TY - BOOK T1 - Stem Cells in Obstetrics and Gynaecology A1 - Fisk NM A1 - Itskovitz-Eldor J Y1 - 2004/// PB - Elsevier CY - London N2 - - ER - TY - BOOK T1 - Basic science in obstetrics & gynaecology A1 - de Swiet M Y1 - 2002/// SN - 0-4430-6150-5 N2 - - ER - TY - BOOK T1 - Infection and pregnancy. Proceedings of the 40th RCOG study group on infection and pregnancy A1 - Regan L A1 - Jivraj S Y1 - 2001/// SN - 1-9003-6444-1 N2 - - ER - TY - BOOK T1 - Maternal-Fetal Medicine and Prenatal Diagnosis A1 - Fisk NM A1 - Y1 - 1998/// PB - Rapid Science CY - London N2 - - ER - TY - BOOK T1 - Fetal Therapy: Invasive and Transplacental A1 - Fisk NM A1 - Moise K Y1 - 1997/// PB - Cambridge University Press CY - Cambridge N2 - - ER - TY - CHAP T1 - The uterine junctional zone A1 - Fusi L A1 - Cloke B A1 - Brosens JJ ED - Brosens I T2 - Adenomyosis. Best Practice and Research in Clinical Obstetrics and Gynaecology Y1 - 2006/// M2 - 20 PB - Elsevier CY - Amsterdam SP - 479 N2 - - ER - TY - CHAP T1 - Hydramnios, oligohydramnios A1 - Taylor, MJO A1 - Fisk, NM ED - James, DK Steer, PJ Weiner, CP Gonik, B T2 - High Risk Pregnancy: Management Options Y1 - 2006/// VL - 2nd PB - Elsevier Saunders CY - London and New York SP - 272 EP - 290 N2 - - ER - TY - CHAP T1 - Scientific basis of twin-twin transfusion syndrome A1 - Dennes, WJB A1 - Sullivan, MFH A1 - Fisk, NM ED - Kilby, M Field, D Critchley, H Baker, P T2 - Multiple Pregnancy Y1 - 2006/// PB - RCOG Press CY - London and New York SP - 167 EP - 181 N2 - - ER - TY - CHAP T1 - Developmental stem cell therapy A1 - Chan, J A1 - O'Donoghue, K A1 - Fisk, NM ED - Studd, J Lin Tan, Seang Chervenak, FA T2 - Progress in Obstetrics and Gynaecology Y1 - 2006/// M2 - 17 PB - Churchill Livingstone CY - London and New York SP - 15 EP - 30 N2 - - ER - TY - CHAP T1 - Twin-to-twin transfusion syndrome A1 - Lewi, L A1 - Deprest, J A1 - Dennes, WJB ED - Van Vugt, J Shulman, LP T2 - Prenatal Medicine Y1 - 2006/// PB - Taylor & Francis CY - New York SP - 447 EP - 472 N2 - - ER - TY - CHAP T1 - Human fetal mesenchymal stem cells. A1 - Chan, J A1 - O'Donoghue, K A1 - Fisk, NM ED - Habib, NA Gordon, MY Levicar, N Jiao, L Thomas-Black, G T2 - Stem Cell Repair and Regeneration Y1 - 2005/// PB - Imperial College Press CY - London and New York SP - 99 EP - 116 N2 - - ER - TY - CHAP T1 - Reproductive disorders and pregnancy outcome A1 - Brosens JJ A1 - Fusi L A1 - Pijenborg R A1 - Brosens I ED - Critchley H, Cameron I and Smith S T2 - Implantation and Early Development Y1 - 2005/// M2 - 19 PB - Royal College of Obstetrics and Gynaecology Press CY - London SP - 240 EP - 252 N2 - - ER - TY - CHAP T1 - Management of twin-twin transfusion syndrome. A1 - Taylor, MJO A1 - Fisk, NM ED - Bllickstein, I Keith, LG T2 - Multiple Pregnancy: Epidemiology, Gestation and Perinatal Outcome Y1 - 2005/// VL - 2nd PB - Taylor & Francis CY - London and New York SP - 552 EP - 570 N2 - - ER - TY - CHAP T1 - Fetal analgesia A1 - Fisk, NM ED - Buonocore, G Bellieni, CV T2 - Pain and Brain Damage in Fetus and Newborn Y1 - 2005/// PB - Foxwell & Davies CY - London and New York SP - 41 EP - 46 N2 - - ER - TY - CHAP T1 - Haematology A1 - Irene A G Roberts A1 - Neil A Murray ED - Janet M Rennie T2 - Roberton's Textbook of Neonatology Y1 - 2005/// VL - Fourth edition PB - Elsevier Churchill Livingstone SN - 0 443 07355 4 SP - 739 EP - 772 N2 - - UR - http://www.elsevierhealth.com ER - TY - CHAP T1 - “Cell death (apoptosis) in human blastocysts” A1 - Hardy K A1 - Spanos S A1 - and Becker DL ED - Veeck L; T2 - Atlas of human blastocysts Y1 - 2003/// PB - Parthenon Publishing SP - 185 EP - 202 N2 - - ER - TY - CHAP T1 - Prenatal/perinatal stress and its impact on psychosocial child development A1 - Glover V ED - Tremblay RE, Barr RG, Peters RDeV T2 - Encyclopedia on early childhood development (online) Y1 - 2003/// PB - Centre of Excellence for Early Childhood Development, Montreal, Canada SP - 1 EP - 5 N2 - - UR - http://www.excellence-jeunesenfants.ca/documents/GloverANGxp.pdf ER - TY - CHAP T1 - Human fetal and maternal stress responses A1 - Gitau R A1 - Fisk NM A1 - Glover V T2 - Stress:Neural, endorcrine and molecular studies Y1 - 2002/// SN - 0-4152-7220-3 SP - 215 EP - 217 N2 - - ER - TY - CHAP T1 - Thrombocytopenia in the newborn A1 - Roberts IAG A1 - Murray NA T2 - Platelets Y1 - 2002/// SN - 0-1249-3951-1 SP - 635 EP - 658 N2 - - ER - TY - CHAP T1 - Differential staining of inner and outer cells to assess mammalian embryo quality A1 - Van Soom A A1 - Boerjan M A1 - Hardy K T2 - Assessment of mammalian embryo quality: invasive and non-invasive techniques Y1 - 2002/// M2 - 11 SN - 1-4020-0581-4 SP - 237 EP - 266 N2 - - ER - TY - CHAP T1 - Thrombocytopenia in the newborn A1 - Roberts IAG A1 - Murray NA T2 - Platelets Y1 - 2002/// SN - 0-1249-3951-1 SP - 635 EP - 658 N2 - - UR - http://NULL ER - TY - CHAP T1 - The menstrual cycle A1 - Smith SK ED - Glasser SR, Aplin JD, Giudice LC & Tabibzadeh S T2 - The endometrium Y1 - 2002/// PB - Taylor & Francis CY - London, UK SP - 73 EP - 85 N2 - - ER - TY - CHAP T1 - Anaemia in newborns, infants and children A1 - Roberts I A1 - Vassilou G T2 - Essential Paediatric Haematology Y1 - 2002/// SN - 9-0582-3179-8 SP - 65 EP - 91 N2 - - ER - TY - CHAP T1 - The oocyte as a machine A1 - Hardy K T2 - Assisted reproductive technology: accomplishments and new horizons Y1 - 2002/// M2 - 5 SN - 0-5218-0121-4 SP - 70 EP - 80 N2 - - ER - TY - CHAP T1 - Recurrent miscarriage A1 - Clifford K A1 - Regan L T2 - Obstetrics & Gynaecology: clinical and basic science aspects Y1 - 2002/// SN - 1-8609-4276-8 SP - 64 EP - 69 N2 - - ER - TY - CHAP T1 - Human fetal and maternal stress responses A1 - Gitau R A1 - Fisk NM A1 - Glover V T2 - Stress:Neural, endorcrine and molecular studies Y1 - 2002/// SN - 0-4152-7220-3 SP - 215 EP - 217 N2 - - ER - TY - CHAP T1 - Angiogenesis and reproduction A1 - Smith S ED - Fauser B T2 - Reproductive medicine: Molecular, cellular and genetic fundamentals Y1 - 2002/// PB - Parthenon Publishing SP - 119 EP - 136 N2 - - ER - TY - CHAP T1 - Apoptosis in mammalian embryos A1 - Hardy K A1 - Spanos S T2 - Assessment of mammalian embryo quality: invasive and non-invasive techniques Y1 - 2002/// M2 - 12 SN - 1-4020-0581-4 SP - 267 EP - 293 N2 - - ER - TY - CHAP T1 - Caesarean sections for all patients? A1 - Fisk NM T2 - The 3rd world congress on controversies in obstetrics gynaecology and infertility Y1 - 2002/// SN - 8-8323-2620-5 SP - 111 EP - 115 N2 - - ER - TY - CHAP T1 - Principles of molecular biology and the application of the Human Genome Project A1 - Smith SK A1 - Charnock-Jones DS ED - Shaw RW, Soutter WP & Stanton SL T2 - Gynaecology Third Edition Y1 - 2002/// PB - Churchill Livingstone CY - London, UK SP - 179 EP - 185 N2 - - ER - TY - CHAP T1 - Selective expansion of fetal mesenchymal stem cells over maternal cells for non-invasive prenatal diagnosis A1 - O'Donoghue K A1 - Campagnoli C A1 - Choolani M A1 - Kumar S A1 - Roberts IAG A1 - Bennett PR A1 - Fisk NM T2 - Early prenatal diagnosis,fetal cells and DNA in the mother. Present state and perspectives Y1 - 2002/// SN - 8-0246-0397-7 SP - 87 EP - 95 N2 - - ER - TY - CHAP T1 - Selevtive expansion of fetal mesenchymal stem cells over maternal cells for non-invasive prenatal diagnosis A1 - O'Donoghue K A1 - Campagnoli C A1 - Choolani M A1 - Kumar S A1 - Roberts IAG A1 - Bennett PR A1 - Fisk NM T2 - Early prenatal diagnosis,fetal cells and DNA in the mother. Present state and perspectives Y1 - 2002/// SN - 8-0246-0397-7 SP - 87 EP - 95 N2 - - ER - TY - CHAP T1 - Angiogenesis and implantation A1 - Smith SK ED - Lessey B T2 - Infertility and reproductive medicine clinics of North America Y1 - 2001/// PB - W B Saunders Company CY - Philadelphia, USA SP - 301 EP - 314 N2 - - ER - TY - CHAP T1 - Caesarean section for everyone? A1 - Fisk NM Y1 - 2001/// SN - 3-8959-9308-5 SP - 29 EP - 30 N2 - - ER - TY - CHAP T1 - Prenatal screening A1 - Fisk NM Y1 - 2001/// SN - 1-8531-5480-6 SP - 103 EP - 142 N2 - - ER - TY - CHAP T1 - Fetal growth restriction:small for gestational age A1 - Fisk NM A1 - Smith RP Y1 - 2001/// M2 - 3rd SN - 0-4430-6365-6 SP - 197 EP - 209 N2 - - ER - TY - CHAP T1 - Sporadic and recurrent miscarriage A1 - Regan L A1 - Clifford K Y1 - 2001/// SN - 0-4430-6365-6 SP - 117 EP - 128 N2 - - ER - TY - CHAP T1 - Infection and pregnancy loss A1 - Regan L A1 - Jivraj S Y1 - 2001/// SN - 1-9003-6444-1 SP - 291 EP - 304 N2 - - ER - TY - CHAP T1 - Pituitary gonadotropins and their disorders A1 - Bremner WJ A1 - Huhtaniemi I A1 - Amory JK ED - KL Becker T2 - Principles and Practice of Endocrinology and Metabolism Y1 - 2001/// VL - 3rd Edition PB - Lippincott, Williams & Wilkins CY - Philadelphia SP - 170 EP - 177 N2 - - ER - TY - CHAP T1 - Apoptosis in the human blastocyst:role of survival factors A1 - Hardy K A1 - Spanos S Y1 - 2001/// SN - 0-3879-5245-4 SP - 144 EP - 154 N2 - - ER - TY - CHAP T1 - Obstetrics, fetal and paediatric A1 - Roberts I A1 - McCloy M Y1 - 2001/// SN - 0-6320-5114-0 SP - 87 EP - 107 N2 - - ER - TY - CHAP T1 - Placental vascular morphogenesis: Introduction and overview A1 - Charnock-Jones DS A1 - Smith SK ED - Augustin HG, Iruela-Arispe ML, Rogers PAW & Smith SK T2 - Vascular morphogenesis in the female reproductive system Y1 - 2001/// PB - Birkhauser CY - Boston, USA SP - 273 EP - 284 N2 - - ER - TY - CHAP T1 - Liver disease in pregnancy A1 - Williamson C A1 - Nelson-Piercy C Y1 - 2001/// M2 - 3rd SN - 1-8564-2193-7 SP - 129 EP - 138 N2 - - ER - TY - CHAP T1 - Using AMCA to label the fetal cell antigen in fetal erythroblasts circumvents heme autofluorescence, enhances cFISH hybridisation efficiency and improves specificity of fetal cell identification A1 - Choolani M A1 - O'Donnell H A1 - Campagnoli C A1 - Kumar S A1 - Bennett P A1 - Fisk NM Y1 - 2001/// SN - 3-8055-7222-0 SP - 74 EP - 81 N2 - - ER - TY - CHAP T1 - Using AMCA to label the fetal cell antigen in fetal erythroblasts circumvents heme autofluorescence, enhances cFISH hybridisation efficiency and improves specificity of fetal cell identification A1 - Choolani M A1 - O'Donnell H A1 - Campagnoli C A1 - Kumar S A1 - Bennett P A1 - Fisk NM Y1 - 2001/// SN - 3-8055-7222-0 SP - 74 EP - 81 N2 - - ER - TY - CHAP T1 - Medical disorders in pregnancy A1 - Nelson-Piercy C A1 - Williamson C Y1 - 2001/// M2 - 3rd SN - 0-4430-6365-6 SP - 275 EP - 297 N2 - - ER - TY - CHAP T1 - Kivekset (The testes) A1 - Huhtaniemi I A1 - Valimaki M ED - M Valimaki, T Sane & L Dunkel T2 - Endokrinologia (Endocrinology) Y1 - 2000/// PB - Duodecim CY - Helsinki, Finland SP - 359 EP - 398 N2 - - ER - TY - CHAP T1 - Gonadotropin receptor mutations A1 - Huhtaniemi I ED - S Melmed T2 - Hormone Action: Basic and Clinical Aspects Y1 - 2000/// PB - BioScientifica Ltd CY - Bristol SP - 131 EP - 144 N2 - - ER - TY - CHAP T1 - Endocrine regulation of male reproduction A1 - Huhtaniemi IT ED - C Wang T2 - Male Reproductive Function Y1 - 1999/// PB - Kluwer Academic Publishers CY - Norwell, MA SP - 1 EP - 18 N2 - - ER - TY - CHAP T1 - Paracrine and autocrine control of Leydig cell function A1 - Huhtaniemi I A1 - El-Hefnawy T A1 - Zhang F-P A1 - Markkula M A1 - Toppari J ED - M Rajalakshmi & PD Griffin T2 - Male Contraception: Present and Future Y1 - 1999/// PB - New Age Intl CY - New Delhi SP - 63 EP - 85 N2 - - ER - TY - CHAP T1 - Gonadotropin receptors A1 - Tena-Sempere M A1 - Huhtaniemi IT ED - BCMK Fauser, AJ Rutherford, JF Strauss III & A Van Steirteghem T2 - Molecular biology in reproductive medicine Y1 - 1999/// PB - Parthenon Publishing CY - New York and Carnforth SP - 165 EP - 200 N2 - - ER - TY - CHAP T1 - Ovarian development: from foetus to adult A1 - Huhtaniemi I ED - R Stanhope T2 - Adolescent Endocrinology Y1 - 1998/// PB - BioScientifica Ltd CY - Bristol SP - 33 EP - 38 N2 - - ER - TY - CHAP T1 - Hormonal regulation of the testis A1 - Huhtaniemi I A1 - Toppari J ED - F Martinez-Garcia & J Regadera T2 - Male Reproduction, a Multidisciplinary Overview Y1 - 1998/// PB - Churchill CY - London SP - 67 EP - 80 N2 - - ER - TY - CHAP T1 - FSH resistance A1 - Aittomaki K A1 - Huhtaniemi I ED - JL Jameson T2 - Contemporary Endocrinology Y1 - 1998/// PB - Humana Press CY - Totowa, NJ SP - 197 EP - 207 N2 - - ER - TY - CHAP T1 - Preterm Labor A1 - Hawkins DF A1 - Fusi L ED - Kurjac T2 - Textbook of Perinatal Medicine II Y1 - 1998/// PB - Pathenon Publishing Group CY - London-New York SP - 1345 EP - 1361 N2 - - ER - TY - CHAP T1 - Inactivating and activating mutations of the FSH receptor gene A1 - Huhtaniemi I ED - AM Spiegel T2 - Contemporary Endicrinology: G Proteins, Receptors and Disease Y1 - 1998/// PB - Humana Press CY - Totowa, NJ SP - 155 EP - 165 N2 - - ER - TY - CHAP T1 - Endocrine regulation of male reproduction A1 - Huhtaniemi I ED - C Wang T2 - Male Reproductive Function Y1 - 1998/// PB - Kluwer Academic Publishers CY - Norwell, MA SP - 1 EP - 18 N2 - - ER - TY - CONF T1 - Preterm labour: Why are we not doing better A1 - Bennett, P U1 - 12th World Congress on Human Reproduction Y1 - 2005/// Y2 - // SP - 464 EP - 464 N2 - - ER - TY - CONF T1 - Molecular biology related to pre-eclampsia A1 - Williamson, C U1 - 15th Congress of Gynaecology, Obstetrics and Reproductive Medicine Y1 - 2005/// Y2 - // VL - 1279 SP - 282 EP - 289 N2 - - ER - TY - CONF T1 - Polymorphisms and male ageing A1 - Jiang, M A1 - Huhtaniemi, I U1 - 2nd Meeting on Endocrine Aspects of Successful Aging Y1 - 2004/// Y2 - // SP - 63 EP - 87 N2 - - ER - TY - CONF T1 - Endocrine regulation of epididymal gene expression A1 - Poutanen, M A1 - Sipila, P A1 - Shariatmadari, R A1 - Pujianto, DA A1 - Jalkanen, J A1 - Huhtaniemi, I U1 - 12th International Congress of Endocrinology Y1 - 2004/// Y2 - // SP - 323 EP - 326 N2 - - ER - TY - CONF T1 - Mutations of gonadotropins and their receptors: Genetic novelty or practical significance? A1 - Huhtaniemi, I U1 - Conference on Updates in Infertility Treatment Y1 - 2004/// Y2 - // SP - 293 EP - 305 N2 - - ER - TY - CONF T1 - Caesarean section for all patients? A1 - Fisk, N U1 - 3rd World Congress on Controversies in Obstetrics, Gynecology and Infertility Y1 - 2002/// Y2 - // SP - 111 EP - 115 N2 - - ER - TY - CONF T1 - Gene-modified animal models for the study of luteinizing hormone and luteinizing hormone receptor function A1 - Zhang, FP A1 - Poutanen, M A1 - Huhtaniemi, I U1 - 12th European Workshop on Molecular and Cellular Endocrinology of the Testis Y1 - 2002/// Y2 - // SP - 85 EP - 97 N2 - - ER - TY - CONF T1 - Functional genomics in reproductive medicine A1 - Smith, SK U1 - 17th World Congress on Fertility and Sterility Y1 - 2002/// Y2 - // SP - 49 EP - 56 N2 - - ER - TY - CONF T1 - Human fetal and maternal stress responses A1 - Gitau, R A1 - Fisk, N A1 - Glover, V U1 - 7th Symposium on Catecholamines and Other Neurotransmitters in Stress Y1 - 2002/// Y2 - // SP - 215 EP - 217 N2 - - ER - TY - CONF T1 - New trends in contraception: men A1 - Huhtaniemi, I U1 - 17th World Congress on Fertility and Sterility Y1 - 2002/// Y2 - // SP - 422 EP - 431 N2 - - ER - TY - CONF T1 - A common genetic variant of luteinizing hormone: physiological and function consequences A1 - Manna PR A1 - Joshi L A1 - Huhtaniemi IT AD - New Delhi, India J1 - Proceedings of International Symposium "Follicular Growth, Ovulation and Fertilizations: Molecular and Clinical Basis" Y1 - 2001/// Y2 - 1999/10// PB - Narosa Publishing House CY - New Delhi SP - 38 EP - 51 N2 - - ER - TY - CONF T1 - Gonadotropin ligand and receptor mutations in disorders of pituitary-gonadal function A1 - Huhtaniemi I U1 - 5th Congress on Control of the Onset of Puberty J1 - Excerpta Medica International Congress Series No. 1202 Y1 - 2000/// SP - 187 EP - 199 N2 - - ER - TY - CONF T1 - Genetic variants of gonadotropins. Syllabus of the Pre-Congress Graduate Course A1 - Huhtaniemi I U1 - 1st European Congress of Andrology AD - d'Avila, Italy J1 - Proceedings Y1 - 2000/// Y2 - 2000/03// SP - 38 EP - 49 N2 - - ER - TY - CONF T1 - Different modes of management for twin twin transfusion syndrome A1 - Fisk, NM U1 - 1st Congress on Controversies in Obstetrics, Gynecology and Infertility Y1 - 1999/// Y2 - // SP - 113 EP - 116 N2 - - ER - TY - CONF T1 - Endometriosis and adenomyosis: a unifying hypothesis A1 - Brosens, JJ A1 - Brosens, I U1 - VIth World Congress on Endometriosis Y1 - 1999/// Y2 - // SP - 11 EP - 16 N2 - - ER - TY - CONF T1 - Caesarean section for all? A1 - Fisk, NM U1 - 1st Congress on Controversies in Obstetrics, Gynecology and Infertility Y1 - 1999/// Y2 - // SP - 217 EP - 219 N2 - - ER - TY - CONF T1 - Growth factors A1 - Smith, SK U1 - 5th International Symposium on GnRH Analogues in Cancer and Human Reproduction Y1 - 1999/// Y2 - // SP - 51 EP - 54 N2 - - ER - TY - CONF T1 - Mutations and polymorphisms in gonadotropin and gonadotropin receptor genes A1 - Huhtaniemi IT U1 - Proceedings of the IV International Congress on Therapy in Andrology J1 - The Human Testis: Its role in Reproduction and Sexuality Y1 - 1999/// PB - Moduzzi Editore CY - Bologna SP - 17 EP - 23 N2 - - ER - TY - CONF T1 - Surgery v pharmacological treatment - Is it stage dependent pharmacology A1 - Smith, SK U1 - 1st Congress on Controversies in Obstetrics, Gynecology and Infertility Y1 - 1999/// Y2 - // SP - 87 EP - 89 N2 - - ER - TY - CONF T1 - Steroid hormone action: modulation of progesterone receptor function in uterine tissues A1 - Brosens, J A1 - Astle, S A1 - Mak, I A1 - White, J U1 - 5th International Symposium on GnRH Analogues in Cancer and Human Reproduction Y1 - 1999/// Y2 - // SP - 33 EP - 49 N2 - - ER - TY - CONF T1 - Follicole-stimulating hormone receptor mutation and fertility A1 - Vaskivuo T A1 - Aittomaki K A1 - Huhtaniemi IT A1 - Tapanainen JS U1 - Proceedings of the European Testic Workshop AD - Capri, Italy Y1 - 1998/03// SP - 295 EP - 306 N2 - - ER - TY - CONF T1 - Cyclooxygenase type-2 selective nonsteroidal anti-inflammatory drugs for inhibition of preterm labor A1 - Slater, DM A1 - Sawdy, R A1 - Dennes, WJB A1 - Allport, V A1 - Bennett, PR U1 - 4th International Congress on Essential Fatty Acids and Eicosanoids Y1 - 1998/// Y2 - // SP - 64 EP - 67 N2 - - ER - TY - CONF T1 - The role of cyclooxygenase-2 in reproduction A1 - Bennett, P A1 - Sawdy, R A1 - Slater, D U1 - William Harvey Research Conference Y1 - 1998/// Y2 - // SP - 171 EP - 183 N2 - - ER - TY - CONF T1 - The indications and patient selection for day case laparoscopic surgery A1 - Smith, S A1 - Darzi, A U1 - 6th World Congress of Endoscopic Surgery Y1 - 1998/// Y2 - // SP - 273 EP - 277 N2 - - ER - TY - CONF T1 - The retroperitoneal approach to laparoscopic colonic surgery A1 - Smith, S A1 - Darzi, A U1 - 6th World Congress of Endoscopic Surgery Y1 - 1998/// Y2 - // SP - 381 EP - 384 N2 - - ER - TY - CONF T1 - Mutations and polymorphisms in the gonadotrophin genes A1 - Huhtaniemi, I A1 - Pettersson, K U1 - Proceedings of the 9th Reinier de Graaf Symposium AD - Nordwilk, Holland Y1 - 1997/// PB - Pathenon Publishing CY - New York SP - 159 EP - 166 N2 - - ER - TY - CONF T1 - Bleeding from an atrophic endometrium A1 - Smith, SK U1 - 8th International Congress on the Menopause Y1 - 1997/// Y2 - // SP - 241 EP - 245 N2 - - ER - TY - CONF T1 - What should a clinical reproductive endocrinologist understand about molecular biology? A1 - Huhtaniemi, I U1 - Synopsis of the 1st Annual ESHRE Winter Training Course in Reproductive Endocrinology AD - Rotterdam Y1 - 1997/01// N2 - - ER - TY - JFULL T1 - The Transcriptional Corepressor RIP140 Regulates Oxidative Metabolism in Skeletal Muscle. A1 - Seth, A A1 - Steel, JH A1 - Nichol, D A1 - Pocock, V A1 - Kumaran, MK A1 - Fritah, A A1 - Mobberley, M A1 - Ryder, TA A1 - Rowlerson, A A1 - Scott, J A1 - Poutanen, M A1 - White, R A1 - Parker, M J1 - Cell Metabolism Y1 - 2007/09// VL - 6 SP - 236 EP - 245 ER - TY - JFULL T1 - Sexual Dimorphism in Superantigen Shock Involves Elevated TNF-{alpha} and TNF-{alpha} induced Hepatic Apoptosis. A1 - Faulkner, L A1 - Altmann, DM A1 - Ellmerich, S A1 - Huhtaniemi, I A1 - Stamp, G A1 - Sriskandan, S J1 - Am J Respir Crit Care Med Y1 - 2007/09/01/ VL - 176 SN - 1073-449X SP - 473 EP - 482 N2 - Rationale: There is conflicting evidence regarding sex differences in the outcome from severe sepsis and toxic shock. Superantigen-mediated toxic shock affects a higher proportion of female patients. Objectives: The objective of the current study was to investigate sexual dimorphism in superantigen-associated sepsis and in superantigen-mediated shock and to identify the key mechanisms responsible for this sex difference. Methods: We measured mortality and serum cytokines after induction of sepsis with isogenic superantigen-positive and superantigen-negative Streptococcus pyogenes in HLA class II transgenics. During superantigen-mediated toxic shock, we measured mortality, T-cell responses, systemic tumor necrosis factor (TNF)-alpha and TNF receptors, TNF-alpha-induced hepatocyte apoptosis, and conditioning of these responses by tamoxifen treatment. Measurements and Main Results: In both superantigen-associated sepsis and in superantigen-mediated shock, serum TNF-alpha was increased in females compared with males. This was not attributable to a detectable difference in splenic TNF-alpha transcription; rather, serum soluble TNF receptors were higher in males. Pretreatment of females with the estrogen receptor modulator tamoxifen increased serum soluble TNF receptors, reduced the early serum TNF-alpha response, and improved mortality in females challenged with staphylococcal enterotoxin B. Lethal superantigen shock was characterized by hepatocyte apoptosis, and was reproduced by injection of TNF-alpha. Females had enhanced susceptibility to TNF-alpha-mediated lethality. TNF-alpha-induced hepatocyte apoptosis was greater in females, and was reduced by tamoxifen pretreatment. Conclusions: Sexual dimorphism in experimental superantigen toxic shock results from increased systemic TNF-alpha in females, coupled with an increased susceptibility to TNF-alpha-induced hepatocyte apoptosis. Both processes are abrogated by estrogen receptor modulators. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17575097&query_hl=1 ER - TY - JFULL T1 - Delay of Postnatal Maturation Sensitizes the Mouse Prostate to Testosterone-Induced Pronounced Hyperplasia: Protective Role of Estrogen Receptor-{beta}. A1 - Savolainen, S A1 - Pakarainen, T A1 - Huhtaniemi, I A1 - Poutanen, M A1 - Mäkelä, S J1 - Am J Pathol Y1 - 2007/09// VL - 171 SN - 0002-9440 SP - 1013 EP - 1022 N2 - The role of estrogens in the etiology of prostate cancer is controversial. To demonstrate the specific effects of estrogens and androgens on the development of the prostatic epithelial hyperplasia, we used luteinizing hormone receptor knockout mice (LuRKO), which are resistant to pituitary regulation mediated by luteinizing hormone, lack postnatal androgen production, and have rudimentary accessory sex glands, the growth of which can be induced with exogenous androgen replacement. This model is thus ideal for the investigation of direct hormonal effects on the prostate. Testosterone, but not 5alpha-dihydrotestosterone, replacement from 21 days of life for 8 weeks induced pronounced hyperplasia and inflammation in the prostates of LuRKO mice. Interestingly, 5alpha-dihydrotestosterone combined with 17beta-estradiol did not induce hyperplasia or inflammation, and treatments with inhibitors of estrogen action, aromatase inhibitor, and ICI 182780 further exacerbated testosterone-induced hyperplastic growth. However, the activation of estrogen receptor (ER)-beta with a specific agonist, DPN [2,3-bis(4-hydroxyphenol)-propionitrile], prevented the development of prostatic hyperplasia and inflammation in testosterone-treated LuRKO mice. Thus, it seems that in the presence of sufficient androgenic stimulation, it is the balance between ER-alpha- and ER-beta-mediated signaling that determines whether estrogens promote hyperplasia or protect the prostate against hyperplastic changes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17640960&query_hl=1 ER - TY - JFULL T1 - Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. A1 - Catalano, RD A1 - Critchley, HO A1 - Heikinheimo, O A1 - Baird, DT A1 - Hapangama, D A1 - Sherwin, JR A1 - Charnock-Jones, DS A1 - Smith, SK A1 - Sharkey, AM J1 - Mol Hum Reprod Y1 - 2007/09// VL - 13 SN - 1360-9947 SP - 641 EP - 654 N2 - In women, a single dose of the antiprogestin mifepristone (RU486) in the secretory phase rapidly renders the endometrium unreceptive and is followed by endometrial breakdown and menstruation within 72 h. This model provides a system to identify progesterone-regulated genes, which may be involved in endometrial receptivity and the induction of menstruation. We used cDNA microarrays to monitor the response of the endometriuim over 24 h following administration of mifepristone in the mid-secretory phase. We identified 571 transcripts whose expression was significantly altered, representing 131 biochemical pathways. These include new progesterone regulated members of the Wnt, matrix metalloproteinase (MMP), prostaglandin (PG) and chemokine regulatory pathways. Transcripts involved in thyroid hormone metabolism and signalling such as type II iodothyronine deiodinase and thyroid receptors were also found to be highly regulated by progesterone antagonism in the endometrium. Transcripts required for thyroid hormone synthesis such as thyroid peroxidase (TPO) and thyroglobulin (TG) were also expressed, indicating that the endometrium may be a site of thyroxin production. These results add to the existing knowledge of the role of the Wnt, chemokine, MMP and PG pathways in receptivity and early menstrual events. They provide in vivo evidence supporting direct or indirect regulation of many new transcripts by progesterone. We have also identified for the first time the very early transcriptional changes in vivo in response to progesterone withdrawal. This greatly increases our understanding of the pathways leading to menstruation and may provide new approaches to diagnose and treat menstrual disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17584828&query_hl=1 ER - TY - JFULL T1 - Does the andropause exist? A1 - Perheentupa, A A1 - Huhtaniemi, I J1 - Nat Clin Pract Endocrinol Metab Y1 - 2007/08/28/ SN - 1745-8374 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17724483&query_hl=1 ER - TY - JFULL T1 - Abnormal Preantral Folliculogenesis in Polycystic Ovaries is Associated with Increased Granulosa Cell Division. A1 - Stubbs, SA A1 - Stark, J A1 - Dilworth, SM A1 - Franks, S A1 - Hardy, K J1 - J Clin Endocrinol Metab Y1 - 2007/08/14/ SN - 0021-972X N2 - Context: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women but its etiology remains obscure. Recent data suggest that an intrinsic abnormality of early follicle development in the ovary is key to the pathogenesis of PCOS. We have recently found that in PCOS the proportion of primordial follicles is decreased with a reciprocal increase in the proportion of primary follicles. Objective: To examine whether the accelerated transition of follicles from primordial to primary stages in polycystic ovaries is due to increased granulosa cell (GC) division. Design: Comparison of expression of minichromosome maintenance protein 2 (MCM2; present in the nuclei of cells which are licensed to divide) in archive tissue from normal and polycystic ovaries. Setting: Laboratory-based study. Patients: 16 women with regular cycles (6 with normal and 10 with polycystic ovaries) and 5 anovulatory women with polycystic ovaries (anovPCO), classified histologically, with reference to menstrual history and ultrasound. Main outcome measure: Presence of MCM2 expression in GCs of 1371 follicles. Results: GC proliferation was increased in anovPCO compared with both normal and ovPCO, with an increased proportion of preantral follicles with MCM2-positive GCs (P t, M1V, W80R, M173T) in ICP. W80R was not present in Caucasians and M1V was detected uniquely in 1 British case. M173T and -1g>t occur both in Caucasian cases and controls, and we found a significant association of M173T with ICP (OR, 3.2; 95% confidence interval, 1.1-11.2; P = .02) when the allele frequencies of both Caucasian cohorts were analyzed together. We demonstrate functional defects in either translation efficiency or activity for 3 of the 4 variants (-1g>t, M1V, M173T). CONCLUSIONS: This is the first report of functional variants in FXR. We propose that these variants may predispose to ICP, and because FXR has a central role in regulating bile and lipid homeostasis they may be associated with other cholestatic and dyslipidemic disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17681172&query_hl=1 ER - TY - JFULL T1 - Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. A1 - Stewart, EA A1 - Gostout, B A1 - Rabinovici, J A1 - Kim, HS A1 - Regan, L A1 - Tempany, CM J1 - Obstet Gynecol Y1 - 2007/08// VL - 110 SN - 0029-7844 SP - 279 EP - 287 N2 - OBJECTIVE: To assess several measures of the long-term outcome of magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata. METHODS: Data on 359 women completing 24-month follow-up in all clinical trials of magnetic resonance-guided focused ultrasound surgery for uterine leiomyomata were analyzed. Quality of life outcomes, measured by the symptom severity score of the Uterine Fibroid Symptoms Quality Of Life Questionnaire were assessed for 24 months after treatment. Clinical endpoints, including uterine shrinkage, the need for additional leiomyoma treatment, and the time to additional leiomyoma treatment, were all assessed. The nonperfused volume ratio after treatment, calculated from the gadolinium-enhanced magnetic resonance imaging after treatment and the best measure of tissue necrosis after treatment, was used to assess outcome based on completeness of leiomyoma ablation. RESULTS: Women undergoing magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata have durable symptom relief, as measured by the symptom severity score at 24 months, with significantly greater improvement with more complete ablation (P<.001). Survival analysis demonstrates a significant reduction in the percentage of women undergoing additional leiomyoma treatment (P=.001) in women in the high nonperfused volume group. The mean shrinkage and mean residual nonperfused volume ratio are both significantly above zero at 6 months in the high nonperfused volume group (P<.001). The incidence of adverse events is low. However, for women with minimal treatment, the risk of additional procedures is high. CONCLUSION: Magnetic resonance-guided focused ultrasound surgery is an effective treatment for uterine leiomyomata and results in sustained symptomatic relief. LEVEL OF EVIDENCE: III. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17666601&query_hl=1 ER - TY - JFULL T1 - Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. A1 - Mak, GK A1 - Enwere, EK A1 - Gregg, C A1 - Pakarainen, T A1 - Poutanen, M A1 - Huhtaniemi, I A1 - Weiss, S J1 - Nat Neurosci Y1 - 2007/08// VL - 10 SN - 1097-6256 SP - 1003 EP - 1011 N2 - The regulation of female reproductive behaviors may involve memories of male pheromone signatures, formed in part by neural circuitry involving the olfactory bulb and hippocampus. These neural structures are the principal sites of adult neurogenesis; however, previous studies point to their independent regulation by sensory and physiological stimuli. Here we report that the pheromones of dominant (but not subordinate) males stimulate neuronal production in both the olfactory bulb and hippocampus of female mice, which are independently mediated by prolactin and luteinizing hormone, respectively. Neurogenesis induced by dominant-male pheromones correlates with a female preference for dominant males over subordinate males, whereas blocking neurogenesis with the mitotic inhibitor cytosine arabinoside eliminated this preference. These results suggest that male pheromones are involved in regulating neurogenesis in both the olfactory bulb and hippocampus, which may be important for female reproductive success. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17603480&query_hl=1 ER - TY - JFULL T1 - Human chorionic gonadotropin (hCG) up-regulates wnt5b and wnt7b in the mammary gland, and hCGbeta transgenic female mice present with mammary Gland tumors exhibiting characteristics of the Wnt/beta-catenin pathway activation. A1 - Kuorelahti, A A1 - Rulli, S A1 - Huhtaniemi, I A1 - Poutanen, M J1 - Endocrinology Y1 - 2007/08// VL - 148 SN - 0013-7227 SP - 3694 EP - 3703 N2 - Transgenic (TG) mice expressing human chorionic gonadotropin (hCG) beta-subunit under the ubiquitin C promoter, presenting with a moderately elevated level of LH/hCG bioactivity develop multiple neoplasms secondary to the endocrine abnormalities, including mammary gland tumors after the age of 9 months. The increased levels of circulating estradiol, progesterone, and prolactin of the TG females after puberty boost the lobuloalveolar development in the mammary gland resulting ultimately in the formation of estrogen and progesterone receptor-negative, malignant tumors. These tumors have a similar histopathology with those observed in TG mice with activated wnt/beta-catenin pathway, showing increased expression of beta-catenin, also a common finding in human breast tumors. Transdifferentiation is observed in mammary tumors of the hCGbeta TG mice, accompanied by abnormal expression of the Wnt genes in the tumorous and nontumorous mammary gland tissue. Specifically we found increased expression of Wnt5b in the TG mammary glands at the age of 3 months and up-regulation of Wnt7b and -5b in the subsequently appearing tumors. Importantly, hCG was found to up-regulate these wnt ligands in mouse mammary gland, independent of the changes in ovarian steroidogenesis. Thus, the hCGbeta-overexpressing TG mice represent a novel model that links enhanced hCG action to dysregulated wnt signaling in the mammary gland, resulting in beta-catenin-stabilizing mammary tumorigenesis. The novel finding of hCG up-regulating wnt7b and wnt5b could contribute to pregnancy-induced breast cancer in humans. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17510243&query_hl=1 ER - TY - JFULL T1 - Role and Regulation of the Serum and Glucocorticoid Regulated Kinase 1 in Fertile and Infertile Human Endometrium. A1 - Feroze-Zaidi, F A1 - Fusi, L A1 - Takano, M A1 - Higham, J A1 - Salker, MS A1 - Goto, T A1 - Edassery, S A1 - Klingel, K A1 - Boini, KM A1 - Palmada, M A1 - Kamps, R A1 - Groothuis, PG A1 - Lam, EW A1 - Smith, SK A1 - Lang, F A1 - Sharkey, AM A1 - Brosens, JJ J1 - Endocrinology Y1 - 2007/07/19/ SN - 0013-7227 N2 - Using cDNA microarray analysis, we identified SGK1 (serum and glucocorticoid regulated kinase 1) as a gene aberrantly expressed in mid-secretory endometrium of women with unexplained infertility. SGK1 is a serine/threonine kinase involved primarily in epithelial ion transport and cell survival responses. Real-time quantitative PCR analysis of a larger, independent sample set timed to coincide with the period of uterine receptivity confirmed increased expression of SGK1 transcripts in infertile women compared to fertile controls. We further demonstrate that SGK1 expression is regulated by progesterone in human endometrium in vivo as well as in explant cultures. During the mid-secretory phase of the cycle, SGK1 mRNA and protein were predominantly but not exclusively expressed in the luminal epithelium and expression in this cellular compartment was higher in infertile women. In the stromal compartment, SGK1 expression was largely confined to decidualizing cells adjacent to the luminal epithelium. In primary culture, SGK1 was induced and phosphorylated upon decidualization of endometrial stromal cells in response to 8-bromo-cAMP and progestin treatment. Moreover, overexpression of SGK1 in decidualizing cells enhanced phosphorylation and cytoplasmic translocation of the forkhead transcription factor FOXO1 and inhibited the expression of PRL, a major decidual marker gene. Conversely, knockdown of endogenous SGK1 by small interfering RNA increased nuclear FOXO1 levels and enhanced PRL expression. The observation that SGK1 targets FOXO1 in differentiating human endometrium, together with its distinct temporal and spatial expression pattern and increased expression in infertile patients, suggest a major role for this kinase in early pregnancy events. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17640988&query_hl=1 ER - TY - JFULL T1 - Amniotic fluid testosterone: relationship with cortisol and gestational age. A1 - Sarkar, P A1 - Bergman, K A1 - Fisk, NM A1 - O'connor, TG A1 - Glover, V J1 - Clin Endocrinol (Oxf) Y1 - 2007/07/18/ SN - 0300-0664 N2 - Introduction Foetal exposure to testosterone is increasingly implicated in the programming of future reproductive and nonreproductive behaviour. Some outcomes associated with prenatal exposure to testosterone may be predicted from exposure to prenatal stress, suggesting a link between them. The peak serum levels of testosterone in the foetus are thought to be around 14-18 weeks' gestation, and we explored testosterone levels at different gestations. Although best investigated in foetal plasma, this is now difficult because of the decline in frequency of foetal blood sampling; in this study, we used amniotic fluid as a biomarker to investigate foetal exposure. Aims To investigate the relationship between amniotic fluid testosterone, amniotic fluid cortisol, foetal gender, and gestational age. Methods Paired amniotic fluid and maternal plasma samples were collected from 264 pregnant women undergoing amniocentesis between 15 and 37 weeks' gestation (median 17 weeks [119 days]). Total testosterone and cortisol in amniotic fluid, and total plasma testosterone (maternal) were measured by radioimmunoassay. Results Amniotic fluid testosterone levels were higher in male than in female foetuses, with a median (interquartile range) of 0.85 nmol/l (0.60-1.17 nmol/l) and 0.28 nmol/l (0.175-0.45 nmol/l), respectively. No relationship between amniotic fluid testosterone and gestational age was detected in either sex. Amniotic fluid testosterone correlated positively with amniotic fluid cortisol in both sexes (r = 0.30 male foetuses, r = 0.33 female foetuses, P < 0.001 for both), and remained significant in multivariate analysis. Conclusion Testosterone in amniotic fluid did not change with gestation in the second and third trimester, raising questions about the timing of the reported early peak in the male foetus. The positive correlation between cortisol and testosterone in amniotic fluid suggests that increased foetal exposure to cortisol may also be associated with increased exposure to testosterone. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17634075&query_hl=1 ER - TY - JFULL T1 - Effect of bisphenol A on human chorionic gonadotrophin-stimulated gene expression of cultured mouse Leydig tumour cells. A1 - Takamiya, M A1 - Lambard, S A1 - Huhtaniemi, IT J1 - Reprod Toxicol Y1 - 2007/07/10/ SN - 0890-6238 N2 - Endocrine disrupting chemicals (EDCs) have been reported to affect the reproductive system of various animal species. However, their specific effects and modes of action on gonadal function remain largely unclear. We studied the effects of a model EDC, bisphenol A (BPA), on human chorionic gonadotrophin (hCG)-stimulated global gene expression of cultured mouse Leydig tumour cells (mLTC-1). The time and dose of BPA exposure were set after semiquantitative (sq) RT-PCR analysis of response of candidate genes (StAR, Cyp17a1 and AR) to 3h at 10mug/l hCG+/-10(-5)M BPA. Affymetrix microarray analysis demonstrated >/=1.5-fold up-regulation of 8- and 10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy. ER - TY - JFULL T1 - A meta-analysis on the influence of inflammatory bowel disease on pregnancy. A1 - Cornish, J A1 - Tan, E A1 - Teare, J A1 - Teoh, TG A1 - Rai, R A1 - Clark, SK A1 - Tekkis, PP J1 - Gut Y1 - 2007/06// VL - 56 SN - 0017-5749 SP - 830 EP - 837 N2 - BACKGROUND: Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management. AIM: To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD. DESIGN: The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls. Patients and SETTING: A total of 3907 patients with IBD (Crohn's disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria. RESULTS: For women with IBD, there was a 1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52 to 2.31; p<0.001) compared with controls. The incidence of low birth weight (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). CONCLUSION: The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17185356&query_hl=1 ER - TY - JFULL T1 - Endometriosis is associated with a decreased risk of pre-eclampsia. A1 - Brosens, IA A1 - De Sutter, P A1 - Hamerlynck, T A1 - Imeraj, L A1 - Yao, Z A1 - Cloke, B A1 - Brosens, JJ A1 - Dhont, M J1 - Hum Reprod Y1 - 2007/06// VL - 22 SN - 0268-1161 SP - 1725 EP - 1729 N2 - BACKGROUND: We postulated that impaired endometrial differentiation in women with pelvic endometriosis predisposes for pre-eclampsia. METHODS: A retrospective case-control study set at the University of Ghent IVF centre. The incidence of pre-eclampsia and pregnancy-induced hypertension (PIH) following the clinical and/or laparoscopic diagnosis of endometriosis-associated infertility (case group; n = 245 pregnancies) was compared with the incidence of these obstetric complications in pregnancies following treatment for male-factor infertility (control group; n = 274 pregnancies). Pregnancy data were obtained by searching electronic databases and postal questionnaires. The case and control groups were matched for age, parity and multiple pregnancies. RESULTS: The incidence of pre-eclampsia was significantly lower in the case group (0.8%) when compared with control group (5.8%) (P = 0.002; odds ratio (OR) = 7.5, 95% confidence interval (CI): 1.7-33.3). Analysis of obstetric outcome in the subgroup of patients with laparoscopic data confirmed the lower risk of pre-eclampsia in the case (1.2%) versus control (7.4%) groups (P = 0.032; OR = 6.6, 95% CI: 1.2-37). PIH occurred in 3.5% and 8.7% of case and control pregnancies, respectively (P = 0.018; OR = 2.6, 95% CI: 1.2-6.0). The odds of developing pre-eclampsia were 5.67 times higher in the control group than in pregnancies following endometriosis-associated infertility. In multiple pregnancies, the odds of developing pre-eclampsia increased 1.93 times per additional child, with or without endometriosis. CONCLUSIONS: We found no evidence that endometriosis predisposes for pre-eclampsia. Instead, the risk of hypertensive disorder in pregnancy is significantly reduced in women with endometriosis-associated infertility. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17452394&query_hl=1 ER - TY - JFULL T1 - The oestrogen metabolite 2-methoxyoestradiol alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand mediates apoptosis in cancerous but not healthy cells of the human endometrium. A1 - Kato, S A1 - Sadarangani, A A1 - Lange, S A1 - Villalón, M A1 - Brañes, J A1 - Brosens, JJ A1 - Owen, GI A1 - Cuello, M J1 - Endocr Relat Cancer Y1 - 2007/06// VL - 14 SN - 1351-0088 SP - 351 EP - 368 N2 - Cancers of the reproductive tract account for 12% of all malignancies in women. As previous studies have shown that oestrogen metabolites can cause apoptosis, we characterised the effect of oestrogen and oestrogen metabolites on non-cancerous and cancerous human endometrial cells. Herein, we demonstrate that 2-methoxyoestradiol (2ME), but not 17beta-oestradiol, induces apoptosis in cancer cell lines and primary cultured tumours of endometrial origin. In contrast, 2ME had no effect on cell viability of corresponding normal tissue. This ability of 2ME to induce apoptosis does not require oestrogen receptor activation, but is associated with increased entry into the G2/M phases of the cell cycle and the activation of both the intrinsic and the extrinsic apoptotic pathways. The selective behaviour of 2ME on cancerous as opposed to normal tissue may be due to a reduction in 17beta-hydroxysteroid dehydrogenase type II levels in cancer cells and to a differential down-regulation of superoxide dismutase. Furthermore, we demonstrate that pre-treatment with 2ME enhances the sensitivity of reproductive tract cancer cells to the apoptotic drug tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), without the loss in cell viability to normal cells incurred by currently chemotherapeutic drugs. In conclusion, 2ME, alone or in combination with TRAIL, may be an effective treatment for cancers of uterine origin with minimal toxicity to corresponding healthy female reproductive tissue. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17639050&query_hl=1 ER - TY - JFULL T1 - Monitoring peripheral blood regulatory T cells on clinically defined groups of kidney transplant recipients. A1 - Sagoo, P A1 - Sawitzki, B A1 - Hernandez-Fuentes, M A1 - Perucha, E A1 - Craciun, L A1 - Brouard, S A1 - Chaprnan, S A1 - Bradeau, C A1 - Peters, B A1 - Roberts, I A1 - Janssen, U A1 - Soulillou, JP A1 - Warrens, AN A1 - Wood, K A1 - Goldman, M A1 - Volk, HD A1 - Lechler, RI J1 - AM J TRANSPLANT Y1 - 2007/05// VL - 7 SN - 1600-6135 SP - 340 EP - 340 ER - TY - JFULL T1 - Quantitative cellular and molecular analysis of the effect of progesterone withdrawal in a murine model of decidualization. A1 - Cheng, CW A1 - Bielby, H A1 - Licence, D A1 - Smith, SK A1 - Print, CG A1 - Charnock-Jones, DS J1 - Biol Reprod Y1 - 2007/05// VL - 76 SN - 0006-3363 SP - 871 EP - 883 N2 - The endometrium is a dynamic tissue that undergoes periodic growth, remodeling and breakdown under the influence of ovarian steroid hormones. To investigate the molecular mechanisms underlying these processes, we used a murine model to mimic the decidualization and regression observed in humans. Ovariectomized mice were treated sequentially with steroid hormones, and subsequently, to induce decidualization, oil was injected into the uterine lumen. The animals were then divided into progesterone-maintained and progesterone-withdrawal groups. In the latter group, a process similar to menstruation was induced. The uterine tissues were collected at several time-points after the induction of decidualization. Histological analysis demonstrated that decidualization and tissue degeneration were successfully induced with similar features to those observed during the human menstrual cycle. Immunohistochemical, morphometric, and microarray-based techniques were used to study the cellular and molecular changes. The volume fractions of leukocytes, macrophages, and neutrophils, but not endothelial cells, increased in decidualized uteri and decreased after major tissue degradation was completed. The microarray data show that the levels of many transcripts that encode immune-related factors changed during the time-course used for this model, and the transcript levels of many of these factors paralleled the changes observed in the volume fractions of the immune cells. The results of the present study suggest that this model is a useful alternative to the use of non-human primates. Our findings also show that immune cells are recruited into the menstruating endometrium, and that immune-related genes are regulated in the uterus throughout menstruation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17251523&query_hl=1 ER - TY - JFULL T1 - Prolonged survival in culture of preantral follicles from polycystic ovaries. A1 - Webber, LJ A1 - Stubbs, SA A1 - Stark, J A1 - Margara, RA A1 - Trew, GH A1 - Lavery, SA A1 - Hardy, K A1 - Franks, S J1 - J Clin Endocrinol Metab Y1 - 2007/05// VL - 92 SN - 0021-972X SP - 1975 EP - 1978 N2 - CONTEXT: In polycystic ovary syndrome (PCOS), an increased proportion of follicles leave the primordial (resting) pool and initiate growth. However, there is little evidence for a reduced reproductive life span (early menopause) in women with PCOS, suggesting that the dynamics of follicle growth, and of follicle loss by atresia, is altered in PCOS. OBJECTIVE: The aim of this study was to investigate the possibility that loss of preantral follicles by atresia is reduced in PCOS, leading to prolonged follicle survival. DESIGN: We compared follicle growth in normal and polycystic ovaries using cultures of small ovarian biopsies. SETTING: Tissue samples were obtained at routine laparoscopy from 12 patients with anovulatory PCOS and 16 controls and processed in an ovarian physiology laboratory. MAIN OUTCOME MEASURES: We performed morphometric analysis of follicle population in tissue fixed at time of biopsy (d 0) or after 5, 10, or 15 d in culture. Analyses included assessment of follicle and oocyte diameter, number and proportion of primordial and growing follicles, and number and proportion of atretic follicles. RESULTS: In tissue fixed on d 0, the proportion of healthy growing follicles was, as expected, greater in ovaries from PCOS patients than in normal ovaries (64 vs. 28%; P = 0.0005), but there were no differences between PCOS and normal tissue during culture. The rate of atresia throughout the period of culture in follicles was, however, significantly lower in PCOS tissue (P < 0.0001). After culture, 80% of follicles in normal ovarian tissue were atretic compared with 53% in PCOS biopsies. CONCLUSION: Follicles from polycystic ovaries demonstrate a decreased rate of atresia in culture, suggesting a mechanism for maintaining a larger follicle pool throughout reproductive life. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17341570&query_hl=1 ER - TY - JFULL T1 - FastFISH: technique for ultrarapid fluorescence in situ hybridization on uncultured amniocytes yielding results within 2 h of amniocentesis A1 - Choolani, M A1 - Ho, SSY A1 - Razvi, K A1 - Ponnusamy, S A1 - Baig, S A1 - Fisk, NM A1 - Biswas, A A1 - R Mol Test P Diagnos Grp J1 - MOL HUM REPROD Y1 - 2007/05// VL - 13 SN - 1360-9947 SP - 355 EP - 359 N2 - Rapid aneuploidy detection methods allow prenatal diagnosis results to be released within 48 h, but not on the same day as the invasive test. We aimed to develop a rapid fluorescence in situ hybridization (FISH) method (FastFISH) that releases accurate results on the same day as amniocentesis. FastFISH was optimized to be completed within 2 h of sample collection using CEP and LSI probes for chromosomes 13, 18, 21, X, Y and DiGeorge syndrome (DGS). The technique was tested on 100 consecutive amniotic fluid samples in a blinded study. It was also validated as a I-day molecular genetic test on three representative fetal tissue samples: chorionic villus, amniotic fluid and fetal blood. In the blinded study, FastFISH results were ready within 2 h of sample collection. Of the 100 amniotic fluid samples, 49 male and 50 female fetuses were identified. One fetus was 47, XXY (Klinefelter syndrome). Three fetuses had trisomy 21. One fetus suspected of DGS by ultrasound was identified as normal. Results of FastFISH analyses in all 100 cases were concordant with their karyotypes (100% accuracy; lower 95% CI, 97.05%). In the 1-day test validation, all results were released on the same day and were concordant with their respective karyotypes. FastFISH allows results to be released on the same day as amniocentesis. It represents the necessary development for a 1-day prenatal diagnosis service. ER - TY - JFULL T1 - Ontogeny of foetal exposure to maternal cortisol using midtrimester amniotic fluid as a biomarker. A1 - Sarkar, P A1 - Bergman, K A1 - Fisk, NM A1 - O'Connor, TG A1 - Glover, V J1 - Clin Endocrinol (Oxf) Y1 - 2007/05// VL - 66 SN - 0300-0664 SP - 636 EP - 640 N2 - OBJECTIVE: There is increasing evidence that antenatal stress has long-lasting effects on child development, but there is less accord on the mechanisms and the gestational window of susceptibility. One possible mechanism is by foetal exposure to maternal cortisol. To explore this, we investigated the relationship between cortisol in maternal plasma and amniotic fluid, and any moderating influence of gestational age. PATIENTS AND MEASUREMENTS: Two hundred and sixty-seven women awaiting amniocentesis for karyotyping were studied. Samples were collected between 0900 and 1730 h. Gestational age was determined to the nearest day by ultrasound biometry and time of collection noted to the nearest 15 min. Total cortisol was measured by radioimmunoassay in paired amniotic fluid and maternal blood samples (n = 267) [gestation range 15-37 weeks, median 17 weeks (119 days)]. RESULTS: Both maternal and amniotic fluid cortisol levels increased with gestation (r = 0.25, P < 0.001; r = 0.33 P < 0.001, respectively). Amniotic fluid cortisol was positively correlated with time of collection (r = 0.22, P < 0.001) and negatively with maternal age (r =-0.24, P < 0.001). There was a positive correlation between amniotic fluid cortisol with maternal plasma levels (r = 0.32, P < 0.001), which persisted after multivariate analysis controlling for gestation, time of collection and maternal age. The association appeared to be dependent on gestational age, being nonsignificant at 15-16 weeks' gestation and increasing in strength thereafter. CONCLUSION: This study shows a positive correlation between maternal and amniotic fluid cortisol levels, which becomes robust from 17 to 18 weeks onwards. The results provide support for the hypothesis that alterations in maternal cortisol may be reflected in amniotic fluid levels from this gestation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17492950&query_hl=1 ER - TY - JFULL T1 - Longitudinal blood flow in shared (arteriovenous anastomoses) and non-shared cotyledons in monochorionic placentae. A1 - Wee, LY A1 - Sullivan, M A1 - Humphries, K A1 - Fisk, NM J1 - Placenta Y1 - 2007/05// VL - 28 SN - 0143-4004 SP - 516 EP - 522 N2 - OBJECTIVES: In this study we aimed to quantitate monochorionic twin placental blood flow in vivo through arterio-venous anastomoses (AVA) and corresponding vessels within normal cotyledons. METHODS: The topography of chorionic plate vasculature was mapped using colour Doppler in ten monochorionic diamniotic twin (MCDA) pregnancies. Cotyledonary flow was derived by insonation of chorionic veins draining normal (n=10) and paired control shared cotyledons (n=10). Venous volume flow was calculated from five determinations of vessel diameter and three of time average mean velocity (TAMV). Measurements were repeated every 2-4 weeks from 18 until 32 weeks' gestation. RESULTS: Blood flow through non-shared and shared cotyledons increased with gestation (p<0.0001). Median flow at 28 weeks through shared cotyledons was 16 ml/min (15-21) (median, interquartile range), lower than in shared cotyledons (31, 25-35) (p<0.001), as was median volume flow across gestation calculated as area under the curve (shared cotyledons 126 (122-167), control cotyledons 269 (214-274), p=0.01). However, velocity was similar, with the difference due to smaller vein diameters draining shared compared to normal cotyledons (mean 3.6mm (SD 0.8) vs. 4.5mm (0.8), p=0.004). Ex vivo quantitation of insonated cotyledons and of all cotyledons confirmed the difference in vein diameter in the placentae studied. CONCLUSIONS: Blood flow through shared cotyledons was lower across gestation than through paired normal cotyledons in the placenta studied due to the smaller diameter of the AVA vessels. The size of AVAs rather than simply their presence and direction may contribute to determining transfusional imbalance in monochorionic twins. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17081605&query_hl=1 ER - TY - JFULL T1 - Osterix Induces Osteogenic Gene Expression but not Differentiation in Primary Human Fetal Mesenchymal Stem Cells. A1 - Kurata, H A1 - Guillot, PV A1 - Chan, J A1 - Fisk, NM J1 - Tissue Eng Y1 - 2007/04/29/ SN - 1076-3279 N2 - The transcription factor osterix (Osx) is a key regulator of osteoblast differentiation and induces bone formation in embryonic but not adult stem cells. We investigated the effect of up-regulating Osx on an intermediate stem cell type, first trimester fetal mesenchymal stem cells (MSCs), which are more expandable than adult MSCs. Human fetal (hf ) MSCs were transduced with a lentiviral vector encoding human Osx. In undifferentiating MSCs cultures, forced expression of Osx stimulated osteopontin and alkaline phosphatase expression. However, Osx did not up-regulate osteocalcin, a late marker of osteoblast differentiation or result in extracellular calcium crystals, indicating that Osx does not directly mediate terminal differentiation in primary hfMSCs. To understand the downstream effects of Osx expression in primary hfMSCs, we next investigated the regulatory relationship between Osx, and the transcription factors Dlx5, Runx2, and Msx2. Osx induced Dlx5 but did not affect Runx2 and Msx2, whereas stealth ribonucleic acid interference of Osx inhibited Dlx5 without affecting expression of Runx2 and Msx2. In conclusion, Osx regulates osteogenic gene expression in hfMSCs but is insufficient to induce terminal osteogenic differentiation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17465876&query_hl=1 ER - TY - JFULL T1 - Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6. A1 - Vuorenoja, S A1 - Rivero-Muller, A A1 - Kiiveri, S A1 - Bielinska, M A1 - Heikinheimo, M A1 - Wilson, DB A1 - Huhtaniemi, IT A1 - Rahman, NA J1 - Mol Cell Endocrinol Y1 - 2007/04/15/ VL - 269 SN - 0303-7207 SP - 38 EP - 45 N2 - Luteinizing hormone (LH/hCG) responsiveness of normal and pathological human adrenal glands as well as the possibility of constitutive expressions of luteinizing hormone receptor (LHR) in adrenal cortex has been reported. Some recent studies showed a correlation between the LHR and abundant GATA-4 expression in both metastasizing and non-metastasizing human adrenocortical tumors, but not in normal adrenals, implicating the putative relevance of LHR and GATA-4 for adrenocortical pathophysiology. However, the physio- and pathophysiological significance of LHR and GATA-4 in the mechanism of adrenocortical tumorigenesis remains unclear. The paucity of suitable models for adrenal tumorigenesis makes the establishment of proper animal models highly important. LHR expression in the murine adrenal gland is an exception and not found in wild-type (WT) animal. We have previously shown that ectopic LHR expression in the murine adrenal gland can be induced by chronically elevated LH levels. We have generated a gonadotropin-responsive adrenal tumor model in gonadectomized transgenic (TG) mice expressing the inhibin alpha promoter/Simian Virus 40 T antigen transgene (inhalpha/Tag). Given the induction of expression and regulation of GATA-4 and GATA-6 zinc finger transcription factors in the gonads by gonadotropins, this review will explore their relationship to LHR expression and their role in adrenocortical tumorigenesis. A functional link between LHR and GATA-4 actions in the adrenal pathophysiology is proposed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17337116&query_hl=1 ER - TY - JFULL T1 - Extragonadal LH/hCG action--not yet time to rewrite textbooks. A1 - Pakarainen, T A1 - Ahtiainen, P A1 - Zhang, FP A1 - Rulli, S A1 - Poutanen, M A1 - Huhtaniemi, I J1 - Mol Cell Endocrinol Y1 - 2007/04/15/ VL - 269 SN - 0303-7207 SP - 9 EP - 16 N2 - Gonadotropins are indispensable in both sexes in the regulation of gonadal sex steroid production and gametogenesis. In addition to their well-established classical actions, numerous recent publications have indicated the presence and function of luteinizing hormone/chorionic gonadotropin receptors (LH/hCG-R) in a variety of extragonadal tissues. However, the physiological significance of such effects has remained unclear. We have generated two genetically modified mouse models, one with excessive production of hCG and the other with targeted disruption of LH/hCG-R gene, and used them to address the functions of LH and hCG. Numerous gonadal and extragonadal phenotypes were found in the models with the two extremes of LH/hCG action. However, when the extragonadal effects were scrutinized in greater detail, they all appeared to arise through modification of gonadal function, either through enhanced or inhibited response to LH/hCG stimulation. Hence, further evidence is needed before the extragonadal LH/hCG-R expression can be considered functionally significant. