased; [Lac] was increased and [Cho], [Cr], and [NAA] decreased; and among the concentration ratios, only [Lac]/[NAA] was increased. Comparison of the normal/mild group with controls revealed no differences in peak-area ratios, relaxation times, or concentration ratios but decreased [NAA], [Cho], and [Cr] were observed in the infants with normal/mild outcome. Comparison of the normal/mild and severe/fatal groups showed increased Lac/NAA and Lac/Cho and decreased NAA/Cr and NAA/Cho peak-area ratios, reduced [NAA], and increased Lac T2 in the infants with the worse outcome.CONCLUSIONS: Metabolite concentrations, in particular [NAA], enhance the prognostic accuracy of cerebral H-1-MR spectroscopy-[NAA] was the only measurable to discriminate among all (control, normal/mild, and severe/fatal outcome) groups. However, peak-area ratios are more useful prognostic indicators than concentration ratios because they depend on metabolite concentrations and T2s, both of which are pathologically modulated. Concentration ratios depend only on the concentrations of the constituent metabolites. Increased Cr T2 may provide an indirect marker of impaired cellular energetics, and similarly, NAA T2 may constitute an index of exclusively neuronal energy status. Our recommendation is to collect data that enable calculation of brain metabolite concentrations. However, if time constraints make this impossible, metabolite peak-area ratios provide the next best method of assigning early prognosis in neonatal encephalopathy. ER - TY - JFULL T1 - Abnormal deep grey matter development following preterm birth detected using deformation-based morphometry. A1 - Boardman, JP A1 - Counsell, SJ A1 - Rueckert, D A1 - Kapellou, O A1 - Bhatia, KK A1 - Aljabar, P A1 - Hajnal, J A1 - Allsop, JM A1 - Rutherford, MA A1 - Edwards, AD J1 - Neuroimage Y1 - 2006/08/01/ VL - 32 SN - 1053-8119 SP - 70 EP - 78 N2 - Preterm birth is a leading risk factor for neurodevelopmental and cognitive impairment in childhood and adolescence. The most common known cerebral abnormality among preterm infants at term equivalent age is a diffuse white matter abnormality seen on magnetic resonance (MR) images. It occurs with a similar prevalence to subsequent impairment, but its effect on developing neural systems is unknown. MR images were obtained at term equivalent age from 62 infants born at 24-33 completed weeks gestation and 12 term born controls. Tissue damage was quantified using diffusion-weighted imaging, and deformation-based morphometry was used to make a non-subjective survey of the whole brain to identify significant cerebral morphological alterations associated with preterm birth and with diffuse white matter injury. Preterm infants at term equivalent age had reduced thalamic and lentiform volumes without evidence of acute injury in these regions (t = 5.81, P < 0.05), and these alterations were more marked with increasing prematurity (t = 7.13, P < 0.05 for infants born at less than 28 weeks) and in infants with diffuse white matter injury (t = 6.43, P < 0.05). The identification of deep grey matter growth failure in association with diffuse white matter injury suggests that white matter injury is not an isolated phenomenon, but rather, it is associated with the maldevelopment of remote structures. This could be mediated by a disturbance to corticothalamic connectivity during a critical period in cerebral development. Deformation-based morphometry is a powerful tool for modelling the developing brain in health and disease, and can be used to test putative aetiological factors for injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16675269&query_hl=1 ER - TY - JFULL T1 - Neurological examination at 6 to 9 months in infants with cystic periventricular leukomalacia. A1 - Ricci, D A1 - Cowan, F A1 - Pane, M A1 - Gallini, F A1 - Haataja, L A1 - Luciano, R A1 - Cesarini, L A1 - Leone, D A1 - Donvito, V A1 - Baranello, G A1 - Rutherford, M A1 - Romagnoli, C A1 - Dubowitz, L A1 - Mercuri, E J1 - Neuropediatrics Y1 - 2006/08// VL - 37 SN - 0174-304X SP - 247 EP - 252 N2 - The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17177152&query_hl=1 ER - TY - JFULL T1 - A rapid method for labelling CD4+ T cells with ultrasmall paramagnetic iron oxide nanoparticles for magnetic resonance imaging that preserves proliferative, regulatory and migratory behaviour in vitro. A1 - Garden, OA A1 - Reynolds, PR A1 - Yates, J A1 - Larkman, DJ A1 - Marelli-Berg, FM A1 - Haskard, DO A1 - Edwards, AD A1 - George, AJ J1 - J Immunol Methods Y1 - 2006/07/31/ VL - 314 SN - 0022-1759 SP - 123 EP - 133 N2 - A number of techniques have been developed to track the migration of T cells in vivo, but they all suffer significant shortcomings, including the examination of selected organs rather than the organism as a whole--thus precluding longitudinal studies--or limitations imposed by poor spatial resolution and the application of ionizing radiation. By conjugating the HIV tat peptide to ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in a reaction yielding a mean valence of 45, a magnetic resonance (MR) contrast agent was synthesised that allowed T cells to be efficiently labelled within just 5 min. The USPIO nanoparticles were incorporated into both the cytoplasm and nucleus of labelled cells, which retained normal in vitro proliferative responses to a polyclonal stimulus; suppressive responses mediated by labelled CD4(+) CD25(+) regulatory T cells; chemotactic responses to the chemokine CXCL-12; and transmigration of an activated endothelial monolayer. We believe that this rapid, efficient and essentially non-toxic approach to labelling both murine and human T cells for MRI holds considerable promise, paving the way for the wider immunological application of this exciting technology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860821&query_hl=1 ER - TY - JFULL T1 - Closing in on the AMPA receptor: synthesis and evaluation of 2-acetyl-1-(4'-chlorophenyl)-6-methoxy-7-[11C]methoxy-1,2,3,4-tetrahydroisoquinoline as a potential PET tracer. A1 - Arstad, E A1 - Gitto, R A1 - Chimirri, A A1 - Caruso, R A1 - Constanti, A A1 - Turton, D A1 - Hume, SP A1 - Ahmad, R A1 - Pilowsky, LS A1 - Luthra, SK J1 - Bioorg Med Chem Y1 - 2006/07/15/ VL - 14 SN - 0968-0896 SP - 4712 EP - 4717 N2 - 2-Acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, one of the most potent non-competitive AMPA antagonists described to date, has been labelled with carbon-11 and tritium and evaluated as a potential ligand for in vivo imaging of AMPA receptors using PET. The carbon-11 labelled compound showed good initial brain uptake in rats, but with rapid clearance and relatively homogenous distribution. In saturation binding studies, the tritiated racemic ligand was found to be highly potent with a Kd of 14.8+/-1.8 nM. We conclude that the low receptor density labelled with this compound, its rapid clearance from the CNS and low specific binding makes it unsuitable as an in vivo PET imaging agent for AMPA receptors. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16621575&query_hl=1 ER - TY - JFULL T1 - Consequential apoptosis in the cerebellum following injury to the developing rat forebrain. A1 - Taylor, DL A1 - Joashi, UC A1 - Sarraf, C A1 - Edwards, AD A1 - Mehmet, H J1 - Brain Pathol Y1 - 2006/07// VL - 16 SN - 1015-6305 SP - 195 EP - 201 N2 - In focal brain lesions, alterations in blood flow and cerebral metabolism can be detected in brain areas remote from the primary injury. The cellular consequences of this phenomenon, originally termed diaschisis, are not fully understood. Here, we report that in two distinct models of forebrain injury, neuronal death in the cerebellum, a site distant to the primary injury, results as consequence of neuronal loss in the forebrain. Fourteen-day-old rats were subjected to unilateral forebrain injury, achieved by either hypoxia-ischemia (right carotid artery ligation and hypoxia) or direct needle injury to brain tissue. At defined times after injury, the presence of apoptosis was investigated by cell morphology, in situ end labeling, electron microscopy and poly-ADP-ribose polymerase (PARP) cleavage. Injury to the rat forebrain following hypoxia-ischemia increased apoptosis in the internal granular and Purkinje cell layers of the cerebellum, a site distant to that of the primary injury. The number of apoptotic cells in the cerebellum was significantly related to cell death in the hippocampus. Similarly, direct needle injury to the forebrain resulted in extensive apoptotic cell death in the cerebellum. These results emphasize the intimate relationship between defined neuronal populations in relatively distant brain areas and suggest a cellular basis for diaschisis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16911476&query_hl=1 ER - TY - JFULL T1 - A genome wide linkage search for breast cancer susceptibility genes. A1 - Smith, P A1 - McGuffog, L A1 - Easton, DF A1 - Mann, GJ A1 - Pupo, GM A1 - Newman, B A1 - Chenevix-Trench, G A1 - kConFab Investigators A1 - Szabo, C A1 - Southey, M A1 - Renard, H A1 - Odefrey, F A1 - Lynch, H A1 - Stoppa-Lyonnet, D A1 - Couch, F A1 - Hopper, JL A1 - Giles, GG A1 - McCredie, MR A1 - Buys, S A1 - Andrulis, I A1 - Senie, R A1 - BCFS, BRCAX Collaborators Group A1 - Goldgar, DE A1 - Oldenburg, R A1 - Kroeze-Jansema, K A1 - Kraan, J A1 - Meijers-Heijboer, H A1 - Klijn, JG A1 - van Asperen, C A1 - van Leeuwen, I A1 - Vasen, HF A1 - Cornelisse, CJ A1 - Devilee, P A1 - Baskcomb, L A1 - Seal, S A1 - Barfoot, R A1 - Mangion, J A1 - Hall, A A1 - Edkins, S A1 - Rapley, E A1 - Wooster, R A1 - Chang-Claude, J A1 - Eccles, D A1 - Evans, DG A1 - Futreal, PA A1 - Nathanson, KL A1 - Weber, BL A1 - Breast Cancer Susceptibility Collaboration (UK) A1 - Rahman, N A1 - Stratton, MR J1 - Genes Chromosomes Cancer Y1 - 2006/07// VL - 45 SN - 1045-2257 SP - 646 EP - 655 N2 - Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome-wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over 1 were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16575876&query_hl=1 ER - TY - JFULL T1 - Epigenetics: an emerging technology in the diagnosis and treatment of cancer. A1 - Stebbing, J A1 - Bower, M A1 - Syed, N A1 - Smith, P A1 - Yu, V A1 - Crook, T J1 - Pharmacogenomics Y1 - 2006/07// VL - 7 SN - 1462-2416 SP - 747 EP - 757 N2 - Transcriptional silencing resulting from changes in epigenetic regulation of gene expression is the most frequent mechanism by which tumor suppressor genes are inactivated in human cancer. Genes participating in numerous functional groups and pathways leading to malignancy are subject to aberrant CpG methylation, with associated downregulation of expression, in human carcinogenesis. Methylation profiling can identify distinct subtypes of common human cancers and may have utility in predicting clinical phenotypes in individual patients, including sensitivity to chemotherapeutic agents. Hypomethylating agents have clinical activity in some hematological malignancies, and there is accumulating evidence correlating clinical response with demethylation and concomitant reactivation of expression of specific target genes. Epigenetic analysis is likely to have an increasingly important part to play in the diagnosis, prognostic assessment and treatment of malignant disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16886899&query_hl=1 ER - TY - JFULL T1 - Hepatic vein transit time of SonoVue: a comparative study with Levovist. A1 - Lim, AK A1 - Patel, N A1 - Eckersley, RJ A1 - Goldin, RD A1 - Thomas, HC A1 - Cosgrove, DO A1 - Taylor-Robinson, SD A1 - Blomley, MJ J1 - Radiology Y1 - 2006/07// VL - 240 SN - 0033-8419 SP - 130 EP - 135 N2 - PURPOSE: To prospectively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Forty patients and 25 healthy volunteers were examined. Subjects fasted, a bolus of SonoVue (0.6 mL) was injected into a cubital fossa vein, and hepatic venous time-intensity profiles were measured with spectral Doppler tracing. This was repeated with two injections of Levovist (2 g) and another injection of SonoVue. Time-intensity curves of spectral Doppler signals of right and middle hepatic veins were analyzed. A sustained signal intensity increase of 10% above baseline levels indicated hepatic vein transit time (HVTT). Carotid artery audio intensity was measured in volunteers. Analysis of variance and t tests were used for statistical analysis. RESULTS: Twelve patients had mild hepatitis; 18, moderate or severe hepatitis; and 10, cirrhosis. Mean HVTTs in control, mild hepatitis, moderate or severe hepatitis, and cirrhosis groups were 38.3 seconds +/- 2.4 (standard error), 47.5 seconds +/- 6.5, 29.5 seconds +/- 10.8, and 17.6 seconds +/- 5.0, respectively, with Levovist (P < .001) and 29.4 seconds +/- 6.9, 27.4 seconds +/- 9.3, 22.9 seconds +/- 4.7, and 16.4 seconds +/- 4.9, respectively, with SonoVue (P < .001). HVTT decreased as severity increased at imaging with both contrast agents. There was no significant difference in HVTT between mild and moderate hepatitis groups with SonoVue; however, there were significant differences in HVTT between all patient groups with Levovist. HVTT of SonoVue was shorter than that of Levovist in all groups (P < .001) except the cirrhosis group; in this group, HVTT of the two contrast agents was similar (P = .05). No difference was observed in mean cardiopulmonary transit time for SonoVue or Levovist (9.1 seconds +/- 2.4 [standard error] and 8.4 seconds +/- 2.5, respectively, P = .18). CONCLUSION: HVTT was significantly shorter with SonoVue than with Levovist; there was no significant difference in cardiopulmonary transit time. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16720867&query_hl=1 ER - TY - JFULL T1 - The effects of APOBEC3G on HBV replication A1 - Mohammed, E A1 - Navaratnam, N A1 - Hoare, JM A1 - McGarvey, MJ J1 - J CLIN VIROL Y1 - 2006/07// VL - 36 SN - 1386-6532 SP - S67 EP - S67 ER - TY - JFULL T1 - Stem cells primed for action: polycomb repressive complexes restrain the expression of lineage-specific regulators in embryonic stem cells. A1 - Jørgensen, HF A1 - Giadrossi, S A1 - Casanova, M A1 - Endoh, M A1 - Koseki, H A1 - Brockdorff, N A1 - Fisher, AG J1 - Cell Cycle Y1 - 2006/07// VL - 5 SN - 1551-4005 SP - 1411 EP - 1414 N2 - Stem cells are characterised by a capacity to self renew and generate progeny capable of differentiating along several defined lineage paths. Embryonic Stem (ES) cells are derived from the inner cell mass (ICM) of early-stage embryos and can contribute to all tissues of the developing embryo. Discovering how ES cell pluripotency and lineage induction is achieved is important for understanding normal development and for successfully applying stem cell-based therapies. A series of recent studies have shown that the chromatin profile of ES cells is unusual and have revealed a critical role for the Polycomb Repressive Complexes (PRCs) in maintaining pluripotency. In human and mouse ES cells many genes that encode transcription factors that are required for lineage specification bind PRC2 and carry bivalent (or opposing) histone signatures, being enriched for conventional indicators of active chromatin such as acetylated H3K9 and methylated H3K4, while lying within domains of repressive trimethylated H3K27. Mutant ES cells that lack H3K27 methylation inappropriately expressed these genes showing that PRC2 represses lineage-specific gene programs in ES cells. Here we discuss the implications of these new discoveries and explore the interdependence of PRC1 and PRC2 in regulating lineage-specific gene expression in ES cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16855402&query_hl=1 ER - TY - JFULL T1 - Guidelines for percutaneous coronary interventions: reply A1 - Silber, S A1 - Albertsson, P A1 - Aviles, FF A1 - Camici, PG A1 - Colombo, A A1 - Hamm, C A1 - Jorgensen, E A1 - Marco, J A1 - Nordrehaug, JE A1 - Ruzyllo, W A1 - Stone, GW A1 - Urban, P A1 - Wijns, W A1 - Task Force Percutaneous Coronary I J1 - EUR HEART J Y1 - 2006/07// VL - 27 SN - 0195-668X SP - 1757 EP - 1759 ER - TY - JFULL T1 - Magnetic resonance imaging in perinatal brain injury: clinical presentation, lesions and outcome. A1 - Rutherford, M A1 - Srinivasan, L A1 - Dyet, L A1 - Ward, P A1 - Allsop, J A1 - Counsell, S A1 - Cowan, F J1 - Pediatr Radiol Y1 - 2006/07// VL - 36 SN - 0301-0449 SP - 582 EP - 592 N2 - Neonatal MR imaging is invaluable in assessing the term born neonate who presents with an encephalopathy. Successful imaging requires adaptations to both the hardware and the sequences used for adults. The perinatal and postnatal details often predict the pattern of lesions sustained and are essential for correct interpretation of the imaging findings, but additional or alternative diagnoses in infants with apparent hypoxic ischaemic encephalopathy should always be considered. Perinatally acquired lesions are usually at their most obvious between 1 and 2 weeks of age. Very early imaging (<3 days) may be useful to make management decisions in ventilated neonates, but abnormalities may be subtle at that stage. Diffusion-weighted imaging is clinically useful for the early identification of ischaemic white matter in the neonatal brain but is less reliable in detecting lesions within the basal ganglia and thalami. The pattern of lesions seen on MRI can predict neurodevelopmental outcome. Additional useful information may be obtained by advanced techniques such as MR angiography, venography and perfusion-weighted imaging. Serial imaging with quantification of both structure size and tissue damage provides invaluable insights into perinatal brain injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16770663&query_hl=1 ER - TY - JFULL T1 - Use of gadolinium chloride as a contrast agent for imaging spruce knots by magnetic resonance A1 - Eberhardt, TL A1 - So, CL A1 - Herlihy, AH A1 - So, PW J1 - WOOD FIBER SCI Y1 - 2006/07// VL - 38 SN - 0735-6161 SP - 527 EP - 534 N2 - Treatments of knot-containing spruce wood blocks with a paramagnetic salt, gadolinium (III) chloride, in combination with solvent pretreatments, were evaluated as strategies to enhance the visualization of wood features by magnetic resonance imaging (MRI). Initial experiments with clear wood and excised knot samples showed differences in moisture uptake after pretreatments with selected solvents. For knot-containing spruce wood blocks, increased detail in the images with an ethanol pretreatment was attributed to the removal of extractives thereby resulting in higher moisture contents for the knot wood. Incorporation of the gadolinium-based contrast agent resulted in an abrupt loss in signal for a zone around each knot. Accordingly, the retention of gadolinium ions appears to be selective, thereby allowing the demarcation of what is likely to be compression wood known to surround softwood knots. Applications include studies on wood anatomy by MRI and the modeling of wood defects. The treatment of wood with contrast agents as such also shows promise as a technique to improve our understanding of the localization of different cell-wall chemistries, especially as they relate to ion exchange capacity. ER - TY - JFULL T1 - A controlled trial of skin-to-skin contact in extremely preterm infants. A1 - Miles, R A1 - Cowan, F A1 - Glover, V A1 - Stevenson, J A1 - Modi, N J1 - Early Hum Dev Y1 - 2006/07// VL - 82 SN - 0378-3782 SP - 447 EP - 455 N2 - BACKGROUND: Extremely preterm birth, even in the absence of significant neurological impairment, is associated with altered pain responses and impaired memory and behaviour. Preterm birth increases the risk of maternal depression and may impede the development of the mother-infant relationship, factors that in turn are also associated with impaired infant outcome. Mother-infant skin-to-skin contact has been recommended as a simple means of ameliorating these effects. METHODS: We conducted a pragmatic, prospective, controlled, intention-to-treat trial in two neonatal intensive care units. Infants born below 32 weeks gestation were recruited within the first week after birth and assigned to a control group receiving standard care, or an intervention group in which mothers were encouraged to provide a session of skin-to-skin contact once daily for 4 weeks. We assessed infant behaviour at time of discharge from hospital, responses to immunisation at 4 and 12 months of age, and memory, behaviour and development at 1 year corrected (postmenstrual) age. Indices of maternal depression, stress, anxiety, lactation performance and infant interaction were assessed at time of infant discharge, 4 months and 1 year. RESULTS: No significant difference was identified in any infant or maternal measure at any time point. CONCLUSIONS: Mother-infant skin-to-skin contact after extremely preterm birth results in neither benefit nor adverse consequences. Although there is no reason to dissuade mothers who wish to provide STS contact, we are unable to recommend resource allocation for the implementation of STS programmes for extremely preterm infants in a neonatal intensive care unit setting. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16458458&query_hl=1 ER - TY - JFULL T1 - Genetic causes of Familial Hypercholesterolaemia in UK patients: relation to plasma lipid levels and coronary heart disease risk. A1 - Humphries, SE A1 - Whittall, RA A1 - Hubbart, CS A1 - Maplebeck, S A1 - Cooper, JA A1 - Soutar, A A1 - Naoumova, R A1 - Thompson, GR A1 - Seed, M A1 - Durrington, PN A1 - Miller, JP A1 - Betteridge, DJ A1 - Neil, HA J1 - J Med Genet Y1 - 2006/06/26/ SN - 1468-6244 N2 - AIMS: In UK patients with clinically-defined definite familial hypercholesterolaemia (FH) to determine the relative frequency of mutations in three different genes (LDLR, APOB, PCSK9), and to examine their impact in development of coronary heart disease (CHD). Subject and METHODS: 409 FH patients (158 with CHD) were studied. The LDLR was partially screened by SSCP (exons 3, 4, 6-10 and 14) and using a commercial kit for gross deletions/rearrangements. APOB (p.R3500Q) and PCSK9 (p.D374Y) were detected by specific assays. Coding exons of PCSK9 were screened by SSCP. RESULTS: Mutations were detected in 253 (61.9%) patients; 236 (57.7%) in LDLR; 10 (2.4%) carried APOB p.Q3500 and 7 (1.7%) PCSK9 p.Y374. No additional mutations were identified in PCSK9. After adjusting for age, sex, smoking and systolic blood pressure, compared to those with no detectable mutation, the odds ratio of having CHD in those with an LDLR mutation was 1.84 (95% CI 1.10-3.06), for APOB 3.40 (0.71-16.36), and for PCSK9 19.96 (1.88-211.5), (p=0.0003 overall). The high risk in LDLR and PCSK9 p.Y374-carrying subjects was partly explained by their higher pre-treatment cholesterol levels (LDLR, PCSK9, no-mutation, 10.29+/-1.85mmol/l, 13.12+/-1.69mmol/l, 9.85+/-1.90mmol/l, p=0.0002). The post-statin treatment lipid profile in PCSK9 p.Y374 carriers was worse than subjects with no identified mutation (LDL-C, 6.77+/-1.82mmol/l versus 4.19+/-1.26mmol/l, p=0.0001, HDL-C 1.09+/-0.27mmol/l versus 1.36+/-0.36mmol/l, p=0.03). CONCLUSIONS: The higher CHD risk in patients carrying PCSK9 p.Y347 or a detected LDLR mutation supports the usefulness of DNA testing in the diagnosis and management of FH patients. Mutations in PCSK9 appear uncommon in UK FH patients. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16801348&query_hl=1 ER - TY - JFULL T1 - A choreography of nicotinic receptors directs the dopamine neuron routine. A1 - Ungless, MA A1 - Cragg, SJ J1 - Neuron Y1 - 2006/06/15/ VL - 50 SN - 0896-6273 SP - 815 EP - 816 N2 - Modulation of the mesocorticolimbic dopamine system by nicotinic acetylcholine receptors (nAChRs) is thought to play an important role in both health and addiction. However, a clear understanding of how these receptors regulate in vivo firing activity has been elusive. In this issue of Neuron, Mameli-Engvall and colleagues report an impressive and thought-provoking series of in vivo experiments combining single-unit recordings from dopamine neurons with nAChR subunit deletions and region-specific lentiviral subunit re-expression. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16772163&query_hl=1 ER - TY - JFULL T1 - Role of microbubble ultrasound contrast agents in the non-invasive assessment of chronic hepatitis C-related liver disease. A1 - Grier, S A1 - Lim, AK A1 - Patel, N A1 - Cobbold, JF A1 - Thomas, HC A1 - Cox, IJ A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/06/14/ VL - 12 SN - 1007-9327 SP - 3461 EP - 3465 N2 - Patients who are chronically infected with the hepatitis C virus often develop chronic liver disease and assessment of the severity of liver injury is required prior to considering viral eradication therapy. This article examines the various assessment methods currently available from gold standard liver biopsy to serological markers and imaging. Ultrasound is one of the most widely used imaging modalities in clinical practice and is already a first-line diagnostic tool for liver disease. Microbubble ultrasound contrast agents allow higher resolution images to be obtained and functional assessments of microvascular change to be carried out. The role of these agents in quantifying the state of hepatic injury is discussed as a viable method of determining the stage and grade of liver disease in patients with hepatitis C. Although currently confined to specialist centres, the availability of microbubble contrast-enhanced ultrasound will inevitably increase in the clinical setting. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16773702&query_hl=1 ER - TY - JFULL T1 - Integrated gene expression profiling and linkage analysis in the rat. A1 - Petretto, E A1 - Mangion, J A1 - Pravanec, M A1 - Hubner, N A1 - Aitman, TJ J1 - Mamm Genome Y1 - 2006/06/12/ SN - 0938-8990 N2 - The combined application of genome-wide expression profiling from microarray experiments with genetic linkage analysis enables the mapping of expression quantitative trait loci (eQTLs) which are primary control points for gene expression across the genome. This approach allows for the dissection of primary and secondary genetic determinants of gene expression. The cis-acting eQTLs in practice are easier to investigate than the trans-regulated eQTLs because they are under simpler genetic control and are likely to be due to sequence variants within the gene itself or its neighboring regulatory elements. These genes are therefore candidates both for variation in gene expression and for contributions to whole-body phenotypes, particularly when these are located within known and relevant physiologic QTLs. Multiple trans-acting eQTLs tend to cluster to the same genetic location, implying shared regulatory control mechanisms that may be amenable to network analysis to identify gene clusters within the same metabolic pathway. Such clusters may ultimately underlie development of individual complex, whole-body phenotypes. The combined expression and linkage approach has been applied successfully in several mammalian species, including the rat which has specific features that demonstrate its value as a model for studying complex traits. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16770484&query_hl=1 ER - TY - JFULL T1 - Sub-wavelength imaging at radio frequency A1 - Wiltshire, MCK A1 - Pendry, JB A1 - Hajnal, JV J1 - J PHYS-CONDENS MAT Y1 - 2006/06/07/ VL - 18 SN - 0953-8984 SP - L315 EP - L321 N2 - A slab of material with a negative permeability can act as a super-lens for magnetic fields and generate images with a sub-wavelength resolution. We have constructed an effective medium using a metamaterial with negative permeability in the region of 24MHz, and used this to form images in free space of radio frequency magnetic sources. Measurements of these images show that a resolution of approximately lambda/64 has been achieved, consistent with both analytical and numerical predictions. ER - TY - JFULL T1 - Integrated gene expression profiling and linkage analysis in the rat. A1 - Petretto, E A1 - Mangion, J A1 - Pravanec, M A1 - Hubner, N A1 - Aitman, TJ J1 - Mamm Genome Y1 - 2006/06// VL - 17 SN - 0938-8990 SP - 480 EP - 489 N2 - The combined application of genome-wide expression profiling from microarray experiments with genetic linkage analysis enables the mapping of expression quantitative trait loci (eQTLs) which are primary control points for gene expression across the genome. This approach allows for the dissection of primary and secondary genetic determinants of gene expression. The cis-acting eQTLs in practice are easier to investigate than the trans-regulated eQTLs because they are under simpler genetic control and are likely to be due to sequence variants within the gene itself or its neighboring regulatory elements. These genes are therefore candidates both for variation in gene expression and for contributions to whole-body phenotypes, particularly when these are located within known and relevant physiologic QTLs. Multiple trans-acting eQTLs tend to cluster to the same genetic location, implying shared regulatory control mechanisms that may be amenable to network analysis to identify gene clusters within the same metabolic pathway. Such clusters may ultimately underlie development of individual complex, whole-body phenotypes. The combined expression and linkage approach has been applied successfully in several mammalian species, including the rat which has specific features that demonstrate its value as a model for studying complex traits. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16783629&query_hl=1 ER - TY - JFULL T1 - Recombineering of a bacterial artificial chromosome for generation of transgenic mice expressing myc-tagged wild type or mutant (D374Y) human PCSK9 A1 - Sun, XM A1 - Eden, ER A1 - Waddington, SN A1 - Soutar, AK J1 - ATHEROSCLEROSIS SUPP Y1 - 2006/06// VL - 7 SN - 1567-5688 SP - 197 EP - 198 ER - TY - JFULL T1 - Magnetic resonance and ultrasound techniques for the evaluation of hepatic fibrosis. A1 - Cobbold, J A1 - Lim A A1 - Wylezinska M A1 - Cunningham C A1 - Crossey M A1 - Thomas H A1 - Patel N A1 - Cox J A1 - Taylor-Robinson J1 - Hepatology Y1 - 2006/06// IS - 6 VL - 43 SP - 1401 EP - 1402 UR - http://www3.interscience.wiley.com/cgi-bin/fulltext/112636849/PDFSTART ER - TY - JFULL T1 - Molecular study of familial hypercholesterolemia in Portugal A1 - Bourbon, M A1 - Alves, AC A1 - Medeiros, AM A1 - Silva, S A1 - Soutar, AK J1 - ATHEROSCLEROSIS SUPP Y1 - 2006/06// VL - 7 SN - 1567-5688 SP - 131 EP - 131 ER - TY - JFULL T1 - Does oxygen concentration used for resuscitation influence outcome of asphyxiated newly born infants treated with hypothermia? Reply A1 - Thoresen, M A1 - Whitelaw, A A1 - Azzopardi, D A1 - Renowden, S A1 - Edwards, AD A1 - Rutherford, MA J1 - PEDIATRICS Y1 - 2006/06// VL - 117 SN - 0031-4005 SP - 2328 EP - 2328 ER - TY - JFULL T1 - Mutation detection in LDLR gene by DHPLC and sequencing A1 - Alves, AC A1 - Soutar, AK A1 - Bourbon, M J1 - ATHEROSCLEROSIS SUPP Y1 - 2006/06// VL - 7 SN - 1567-5688 SP - 136 EP - 136 ER - TY - JFULL T1 - Genome-wide expression analysis of cells expressing wild-type or gain of function mutant (D374Y) PCSK9 A1 - Chester, A A1 - Sun, XM A1 - Soutar, AK A1 - Lipoprotein Grp J1 - ATHEROSCLEROSIS SUPP Y1 - 2006/06// VL - 7 SN - 1567-5688 SP - 306 EP - 306 ER - TY - JFULL T1 - New clinical applications of magnetic resonance-guided focused ultrasound. A1 - Gedroyc, WM J1 - Top Magn Reson Imaging Y1 - 2006/06// VL - 17 SN - 0899-3459 SP - 189 EP - 194 N2 - Magnetic resonance-guided ultrasound delivers destructive energy into deep body structures with great accuracy and repeatability with an excellent safety profile. The use of this technology for the treatment of uterine fibroids is already becoming widespread. This article reviews the further areas of magnetic resonance-guided focused ultrasound application that are evolving and how they will be applied to other parts of the body. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17414076&query_hl=1 ER - TY - JFULL T1 - Guidelines on the management of stable angina pectoris: executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. A1 - Fox, K A1 - Garcia, MA A1 - Ardissino, D A1 - Buszman, P A1 - Camici, PG A1 - Crea, F A1 - Daly, C A1 - De Backer, G A1 - Hjemdahl, P A1 - Lopez-Sendon, J A1 - Marco, J A1 - Morais, J A1 - Pepper, J A1 - Sechtem, U A1 - Simoons, M A1 - Thygesen, K A1 - Priori, SG A1 - Blanc, JJ A1 - Budaj, A A1 - Camm, J A1 - Dean, V A1 - Deckers, J A1 - Dickstein, K A1 - Lekakis, J A1 - McGregor, K A1 - Metra, M A1 - Morais, J A1 - Osterspey, A A1 - Tamargo, J A1 - Zamorano, JL A1 - Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology A1 - ESC Committee for Practice Guidelines (CPG) J1 - Eur Heart J Y1 - 2006/06// VL - 27 SN - 0195-668X SP - 1341 EP - 1381 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16735367&query_hl=1 ER - TY - JFULL T1 - Functional analysis of chimaeras of the low density- and very low density lipoprotein receptors (LDLR and VLDLR) A1 - Patel, DD A1 - Norman, D A1 - Knight, BL A1 - Soutar, AK J1 - ATHEROSCLEROSIS SUPP Y1 - 2006/06// VL - 7 SN - 1567-5688 SP - 515 EP - 515 ER - TY - JFULL T1 - Sequential neurological examinations in infants with neonatal encephalopathy and low apgar scores: relationship with brain MRI. A1 - Ricci, D A1 - Guzzetta, A A1 - Cowan, F A1 - Haataja, L A1 - Rutherford, M A1 - Dubowitz, L A1 - Mercuri, E J1 - Neuropediatrics Y1 - 2006/06// VL - 37 SN - 0174-304X SP - 148 EP - 153 N2 - OBJECTIVE: The aims of this study were to (a) describe the evolution of neurological signs after the neonatal period in infants with neonatal encephalopathy and abnormal outcome and (b) to establish the relationship between the evolution of neurological signs and patterns of lesions on brain MRI. PATIENTS: Fifteen children with low Apgar scores, abnormal neurological signs at the end of the neonatal period, and abnormal outcome were examined at 1 - 2 weeks, 5 - 7 weeks, and 6 months. All the infants had at least one MRI scan performed in the neonatal period. RESULTS: All infants had persistent abnormalities on all examinations performed but the severity of neurological impairment was variable and was related to the pattern of brain lesions. Infants with severe basal ganglia and white matter lesions showed abnormal axial and limb tone, movements, and visual function on all the examinations and none achieved independent sitting. In infants with moderate basal ganglia lesions and/or severe white matter changes, visual function and feeding improved by 5 - 7 weeks and were still normal at 6 months while limb tone, which was reduced in the first weeks, appeared to be normal at 5 - 6 weeks but was found to be increased at 6 months; all were able to sit unsupported at 2 years and most of them achieved the ability to walk with support. CONCLUSIONS: Our results suggest that the evolution of the neurological patterns after the neonatal period in infants with persisting neonatal abnormalities depends on their pattern of brain lesions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16967366&query_hl=1 ER - TY - JFULL T1 - Genetic diagnosis of familial hypercholesterolemia: Novel genes and techniques A1 - Tosi, I A1 - Toledo-Leiva, P A1 - Neuwirth, C A1 - Naoumova, RP A1 - Soutar, AK J1 - ATHEROSCLEROSIS SUPP Y1 - 2006/06// VL - 7 SN - 1567-5688 SP - 128 EP - 129 ER - TY - JFULL T1 - The spectrum of mutations and molecular pathogenesis of hemophilia A in 181 Portuguese patients A1 - David, D A1 - Ventura, C A1 - Moreira, I A1 - Diniz, MJ A1 - Antunes, M A1 - Tavares, A A1 - Araujo, F A1 - Morais, S A1 - Campos, M A1 - Lavinha, J A1 - Kemball-Cook, G J1 - HAEMATOL-HEMATOL J Y1 - 2006/06// VL - 91 SN - 0390-6078 SP - 840 EP - 843 N2 - Disease-causing alterations within the F8 gene were identified in 177 hemophilia A families of Portuguese origin. The spectrum of non-inversion F8 mutations in 101 families included 67 different alterations, namely: 36 missense, 8 nonsense and 4 splice site mutations, as well as 19 insertions/deletions. Thirty-four of these mutations are novel. Molecular modeling allowed prediction of the conformational changes introduced by selected amino acid substitutions and their correlation with the patients' phenotypes. The relatively frequent, population-specific, missense mutations together with de novo alterations can lead to significant differences in the spectrum of F8 mutations among different populations. ER - TY - JFULL T1 - Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encephalopathy. A1 - Grover, VP A1 - Dresner, MA A1 - Forton, DM A1 - Counsell, S A1 - Larkman, DJ A1 - Patel, N A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - World J Gastroenterol Y1 - 2006/05/21/ VL - 12 SN - 1007-9327 SP - 2969 EP - 2978 N2 - Hepatic encephalopathy (HE) is a common neuro-psychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging (MRI) techniques provide a non-invasive means of assessment of changes in brain volume (coregistered MRI) and impaired brain function (fMRI), while proton magnetic resonance spectroscopy (1H MRS) detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16718775&query_hl=1 ER - TY - JFULL T1 - Attenuated spread of X-inactivation in an X;autosome translocation. A1 - Popova, BC A1 - Tada, T A1 - Takagi, N A1 - Brockdorff, N A1 - Nesterova, TB J1 - Proc Natl Acad Sci U S A Y1 - 2006/05/16/ VL - 103 SN - 0027-8424 SP - 7706 EP - 7711 N2 - X inactivation in female mammals involves transcriptional silencing of an entire chromosome in response to a cis-acting noncoding RNA, the X inactive-specific transcript (Xist). Xist can also inactivate autosomal sequences, for example, in X;autosome translocations; but here, silencing appears to be relatively inefficient. This variation has been attributed to either attenuated spreading of Xist RNA at the onset of X inactivation or inefficient maintenance of autosomal silencing. Evidence to date has favored the latter. Here, we demonstrate attenuated spreading of Xist RNA at the onset of X inactivation in the T(X;4)37H X;autosome translocation. Our findings provide direct evidence that underlying chromosome/chromatin features can disrupt spreading of the primary inactivating signal. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16679409&query_hl=1 ER - TY - JFULL T1 - Magnetic resonance imaging in perinatal brain injury: clinical presentation, lesions and outcome. A1 - Rutherford, M A1 - Srinivasan, L A1 - Dyet, L A1 - Ward, P A1 - Allsop, J A1 - Counsell, S A1 - Cowan, F J1 - Pediatr Radiol Y1 - 2006/05/16/ SN - 0301-0449 N2 - Neonatal MR imaging is invaluable in assessing the term born neonate who presents with an encephalopathy. Successful imaging requires adaptations to both the hardware and the sequences used for adults. The perinatal and postnatal details often predict the pattern of lesions sustained and are essential for correct interpretation of the imaging findings, but additional or alternative diagnoses in infants with apparent hypoxic ischaemic encephalopathy should always be considered. Perinatally acquired lesions are usually at their most obvious between 1 and 2 weeks of age. Very early imaging (<3 days) may be useful to make management decisions in ventilated neonates, but abnormalities may be subtle at that stage. Diffusion-weighted imaging is clinically useful for the early identification of ischaemic white matter in the neonatal brain but is less reliable in detecting lesions within the basal ganglia and thalami. The pattern of lesions seen on MRI can predict neurodevelopmental outcome. Additional useful information may be obtained by advanced techniques such as MR angiography, venography and perfusion-weighted imaging. Serial imaging with quantification of both structure size and tissue damage provides invaluable insights into perinatal brain injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16703343&query_hl=1 ER - TY - JFULL T1 - Acquisition and extinction of gene expression programs are separable events in heterokaryon reprogramming. A1 - Terranova, R A1 - Pereira, CF A1 - Du Roure, C A1 - Merkenschlager, M A1 - Fisher, AG J1 - J Cell Sci Y1 - 2006/05/15/ VL - 119 SN - 0021-9533 SP - 2065 EP - 2072 N2 - Although differentiated cells normally retain cell-type-specific gene expression patterns throughout their lifetime, cell identity can sometimes be modified or reversed in vivo by transdifferentiation, or experimentally through cell fusion or by nuclear transfer. To examine the epigenetic changes that are required for the dominant conversion of lymphocytes to muscle, we generated heterokaryons between human B lymphocytes and mouse C2C12 myotubes. We show that within 2 days of heterokaryon formation lymphocyte nuclei adopt an architecture resembling that of muscle and then initiate the expression of muscle-specific genes in the same temporal order as developing muscle. The establishment of this muscle-specific program is coordinated with the shutdown of several lymphocyte-associated genes. Interestingly, erasing lymphocyte identity in reprogrammed cells requires histone deacetylase (HDAC) activity. Inhibition of HDAC activity during reprogramming selectively blocks the silencing of lymphocyte-specific genes but does not prevent the establishment of muscle-specific gene expression. Successful reprogramming is therefore shown to be a multi-step process in which the acquisition and extinction of lineage-specific gene programs are separable events. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16638804&query_hl=1 ER - TY - JFULL T1 - Chromatin signatures of pluripotent cell lines. A1 - Azuara, V A1 - Perry, P A1 - Sauer, S A1 - Spivakov, M A1 - Jørgensen, HF A1 - John, RM A1 - Gouti, M A1 - Casanova, M A1 - Warnes, G A1 - Merkenschlager, M A1 - Fisher, AG J1 - Nat Cell Biol Y1 - 2006/05// VL - 8 SN - 1465-7392 SP - 532 EP - 538 N2 - Epigenetic genome modifications are thought to be important for specifying the lineage and developmental stage of cells within a multicellular organism. Here, we show that the epigenetic profile of pluripotent embryonic stem cells (ES) is distinct from that of embryonic carcinoma cells, haematopoietic stem cells (HSC) and their differentiated progeny. Silent, lineage-specific genes replicated earlier in pluripotent cells than in tissue-specific stem cells or differentiated cells and had unexpectedly high levels of acetylated H3K9 and methylated H3K4. Unusually, in ES cells these markers of open chromatin were also combined with H3K27 trimethylation at some non-expressed genes. Thus, pluripotency of ES cells is characterized by a specific epigenetic profile where lineage-specific genes may be accessible but, if so, carry repressive H3K27 trimethylation modifications. H3K27 methylation is functionally important for preventing expression of these genes in ES cells as premature expression occurs in embryonic ectoderm development (Eed)-deficient ES cells. Our data suggest that lineage-specific genes are primed for expression in ES cells but are held in check by opposing chromatin modifications. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16570078&query_hl=1 ER - TY - JFULL T1 - Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome. A1 - Davies, JK A1 - Wells, DJ A1 - Liu, K A1 - Whitrow, HR A1 - Daniel, TD A1 - Grignani, R A1 - Lygate, CA A1 - Schneider, JE A1 - Noël, G A1 - Watkins, H A1 - Carling, D J1 - Am J Physiol Heart Circ Physiol Y1 - 2006/05// VL - 290 SN - 0363-6135 SP - H1942 EP - H1951 N2 - AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that plays a key role in the regulation of energy metabolism. In humans, mutations in the gamma2-subunit of AMPK cause cardiac hypertrophy associated with Wolff-Parkinson-White syndrome, characterized by ventricular preexcitation. The effect of these mutations on AMPK activity and in development of the disease is enigmatic. Here we report that transgenic mice with cardiac-specific expression of gamma2 harboring a mutation of arginine residue 531 to glycine (RG-TG) develop a striking cardiac phenotype by 4 wk of age, including hypertrophy, impaired contractile function, electrical conduction abnormalities, and marked glycogen accumulation. At this stage, AMPK activity isolated from hearts of RG-TG mice was almost completely abolished but could be restored after phosphorylation by an upstream AMPK kinase. At 1 wk of age, there was no detectable evidence of a cardiac phenotype, and AMPK activity in RG-TG hearts was similar to that in nontransgenic, control mice. We propose that mutations in gamma2 lead to suppression of total cardiac AMPK activity secondary to increased glycogen accumulation. The subsequent decrease in AMPK activity provides a mechanism that may explain the development of cardiac hypertrophy in this model. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16339829&query_hl=1 ER - TY - JFULL T1 - CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK A1 - Watt, MJ A1 - Dzamko, N A1 - Thomas, WG A1 - Rose-John, S A1 - Ernst, M A1 - Carling, D A1 - Kemp, BE A1 - Febbraio, MA A1 - Steinberg, GR J1 - NAT MED Y1 - 2006/05// VL - 12 SN - 1078-8956 SP - 541 EP - 548 N2 - Ciliary neurotrophic factor (CNTF) induces weight loss and improves glucose tolerance in humans and rodents. CNTF is thought to act centrally by inducing hypothalamic neurogenesis to modulate food intake and peripherally by altering hepatic gene expression, in a manner similar to that of leptin. Here, we show that CNTF signals through the CNTFR alpha-IL-6R-gp130 beta receptor complex to increase fatty-acid oxidation and reduce insulin resistance in skeletal muscle by activating AMP-activated protein kinase (AMPK), independent of signaling through the brain. Thus, our findings further show that the antiobesogenic effects of CNTF in the periphery result from direct effects on skeletal muscle, and that these peripheral effects are not suppressed by diet-induced or genetic models of obesity, an essential requirement for the therapeutic treatment of obesity-related diseases. ER - TY - JFULL T1 - Respiratory gating of cardiac PET data in list-mode acquisition. A1 - Livieratos, L A1 - Rajappan, K A1 - Stegger, L A1 - Schafers, K A1 - Bailey, DL A1 - Camici, PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2006/05// VL - 33 SN - 1619-7070 SP - 584 EP - 588 N2 - PURPOSE: Respiratory motion has been identified as a source of artefacts in most medical imaging modalities. This paper reports on respiratory gating as a means to eliminate motion-related inaccuracies in PET imaging. METHODS: Respiratory gating was implemented in list mode with physiological signal recorded every millisecond together with the PET data. Respiration was monitored with an inductive respiration monitor using an elasticised belt around the patient's chest. Simultaneous ECG gating can be maintained independently by encoding ECG trigger signal into the list-mode data. Respiratory gating is performed in an off-line workstation with gating parameters defined retrospectively. The technique was applied on a preliminary set of patient data with C(15)O. RESULTS: Motion was visually observed in the cine displays of the sagittal and coronal views of the reconstructed respiratory gated images. Significant changes in the cranial-caudal position of the heart could be observed. The centroid of the cardiac blood pool showed an excursion of 4.5-16.5 mm (mean 8.5+/-4.8 mm) in the cranial-caudal direction, with more limited excursion of 1.1-7.0 mm (mean 2.5+/-2.2 mm) in the horizontal direction and 1.3-3.7 mm (mean 2.4+/-0.9 mm) in the vertical direction. CONCLUSION: These preliminary data show that the extent of motion involved in respiration is comparable to myocardial wall thickness, and respiratory gating may be considered in order to reduce this effect in the reconstructed images. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16416329&query_hl=1 ER - TY - JFULL T1 - Parallel imaging. A1 - Hajnal, JV A1 - Larkman, DJ J1 - NMR Biomed Y1 - 2006/05// VL - 19 SN - 0952-3480 SP - 287 EP - 287 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16705629&query_hl=1 ER - TY - JFULL T1 - Reliable identification of the auditory thalamus using multi-modal structural analyses. A1 - Devlin, JT A1 - Sillery, EL A1 - Hall, DA A1 - Hobden, P A1 - Behrens, TE A1 - Nunes, RG A1 - Clare, S A1 - Matthews, PM A1 - Moore, DR A1 - Johansen-Berg, H J1 - Neuroimage Y1 - 2006/05/01/ VL - 30 SN - 1053-8119 SP - 1112 EP - 1120 N2 - The medial geniculate body (MGB) of the thalamus is a key component of the auditory system. It is involved in relaying and transforming auditory information to the cortex and in top-down modulation of processing in the midbrain, brainstem, and ear. Functional imaging investigations of this region in humans, however, have been limited by the difficulty of distinguishing MGB from other thalamic nuclei. Here, we introduce two methods for reliably delineating MGB anatomically in individuals based on conventional and diffusion MRI data. The first uses high-resolution proton density weighted scanning optimized for subcortical grey-white contrast. The second uses diffusion-weighted imaging and probabilistic tractography to automatically segment the medial and lateral geniculate nuclei from surrounding structures based on their distinctive patterns of connectivity to the rest of the brain. Both methods produce highly replicable results that are consistent with published atlases. Importantly, both methods rely on commonly available imaging sequences and standard hardware, a significant advantage over previously described approaches. In addition to providing useful approaches for identifying the MGB and LGN in vivo, our study offers further validation of diffusion tractography for the parcellation of grey matter regions on the basis of their connectivity patterns. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16473021&query_hl=1 ER - TY - JFULL T1 - Comparison of myocardial blood flow and coronary flow reserve during dobutamine and adenosine stress: Implications for pharmacologic stress testing in coronary artery disease. A1 - Jagathesan, R A1 - Barnes, E A1 - Rosen, SD A1 - Foale, RA A1 - Camici, PG J1 - J Nucl Cardiol Y1 - 2006/05// VL - 13 SN - 1071-3581 SP - 324 EP - 332 N2 - BACKGROUND: Mechanistic differences between pharmacologic stressors may offer different clinical benefits. Therefore the effects of dobutamine and adenosine on absolute myocardial blood flow (MBF) and coronary flow reserve (CFR) were compared. METHODS AND RESULTS: We divided 36 patients (mean age, 61 +/- 8 years) with coronary artery disease into 2 groups based on stenosis severity as follows: greater than 50% but less than 75% (n = 16) and greater than 75% (n = 20). In addition, 18 normal volunteers (mean age, 46 +/- 7 years) served as control subjects. Groups of equal sizes received either dobutamine or adenosine. MBF at rest and peak MBF were measured by use of positron emission tomography in territories subtended by the stenosis (ischemic) and remote myocardium (remote), whereas left ventricular MBF was used in control subjects. CFR was calculated as peak MBF divided by MBF at rest. CFR was significantly greater with adenosine than with dobutamine stress in control subjects and remote CFR. Ischemic CFR was blunted to a similar degree with each stressor. Therefore adenosine achieved flow heterogeneity across all coronary stenosis severities greater than 50%. However, dobutamine achieved flow heterogeneity only in the presence of a severe coronary stenosis greater than 75% despite provoking a greater ischemic stimulus. CONCLUSION: Adenosine stress demonstrated a higher sensitivity and dobutamine demonstrated a higher specificity with quantitative perfusion imaging. Therefore adenosine is superior for diagnostic perfusion imaging, whereas dobutamine is better suited in combination with visual imaging and in the functional assessment of a known coronary stenosis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16750776&query_hl=1 ER - TY - JFULL T1 - Occurrence of regional left ventricular dysfunction in patients undergoing standard and biofeedback dialysis. A1 - Selby, NM A1 - Lambie, SH A1 - Camici, PG A1 - Baker, CS A1 - McIntyre, CW J1 - Am J Kidney Dis Y1 - 2006/05// VL - 47 SN - 1523-6838 SP - 830 EP - 841 N2 - BACKGROUND: Cardiac failure and cardiovascular death are extremely prevalent in dialysis patients. Recurrent subclinical myocardial ischemia is important in the genesis of heart failure in nondialysis patients. We examined whether this phenomenon occurs in response to the stress of hemodialysis (HD). METHODS: Eight patients prone to intradialytic hypotension were recruited for a randomized crossover study to compare the development of left ventricular regional wall motion abnormalities during standard (HD) and biofeedback dialysis. Patients underwent serial echocardiography with quantitative analysis to assess ejection fraction and regional left ventricular systolic function during both types of dialysis. Blood pressure and hemodynamic variables also were measured by using continuous pulse wave analysis. RESULTS: Forty-two new regional wall motion abnormalities developed in all 8 patients during HD compared with 23 regional wall motion abnormalities that developed in 7 patients during biofeedback dialysis (odds ratio, 1.8; 95% confidence interval, 1.1 to 3.0). The majority of regional wall motion abnormalities showed improvement in function by 30 minutes postdialysis. Overall mean regional function was significantly more impaired during HD (P = 0.022). At peak stress, ejection fraction (measured by percentage of change from baseline) was significantly lower during HD (P = 0.043). Blood pressure was higher during biofeedback dialysis, with significantly fewer episodes of hypotension (odds ratio, 2.0; 95% confidence interval, 1.01 to 4.4). Significantly smaller decreases in stroke volume and cardiac output and a greater increment in pulse rate were observed during biofeedback dialysis. CONCLUSION: This study shows that reversible left ventricular wall motion abnormalities develop during dialysis with ultrafiltration. We also show that this phenomenon can be ameliorated by the improved hemodynamic stability of biofeedback dialysis and therefore is a potential target for intervention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16632022&query_hl=1 ER - TY - JFULL T1 - Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: The GENOMOS study (vol 3, pg 223, 2006) A1 - Ralston, SH A1 - Uitterlinden, AG A1 - Brandi, ML A1 - Balcells, S A1 - Langdahl, BL A1 - Lips, P A1 - Lorenc, R A1 - Obermayer-Pietsch, B A1 - Scollen, S A1 - Bustamante, M A1 - Husted, LB A1 - Carey, AH A1 - Diez-Perez, A A1 - Dunning, AM A1 - Falchetti, A A1 - Karczmarewicz, E A1 - Kruk, M A1 - van Leeuwen, JPTM A1 - van Meurs, JBJ A1 - Mangion, J A1 - McGuigan, FEA A1 - Mellibovsky, L A1 - del Monte, F A1 - Pols, HAP A1 - Reeve, J A1 - Reid, DM A1 - Renner, W A1 - Rivadeneira, F A1 - van Schoor, NM A1 - Sherlock, RE A1 - Ioannidis, JPA A1 - GENOMOS Investigators J1 - PLOS MED Y1 - 2006/05// VL - 3 SN - 1549-1277 SP - 704 EP - 704 ER - TY - JFULL T1 - Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. A1 - Branco, MR A1 - Pombo, A J1 - PLoS Biol Y1 - 2006/05// VL - 4 SN - 1545-7885 SP - e138 EP - e138 N2 - After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16623600&query_hl=1 ER - TY - JFULL T1 - White matter damage in neonatal enterovirus meningoencephalitis. A1 - Verboon-Maciolek, MA A1 - Groenendaal, F A1 - Cowan, F A1 - Govaert, P A1 - van Loon, AM A1 - de Vries, LS J1 - Neurology Y1 - 2006/04/25/ VL - 66 SN - 1526-632X SP - 1267 EP - 1269 N2 - The authors report six neonates with enteroviral meningoencephalitis. Five infants presented with prolonged seizures, and one presented with systemic enteroviral disease. Cranial ultrasonography showed increased echogenicity in the periventricular white matter, and MRI confirmed mild to severe white matter damage in all infants, which looked similar to periventricular leukomalacia. Two infants developed cerebral palsy: one was neurologically suspect at age 18 months, and three were developmentally normal. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16636251&query_hl=1 ER - TY - JFULL T1 - Splicing speckles are not reservoirs of RNA polymerase II, but contain an inactive form, phosphorylated on serine2 residues of the C-terminal domain. A1 - Xie, SQ A1 - Martin, S A1 - Guillot, PV A1 - Bentley, DL A1 - Pombo, A J1 - Mol Biol Cell Y1 - 2006/04// VL - 17 SN - 1059-1524 SP - 1723 EP - 1733 N2 - "Splicing speckles" are major nuclear domains rich in components of the splicing machinery and polyA(+) RNA. Although speckles contain little detectable transcriptional activity, they are found preferentially associated with specific mRNA-coding genes and gene-rich R bands, and they accumulate some unspliced pre-mRNAs. RNA polymerase II transcribes mRNAs and is required for splicing, with some reports suggesting that the inactive complexes are stored in splicing speckles. Using ultrathin cryosections to improve optical resolution and preserve nuclear structure, we find that all forms of polymerase II are present, but not enriched, within speckles. Inhibition of polymerase activity shows that speckles do not act as major storage sites for inactive polymerase II complexes but that they contain a stable pool of polymerase II phosphorylated on serine(2) residues of the C-terminal domain, which is transcriptionally inactive and may have roles in spliceosome assembly or posttranscriptional splicing of pre-mRNAs. Paraspeckle domains lie adjacent to speckles, but little is known about their protein content or putative roles in the expression of the speckle-associated genes. We find that paraspeckles are transcriptionally inactive but contain polymerase II, which remains stably associated upon transcriptional inhibition, when paraspeckles reorganize around nucleoli in the form of caps. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16467386&query_hl=1 ER - TY - JFULL T1 - Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. A1 - Ralston, SH A1 - Uitterlinden, AG A1 - Brandi, ML A1 - Balcells, S A1 - Langdahl, BL A1 - Lips, P A1 - Lorenc, R A1 - Obermayer-Pietsch, B A1 - Scollen, S A1 - Bustamante, M A1 - Husted, LB A1 - Carey, AH A1 - Diez-Perez, A A1 - Dunning, AM A1 - Falchetti, A A1 - Karczmarewicz, E A1 - Kruk, M A1 - van Leeuwen, JP A1 - van Meurs, JB A1 - Mangion, J A1 - McGuigan, FE A1 - Mellibovsky, L A1 - del Monte, F A1 - Pols, HA A1 - Reeve, J A1 - Reid, DM A1 - Renner, W A1 - Rivadeneira, F A1 - van Schoor, NM A1 - Sherlock, RE A1 - Ioannidis, JP A1 - GENOMOS Investigators J1 - PLoS Med Y1 - 2006/04// VL - 3 SN - 1549-1676 SP - e90 EP - e90 N2 - BACKGROUND: Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. METHODS AND FINDINGS: Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups (p < 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), (p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses. CONCLUSIONS: Allowing for the inevitable heterogeneity between participating teams, this study-which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene-demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16475872&query_hl=1 ER - TY - JFULL T1 - Proton and 31-phosphorus neurospectroscopy in the study of membrane phospholipids and fatty acid intervention in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis) and dyslexia. A1 - Puri, BK J1 - Int Rev Psychiatry Y1 - 2006/04// VL - 18 SN - 0954-0261 SP - 145 EP - 147 N2 - Neurospectroscopy allows biochemical processes in the brain to be studied non-invasively. At magnetic field strengths of 1.5 T or higher, cerebral proton neurospectroscopy allows the ascertainment of values of myo-inositol, choline-containing compounds, creatine, glutamate, glutamine, and N-acetyl aspartate. At similar field strengths, cerebral 31-phosphorus neurospectroscopy allows the ascertainment of values of phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and the gamma, alpha and beta nucleotide triphosphate (mainly adenosine triphosphate) resonances. Since choline is a common polar head group at the Sn3 position of membrane phospholipid molecules, a raised level of free choline, as indexed by proton neurospectroscopy, can indicate relatively low anabolism of membrane phospholipid molecules. Furthermore, the choline peak includes phosphorylcholine and glycerophosphorylcholine and even ethanolamine. The phosphomonoesters peak measured using 31-phosphorus spectroscopy includes major contributions from phosphocholine, phosphoethanolamine and L-phosphoserine, which are important precursors of membrane phospholipids, while the phosphodiesters peak includes contributions from glycerophosphocholine and glycerophosphoethanolamine, which are important products of membrane phospholipid catabolism. Hence proton neurospectroscopy and 31-phosphorus neurospectroscopy can yield important information relating to the metabolism of cerebral membrane phospholipids. The application of these techniques to the investigation of membrane phospholipid metabolism in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis or M.E.) and dyslexia is described. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16777668&query_hl=1 ER - TY - JFULL T1 - Chromatin structure and gene regulation in T cell development and function A1 - Wilson, CB A1 - Merkenschlager, M J1 - CURR OPIN IMMUNOL Y1 - 2006/04// VL - 18 SN - 0952-7915 SP - 143 EP - 151 N2 - Transcription factors control gene expression programs in the context of the chromatin structure of their target genes. DNA methylation, post-translational histone modifications such as acetylation and methylation, and higher order chromatin organization allow the maintenance of gene expression patterns through mitosis, but how do they accommodate developmentally regulated changes in gene expression programs? Although histone acetylation and deacetylation are in dynamic equilibrium and mechanisms for the removal of methyl groups from histories are emerging, the extent to which there is active demethylation of DNA remains controversial. Looking at chromatin in the three-dimensional space of the nucleus, recent work demonstrates that gene regulation involves contacts between regulatory elements within genes or gene clusters on the same chromosome (in cis) and between different chromosomes (in trans). Finally, non-coding RNAs make a significant contribution to transcriptional and post-transcriptional gene silencing. Together, these advances contribute to an understanding of how gene expression programs are established, maintained and modified during development. ER - TY - JFULL T1 - Prediction of specific absorption rate in mother and fetus associated with MRI examinations during pregnancy. A1 - Hand, JW A1 - Li, Y A1 - Thomas, EL A1 - Rutherford, MA A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2006/04// VL - 55 SN - 0740-3194 SP - 883 EP - 893 N2 - There is uncertainty regarding the risk posed by magnetic resonance imaging (MRI) examinations to pregnant patients. The most frequently used methods, such as single-shot fast spin echo (ssFSE), often require operation at the specific absorption rate (SAR) limits imposed by safety guidelines. With the introduction of higher-field systems, such limits will be even more significant for fetal imaging. An electromagnetic solver based on the time domain finite integration technique (FIT) was used to predict SAR in an anatomically realistic model of a pregnant patient (28 weeks' gestation) associated with the radiofrequency (RF) fields from birdcage body coils typical of 1.5 T and 3 T MRI systems (i.e., operating at approximately 64 and 127 MHz, respectively). The results suggest that 1) the highest local SAR is in the mother, with the fetus being exposed to a peak of approximately 40-60% of that value at 64 MHz, increasing to approximately 50-70% at 127 MHz; 2) compliance with U.S. Food and Drug Administration (FDA) and International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines requires control of SAR values averaged over 1 g or 10 g of tissue, respectively; and 3) compliance with Medical Device Agency (MDA) guidelines requires control of the maximum SAR(10g) within the fetus. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16508913&query_hl=1 ER - TY - JFULL T1 - Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids (vol 85, pg 22, 2006) A1 - Stewart, E A1 - Gostout, B A1 - Gedroyc, WM J1 - FERTIL STERIL Y1 - 2006/04// VL - 85 SN - 0015-0282 SP - 1072 EP - 1072 ER - TY - JFULL T1 - An overview of cytidine deaminases. A1 - Navaratnam, N A1 - Sarwar, R J1 - Int J Hematol Y1 - 2006/04// VL - 83 SN - 0925-5710 SP - 195 EP - 200 N2 - Enzymes that deaminate cytidine to uridine play an important role in a variety of pathways from bacteria to man. Ancestral members of this family were able to deaminate cytidine only in a mononucleotide or nucleoside context. Recently, a family of enzymes has been discovered with the ability to deaminate cytidines on RNA or DNA. The first member of this new family is APOBEC1, which deaminates apolipoprotein B messenger RNA to generate a premature stop codon. APOBEC1 has the conserved active site motif found in Escherichia coli cytidine deaminase. In addition, APOBEC1 has a unique motif containing 2 phenylalanine residues and an insert of 4 amino acid residues across the active site motif. This motif is present in APOBEC family members including activation-induced cytidine deaminase (AID), APOBEC2, and APOBEC3A through APOBEC3G. AID is essential for initiating class-switch recombination, somatic hypermutation, and gene conversion. The APOBEC3 family is unique to primates. APOBEC3G is able to protect cells from human immunodeficiency virus and other viral infections. This function is not unique to APOBEC3G; other APOBEC3 family members also have this ability. Overexpression of enzymes in this family can cause cancer, suggesting that the genes for the APOBEC family of proteins are proto-oncogenes. Recent advances in the understanding of the mechanism of action of this family are summarized in this review. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16720547&query_hl=1 ER - TY - JFULL T1 - Perinatal infections, prematurity and brain injury. A1 - Edwards, AD A1 - Tan, S J1 - Curr Opin Pediatr Y1 - 2006/04// VL - 18 SN - 1040-8703 SP - 119 EP - 124 N2 - PURPOSE OF REVIEW: The association between perinatal infection and brain injury is widely accepted but a cause-and-effect relationship has not yet been proven. This article summarizes available evidence and current primary publications for debate. RECENT FINDINGS: Work completed during the review period has reinforced current understanding of perinatal infection, prematurity and brain injury. In animal experiments: lipopolysaccharides have been further implicated in brain injury, not only as a cause of brain injury but also as mediators of preconditioning and protection. Recent studies suggest that cerebral injury following low-dose lipopolysaccharide administration may become compensated in adulthood. Other studies have emphasized the complexity of the response by showing that plasma cytokine levels may not reflect those in the central nervous system or inflammatory events in the brain. SUMMARY: Perinatal infection and maternofetal inflammation is strongly associated with preterm birth. Inflammation probably represents an important mechanism for cerebral damage, and both overt lesions and maldevelopment can result. Epidemiological data and multiple animal models to link infection, inflammation and brain damage exist, but proof of causation is elusive. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16601489&query_hl=1 ER - TY - JFULL T1 - Glycomics investigation into insulin action. A1 - Parry, S A1 - Hadaschik, D A1 - Blancher, C A1 - Kumaran, MK A1 - Bochkina, N A1 - Morris, HR A1 - Richardson, S A1 - Aitman, TJ A1 - Gauguier, D A1 - Siddle, K A1 - Scott, J A1 - Dell, A J1 - Biochim Biophys Acta Y1 - 2006/04// VL - 1760 SN - 0006-3002 SP - 652 EP - 668 N2 - Defects in glycosylation are becoming increasingly associated with a range of human diseases. In some cases, the disease is caused by the glycosylation defect, whereas in others, the aberrant glycosylation may be a consequence of the disease. The implementation of highly sensitive and rapid mass spectrometric screening strategies for profiling the glycans present in model biological systems is revealing valuable insights into disease phenotypes. In addition, glycan screening is proving useful in the analysis of knock-out mice where it is possible to assess the role of glycosyltransferases and glycosidases and what function they have at the cellular and whole organism level. In this study, we analysed the effect of insulin on the glycosylation of 3T3-L1 cells and the effect of insulin resistance on glycosylation in a mouse model. Transcription profiling of 3T3-L1 cells treated with and without insulin revealed expression changes of several glycogenes. In contrast, mass spectrometric screening analysis of the glycans from these cells revealed very similar profiles suggesting that any changes in glycosylation were most likely on specific proteins rather than a global phenomenon. A fat-fed versus carbohydrate-fed mouse insulin resistant model was analysed to test the consequences of chronic insulin resistance. Muscle and liver N-glycosylation profiles from these mice are reported. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16473469&query_hl=1 ER - TY - JFULL T1 - Reduced fractional anisotropy on diffusion tensor magnetic resonance imaging after hypoxic-ischemic encephalopathy. A1 - Ward, P A1 - Counsell, S A1 - Allsop, J A1 - Cowan, F A1 - Shen, Y A1 - Edwards, D A1 - Rutherford, M J1 - Pediatrics Y1 - 2006/04// VL - 117 SN - 1098-4275 SP - e619 EP - e630 N2 - OBJECTIVE: Apparent diffusion coefficients (ADC) that are measured by diffusion-weighted imaging are reduced in severe white matter (WM) and in some severe basal ganglia and thalamic (BGT) injury in infants who present with hypoxic-ischemic encephalopathy (HIE). However, ADC values may pseudonormalize or even be high during this time in some less severe but clinically significant injuries. We hypothesized that fractional anisotropy (FA), a measure of the directional diffusivity of water made using diffusion tensor imaging, may be abnormal in these less severe injuries; therefore, the objective of this study was to use diffusion tensor imaging to measure ADC and FA in infants with moderate and severe hypoxic-ischemic brain injury. METHODS: Twenty infants with HIE and 7 normal control infants were studied. All infants were born at >36 weeks' gestational age, and MRI scans were obtained within 3 weeks of delivery. Data were examined for normality, and comparisons were made using analysis of variance or Kruskal-Wallis as appropriate. RESULTS: During the first week, FA values were decreased with both severe and moderate WM and BGT injury as assessed by conventional imaging, whereas ADC values were reduced only in severe WM injury and some severe BGT injury. Abnormal ADC values pseudonormalized during the second week, whereas FA values continued to decrease. CONCLUSION: FA is reduced in moderate brain injury after HIE. A low FA may reflect a breakdown in WM organization. Moderate BGT injury may result in atrophy but not overt infarction; it is possible that delayed apoptosis is more marked than immediate necrosis, and this may account for normal early ADC values. The accompanying low FA within some severe and all moderate gray matter lesions, which is associated with significant later impairment, may help to confirm clinically significant abnormality in infants with normal ADC values. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16510613&query_hl=1 ER - TY - JFULL T1 - Unwarranted caution from the EU will affect MRI use and patient care A1 - Young, I A1 - McRobbie, D A1 - Keevil, S A1 - Taylor, A J1 - BRIT J HOSP MED Y1 - 2006/04// VL - 67 SP - 174 EP - 175 ER - TY - JFULL T1 - Variations due to analysis technique in intracellular pH measurements in simulated and in vivo 31P MR spectra of the human brain. A1 - Hamilton, G A1 - Allsop, JM A1 - Patel, N A1 - Forton, DM A1 - Thomas, HC A1 - O'Sullivan, CP A1 - Hajnal, JV A1 - Taylor-Robinson, SD J1 - J Magn Reson Imaging Y1 - 2006/04// VL - 23 SN - 1053-1807 SP - 459 EP - 464 N2 - PURPOSE: To investigate variation in pH generated by different analysis techniques and to find the most robust method, 31P MR brain spectra were acquired in vivo. Three different methods were used to measure the chemical shift of inorganic phosphate (Pi) relative to phosphocreatine (PCr). MATERIALS AND METHODS: Eight healthy volunteers were scanned four times, and manual measurement of the chemical shift in a frequency domain spectrum using the manufacturer's software was compared with values produced by a frequency-domain analysis method (NMR1) and a prior-knowledge-based time-domain technique (MRUI). To explain the in vivo data, simulations of brain spectra, modified in ways typical of real variations in vivo, were produced and the pH was measured using manual measurement and MRUI. RESULTS: Different measurement techniques produced systematically different pH values, with manual measurement producing the lowest variability (manual measurement: pH = 6.999, CoV = 0.297; NMR1: pH = 7.042, CoV = 0.501; MRUI: pH = 7.036, CoV = 0.606). While MRUI more accurately measured the pH of unaltered simulations, it was systematically affected by altering the simulated spectra. Manual measurement was unaffected. CONCLUSION: Manual measurement produces the most consistent pH value, and there is no benefit in using more complex automated spectral fitting methods to measure the pH. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16506142&query_hl=1 ER - TY - JFULL T1 - High-resolution magnetic resonance imaging sinc-interpolation-based subvoxel registration and semi-automated quantitative lateral ventricular morphology employing threshold computation and binary image creation in the study of fatty acid interventions in schizophrenia, depression, chronic fatigue syndrome and Huntington's disease. A1 - Puri, BK J1 - Int Rev Psychiatry Y1 - 2006/04// VL - 18 SN - 0954-0261 SP - 149 EP - 154 N2 - Serial high-resolution structural magnetic resonance imaging scans of the brain can now be precisely aligned, with six degrees of freedom (three mutually orthogonal translational and three rotational degrees of freedom around three mutually orthogonal axes), using a rigid-body subvoxel registration technique. This is driven by the in-plane point spread function for images acquired in the Fourier domain with data obtained over a bounded region of k-space, namely the sinc interpolation function, where sinc z = (sin z)/z, with z being any complex number (including zero). Computational subtraction of the three-dimensional Cartesian spatial representation matrices of serially acquired scan data allows for the determination of structural cerebral changes with great precision, since voxel signals from unchanged structures are almost completely cancelled. Thus changes readily show up against a background of noise. Furthermore, lateral ventricular changes can now be accurately quantified using a semi-automated method involving contour production, threshold computation, binary image creation and ventricular extraction. These techniques have been applied to the investigation of the effects on cerebral structure of intervention with fatty acids, particularly the long-chain polyunsaturated n-3 fatty acid eicosapentaenoic acid (EPA), in disorders such as schizophrenia, treatment-resistant depression, chronic fatigue syndrome (myalgic encephalomyelitis or ME), and Huntington's disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16777669&query_hl=1 ER - TY - JFULL T1 - LKB1: a sweet side to Peutz-Jeghers syndrome? A1 - Carling, D J1 - Trends Mol Med Y1 - 2006/04// VL - 12 SN - 1471-4914 SP - 144 EP - 147 N2 - The recent discovery that the tumour suppressor LKB1 is an upstream kinase in the AMP-activated protein kinase (AMPK) cascade provided a molecular link between energy metabolism and cancer. A recent study by Shaw and colleagues elucidated the role of LKB1 in type 2 diabetes. Deletion of the gene encoding LKB1 in the liver leads to marked hyperglycaemia as a consequence of increased gluconeogenic gene expression and hepatic glucose output. Importantly, the absence of LKB1 in the liver abolishes the effect of lowering glucose level caused by metformin, a drug that is widely used for the treatment of type 2 diabetes. These findings should help solve the mystery surrounding the function of metformin, which has lasted for >30 years. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16530014&query_hl=1 ER - TY - JFULL T1 - Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver A1 - Nathwani, AC A1 - Gray, JT A1 - Ng, CYC A1 - Zhou, JF A1 - Spence, Y A1 - Waddington, SN A1 - Tuddenham, EGD A1 - Kemball-Cook, G A1 - McIntosh, J A1 - Boon-Spijker, M A1 - Mertens, K A1 - Davidoff, AM J1 - BLOOD Y1 - 2006/04/01/ VL - 107 SN - 0006-4971 SP - 2653 EP - 2661 N2 - Transduction with recombinant adenoassociated virus (AAV) vectors is limited by the need to convert its single-stranded (ss) genome to transcriptionally active double-stranded (ds) forms. For AAV-mediated hemophilia B (HB) gene therapy, we have overcome this obstacle by constructing a liver-restricted mini-human factor IX (hFIX) expression cassette that can be packaged as complementary dimers within individual AAV particles. Molecular analysis of murine liver transduced with these self-complementary (sc) vectors demonstrated rapid formation of active ds-linear genomes that persisted stably as concatamers or monomeric circles. This unique property resulted in a 20-fold improvement in hFIX expression in mice over comparable ssAAV vectors. Administration of only 1 x 10(10) scAAV particles led to expression of hFIX at supraphysiologic levels (81 U/mL) and correction of the bleeding diathesis in FIX knock-out mice. Of importance, therapeutic levels of hFIX (3%-30% of normal) were achieved in nonhuman primates using a significantly lower dose of scAAV than required with ssAAV. Furthermore, AAV5-pseudotyped scAAV vectors mediated successful transduction in macaques with pre-existing immunity to AAV8. Hence, this novel vector represents an important advance for hemophilia B gene therapy. ER - TY - JFULL T1 - Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex. A1 - De Paola, V A1 - Holtmaat, A A1 - Knott, G A1 - Song, S A1 - Wilbrecht, L A1 - Caroni, P A1 - Svoboda, K J1 - Neuron Y1 - 2006/03/16/ VL - 49 SN - 0896-6273 SP - 861 EP - 875 N2 - We imaged axons in layer (L) 1 of the mouse barrel cortex in vivo. Axons from thalamus and L2/3/5, or L6 pyramidal cells were identified based on their distinct morphologies. Their branching patterns and sizes were stable over times of months. However, axonal branches and boutons displayed cell type-specific rearrangements. Structural plasticity in thalamocortical afferents was mostly due to elongation and retraction of branches (range, 1-150 microm over 4 days; approximately 5% of total axonal length), while the majority of boutons persisted for up to 9 months (persistence over 1 month approximately 85%). In contrast, L6 axon terminaux boutons were highly plastic (persistence over 1 month approximately 40 %), and other intracortical axon boutons showed intermediate levels of plasticity. Retrospective electron microscopy revealed that new boutons make synapses. Our data suggest that structural plasticity of axonal branches and boutons contributes to the remodeling of specific functional circuits. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16543134&query_hl=1 ER - TY - JFULL T1 - Relevance of coronary microvascular flow impairment to long-term remodeling and systolic dysfunction in hypertrophic cardiomyopathy. A1 - Olivotto, I A1 - Cecchi, F A1 - Gistri, R A1 - Lorenzoni, R A1 - Chiriatti, G A1 - Girolami, F A1 - Torricelli, F A1 - Camici, PG J1 - J Am Coll Cardiol Y1 - 2006/03/07/ VL - 47 SN - 1558-3597 SP - 1043 EP - 1048 N2 - OBJECTIVES: This study sought to evaluate whether the entity of microvascular dysfunction, assessed by positron emission tomography (PET), predicts the long-term development of left ventricular (LV) remodeling and systolic dysfunction in hypertrophic cardiomyopathy (HCM). BACKGROUND: A subgroup of patients with HCM developed LV dilation and systolic impairment. A causal role of coronary microvascular dysfunction has been suggested as the underlying pathophysiological mechanism. METHODS: Fifty-one patients (New York Heart Association functional class I to II) were followed up for 8.1 +/- 2.1 years after measurement of resting and dipyridamole (Dip) myocardial blood flow (MBF). Left ventricular systolic dysfunction was defined as an ejection fraction (LVEF) <50%. RESULTS: The Dip-MBF was blunted in HCM patients compared with a group of healthy control patients (1.50 +/- 0.69 ml/min/g vs. 2.71 +/- 0.94 ml/min/g; p < 0.001). At final evaluation, 11 patients (22%) had an LVEF <50%; in most (n = 7), systolic dysfunction was associated with a significant increase in LV cavity dimensions (>5 mm) during follow-up. These 11 patients showed lower Dip-MBF than the 40 with preserved LV function (1.04 +/- 0.38 ml/min/g vs. 1.63 +/- 0.71 ml/min/g, respectively; p = 0.001); Dip-MBF was particularly blunted in five patients with clinical progression to severe heart failure symptoms or death (Dip-MBF 0.89 +/- 0.15 ml/min/g). At multivariate analysis, the two independent predictors of systolic dysfunction were Dip-MBF in the lowest tertile (<1.1 ml/min/g; relative hazard, 7.5; p = 0.038) and an end-diastolic LV dimension in the highest tertile (>45 mm; relative hazard, 12.3; p = 0.031). CONCLUSIONS: Severe microvascular dysfunction is a potent long-term predictor of adverse LV remodeling and systolic dysfunction in HCM. Our findings indicate microvascular dysfunction as a potential target for prevention of disease progression and heart failure in HCM. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16516091&query_hl=1 ER - TY - JFULL T1 - Insulin antagonizes ischemia-induced Thr(172) phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser(485/491) A1 - Horman, S A1 - Vertommen, D A1 - Heath, R A1 - Neumann, D A1 - Mouton, V A1 - Woods, A A1 - Schlattner, U A1 - Walliman, T A1 - Carling, D A1 - Hue, L A1 - Rider, MH J1 - J BIOL CHEM Y1 - 2006/03/03/ VL - 281 SN - 0021-9258 SP - 5335 EP - 5340 N2 - Previous studies showed that insulin antagonizes AMP-activated protein kinase activation by ischemia and that protein kinase B might be implicated. Here we investigated whether the direct phosphorylation of AMP-activated protein kinase by protein kinase B might participate in this effect. Protein kinase B phosphorylated recombinant bacterially expressed AMP-activated protein kinase heterotrimers at Ser(485) of the alpha 1-subunits. In perfused rat hearts, phosphorylation of the alpha 1/alpha 2 AMP-activated protein kinase subunits on Ser(485)/Ser(491) was increased by insulin and insulin pretreatment decreased the phosphorylation of the alpha-subunits at Thr(172) in a subsequent ischemic episode. It is proposed that the effect of insulin to antagonize AMP-activated protein kinase activation involves a hierarchical mechanism whereby Ser(485)/Ser(491) phosphorylation by protein kinase B reduces subsequent phosphorylation of Thr(172) by LKB1 and the resulting activation of AMP-activated protein kinase. ER - TY - JFULL T1 - Developmentally regulated changes in c-Jun N-terminal kinase signalling determine the apoptotic response of oligodendrocyte lineage cells. A1 - Pirianov, G A1 - Jesurasa, A A1 - Mehmet, H J1 - Cell Death Differ Y1 - 2006/03// VL - 13 SN - 1350-9047 SP - 531 EP - 533 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16322755&query_hl=1 ER - TY - JFULL T1 - A major new initiative to improve treatment for children A1 - Smyth, RL A1 - Edwards, AD J1 - ARCH DIS CHILD Y1 - 2006/03// VL - 91 SN - 0003-9888 SP - 212 EP - 213 ER - TY - JFULL T1 - Nigral degeneration and striatal dopaminergic dysfunction in idiopathic and Parkin-linked Parkinson's disease. A1 - Hu, MT A1 - Scherfler, C A1 - Khan, NL A1 - Hajnal, JV A1 - Lees, AJ A1 - Quinn, N A1 - Wood, NW A1 - Brooks, DJ J1 - Mov Disord Y1 - 2006/03// VL - 21 SN - 0885-3185 SP - 299 EP - 305 N2 - We have used MR segmented inversion recovery ratio imaging (SIRRIM) of the substantia nigra pars compacta to detect and correlate nigral signal change in idiopathic Parkinson's disease (PD) and parkin patients with striatal (18)F-dopa uptake. Nine PD patients, nine parkin patients, and eight control subjects were studied with a combination of MR inversion recovery sequences sensitive to nigral cell loss. Blinded independent observer rating and quantified nigral signal analysis were performed on all subjects. Striatal regions of interest were defined on T(1)-weighted MRI co-registered to (18)F-dopa positron emission tomography. On blinded observer rating of the SIRRIM dorsal and ventral nigral images, 25% (2/8) of control subjects, 44% (4/9) of PD patients, and 67% (6/9) of parkin patients were classified as abnormal. Quantified total nigral signal intensities were reduced to a greater extent in the parkin compared to PD patients. There was a greater predilection for signal reduction in the ventral nigral slice of the PD compared to the parkin patient group, who showed a more uniform involvement. All PD and parkin patients were discriminated from controls on the basis of caudate and putamen (18)F-dopa Ki reductions. Our results suggest that MR segmented inversion recovery ratio imaging shows poor sensitivity for discriminating parkin and idiopathic PD patients from normal controls. Where nigral signal abnormalities were seen, parkin patients manifested generalized nigral cell loss with widespread striatal dopamine terminal dysfunction compared with the lateral nigral targeting seen in PD and selective loss of putamen (18)F-dopa uptake. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16211589&query_hl=1 ER - TY - JFULL T1 - Smaller cerebellar volumes in very preterm infants at term-equivalent age are associated with the presence of supratentorial lesions. A1 - Srinivasan, L A1 - Allsop, J A1 - Counsell, SJ A1 - Boardman, JP A1 - Edwards, AD A1 - Rutherford, M J1 - AJNR Am J Neuroradiol Y1 - 2006/03// VL - 27 SN - 0195-6108 SP - 573 EP - 579 N2 - BACKGROUND AND PURPOSE: Traditionally cerebellar functions are thought to be related to control of tone, posture, gait, and coordination of skilled motor activity. However, there is an increasing body of evidence implicating the cerebellum in cognition, language, memory, and motor learning. Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioral and emotional disturbances. The role of the cerebellum in these adverse outcomes is unclear. OBJECTIVE: The objective of this study was to determine whether absolute cerebellar volumes differ between term-equivalent preterm infants and term-born control infants and to assess whether cerebellar volume is influenced by any possible antenatal, perinatal, and postnatal factors. METHODS: The study compared the MR imaging cerebellar volume by using a manual quantification program of 113 preterm infants at term-equivalent age and 15 term-born control infants. RESULTS: The median cerebellar volume of preterm at term-equivalent age was 25.4 cm3 and that of term-born control infants was 26.9 cm3. On initial analysis, there was a significant median difference of 2.0 cm3 (95% CI, 1.2 cm3 to 2.7 cm3) (2-sided P < .0001). However multiple regression analysis of perinatal variables showed that only infants with supratentorial lesions (P = .003) were significantly associated with the reduction in cerebellar volumes. The median cerebellar volumes were the following: supratentorial lesions, 18.9 cm3; no supratentorial lesions, 26.1 cm3; and term infants, 26.9 cm3 (analysis of variance, P < .0001). Hence, there was no significant difference in cerebellar volumes of preterm infants at term-equivalent age in the absence of supratentorial lesions. The median vermal volumes were 0.7 cm3 and were significantly related to cerebellar volumes both in preterm infants with and without lesions and in term-control infants. CONCLUSION: Premature infants at term-equivalent age have similar total cerebellar and vermal volumes compared with term infants in the presence of normal brain imaging. Reduced cerebellar volume in preterm infants at term-equivalent age is seen in association with supratentorial pathology such as hemorrhagic parenchymal infarction, intraventricular hemorrhage with dilation, and periventricular leukomalacia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16551994&query_hl=1 ER - TY - JFULL T1 - The effects of Apobec 3G on HBV replication A1 - Mohammed, E A1 - Navaratnam, N A1 - Hoare, J A1 - McGarvey, M J1 - J GASTROEN HEPATOL Y1 - 2006/03// VL - 21 SN - 0815-9319 SP - A218 EP - A218 ER - TY - JFULL T1 - Coronary microvascular dysfunction in male patients with Anderson-Fabry disease and the effect of treatment with alpha galactosidase A. A1 - Elliott, PM A1 - Kindler, H A1 - Shah, JS A1 - Sachdev, B A1 - Rimoldi, OE A1 - Thaman, R A1 - Tome, MT A1 - McKenna, WJ A1 - Lee, P A1 - Camici, PG J1 - Heart Y1 - 2006/03// VL - 92 SN - 1468-201X SP - 357 EP - 360 N2 - OBJECTIVE: To measure coronary flow reserve (CFR), an index of microvascular function, in Anderson-Fabry disease (AFD) at baseline and after enzyme replacement therapy (ERT). METHODS AND RESULTS: Mean (SD) myocardial blood flow (MBF) at rest and during hyperaemia (adenosine 140 microg/kg/min) was measured in 10 male, non-smoking patients (53.8 (10.9) years, cholesterol 5.5 (1.3) mmol/l) and in 24 age matched male, non-smoking controls (52.0 (7.6) years, cholesterol 4.5 (0.6) mmol/l) by positron emission tomography (PET). Resting and hyperaemic MBF and CFR (hyperaemic/resting MBF) were reduced in patients compared with controls (0.99 (0.17) v 1.17 (0.25) ml/g/min, p < 0.05; 1.37 (0.32) v 3.44 (0.78) ml/g/min, p < 0.0001; and 1.41 (0.39) v 3.03 (0.85), p < 0.0001, respectively). This coronary microvascular dysfunction was independent of cholesterol concentrations. PET was repeated in five patients after 10.1 (2.3) months of ERT; resting and hyperaemic MBF and CFR were unchanged after ERT (0.99 (0.16) v 0.99 (0.16) ml/g/min; 1.56 (0.29) v 1.71 (0.3) ml/g/min; and 1.6 (0.37) v 1.74 (0.28), respectively; all not significant). CONCLUSIONS: The results of the present study show that patients with AFD have very abnormal coronary microvascular function. These preliminary data suggest that ERT has no effect on coronary microvascular dysfunction. Further work is necessary to determine whether treatment at an earlier stage in the course of the disease may improve coronary microvascular function in patients with AFD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16085718&query_hl=1 ER - TY - JFULL T1 - Therapeutic hypothermia following perinatal asphyxia. A1 - Edwards, AD A1 - Azzopardi, DV J1 - Arch Dis Child Fetal Neonatal Ed Y1 - 2006/03// VL - 91 SN - 1359-2998 SP - F127 EP - F131 N2 - Well constructed and carefully analysed trials of hypothermic neural rescue therapy for infants with neonatal encephalopathy have recently been reported. The data suggest that either selective head cooling or total body cooling reduces the combined chance of death or disability after birth asphyxia. However, as there are still unanswered questions about these treatments, many may still feel that further data are needed before health care policy can be changed to make cooling the standard of care for all babies with suspected birth asphyxia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16492950&query_hl=1 ER - TY - JFULL T1 - Correction of severe anaemia using immuno-regulated gene therapy is achieved by restoring the early erythroblast compartment. A1 - Du Roure, C A1 - Takács, K A1 - Maxwell, PH A1 - Roberts, I A1 - Dazzi, F A1 - Cannella, L A1 - Merkenschlager, M A1 - Fisher, AG J1 - Br J Haematol Y1 - 2006/03// VL - 132 SN - 0007-1048 SP - 608 EP - 614 N2 - Patients with chronic renal failure usually require exogenous erythropoietin (epo) to alleviate anaemia resulting from inadequate epo production by the kidneys. We have recently shown that severe anaemia in genetically manipulated epo-deficient mice (EpoTAg) can be corrected by adoptively transferred epo-producing lymphocytes. The aim of this study was to investigate the precise effects of human epo administration by this route on erythropoietic development in epo-deficient mice. The erythroblast compartments of untreated and treated EpoTAg mice were analysed in comparison with wild-type mice. The early erythroblast population was reduced in the bone marrow of epo-deficient mice, whilst the number of erythroid colony-forming units (CFU-E) was not significantly compromised. This paucity in marrow early erythroblasts was restored to normal values in treated mutant mice. In addition, the early erythroblast population was expanded in the spleens of treated animals. These findings show that the early erythroblasts are important targets of epo and that epo corrects anaemia of epo-deficient mice by restoring marrow function and splenic erythropoiesis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16445835&query_hl=1 ER - TY - JFULL T1 - Technical report: Magnetic resonance direct thrombus imaging at 3 T field strength in patients with lower limb deep vein thrombosis: a feasibility study. A1 - Schmitz, SA A1 - O'Regan, DP A1 - Gibson, D A1 - Cunningham, C A1 - Fitzpatrick, J A1 - Allsop, J A1 - Larkman, DJ A1 - Hajnal, JV J1 - Clin Radiol Y1 - 2006/03// VL - 61 SN - 0009-9260 SP - 282 EP - 286 N2 - AIM: To investigate the feasibility of imaging lower limb deep vein thrombosis using magnetic resonance imaging (MRI) at 3.0 T magnetic field strength with an optimized a T1 magnetization prepared rapid gradient echo technique (MP-RAGE) in patients with normal volunteers as controls. MATERIALS AND METHODS: Patients with deep vein thrombosis (n = 4), thrombophlebitis (n = 2) and healthy volunteers (n = 9) were studied. MRI of the distal thigh and upper calf was performed at 3.0 T with MP-RAGE using two pre-pulses to suppress blood and fat (flip angle 15 degrees, echo time 5 ms, and repetition time 10 ms). A qualitative analysis was performed for detection of thrombi and image quality. Contrast-to-noise ratios were determined in thrombosed and patent veins. RESULTS: Thrombi were clearly visible as high-signal intensity structures with good suppression of the anatomical background. A blinded reader accurately diagnosed 15 out of 16 cases. The contrast-to-noise ratio measurements showed a positive contrast of thrombus over background muscle 16.9 (SD 4.3, 95% CI: 12.5-21.3) and a negative contrast of the lumen to muscle in patent veins of normal volunteers -7.8 (SD 4.3, 95% CI: -11.1 to -4.5), with p = 0.0015. CONCLUSION: Thrombi generate high signal intensity at 3.0 T allowing for their direct visualization if flowing blood, stationary blood and fat are sufficiently suppressed. This preliminary data supports the development of these techniques for other vascular applications. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16488211&query_hl=1 ER - TY - JFULL T1 - Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. A1 - Aitman, TJ A1 - Dong, R A1 - Vyse, TJ A1 - Norsworthy, PJ A1 - Johnson, MD A1 - Smith, J A1 - Mangion, J A1 - Roberton-Lowe, C A1 - Marshall, AJ A1 - Petretto, E A1 - Hodges, MD A1 - Bhangal, G A1 - Patel, SG A1 - Sheehan-Rooney, K A1 - Duda, M A1 - Cook, PR A1 - Evans, DJ A1 - Domin, J A1 - Flint, J A1 - Boyle, JJ A1 - Pusey, CD A1 - Cook, HT J1 - Nature Y1 - 2006/02/16/ VL - 439 SN - 1476-4687 SP - 851 EP - 855 N2 - Identification of the genes underlying complex phenotypes and the definition of the evolutionary forces that have shaped eukaryotic genomes are among the current challenges in molecular genetics. Variation in gene copy number is increasingly recognized as a source of inter-individual differences in genome sequence and has been proposed as a driving force for genome evolution and phenotypic variation. Here we show that copy number variation of the orthologous rat and human Fcgr3 genes is a determinant of susceptibility to immunologically mediated glomerulonephritis. Positional cloning identified loss of the newly described, rat-specific Fcgr3 paralogue, Fcgr3-related sequence (Fcgr3-rs), as a determinant of macrophage overactivity and glomerulonephritis in Wistar Kyoto rats. In humans, low copy number of FCGR3B, an orthologue of rat Fcgr3, was associated with glomerulonephritis in the autoimmune disease systemic lupus erythematosus. The finding that gene copy number polymorphism predisposes to immunologically mediated renal disease in two mammalian species provides direct evidence for the importance of genome plasticity in the evolution of genetically complex phenotypes, including susceptibility to common human disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16482158&query_hl=1 ER - TY - JFULL T1 - eQTL Explorer: integrated mining of combined genetic linkage and expression experiments. A1 - Mueller, M A1 - Goel, A A1 - Thimma, M A1 - Dickens, NJ A1 - Aitman, TJ A1 - Mangion, J J1 - Bioinformatics Y1 - 2006/02/15/ VL - 22 SN - 1367-4803 SP - 509 EP - 511 N2 - The development of computational resources to visualize and explore data from combined genome-wide expression and linkage studies is essential for the development of testable hypotheses. eQTL Explorer stores expression profiles, linkage data and information from external sources in a relational database and enables simultaneous visualization and intuitive interpretation of the combined data via a Java graphical interface. eQTL Explorer provides a new and powerful tool to interrogate these very large and complex datasets. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16357031&query_hl=1 ER - TY - JFULL T1 - Potential application of embryonic stem cells in Parkinson’s disease: drug screening and cell therapy A1 - Ho HY A1 - Li, M J1 - Regenerative Med Y1 - 2006/02// VL - 1 SP - 175 EP - 182 ER - TY - JFULL T1 - Diffusion tensor and magnetisation transfer imaging of the brain at 3T in patients with cirrhosis and hepatic encephalopathy A1 - Grover, VP A1 - Counsell, SJ A1 - Forton, DM A1 - Bradford, EJ A1 - Saxby, BK A1 - Thomas, HC A1 - Hajnal, JV A1 - Taylor-Robinson, SD J1 - J HEPATOL Y1 - 2006/02// VL - 44 SN - 0168-8278 SP - S75 EP - S76 ER - TY - JFULL T1 - Hypothermia and perinatal asphyxia: executive summary of the National Institute of Child Health and Human Development workshop. A1 - Higgins, RD A1 - Raju, TN A1 - Perlman, J A1 - Azzopardi, DV A1 - Blackmon, LR A1 - Clark, RH A1 - Edwards, AD A1 - Ferriero, DM A1 - Gluckman, PD A1 - Gunn, AJ A1 - Jacobs, SE A1 - Eicher, DJ A1 - Jobe, AH A1 - Laptook, AR A1 - LeBlanc, MH A1 - Palmer, C A1 - Shankaran, S A1 - Soll, RF A1 - Stark, AR A1 - Thoresen, M A1 - Wyatt, J J1 - J Pediatr Y1 - 2006/02// VL - 148 SN - 0022-3476 SP - 170 EP - 175 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16492424&query_hl=1 ER - TY - JFULL T1 - Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age. A1 - Counsell, SJ A1 - Shen, Y A1 - Boardman, JP A1 - Larkman, DJ A1 - Kapellou, O A1 - Ward, P A1 - Allsop, JM A1 - Cowan, FM A1 - Hajnal, JV A1 - Edwards, AD A1 - Rutherford, MA J1 - Pediatrics Y1 - 2006/02// VL - 117 SN - 1098-4275 SP - 376 EP - 386 N2 - OBJECTIVE: Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants. METHODS: Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum. RESULTS: Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied. CONCLUSIONS: These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16452356&query_hl=1 ER - TY - JFULL T1 - Colour doppler ultrasound of the lumbar arteries: a novel application and reproducibility study in healthy subjects. A1 - Espahbodi, S A1 - Humphries, KN A1 - Doré, CJ A1 - McCarthy, ID A1 - Standfield, NJ A1 - Cosgrove, DO A1 - Hughes, SP J1 - Ultrasound Med Biol Y1 - 2006/02// VL - 32 SN - 0301-5629 SP - 171 EP - 182 N2 - Lumbar arteries are important because they are the main source of blood supply to the lumbar spine structures. However, these vessels and their flow characteristics have received little attention and their role in conditions such as low back pain remains unclear. The present study 1. describes the application of duplex ultrasonography in the assessment of lumbar artery blood flow and 2. evaluates the interobserver and intraobserver reproducibility of lumbar artery Doppler velocimetry. A total of 13 healthy volunteers were evaluated by two different examiners successively on the same day and measurements repeated by the same examiners 1 week later. Peak systolic velocities of lumbar arteries were recorded at an optimal angle below 60 degrees . Overall mean peak systolic velocity (+/-SD) for lumbar arteries was 0.158 +/- 0.051 m/s, and mean Doppler angle (+/-SD) was 24.6 +/- 14.5 degrees . For interobserver variability, the coefficient of variation was 23.4% and SD of differences 0.037 m/s. Reliable results of lumbar artery Doppler velocimetry demonstrate its applicability in future clinical investigations in patients with low back disorders. (E-mail: ). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16464662&query_hl=1 ER - TY - JFULL T1 - Synthesis and characterization of N-(2-chloro-5-methylthiophenyl)-N '-(3-methylthiophenyl)-N '- [C-11]methylguanidine [C-11]CNS 5161, a candidate PET tracer for functional imaging of NMDA receptors A1 - Zhao, YJ A1 - Robins, E A1 - Turton, D A1 - Brady, F A1 - Luthra, SK A1 - Arstad, E J1 - J LABELLED COMPD RAD Y1 - 2006/02// VL - 49 SN - 0362-4803 SP - 163 EP - 170 N2 - N-methyl-D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission and are linked to a variety of acute and chronic neurodegenerative diseases including epilepsy, schizophrenia, Parkinson's disease and drug abuse. N-(2-chloro-5-methylthiophenyl)-N'-(3-methylthiophenyl)-N'-methylguanidine (CNS 5161) is a high affinity ligand (Ki = 1.87 +/- 0.25 nM) for the NMDA PCP site, which potentially can be used for functional imaging of this receptor. Herein we report the synthesis of the corresponding positron emission tomography (PET) tracer [C-11]CNS 5161 by means of [C-11]methylation of the desmethyl guanidine precursor. [C-11]CNS 5161 was synthesized with a decay corrected radiochemical yield of 10% within 45 min after end of bombardment (EOB). The final product was prepared in a sterile saline solution suitable for clinical studies with a radiochemical purity of > 96% and a specific activity of 41 GBq/mmol at time of injection. Copyright (c) 2005 John Wiley & Sons, Ltd. ER - TY - JFULL T1 - Preparation of organotypic hippocampal slice cultures for long-term live imaging. A1 - Gogolla, N A1 - Galimberti, I A1 - DePaola, V A1 - Caroni, P J1 - Nat Protoc Y1 - 2006/// VL - 1 SN - 1750-2799 SP - 1165 EP - 1171 N2 - This protocol details a method to establish organotypic slice cultures from mouse hippocampus, which can be maintained for several months. The cultures are based on the interface method, which does not require special equipment, is easy to execute and yields slice cultures that can be imaged repeatedly--from when they are isolated at postnatal day 6-9, and up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Monitoring of defined cellular and molecular components in the slices can be achieved by preparing slices from transgenic mice or by introducing transgenes through transfection or viral vectors. This protocol can be completed in 3 h. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17406399&query_hl=1 ER - TY - JFULL T1 - Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. A1 - Williams, RR A1 - Azuara, V A1 - Perry, P A1 - Sauer, S A1 - Dvorkina, M A1 - Jørgensen, H A1 - Roix, J A1 - McQueen, P A1 - Misteli, T A1 - Merkenschlager, M A1 - Fisher, AG J1 - J Cell Sci Y1 - 2006/01/01/ VL - 119 SN - 0021-9533 SP - 132 EP - 140 N2 - Determining how genes are epigenetically regulated to ensure their correct spatial and temporal expression during development is key to our understanding of cell lineage commitment. Here we examined epigenetic changes at an important proneural regulator gene Mash1 (Ascl1), as embryonic stem (ES) cells commit to the neural lineage. In ES cells where the Mash1 gene is transcriptionally repressed, the locus replicated late in S phase and was preferentially positioned at the nuclear periphery with other late-replicating genes (Neurod, Sprr2a). This peripheral location was coupled with low levels of histone H3K9 acetylation at the Mash1 promoter and enhanced H3K27 methylation but surprisingly location was not affected by removal of the Ezh2/Eed HMTase complex or several other chromatin-silencing candidates (G9a, SuV39h-1, Dnmt-1, Dnmt-3a and Dnmt-3b). Upon neural induction however, Mash1 transcription was upregulated (>100-fold), switched its time of replication from late to early in S phase and relocated towards the interior of the nucleus. This spatial repositioning was selective for neural commitment because Mash1 was peripheral in ES-derived mesoderm and other non-neural cell types. A bidirectional analysis of replication timing across a 2 Mb region flanking the Mash1 locus showed that chromatin changes were focused at Mash1. These results suggest that Mash1 is regulated by changes in chromatin structure and location and implicate the nuclear periphery as an important environment for maintaining the undifferentiated state of ES cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16371653&query_hl=1 ER - TY - JFULL T1 - Overexpression of the chloride channel CIC-3 in intracellular vesicles of neuroendocrine cells confers chemotherapy resistance to etoposide A1 - Weylandt, KH A1 - Nebrig, M A1 - Wiedenmann, B A1 - Sardini, A J1 - NEUROENDOCRINOLOGY Y1 - 2006/// VL - 83 SN - 0028-3835 SP - 62 EP - 62 ER - TY - JFULL T1 - Gene regulation and large-scale chromatin organization in the nucleus. A1 - Dillon, N J1 - Chromosome Res Y1 - 2006/// VL - 14 SN - 0967-3849 SP - 117 EP - 126 N2 - Regulation of gene expression involves a number of different levels of organization in the cell nucleus. The main agents of transcriptional control are the cis-acting sequences in the immediate vicinity of a gene, which combine to form the functional unit or domain. Contacts between these sequences through the formation of chromatin loops forms the most basic level of organization. The activity of functional domains is also influenced by higher order chromatin structures that impede or permit access of factors to the genes. Epigenetic modifications can maintain and propagate these active or repressive chromatin structures across large genomic regions or even entire chromosomes. There is also evidence that transcription is organized into structures called 'factories' and that this can lead to inter-chromosomal contacts between genes that have the potential to influence their regulation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16506101&query_hl=1 ER - TY - JFULL T1 - Quantification of growth and motion using non-rigid registration A1 - Rueckert, D A1 - Chandrashekara, R A1 - Ajabar, P A1 - Bhatia, KK A1 - Boardman, JP A1 - Srinivasan, L A1 - Rutherford, MA A1 - Dyet, LE A1 - Edwards, AD A1 - Hajnal, JV A1 - Mohiaddin, R J1 - LECT NOTES COMPUT SC Y1 - 2006/// VL - 4241 SN - 0302-9743 SP - 49 EP - 60 N2 - Three-dimensional (3D) and four-dimensional (4D) imaging of dynamic structures is a rapidly developing area of research in medical imaging. Non-rigid registration plays an important role for the analysis of these datasets. In this paper we will show some of the work of our group using non-rigid registration techniques for the detection of temporal changes such as growth in brain MR images. We will also show how non-rigid registration can be used to analyze the motion of the heart from cardiac MR images. ER - TY - JFULL T1 - Multiclassifier fusion in human brain MR segmentation: modelling convergence. A1 - Heckemann, RA A1 - Hajnal, JV A1 - Aljabar, P A1 - Rueckert, D A1 - Hammers, A J1 - Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv Y1 - 2006/// VL - 9 SP - 815 EP - 822 N2 - Segmentations of MR images of the human brain can be generated by propagating an existing atlas label volume to the target image. By fusing multiple propagated label volumes, the segmentation can be improved. We developed a model that predicts the improvement of labelling accuracy and precision based on the number of segmentations used as input. Using a cross-validation study on brain image data as well as numerical simulations, we verified the model. Fit parameters of this model are potential indicators of the quality of a given label propagation method or the consistency of the input segmentations used. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354848&query_hl=1 ER - TY - JFULL T1 - Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation. A1 - Rimoldi, O A1 - Schäfers, KP A1 - Boellaard, R A1 - Turkheimer, F A1 - Stegger, L A1 - Law, MP A1 - Lammerstma, AA A1 - Camici, PG J1 - J Nucl Med Y1 - 2006/01// VL - 47 SN - 0161-5505 SP - 163 EP - 172 N2 - The purpose of this study was to assess the feasibility and accuracy of quantifying subendocardial and subepicardial myocardial blood flow (MBF) and the relative coronary flow reserves (CFR) using (15)O-labeled water (H(2)(15)O) and 3-dimensional-only PET. METHODS: Eight pigs were scanned with H(2)(15)O and (15)O-labeled carbon monoxide (C(15)O) after partially occluding the circumflex (n = 3) or the left anterior descending (n = 5) coronary artery, both at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres were injected during each of the H(2)(15)O scans. RESULTS: In a total of 256 paired measurements of MBF, ranging from 0.30 to 4.46 mL.g(-1).min(-1), microsphere and PET MBF were fairly well correlated. The mean difference between the 2 methods was -0.01 +/- 0.52 mL.g(-1).min(-1) with 95% of the differences lying between the limits of agreement of -1.02 and 1.01 mL.g(-1).min(-1). CFR was significantly reduced (P < 0.05) in the ischemic subendocardium (PET = 1.12 +/- 0.45; microspheres = 1.09 +/- 0.50; P = 0.86) and subepicardium (PET = 1.2 +/- 0.35; microspheres = 1.32 +/- 0.5; P = 0.39) in comparison with remote subendocardium (PET = 1.7 +/- 0.62; microspheres = 1.64 +/- 0.61; P = 0.68) and subepicardium (PET = 1.79 +/- 0.73; microspheres = 2.19 +/- 0.86; P = 0.06). CONCLUSION: Dynamic measurements using H(2)(15)O and a 3-dimensional-only PET tomograph allow regional estimates of the transmural distribution of MBF over a wide flow range, although transmural flow differences were underestimated because of the partial-volume effect. PET subendocardial and subepicardial CFR were in good agreement with the microsphere values. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16391201&query_hl=1 ER - TY - JFULL T1 - Long-term live imaging of neuronal circuits in organotypic hippocampal slice cultures. A1 - Gogolla, N A1 - Galimberti, I A1 - DePaola, V A1 - Caroni, P J1 - Nat Protoc Y1 - 2006/// VL - 1 SN - 1750-2799 SP - 1223 EP - 1226 N2 - This protocol details a method for imaging organotypic slice cultures from the mouse hippocampus. The cultures are based on the interface method, which does not require special equipment, is easy to execute, and yields slice cultures that can be imaged repeatedly after they are isolated on postnatal day 6-9 and for up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Time-lapse imaging is based on transgenes expressed in the mice, or on constructs introduced through transfection or viral vectors; it can reveal processes that develop over time periods ranging from seconds to months. Imaging can be repeated at least eight times without detectable morphological damage to neurons. Subsequent to imaging, the slices can be processed for immunocytochemistry or electron microscopy, to collect further information about the structures that have been imaged. This protocol can be completed in 35 min. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17406405&query_hl=1 ER - TY - JFULL T1 - Beyond the g-factor limit in sensitivity encoding using joint histogram entropy. A1 - Larkman, DJ A1 - Batchelor, PG A1 - Atkinson, D A1 - Rueckert, D A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2006/01// VL - 55 SN - 0740-3194 SP - 153 EP - 160 N2 - The maximum practical speed-up that can be achieved using parallel imaging methods is widely accepted to be limited by g-factor noise. An approximate expression for the g-factor noise as a function of the principal eigenvector of the inverse sensitivity matrix is derived. This formulation allows g-factor enhanced noise to be reduced by a constrained optimization procedure with joint image histogram entropy between a reference image and a SENSE image as an image quality metric. The reference image does not need to have identical resolution or contrast. The reference image may also be used for coil calibration. The limits of the method are explored using simulated and real array coil data with high g-factor using a variety of contrast and resolution combinations. The method preserves image structure, contrast, and lesions even when these were not observable in the reference data. In all cases g-factor was dramatically reduced. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16342149&query_hl=1 ER - TY - JFULL T1 - Segmentation of brain MRI in young children. A1 - Murgasova, M A1 - Dyet, L A1 - Edwards, D A1 - Rutherford, M A1 - Hajnal, JV A1 - Rueckert, D J1 - Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv Y1 - 2006/// VL - 9 SP - 687 EP - 694 N2 - This paper describes an automatic tissue segmentation algorithm for brain MRI of young children. Existing segmentation methods developed for the adult brain do not take into account the specific tissue properties present in the brain MRI of young children. We examine the suitability of state-of-the-art methods developed for the adult brain when applied to the segmentation of the young child brain MRI. We develop a method of creation of a population-specific atlas from young children using a single manual segmentation. The method is based on non-linear propagation of the segmentation into population and subsequent affine alignment into a reference space and averaging. Using this approach we significantly improve the performance of the popular EM segmentation algorithm on brain MRI of young children. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354950&query_hl=1 ER - TY - JFULL T1 - List-mode affine rebinning for respiratory motion correction in PET cardiac imaging A1 - Chung, AJ A1 - Camici, PG A1 - Yang, GZ J1 - LECT NOTES COMPUT SC Y1 - 2006/// VL - 4091 SN - 0302-9743 SP - 293 EP - 300 N2 - Positron Emission Tomography (PET) is an established functional imaging modality but its practical deployment is hampered by motion artefacts. This paper proposes a method for correcting reconstructed PET images through a list-mode rebinning process. Respiratory motion is compensated for by applying 2D affine transforms to the respiratory gated sequence of line-of-response events prior to image reconstruction. The affine transforms are derived from a non-rigid 3D/3D registration model derived from retrospectively gated MRI acquisitions of the same patient with free-breathing. The proposed motion correction scheme is evaluated with a simulation framework where the improvement in image quality is assessed by using data acquired from 10 normal subjects. ER - TY - JFULL T1 - Staining protocol for organotypic hippocampal slice cultures. A1 - Gogolla, N A1 - Galimberti, I A1 - DePaola, V A1 - Caroni, P J1 - Nat Protoc Y1 - 2006/// VL - 1 SN - 1750-2799 SP - 2452 EP - 2456 N2 - This protocol details a method to immunostain organotypic slice cultures from mouse hippocampus. The cultures are based on the interface method, which does not require special equipment, is easy to execute and yields slice cultures that can be imaged repeatedly, from the time of isolation at postnatal day 6-9 up to 6 months in vitro. The preserved tissue architecture facilitates the analysis of defined hippocampal synapses, cells and entire projections. Time-lapse imaging is based on transgenes expressed in the mice or on constructs introduced through transfection or viral vectors; it can reveal processes that develop over periods ranging from seconds to months. Subsequent to imaging, the slices can be processed for immunocytochemistry to collect further information about the imaged structures. This protocol can be completed in 3 d. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17406491&query_hl=1 ER - TY - JFULL T1 - Use of gadolinium chloride as a contrast agent for imaging spruce knots by magnetic resonance A1 - Eberhardt T A1 - So CL A1 - Herlihy AH A1 - So PW J1 - Wood and Fibre Science Y1 - 2006/// VL - 38(3) SP - 527 EP - 534 ER - TY - JFULL T1 - A single point mutation in the low-density lipoprotein receptor switches the degradation of its mature protein from the proteasome to the lysosome. A1 - Martín de Llano, JJ A1 - Fuertes, G A1 - Andreu, EJ A1 - Puig, O A1 - Chaves, FJ A1 - Soutar, AK A1 - Armengod, ME A1 - Knecht, E J1 - Int J Biochem Cell Biol Y1 - 2006/// VL - 38 SN - 1357-2725 SP - 1340 EP - 1351 N2 - Pathogenic mutations in the low-density lipoprotein receptor prevent cholesterol uptake and cause familial hypercholesterolemia. In comparison to the biogenesis and endocytic trafficking of this receptor and some of its mutants, their degradation mechanisms are not well understood. Therefore, to gain some insights into this aspect, we analyzed the effects of proteasomal and lysosomal inhibitors on the levels of the wild type low-density lipoprotein receptor and a mutant form, C358Y, which was prevalent in a sample of Spanish familial hypercholesterolemia patients. In transfected cells, the mutant C358Y exhibited lower activity than the wild type receptor, as well as retarded post-translational processing of its precursor to the mature form. Interestingly, about 30% of the mutant precursor was degraded by a lysosomal pathway. Moreover, its mature form was more rapidly degraded than the wild type receptor (half lives of 5.3 and 10.9 h, respectively) and its degradation was exclusively dependent on a lysosomal pathway. In contrast, the mature form of the wild type receptor was mainly degraded by proteasomes and, to a minor extent (30%), by lysosomes. We conclude that a single mutation in the low-density lipoprotein receptor switches the degradation of the mature receptor from a proteasomal to a lysosomal pathway which degrades the protein at a faster rate. This suggests cooperation of proteasomes and lysosomes in the degradation of the low-density lipoprotein receptor and adds an intriguing new aspect to our understanding of receptor-mediated endocytosis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16530458&query_hl=1 ER - TY - JFULL T1 - Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. A1 - Stewart, EA A1 - Rabinovici, J A1 - Tempany, CM A1 - Inbar, Y A1 - Regan, L A1 - Gostout, B A1 - Gastout, B A1 - Hesley, G A1 - Kim, HS A1 - Hengst, S A1 - Gedroyc, WM A1 - Gedroye, WM J1 - Fertil Steril Y1 - 2006/01// VL - 85 SN - 1556-5653 SP - 22 EP - 29 N2 - OBJECTIVE: To assess outcomes at 6 and 12 months after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for symptomatic uterine leiomyomas. DESIGN: Multicenter clinical trial. SETTING: Academic medical centers. PATIENT(S): Premenopausal women with symptomatic uterine leiomyomas and no plans for future pregnancy (n = 109 at 6 months and n = 82 at 12 months). INTERVENTION(S): A single treatment session of MRgFUS for uterine fibroids. MAIN OUTCOME MEASURE(S): Reduction in fibroid symptoms as measured by the symptom severity score (SSS) of the Uterine Fibroid Quality-of-Life Instrument (UFS-QOL), the only validated measure of leiomyoma symptomatology. A 10-point reduction in the SSS was selected as the targeted improvement. RESULT(S): Seventy-one percent of women undergoing MRgFUS reached the targeted symptom reduction at 6 months, and 51% reached this at 12 months. The magnitude of improvement in SSS was greater than predicted, with subjects having a mean decrease of 39% and 36% at 6 and 12 months, respectively. This paralleled the improvement seen using the short form-36 instrument. A modest volume reduction similar in magnitude to the treated volume was seen. The incidence of adverse events was low. CONCLUSION(S): MRgFUS treatment results in short-term symptom reduction for women with symptomatic uterine leiomyomas with an excellent safety profile. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16412721&query_hl=1 ER - TY - JFULL T1 - The hypothalamus, hormones, and hunger: alterations in human obesity and illness. A1 - Goldstone, AP J1 - Prog Brain Res Y1 - 2006/// VL - 153 SN - 0079-6123 SP - 57 EP - 73 N2 - Obesity is a major global epidemic, with over 300 million obese people worldwide, and nearly 1 billion overweight adults. Being overweight carries significant health risks, reduced quality of life, and impaired socioeconomic success, with profound consequences for health expenditure. The most successful treatment for obesity is gastric bypass surgery, which acts in part by reducing appetite through alterations in gut hormones. Circulating gut hormones, secreted or suppressed after eating food, act in the brain, particularly the hypothalamus, to alter hunger and fullness. Stomach-derived ghrelin increases food intake even in those with anorexia from chronic illness, while pancreatic polypeptide (PP), intestinal peptide YY 3-36 (PYY), oxyntomodulin, and other hormones reduce food intake and appetite. While obese subjects have appropriate reductions in orexigenic ghrelin, other gut-hormone disturbances may contribute to obesity such as reduced anorexigenic PYY and PP. Prader-Willi syndrome (PWS) arises from the loss of paternally inherited genes on chromosome 15q11-13, leading to life-threatening insatiable hunger and obesity from early childhood, through developmental brain, particularly hypothalamic defects. The study of genetically homogenous causes of abnormal-feeding behavior helps our understanding of appetite regulation. PWS subjects have inappropriately elevated plasma ghrelin for their obesity, at least partly explained by preserved insulin sensitivity. It remains unproven if their hyperghrelinemia or other gut-hormone abnormalities contribute to the hyperphagia in PWS, in addition to brain defects. Postmortem human hypothalamic studies and generation of animal models of PWS can also provide insight into the pathophysiology of abnormal-feeding behavior. Changes in orexigenic NPY and AGRP hypothalamic neurons, or anorexigenic oxytocin neurons have been found in illness and PWS. Functional neuroimaging studies, using PET and fMRI, will also allow us to tease apart the hormonal and brain pathways responsible for controlling human appetite, and their defects in obesity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16876568&query_hl=1 ER - TY - JFULL T1 - 'Dorsal vulnerability' and patterns of visuo-cognitive deficit following very premature birth A1 - Atkinson, J A1 - Braddick, OJ A1 - Nardini, M A1 - Anker, SE A1 - Cowan, FM A1 - D Edwards, A A1 - Rutherford, MA J1 - PERCEPTION Y1 - 2006/// VL - 35 SN - 0301-0066 SP - 3 EP - 3 ER - TY - JFULL T1 - Myocardial ischaemia and metabolic memory. A1 - Camici, PG J1 - Eur J Nucl Med Mol Imaging Y1 - 2006/01// VL - 33 SN - 1619-7070 SP - 4 EP - 5 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16237570&query_hl=1 ER - TY - JFULL T1 - Distribution of different phosphorylated forms of RNA polymerase II in relation to Cajal and PML bodies in human cells: an ultrastructural study. A1 - Xie, SQ A1 - Pombo, A J1 - Histochem Cell Biol Y1 - 2006/01// VL - 125 SN - 0948-6143 SP - 21 EP - 31 N2 - The mammalian nucleus is a highly organised organelle that contains many subcompartments with roles in DNA replication and repair, gene expression and RNA processing. Cajal and promyelocytic leukaemia (PML) bodies are discrete nuclear structures with specific molecular signatures. RNA polymerase II and many transcription factors have been identified within these compartments by immunofluorescence microscopy, suggesting a role in polymerase II assembly or transcriptional activity. Here, we have examined the presence of different phosphorylated forms of polymerase II and newly made RNA in Cajal and PML bodies using high-resolution imaging of ultrathin cryosections (approximately 120 nm thick) with fluorescence and electron microscopes. We show that Cajal bodies contain polymerase II phosphorylated on Ser5, and not the Ser2-phosphorylated (active) form or newly made RNA. The presence of polymerase II in the absence of transcriptional activity suggests that Cajal bodies have roles in polymerase assembly or transport, but not in gene transcription. PML bodies contain no detectable polymerase II or nascent RNA in HeLa cells, at the resolution achieved by electron microscopy, but are often surrounded by these markers at distances>25 nm. These results support the view that although PML bodies are present in transcriptionally active areas of the nucleus, they are not generally sites of polymerase II assembly, transport or activity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16187066&query_hl=1 ER - TY - JFULL T1 - Negative correlation between the volumetric niacin response and cerebral inorganic phosphate in male patients with schizophrenia who have seriously and dangerously violently offended: A 31-phosphorus magnetic resonance spectroscopy study A1 - Puri, BK A1 - Richardson, AJ A1 - Counsell, SJ A1 - Ward, PE A1 - Bustos, MG A1 - Hamilton, G A1 - Bhakoo, KK A1 - Treasaden, IH J1 - SCHIZOPHR RES Y1 - 2006/01// VL - 81 SN - 0920-9964 SP - 257 EP - 257 ER - TY - JFULL T1 - Designing for e-Health: recurring scenarios in developing grid-based medical imaging systems. A1 - Geddes, J A1 - Mackay, C A1 - Lloyd, S A1 - Simpson, A A1 - Power, D A1 - Russell, D A1 - Jirotka, M A1 - Katzarova, M A1 - Rossor, M A1 - Fox, N A1 - Fletcher, J A1 - Hill, D A1 - McLeish, K A1 - Chen, Y A1 - Hajnal, JV A1 - Lawrie, S A1 - Job, D A1 - McIntosh, A A1 - Wardlaw, J A1 - Sandercock, P A1 - Palmer, J A1 - Perry, D A1 - Procter, R A1 - Ure, J A1 - Hartswood, M A1 - Slack, R A1 - Voss, A A1 - Ho, K A1 - Bath, P A1 - Clarke, W A1 - Watson, G J1 - Stud Health Technol Inform Y1 - 2006/// VL - 120 SN - 0926-9630 SP - 336 EP - 347 N2 - The paper draws on a number of Grid projects, particularly on the experience of NeuroGrid, a UK project in the Neurosciences tasked with developing a Grid-based collaborative research environment to support the sharing of digital images and patient data across multiple distributed sites. It outlines recurrent socio-technical issues, highlighting the challenges of scaling up technological networks in advance of the regulatory networks which normally regulate their use in practice. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16823151&query_hl=1 ER - TY - JFULL T1 - Diagnostic efficacy of SonoVue (R), a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study A1 - Sidhu, PS A1 - Allan, PL A1 - Cattin, F A1 - Cosgrove, DO A1 - Davies, AH A1 - Do, DD A1 - Karakagil, S A1 - Langholz, J A1 - Legemate, DA A1 - Martegani, A A1 - Llull, JB A1 - Pezzoli, C A1 - Spinazzi, A J1 - BRIT J RADIOL Y1 - 2006/01// VL - 79 SN - 0007-1285 SP - 44 EP - 51 N2 - The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue (R) microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p <= 0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p < 0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease. ER - TY - JFULL T1 - Deformation based morphometry analysis of serial magnetic resonance images of mouse brains A1 - Maheswaran, S A1 - Barjat, H A1 - Bate, S A1 - Hartkens, T A1 - Hill, DLG A1 - James, MF A1 - Tilling, L A1 - Upton, N A1 - Hajnal, J A1 - Rueckert, D J1 - LECT NOTES COMPUT SC Y1 - 2006/// VL - 4057 SN - 0302-9743 SP - 58 EP - 65 N2 - Deformation based morphometry is used to detect differences in in-vivo Magnetic Resonance Image (MRI) of the mouse brain obtained from two transgenic strains: TASTPM mice that over-express proteins associated with Alzheimer's disease, and wild-type mice. MRI was carried out at four time points. We compare two different methods to detect group differences in the longitudinal and cross-sectional data. Both methods are based on non-rigid registration of the images to a mouse brain atlas. The whole brain volume measurements on 27 TASTPM and wild-type animals are reproducible to within 0.4% of whole brain volume. The agreement between different methods for measuring volumes in a serial study is shown. The ability to quantify changes in growth between strains in whole brain, hippocampus and cerebral cortex is demonstrated. ER - TY - JFULL T1 - Permanent partial phenotypic correction and tolerance in a mouse model of hemophilia B by stem cell gene delivery of human factor IX. A1 - Bigger, BW A1 - Siapati, EK A1 - Mistry, A A1 - Waddington, SN A1 - Nivsarkar, MS A1 - Jacobs, L A1 - Perrett, R A1 - Holder, MV A1 - Ridler, C A1 - Kemball-Cook, G A1 - Ali, RR A1 - Forbes, SJ A1 - Coutelle, C A1 - Wright, N A1 - Alison, M A1 - Thrasher, AJ A1 - Bonnet, D A1 - Themis, M J1 - Gene Ther Y1 - 2006/01// VL - 13 SN - 0969-7128 SP - 117 EP - 126 N2 - Immune responses against an introduced transgenic protein are a potential risk in many gene replacement strategies to treat genetic disease. We have developed a gene delivery approach for hemophilia B based on lentiviral expression of human factor IX in purified hematopoietic stem cells. In both normal C57Bl/6J and hemophilic 129/Sv recipient mice, we observed the production of therapeutic levels of human factor IX, persisting for at least a year with tolerance to human factor IX antigen. Secondary and tertiary recipients also demonstrate long-term production of therapeutic levels of human factor IX and tolerance, even at very low levels of donor chimerism. Furthermore, in hemophilic mice, partial functional correction of treated mice and phenotypic rescue is achieved. These data show the potential of a stem cell approach to gene delivery to tolerize recipients to a secreted foreign transgenic protein and, with appropriate modification, may be of use in developing treatments for other genetic disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16163377&query_hl=1 ER - TY - JFULL T1 - Diffeomorphic registration using B-splines. A1 - Rueckert, D A1 - Aljabar, P A1 - Heckemann, RA A1 - Hajnal, JV A1 - Hammers, A J1 - Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv Y1 - 2006/// VL - 9 SP - 702 EP - 709 N2 - In this paper we propose a diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. In contrast to existing non-rigid registration methods based on FFDs the proposed diffeomorphic non-rigid registration algorithm based on free-form deformations (FFDs) which are modelled by B-splines. To construct a diffeomorphic transformation we compose a sequence of free-form deformations while ensuring that individual FFDs are one-to-one transformations. We have evaluated the algorithm on 20 normal brain MR images which have been manually segmented into 67 anatomical structures. Using the agreement between manual segmentation and segmentation propagation as a measure of registration quality we have compared the algorithm to an existing FFD registration algorithm and a modified FFD registration algorithm which penalises non-diffeomorphic transformations. The results show that the proposed algorithm generates diffeomorphic transformations while providing similar levels of performance as the existing FFD registration algorithm in terms of registration accuracy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354834&query_hl=1 ER - TY - JFULL T1 - Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis. A1 - Taylor, PC A1 - Steuer, A A1 - Gruber, J A1 - McClinton, C A1 - Cosgrove, DO A1 - Blomley, MJ A1 - Marsters, PA A1 - Wagner, CL A1 - Maini, RN J1 - Arthritis Rheum Y1 - 2006/01// VL - 54 SN - 0004-3591 SP - 47 EP - 53 N2 - OBJECTIVE: To compare the impact of immediate and delayed introduction of anti-tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). METHODS: Twenty-four patients with erosive early RA (duration < 3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high-frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system. RESULTS: From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between-group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076). CONCLUSION: The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16385521&query_hl=1 ER - TY - JFULL T1 - The feasibility of MR-image guided prostate biopsy using piezoceramic motors inside or near to the magnet isocentre. A1 - Elhawary, H A1 - Zivanovic, A A1 - Rea, M A1 - Davies, B A1 - Besant, C A1 - McRobbie, D A1 - de Souza, N A1 - Young, I A1 - Lampérth, M J1 - Med Image Comput Comput Assist Interv Int Conf Med Image Comput Comput Assist Interv Y1 - 2006/// VL - 9 SP - 519 EP - 526 N2 - The excellent soft tissue contrast of Magnetic Resonance Imaging (MRI) has encouraged the development of MRI compatible systems capable of combining the advantages of robotic manipulators with high quality anatomical images. Continuing this development, a new five DOF prostate biopsy manipulator has been designed for use inside a closed 1.5T MRI scanner. Space constraints in the bore and the current trend to restrict field strength exposure for operators indicate that a master-slave configuration is ideal for controlling the robotic system from outside the bore. This system has been designed to work with piezoceramic motors and optical encoders placed inside or near the field of view of the scanner, using real time image guidance for targeting biopsies to specific lesions in the prostate. MRI tests have been performed to prove the feasibility of this concept and a one DOF proof-of-concept test rig implementing closed loop position control has been tested and is presented here. A first prototype of the slave manipulator has been designed and manufactured incorporating this new technology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17354930&query_hl=1 ER - TY - JFULL T1 - N-acetylaspartate metabolism in neural cells. A1 - Bhakoo, KK A1 - Craig, T A1 - Pearce, D J1 - Adv Exp Med Biol Y1 - 2006/// VL - 576 SN - 0065-2598 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16802703&query_hl=1 ER - TY - JFULL T1 - Expression of RPIP9 (Rap2 interacting protein 9) is activated in breast carcinoma and correlates with a poor prognosis. A1 - Raguz, S A1 - De Bella, MT A1 - Slade, MJ A1 - Higgins, CF A1 - Coombes, RC A1 - Yagüe, E J1 - Int J Cancer Y1 - 2005/12/20/ VL - 117 SN - 0020-7136 SP - 934 EP - 941 N2 - MDR1 is upregulated in many tumors. We have previously detected activation of the MDR1 upstream promoter in metastatic breast cancer cells. MDR1 overlaps with an uncharacterized gene transcribed from the opposite strand, coding for Rap2 interacting protein 9 (RPIP9). Rap2 belongs to the Ras superfamily of GTPases, whose role in breast cancer remains unknown. We developed sensitive methods for detecting and quantifying RPIP9 mRNA and used it to identify these transcripts in normal human tissues, 60 biopsies of primary breast carcinoma, in isolated epithelial cells both from the primary tumor and from associated lymph nodes, and from bone marrow biopsies of 74 breast cancer patients. RPIP9 is expressed at high levels in normal testis, brain and adrenal gland, and at very low levels in normal breast. Tumorigenic breast carcinoma cell lines expressed RPIP9, whereas MCF-10A and HBL-100 that do not form tumors in nude mice had undetectable levels of RPIP9 mRNA. RPIP9 was activated in a high proportion of breast carcinomas (61.6%; n = 60) and a significant correlation with metastatic lymph node invasion (N = 0-3 vs. N > 3, where N = number of lymph nodes invaded; p = 0.031) was found. RPIP9 mRNA could be detected in malignant epithelial cells isolated from the primary tumor and from metastasized lymph nodes as well as in the bone marrow of significantly more poor-prognosis (N > 3) than better-prognosis (N = 0-3) patients (p = 0.001). Therefore, activation of RPIP9 occurs during the malignant breast epithelial transformation and increases with progression toward an invasive phenotype. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15986426&query_hl=1 ER - TY - JFULL T1 - EPCR Ser219Gly: elevated sEPCR, prothrombin F1+2, risk for coronary heart disease, and increased sEPCR shedding in vitro. A1 - Ireland, H A1 - Konstantoulas, CJ A1 - Cooper, JA A1 - Hawe, E A1 - Humphries, SE A1 - Mather, H A1 - Goodall, AH A1 - Hogwood, J A1 - Juhan-Vague, I A1 - Yudkin, JS A1 - di Minno, G A1 - Margaglione, M A1 - Hamsten, A A1 - Miller, GJ A1 - Bauer, KA A1 - Kim, YT A1 - Stearns-Kurosawa, DJ A1 - Kurosawa, S J1 - Atherosclerosis Y1 - 2005/12// VL - 183 SN - 0021-9150 SP - 283 EP - 292 N2 - We have progressively analysed three studies of coronary heart disease (CHD) for a variant in EPCR (Ser219Gly). Initially, in a prospective study, NPHSII, while no overall CHD-risk was identified in heterozygotes, homozygotes for 219Gly exhibited a three-fold elevated risk (HR 3.3, CI 1.22-8.96). In diabetics within NPHSII, there was a suggestion that 219Gly+ was associated with elevated CHD-risk (HR 1.89, CI 0.39-9.06) although numbers were small. To further assess the effect of the variant in diabetes, a case-control study of MI, HIFMECH, was used, in which previous analysis had defined a group with metabolic syndrome, by factor analysis. A significant CHD-risk interaction was identified between genotype and the 'metabolic syndrome' factor (interaction p=0.009). To further assess CHD-risk for this variant in type-2 diabetes and to assess the effect of the variant upon thrombin generation and plasma levels of soluble EPCR, a cross-sectional study of type-2 diabetes was used. A significant CHD-risk was identified for European Whites (OR 2.84, CI 1.38-5.85) and Indian Asians in this study (OR 1.6, CI 1.00-2.57) and the frequency of 219Gly was two-fold higher in Indian Asians. Soluble EPCR levels were strongly associated with genotype, with homozygotes for 219Gly having four-fold higher levels (p<0.0001). In vitro studies of EPCR-transfected cells suggested increased basal release of sEPCR from cells expressing the 219Gly EPCR phenotype. Furthermore, in base-line samples from NPHSII and in the diabetic study, a significant increase in prothrombin F1+2 level was observed for 219Gly. The increased CHD-risk and thrombin generation appears to be acting through increased shedding of the Gly allele from the cell surface. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15921688&query_hl=1 ER - TY - JFULL T1 - The MHG box transcription factor Sox4 contributes to the development of the endocrine pancreas A1 - Wilson, ME A1 - Yang, KY A1 - Kalousova, A A1 - Lau, J A1 - Kosaka, Y A1 - Lynn, FC A1 - Wang, JH A1 - Mrejen, C A1 - Episkopou, V A1 - Clevers, HC A1 - German, MS J1 - DIABETES Y1 - 2005/12// VL - 54 SN - 0012-1797 SP - 3402 EP - 3409 N2 - To investigate the role of the Sry/hydroxymethylglutaryl box (Sox) transcription factors in the development of the pancreas, we determined the expression pattern of Sox factors in the developing mouse pancreas. By RT-PCR, we detected the presence of multiple Sox family members in both the developing pancreas and mature islets and then focused on two factors, Sox2 and Sox4. The expression field of Sox2, which plays a role in the maintenance of some stem cell populations, included the developing duodenum, but Sox2 was specifically excluded from the pancreatic buds. In contrast, Sox4 was detected broadly in the early pancreatic buds and eventually became restricted to the nuclei of all islet cells in the adult mouse. Mice homozygous for a null mutation of the sox4 gene showed normal pancreatic bud formation and endocrine cell differeniiation up to embryonic day 12.5. Beyond that date, cultured pancreatic explants lacking sox4 failed to form normal islets. Instead, a markedly reduced number of endocrine cells were found scattered through the explant. We show here that several Sox transcription factors are expressed in the developing pancreas and in the islet, and that one of these factors, Sox4, is required for the normal development of pancreatic islets. ER - TY - JFULL T1 - Involvement of catecholamine neurotransmission in the rat anterior cingulate in effort-related decision making A1 - Schweimer, J A1 - Saft, S A1 - Hauber, W J1 - BEHAV NEUROSCI Y1 - 2005/12// VL - 119 SN - 0735-7044 SP - 1687 EP - 1692 N2 - This study examined whether catecholamine-mediated signals in the anterior cingulate cortex (ACC) contribute to effort-based decision making. Rats were tested after 6-hydroxydopamine or vehicle infusions into the ACC in a T maze cost-benefit task in which the rats could choose either to climb a barrier to obtain a high reward in one arm or run into the other arm without a barrier to obtain a low reward. Results demonstrate that infusions of 6-hydroxydopamine induced a near total loss of tyrosine hydroxylase-positive fibers in the ACC. Unlike sham-lesioned rats, 6-hydroxydopamine-lesioned rats exhibited a reduced preference for the high-cost-high-reward response option when given the choice of obtaining a low reward with little effort. Thus, catecholamine-mediated signals in the ACC could play a role in effort-based decision making. ER - TY - JFULL T1 - Angiogenesis imaging in the management of prostate cancer A1 - Padhani, AR A1 - Harvey, CJ A1 - Cosgrove, DO J1 - NAT CLIN PRACT UROL Y1 - 2005/12// VL - 2 SP - 596 EP - 607 N2 - Angiogenesis is an integral part of benign prostatic hyperplasia, is associated with prostatic intraepithelial neoplasia and is a key factor in the growth and metastasis of prostate cancer. This review focuses on ultrasound and dynamic MRI in the evaluation of prostate cancer angiogenesis, and compares these techniques to functional CT and hydrogen magnetic resonance spectroscopic imaging. Image-based evaluation of angiogenesis in the prostate has established clinical roles in lesion detection, tumor staging and the detection of suspected tumor recurrence. One limitation of all these imaging techniques, however, is inadequate lesion characterization, particularly in differentiating prostatitis from cancer in the peripheral zone of the prostate, and in distinguishing between benign prostatic hyperplasia and central-gland tumors. Ultimately, local availability, expertise and the need to minimize patients' radiation burden will influence which technique is used in prostatic evaluations. ER - TY - JFULL T1 - Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response. A1 - Naoumova, RP A1 - Tosi, I A1 - Patel, D A1 - Neuwirth, C A1 - Horswell, SD A1 - Marais, AD A1 - van Heyningen, C A1 - Soutar, AK J1 - Arterioscler Thromb Vasc Biol Y1 - 2005/12// VL - 25 SN - 1524-4636 SP - 2654 EP - 2660 N2 - OBJECTIVE: Analysis of long-term (30 years) clinical history and response to treatment of 13 patients with the D374Y mutation of PCSK9 (PCSK9 patients) from 4 unrelated white British families compared with 36 white British patients with heterozygous familial hypercholesterolemia attributable to 3 specific mutations in the low-density lipoprotein (LDL) receptor gene (LDLR) known to cause severe phenotype. METHODS AND RESULTS: The PCSK9 patients, when compared with the LDLR patients, were younger at presentation (20.8+/-14.7 versus 30.2+/-15.7 years; P=0.003), had higher pretreatment serum cholesterol levels (13.6+/-2.9 versus 9.6+/-1.6 mmol/L; P=0.004) that remained higher during treatment with simvastatin (10.1+/-3.0 versus 6.5+/-0.9 mmol/L; P=0.006), atorvastatin (9.6+/-2.9 versus 6.4+/-1.0 mmol/L; P=0.006), or current lipid-lowering therapy, including LDL apheresis and partial ileal bypass in 2 PCSK9 patients (7.0+/-1.6 versus 5.4+/-1.0 mmol/L; P=0.001), and were affected >10 years earlier by premature coronary artery disease (35.2+/-4.8 versus 46.8+/-8.9 years; P=0.002). LDL from PCSK9 patients competed significantly less well for binding to fibroblast LDL receptors than LDL from either controls or LDLR patients. CONCLUSIONS: These British PCSK9 patients with the D374Y mutation have an unpredictably severe clinical phenotype, which may be a unique feature for this cohort, and requires early and aggressive lipid-lowering management to prevent cardiovascular complications. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16224054&query_hl=1 ER - TY - JFULL T1 - Padé methods for reconstruction and feature extraction in magnetic resonance imaging. A1 - Callaghan, MF A1 - Larkman, DJ A1 - Hajnal, JV J1 - Magn Reson Med Y1 - 2005/12// VL - 54 SN - 0740-3194 SP - 1490 EP - 1502 N2 - Methods utilizing Padé approximants are investigated for implementation with magnetic resonance imaging data and are presented both for direct image reconstruction and for feature extraction. Padé approximants are a numerical tool that can be used to accelerate the convergence of a slowly converging sequence by estimating the fully converged sequence values from early data points. Padé approximants can be calculated directly from k-space data by solving a set of linear matrix equations to produce signal values for any desired location in the image domain. This gives an estimate of the fully converged signal intensity at each pixel location in the image, raising the possibility of reconstructing a better estimate of the object from a reduced data set. These methods have been tested on phantom and human data both for image reconstruction and for feature extraction. In image reconstruction, considerable convergence acceleration can be achieved, with steep intensity boundaries reproduced in keeping with higher resolution reconstructions and oscillatory truncation artifact characteristic of Fourier reconstruction removed. The convergence acceleration is variable and there is the possibility of fine detail suppression when insufficient data are included. The use of Padé methods as a tool for feature extraction has shown good agreement with extraction from high-resolution reference data. In this approach the edge information comes intrinsically from Padé reconstruction. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16254953&query_hl=1 ER - TY - JFULL T1 - TGF-beta/nodal signalling can be regulated by post-transcriptional control of Arkadia RNAs A1 - Dixon, JE A1 - Episkopou, V J1 - GENET RES Y1 - 2005/12// VL - 86 SN - 0016-6723 SP - 233 EP - 233 ER - TY - JFULL T1 - The epigenetic basis for embryonic stem cell pluripotency. A1 - Szutorisz, H A1 - Dillon, N J1 - Bioessays Y1 - 2005/12// VL - 27 SN - 0265-9247 SP - 1286 EP - 1293 N2 - As well as having the remarkable ability to differentiate into all of the cell types in the embryo, embryonic stem (ES) cells also have the capacity to divide and self-renew. Maintenance of pluripotency through repeated cell divisions indicates that the developmental plasticity of ES cells has a specific epigenetic basis. We propose that tightly localised regions of histone modification are formed in ES cells by binding of sequence-specific transcription factors at genes that are destined for expression at later stages of differentiation. These 'early transcription competence marks' would help to maintain pluripotency by preventing the spread of repressive chromatin modifications. We further propose that the presence of discrete histone modification marks in pluripotent cells facilitates the binding of lineage-specific and general transcription factors to the marked regions as ES cells commit to different fates. By helping to organise the precisely timed responses of genes to the signals that determine lineage choice, the gene-specific localised epigenetic marks would play a key role in the establishment of complex gene expression programmes in differentiating cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16299767&query_hl=1 ER - TY - JFULL T1 - Investigations on the efficiency of cardiac-gated methods for the acquisition of diffusion-weighted images. A1 - Nunes, RG A1 - Jezzard, P A1 - Clare, S J1 - J Magn Reson Y1 - 2005/11// VL - 177 SN - 1090-7807 SP - 102 EP - 110 N2 - Diffusion-weighted images are inherently very sensitive to motion. Pulsatile motion of the brain can give rise to artifactual signal attenuation leading to over-estimation of the apparent diffusion coefficients, even with snapshot echo planar imaging. Such miscalculations can result in erroneous estimates of the principal diffusion directions. Cardiac gating can be performed to confine acquisition to the quiet portion of the cycle. Although effective, this approach leads to significantly longer acquisition times. On the other hand, it has been demonstrated that pulsatile motion is not significant in regions above the corpus callosum. To reduce acquisition times and improve the efficiency of whole brain cardiac-gated acquisitions, the upper slices of the brain can be imaged during systole, reserving diastole for those slices most affected by pulsatile motion. The merits and disadvantages of this optimized approach are investigated here, in comparison to a more standard gating method and to the non-gated approach. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16112886&query_hl=1 ER - TY - JFULL T1 - Matrix description of general motion correction applied to multishot images. A1 - Batchelor, PG A1 - Atkinson, D A1 - Irarrazaval, P A1 - Hill, DL A1 - Hajnal, J A1 - Larkman, D J1 - Magn Reson Med Y1 - 2005/11// VL - 54 SN - 0740-3194 SP - 1273 EP - 1280 N2 - Motion of an object degrades MR images, as the acquisition is time-dependent, and thus k-space is inconsistently sampled. This causes ghosts. Current motion correction methods make restrictive assumptions on the type of motions, for example, that it is a translation or rotation, and use special properties of k-space for these transformations. Such methods, however, cannot be generalized easily to nonrigid types of motions, and even rotations in multiple shots can be a problem. Here, a method is presented that can handle general nonrigid motion models. A general matrix equation gives the corrupted image from the ideal object. Thus, inversion of this system allows us to get the ideal image from the corrupted one. This inversion is possible by efficient methods mixing Fourier transforms with the conjugate gradient method. A faster but empirical inversion is discussed as well as methods to determine the motion. Simulated three-dimensional affine data and two-dimensional pulsation data and in vivo nonrigid data are used for demonstration. All examples are multishot images where the object moves between shots. The results indicate that it is now possible to correct for nonrigid types of motion that are representative of many types of patient motion, although computation times remain an issue. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16155887&query_hl=1 ER - TY - JFULL T1 - ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. A1 - Speck, C A1 - Chen, Z A1 - Li, H A1 - Stillman, B J1 - Nat Struct Mol Biol Y1 - 2005/11// VL - 12 SN - 1545-9993 SP - 965 EP - 971 N2 - Binding of Cdc6 to the origin recognition complex (ORC) is a key step in the assembly of a pre-replication complex (pre-RC) at origins of DNA replication. ORC recognizes specific origin DNA sequences in an ATP-dependent manner. Here we demonstrate cooperative binding of Saccharomyces cerevisiae Cdc6 to ORC on DNA in an ATP-dependent manner, which induces a change in the pattern of origin binding that requires the Orc1 ATPase. The reaction is blocked by specific origin mutations that do not interfere with the interaction between ORC and DNA. Single-particle reconstruction of electron microscopic images shows that the ORC-Cdc6 complex forms a ring-shaped structure with dimensions similar to those of the ring-shaped MCM helicase. The ORC-Cdc6 structure is predicted to contain six AAA+ subunits, analogous to other ATP-dependent protein machines. We suggest that Cdc6 and origin DNA activate a molecular switch in ORC that contributes to pre-RC assembly. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16228006&query_hl=1 ER - TY - JFULL T1 - Functional intrinsic and extrinsic apoptotic pathways in human fetal mesenchymal stem cells. A1 - Kennea, NL A1 - Stratou, C A1 - Naparus, A A1 - Fisk, NM A1 - Mehmet, H J1 - Cell Death Differ Y1 - 2005/11// VL - 12 SN - 1350-9047 SP - 1439 EP - 1441 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15962008&query_hl=1 ER - TY - JFULL T1 - The role of enhancers as centres for general transcription factor recruitment. A1 - Szutorisz, H A1 - Dillon, N A1 - Tora, L J1 - Trends Biochem Sci Y1 - 2005/11// VL - 30 SN - 0968-0004 SP - 593 EP - 599 N2 - Activation of eukaryotic genes requires a tight temporal control of trans-acting-factor binding to different types of sequence elements. General transcription factors (GTFs) have a central role in the regulation of RNA polymerase II (Pol II) function because they are involved in the initiation of transcription at all class II promoters. Recent studies have shown that GTFs and Pol II are recruited to enhancer elements and that this binding is an early event in gene activation. We propose that an important role of some enhancers is to function as nucleation centres for the assembly of the pre-initiation complex to regulate the timing of gene activation during development, differentiation and the cell cycle. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16126390&query_hl=1 ER - TY - JFULL T1 - The reorganisation of constitutive heterochromatin in differentiating muscle requires HDAC activity. A1 - Terranova, R A1 - Sauer, S A1 - Merkenschlager, M A1 - Fisher, AG J1 - Exp Cell Res Y1 - 2005/11/01/ VL - 310 SN - 0014-4827 SP - 344 EP - 356 N2 - Constitutive heterochromatin was once thought to be remarkably stable in composition and transcriptionally inert, but has recently been shown to be surprisingly dynamic. Here, we show that terminal muscle differentiation results in a global reorganisation and spatial clustering of constitutive heterochromatin. This is accompanied by enhanced histone H3K9 and H4K20 tri-methylation across major satellite regions and increased levels of major and minor satellite-encoded transcripts. Histone deacetylase (HDAC) activity is known to be important for initiating muscle differentiation. However, here, we show that low doses of HDAC inhibitors applied after the onset of muscle differentiation prevent the spatial reorganisation of constitutive heterochromatin while allowing terminal differentiation to proceed. Under these conditions, HDAC inhibition interferes with histone methylation and blocks centromere clustering, but does not prevent the temporal expression of muscle regulatory factors or the accumulation of centromere-derived transcripts. The demonstration that HDAC activity is required for spatial relocation of centromeres in differentiating muscle provides a convenient system in which the molecular drivers of differentiation-induced chromosome repositioning can be dissected. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16182285&query_hl=1 ER - TY - JFULL T1 - First evidence that one or more rare genetic polymorphisms with high penetrance may be involved in the aetiology of endometriosis A1 - Zondervan, KT A1 - Lin, J A1 - Dawson, G A1 - Zabaneh, D A1 - Smith, V A1 - Bennett, S A1 - Lambert, A A1 - Carey, A A1 - Weeks, DE A1 - Treloar, SA A1 - Montgomery, GW A1 - Nyholt, DR A1 - Martin, NG A1 - Cardon, LR A1 - MacKay, I A1 - Mangion, J A1 - Kennedy, SH J1 - GENET EPIDEMIOL Y1 - 2005/11// VL - 29 SN - 0741-0395 SP - 292 EP - 292 ER - TY - JFULL T1 - Global hypomethylation of the genome in XX embryonic stem cells. A1 - Zvetkova, I A1 - Apedaile, A A1 - Ramsahoye, B A1 - Mermoud, JE A1 - Crompton, LA A1 - John, R A1 - Feil, R A1 - Brockdorff, N J1 - Nat Genet Y1 - 2005/11// VL - 37 SN - 1061-4036 SP - 1274 EP - 1279 N2 - Embryonic stem (ES) cells are important tools in the study of gene function and may also become important in cell therapy applications. Establishment of stable XX ES cell lines from mouse blastocysts is relatively problematic owing to frequent loss of one of the two X chromosomes. Here we show that DNA methylation is globally reduced in XX ES cell lines and that this is attributable to the presence of two active X chromosomes. Hypomethylation affects both repetitive and unique sequences, the latter including differentially methylated regions that regulate expression of parentally imprinted genes. Methylation of differentially methylated regions can be restored coincident with elimination of an X chromosome in early-passage parthenogenetic ES cells, suggesting that selection against loss of methylation may provide the basis for X-chromosome instability. Finally, we show that hypomethylation is associated with reduced levels of the de novo DNA methyltransferases Dnmt3a and Dnmt3b and that ectopic expression of these factors restores global methylation levels. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16244654&query_hl=1 ER - TY - JFULL T1 - Drug resistance in cancer. A1 - Yagüe, E A1 - Raguz, S J1 - Br J Cancer Y1 - 2005/10/31/ VL - 93 SN - 0007-0920 SP - 973 EP - 976 N2 - Cancer Research UK has recently sponsored a meeting, organized by the UK Medical Research Council, on cancer drug resistance. Several of the molecular mechanisms responsible for this clinical outcome, such as DNA interstrand crosslink repair, apoptosis evasion, cytochrome P450 and P-glycoprotein, were discussed. There was a special focus on leukaemia, breast and ovarian cancer, and the potential use of positron-emission tomography to study anticancer-drug resistance. The progress made in translating these findings to the clinic, like Gefitinib, P-glycoprotein phenotyping, or genome-wide analysis technology, was also discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16234820&query_hl=1 ER - TY - JFULL T1 - Coronary microcirculatory function in hypertensive patients with left ventricular hypertrophy is inversely related to systolic blood pressure A1 - Camici, PG A1 - Rosen, SD A1 - Wilkins, M A1 - Rimoldi, OE J1 - CIRCULATION Y1 - 2005/10/25/ VL - 112 SN - 0009-7322 SP - U532 EP - U533 ER - TY - JFULL T1 - Systemic administration of NG-Monomethyl-1-Arginine in addition to adenosine improves maximum myocardial blood flow in territories subtended by stenotic coronaries A1 - Kaufmann, PA A1 - Rimoldi, OE A1 - Gnecchi-Ruscone, T A1 - Luscher, TF A1 - Camici, PG J1 - CIRCULATION Y1 - 2005/10/25/ VL - 112 SN - 0009-7322 SP - U781 EP - U782 ER - TY - JFULL T1 - Absolute quantification of subendocardial and subepicardial blood flow using oxygen-15 labeled water and positron emission tomography A1 - Rimoldi, OE A1 - Schafers, KP A1 - Turkheimer, F A1 - Law, MP A1 - Lammertsma, AA A1 - Camici, PG J1 - CIRCULATION Y1 - 2005/10/25/ VL - 112 SN - 0009-7322 SP - U825 EP - U826 ER - TY - JFULL T1 - A comparison of MR cholangiopancreatography at 1.5 and 3.0 Tesla. A1 - O'Regan, DP A1 - Fitzgerald, J A1 - Allsop, J A1 - Gibson, D A1 - Larkman, DJ A1 - Cokkinos, D A1 - Hajnal, JV A1 - Schmitz, SA J1 - Br J Radiol Y1 - 2005/10// VL - 78 SN - 0007-1285 SP - 894 EP - 898 N2 - Clinical MR systems operating at 3.0 Tesla have the potential to significantly improve spatial resolution due to the boost in intrinsic signal to noise ratio. However, body imaging at these field strengths presents a number of technical challenges. We performed a prospective pilot study in which 10 patients underwent an MR cholangiopancreatography (MRCP) examination consecutively on 1.5 and 3.0 Tesla systems (both Philips Intera). An axial half Fourier segmented turbo spin echo (HASTE) sequence and a coronal thick-slab 2D turbo-spin echo (TSE) sequence were compared on both systems. A reader measured the signal intensity (SI) ratios of common bile duct (CBD): liver, and CBD: fat on HASTE images and CBD: liver on the TSE images. A second reader performed a qualitative analysis of the intrahepatic and extrahepatic biliary anatomy. Quantitative data was compared using the paired t-test and qualitative data with the paired Wilcoxon signed rank test with p < 0.05. The quantitative analysis of the HASTE sequences showed a slightly higher signal intensity ratio (CBD:liver) at 3.0 Tesla compared with 1.5 Tesla (8.1 vs 5.6, p = 0.002). No significant difference was found between the SI ratios of (CBD:fat) on HASTE images or (CBD:liver) on TSE images. The qualitative analysis showed superior image quality of 3.0 Tesla over 1.5 Tesla images on both HASTE (31 vs 25, p = 0.032), and TSE sequences (34 vs 28, p = 0.043). This pilot study shows that MRCP is feasible at 3.0 Tesla with some improvement in image quality and signal characteristics. Further development may be achieved with sequence optimization and improved coil design. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16177011&query_hl=1 ER - TY - JFULL T1 - ABCA1 mRNA expression correlates with MMP-9 expression in atherosclerotic tissues A1 - Soumian, S A1 - Albrecht, C A1 - Sardini, A A1 - Davies, AH A1 - Gibbs, RJ J1 - BRIT J SURG Y1 - 2005/10// VL - 92 SN - 0007-1323 SP - 1303 EP - 1303 ER - TY - JFULL T1 - The internal capsule in neonatal imaging. A1 - Cowan, FM A1 - de Vries, LS J1 - Semin Fetal Neonatal Med Y1 - 2005/10// VL - 10 SN - 1744-165X SP - 461 EP - 474 N2 - The internal capsule is highly visible on conventional magnetic resonance imaging (MRI). It is myelinating rapidly at term, and the time course of its maturation is well known. It carries the major motor and sensory pathways to and from the cortex and the spinal cord. Additionally, fibres from the thalamus pass through it connecting to most regions of the cortex. It is therefore of vital importance, and damage to it has severe consequences. Its abnormal appearance on conventional MRI is a good predictor of an abnormal motor outcome in different clinical situations encountered in perinatal medicine. Its normal appearance on conventional MR images at term age is usually associated with a relatively normal motor outcome. More recently, diffusion-weighted and diffusion tensor imaging have allowed a much more sophisticated assessment of its maturation and connectivity; this has already led to a better understanding of how its development is affected by preterm birth and by hypoxic-ischaemic brain injury. Future studies will assess the relevance of these findings not only for motor outcome but also for cognitive, visual and sensory abilities. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16002354&query_hl=1 ER - TY - JFULL T1 - Recent advances in imaging the fetus and newborn. A1 - Cowan, FM A1 - Rutherford, M J1 - Semin Fetal Neonatal Med Y1 - 2005/10// VL - 10 SN - 1744-165X SP - 401 EP - 402 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15996540&query_hl=1 ER - TY - JFULL T1 - A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection. A1 - Forton, DM A1 - Allsop, JM A1 - Cox, IJ A1 - Hamilton, G A1 - Wesnes, K A1 - Thomas, HC A1 - Taylor-Robinson, SD J1 - AIDS Y1 - 2005/10// VL - 19 Suppl 3 SN - 0269-9370 SP - S53 EP - S63 N2 - Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. Although there are a large number of potential explanations for these symptoms, including a history of substance abuse and associated personality types, or the effect of the diagnosis of HCV infection itself, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be wholly attributed to substance abuse, co-existent depression or hepatic encephalopathy. Impairments are predominantly in the domains of attention, concentration and information processing speed. Furthermore, in-vivo cerebral magnetic resonance spectroscopy studies in patients with hepatitis C and normal liver function have reported elevations in cerebral choline-containing compounds and reductions in N-acetyl aspartate, suggesting that a biological mechanism may underlie the cognitive findings. The recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16251829&query_hl=1 ER - TY - JFULL T1 - Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischemic encephalopathy. A1 - Rutherford, MA A1 - Azzopardi, D A1 - Whitelaw, A A1 - Cowan, F A1 - Renowden, S A1 - Edwards, AD A1 - Thoresen, M J1 - Pediatrics Y1 - 2005/10// VL - 116 SN - 1098-4275 SP - 1001 EP - 1006 N2 - Hypothermia induced by whole-body cooling (WBC) and selective head cooling (SHC) both reduce brain injury after hypoxia-ischemia in newborn animals, but it is not known how these treatments affect the incidence or pattern of brain injury in human newborns. To assess this, 14 term infants with hypoxic-ischemic encephalopathy (HIE) treated with SHC, 20 infants with HIE treated with WBC, and 52 noncooled infants with HIE of similar severity were studied with magnetic resonance imaging in the neonatal period. Infants fulfilling strict criteria for HIE were recruited into the study after assessment of an amplitude-integrated electroencephalography (aEEG). Cooling was commenced within 6 hours of birth and continued for 48 to 72 hours. Hypothermia was not associated with unexpected or unusual lesions, and the prevalence of intracranial hemorrhage was similar in all 3 groups. Both modes of hypothermia were associated with a decrease in basal ganglia and thalamic lesions, which are predictive of abnormal outcome. This decrease was significant in infants with a moderate aEEG finding but not in those with a severe aEEG finding. A decrease in the incidence of severe cortical lesions was seen in the infants treated with SHC. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16199715&query_hl=1 ER - TY - JFULL T1 - Multi-protein complexes involved in muscle diseases A1 - Tinsley, CL A1 - Esapa, CT A1 - Benson, MA A1 - Waite, AJ A1 - Locke, M A1 - Blake, DJ J1 - NEUROMUSCULAR DISORD Y1 - 2005/10// VL - 15 SN - 0960-8966 SP - 717 EP - 717 ER - TY - JFULL T1 - Differential brain growth in the infant born preterm: current knowledge and future developments from brain imaging. A1 - Counsell, SJ A1 - Boardman, JP J1 - Semin Fetal Neonatal Med Y1 - 2005/10// VL - 10 SN - 1744-165X SP - 403 EP - 410 N2 - Preterm birth is associated with a high prevalence of neuropsychiatric impairment in childhood and adolescence, but the neural correlates underlying these disorders are not fully understood. Quantitative magnetic resonance imaging techniques have been used to investigate subtle differences in cerebral growth and development among children and adolescents born preterm or with very low birth weight. Diffusion tensor imaging and computer-assisted morphometric techniques (including voxel-based morphometry and deformation-based morphometry) have identified abnormalities in tissue microstructure and cerebral morphology among survivors of preterm birth at different ages, and some of these alterations have specific functional correlates. This chapter reviews the literature reporting differential brain development following preterm birth, with emphasis on the morphological changes that correlate with neuropsychiatric impairment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15993667&query_hl=1 ER - TY - JFULL T1 - Magnetic resonance guidance of thermal ablation. A1 - Gedroyc, WM J1 - Top Magn Reson Imaging Y1 - 2005/10// VL - 16 SN - 0899-3459 SP - 339 EP - 353 N2 - The aim of this study is to describe all aspects of the process of using MR imaging to control thermal ablation procedures and the strengths and weaknesses of the individual thermal ablation modalities in relation to their use in the MR environment. Magnetic resonance thermal sequences, MR scanner configurations, and the different thermal ablation modalities are discussed in the context of how they are commonly used in MR scanners to provide optimal image guidance of therapy. The outcomes of completed research on some of the applications of thermal tissue ablation using MR guidance are described to indicate how these processes may impact patient treatment. At the end of this review, the reader should have an understanding of how MR guidance of thermal ablation may be carried out, in what areas it is currently most used, and were it may develop in the near future. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16924168&query_hl=1 ER - TY - JFULL T1 - Ethyl-EPA in Huntington's disease: A double blind, randomised, placebo controlled trial A1 - Murck, H A1 - Manku, M A1 - Puri, BK A1 - Leavitt, BR A1 - Hayden, MR A1 - Ross, CA A1 - Rosenblatt, A A1 - Greenamyre, JT A1 - Hersch, S A1 - Vaddadi, KS J1 - J NEUROL NEUROSUR PS Y1 - 2005/10// VL - 76 SN - 0022-3050 ER - TY - JFULL T1 - Universal DNA primers amplify bacterial DNA from human fetal membranes and link Fusobacterium nucleatum with prolonged preterm membrane rupture. A1 - Cahill, RJ A1 - Tan, S A1 - Dougan, G A1 - O'Gaora, P A1 - Pickard, D A1 - Kennea, N A1 - Sullivan, MH A1 - Feldman, RG A1 - Edwards, AD J1 - Mol Hum Reprod Y1 - 2005/10// VL - 11 SN - 1360-9947 SP - 761 EP - 766 N2 - A large number of bacterial species have been identified in fetal membranes after preterm labour (PTL) associated with intrauterine infection by microbiological culture. In this study, we have investigated a molecular and bioinformatic approach to organism identification which surmounts the need for specific and diverse microbiological culture conditions required by conventional methods. Samples of fetal membranes were taken from 37 preterm infants, and 6 normal term controls delivered by caesarean section, in which bacteria had been detected by in situ hybridization of 16S ribosomal RNA using a generic probe. Degenerate primers were designed to amplify bacterial 16S ribosomal DNA by PCR and used to amplify bacterial DNA from human fetal membranes. Amplicons were cloned, sequenced and bacteria were identified bioinformatically by comparison of sequences with known bacterial DNA genomes. In situ hybridization using an organism specific probe was then used to confirm the presence of the commonest identified organism in tissue samples. Bacterial DNA amplified from 15/43 samples, all from preterm deliveries, and the bioinformatic approach identified organisms in all cases. Multiple bacteria were identified including Mycoplasma hominis, Pasturella multocida, Pseudomonas PH1, Escherichia coli and Prevotella bivia. The commonest organism Fusobacterium nucleatum was found in 9/15 (60%) of samples. Ten of the 12 samples obtained after prolonged membrane rupture were positive for bacterial DNA, and 7 of these (70%) contained DNA from F. nucleatum. Bacteria from fetal membranes may be identified by molecular and bioinformatic methods. Further work is warranted to investigate the apparent linkage between F. nucleatum, fetal membrane rupture and preterm delivery. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16254004&query_hl=1 ER - TY - JFULL T1 - Advanced MR techniques in the term-born neonate with perinatal brain injury. A1 - Rutherford, MA A1 - Ward, P A1 - Malamatentiou, C J1 - Semin Fetal Neonatal Med Y1 - 2005/10// VL - 10 SN - 1744-165X SP - 445 EP - 4