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17350753&query_hl=1 ER - TY - JFULL T1 - Use of hecate-chorionic gonadotropin beta conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors. A1 - Rivero-Müller, A A1 - Vuorenoja, S A1 - Tuominen, M A1 - Wacławik, A A1 - Brokken, LJ A1 - Ziecik, AJ A1 - Huhtaniemi, I A1 - Rahman, NA J1 - Mol Cell Endocrinol Y1 - 2007/04/15/ VL - 269 SN - 0303-7207 SP - 17 EP - 25 N2 - Improvement of cancer treatment is a major challenge of medical research. Despite the immense efforts made in the improvement of diagnosis and treatment, cancer remains a major concern and cause of morbidity and mortality. Most of the modern anti-neoplastic therapies have severe side effects, and tumor cells often develop drug resistance. There is promise in the new generation of treatments (gene therapy, immunotherapy, vaccines, etc.) that are under development, but the efficacies and side effects of such therapies have so far been disappointing. Receptor-based therapies are not new, but many normal cells also present the same receptors reducing the specificity of such approaches. Several lytic peptides have been investigated because of they appear to kill cancer cells due to changes of their membrane potential. Thus, linking receptor-specific ligands to lytic peptides is expected to augment the specificity of targeting and decrease the toxicity of lytic peptides on normal cells. One such polypeptide is hecate (an analogue to the bee venom main component, melittin) that preferentially kills cancer cells at low doses. When this peptide is fused with the 81-95 amino acid fragment of chorionic gonadotropin-beta (CGbeta) subunit (hecate-CGbeta), it targets cells expressing luteinizing hormone receptor (LHR), even at very low doses, or when LHR is expressed at low level. Our recent data showed that this peptide conjugate is efficient in destroying LHR-positive cells in xenografts and more importantly in transgenic mouse models developing LHR-positive somatic cell tumors in gonads. The mechanism of action of hecate-CGbeta after binding to LHR is destruction of cell membranes resulting in rapid cell death by necrosis with minimal side effects. This review summarizes our findings on the action of this novel peptide and considers the future potential of this family of targeting peptides in the treatment of neoplasias. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17363137&query_hl=1 ER - TY - JFULL T1 - Fetomaternal cell trafficking and the stem cell debate - Gender matters A1 - Bianchi, DW A1 - Fisk, NM J1 - JAMA-J AM MED ASSOC Y1 - 2007/04/04/ VL - 297 SN - 0098-7484 SP - 1489 EP - 1491 ER - TY - JFULL T1 - A multi-centre prospective observational study of platelet transfusion practice in neonates with severe thrombocytopenia A1 - Stanworth, S A1 - Ballard, S A1 - Casbard, A A1 - Murphy, M A1 - Roberts, I A1 - Murray, N A1 - PlaNet Study Grp J1 - BRIT J HAEMATOL Y1 - 2007/04// VL - 137 SN - 0007-1048 SP - 35 EP - 36 ER - TY - JFULL T1 - Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse. A1 - Chan, J A1 - Waddington, SN A1 - O'Donoghue, K A1 - Kurata, H A1 - Guillot, PV A1 - Gotherstrom, C A1 - Themis, M A1 - Morgan, JE A1 - Fisk, NM J1 - Stem Cells Y1 - 2007/04// VL - 25 SN - 1066-5099 SP - 875 EP - 884 N2 - Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the absence of dystrophin in muscle. Affected boys suffer from incurable progressive muscle weakness, leading to premature death. Stem cell transplantation may be curative, but is hampered by the need for systemic delivery and immune rejection. To address these barriers to stem cell therapy in DMD, we investigated a fetal-to-fetal transplantation strategy. We investigated intramuscular, intravascular, and intraperitoneal delivery of human fetal mesenchymal stem cells (hfMSCs) into embryonic day (E) 14-16 MF1 mice to determine the most appropriate route for systemic delivery. Intramuscular injections resulted in local engraftment, whereas both intraperitoneal and intravascular delivery led to systemic spread. However, intravascular delivery led to unexpected demise of transplanted mice. Transplantation of hfMSCs into E14-16 mdx mice resulted in widespread long-term engraftment (19 weeks) in multiple organs, with a predilection for muscle compared with nonmuscle tissues (0.71% vs. 0.15%, p < .01), and evidence of myogenic differentiation of hfMSCs in skeletal and myocardial muscle. This is the first report of intrauterine transplantation of ontologically relevant hfMSCs into fully immunocompetent dystrophic fetal mice, with systemic spread across endothelial barriers leading to widespread long-term engraftment in multiple organ compartments. Although the low-level of chimerism achieved is not curative for DMD, this approach may be useful in other severe mesenchymal or enzyme deficiency syndromes, where low-level protein expression may ameliorate disease pathology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17185606&query_hl=1 ER - TY - JFULL T1 - The effect of mechanical stretch on cyclooxygenase type 2 expression and activator protein-1 and nuclear factor-kappaB activity in human amnion cells. A1 - Mohan, AR A1 - Sooranna, SR A1 - Lindstrom, TM A1 - Johnson, MR A1 - Bennett, PR J1 - Endocrinology Y1 - 2007/04// VL - 148 SN - 0013-7227 SP - 1850 EP - 1857 N2 - Stretch of the uterus plays a role in parturition. Uterine stretch also leads to stretch of the fetal membranes, including the amnion, an important source of prostaglandin E2 (PGE2). We tested the hypothesis that stretch of the amnion leads to increased cyclooxygenase (COX)-2 expression and PGE2 synthesis and investigated the mechanisms involved. We obtained amnion from women undergoing term elective cesarean section and isolated amnion epithelial cells. These cells were subjected to 11% static stretch. Stretch increased COX-2 expression and PGE2 production. EMSA studies showed that stretch increased both activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) DNA binding at 1 and 6 h. In contrast, IL-1beta increased both AP-1 and NF-kappaB DNA binding at 1 h only. Chromatin immunoprecipitation studies confirmed that stretch increased binding of NF-kappaB to the COX-2 promoter in vivo. Stretch had no effect on inhibitory-kappaBalpha (IkappaBalpha) levels at the early time points but caused a decrease at 4 h. IL-1beta stimulation decreased IkappaBalpha levels after 30 min. MG132, a proteasome inhibitor, inhibited only the second stretch-induced increase in NF-kappaB binding. This suggests that stretch initially activates NF-kappaB via a nonclassical pathway, which does not involve the inhibitory-kappa kinase-induced degradation of IkappaBalpha. The second peak of NF-kappaB activation may be mediated by the classical mechanism. Stretch of the amnion may contribute to increased expression of COX-2- and other AP-1- and NF-kappaB-regulated genes with the onset of labor in the human. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17218407&query_hl=1 ER - TY - JFULL T1 - Role of atypical protein kinase C isozymes and NF-kappa B in IL-1 beta-induced expression of cyclooxygenase-2 in human myometrial smooth muscle cells A1 - Duggan, SV A1 - Lindstrom, T A1 - Iglesias, T A1 - Bennett, PR A1 - Mann, GE A1 - Bartlett, SR J1 - J CELL PHYSIOL Y1 - 2007/03// VL - 210 SN - 0021-9541 SP - 637 EP - 643 N2 - Increased myometrial expression of cyclooxygenase-2 (Cox-2) at term results from elevated local levels of inflammatory cytokines, and its inhibition provides a potential route for intervention in human pre-term labor. We have identified a role for atypical protein kinase C (PKC) isozynnes in IL-1 beta-induced Cox-2 expression ill human myometrial smooth muscle cells (HMSMC). The PKC inhibitor GF109203X (10 mu M) inhibited IL-1 beta-induced Cox-2 protein and RNA expression, which were also reduced by MAPK and nuclear factor kappa B (NF-kappa B) inhibitors. GF109203X did not affect MAPK activities, and neither did it replicate the effect of p38 MAPK inhibition on Cox-2 mRNA stability, Suggesting that PKC operates through an independent mechanism. The effect of GF109203X remained intact after depletion of conventional and novel PKC isozymes by phorbol ester pre-treatment. In contrast LY379196 (10 mu M), which at micromolar concentrations inhibits all but atypical PKCs, did not affect Cox-2 expression. A peptide corresponding to the pseudosubstrate sequence of atypical PKCs blocked Cox-2 protein expression, whereas the sequence from conventional PKCs was ineffective. GF109203X did not affect NF-kappa B binding to nuclear proteins, but strongly reduced NF-kappa B-dependent transcription in luciferase reporter assays. Our findings indicate that L-1 beta-induced Cox-2 expression in HMSMC in Culture requires p38-MAPK-mediated mRNA stabilization and an independent activation of Cox-2 transcription which is dependent on the action of atypical PKCs, probably through direct Stimulation of the transactivating activity of NF-kappa B. ER - TY - JFULL T1 - Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? A1 - Talge, NM A1 - Neal, C A1 - Glover, V A1 - Early Stress Transnational Res Pre J1 - J CHILD PSYCHOL PSYC Y1 - 2007/03// VL - 48 SP - 245 EP - 261 N2 - We review a significant body of evidence from independent prospective studies that if a mother is stressed while pregnant, her child is substantially more likely to have emotional or cognitive problems, including an increased risk of attentional deficit/hyperactivity, anxiety, and language delay. These findings are independent of effects due to maternal postnatal depression and anxiety. We still do not know what forms of anxiety or stress are most detrimental, but research suggests that the relationship with the partner can be important in this respect. The magnitude of these effects is clinically significant, as the attributable load of emotional/behavioral problems due to antenatal stress and/or anxiety is approximately 15%. Animal models suggest that activity of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal end-product cortisol are involved in these effects in both mother and offspring. The fetal environment can be altered if stress in the mother changes her hormonal profile, and in humans, there is a strong correlation between maternal and fetal cortisol levels. However, many problems remain in understanding the mechanisms involved in this interaction. For example, maternal cortisol responses to stress decline over the course of pregnancy, and earlier in pregnancy, the link between maternal and fetal cortisol is less robust. It is possible that the effects of maternal anxiety and stress on the developing fetus and child are moderated by other factors such as a maternal diet (e.g., protein load). It is suggested that extra vigilance or anxiety, readily distracted attention, or a hyper-responsive HPA axis may have been adaptive in a stressful environment during evolution, but exists today at the cost of vulnerability to neurodevelopmental disorders. ER - TY - JFULL T1 - The effects of oxygen concentration on in vitro output of prostaglandin E2 and interleukin-6 from human fetal membranes. A1 - Al-Asmakh, M A1 - Race, H A1 - Tan, S A1 - Sullivan, MH J1 - Mol Hum Reprod Y1 - 2007/03// VL - 13 SN - 1360-9947 SP - 197 EP - 201 N2 - Labour at all gestational ages has clear biochemical parallels with an inflammatory response, typified by the increased output of prostaglandins (PGs) and cytokines within the pregnant uterus. The main sources are the fetal membranes, including the amnion, chorion and decidua, and it is well established that stimuli [bacteria, bacterial endotoxins, interleukin (IL)-1beta, corticotrophin releasing hormone and platelet activating factor], as well as negative regulators (progesterone and IL-10), control the net output of PGs and cytokines in vitro. In this study, we have investigated the effect of oxygen tension on fetal membrane biology, as a reconsideration of the literature suggests that fetal membranes are normally exposed to approximately 3% O(2) (approximately 20 mmHg) in vivo, rather than the 20% O(2) (150 mmHg) used for in vitro culture. The output of prostaglandin E(2) from non-activated fetal membranes in response to IL-1beta was decreased by approximately 80% at 16 and 24 h of culture, whereas the inhibition of IL-6 production was time-dependent, reaching 90% after 16 h and 50% after 24 h. Tissues obtained after labour (or after the activation of inflammatory processes leading to labour) were not inhibited by the low levels of oxygen, indicating that only before the onset of labour does oxygen regulate fetal membrane biology. The data identify oxygen as a regulator of fetal membrane inflammatory functions during human pregnancy, and its mechanism of action requires further study. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17208929&query_hl=1 ER - TY - JFULL T1 - Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. A1 - Guillot, PV A1 - Gotherstrom, C A1 - Chan, J A1 - Kurata, H A1 - Fisk, NM J1 - Stem Cells Y1 - 2007/03// VL - 25 SN - 1066-5099 SP - 646 EP - 654 N2 - The biological properties of stem cells are key to the success of cell therapy, for which MSC are promising candidates. Although most therapeutic applications to date have used adult bone marrow MSC, increasing evidence suggests that MSC from neonatal and mid-gestational fetal tissues are more plastic and grow faster. Fetal stem cells have been isolated earlier in development, from first-trimester blood and hemopoietic organs, raising the question of whether they are biologically closer to embryonic stem cells and thus have advantages over adult bone marrow MSC. In this study, we show that human first-trimester fetal blood, liver, and bone marrow MSC but not adult MSC express the pluripotency stem cell markers Oct-4, Nanog, Rex-1, SSEA-3, SSEA-4, Tra-1-60, and Tra-1-81. In addition, fetal MSC, irrespective of source, had longer telomeres (p < .001), had greater telomerase activity (p < .01), and expressed more human telomerase reverse transcriptase (p < .01). Fetal MSC were also more readily expandable and senesced later in culture than their adult counterparts (p < .01). Compared with adult MSC, first-trimester fetal tissues constitute a source of MSC with characteristics that appear advantageous for cell therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17124009&query_hl=1 ER - TY - JFULL T1 - Placental mesenchymal stem cells. A1 - Chan, J A1 - Kennea, NL A1 - Fisk, NM J1 - Am J Obstet Gynecol Y1 - 2007/02// VL - 196 SN - 1097-6868 SP - e18; author reply e18 EP - e19; author reply e19 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16959209&query_hl=1 ER - TY - JFULL T1 - Expression in human trophoblast and choriocarcinoma cell lines, BeWo, Jeg-3 and JAr of genes involved in the hepatobiliary-like excretory function of the placenta A1 - Serrano, MA A1 - Macias, RIR A1 - Briz, O A1 - Monte, MJ A1 - Blazquez, AG A1 - Williamson, C A1 - Kubitz, R A1 - Marin, JJG J1 - PLACENTA Y1 - 2007/02// VL - 28 SN - 0143-4004 SP - 107 EP - 117 N2 - Using cytokeratin-7-positive trophoblast cells (hTr) isolated from human term placentas and the choriocarcinoma cell lines (hCC) BeWo, Jeg-3 and JAr, the expression of genes involved in the hepatobiliary excretion of cholephilic compounds was investigated by RT-PCR/sequencing followed by measurement of the absolute abundance of mRNA by real-time RT-PCR. Although mRNA of BSEP was detectable and its expression confirmed by Western blotting, its very low expression (higher in hTr than in whole placenta and hCC) did not permit its detection by immunohistochemistry. In hTr, the expression was high for OATP-B/2B1, OATP-8/1B3, MRP1, MRP3, BCRP, FIC1, RAR alpha, FXR and SHP, low for OST alpha MRP2, MRP4, MRP8, MDR1, CAR and SXR, very low for OATP-A/1A2 and MDR3, and not detectable for OATP-C/1B1, HNF1 alpha and HNF4. Expression patterns in hCC mimicked those in hTr, although some important cell line-specific differences were found. The functionality of transporters expressed in hCC was confirmed by their ability to take up and export estradiol 17 beta-D-glucuronide in a self-inhibitable and temperature-sensitive manner. In conclusion, several transporters, export pumps, and nuclear receptors involved in the liver excretory function may play a similar role in the placenta, whose specific aspects can be studied by selectively using BeWo, Jeg-3 or JAr cells. (c) 2006 Elsevier Ltd. All rights reserved. ER - TY - JFULL T1 - Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review. A1 - Jindal, P A1 - Regan, L A1 - Fourkala, EO A1 - Rai, R A1 - Moore, G A1 - Goldin, RD A1 - Sebire, NJ J1 - Hum Reprod Y1 - 2007/02// VL - 22 SN - 0268-1161 SP - 313 EP - 316 N2 - BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17008326&query_hl=1 ER - TY - JFULL T1 - GATA transcription factors in adrenal development and tumors. A1 - Parviainen, H A1 - Kiiveri, S A1 - Bielinska, M A1 - Rahman, N A1 - Huhtaniemi, IT A1 - Wilson, DB A1 - Heikinheimo, M J1 - Mol Cell Endocrinol Y1 - 2007/02// VL - 265-266 SN - 0303-7207 SP - 17 EP - 22 N2 - Of the six GATA transcription factors, GATA-4 and GATA-6 are expressed in the mouse and human adrenal with distinct developmental profiles. GATA-4 is confined to the fetal cortex, i.e. to the less differentiated proliferating cells, while GATA-6 is expressed both in the fetal and adult adrenal. In vitro, GATA-4 regulates inhibin-alpha and steroidogenic factor-1 implicated in normal adrenal function. GATA-6 probably has roles in the development and differentiation of adrenocortical cells, and in the regulation of steroidogenesis. GATA-4 expression is dramatically upregulated and GATA-6 downregulated in gonadotropin dependent mouse adrenocortical tumors. This is accompanied by the appearance of luteinizing hormone receptor (LHR). In vitro, GATA-4 transactivates LHR promoter, and gonadotropins upregulate GATA-4 levels. Human adrenal tumors occasionally express GATA-4, whereas GATA-6 levels are usually lower than normal. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17207921&query_hl=1 ER - TY - JFULL T1 - Disordered follicle development in ovaries of prenatally androgenized ewes. A1 - Forsdike, RA A1 - Hardy, K A1 - Bull, L A1 - Stark, J A1 - Webber, LJ A1 - Stubbs, S A1 - Robinson, JE A1 - Franks, S J1 - J Endocrinol Y1 - 2007/02// VL - 192 SN - 0022-0795 SP - 421 EP - 428 N2 - Exposure to excess androgens in utero induces irreversible changes in gonadotrophin secretion and results in disrupted reproductive endocrine and ovarian function in adulthood, in a manner reminiscent of the common clinical endocrinopathy of polycystic ovary syndrome (PCOS). We have recently identified an abnormality in early follicle development in PCOS which we suggested might be an androgenic effect. We propose that altered ovarian function in androgenized ewes is due to prenatal androgens not only causing an abnormality of gonadotrophin secretion, but also exerting a direct effect on the early stages of folliculogenesis. Therefore, in this study, we explored the possible differences between small preantral follicles in the ovarian cortex of androgenized female lambs with those of normal lambs. At 8 months of age, small ovarian cortical biopsies (approximately 5 mm3) were obtained at laparotomy from nine female lambs that had been exposed to androgens in utero from embryonic days 30 to 90 of a 147-day pregnancy, and 11 control female lambs. Further, ovarian tissue was obtained at 20 months of age from ten androgenized and nine control animals. Tissue was either fixed immediately for histology or cultured for up to 15 days prior to fixing. The number of follicles in haematoxylin and eosin-stained sections was counted and recorded along with the stage of development. Before culture, the total follicle density (follicles/mm3 tissue) was not statistically significantly different between the two types of ovary at either 8 or 20 months of age. Furthermore, there were no statistically significant differences in the density of follicles at each stage of development. However, there was a lower percentage of primordial follicles, but a higher percentage of primary follicles, in biopsies taken at 8 months from androgenized lambs when compared with controls. At 20 months, the proportions of follicles at the primordial and primary stages were not significantly different between the two groups, but this was mainly attributable to an increase in the proportion of growing follicles in biopsies from control animals. Culture of ovarian cortex from 8-month-old lambs resulted in a progressive increase in the proportion of growing follicles when compared with tissue fixed on the day of surgery. However, there was no difference between androgenized and control tissue in the percentage of growing follicles. The increase in the proportion of growing follicles in the cortex of androgenized animals is reminiscent of similar observations in human polycystic ovaries and suggests that excess exposure to androgen in early life plays a part in the accelerated progression of follicle development from the primordial to the primary stage in polycystic ovaries. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17283242&query_hl=1 ER - TY - JFULL T1 - Prenatal stressful life events predict child cognitive outcomes A1 - Bergman, KM A1 - Sarkar, P A1 - O'Connor, TG A1 - Modi, N A1 - Glover, V J1 - EARLY HUM DEV Y1 - 2007/02// VL - 83 SN - 0378-3782 SP - 136 EP - 136 ER - TY - JFULL T1 - Phenotypic characterisation of mice with exaggerated and missing LH/hCG action. A1 - Ahtiainen, P A1 - Rulli, S A1 - Pakarainen, T A1 - Zhang, FP A1 - Poutanen, M A1 - Huhtaniemi, I J1 - Mol Cell Endocrinol Y1 - 2007/01/02/ VL - 260-262 SN - 0303-7207 SP - 255 EP - 263 N2 - In order to study the physiology and pathophysiology of gonadotrophin action, we have produced transgenic (TG) mice overexpressing human chorionic gonadotrophin (hCG) alpha and beta subunits (hCG+ mice) and knockout (KO) mice for the luteinising hormone receptor (LHR; LuRKO mice). The two extremes in LH function, i.e. strong LH/hCG stimulation and total blockade of this action, confirm numerous earlier concepts about LH function, but they also reveal new aspects about gonadal function during excessive LH production and in the absence of this trophic stimulus. The purpose of this review is to summarise the key findings on these two genetically modified mouse models. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17029767&query_hl=1 ER - TY - JFULL T1 - An additional radial wrist extensor and its clinical significance. A1 - Nayak, SR A1 - Madhan Kumar, SJ A1 - Krishnamurthy, A A1 - Prabhu, LV A1 - Ranade, AV A1 - Rai, R A1 - Ramanathan, L J1 - Ann Anat Y1 - 2007/// VL - 189 SN - 0940-9602 SP - 283 EP - 286 N2 - The knowledge of anatomical variations in the antebrachial and dorsal regions of the arm and hand are useful in hand surgery. The extensor carpi radialis intermedius and extensor carpi radialis accessorius are two classic variants described for the radial wrist extensors, in the antebrachial region. We report an additional extensor carpi radialis muscle taking origin from the common extensor origin, between the extensor carpi radialis longus and extensor digitorum communis. The tendon of the variant muscle divides below the abductor pollicis longus and becomes attached to the base of the second and third metacarpal bone. Due to its considerable size and independent origin from the lateral epicondyle, we suggest the present variation should be named extensor carpi radialis tertius. The clinical significance of the present variation is discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17534036&query_hl=1 ER - TY - JFULL T1 - Vascular development is disrupted by endothelial cell-specific expression of the anti-apoptotic protein Bcl-2. A1 - Duval, H A1 - Johnson, N A1 - Li, J A1 - Evans, A A1 - Chen, S A1 - Licence, D A1 - Skepper, J A1 - Charnock-Jones, DS A1 - Smith, S A1 - Print, C J1 - Angiogenesis Y1 - 2007/// VL - 10 SN - 0969-6970 SP - 55 EP - 68 N2 - Endothelial cell (EC) apoptosis has been detected in remodelling blood vessels in vivo, and inhibition of EC apoptosis appears to alter vascular morphogenesis in vitro, suggesting that EC apoptosis may play a role in blood vessel remodelling. However, apoptotic EC are difficult to quantify in vivo, and studies of the incidence of EC apoptosis and the sites at which it occurs in vivo have produced contradictory results. Therefore, the specific biological roles played by EC apoptosis remain unclear. Here, we have used a transgenic approach to determine the biological function of EC apoptosis in vivo. Anti-apoptotic Bcl-2 transgenes were expressed in mice under control of the EC-specific tie2 promoter. These transgenic mice died during the second half of gestation. While the development and remodelling of large vessels including aortic arch arteries and great veins proceeded normally, abnormally dense and disorganised networks of small vessels were present in the skin and internal organs. In addition, vessel organisation and lumen formation were disrupted in the placental labyrinth. This study provides direct experimental evidence that endothelial cell apoptosis plays an essential role during embryogenesis. Our results suggest that EC apoptosis plays an important role in determining the structure of the microcirculation but may be dispensable for large vessel development. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17149535&query_hl=1 ER - TY - JFULL T1 - Assisted large fragment insertion by Red/ET-recombination (ALFIRE)--an alternative and enhanced method for large fragment recombineering. A1 - Rivero-Müller, A A1 - Lajić, S A1 - Huhtaniemi, I J1 - Nucleic Acids Res Y1 - 2007/// VL - 35 SN - 1362-4962 SP - e78 EP - e78 N2 - Functional genomics require manipulation and modification of large fragments of the genome. Such manipulation has only recently become more efficient due to the discovery of different techniques based on homologous recombination. However, certain limitations of these strategies still exist since insertion of homology arms (HAs) is often based on amplification of DNA sequences with PCR. Large quantities of PCR products longer than 4-5 kb can be difficult to obtain and the risk of mutations or mismatches increases with the size of the template that is being amplified. This can be overcome by adding HAs by conventional cloning techniques, but with large fragments such as entire genes the procedure becomes time-consuming and tedious. Second, homologous recombination techniques often require addition of antibiotic selection genes, which may not be desired in the final construct. Here, we report a method to overcome the size and selection marker limitations by a two- or three-step procedure. The method can insert any fragment into small or large episomes, without the need of an antibiotic selection gene. We have humanized the mouse luteinizing hormone receptor gene (Lhcgr) by inserting a approximately 55 kb fragment from a BAC clone containing the human Lhcgr gene into a 170 kb BAC clone comprising the entire mouse orthologue. The methodology is based on the rationale to introduce a counter-selection cassette flanked by unique restriction sites and HAs for the insert, into the vector that is modified. Upon enzymatic digestion, in vitro or in Escherichia coli, double-strand breaks are generated leading to recombination between the vector and the insert. The procedure described here is thus an additional powerful tool for manipulating large and complex genomic fragments. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17517785&query_hl=1 ER - TY - JFULL T1 - Vascular development in embryoid bodies: quantification of transgenic intervention and antiangiogenic treatment. A1 - Evans, AL A1 - Bryant, J A1 - Skepper, J A1 - Smith, SK A1 - Print, CG A1 - Charnock-Jones, DS J1 - Angiogenesis Y1 - 2007/// VL - 10 SN - 0969-6970 SP - 217 EP - 226 N2 - It has become increasingly clear that the investigation of vascular development is best considered in the context of a whole tissue environment since in vivo endothelial cells interact closely with other cell types. Murine embryoid bodies have been used as a model for the early development of a vascular network and are amenable to genetic manipulation and treatment with soluble modulators. However, quantifying morphological changes in these complex three-dimensional structures is challenging. In this paper we describe protocols to culture embryoid bodies on a large scale to study vascular development together with methods to quantify changes seen when antiangiogenic agents or endothelial cell-specific transgenes are introduced. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17577673&query_hl=1 ER - TY - JFULL T1 - Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium. A1 - Berndt, S A1 - Perrier d'Hauterive, S A1 - Blacher, S A1 - Péqueux, C A1 - Lorquet, S A1 - Munaut, C A1 - Applanat, M A1 - Hervé, MA A1 - Lamandé, N A1 - Corvol, P A1 - van den Brûle, F A1 - Frankenne, F A1 - Poutanen, M A1 - Huhtaniemi, I A1 - Geenen, V A1 - Noël, A A1 - Foidart, JM J1 - FASEB J Y1 - 2006/12// VL - 20 SN - 1530-6860 SP - 2630 EP - 2632 N2 - Successful embryo development requires an extensive endometrial angiogenesis in proximity of implantation site. The glycoprotein hCG is produced even before implantation by trophoblast in normal pregnancy. In this manuscript, we demonstrate an angiogenic effect of hCG in several in vivo (chick chorioallantoïc membrane, matrigel plug assay, aortic ring assay) and in vitro experimental models. In contrast, human placental lactogen (hPL) did not display angiogenic properties. LH/hCG receptor was detected in endothelial cells by reverse-transcriptase polymerase chain reaction (RT-PCR) and by Western blotting. In mice aortic ring assay, angiostimulation by hCG was abrogated by deletion of LH/hCG receptor (LuRKO mice). Use of recombinant hCG and anti-hCG antibody (Ab) further confirmed the specificity of this angiogenic activity. By using dibutyryl cAMP, adenylate cyclase, or protein kinase A inhibitors, we demonstrate that hCG-mediated angiogenesis involves adenylyl-cyclase-protein kinase A activation. Addition of hCG to endometrial epithelial epithelial cells, but not to cultured endothelial cells, stimulated vascular endothelial growth factor (VEGF). VEGF and hCG also displayed additive activities. Altogether, these data demonstrate that peritrophoblastic angiostimulation may result from a paracrine dialogue between trophoblast, epithelial, and endothelial cells through hCG and VEGF. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17065221&query_hl=1 ER - TY - JFULL T1 - The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks. A1 - Parker, MG A1 - Christian, M A1 - White, R J1 - Biochem Soc Trans Y1 - 2006/12// VL - 34 SN - 0300-5127 SP - 1103 EP - 1106 N2 - NRs (nuclear receptors) regulate the expression of specific gene networks in target cells by recruiting cofactor complexes involved in chromatin remodelling and in the assembly of transcription complexes. The importance of activating gene expression, in metabolic tissues, is well established, but the contribution of transcriptional inhibition is less well defined. In this review, we highlight a crucial role for RIP140 (receptor-interacting protein 140), a transcriptional co-repressor for NR, in the regulation of metabolic gene expression. Many genes involved in lipid and carbohydrate metabolism are repressed by RIP140 in adipose and muscle. The repressive function of RIP140 results from its ability to bridge NRs to repressive enzyme complexes that modify DNA and histones. In the absence of RIP140, expression from many metabolic genes is increased so that mice exhibit a lean phenotype and resistance to high-fat-diet-induced obesity and display increased glucose tolerance and insulin sensitivity. We propose that a functional interplay between transcriptional activators and the co-repressor RIP140 is an essential process in metabolic regulation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17073760&query_hl=1 ER - TY - JFULL T1 - Human homologs of the putative G protein-coupled membrane progestin receptors (mPRalpha, beta, and gamma) localize to the endoplasmic reticulum and are not activated by progesterone. A1 - Krietsch, T A1 - Fernandes, MS A1 - Kero, J A1 - Lösel, R A1 - Heyens, M A1 - Lam, EW A1 - Huhtaniemi, I A1 - Brosens, JJ A1 - Gellersen, B J1 - Mol Endocrinol Y1 - 2006/12// VL - 20 SN - 0888-8809 SP - 3146 EP - 3164 N2 - The steroid hormone progesterone exerts pleiotrophic functions in many cell types. Although progesterone controls transcriptional activation through binding to its nuclear receptors, it also initiates rapid nongenomic signaling events. Recently, three putative membrane progestin receptors (mPRalpha, beta, and gamma) with structural similarity to G protein-coupled receptors have been identified. These mPR isoforms are expressed in a tissue-specific manner and belong to the larger, highly conserved family of progestin and adiponectin receptors found in plants, eubacteria, and eukaryotes. The fish mPRalpha has been reported to mediate progesterone-dependent MAPK activation and inhibition of cAMP production through coupling to an inhibitory G protein. To functionally characterize the human homologs, we established human embryonic kidney 293 and MDA-MB-231 cell lines that stably express human mPRalpha, beta, or gamma. For comparison, we also established cell lines expressing the mPRalpha cloned from the spotted seatrout (Cynoscion nebulosus) and Japanese pufferfish (Takifugu rubripes). Surprisingly, we found no evidence that human or fish mPRs regulate cAMP production or MAPK (ERK1/2 or p38) activation upon progesterone stimulation. Furthermore, the mPRs did not couple to a highly promiscuous G protein subunit, Galpha(q5i), in transfection studies or provoke Ca(2+) mobilization in response to progesterone. Finally, we demonstrate that transfected mPRs, as well as endogenous human mPRalpha, localize to the endoplasmic reticulum, and that their expression does not lead to increased progestin binding either in membrane preparations or in intact cells. Our results therefore do not support the concept that mPRs are plasma membrane receptors involved in transducing nongenomic progesterone actions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16959873&query_hl=1 ER - TY - JFULL T1 - Stage I Twin-twin transfusion syndrome A1 - O'Donoghue, K A1 - Cartwright, E A1 - Fisk, NM J1 - AM J OBSTET GYNECOL Y1 - 2006/12// VL - 195 SN - 0002-9378 SP - S186 EP - S186 ER - TY - JFULL T1 - Gonadotrophin resistance. A1 - Huhtaniemi, I A1 - Alevizaki, M J1 - Best Pract Res Clin Endocrinol Metab Y1 - 2006/12// VL - 20 SN - 1521-690X SP - 561 EP - 576 N2 - Gonadotrophin resistance is caused by inactivating mutations in receptors (Rs) of the two gonadotrophins, i.e. luteinizing hormone (LH) and follicle-stimulating hormone (FSH), presenting as hypergonadotrophic hypogonadism and infertility/subfertility in both sexes. These conditions are extremely rare, but must be kept in mind upon differential diagnosis of disorders of sexual maturation, hypogonadism and infertility. In 46,XY individuals inactivation of LHR causes a disturbance in male-type sexual differentiation that ranges from male pseudohermaphroditism (complete lack of genital masculinization) to mild conditions such as cryptorchidism and hypospadias, depending on completeness of the receptor inactivation. In women, the phenotype is milder, presenting mainly as anovulatory amenorrhoea and hypo-oestrogenization. Inactivation of FSHR causes in otherwise normally masculinized men small testis size and variably reduced spermatogenesis, but not azoospermia or absolute infertility. In women the phenotype is more severe, with primary or early secondary amenorrhoea, arrested follicular maturation and anovulatory infertility. Incomplete forms with milder phenotype and partial responsiveness to FSH have also been described. Although gonadotrophin resistance is a very rare condition, its correct diagnosis is important for the selection of adequate treatment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17161332&query_hl=1 ER - TY - JFULL T1 - International Union of Pharmacology. LXIV. Estrogen receptors A1 - Dahlman-Wright, K A1 - Cavailles, V A1 - Fuqua, SA A1 - Jordan, VC A1 - Katzenellenbogen, JA A1 - Korach, KS A1 - Maggi, A A1 - Muramatsu, M A1 - Parker, MG A1 - Gustafsson, JA J1 - PHARMACOL REV Y1 - 2006/12// VL - 58 SN - 0031-6997 SP - 773 EP - 781 ER - TY - JFULL T1 - Microchimeric fetal cells contribute to tissue repair after pregnancy A1 - O'Donoghue, K A1 - Sultan, HA A1 - Anderson, JR A1 - Fisk, NM J1 - AM J OBSTET GYNECOL Y1 - 2006/12// VL - 195 SN - 0002-9378 SP - S102 EP - S102 ER - TY - JFULL T1 - Abnormally small BCR-ABL transcripts in CML patients before and during imatinib treatment. A1 - Khorashad, JS A1 - Lipton, JH A1 - Marin, D A1 - Milojkovic, D A1 - Cross, NCP A1 - Dibb, N A1 - Melo, JV A1 - Kamel-Reid, S A1 - Goldman, JM A1 - Apperley, JF A1 - Kaeda, JS J1 - BLOOD Y1 - 2006/11/16/ VL - 108 SN - 0006-4971 SP - 611A EP - 611A ER - TY - JFULL T1 - A multi-centre prospective observational study of platelet transfusion practice in neonates with severe thrombocytopenia. A1 - Murray, N A1 - Ballard, S A1 - Casbard, A A1 - Murphy, M A1 - Roberts, I A1 - Stanworth, S A1 - PlaNeT Study Grp J1 - BLOOD Y1 - 2006/11/16/ VL - 108 SN - 0006-4971 SP - 287A EP - 287A ER - TY - JFULL T1 - Trisomy 21 expands the megakaryocyte-erythroid progenitor compartment in human fetal liver-implications for down syndrome AMKL. A1 - Tunstall-Pedoe, O A1 - De la Fuente, J A1 - Bennett, PR A1 - Fisk, NM A1 - Vyas, P A1 - Roberts, IG J1 - BLOOD Y1 - 2006/11/16/ VL - 108 SN - 0006-4971 SP - 170A EP - 170A ER - TY - JFULL T1 - Suppression of receptor interacting protein 140 repressive activity by protein arginine methylation A1 - Huq, MDM A1 - Gupta, P A1 - Tsai, NP A1 - White, R A1 - Parker, MG A1 - Wei, LN J1 - EMBO J Y1 - 2006/11/01/ VL - 25 SN - 0261-4189 SP - 5094 EP - 5104 N2 - Receptor interacting protein 140 (RIP140), a ligand-dependent corepressor for nuclear receptors, can be modified by arginine methylation. Three methylated arginine residues, at Arg-240, Arg-650, and Arg-948, were identified by mass spectrometric analysis. Site-directed mutagenesis studies demonstrated the functionality of these arginine residues. The biological activity of RIP140 was suppressed by protein arginine methyltransferase 1 (PRMT1) due to RIP140 methylation, which reduced the recruitment of histone deacetylases to RIP140 and facilitated its nuclear export by enhancing interaction with exportin 1. A constitutive negative (Arg/Ala) mutant of RIP140 was resistant to the effect of PRMT1, and a constitutive positive (Arg/Phe) mutation mimicked the effect of arginine methylation. The biological activities of the wild type and the mutant proteins were examined in RIP140-null MEF cells. This study uncovered a novel means to inactivate, or suppress, RIP140, and demonstrated protein arginine methylation as a critical type of modification for corepressor. ER - TY - JFULL T1 - Fetal stem cells: betwixt and between. A1 - Guillot, PV A1 - O'Donoghue, K A1 - Kurata, H A1 - Fisk, NM J1 - Semin Reprod Med Y1 - 2006/11// VL - 24 SN - 1526-8004 SP - 340 EP - 347 N2 - Fetal stem cells can be isolated not only from fetal blood and hemopoietic organs in early pregnancy, but from a variety of somatic organs as well as amniotic fluid and placenta throughout gestation. Fetal blood is a rich source of hemopoietic stem cells, which proliferate more rapidly than those in cord blood or adult bone marrow. First-trimester fetal blood, liver, and bone marrow also contain a population of mesenchymal stem cells, which appear to be more primitive with greater multipotentiality than their adult counterparts. Fetal stem cells may thus represent an intermediate cell type in the current debate focusing on dichotomized adult versus embryonic stem cells, and thus prove advantageous as a source for downstream cell therapy applications. They have also been implicated in fetomaternal trafficking in pregnancy, and in long-term microchimerism in postreproductive women. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17123229&query_hl=1 ER - TY - JFULL T1 - Regulation of the SUMO pathway sensitizes differentiating human endometrial stromal cells to progesterone. A1 - Jones, MC A1 - Fusi, L A1 - Higham, JH A1 - Abdel-Hafiz, H A1 - Horwitz, KB A1 - Lam, EW A1 - Brosens, JJ J1 - Proc Natl Acad Sci U S A Y1 - 2006/10/31/ VL - 103 SN - 0027-8424 SP - 16272 EP - 16277 N2 - cAMP is required for differentiation of human endometrial stromal cells (HESCs) into decidual cells in response to progesterone, although the underlying mechanism is not well understood. We now demonstrate that cAMP signaling attenuates ligand-dependent sumoylation of the progesterone receptor (PR) in HESCs. In fact, decidualization is associated with global hyposumoylation and redistribution of small ubiquitin-like modifier (SUMO)-1 conjugates into distinct nuclear foci. This altered pattern of global sumoylation was not attributable to impaired maturation of SUMO-1 precursor or altered expression of E1 (SAE1/SEA2) or E2 (Ubc9) enzymes but coincided with profound changes in the expression of E3 ligases and SUMO-specific proteases. Down-regulation of several members of the protein inhibitors of activated STAT (PIAS) family upon decidualization pointed toward a role of these E3 ligases in PR sumoylation. We demonstrate that PIAS1 interacts with the PR and serves as its E3 SUMO ligase upon activation of the receptor. Furthermore, we show that silencing of PIAS1 not only enhances PR-dependent transcription but also induces expression of prolactin, a decidual marker gene, in progestin-treated HESCs without the need of simultaneous activation of the cAMP pathway. Our findings demonstrate how dynamic changes in the SUMO pathway mediated by cAMP signaling determine the endometrial response to progesterone. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17053081&query_hl=1 ER - TY - JFULL T1 - RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis. A1 - Nichol, D A1 - Christian, M A1 - Steel, JH A1 - White, R A1 - Parker, MG J1 - J Biol Chem Y1 - 2006/10/27/ VL - 281 SN - 0021-9258 SP - 32140 EP - 32147 N2 - RIP140 is a corepressor for nuclear receptors that regulates energy expenditure in adipose tissue by suppressing the expression of clusters of metabolic genes involved in glucose and lipid metabolism. The gene encoding RIP140/Nrip1 contains only one coding exon but has multiple promoters and 5' non-coding exons that are subject to alternative splicing. In adipocytes we have defined a promoter, referred to as P2, that is preferentially utilized and activated during adipogenesis. Expression studies and chromatin immunoprecipitation experiments indicate that estrogen-related receptor alpha (ERRalpha), the level of which increases during adipogenesis in parallel with RIP140, stimulates transcription from the P2 promoter. Further analysis indicates that ERRalpha is capable of activating RIP140 gene transcription by two mechanisms, directly by binding to an estrogen receptor element/ERR element at -650/-633 and indirectly through Sp1 binding sites in the proximal promoter. Thus, the up-regulation of RIP140 by ERRalpha during adipogenesis may provide an inhibitory feedback mechanism to control the expression of many nuclear receptor target genes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16923809&query_hl=1 ER - TY - JFULL T1 - Novel epididymal protease inhibitors with Kazal or WAP family domain. A1 - Jalkanen, J A1 - Kotimäki, M A1 - Huhtaniemi, I A1 - Poutanen, M J1 - Biochem Biophys Res Commun Y1 - 2006/10/13/ VL - 349 SN - 0006-291X SP - 245 EP - 254 N2 - The epididymal maturation of spermatozoa is regulated by changes in the luminal ion concentration and the processing of the sperm surface membrane by several glycosidases and proteases. In the present study, we identified five novel protease inhibitors that are highly expressed in the mouse epididymis. Four of the proteins were found to belong to the Kazal protease inhibitor family and were named SPINK8, SPINK10, SPINK11, and SPINK12, whereas one of the proteins, WFDC10, contained the WAP four-disulfide core domain structure. The novel genes showed very specific segmental expression patterns. The expression of all the five genes was regulated by testis-derived factors and decreased after gonadectomy. With the exception of Spink11, mRNA levels could be restored by testosterone replacement. We hypothesize that the protease inhibitors discovered represent a group of epididymal genes that contribute to the regulation of sperm maturation by regulating the proteolytic processing of the sperm membrane during epididymal transit. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16930550&query_hl=1 ER - TY - JFULL T1 - High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation. A1 - Pasquini, L A1 - Wimalasundera, RC A1 - Fichera, A A1 - Barigye, O A1 - Chappell, L A1 - Fisk, NM J1 - Ultrasound Obstet Gynecol Y1 - 2006/10// VL - 28 SN - 0960-7692 SP - 681 EP - 687 N2 - OBJECTIVES: Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm. METHODS: This is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation managed with serial ultrasound surveillance, medical amnioreduction and elective Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and change in AFI in monoamniotic pregnancies managed with oral sulindac was compared with 40 gestation-matched monochorionic-diamniotic controls. RESULTS: Among 44 monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks' gestation satisfied the inclusion criteria. All fetuses survived to 28 days postnatally despite early prenatal cord entanglement in all but one case. Whereas AFI remained stable throughout gestation in the controls, the AFI fell in those patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20 weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across gestation = 0.001) but mainly remained within normal limits. Fetal lie was stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the control group (P < 0.0001). CONCLUSIONS: Cord entanglement appears unpreventable, as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to more stable fetal lie, and may prevent intrauterine death by diminishing the risk of constricting cords that are already entangled. Perinatal survival in monoamniotic pregnancies managed by a regime of sulindac from 20 weeks' gestation, close ultrasound surveillance and elective abdominal delivery at 32 weeks' gestation seems empirically higher than that in the literature. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17001748&query_hl=1 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 - Pragmatic comparison of beta2-agonist side effects within the Worldwide Atosiban versus Beta Agonists study. A1 - Chan, J A1 - Cabrol, D A1 - Ingemarsson, I A1 - Marsal, K A1 - Moutquin, JM A1 - Fisk, NM J1 - Eur J Obstet Gynecol Reprod Biol Y1 - 2006/09// VL - 128 SN - 0301-2115 SP - 135 EP - 141 N2 - OBJECTIVE: While beta2-agonists for the acute treatment of preterm labour unequivocally reduce the odds of delivery within 48 h and 7 days, they have been associated with substantial maternal and fetal side effects. We aimed to compare side effect profiles of beta2-agonist tocolytics. STUDY DESIGN: Pragmatic comparison of ritodrine, salbutamol and terbutaline from re-analysis of data obtained within three comparator arms of three simultaneous comparable randomised controlled trials of beta2-agonists against atosiban in 742 women in preterm labour. The prevalence of categoric side effects between treatment groups was analysed using a chi2 test. The differences in continuous variables between treatment groups were analysed in analyses of covariance. RESULTS: The prevalence of categoric side effects was similar with the three drugs, with the exception of the subjective symptom of palpitations (ritodrine 24.0%, terbutaline 9.3% and salbutamol 12.3%, P=0.003). There were also some differences in maternal diastolic blood pressure (P<0.001) and serum glucose levels (P<0.001), although these were small (<3 mmHg and < or =2.8 mmol/L, respectively) and clinically unimportant. CONCLUSION: Side effects were common with all three drugs. Thus, choosing one beta2-agonist over the other to minimise side effects has little rationale, especially now that safer tocolytics are available. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16504369&query_hl=1 ER - TY - JFULL T1 - Influence of physical activity on calcaneal quantitative ultrasound (QUS): Results from the European male ageing study (EMAS). A1 - Pye, SR A1 - O'Neill, TW A1 - Boonen, S A1 - Borghs, H A1 - Vanderschueren, D A1 - Adams, JE A1 - Bartfai, G A1 - Casanueva, F A1 - Finn, JD A1 - Forti, G A1 - Giwercman, A A1 - Huhtaniemi, I A1 - Kula, K A1 - Punab, M A1 - Silman, AJ A1 - Wu, FC J1 - J BONE MINER RES Y1 - 2006/09// VL - 21 SN - 0884-0431 SP - S172 EP - S172 ER - TY - JFULL T1 - Weak noncovalent Si center dot center dot center dot F-C interactions stabilized fluoroalkylated rod-like polysilanes as ultrasensitive chemosensors A1 - Saxena, A A1 - Rai, R A1 - Kim, SY A1 - Fujiki, M A1 - Naito, M A1 - Okoshi, K A1 - Kwak, G J1 - J POLYM SCI POL CHEM Y1 - 2006/09/01/ VL - 44 SN - 0887-624X SP - 5060 EP - 5075 N2 - Noncovalent interactions, such as hydrogen bonding, metal coordination, and pi-pi stacking, are increasingly being utilized to develop well-ordered and self-organized supramolecular materials. Recently, new types of nonclassical weak interactions, such as C-H-...pi, C-(HF)-F-...-C, and C-(HO)-O-..., have been exploited in stabilizing the specific conformations of molecules and molecular assemblies in the solid state. These noncovalent interactions play an important role in materials comprised of polymer chains, because cooperative effects from a large number of weak interactions can lead to drastic changes in its conformation, several properties, and functionalities. The programmed design of synthetic helical polymer with well-defined molecular conformation has been the main subject in modern polymer science and engineering. Silicon-catenated polysilane is an ideal helical silicon quantum wire and polymers with unique photophysical properties. The present review highlights the spectroscopic evidences for through-space weak (SiF)-F-...-C interaction in poly(methyl-3,3,3-trifluoropropylsilane) (1) in noncoordinating and coordinating solvents by means of NMR (Si-29 and F-19) and IR spectroscopies, and viscometric measurement. It was found that 1 is applicable for chemosensors with an extremely high sensitivity and selectivity toward fluoride ions in tetrahydrofuran (THF) and with high sensitivity for nitroaromatic compounds, detected by a decrease in the photoluminescence intensity in THF and in thin solid film. (c) 2006 Wiley Periodicals, Inc. ER - TY - JFULL T1 - The risk of pre-eclampsia is decreased in women with endometriosis. A1 - Brosens, I A1 - De Sutter, P A1 - Hamerlynck, T A1 - Imeraj, L A1 - Brosens, JJ A1 - Dhont, M J1 - FERTIL STERIL Y1 - 2006/09// VL - 86 SN - 0015-0282 SP - S269 EP - S269 ER - TY - JFULL T1 - Determination of androgen bioactivity in human serum samples using a recombinant cell based in vitro bioassay. A1 - Roy, P A1 - Franks, S A1 - Read, M A1 - Huhtaniemi, IT J1 - J Steroid Biochem Mol Biol Y1 - 2006/09// VL - 101 SN - 0960-0760 SP - 68 EP - 77 N2 - The present study describes the development and optimization of a cell-based reporter assay for the determination of androgen bioactivity levels in human serum samples. Towards this end, human embryonic kidney (HEK) 293 cells were cotransfected with two plasmids, one encoding the mouse mammary tumor virus (MMTV)-driven luciferase reporter gene and the other the SV40 promoter-driven human androgen receptor (AR), and a stable cell line, expressing human AR and androgen-responsive luciferase was established by antibiotic selection. RT-PCR confirmed proper transcription and stable integration of AR in the cell line. On stimulation of the cells with testosterone (T) for 24h, luciferase activity was increased in dose-dependent fashion up to 15-fold, with the minimum effective concentration of T being 0.03 nmol/l. T-induced reporter gene expression of the cells was inhibited by the anti-androgens cyproterone acetate and hydroxyflutamide. Upon stimulation with non-androgenic steroids like estradiol, progesterone, dexamethasone and cortisol, the cells showed only marginal activity except for a weak glucocorticoid effect at high concentration. The cells also responded well to various chemicals (mostly pesticides, their metabolites and common industrial chemicals) with known androgenic activity. The cell line was further optimized by measuring the levels of androgens from male and female serum samples. Our data indicated that the cells can be used to estimate androgen bioactivity in serum of females suffering from polycystic ovary syndrome (PCOS) and males of different age groups. In conclusion, we demonstrate that the bioassay based on this cell line provides a reliable method to determine serum levels of androgen bioactivity from biological samples even at the low concentrations present in female circulation. The 96-well plate format makes the assay suitable for high throughput measurements. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16893644&query_hl=1 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 - Recurrent miscarriage. A1 - Rai, R A1 - Regan, L J1 - Lancet Y1 - 2006/08/12/ VL - 368 SN - 1474-547X SP - 601 EP - 611 N2 - Many human conceptions are genetically abnormal and end in miscarriage, which is the commonest complication of pregnancy. Recurrent miscarriage, the loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive. It is associated with psychological morbidity, and has often proven to be frustrating for both patient and clinician. A third of women attending specialist clinics are clinically depressed, and one in five have levels of anxiety that are similar to those in psychiatric outpatient populations. Many conventional beliefs about the cause and treatment of women with recurrent miscarriage have not withstood scrutiny, but progress has been made. Research has emphasised the importance of recurrent miscarriage in the range of reproductive failure linking subfertility and late pregnancy complications and has allowed us to reject practice based on anecdotal evidence in favour of evidence-based management. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16905025&query_hl=1 ER - TY - JFULL T1 - The SWI/SNF chromatin remodeling subunit BAF57 is a critical regulator of estrogen receptor function in breast cancer cells. A1 - García-Pedrero, JM A1 - Kiskinis, E A1 - Parker, MG A1 - Belandia, B J1 - J Biol Chem Y1 - 2006/08/11/ VL - 281 SN - 0021-9258 SP - 22656 EP - 22664 N2 - Estrogen receptors (ERs) play critical roles in both normal mammary gland development and in the formation and progression of breast tumors, constituting a major therapeutic target for breast cancer treatment. We have previously described that ER transcriptional activity is potentiated by BAF57, a core subunit of the mammalian SWI/SNF chromatin remodeling complex. Here we provide evidence demonstrating an important role for BAF57 as regulator of ER functions in breast cancer cells. Different experimental manipulations leading to the abrogation of BAF57 expression and/or function severely reduced the expression of various endogenous ER target genes and blocked estrogen-stimulated proliferation in ZR-75-1 breast cancer cells. Moreover, using a structure-function analysis, we have defined the protein domains required for the functional interaction between ERalpha and BAF57, including a key region within the hinge of ERalpha that is essential for BAF57 recruitment and its function on ER-mediated transcription. Interestingly, we found that BAF57 is an ER subtype-selective modulator that specifically regulates ERalpha-mediated transcription. Taken together, our results suggest that targeting BAF57 could represent a new way to effectively inhibit the action of ERalpha. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16769725&query_hl=1 ER - TY - JFULL T1 - Differential endocrine regulation of genes enriched in initial segment and distal caput of the mouse epididymis as revealed by genome-wide expression profiling. A1 - Sipilä, P A1 - Pujianto, DA A1 - Shariatmadari, R A1 - Nikkilä, J A1 - Lehtoranta, M A1 - Huhtaniemi, IT A1 - Poutanen, M J1 - Biol Reprod Y1 - 2006/08// VL - 75 SN - 0006-3363 SP - 240 EP - 251 N2 - We have performed genome-wide expression profiling of endocrine regulation of genes expressed in the mouse initial segment (IS) and distal caput of the epididymis by using Affymetrix microarrays. The data revealed that of the 15 020 genes expressed in the epididymis, 35% were enriched in one of the two regions studied, indicating that differential functions can be attributed to the IS and the more distal caput regions. The data, furthermore, showed that 27% of the genes expressed in the IS and/or distal caput epididymidis are under the regulation of testicular factors present in the duct fluid, while bloodborne androgens can regulate for 14% of them. This is in line with the high testis dependency of epididymal physiology. We then focused on genes with moderate or strong expression, showing strict segment enrichment and strong dependency on testicular factors. Analyses of the 59 genes, including upregulated and downregulated genes, fulfilling the criteria indicated that the expression of 18 (17 downregulated genes; 1 upregulated gene) of 19 gonadectomy-responsive genes enriched in the IS was not maintained by the androgen treatment, whereas the expression of all six downregulated genes enriched in the distal caput and the majority of those with no strict segment enrichment of expression (28 of 34; consisting of 23 downregulated and 5 upregulated genes) were maintained by androgens. Hence, it is evident that testicular factors other than androgens are important for the expression of IS-enriched genes, whereas the expression of distal caput-enriched genes is typically regulated by androgens. Identical data were obtained by independent clustering analyses performed for the expression data of 3626 epididymal genes. Several novel genes with putative involvement in epididymal sperm maturation, such as a disintegrin and metallopeptidase domain 28 (Adam28) and a solute carrier organic anion transporter family, member 4C1 (Slco4c1), were identified, indicating that this approach is successful for identifying novel epididymal genes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16641146&query_hl=1 ER - TY - JFULL T1 - Antenatal maternal stress/anxiety and effects on child neurodevelopment A1 - Glover, V J1 - EARLY HUM DEV Y1 - 2006/08// VL - 82 SN - 0378-3782 SP - 534 EP - 534 ER - TY - JFULL T1 - The uterine junctional zone. A1 - Fusi, L A1 - Cloke, B A1 - Brosens, JJ J1 - Best Pract Res Clin Obstet Gynaecol Y1 - 2006/08// VL - 20 SN - 1521-6934 SP - 479 EP - 491 N2 - Magnetic resonance imaging has revealed that the endometrio-myometrial interface constitutes a distinct, hormone-dependent uterine compartment termed the junctional zone. In the non-pregnant uterus, highly specialized contraction waves originate exclusively from the junctional zone and participate in the regulation of diverse reproductive events, such as sperm transport, embryo implantation, and menstrual shedding. Conversely, growing evidence suggests that disruption of the normal endometrio-myometrial interface plays an integral role in diverse reproductive disorders. This chapter reviews our current understanding of the mechanisms that govern the cyclic changes in the uterine junctional zone and summarizes the evidence implicating the endometrio-myometrial interface in normal uterine physiology and pathological processes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16631411&query_hl=1 ER - TY - JFULL T1 - Study of the electronic and optical bonding properties of doped SnO2 A1 - Rai, R A1 - Senguttuvan, TD A1 - Lakshmikumar, ST J1 - COMP MATER SCI Y1 - 2006/08// VL - 37 SN - 0927-0256 SP - 15 EP - 19 N2 - Numerous metal oxide semiconductor materials were reported to be usable as semiconductor gas sensor, such as ZnO, SnO2, TiO2 and so on. These materials have non-stoichiometric structure so free electron originating from oxygen vacancies contribute to electrical conductivity. The interaction of different gas compounds with an oxide surface may lead to changes in the lattice oxygen content at the surface in addition to changes in the amount of adsorbed species. The samples of Cu doped SnO2 have been synthesized by solid-state reaction method. Some aspects of crystal structure of the compound at room temperature were studied using X-ray diffraction technique. The XRD study of the compound shows that there is a change in the crystal structure of SnO2 on substitutions of CuO. The patterns of the SnO2 sample are indexed as tetragonal perovskite type with a = 7.3928 angstrom, c = 5.2879 angstrom but on substitution of CuO the structure becomes orthorhombic with lattice constant a = 21.8594 angstrom, b = 5.3200 angstrom, c = 5.1803 angstrom. Several bands due to fundamentals, overtones and combination of OH, Sn-O and Sn-O-Sn entities appear in 4000-800 cm(-1) range. (c) 2005 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - Metabolic regulation by the nuclear receptor corepressor RIP140. A1 - Christian, M A1 - White, R A1 - Parker, MG J1 - Trends Endocrinol Metab Y1 - 2006/08// VL - 17 SN - 1043-2760 SP - 243 EP - 250 N2 - Whereas the importance of activating gene expression in metabolic pathways to control energy homeostasis is well established, the contribution of transcriptional inhibition is less well defined. In this review we highlight a crucial role of RIP140, a transcriptional corepressor for nuclear receptors, in the regulation of energy expenditure. Mice devoid of the RIP140 gene are lean, exhibit resistance to high-fat-diet-induced obesity, and have increased glucose tolerance and insulin sensitivity. Consistent with these observations, RIP140 suppresses the expression of gene clusters that are involved in lipid and carbohydrate metabolism, including fatty acid oxidation, oxidative phosphorylation and mitochondrial uncoupling. Therefore, the functional interplay between transcriptional activators and the corepressor RIP140 is an essential process in metabolic regulation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16815031&query_hl=1 ER - TY - JFULL T1 - Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-alpha in menstrual endometrium and effluent in women with menorrhagia. A1 - Malik, S A1 - Day, K A1 - Perrault, I A1 - Charnock-Jones, DS A1 - Smith, SK J1 - Hum Reprod Y1 - 2006/08// VL - 21 SN - 0268-1161 SP - 2158 EP - 2166 N2 - BACKGROUND: Heavy regular menstrual periods (menorrhagia) are an important cause of ill health in women and remain the leading indication for hysterectomy. Abnormalities of the endometrial blood vessels are among the possible causes of this condition. Many different factors affect endothelial cell growth, function and vessel remodelling. We sought to determine whether the levels of vascular endothelial growth factor-A (VEGF-A), tumour necrosis factor-alpha (TNF-alpha), matrix metalloproteinase (MMP)-2 and MMP-9 and soluble VEGF receptor-1 (VEGF-R1) were altered in the menstrual effluent of women with objective menorrhagia. We have also quantitated the VEGF-A mRNA in the menstruated endometrium. METHODS AND RESULTS: We recruited 37 women and determined their menstrual blood loss (MBL) over two cycles and collected menstrual effluent during the 2nd day of bleeding for 4 h. There was no difference in the total level of VEGF-A, and neither latent MMP. However, the concentration of VEGF-A was significantly reduced in the women with menorrhagia, as was the VEGF-A mRNA level. In addition, the active forms of both MMPs were markedly reduced and the total sVEGF-R1 as well as the TNF-alpha content were increased. CONCLUSIONS: This is the first study to show abnormalities of factors important for endothelial cell behaviour in the endometrium of women with menorrhagia. This may underlie the disordered vessel structure and/or function in this condition. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16585124&query_hl=1 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 - 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 - Mutations along the pituitary-gonadal axis affecting sexual maturation: novel information from transgenic and knockout mice. A1 - Huhtaniemi, I J1 - Mol Cell Endocrinol Y1 - 2006/07/25/ VL - 254-255 SN - 0303-7207 SP - 84 EP - 90 N2 - During the last 10 years, numerous activating and inactivating mutations have been detected in the genes encoding the two gonadotrophins, luteinising hormone (LH) and follicle-stimulating hormone (FSH), as well as their cognate receptors (R), LHR and FSHR. Because activation of the hypothalamic-pituitary-gonadal axis is a crucial event in the onset and progression of puberty, mutations affecting gonadotrophin action have major influence on this developmental process. Many of the phenotypic effects observed have been expected on the basis of the existing information about gonadotrophin action (e.g. delayed puberty), but also many unexpected findings have been made, including the lack of phenotype in women with activating LHR mutations, and the discrepancy in phenotypes of men with inactivating mutations of FSHbeta (azoospermia and infertility) and FSHR (oligozoospermia and subfertility). Some of the possible mutations, such as inactivating LHbeta and activating FSHR mutations in women, have not yet been detected. Genetically modified mice provide relevant phenocopies for the human mutations and serve as good models for studies on molecular pathogenesis of these conditions. They may also predict phenotypes of the mutations that have not yet been detected in humans. We review here briefly the effects of gonadotrophin subunit and receptor mutations on puberty in humans and contrast the information with findings on genetically modified mice with similar mutations. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16730882&query_hl=1 ER - TY - JFULL T1 - Making the UK's National Health Service cost effective A1 - Smith, SK J1 - LANCET Y1 - 2006/07/22/ VL - 368 SN - 0140-6736 SP - 286 EP - 286 ER - TY - JFULL T1 - Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome. A1 - Francis, J A1 - Rai, R A1 - Sebire, NJ A1 - El-Gaddal, S A1 - Fernandes, MS A1 - Jindal, P A1 - Lokugamage, A A1 - Regan, L A1 - Brosens, JJ J1 - Mol Hum Reprod Y1 - 2006/07// VL - 12 SN - 1360-9947 SP - 435 EP - 442 N2 - Antiphospholipid syndrome (APS), characterized by circulating antiphospholipid (aPL) antibodies, is a major cause of early pregnancy failure and placental insufficiency. In this study, we examined whether impaired endometrial differentiation before conception contributes to the high incidence of pregnancy complications in APS. Timed secretory endometrial biopsies were obtained from a cohort of women with recurrent pregnancy loss (RPL). Real-time quantitative (RTQ)-PCR was used to determine the expression levels of transcripts that encode for decidual markers, proinflammatory cytokines and complement regulatory proteins. Expression of decidual markers such as prolactin (PRL), tissue factor (TF) and signal transducer and activator of transcription 5 (Stat5), but not insulin-like growth factor-binding protein 1 (IGFBP-1), was significantly lower in samples obtained from aPL(+) patients (n = 24) when compared with aPL(-) group (n = 58) (P < 0.05). The abundance of transcripts encoding for interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha) or Stat1 did not differ significantly between both groups (P >/= 0.05). However, analysis of transcripts that encode for complement regulatory proteins showed a marked decrease in decay-accelerating factor (DAF/CD55) levels in aPL(+) patients (P = 0.005), which was mimicked at protein level as demonstrated by immunohistochemistry. In summary, patients with RPL have distinct endometrial gene expression profiles depending on the presence or absence of circulating aPL antibodies. In APS, impaired endometrial differentiation and lower DAF/CD55 expression before conception may compromise implantation and predispose to complement-mediated pregnancy failure. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16735457&query_hl=1 ER - TY - JFULL T1 - Retreatment with peginterferon alpha-2a (40KD) (Pegasys (R)) plus ribavirin (Copegus (R)) in patients in whom pegylated interferon alpha-2b (12KD)/ribavirin has failed: planned week-12 efficacy and safety analysis of the repeat study A1 - Marcellin, P A1 - Teuber, G A1 - Freilich, B A1 - Weiland, O A1 - Di Bisceglie, A A1 - Brandao-Mello, C A1 - Canva, V A1 - Andreone, P A1 - Rai, R A1 - Jensen, D J1 - J CLIN VIROL Y1 - 2006/07// VL - 36 SN - 1386-6532 SP - S142 EP - S142 ER - TY - JFULL T1 - Suppression of gonadotropins inhibits gonadal tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene (vol 138, pg 3521, 1997) A1 - Huhtaniemi, I J1 - ENDOCRINOLOGY Y1 - 2006/07// VL - 147 SN - 0013-7227 SP - 3317 EP - 3317 ER - TY - JFULL T1 - The HPA axis and perinatal depression: a hypothesis. A1 - Kammerer, M A1 - Taylor, A A1 - Glover, V J1 - Arch Womens Ment Health Y1 - 2006/07// VL - 9 SN - 1434-1816 SP - 187 EP - 196 N2 - Episodes of depression and anxiety are as common during pregnancy as postpartum. Some start in pregnancy and resolve postpartum, others are triggered by parturition and some are maintained throughout. In order to determine any biological basis it is important to delineate these different subtypes. During pregnancy, as well as the rise in plasma oestrogen and progesterone there is a very large increase in plasma corticotropin releasing hormone (CRH), and an increase in cortisol. The latter reaches levels found in Cushing's syndrome and major melancholic depression. Levels of all these hormones drop rapidly on parturition.We here suggest that the symptoms of antenatal and postnatal depression may be different, and linked in part with differences in the function of the hypothalamic pituitary adrenal (HPA) axis. There are two subtypes of major depression, melancholic and atypical, with some differences in symptom profile, and these subtypes are associated with opposite changes in the HPA axis. Antenatal depression may be more melancholic and associated with the raised cortisol of pregnancy, whereas postnatal depression may be more atypical, triggered by cortisol withdrawal and associated with reduced cortisol levels. There is evidence that after delivery some women experience mild bipolar II depression, and others experience post traumatic stress disorder. Both of these are associated with atypical depression. It may also be that some women are genetically predisposed to depression of the melancholic type and some to depression of the atypical type. These women may be more or less vulnerable to depression at the different stages of the perinatal period. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16708167&query_hl=1 ER - TY - JFULL T1 - Identification of BAF57 mutations in human breast cancer cell lines. A1 - Kiskinis, E A1 - García-Pedrero, JM A1 - Villaronga, MA A1 - Parker, MG A1 - Belandia, B J1 - Breast Cancer Res Treat Y1 - 2006/07// VL - 98 SN - 0167-6806 SP - 191 EP - 198 N2 - Accumulating genetic and biochemical evidences support a role for the SWI/SNF chromatin-remodeling complex in cancer development and multiple core subunits of these complexes have been found to function as tumor suppressor genes. The core SWI/SNF subunit BAF57 mediates direct interactions with estrogen and androgen receptors (ER and AR) regulating their transcriptional activity. BAF57 gene maps to chromosome band 17 q21 in close proximity to the BRCA1 gene. This locus has been associated with frequent loss of heterozygosity (LOH) and allelic imbalance in breast cancers; however, BRCA1 mutations are rare events in sporadic breast cancer with LOH in the region, suggesting that another tumor suppressor gene resides in this area. All these reasons prompted us to screen for mutations in the BAF57 gene using a panel of the most commonly used human breast cancer cell lines. All cell lines analysed contain wild-type copies of BAF57 gene with the only exception of the breast ductal carcinoma cell line BT549. Sequencing of genomic DNA and cDNA generated from BT549 mRNA demonstrated the presence of a CA dinucleotide insertion in exon 5 of BAF57. The absence of wild-type BAF57 alleles indicates that this is a biallelic inactivating mutation that causes a frameshift and as a consequence a premature stop codon leading to a truncated BAF57 protein. A functional characterisation of the truncated BAF57 showed that it has lost the ability to bind to ER but still binds to the nuclear receptor coactivator SRC1e. Furthermore, we observed that the expression of the truncated BAF57 increased the ability of SRC1e to potentiate transcriptional activation by ERalpha, suggesting that mutations in BAF57 could contribute to the oncogenic transformation in breast cancer cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16538531&query_hl=1 ER - TY - JFULL T1 - Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata. A1 - Smart, OC A1 - Hindley, JT A1 - Regan, L A1 - Gedroyc, WG J1 - Obstet Gynecol Y1 - 2006/07// VL - 108 SN - 0029-7844 SP - 49 EP - 54 N2 - OBJECTIVE: Magnetic-resonance-guided focused ultrasound is a novel, noninvasive technique of thermoablation for uterine leiomyomata. The hypothesis of this study was that pretreatment of leiomyomata with gonadotrophin-releasing hormone (GnRH) agonists would allow effective treatment of larger uterine leiomyomata, increasing the number of women who could benefit from this technique. METHODS: We report a prospective study of women with leiomyomata in excess of 10 cm in diameter who received GnRH agonist before magnetic-resonance-guided focused ultrasound treatment. Eligible participants were recruited from the gynecology outpatient clinics. Entry criteria were a minimal leiomyoma symptom severity score and confirmation of uterine dimensions based on screening magnetic resonance imaging. These women received a 3-month course of GnRH agonists followed by magnetic-resonance-guided focused ultrasound treatment. The primary outcome measurement was reported change in symptom severity score as judged by the Uterine Fibroid Symptom and Quality of Life questionnaire. Comparison was made at enrollment, treatment, and at 3, 6, and 12 months posttreatment. A secondary outcome was the measured change in target leiomyoma volume. RESULTS: Forty-nine women were enrolled in the study. There was a 45% reduction in median symptom severity score at 6 months and 48% at 12 months posttreatment, with 83% of women achieving at least a 10-point reduction in symptom scoring at 6 months and 89% at 12 months (P < .001). There was an average reduction in target leiomyoma volume of 21% overall at 6 months (P < .001) and 37% at 12 months (P < .001). No serious infective complications or emergency operative interventions were recorded. CONCLUSION: The use of GnRH agonist therapy before magnetic-resonance-guided focused ultrasound improves the thermoablative treatment effect. LEVEL OF EVIDENCE: II-3. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16816055&query_hl=1 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 - Genetically modified mouse models in studies of luteinising hormone action. A1 - Huhtaniemi, I A1 - Ahtiainen, P A1 - Pakarainen, T A1 - Rulli, SB A1 - Zhang, FP A1 - Poutanen, M J1 - Mol Cell Endocrinol Y1 - 2006/06/27/ VL - 252 SN - 0303-7207 SP - 126 EP - 135 N2 - Numerous genetically modified mouse models have recently been developed for the study of the pituitary-gonadal interactions. They include spontaneous or engineered knockouts (KO) of the gonadotrophin-releasing hormone (GnRH) and its receptor, the gonadotrophin common-alpha(Calpha), luteinising hormone (LH) beta and follicle-stimulating hormone (FSH) beta subunits, and the two gonadotrophin receptors (R), LHR and FSHR. In addition, there are also transgenic (TG) mice overexpressing gonadotrophin subunits and producing supraphysiological levels of these hormones. These models have offered relevant phenocopies for similar mutations in humans and to a great extent expanded our knowledge on normal and pathological functions of the hypothalamic-pituitary-gonadal (HPG) axis. The purpose of this article is to review some of our recent findings on two such mouse models, the LHR KO mouse (LuRKO), and the hCG overexpressing TG mouse (hCG+). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16675102&query_hl=1 ER - TY - JFULL T1 - Serum testosterone and brachial endothelial function in aging men A1 - Makinen, JI A1 - Perheentupa, A A1 - Irjala, K A1 - Pollanen, P A1 - Makinen, J A1 - Huhtaniemi, I A1 - Raitakari, OT J1 - ATHEROSCLEROSIS SUPP Y1 - 2006/06// VL - 7 SN - 1567-5688 SP - 221 EP - 221 ER - TY - JFULL T1 - FOXO3a inhibition confers resistance to apoptosis induced by oxidative stress in decidualizing human endometrial stromal cells A1 - Kajihara, T A1 - Ishihara, O A1 - Fusi, L A1 - Higham, JM A1 - Brosens, JJ J1 - HUM REPROD Y1 - 2006/06// VL - 21 SN - 0268-1161 SP - I186 EP - I186 ER - TY - JFULL T1 - Maternal anxiety at amniocentesis and plasma cortisol. A1 - Sarkar, P A1 - Bergman, K A1 - Fisk, NM A1 - Glover, V J1 - Prenat Diagn Y1 - 2006/06// VL - 26 SN - 0197-3851 SP - 505 EP - 509 N2 - OBJECTIVES: To assess whether anticipation of amniocentesis is linked with maternal anxiety, and whether this anxiety is associated with increased maternal plasma cortisol. METHODS: Two hundred and fifty-four women awaiting a morning amniocentesis for karyotyping (gestation range 15-37 weeks, median 17 weeks) completed Spielberger state and trait anxiety inventory (STAI) questionnaires, and provided blood samples immediately before the procedure for cortisol assay. Six hundred and five women at mean gestation of 20 weeks, attending the same hospital for routine ultrasound but not for amniocentesis, also completed Spielberger STAI questionnaires and served as a comparison group for the anxiety ratings. RESULTS: Mean state and trait anxiety scores (+/- SD) in the comparison group of 605 women at mean gestation of 20 weeks were 36.1 +/- 10.2 (range 20-70) and 35.6 +/- 8.9 (range 20-73), respectively. The mean state anxiety score (+/-SD) of 49.8 +/- 14.0 (range 20-77) of the amniocentesis group was considerably higher than the comparison group (p < 0.001), although the mean trait anxiety score in the amniocentesis group was similar at 36.4 +/- 8.6 (range 21-60). The state, but not trait, anxiety correlated with plasma cortisol (r = 0.176, p = 0.005). Maternal cortisol in the amniocentesis group increased with gestational age (r = 0.310, p < 0.001), whereas state anxiety scores showed no significant change with increase in gestational age (r = - 0.042, ns). Multivariate analysis demonstrated that maternal state anxiety was positively correlated with plasma cortisol independent of gestation and time of collection. CONCLUSION: Women awaiting amniocentesis experience a high state anxiety associated with modestly increased plasma cortisol. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16683297&query_hl=1 ER - TY - JFULL T1 - Prevelence of hyperglycemia among new adult patients at a county ambulatory screening clinic A1 - Torke, NS A1 - Boral, L A1 - Gandhi, S A1 - Rai, R A1 - Mukarram, M J1 - CLIN CHEM Y1 - 2006/06// VL - 52 SN - 0009-9147 SP - A101 EP - A101 ER - TY - JFULL T1 - The adrenal gland may be a target of LH action in postmenopausal women. A1 - Alevizaki, M A1 - Saltiki, K A1 - Mantzou, E A1 - Anastasiou, E A1 - Huhtaniemi, I J1 - Eur J Endocrinol Y1 - 2006/06// VL - 154 SN - 0804-4643 SP - 875 EP - 881 N2 - OBJECTIVE: LH receptor expression and function have been demonstrated in the human adrenal cortex, but their involvement in normal adrenal function remains elusive. Because cortisol levels have been reported to be higher in postmenopausal women than in age-matched men, the aim of the present study was to investigate a possible association of adrenal function with the elevated LH levels in postmenopausal women. DESIGN AND METHODS: A group of 112 endocrinologically normal postmenopausal women (mean age 67.6, range 50-88 years) was evaluated. A basal fasting morning sample of peripheral blood was taken for the determination of LH, cortisol, dehydroepiandrosterone-sulphate (DHEA-S), oestradiol (E2), testosterone, sex hormone-binding globulin (SHBG), insulin and glucose. Information about reproductive function, anthropometric parameters and arterial blood pressure was recorded. RESULTS: The correlation of LH and cortisol was bimodally distributed, with a significant linear correlation up to the LH level of 41 U/l (n = 78, P<0.01), after which the increase of cortisol levelled off. Significant associations were also found between serum DHEA-S and LH levels (P<0.05), as well as between cortisol and testosterone (P<0.0001), but not between E2 and LH. Multivariate analysis showed that the association of cortisol with LH was independent of age and testosterone; the association of DHEA-S with LH was independent of E2, cortisol and age. Significant associations were also found between E2, testosterone and DHEA-S levels (P<0.001). CONCLUSIONS: These results indicate that adrenal cortisol and DHEA-S production may be stimulated by the highly elevated postmenopausal levels of LH; the physiological significance of this association and plausible contribution to the metabolic syndrome observed after the menopause remain to be evaluated. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16728548&query_hl=1 ER - TY - JFULL T1 - Death or survival--progesterone-dependent cell fate decisions in the human endometrial stroma. A1 - Brosens, JJ A1 - Gellersen, B J1 - J Mol Endocrinol Y1 - 2006/06// VL - 36 SN - 0952-5041 SP - 389 EP - 398 N2 - The human endometrium undergoes cyclical waves of proliferation, differentiation and apoptosis in response to the rise and fall in ovarian oestradiol and progesterone levels. These hormonal responses in endometrial cells must be tightly kept in check to safeguard tissue homeostasis throughout reproductive life. The discovery that differentiating endometrium highly expresses the tumour suppressor p53, the forkhead transcription factor FOXO1, and promyelocytic leukaemia zinc finger protein (PLZF) has provided new insights into the molecular basis of life and death decisions in response to sex steroid hormones. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16720711&query_hl=1 ER - TY - JFULL T1 - Peripheral blood natural killer cells and recurrent miscarriage - a prospective study A1 - Rai, R A1 - Backos, M A1 - Francis, J A1 - Brosens, J A1 - Regan, L J1 - HUM REPROD Y1 - 2006/06// VL - 21 SN - 0268-1161 SP - I11 EP - I11 ER - TY - JFULL T1 - Regulation of the human oxytocin receptor by nuclear factor-kappaB and CCAAT/enhancer-binding protein-beta. A1 - Terzidou, V A1 - Lee, Y A1 - Lindström, T A1 - Johnson, M A1 - Thornton, S A1 - Bennett, PR J1 - J Clin Endocrinol Metab Y1 - 2006/06// VL - 91 SN - 0021-972X SP - 2317 EP - 2326 N2 - CONTEXT: Increased myometrial sensitivity to oxytocin at term is mediated through increased oxytocin receptor (OTR) expression. OTR promoter contains putative transcription factor-binding sites for activating protein-1 (AP-1), CCAAT/enhancer-binding protein (C/EBP), and nuclear factor-kappaB (NF-kappaB), which may be activated by IL-1beta, whose concentrations increase with labor. OBJECTIVE: The objective of this study was to examine the effect of IL-1beta on OTR expression and the roles of AP-1, C/EBP, and NF-kappaB in OTR promoter function. RESULTS: IL-1beta induces an increase in OTR mRNA concentrations and OTR ligand binding in myometrial cells, which is maximal at 4 h and decreased after 20 h. IL-1beta activates the transcription factors AP-1 C/EBPbeta, and NF-kappaB. Using computer-based analysis and EMSA studies, we have identified three AP-1, nine C/EBP, and three NF-kappaB DNA-binding sites in the OTR promoter. In transient transfection studies, OTR promoter activity was increased by C/EBPbeta and NF-kappaB, but not by AP-1. C/EBPbeta and NF-kappaB together had a synergistic action in the induction of OTR promoter activity. Site-directed mutagenesis of each individual C/EBP and NF-kappaB site had no effect on the ability of C/EBPbeta, NF-kappaB, or their combination to activate OTR promoter. However, mutation of both NF-kappaB sites inhibited promoter activation by NF-kappaB alone, but not that by the combination of C/EBPbeta and NF-kappaB. Deletion studies showed that a region between -851 and -656 of the OTR confers responsiveness to the combination of C/EBPbeta and NF-kappaB. CONCLUSION: IL-1beta has a biphasic effect on OTR expression in myometrial cells, and C/EBP and NF-kappaB play synergistic roles in OTR promoter activation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16569740&query_hl=1 ER - TY - JFULL T1 - Identification of novel epididymal genes by expression profiling and in silico gene discovery. A1 - Jalkanen, J A1 - Shariatmadari, R A1 - Pujianto, DA A1 - Sipilä, P A1 - Huhtaniemi, I A1 - Poutanen, M J1 - Mol Cell Endocrinol Y1 - 2006/05/16/ VL - 250 SN - 0303-7207 SP - 163 EP - 168 N2 - We have used both the UniGene RIKEN epididymal EST library and the Affymetrix microarray profiling for identifying novel epididymal genes in mouse. The use of ESTs is a complementary approach to Affymetrix arrays for identifying novel epididymal genes, while only 32% and 28% of ESTs of unknown genes were present in the U74v.2Set and MG 430 2.0 version Affymetrix arrays, respectively. As expected, the probe set for a notably larger proportion of known genes was present in the Affymetrix arrays, and the coverage was greatly improved by the newer array version. Furthermore, many genes with more than five ESTs in the UniGene library showed variable levels of expression in both versions of the Affymetrix arrays. However, both the Affymetrix and EST data correlated well with that obtained by quantitative RT-PCR, and thus, we conclude that the findings of high EST number but only limited expression in the arrays could be considered as false negatives in the Affymetrix arrays. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16413671&query_hl=1 ER - TY - JFULL T1 - Genetic thrombophilic mutations among couples with recurrent miscarriage. A1 - Jivraj, S A1 - Rai, R A1 - Underwood, J A1 - Regan, L J1 - Hum Reprod Y1 - 2006/05// VL - 21 SN - 0268-1161 SP - 1161 EP - 1165 N2 - BACKGROUND: Some cases of recurrent first trimester miscarriage (RM)-the loss of three or more consecutive pregnancies at <12 weeks' gestation-have a thrombotic aetiology. METHODS: We determined (i) the prevalence of three thrombophilic mutations [factor V Leiden (FVL), prothrombin G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR) C677T] amongst 357 Caucasian couples with RM and 68 parous Caucasian couples with no history of miscarriage and (ii) the prospective outcome of untreated pregnancies amongst couples with RM in which either partner carried a thrombophilic mutation. RESULTS: The allele frequencies of FVL (2%), PTG (2%) and MTHFR C677T (31%) were similar between cases and controls. The prevalence of multiple thrombophilic mutations (greater than one mutation) was also similar between cases and controls. Amongst couples in whom either partner carried greater than one thrombophilic allele, the relative risk of miscarriage in a future untreated pregnancy was 1.9 (95% confidence interval, 1.3-2.8) compared with those couples who carried no thrombophilic mutation. CONCLUSION: The prevalence of thrombophilic mutations is similar in couples with RM and parous controls. In couples with RM, multiple genetic thrombophilic mutations in either partner significantly increases the risk of miscarriage in a subsequent pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16431900&query_hl=1 ER - TY - JFULL T1 - The role of mesenchymal stem cells in haemopoiesis. A1 - Dazzi, F A1 - Ramasamy, R A1 - Glennie, S A1 - Jones, SP A1 - Roberts, I J1 - Blood Rev Y1 - 2006/05// VL - 20 SN - 0268-960X SP - 161 EP - 171 N2 - The ontogeny of haemopoiesis during fetal life and the differentiation of blood cells in adult life depend upon a fully competent microenvironment to provide appropriate signals via production of soluble factors and cell contact interactions. The cellular constituents of the microenvironment, also defined as the haemopoietic niche, largely derive from a common progenitor of mesenchymal origin. Mesenchymal stem cells (MSC), initially identified in adult bone marrow, have also been described in fetal haemopoietic tissues where they accompany the migration of haemopoietic development. Their precise identity remains ill-defined because of the lack of specific markers. Their ability to self-renew and differentiate into tissues of mesodermal origin (osteocytes, adipocytes, chondrocytes) and their lack of expression of haemopoietic molecules are currently the main criteria for isolation. In the bone marrow the most important elements of the niche appear to be osteoblasts, whilst a less defined population of fibroblasts regulates the maturation of immature T cells in the thymus. Recently, MSC have been shown to exert a profound immunosuppressive effect on polyclonal as well as antigen-specific T cell responses by inducing a state of division arrest anergy. Thus, the multipotent capacity of MSC, their role in supporting haemopoiesis, and their immunoregulatory activity make MSC particularly attractive for therapeutic exploitation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16364518&query_hl=1 ER - TY - JFULL T1 - Genes encoding bile acid, phospholipid and anion transporters are expressed in a human fetal cardiomyocyte culture. A1 - Gorelik, J A1 - Patel, P A1 - Ng'andwe, C A1 - Vodyanoy, I A1 - Diakonov, I A1 - Lab, M A1 - Korchev, Y A1 - Williamson, C J1 - BJOG Y1 - 2006/05// VL - 113 SN - 1470-0328 SP - 552 EP - 558 N2 - OBJECTIVES: To establish a human fetal cardiomyocyte culture and to investigate whether the genes that encode transporters that may influence influx or efflux of bile acids are expressed in human fetal cardiomyocytes. DESIGN: Laboratory study. SETTING: Imperial College London. SAMPLE: Six fetal hearts were obtained at the time of termination of pregnancy at 12-13 weeks of gestation and used to generate primary human cardiomyocyte cultures. METHODS: To confirm the presence of cardiomyocytes, the cells were incubated with monoclonal antibodies to sarcomeric alpha-actinin and anticardiac myosin heavy chain. Real-time reverse transcription polymerase chain reaction was used to establish whether transcripts of genes that may influence bile acid transport are present in the culture (NTCP, BSEP, MDR3, FIC1, MRP2, MRP3, OATP-A, OATP-C, OATP-D, OATP-E) and whether taurocholate administration alters messenger RNA (mRNA) expression. MAIN OUTCOME MEASURES: Relative mRNA expression of genes of interest. RESULTS: Real-time polymerase chain reaction demonstrated the presence of mRNA for BSEP, MDR3, FIC1, OATP-C, OATP-D and OATP-E in fetal heart. Four transcripts remained in the cardiomyocyte culture (BSEP, MDR3, FIC1 and OATP-D), and we demonstrated the influence of taurocholate on gene expression. CONCLUSIONS: We have developed an in vitro model of the fetal heart that may be used for studies of the cardiac effect of endobiotics, e.g. bile acids, or of specific agents that may be used to treat the mother or fetus in pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16637898&query_hl=1 ER - TY - JFULL T1 - Determinants of flow along arterio-arterial anastomoses in monochorionic placentae by dynamic computer modelling of chorionic plate vasculature. A1 - Denbow, ML A1 - Talbert, D A1 - Fisk, NM J1 - Prenat Diagn Y1 - 2006/05// VL - 26 SN - 0197-3851 SP - 433 EP - 442 N2 - OBJECTIVES: To investigate anatomical and physiological determinants of inter-fetal transfusion along arterio-arterial (AA) anastomoses in monochorionic placentae. METHODS: A computer model of chorionic arterial vasculature was constructed in QuickBASIC using data collected from experimentation and the published literature. After validating the model, the influence of various physiological and anatomical variables on anastomotic flow rates was examined. RESULTS: AA anastomotic flow rates were significantly related to changes in fetal mean arterial pressure (p < 0.0001) and heart rate (p < 0.0005). AA flow rates were also related to the imbalance in number of arterio-venous (AV) anastomoses, to placental territory share, and to the branch number of the AA anastomosis (AAAs) from the chorionic arterial tree. CONCLUSIONS: Net blood flow and direction along AA anastomoses are influenced by fetal cardiac output, by the presence of compensatory AV anastomoses, and by the branch number of the chorionic arteries connected by the anastomosis. This study provides insight into the determinants of chronic transfusional imbalance as well as acute inter-fetal transfusion. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16548009&query_hl=1 ER - TY - JFULL T1 - Histomorphometric characterisation of shared and non-shared cotyledonary villus territories of monochorionic placentae in relation to pregnancy complications. A1 - Wee, LY A1 - Sebire, NJ A1 - Bhundia, J A1 - Sullivan, M A1 - Fisk, NM J1 - Placenta Y1 - 2006/04// VL - 27 SN - 0143-4004 SP - 475 EP - 482 N2 - OBJECTIVE: Theoretical estimates and physiological inferences suggest that the structure of a shared cotyledon differs from a non-shared cotyledon. The aim of this study was to characterise the histomorphometry of terminal villi in shared and non-shared cotyledons in monochorionic placentae, both from uncomplicated twins and from those with twin-twin transfusion syndrome (TTTS) or discordant growth restriction (DeltaIUGR). METHODS: Forty-one monochorionic placentae from Caucasian non-smokers were obtained at caesarean section. Their vascular anatomy and placental territories were ascertained by dye injection. After fixation, full thickness histological blocks were obtained by systematic random sampling from each twin's territory and the shared cotyledons. Fifty randomly selected terminal villi were assessed for: (i) median villus diameter (ii) median villus capillary diameter (iii) median fetomaternal diffusion distance (iv) median no. of capillaries/villus (v) degree of vascularization (median percentage cross-sectional area of terminal villi occupied by capillaries) using a stage micrometer and image analysis programme. The histomorphometric findings were then correlated with birthweight discordance, placental territory discordance and DeltaAVAs (no. of AVAs from smaller twin (donor) to larger twin (recipient) minus no. of AVAs from larger to smaller twin). RESULTS: Histomorphometric variables were similar in shared and non-shared cotyledons of uncomplicated MCDA twins. However, the median diameter of terminal villi in shared cotyledons in DeltaIUGR and TTTS placentae was significantly smaller [51.2 microm (48.2-58.3), p<0.001 and 52.6 microm (53.1-50.4), p<0.001], and had a similar number of smaller capillaries, larger fetomaternal diffusion distance and reduced vascularization compared to non-shared IUGR and TTTS placentae. However, Deltadiameter (defined as the difference between median diameters of terminal villi in large minus small twins' territories) rose with increasing birthweight discordance (Pearson correlation coefficient=0.82, p<0.001). Multiple linear regression analysis revealed that Deltadiameter was influenced by placental territory discordance (p<0.001) and birthweight discordance (p<0.01): log10 Deltadiameter=1.38+(0.01 x birthweight discordance)+(0.56 x log10 placental territory discordance) (R2=0.82, p<0.001), but there was no significant relationship with DeltaAVA and AAA. In the TTTS group, Deltadiameter correlated significantly with DeltaAVA only: log10Deltadiameter=1.44+(0.02 x DeltaAVA) (R2=0.3, p<0.001). CONCLUSIONS: This is the first study to characterise the histomorphometry of shared and non-shared cotyledons in MC twins. The findings suggest that abnormal placentation, rather than placental vascular anatomy may be responsible for DeltaIUGR in MC twins, whereas TTTS arises from imbalance in interfetal transfusion with resultant differing terminal villus histomorphometric features in donor, recipient and shared cotyledons. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16023205&query_hl=1 ER - TY - JFULL T1 - Heparin prevents programmed cell death in human trophoblast. A1 - Hills, FA A1 - Abrahams, VM A1 - González-Timón, B A1 - Francis, J A1 - Cloke, B A1 - Hinkson, L A1 - Rai, R A1 - Mor, G A1 - Regan, L A1 - Sullivan, M A1 - Lam, EW A1 - Brosens, JJ J1 - Mol Hum Reprod Y1 - 2006/04// VL - 12 SN - 1360-9947 SP - 237 EP - 243 N2 - Heparin is used clinically for the prevention of pregnancy complications associated with prothrombotic disorders, especially antiphospholipid antibody syndrome. Recent studies have suggested that heparin may exert direct effects on placental trophoblast, independently of its anticoagulant activity. We now demonstrate that heparin abrogates apoptosis of primary first trimester villous trophoblast in response to treatment with the pro-inflammatory cytokines interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. This multifunctional glycosaminoglycan also inhibited apoptosis induced by other agents, including staurosporin, broad-spectrum kinase inhibitor and thrombin. Furthermore, heparin attenuated caspase-3 activity, a hallmark of apoptosis, in human first trimester villous and extravillous trophoblast cell lines treated with peptidoglycan, a Toll-like receptor-2 agonist isolated from Staphylococcus aureus. The ability of heparin to antagonize cell death induced by such diverse apoptotic signals suggested that it acts as a survival factor for human trophoblast. We demonstrate that heparin, like epidermal growth factor (EGF) and heparin-binding EGF (HB-EGF), elicits phosphorylation of the EGF receptor and activation of the phosphatidyl inositol 3-kinase (PI3K)-, the extracellular signal-related kinase 1/2 (ERK1/2)- and the c-Jun NH2 terminal kinase (JNK)-signal transduction pathways in primary villous trophoblast. In summary, we have demonstrated that heparin activates multiple anti-apoptotic pathways in human trophoblast. Our results suggest that heparin may be useful in the management of at-risk patients, even in the absence of an identifiable thrombophilic disorder. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16556679&query_hl=1 ER - TY - JFULL T1 - Glucose production in the human placenta. A1 - Leonce, J A1 - Brockton, N A1 - Robinson, S A1 - Venkatesan, S A1 - Bannister, P A1 - Raman, V A1 - Murphy, K A1 - Parker, K A1 - Pavitt, D A1 - Teoh, TG A1 - Regan, L A1 - Burchell, A A1 - Steer, P A1 - Johnston, DG J1 - Placenta Y1 - 2006/04// VL - 27 Suppl A SN - 0143-4004 SP - S103 EP - S108 N2 - Glucose transfer from mother to fetus by placental facilitated diffusion is the dominant mechanism by which the fetus acquires glucose. In small for gestational age pregnancies, fetal glucose concentrations tend to be lower than normal and this persists following delivery. GLUT1 is the major glucose transporter in human placenta but there is no evidence of GLUT1 deficiency as a cause of the lower fetal glucose concentration in small for gestational age pregnancy. The physiological and pathological roles of the other glucose transporters (and there are 14 currently described) are unknown. In recent years, the possibility has been raised that the placenta is itself capable of supplying glucose for fetal needs. This hypothesis derived from glucose isotope studies in normal pregnancy, where dilution of glucose isotope was demonstrated in blood samples taken from the fetal circulation during intravenous infusion of glucose isotope in the mother. Although other gluconeogenic enzymes were known to be present, the placenta was previously considered incapable of glucose secretion because it lacked functional glucose-6-phosphatase. Recent studies, however, have suggested that specific glucose-6-phosphatase may be present in placenta but it may be the product of a different gene from conventional hepatic glucose-6-phosphatase. The presence of the specific transporters necessary for glucose-6-phosphatase activity is currently being investigated. The role of placental glucose secretion in normal and growth-restricted pregnancies is an area of current study. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16618444&query_hl=1 ER - TY - JFULL T1 - Functional characterization of embryonic stem cell-derived cardiomyocytes using scanning ion conductance microscopy. A1 - Gorelik, J A1 - Ali, NN A1 - Shevchuk, AI A1 - Lab, M A1 - Williamson, C A1 - Harding, SE A1 - Korchev, YE J1 - Tissue Eng Y1 - 2006/04// VL - 12 SN - 1076-3279 SP - 657 EP - 664 N2 - We report here the novel use of scanning ion conductance microscopy (SICM) to produce surface images of embryonic stem cell-derived cardiomyocytes (ESCM) to identify individual contracting cardiomyocytes among different cell types. By measuring amplitude and rhythm we can quantitate contraction of ESCM. This method gives, within the same experiment, an assessment of the number and position of ESCM within the layer of mixed cell types, as well as an accurate measure of the response of individual ESCM. Using different modulators of contraction as examples we showed how SICM could be used for recording their responses. We subsequently demonstrated that this model can be used to investigate the protective effect of antiarrhythmogenic drugs. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16674281&query_hl=1 ER - TY - JFULL T1 - The importance of cysteine cathepsin proteases for placental development A1 - Varanou, A A1 - Withington, SL A1 - Lakasing, L A1 - Williamson, C A1 - Burton, GJ A1 - Hemberger, M J1 - J MOL MED-JMM Y1 - 2006/04// VL - 84 SN - 0946-2716 SP - 305 EP - 317 N2 - The typically lysosomal family of cysteine cathepsin proteases has been implicated in the development of the placenta, in particular from studies in the mouse. Here, we analysed overall expression, regulation and presence of transcript isoforms of cysteine cathepsins during human extra-embryonic development. All 11 family members are expressed in human placental tissues, and many are differentially regulated during gestation. Several cysteine cathepsins exhibit deregulated expression levels in placentas from pregnancies complicated by pre-eclampsia. The localization of cathepsin B predominantly in placental and decidual macrophages suggests a role in the physiological functions of these cells in mediating villous angiogenesis and decidual apoptosis. Cathepsin L levels are highest in a subpopulation of invasive cytotrophoblasts. Reflecting the expression pattern of two murine cathepsins, these data give insights into the evolutionary conservation of cathepsin function that is not necessarily exhibited by gene pairs defined by highest sequence similarity. Furthermore, cathepsin L protein localization in uterine epithelial cells demonstrates the in vivo occurrence of intranuclear cathepsin L isoforms. The zonally restricted expression of cathepsins in the syncytiotrophoblast may be important for the metabolic breakdown of maternal nutrients. Overall, the distribution and abnormal expression levels in pre-eclamptic placentas indicate that cysteine cathepsins may play important roles during normal placentation and in the etiology of pre-eclampsia. ER - TY - JFULL T1 - Peginterferon alfa-2a (40KD) (Pegasys (R)) plus ribavirin (RBV) (Copegus (R)) in pegylated interferon alfa-2b (12KD)/Ribavirin non-responders with cirrhosis/advanced fibrosis: Interim analysis of the REPEAT study A1 - Gitlin, N A1 - Di Bisceglie, A A1 - Marcellin, P A1 - Bonkovsky, H A1 - Rai, R A1 - Rizzetto, M A1 - Teuber, G A1 - Jensen, D J1 - GASTROENTEROLOGY Y1 - 2006/04// VL - 130 SN - 0016-5085 SP - A838 EP - A838 ER - TY - JFULL T1 - The effects of sex steroid hormones and interleukin-1-beta on MUC1 expression in endometrial epithelial cell lines. A1 - Horne, AW A1 - Lalani, EN A1 - Margara, RA A1 - White, JO J1 - Reproduction Y1 - 2006/04// VL - 131 SN - 1470-1626 SP - 733 EP - 742 N2 - Oestrogen, progesterone and paracrine signals from the embryo have been associated with the overall control of implantation. Changes in the expression of the heavily glycosylated transmembrane glycoprotein MUC1 mucin on the endometrial epithelium are also thought to be important for embryo attachment. Increased MUC1 expression has been correlated with elevated progesterone levels in the secretory phase of the menstrual cycle. Embryonic control of endometrial receptivity through changes in MUC1 expression could be achieved through the interleukin-1 system. Four endometrial epithelial cell lines (HEC1A, HEC1B, Ishikawa and RL592) were treated with oestrogen and progesterone (with or without interleukin-1-beta) and were subjected to immunocytochemistry and flow cytometric analysis to determine MUC1 production using MUC1 antibodies. HEC1A (oestrogen receptor (ER) and progesterone receptor (PR) positive) and HEC1B (ER positive and PR negative) were transfected with the MUC1 promoter, underwent similar treatment regimes and the activity of the MUC1 promoter relative to their untreated controls was determined using a chloramphenicol acetyltransferase (CAT) enzyme-linked immunoassay. Using the cell lines, we determined that endometrial MUC1 expression is up-regulated by progesterone, consistent with the in vivo increases in MUC1 related to high progesterone levels. We also revealed that neither oestrogen, nor interleukin-1-beta, appear to modulate MUC1. Progesterone-dependent regulation of MUC1 is likely to be an important factor in determining endometrial receptivity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16595724&query_hl=1 ER - TY - JFULL T1 - Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study A1 - Wu, O A1 - Robertson, L A1 - Twaddle, S A1 - Lowe, GDO A1 - Clark, P A1 - Greaves, M A1 - Walker, ID A1 - Langhorne, P A1 - Brenkel, I A1 - Regan, L A1 - Greer, IA J1 - HEALTH TECHNOL ASSES Y1 - 2006/04// VL - 10 SP - 1 EP - + N2 - Objectives: To assess the risk of clinical complications associated with thrombophilia in three high-risk patient groups: women using oral oestrogen preparations, women during pregnancy and patients undergoing major orthopaedic surgery. To assess the effectiveness of prophylactic treatments in preventing venous thromboembolism (VTE) and adverse pregnancy outcomes in women with thrombophilia during pregnancy and VTE in patients with thrombophilia, undergoing major orthopaedic surgery. To evaluate the relative cost-effectiveness of universal and selective VTE history-based screening for thrombophilia compared with no screening in the three high-risk patient groups.Data sources: Electronic databases including MEDLINE, EMBASE, and four other major databases were searched up to June 2003.Review methods: In order to assess the risk of clinical complications associated with thrombophilia, a systematic review of the literature on VTE and thrombophilia in women using oral oestrogen preparations and patients undergoing major orthopaedic surgery; and studies of VTE and adverse obstetric complications in women with thrombophilia during pregnancy was carried out. Meta-analysis was used to calculate pooled odds ratios (ORs) associated with individual clinical outcomes, stratified by thrombophilia type and were calculated for each patient group. To assess the effectiveness of prophylaxis, a systematic review was carried out on the use of prophylaxis in the prevention of VTE and pregnancy loss in pregnant women with thrombophilic defects and the use of thromboprophylaxis in the prevention of VTE in patients with thrombophilia undergoing major elective orthopaedic surgery. Relevant data were summarised according to the patient groups and stratified according to the types of prophylaxis. A narrative summary was provided; where appropriate, meta-analysis was conducted. An incremental cost-effectiveness analysis was then carried out, from the perspective of the NHS in the UK. A decision analytical model was developed to simulate the clinical consequences of four thrombophilia screening scenarios. Results from the meta-analyses, information from the literature and results of two Delphi studies of clinical management of VTE and adverse pregnancy complications were incorporated into the model. Only direct health service costs were measured and unit costs for all healthcare resources used were obtained from routinely collected data and the literature. Cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs); an estimate of the cost per adverse clinical complication prevented, comparing screening with no screening, were calculated for each patient group.Results: In the review of risk of clinical complications, 81 studies were included, nine for oral oestrogen preparations, 72 for pregnancy and eight for orthopaedic surgery. For oral contraceptive use, significant associations of the risk of VTE were found in women with factor V Leiden ( FVL); deficiencies of antithrombin, protein C, or protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For hormone replacement therapy ( HRT), a significant association was found in women with FVL. The highest risk in pregnancy was found for FVL and VTE, in particular, homozygous carriers of this mutation are 34 times more likely to develop VTE in pregnancy than non-carriers. Significant risks for individual thrombophilic defects were also established for early, recurrent and late pregnancy loss; preeclampsia; placental abruption; and intrauterine growth restriction. Significant associations were found between FVL and high factor VIIIc and postoperative VTE following elective hip or knee replacement surgery. Prothrombin G20210A was significantly associated with postoperative pulmonary embolism. However, antithrombin deficiency, MTHFR and hyperhomocysteinaemia were not associated with increased risk of postoperative VTE. In the review of the effectiveness of prophylaxis, based on available data from eight studies, low-dose aspirin and heparin was found to be the most effective in preventing pregnancy loss in thrombophilic women during pregnancy, while aspirin alone was the most effective in preventing minor bleeding. All the studies on thrombophilia and major elective orthopaedic surgery included in the review of risk complications were also used in the review of the effectiveness of thromboprophylaxis. However, there were insufficient data to determine the relative effectiveness of different thromboprophylaxis in preventing VTE in this patient group. For the cost-effectiveness analysis, of all the patient groups evaluated, universal screening of women prior to prescribing HRT was the most cost-effective ( ICER 6824) pound. In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy ( ICER 202,402) pound. Selective thrombophilia screening based on previous personal and/or family history of VTE was more cost-effective than universal screening in all the patient groups evaluated.Conclusions: Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 ( 95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in nonusers of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established. ER - TY - JFULL T1 - Regioselective Staudinger reaction for the synthesis of N-1 modified aminoglycosides A1 - Rai, R A1 - Chang, CWT J1 - ABSTR PAP AM CHEM S Y1 - 2006/03/26/ VL - 231 ER - TY - JFULL T1 - Design, synthesis and SAR of novel, heterocyclic Factor VIIa inhibitors A1 - Rai, R A1 - Kolesnikov, A A1 - Sprengeler, PA A1 - Torkelson, S A1 - Ton, T A1 - Hendrix, J A1 - Stephens, R A1 - Shrader, WD A1 - Katz, BA A1 - Yu, C A1 - Cabuslay, R A1 - Sanford, E A1 - Janc, J A1 - Gjerstad, E A1 - Young, WB J1 - ABSTR PAP AM CHEM S Y1 - 2006/03/26/ VL - 231 ER - TY - JFULL T1 - Transgenic mice expressing p450 aromatase as a model for male infertility associated with chronic inflammation in the testis. A1 - Li, X A1 - Strauss, L A1 - Kaatrasalo, A A1 - Mayerhofer, A A1 - Huhtaniemi, I A1 - Santti, R A1 - Mäkelä, S A1 - Poutanen, M J1 - Endocrinology Y1 - 2006/03// VL - 147 SN - 0013-7227 SP - 1271 EP - 1277 N2 - Our previous studies have shown that transgenic male mice expressing human P450 aromatase (AROM+) are infertile. In the present study, we followed the testis phenotype up to 15 months of age in these mice. The testes of the old AROM+ mice showed Leydig cell hypertrophy and hyperplasia, as indicated by the staining for steroidogenic enzymes and androgen and estrogen receptors. However, the Leydig cell adenomas did not show signs of malignization. In contrast, we observed a marked increase in the number of activated macrophages in the testicular interstitium of the aging AROM+ mice. The macrophages were further shown to express high levels of CD68 (a monocyte/macrophage marker) and secrete TNFalpha, indicating strong activation, presumably by estrogen exposure. The increased activity of the macrophages was associated with Leydig cell depletion (analyzed at the age of 9 and 15 months) and an increased number of mast cells and fibrosis in the testicular interstitium. Interestingly, similar findings have been made in testes of infertile men. Hence, the aging AROM+ males present with a phenocopy of inflammation-associated infertility in men, providing a model for further studies on the putative link among estrogens, orchitis, and infertility. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16306085&query_hl=1 ER - TY - JFULL T1 - Neonatal thrombocytopenia. A1 - Roberts, IA A1 - Murray, NA J1 - Curr Hematol Rep Y1 - 2006/03// VL - 5 SN - 1541-0714 SP - 55 EP - 63 N2 - Neonatal thrombocytopenia is a common clinical problem. The majority of episodes are early-onset thrombocytopenias due to impaired fetal megakaryocytopoiesis associated with placental insufficiency; the commonest causes of severe early-onset thrombocytopenia are immune thrombocytopenias, congenital infections, and asphyxia. By contrast, about 90% of cases of severe thrombocytopenia presenting after the first few days of life are due to late-onset bacterial sepsis, necrotizing enterocolitis, or both. Although clinically stable neonates tolerate relatively low platelet counts without significant risk of hemorrhage, ill or clinically unstable neonates with profound thrombocytopenia often have a poor outcome. Currently, the only therapy is platelet transfusion. Despite many published guidelines for platelet transfusion in the newborn, however, there have been no randomized trials to define the safe lower limit for platelet counts in sick neonates. The platelet threshold at which the benefits of transfusion outweigh the risks in neonates remains unclear. Well-designed trials are urgently needed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16537047&query_hl=1 ER - TY - JFULL T1 - Agent-based optimization for product family design A1 - Rai, R A1 - Allada, V J1 - ANN OPER RES Y1 - 2006/03// VL - 143 SN - 0254-5330 SP - 147 EP - 156 N2 - This paper presents a two-step approach to determine the optimal platform level for a selected set of product families and their variants. The first step employs a multi-objective optimization using an agent-based framework to determine the Pareto-design solutions for a given set of modules. The second step performs a post optimization analysis that includes application of the quality loss function (QLF) to determine the optimal platform level. The post optimization analysis yields the optimal platform level for a related set of product families and their variants. We demonstrate the working of the proposed method by using an example problem. ER - TY - JFULL T1 - Inflammation and sex steroid receptors: a motif for change. A1 - Brosens, JJ A1 - Lam, EW A1 - Parker, MG J1 - Cell Y1 - 2006/02/10/ VL - 124 SN - 0092-8674 SP - 466 EP - 468 N2 - Homeostasis in reproductive tissues requires integration of hormonal and inflammatory signals. In this issue of Cell, Zhu et al. (2006) discover that proinflammatory signals switch repressed steroid hormone receptors into transcriptional activators by targeting TAB2, an adaptor protein that tethers corepressors. These findings have implications for the treatment of endocrine-resistant cancers. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16469693&query_hl=1 ER - TY - JFULL T1 - Dexamethasone in the treatment of obstetric cholestasis: a case series. A1 - Diac, M A1 - Kenyon, A A1 - Nelson-Piercy, C A1 - Girling, J A1 - Cheng, F A1 - Tribe, RM A1 - Goodman, J A1 - Shennan, A A1 - Williamson, C J1 - J Obstet Gynaecol Y1 - 2006/02// VL - 26 SN - 0144-3615 SP - 110 EP - 114 N2 - Twelve women with obstetric cholestasis were given dexamethasone after failure to respond to ursodeoxycholic acid. Clinical improvement was achieved in eight cases, without complete resolution of symptoms. Biochemical response was achieved in seven cases. All but two cases had good correlation between clinical and biochemical response. Women of Asian and South American origin were more likely to respond to dexamethasone than Caucasians. There were no reported maternal or fetal side-effects. However, the subsequent consequences of dexamethasone treatment for the mother and fetus have not been thoroughly evaluated. Therefore, even in Asian and South American women, larger studies of dexamethasone are required before this treatment can be recommended as a universally safe and effective treatment for obstetric cholestasis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16483964&query_hl=1 ER - TY - JFULL T1 - Peripheral blood NK cell levels are not predictive of future pregnancy outcome amongst women with recurrent miscarriage - A prospective study. A1 - Rai, R A1 - Backos, M A1 - Francis, J A1 - Brosens, J A1 - Regan, L J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 354A EP - 354A ER - TY - JFULL T1 - Interleukin-1beta phosphorylates serine 294 of progesterone receptor B via c-jun n-terminal kinase in human myometrium. A1 - Sooranna, SR A1 - Lian, ZQ A1 - Engineer, N A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 247A EP - 247A ER - TY - JFULL T1 - Toll-like receptor 4 and its activation during term and preterm labour A1 - Loudon, JA A1 - Lee, YS A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 283A EP - 283A ER - TY - JFULL T1 - Identification of transcripts regulated by antagonizing the action of VEGF-A in endometrium at the time of implantation. A1 - Sharkey, AM A1 - Catalano, R A1 - Sengupta, J A1 - Ghosh, D A1 - Charnock-Jones, S A1 - Smith, SK J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 264A EP - 264A ER - TY - JFULL T1 - Successful prevention of second trimester pregnancy loss using high cervical cerclage. A1 - Heeps, A A1 - Crouch, N A1 - Backos, M A1 - Brosens, J A1 - Higham, J A1 - Rai, R A1 - Regan, L J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 333A EP - 333A ER - TY - JFULL T1 - Upstream activation of phospholipase C and protein kinase C precedes stretch stimulated MAPK phosphorylation in human uterine myocytes. A1 - Engineer, N A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 246A EP - 246A ER - TY - JFULL T1 - The role of non-receptor tyrosine kinases in the expression of pro-labour genes in human myometrium. A1 - Engineer, N A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 246A EP - 246A ER - TY - JFULL T1 - Heparin prevents programmed cell death in human trophoblast. A1 - Regan, L A1 - Hills, F A1 - Abrahams, V A1 - Gonzalez-Timon, B A1 - Francis, J A1 - Hinkson, L A1 - Rai, R A1 - Mor, G A1 - Lam, E A1 - Brosens, J J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 353A EP - 353A ER - TY - JFULL T1 - Molecular mechanisms of insulin-like growth factor-I mediated regulation of the steroidogenic acute regulatory protein in mouse leydig cells. A1 - Manna, PR A1 - Chandrala, SP A1 - King, SR A1 - Jo, Y A1 - Counis, R A1 - Huhtaniemi, IT A1 - Stocco, DM J1 - Mol Endocrinol Y1 - 2006/02// VL - 20 SN - 0888-8809 SP - 362 EP - 378 N2 - Growth factors are known to play diverse roles in steroidogenesis, a process regulated by the mitochondrial steroidogenic acute regulatory (StAR) protein. The mechanism of action of one such growth factor, IGF-I, was investigated in mouse Leydig tumor (mLTC-1) cells to determine its potential role in the regulation of StAR expression. mLTC-1 cells treated with IGF-I demonstrated temporal and concentration-dependent increases in StAR expression and steroid synthesis. However, IGF-I had no effect on cytochrome P450 side-chain cleavage or 3beta-hydroxysteroid dehydrogenase protein levels. IGF-I was capable of augmenting N,O'-dibutyrl-cAMP-stimulated steroidogenic responsiveness in these cells. The steroidogenic potential of IGF-I was also confirmed in primary cultures of isolated mouse Leydig cells. IGF-I increased phosphorylation of ERK1/2, an event inhibited by the MAPK/ERK inhibitors, PD98059 and U0126. Interestingly, inhibition of ERK activity enhanced IGF-I-mediated StAR protein expression, but phosphorylation of StAR was undetectable, an observation in contrast to that seen with N,O'-dibutyrl-cAMP signaling. Further studies demonstrated that these events were tightly correlated with the expression of dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1 and scavenger receptor class B type 1. Whereas both protein kinase A and protein kinase C signaling were involved in the IGF-I-mediated steroidogenic response, the majority of the effects of IGF-I were found to be mediated by the protein kinase C pathway. Transcriptional activation of the StAR gene by IGF-I was influenced by several transcription factors, its up-regulation being dependent on phosphorylation of the cAMP response element-binding protein (CREB) and the activator protein 1 family member, c-Jun. Conversely, StAR gene transcription was markedly inhibited by expression of nonphosphorylatable CREB (Ser(133)Ala), dominant negative A-CREB, and dominant negative c-Jun (TAM-67) mutants. Collectively, the present studies identify molecular events in IGF-I signaling that may influence testicular growth, development, and the Leydig cell steroidogenic machinery through autocrine/paracrine regulation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16166197&query_hl=1 ER - TY - JFULL T1 - Activating protein-1 may mediate estrogen responsiveness of the progesterone receptor gene in human myocytes. A1 - Lee, YS A1 - Johnson, MR A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 240A EP - 240A ER - TY - JFULL T1 - The effect of pro-inflammatory cytokines and prostaglandins on prostanoid receptor mRNA expression in human myometrium. A1 - Liang, ZQ A1 - Engineer, N A1 - Chakravarty, S A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 133A EP - 133A ER - TY - JFULL T1 - Menstrua effluent in endometriosis shows no difference in volume, VEGF-A, MMP2 and MMP9 or sFLT A1 - Malik, S A1 - Day, K A1 - Perrault, I A1 - Charnock-Jones, DS A1 - Smith, SK J1 - REPROD BIOMED ONLINE Y1 - 2006/02// VL - 12 SP - 174 EP - 181 N2 - Since retrograde menstruation is considered a key event in the aetiology of endometriosis, this study sought to determine whether the menstrual effluent of women with this condition is different from that of those with a normal pelvis. As the amount of blood lost during menstruation is thought to be higher in this group, measured objective menstrual blood loss (MBL) was measured. In addition, factors enhancing both ectopic implantation of endometrium and its subsequent growth (by establishing a neo-vasculature) were chosen for study. Our hypothesis was that they are increased in the menstrual effluent of women with endometriosis. The study showed that at the time of menstruation, there is no difference in MBL or in the volume of menstrual effluent between women with endometriosis and those with a normal pelvis at laparoscopy. In addition, vascular endothelial growth factor-A (VEGF-A) message and protein, soluble truncated receptor sVEGF-R1 (sFLT), matrix metalloproteinase (MMP) 2 and MMP9 activities were also shown to be similar between the two groups. It is concluded that the enhanced expression of VEGF-A and NIMP in the peritoneal fluid and ectopic lesions of endometriotic patients may be a secondary event, resulting from an innate difference in peritoneal and systemic factors rather than in the endometrium, causing an abnormal peritoneal response to menstrual debris and facilitating its ectopic implantation. ER - TY - JFULL T1 - Chromatin immunoprecipitation analysis of NFkappaB binding in the COX-2 promoter A1 - Lim, SE A1 - Lee, YS A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 284A EP - 285A ER - TY - JFULL T1 - Expression of endometrial complement regulatory proteins in antiphospholipid syndrome. A1 - Rai, R A1 - Brosens, J A1 - Sebire, N A1 - Francis, J A1 - Goldin, R A1 - Regan, L J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 355A EP - 355A ER - TY - JFULL T1 - Development of polycystic ovary syndrome: involvement of genetic and environmental factors. A1 - Franks, S A1 - McCarthy, MI A1 - Hardy, K J1 - Int J Androl Y1 - 2006/02// VL - 29 SN - 0105-6263 N2 - We have recently proposed that polycystic ovary syndrome (PCOS) has its origin in fetal life. This hypothesis is based on data from animal models (rhesus monkey or sheep that have been exposed prenatally to high doses of androgen) and is supported by clinical studies. It is suggested that, in human females, exposure to excess androgen, at any stage from fetal development of the ovary to the onset of puberty, leads to many of the characteristic features of PCOS, including abnormalities of luteinizing hormone secretion and insulin resistance. It is likely that, in humans with PCOS, the development of the PCOS phenotype results primarily from a genetic predisposition for the fetal ovary to hypersecrete androgen. At present, it is unclear whether the maternal environment directly influences the development of PCOS in the offspring. Maternal androgen excess is unlikely to affect the fetus, because the placenta presents an effective barrier, but metabolic disturbances during pregnancy could affect development of the syndrome in the fetus. In postnatal life, the natural history of PCOS can be further modified by factors affecting insulin secretion and/or action, most importantly, nutrition. We now have evidence for a disorder of early follicular development in the polycystic ovary that is consistent with an increased population of primordial follicles in the fetal ovary. It remains to be determined whether this phenomenon is the cause or the effect of increased exposure to androgen within the ovary. PCOS is the commonest endocrine disorder in women. It is not only a very prevalent cause of anovulatory infertility, menstrual disturbances and hirsutism, but it is also a major risk factor for the development of type 2 diabetes mellitus in later life. The aetiology of the syndrome remains uncertain but there is increasing evidence for a genetic basis. PCOS very often becomes clinically manifest during adolescence with maturation of the hypothalamic-pituitary-ovarian axis but the genesis of the syndrome may be during very early development - perhaps even in utero. In this review, this hypothesis is explored in the light of clinical, biochemical and genetic research. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16390494&query_hl=1 ER - TY - JFULL T1 - Mechanical stretch activates NF kappa B via the map kinases ERK and JNK in human amnion cells. A1 - Mohan, AR A1 - Sooranna, SR A1 - Johnson, MR A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 246A EP - 247A ER - TY - JFULL T1 - Activation of the AKT/PKB signal transduction pathway by mechanical stretch and interleukin-1beta in human myometrium. A1 - Sooranna, SR A1 - Engineer, N A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2006/02// VL - 13 SN - 1071-5576 SP - 247A EP - 247A ER - TY - JFULL T1 - Physical interaction and mutual transrepression between CCAAT/enhancer-binding protein beta and the p53 tumor suppressor. A1 - Schneider-Merck, T A1 - Pohnke, Y A1 - Kempf, R A1 - Christian, M A1 - Brosens, JJ A1 - Gellersen, B J1 - J Biol Chem Y1 - 2006/01/06/ VL - 281 SN - 0021-9258 SP - 269 EP - 278 N2 - The tumor suppressor protein p53 is not only involved in defending cells against genotoxic insults but is also implicated in differentiation processes, a function that it shares with the CCAAT/enhancer-binding protein beta (C/EBPbeta). We previously reported an up-regulation of both factors in the cycle-dependent differentiation process of human endometrial stromal cells, termed decidualization. C/EBPbeta-mediated activation of a decidualization marker, the decidual prolactin promoter, was antagonized by p53. Here we report that C/EBPbeta in turn represses the transcriptional activity of p53. Competition for limiting amounts of coactivator CREB-binding protein/p300 was ruled out as the underlying mechanism of transrepression. Physical interaction between p53 and C/EBPbeta was demonstrated in vitro and in vivo and shown to depend on the C-terminal domains of both proteins. In gel shift experiments, C/EBPbeta reduced complex formation between p53 and its response element. Conversely, p53 strongly inhibited binding of endogenous C/EBPbeta from endometrial stromal cells to the C/EBP-responsive region in the decidual prolactin promoter. The observed negative cross-talk between p53 and C/EBPbeta is likely to impact expression of their respective target genes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16227626&query_hl=1 ER - TY - JFULL T1 - FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance. A1 - Taylor, JR A1 - Brownlow, N A1 - Domin, J A1 - Dibb, NJ J1 - Oncogene Y1 - 2006/01/05/ VL - 25 SN - 0950-9232 SP - 147 EP - 151 N2 - The kinase inhibitor imatinib is used in the treatment of chronic myeloid leukaemia, where it targets the intracellular Bcr-Abl tyrosine kinase, and gastrointestinal stromal tumours, where it targets either the KIT or PDGF tyrosine kinase receptors. Here, we report that imatinib is also an effective inhibitor of the closely related FMS receptor for macrophage colony stimulating factor and that mutation of Asp 802 of FMS to Val confers imatinib resistance. Imatinib readily reverted the transformed phenotype of haemopoietic and fibroblast cell lines that express the oncogene v-fms and also inhibited the growth of the Bacl.2F5 macrophage cell line. The cellular IC50 value of imatinib for FMS was similar to those for Bcr-Abl and KIT. Consequently, imatinib may also prove effective for the treatment of diseases whose progression is dependent upon macrophage-colony stimulating factor, this includes certain aspects of cancer and inflammation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16170366&query_hl=1 ER - TY - JFULL T1 - Nuclear receptor regulation gears up another Notch. A1 - Belandia, B A1 - Parker, MG J1 - Nucl Recept Signal Y1 - 2006/// VL - 4 SN - 1550-7629 SP - e001 EP - e001 N2 - In this perspective we describe examples of crosstalk between nuclear receptors (NRs) and Notch signaling by means of direct functional interactions between components of both pathways. This crosstalk may provide eukaryotic organisms with molecular mechanisms for the coordination of llong-distance endocrine signals with cell-to-cell juxtacrine communication. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16604164&query_hl=1 ER - TY - JFULL T1 - Paclitaxel-induced nuclear translocation of FOXO3a in breast cancer cells is mediated by c-Jun NH2-terminal kinase and Akt. A1 - Sunters, A A1 - Madureira, PA A1 - Pomeranz, KM A1 - Aubert, M A1 - Brosens, JJ A1 - Cook, SJ A1 - Burgering, BM A1 - Coombes, RC A1 - Lam, EW J1 - Cancer Res Y1 - 2006/01/01/ VL - 66 SN - 0008-5472 SP - 212 EP - 220 N2 - The microtubule-targeting compound paclitaxel is often used in the treatment of endocrine-resistant or metastatic breast cancer. We have previously shown that apoptosis of breast cancer cells in response to paclitaxel is mediated by induction of FOXO3a expression, a transcription factor downstream of the phosphatidylinositol-3-kinase/Akt signaling pathway. To further investigate its mechanism of action, we treated MCF-7 cells with paclitaxel and showed a dose-dependent increase in nuclear localization of FOXO3a, which coincided with decreased Akt signaling but increased c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) activity. Flow cytometry revealed that paclitaxel-induced apoptosis of MCF-7 cells and of other paclitaxel-sensitive breast cancer cell lines was maintained in the presence of inhibitors of p38 (SB203580) or mitogen-activated protein/ERK kinase 1 signaling (PD98059) but abrogated when cells were treated with the JNK1/2 inhibitor SP600125. SP600125 reversed Akt inhibition and abolished FOXO3a nuclear accumulation in response to paclitaxel. Moreover, conditional activation of JNK mimicked paclitaxel activity and led to dephosphorylation of Akt and FOXO3a. Furthermore, mouse embryonic fibroblasts (MEF) derived from JNK1/2 knockout mice displayed very high levels of active Akt, and in contrast to wild-type MEFs, paclitaxel treatment did not alter Akt activity or elicit FOXO3a nuclear translocation. Taken together, the data show that cell death of breast cancer cells in response to paclitaxel is dependent upon JNK activation, resulting in Akt inhibition and increased FOXO3a activity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16397234&query_hl=1 ER - TY - JFULL T1 - Progestins regulate the expression and activity of the forkhead transcription factor FOXO1 in differentiating human endometrium. A1 - Labied, S A1 - Kajihara, T A1 - Madureira, PA A1 - Fusi, L A1 - Jones, MC A1 - Higham, JM A1 - Varshochi, R A1 - Francis, JM A1 - Zoumpoulidou, G A1 - Essafi, A A1 - Fernandez de Mattos, S A1 - Lam, EW A1 - Brosens, JJ J1 - Mol Endocrinol Y1 - 2006/01// VL - 20 SN - 0888-8809 SP - 35 EP - 44 N2 - Menstruation, or cyclic shedding of nonpregnant endometrial tissue with associated bleeding, occurs only in humans and a few other species. This breakdown of the endometrium in response to falling ovarian progesterone levels is a complex process, characterized by local leukocyte infiltration, expression and activation of matrix metalloproteinases, and apoptosis. Spontaneous decidualization (differentiation) of the stromal compartment precedes the cyclic shedding of the endometrium in various menstruating species but the mechanisms that link these processes are not understood. In this study, we identified FOXO1 as a key transcription factor responsible for mediating apoptosis of decidualized human endometrial stromal cells (HESCs) in response to progesterone withdrawal. We demonstrate that medroxyprogesterone acetate (MPA, a synthetic progestin) enhances the expression of FOXO1 in differentiating HESCs while simultaneously inducing cytoplasmic retention and inactivation of FOXO1. Withdrawal of MPA from decidualized HESCs results in rapid nuclear accumulation of FOXO1, increased BIM expression, a proapoptotic FOXO1 target gene, and cell death. Conversely, silencing of FOXO1 expression completely abolishes cell death induced by MPA withdrawal. In summary, the observation that differentiating HESCs become dependent on progesterone signaling for survival through induction and reversible inactivation of FOXO1 suggests a novel mechanism that links decidualization of the endometrium to menstruation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16123151&query_hl=1 ER - TY - JFULL T1 - Anti-inflammatory and immunosuppressive drugs and reproduction. A1 - Østensen, M A1 - Khamashta, M A1 - Lockshin, M A1 - Parke, A A1 - Brucato, A A1 - Carp, H A1 - Doria, A A1 - Rai, R A1 - Meroni, P A1 - Cetin, I A1 - Derksen, R A1 - Branch, W A1 - Motta, M A1 - Gordon, C A1 - Ruiz-Irastorza, G A1 - Spinillo, A A1 - Friedman, D A1 - Cimaz, R A1 - Czeizel, A A1 - Piette, JC A1 - Cervera, R A1 - Levy, RA A1 - Clementi, M A1 - De Carolis, S A1 - Petri, M A1 - Shoenfeld, Y A1 - Faden, D A1 - Valesini, G A1 - Tincani, A J1 - Arthritis Res Ther Y1 - 2006/// VL - 8 SN - 1478-6362 SP - 209 EP - 209 N2 - Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16712713&query_hl=1 ER - TY - JFULL T1 - Inhibitory effect of erythropoietin on contractility of human chorionic plate vessels. A1 - Jain, V A1 - Lim, M A1 - Longo, M A1 - Fisk, NM J1 - Am J Obstet Gynecol Y1 - 2006/01// VL - 194 SN - 1097-6868 SP - 246 EP - 246 N2 - OBJECTIVE: Placenta is a major source of erythropoietin production in the fetus; hypoxia is associated with elevated erythropoietin levels in the fetal circulation. We investigated fetoplacental vascular reactivity after exposure to erythropoietin in vitro. STUDY DESIGN: Third-order chorionic plate arteries from human term placentae were incubated in culture medium with or without erythropoietin (3 U/mL) for 24 hours. Vessels were mounted in a myograph for isometric tension recording, and their responses to vasopressors and vasorelaxants were studied. RESULTS: Contractile responses to endothelin-1 and the thromboxane analogue U46619 were decreased in erythropoietin-exposed vessels compared with controls. Relaxant responses to the nitric oxide donor sodium nitroprusside and the phosphodiesterase inhibitor papaverine were not influenced by erythropoietin. CONCLUSION: Exposure to elevated levels of erythropoietin has an inhibitory effect on contractile responses in human placental chorionic plate arteries. We speculate that this may improve fetoplacental perfusion in hypoxic fetuses with elevated erythropoietin production. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16389039&query_hl=1 ER - TY - JFULL T1 - Isatin interaction with glyceraldehyde-3-phosphate dehydrogenase, a putative target of neuroprotective drugs: partial agonism with deprenyl A1 - Medvedev, A A1 - Buneeva, O A1 - Gnedenko, O A1 - Fedchenko, V A1 - Medvedeva, M A1 - Ivanov, Y A1 - Glover, V A1 - Sandler, M J1 - J NEURAL TRANSM-SUPP Y1 - 2006/// SN - 0303-6995 SP - 97 EP - 103 N2 - There is evidence that the binding of deprenyl, a monoamine oxidase (MAO) B inhibitor, and other propargylamines to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is primarily responsible for their neuroprotective and antiapoptotic effects. Thus, GAPDH may be a target for other neuroprotective drugs. Using two independent approaches, radioligand analysis and an optical biosensor technique, we demonstrate here that GAPDH also interact; with the endogenous, reversible MAO B inhibitor, isatin. Deprenyl inhibited both [H-3]isatin binding to GAPDH, and the binding of this enzyme to an isatin analogue, 5-aminoisatin, immobilized on to an optical biosensor ell. Another MAO inhibitor, tranylcypromine, was ineffective. Both deprenyl and isatin inhibited GAPDH-mediated cleavage of E. coli tRNA. and :heir effects were not additive. We suggest that isatin may be an endogenous partial functional agonist of deprenyl in its effect on GAPDH and GAPDH-mediated RNA cleavage. Changes in level of endogenous isatin may influence the neuroprotective effect of deprenyl in vivo. ER - TY - JFULL T1 - Management of Evans syndrome. A1 - Norton, A A1 - Roberts, I J1 - Br J Haematol Y1 - 2006/01// VL - 132 SN - 0007-1048 SP - 125 EP - 137 N2 - Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of known underlying aetiology. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. First-line therapy is usually corticosteroids and/or intravenous immunoglobulin, to which most patients respond; however, relapse is frequent. Options for second-line therapy include immunosuppressive drugs, especially ciclosporin or mycophenolate mofetil; vincristine; danazol or a combination of these agents. More recently a small number of patients have been treated with rituximab, which induces remission in the majority although such responses are often sustained for <12 months and the long-term effects in children are unclear. Splenectomy may also be considered although long-term remissions are less frequent than in uncomplicated ITP. For very severe and refractory cases stem cell transplantation (SCT) offers the only chance of long-term cure. The limited data available suggest that allogeneic SCT may be superior to autologous SCT but both carry risks of severe morbidity and of transplant-related mortality. Cure following reduced-intensity conditioning has now been reported and should be considered for younger patients in the context of controlled clinical trials. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16398647&query_hl=1 ER - TY - JFULL T1 - Both testosterone and follicle-stimulating hormone independently inhibit spermatogonial differentiation in irradiated rats. A1 - Shetty, G A1 - Weng, CC A1 - Meachem, SJ A1 - Bolden-Tiller, OU A1 - Zhang, Z A1 - Pakarinen, P A1 - Huhtaniemi, I A1 - Meistrich, ML J1 - Endocrinology Y1 - 2006/01// VL - 147 SN - 0013-7227 SP - 472 EP - 482 N2 - Simultaneous suppression of both testosterone and FSH with GnRH antagonists (GnRH-ant) reverses the radiation-induced block in spermatogonial differentiation in F1 hybrids of Lewis and Brown-Norway rats. Although addition of exogenous testosterone restores the block, it also raises FSH, and hence it had not been possible to conclusively determine which hormone was inhibiting spermatogonial differentiation. In the present study, we establish the relative roles of testosterone and FSH in this inhibition using three different approaches. The first approach involved the treatment of irradiated rats, in which differentiation was stimulated by GnRH-ant plus flutamide, with FSH for 2 wk; the FSH reduced the percentage of tubules that were differentiated (TDI) by about 2-fold, indicating that FSH does have an inhibitory role. The second approach involved treatment of irradiated, hypophysectomized rats with exogenous testosterone for 10 wk; testosterone also reduced the TDI, demonstrating that testosterone had a definite inhibitory effect, independent of pituitary hormones. Furthermore, in this protocol we showed that TDI in the hypophysectomized testosterone-treated group, which had higher intratesticular testosterone levels but lacked FSH, was slightly higher than the TDI in a GnRH-antagonist-testosterone-treated group of irradiated rats, which had normal physiological levels of FSH; this result supports a role for endogenous FSH in suppressing spermatogonial differentiation in the latter group. The third approach involved injection of an active anti-FSH antibody for 10 d in untreated, GnRH-ant plus flutamide-treated, or GnRH-ant plus testosterone-treated irradiated rats. This was not sufficient to increase the TDI. However, flutamide given in a similar treatment schedule did increase the TDI in GnRH-ant plus testosterone-treated rats. We conclude that both testosterone and FSH individually inhibit spermatogonial differentiation after irradiation, but testosterone is a more highly potent inhibitor than is FSH. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16210366&query_hl=1 ER - TY - JFULL T1 - ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases. A1 - Lopez-Garcia, J A1 - Periyasamy, M A1 - Thomas, RS A1 - Christian, M A1 - Leao, M A1 - Jat, P A1 - Kindle, KB A1 - Heery, DM A1 - Parker, MG A1 - Buluwela, L A1 - Kamalati, T A1 - Ali, S J1 - Nucleic Acids Res Y1 - 2006/// VL - 34 SN - 1362-4962 SP - 6126 EP - 6136 N2 - The regulation of gene expression by estrogen receptor-alpha (ERalpha) requires the coordinated and temporal recruitment of diverse sets of transcriptional co-regulator complexes, which mediate nucleosome remodelling and histone modification. Using ERalpha as bait in a yeast two-hybrid screen, we have identified a novel ERalpha-interacting protein, ZNF366, which is a potent corepressor of ERalpha activity. The interaction between ZNF366 and ERalpha has been confirmed in vitro and in vivo, and is mediated by the zinc finger domains of the two proteins. Further, we show that ZNF366 acts as a corepressor by interacting with other known ERalpha corepressors, namely RIP140 and CtBP, to inhibit expression of estrogen-responsive genes in vivo. Together, our results indicate that ZNF366 may play an important role in regulating the expression of genes in response to estrogen. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17085477&query_hl=1 ER - TY - JFULL T1 - Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes. A1 - Powelka, AM A1 - Seth, A A1 - Virbasius, JV A1 - Kiskinis, E A1 - Nicoloro, SM A1 - Guilherme, A A1 - Tang, X A1 - Straubhaar, J A1 - Cherniack, AD A1 - Parker, MG A1 - Czech, MP J1 - J Clin Invest Y1 - 2006/01// VL - 116 SN - 0021-9738 SP - 125 EP - 136 N2 - Using an siRNA-based screen, we identified the transcriptional corepressor RIP140 as a negative regulator of insulin-responsive hexose uptake and oxidative metabolism in 3T3-L1 adipocytes. Affymetrix GeneChip profiling revealed that RIP140 depletion upregulates the expression of clusters of genes in the pathways of glucose uptake, glycolysis, TCA cycle, fatty acid oxidation, mitochondrial biogenesis, and oxidative phosphorylation in these cells. Conversely, we show that reexpression of RIP140 in mouse embryonic fibroblasts derived from RIP140-null mice downregulates expression of many of these same genes. Consistent with these microarray data, RIP140 gene silencing in cultured adipocytes increased both conversion of [14C]glucose to CO2 and mitochondrial oxygen consumption. RIP140-null mice, previously reported to resist weight gain on a high-fat diet, are shown here to display enhanced glucose tolerance and enhanced responsiveness to insulin compared with matched wild-type mice upon high-fat feeding. Mechanistically, RIP140 was found to require the nuclear receptor ERRalpha to regulate hexose uptake and mitochondrial proteins SDHB and CoxVb, although it likely acts through other nuclear receptors as well. We conclude that RIP140 is a major suppressor of adipocyte oxidative metabolism and mitochondrial biogenesis, as well as a negative regulator of whole-body glucose tolerance and energy expenditure in mice. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16374519&query_hl=1 ER - TY - JFULL T1 - In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer. A1 - Saidi, SA A1 - Holland, CM A1 - Charnock-Jones, DS A1 - Smith, SK J1 - Mol Cancer Y1 - 2006/// VL - 5 SN - 1476-4598 SP - 13 EP - 13 N2 - Fenofibrate, an agonist of PPAR-alpha, in doses above 25 microM, inhibits proliferation and induces apoptosis in Ishikawa endometrial cancer cells. We show that these effects are potentiated by retinoic acid, an agonist of the retinoid-X-receptor. DNA content analysis shows that G1/S phase progression through the cell cycle is inhibited. Independent Component Analysis of gene microarray experiments demonstrated downregulation of Cyclin D1 (CCND1) and associated changes in cell cycle gene expression. Expression of PPAR-alpha mRNA was reduced by >75% using RNA-interference but this resulted in only minor changes in biological effects. A nude mouse model of endometrial carcinoma was used to investigate the effect of fenofibrate in vivo but failed to show consistent inhibition of tumour growth. CONCLUSION: The combination of fenofibrate and retinoic acid is a potent inhibitor of Ishikawa endometrial cancer cell growth in vitro. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16569247&query_hl=1 ER - TY - JFULL T1 - Red blood cell transfusion in neonates A1 - Murray, N A1 - Roberts, I A1 - Stanworth, S J1 - PEDIATRICS Y1 - 2005/12// VL - 116 SN - 0031-4005 SP - 1609 EP - 1609 ER - TY - JFULL T1 - The role of CCAAT/enhancer-binding protein beta in the transcriptional regulation of COX-2 in human amnion. A1 - Lee, YS A1 - Terzidou, V A1 - Lindstrom, T A1 - Johnson, M A1 - Bennett, PR J1 - Mol Hum Reprod Y1 - 2005/12// VL - 11 SN - 1360-9947 SP - 853 EP - 858 N2 - Human labour is associated with increased prostaglandin synthesis within the uterus by the action of the inducible type-2 cyclo-oxygenase enzyme (COX-2). A major source of prostaglandin is the fetal membranes, in particular the amnion, in which expression of COX-2 increases in late pregnancy and with labour. The COX-2 gene promoter contains several putative transcription factor binding sites including those for NF-kappaB, AP-1 and C/EBP and therefore has the features of a rapid response gene. We have previously shown that, in amnion, the NF-kappaB DNA-binding sites in the COX-2 promoter are essential for gene expression and that there is an increase in NF-kappaB activity in amnion with the onset of labour. In this study, we demonstrate that in primary human amnion cells, CCAAT/enhancer-binding protein beta (C/EBPbeta) DNA-binding sites are crucial for the function of the COX-2 gene promoter. Three potential C/EBPbeta DNA-binding sites were identified within the COX-2 promoter which were shown to bind to C/EBPbeta but not to C/EBPalpha, C/EBPdelta, CREB (cAMP responsive element modulator) or CREM. Luciferase reporter constructs with site-directed mutagenesis of the three C/EBPbeta sites in the COX-2 promoter showed reduced expression of luciferase in transient transfection studies. However, comparison of C/EBPbeta protein levels and their DNA-binding activity from cells obtained before and after labour showed no significant differences. This suggests that although C/EBPbeta plays an essential constitutive role in the expression of COX-2, C/EBPbeta may not be directly involved in its regulation in association with human labour. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16399783&query_hl=1 ER - TY - JFULL T1 - The effects of acute relaxation on indices of anxiety during pregnancy. A1 - Teixeira, J A1 - Martin, D A1 - Prendiville, O A1 - Glover, V J1 - J Psychosom Obstet Gynaecol Y1 - 2005/12// VL - 26 SN - 0167-482X SP - 271 EP - 276 N2 - OBJECTIVES: Antenatal maternal anxiety has adverse effects on the fetus and the child. In this study we determined whether a short period of directed or of passive relaxation reduced maternal self-rated anxiety, heart rate, plasma catecholamines, cortisol and uterine artery resistance index, in pregnant women. METHODS: Fifty-eight women (28-32 wks gestation) were assigned randomly to a session of directed active or passive (sitting quietly) relaxation. Spielberger self-rating anxiety questionnaires were completed, and a venous blood sample taken, before and after a Doppler scan. RESULTS: Both active and passive relaxation significantly reduced State Anxiety and maternal heart rate, but the effect was significantly greater with the active relaxation. In contrast, the passive relaxation significantly reduced noradrenaline levels whereas active did not. Adrenaline levels were not changed significantly with either type of relaxation. Both methods significantly reduced cortisol, with a trend for the passive to have a greater effect. The active relaxation had no effect on uterine artery blood flow, whereas there was a statistically significant, but clinically negligible, increase in mean resistance index after passive relaxation. CONCLUSION: Both methods reduced maternal State Anxiety and heart rate, the active method more so. However there was a striking lack of correlation with the other biological indices studied. In order to reduce specific biological effects of anxiety during pregnancy, different methods may be needed from those which are most effective at reducing subjective anxiety. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16457423&query_hl=1 ER - TY - JFULL T1 - Glucocorticoid exposure in preterm babies predicts saliva cortisol response to immunization at 4 months. A1 - Glover, V A1 - Miles, R A1 - Matta, S A1 - Modi, N A1 - Stevenson, J J1 - Pediatr Res Y1 - 2005/12// VL - 58 SN - 0031-3998 SP - 1233 EP - 1237 N2 - Preterm babies are exposed to multiple stressors and this may have long-term effects. In particular, high levels of endogenous cortisol might have a programming effect on the hypothalamic-pituitary-adrenal axis as may administered glucocorticoids. In this study, we aimed to test the hypothesis that the level of endogenous and exogenous glucocorticoid exposure during the neonatal period predicts the saliva cortisol response to immunization at 4 mo of age. We followed 45 babies born below 32 wk gestation. We showed that their concentration of plasma cortisol during the first 4 wk was 358, 314, 231, and 195 nmol/L cortisol, respectively (geometric mean). This is four to seven times higher than fetal levels at the same gestational age range. We used routine immunization at 4 mo and 12 mo as a stressor and measured the change in saliva cortisol as the stress response. Mean circulating cortisol in the first 4 wk predicted the cortisol response at 4 but not at 12 mo. Path analysis showed that birthweight for gestational age, therapeutic antenatal steroids, and therapeutic postnatal steroids also contributed to the magnitude of the saliva cortisol response at 4 mo. This provides evidence that the magnitude of glucocorticoid exposure, both endogenous and exogenous, may have an effect on later stress responses. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16306199&query_hl=1 ER - TY - JFULL T1 - Prostanoid receptors in human uterine myocytes: the effect of reproductive state and stretch. A1 - Sooranna, SR A1 - Grigsby, P A1 - Myatt, L A1 - Bennett, PR A1 - Johnson, MR J1 - Mol Hum Reprod Y1 - 2005/12// VL - 11 SN - 1360-9947 SP - 859 EP - 864 N2 - In the human, prostanoids are known to be important mediators of uterine relaxation and contraction during pregnancy and parturition. We have previously shown that stretch of uterine smooth muscle cells increased prostaglandin H synthase 2 (PGHS-2) mRNA expression, PGHS-2 peptide synthesis and activity, however, the net effect on uterine contractility of this increase in prostaglandin synthesis would be determined by the expression of the different prostanoid receptors. Therefore, the aims of this study were to establish the expression of prostanoid receptor mRNA in uterine myocytes obtained from women in different reproductive states and to test the hypothesis that stretch of uterine myocytes alters prostanoid receptor mRNA expression to promote uterine contractility. Myocytes were isolated from women undergoing hysterectomy (NP) and pregnant women undergoing LSCS either before (NL) or after the onset of labour (L) and were subjected to 11% stretch for 1 h (n = 6 in all cases). Copy numbers of the individual receptors varied widely with reproductive state but followed the pattern: FP > IP = DP = EP-4 > TP = EP-3 = EP-2 > EP-1. FP mRNA expression was significantly lower in the NL group compared to the NP group and EP-3, EP-4 and TP mRNA expression was significantly lower in both NL and L groups compared to NP group levels. The level of mRNA expression of EP-1, EP-2, DP and IP did not differ between NP, NL and L groups. Stretch of cells derived from the NP group resulted in a significant decrease in EP-4 mRNA expression alone and of the NL group a significant decrease in EP-2 mRNA expression alone. Stretch had no effect on cells derived from the L group. These data show that pregnancy is associated with a significant reduction in 3 of 4 pro-contraction associated prostanoid receptor mRNA expression and 1 of 4 pro-relaxant. Stretch elicited no consistent change in prostanoid receptor mRNA expression. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16421214&query_hl=1 ER - TY - JFULL T1 - Stem cell transplantation: Impact of high efficiency particulate air (HEPA) vs. non-HEPA BMT unit on transplant outcome: A single centre experience from India. A1 - Nair, V A1 - Sharma, A A1 - Mishra, DK A1 - Chopra, GS A1 - Kotwal, J A1 - Agarwal, MB A1 - Bhandari, NK A1 - Rai, R J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 415B EP - 415B ER - TY - JFULL T1 - Chimeric anti CD-20 monoclonal antibody-rituximab in refractory childhood idiopathic thrombocytopenic purpura: An Indian experience. A1 - Sharma, A A1 - Nair, V A1 - Mishra, DK A1 - Kotwal, J A1 - Chopra, GS A1 - Bhandari, NK A1 - Agarwal, MB A1 - Rai, R J1 - BLOOD Y1 - 2005/11/16/ VL - 106 SN - 0006-4971 SP - 82B EP - 82B ER - TY - JFULL T1 - Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: a study on hCG overexpressing transgenic mice. A1 - Ahtiainen, P A1 - Rulli, SB A1 - Shariatmadari, R A1 - Pelliniemi, LJ A1 - Toppari, J A1 - Poutanen, M A1 - Huhtaniemi, IT J1 - Oncogene Y1 - 2005/11/10/ VL - 24 SN - 0950-9232 SP - 7301 EP - 7309 N2 - We have previously demonstrated that male transgenic (TG) mice overexpressing human chorionic gonadotropin (hCG+) develop reproductive organ defects, but no tumors, in adult age. In this study, the effects of persistently elevated hCG were followed in TG males between day 5 postpartum and adulthood. Leydig cell (LC) adenomas were found in prepubertal mice, most prominently at the age of 10 days, but not in adult age. Serum testosterone concentrations were significantly increased in TG males at all ages studied. The phenotype of the prepubertal hCG+ males resembled that found in boys upon expression of constitutively activating luteinizing hormone (LH) receptor mutations. The temporal expression patterns of the fetal LC marker gene, thrombospondin 2, and those of adult LCs, hydroxysteroid dehydrogenase-6, delta5-3-beta and prostaglandin D synthase, were similar in wild-type and hCG+ males. Hence, the postnatal adenomas resemble functionally fetal LCs, and only these cells are susceptible to hCG-induced tumorigenesis. Our findings demonstrate a novel intriguing difference between the fetal and adult LC populations and provide further insight into the potential tumorigenic effects of gonadotropins. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16007123&query_hl=1 ER - TY - JFULL T1 - Progesterone reguration of FOXO1 expression and activity coordinates endometrial decidualization and menstrual shedding A1 - Kajihara, T A1 - Ishihara, O A1 - Brosens, J J1 - PLACENTA Y1 - 2005/11// VL - 26 SN - 0143-4004 SP - A9 EP - A9 ER - TY - JFULL T1 - Identification of genes regulated by interleukin-1 beta in human endometrial stromal cells A1 - Rossi, M A1 - Sharkey, AM A1 - Vigano, P A1 - Fiore, G A1 - Furlong, R A1 - Florio, P A1 - Ambrosini, G A1 - Smith, SK A1 - Petraglia, F J1 - REPRODUCTION Y1 - 2005/11// VL - 130 SN - 1470-1626 SP - 721 EP - 729 N2 - Interleukin-1 beta (IL-1 beta) is an important immune regulatory factor that in human endometrium plays a role in both menstruation and implantation in the event of pregnancy. It promotes inflammatory-like processes and also stimulates tissue remodelling. We present a cDNA microarray study documenting the major effects of IL-1 beta on gene expression in stromal cells from human endometrium. Endometrial stromal cells from five normal healthy women at the mid secretory phase were cultured with or without IL-1 beta at 50 and 500 pg/ml for 48 h. cDNA microarrays were used to compare the levels of gene expression in total RNA isolated from cells stimulated with IL-1 beta. These cDNA arrays were produced containing 15 164 sequence-verified clones, which included genes known to be important in angiogenesis, immune modulators, apoptosis, cell signalling, extracellular matrix (ECM) remodelling and cell cycle regulation. Genes which were regulated by IL-1 beta were identified by analysis of the microarray data using the Significance Analysis of Microarrays software package. Upregulated (n = 23) and downregulated (n = 6) different genes were observed, which changed at least 3-fold, at a false discovery rate of less than 2% (P < 0.02). Our results have identified genes regulated by IL-1 beta, which are involved in leukocyte recruitment, ECM remodelling and other cellular functions. Changes in three genes, IL-8, colony-stimulating factor 2 and aldo-keto reductase family 1 member 1, which were upregulated by IL-1 beta, were verified using real-time PCR. Novel functions regulated by IL-1 beta in endometrium, including genes involved in free radical protection, and fatty acid metabolism were also identified. These results also provide new insights into the role of IL-1 beta in disorders of the endometrium, especially in implantation-related infertility and endometriosis, in which this cytokine plays a major role. ER - TY - JFULL T1 - The expression of minichromosome maintenance protein-2 in normal and abnormal megakaryocytes and comparison with the proliferative marker Ki-67. A1 - Lampert, IA A1 - Horncastle, D A1 - Dilworth, S A1 - Roberts, I A1 - Alison, MR A1 - Naresh, KN J1 - Br J Haematol Y1 - 2005/11// VL - 131 SN - 0007-1048 SP - 490 EP - 494 N2 - The minichromosome maintenance (Mcm) and Cdc6 proteins are important regulators of eucaryotic DNA replication. In most normal tissues, a similar proportion of cells express Mcm-2 and Ki-67. The present study showed that in both normal and abnormal states, the proportion of megakaryocytes expressing Mcm-2 is roughly seven times as many as those that express Ki-67. This is likely to be related to the process of endomitosis and endoreduplication. We also demonstrated that a significantly lower proportion of megakaryocytes in myelodysplastic syndrome express Mcm-2. These findings provide new insights into megakaryocyte biology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16281941&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 - Programming of cardiovascular function: Differential effects of pre- and postnatal maternal stress A1 - Igosheva, N A1 - Taylor, P A1 - Poston, L A1 - Glover, V J1 - PEDIATR RES Y1 - 2005/11// VL - 58 SN - 0031-3998 SP - 1096 EP - 1097 ER - TY - JFULL T1 - The role of nuclear factor kappa B in human labour. A1 - Lindström, TM A1 - Bennett, PR J1 - Reproduction Y1 - 2005/11// VL - 130 SN - 1470-1626 SP - 569 EP - 581 N2 - Preterm birth remains the leading cause of perinatal mortality and morbidity, largely as a result of a poor understanding of the precise mechanisms controlling labour onset in humans. Inflammation has long been recognised as a key feature of both preterm and term labour, with an influx of inflammatory cells into the uterus and elevated levels of pro-inflammatory cytokines observed during parturition. Nuclear factor kappa B (NF-kappaB) is a transcription factor family classically associated with inflammation. Accumulating evidence points to a role for NF-kappaB in the physiology and pathophysiology of labour. NF-kappaB activity increases with labour onset and is central to multiple prolabour pathways. Premature or aberrant activation of NF-kappaB may thus contribute to preterm labour. The current understanding of NF-kappaB in the context of human labour is discussed here. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16264088&query_hl=1 ER - TY - JFULL T1 - RIP140-targeted repression of gene expression in adipocytes. A1 - Christian, M A1 - Kiskinis, E A1 - Debevec, D A1 - Leonardsson, G A1 - White, R A1 - Parker, MG J1 - Mol Cell Biol Y1 - 2005/11// VL - 25 SN - 0270-7306 SP - 9383 EP - 9391 N2 - Ligand-dependent repression of nuclear receptor activity forms a novel mechanism for regulating gene expression. To investigate the intrinsic role of the corepressor RIP140, we have monitored gene expression profiles in cells that express or lack the RIP140 gene and that can be induced to undergo adipogenesis in vitro. In contrast to normal white adipose tissue and in vitro-differentiated wild-type adipocytes, RIP140-null cells show elevated energy expenditure and express high levels of the uncoupling protein 1 gene (Ucp1), carnitine palmitoyltransferase 1b, and the cell-death-inducing DFF45-like effector A. Conversely, all these changes are abrogated by the reexpression of RIP140. Analysis of the Ucp1 promoter showed RIP140 recruitment to a key enhancer element, demonstrating a direct role in repressing gene expression. Therefore, reduction in the levels of RIP140 or prevention of its recruitment to nuclear receptors may provide novel mechanisms for the control of energy expenditure in adipose cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16227589&query_hl=1 ER - TY - JFULL T1 - Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75. A1 - Carvajal, A A1 - Espinoza, N A1 - Kato, S A1 - Pinto, M A1 - Sadarangani, A A1 - Monso, C A1 - Aranda, E A1 - Villalon, M A1 - Richer, JK A1 - Horwitz, KB A1 - Brosens, JJ A1 - Owen, GI J1 - Breast Cancer Res Treat Y1 - 2005/11// VL - 94 SN - 0167-6806 SP - 171 EP - 183 N2 - Progesterone in hormone replacement therapy (HRT) preparations increases, while hysterectomy greatly reduces, the incidence of breast cancer. Cross-talk between the progesterone and growth factor signaling pathways occurs at multiple levels and this maybe a key factor in breast cancer survival and progression. To test this hypothesis, we characterized the effect of progesterone pre-treatment on the sensitization of the epidermal growth factor (EGF) signaling pathway to EGF in the breast cancer cell line ZR-75. For the first time in ZR-75 cells and in agreement with previous work using synthetic progestins, we demonstrate that pre-treatment with the natural ligand progesterone increases EGF receptor (EGFR) levels and subsequent ligand-dependent phosphorylation. Downstream we demonstrate that progesterone alone increases erk-1 + 2 phosphorylation, potentiates EGF-phosphorylated erk-1 + 2 and maintains these levels elevated for 24 h; over 20 h longer than in vehicle treated cells. Additionally, progesterone increased the levels of STAT5, another component of the EGF signaling cascade. Progesterone increased EGF mediated transcription of a c-fos promoter reporter and the nuclear localization of the native c-fos protein. Furthermore, progesterone and EGF both alone and in combination, significantly increase cell proliferation. Several results presented herein demonstrate the conformity between the action of the natural ligand progesterone with that of synthetic progestins such as MPA and R5020 and allows the postulation that the progestin/progesterone-dependent increase of EGF signaling provides a survival advantage to burgeoning cancer cells and may contribute to the breast cancer risk associated with endogenous progesterone and with progestin-containing HRT. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16175315&query_hl=1 ER - TY - JFULL T1 - Patients with PSC have better outcomes after live-donor than cadaveric liver transplantation A1 - Maheshwari, A A1 - Singh, A A1 - Maley, W A1 - Rai, R J1 - HEPATOLOGY Y1 - 2005/10// VL - 42 SN - 0270-9139 SP - 451A EP - 451A ER - TY - JFULL T1 - Histomorphometric characterisation of shared and non-shared cotyledonary villus territories in monochorionic placentae in relation to pregnancy complications A1 - Wee, LY A1 - Sebire, NJ A1 - Sullivan, M A1 - Fisk, NM J1 - J PATHOL Y1 - 2005/10// VL - 207 SN - 0022-3417 SP - 1 EP - 1 ER - TY - JFULL T1 - Anti-müllerian hormone protein expression is reduced during the initial stages of follicle development in human polycystic ovaries. A1 - Stubbs, SA A1 - Hardy, K A1 - Da Silva-Buttkus, P A1 - Stark, J A1 - Webber, LJ A1 - Flanagan, AM A1 - Themmen, AP A1 - Visser, JA A1 - Groome, NP A1 - Franks, S J1 - J Clin Endocrinol Metab Y1 - 2005/10// VL - 90 SN - 0021-972X SP - 5536 EP - 5543 N2 - CONTEXT: Polycystic ovary syndrome, the most common cause of anovulatory infertility, is characterized by disordered folliculogenesis, notably increased progression from the primordial to the primary stages. This ovarian phenotype is similar to that observed in mice lacking anti-müllerian hormone (AMH). OBJECTIVE: The objective of this study is to investigate whether AMH is involved in accelerating the transition of follicles from primordial to primary stages in polycystic ovaries. DESIGN: This study compares AMH expression in archive tissue from normal and polycystic ovaries. SETTING: This is a laboratory-based study. PATIENTS: Ovarian tissue from seven normoovulatory women and 16 women with polycystic ovaries (five of whom were anovulatory) was used in this study. Ovaries were classified by histology and with reference to menstrual cycle history and ultrasound. MAIN OUTCOME MEASURE: Presence and intensity of AMH expression in 1403 follicles was the main outcome measure. RESULTS: AMH was observed from the primordial stage onward. AMH immunostaining was observed in significantly fewer primordial (P = 0.007) and transitional follicles (P = 0.001) in ovaries from anovulatory women with polycystic ovaries compared with women with regular cycles and either normal or polycystic ovaries. AMH-negative follicles had fewer pregranulosa cells in the largest cross-section of the follicle at both the primordial (median, four and six for AMH-negative and -positive follicles, respectively; P < 0.0001) and transitional stages (median six and nine; P < 0.0007) in normal tissue, and fewer at the transitional stage (median, seven and 11; P < 0.0001) in tissue from anovulatory women with polycystic ovaries. This suggests that AMH expression is associated with granulosa cell mitosis. CONCLUSIONS: These findings indicate a relative deficiency of AMH in primordial and transitional follicles in ovaries from anovulatory women with polycystic ovaries. This may contribute to disordered early follicle development in polycystic ovary syndrome. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16030171&query_hl=1 ER - TY - JFULL T1 - FXR mutations in intrahepatic cholestasis of pregnancy A1 - van Mil, S A1 - Dixon, PH A1 - Christian, M A1 - Mullenbach, R A1 - Shevchuk, L A1 - Chambers, J A1 - Cheng, F A1 - White, R A1 - Parker, M A1 - Williamson, C J1 - HEPATOLOGY Y1 - 2005/10// VL - 42 SN - 0270-9139 SP - 461A EP - 461A ER - TY - JFULL T1 - Interim safety analysis of patients enrolled in the randomized, international retreatment with PEGASYS (R) in patients not responding to prior peginterferon alfa-2b/ribavirin (RBV) combination therapy (repeat) study A1 - Marcellin, P A1 - Freilich, B A1 - Andreone, P A1 - Brandao-Mello, CE A1 - Di Bisceglie, A A1 - Rai, R A1 - Jensen, D J1 - HEPATOLOGY Y1 - 2005/10// VL - 42 SN - 0270-9139 SP - 657A EP - 658A ER - TY - JFULL T1 - Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient. A1 - Mahieu-Caputo, D A1 - Meulemans, A A1 - Martinovic, J A1 - Gubler, MC A1 - Delezoide, AL A1 - Muller, F A1 - Madelenat, P A1 - Fisk, NM A1 - Dommergues, M J1 - Pediatr Res Y1 - 2005/10// VL - 58 SN - 0031-3998 SP - 685 EP - 688 N2 - Despite advances in treatment, twin-to-twin transfusion syndrome (TTTS) still carries a high risk for perinatal mortality and morbidity. Simple blood transfer from the donor to the recipient twin cannot explain all of the features of this disease, in particular the recipient's hypertensive cardiomyopathy. We report a case in which TTTS resulted in preterm delivery with early neonatal death of both twins, allowing assessment of the renin angiotensin system (RAS) status of each fetus, both by cord blood renin and aldosterone assay and by renal immunohistochemistry. The donor had severe oliguria/oligohydramnios, whereas the recipient, in addition to severe polyuria/polyhydramnios, had cardiomyopathy, atrioventricular regurgitation, and ascites. Although immunohistochemistry demonstrated that renal secretion of renin was up-regulated in the donor and down-regulated in the recipient, cord blood levels of renin and aldosterone were similar, with high renin levels in both twins. This observation supports the hypothesis that despite renal RAS down-regulation, the recipient is exposed to RAS effectors elaborated in the donor and transferred via placental shunts. This may contribute to cardiomyopathy and hypertension in the recipient, which cannot be accounted for by hypervolemia alone. We thus hypothesized that in TTTS, the recipient's hypertensive cardiomyopathy could be due to a mechanism similar to the classical model of hypertension referred to as "2 kidneys-1 clip." Thus the hypovolemic donor twin, comparable to the clipped kidney, produces vasoactive hormones that compromise the recipient, comparable to the normal kidney, causing hypertension and cardiomyopathy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16189193&query_hl=1 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 - Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis A1 - Wu, O A1 - Robertson, L A1 - Twaddle, S A1 - Lowe, G A1 - Clark, P A1 - Walker, I A1 - Brenkel, I A1 - Greaves, M A1 - Langhorne, P A1 - Regan, L A1 - Greer, I A1 - Thrombosis Risk Economic Assesmen J1 - BRIT J HAEMATOL Y1 - 2005/10// VL - 131 SN - 0007-1048 SP - 80 EP - 90 N2 - Laboratory testing for the identification of heritable thrombophilia in high-risk patient groups have become common practice; however, indiscriminate testing of all patients is unjustified. The objective of this study was to evaluate the cost-effectiveness of universal and selective history-based thrombophilia screening relative to no screening, from the perspective of the UK National Health Service, in women prior to prescribing combined oral contraceptives and hormone replacement therapy, women during pregnancy and patients prior to major orthopaedic surgery. A decision analysis model was developed, and data from meta-analysis, the literature and two Delphi studies were incorporated in the model. Incremental cost-effectiveness ratios (ICERs) for screening compared with no screening was calculated for each patient group. Of all the patient groups evaluated, universal screening of women prior to prescribing hormone replacement therapy was the most cost-effective (ICER 6824) pound. In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER 202 pound 402). Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism was more cost-effective than universal screening in all the patient groups evaluated. ER - TY - JFULL T1 - Knockout of luteinizing hormone receptor abolishes the effects of follicle-stimulating hormone on preovulatory maturation and ovulation of mouse graafian follicles. A1 - Pakarainen, T A1 - Zhang, FP A1 - Nurmi, L A1 - Poutanen, M A1 - Huhtaniemi, I J1 - Mol Endocrinol Y1 - 2005/10// VL - 19 SN - 0888-8809 SP - 2591 EP - 2602 N2 - It is considered a dogma that a secretory peak of LH is indispensable as the trigger of ovulation. However, earlier studies on hypophysectomized rodents have shown that stimulation with recombinant FSH, devoid of any LH activity, is able to boost the final stages of follicular maturation and trigger ovulation. As the expression of ovarian LH receptors (LHRs) still persists after hypophysectomy, such studies cannot totally exclude the possibility that LHR activation is involved in the apparently pure FSH effects. To revisit this question, we analyzed in LHR knockout (LuRKO) mice the progression of folliculogenesis and induction of ovulation by human chorionic gonadotropin and human recombinant FSH treatments. The results provide clear evidence that follicular development and ovulation could not be induced by high doses of FSH in the absence of LHR expression. Ovarian histology and oocyte analyses indicated that follicular maturation did not advance in LuRKO mice beyond the antral follicle stage. Neither were ovulations detected in LuRKO ovaries after any of the gonadotropin treatments. The ovarian resistance to FSH treatment in the absence of LHR was confirmed by real-time RT-PCR and immunohistochemical analyses of a number of gonadotropin-dependent genes, which only responded to the treatments in wild-type control mice. Negative findings were not altered by estradiol priming preceding the gonadotropin stimulations. Hence, the present study shows that, in addition to ovulation, the expression of LHR is essential for follicular maturation in the progression from antral to preovulatory stage. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15941853&query_hl=1 ER - TY - JFULL T1 - The expression pattern of MUC1 glycoforms and other biomarkers of endometrial receptivity in fertile and infertile women. A1 - Horne, AW A1 - Lalani, EN A1 - Margara, RA A1 - Ryder, TA A1 - Mobberley, MA A1 - White, JO J1 - Mol Reprod Dev Y1 - 2005/10// VL - 72 SN - 1040-452X SP - 216 EP - 229 N2 - Changes in the surface epithelium of the endometrium, characterized in part by alterations in cell-surface molecules, sex steroid receptors and the appearance of pinopodes, coincide with the window of endometrial receptivity in the menstrual cycle. This study was performed to evaluate the usefulness of hematoxylin and eosin staining, scanning and transmission microscopy, and MUC1 glycoform, sex steroid receptor, and interleukin receptor (type 1) expression as biomarkers of endometrial receptivity using carefully characterized clinical fertile and infertile groups of women. Using a combination of immunohistochemistry and scanning electron microscopy (SEM) called scanning immunoelectron microscopy (SIM), we confirmed that MUC1 mucin was not associated with the endometrial pinopodes, which have been linked with embryo adhesion. We also showed that failure of embryo implantation was associated with an abnormal endometrial expression of MUC1 mucin, and retention of nuclear progesterone receptor (PR) particularly in epithelial cells. Hematoxylin and eosin staining, transmission electron microscopy (TEM), SEM in isolation and immunohistochemistry for interleukin receptor were not shown to be useful markers. Progesterone-dependent regulation of MUC1 appears to be an important factor in determining endometrial receptivity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15971251&query_hl=1 ER - TY - JFULL T1 - Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues. A1 - Fernandes, MS A1 - Pierron, V A1 - Michalovich, D A1 - Astle, S A1 - Thornton, S A1 - Peltoketo, H A1 - Lam, EW A1 - Gellersen, B A1 - Huhtaniemi, I A1 - Allen, J A1 - Brosens, JJ J1 - J Endocrinol Y1 - 2005/10// VL - 187 SN - 0022-0795 SP - 89 EP - 101 N2 - Rapid non-genomic actions of progesterone are implicated in many aspects of female reproduction. Recently, three human homologues of the fish membrane progestin receptor (mPR) have been identified. We combined bioinformatic analysis with expression profiling to define further the role of these mPRs in human reproductive tissues. Sequence analysis confirmed that the mPRs belong to a larger, highly conserved family of proteins, termed 'progestin and adiponectin receptors' (PAQRs). A comparison of the expression of mPR transcripts with that of two related PAQR family members, PAQRIII and PAQRIX, in cycling endometrium and pregnancy tissues revealed markedly divergent expression levels and profiles. For instance, endometrial expression of mPRalpha and gamma and PAQRIX was cycle-dependent whereas the onset of parturition was associated with a marked reduction in myometrial mPRalpha and beta transcripts. Interestingly, mPRalpha and PAQRIX were most highly expressed in the placenta, and the tissue expression levels of both genes correlated inversely with that of the nuclear PR. Phylogenetic analysis demonstrated that PAQRIX belongs to the mPR subgroup of proteins. We also validated a polyclonal antibody raised against the carboxy-terminus of human mPRalpha. Immunohistochemical analysis demonstrated more intense immunoreactivity in placental syncytiotrophoblasts than in endometrial glands or stroma. The data suggest important functional roles for mPRalpha, and possibly PAQRIX, in specific reproductive tissues, particularly those that express low levels of nuclear PR. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16214944&query_hl=1 ER - TY - JFULL T1 - What have gonadotrophin overexpressing transgenic mice taught us about gonadal function? A1 - Rulli, SB A1 - Huhtaniemi, I J1 - Reproduction Y1 - 2005/09// VL - 130 SN - 1470-1626 SP - 283 EP - 291 N2 - The two gonadotrophins, follicle-stimulating hormone and luteinising hormone, are pivotal regulators of the development and maintenance of normal fertility by maintaining testicular and ovarian endocrine function and gametogenesis. Too low gonadotrophin secretion, i.e. hypogonadotrophic hypogonadism, is a common cause of infertility. But there are also physiological and pathophysiological conditions where gonadotrophin secretion and/or action are either transiently or chronically elevated, such as pregnancy, pituitary tumours, polycystic ovarian syndrome, activating gonadotrophin receptor mutations, perimenopause and menopause. These situations can be either the primary or secondary cause of infertility and gonadal pathologies in both sexes. Also the role of gonadotrophins as tumour promoters is possible. Recently, the possibility to combine information from genetically modified mice and human phenotypes in connection with mutations of gonadotrophin or gonadotrophin receptor genes has elucidated many less well known mechanisms involved in dysregulation of gonadotrophin function. Among the genetically modified mouse models, transgenic mice with gonadotrophin hypersecretion have been developed during the last few years. In this review, we describe the key findings on transgenic mouse models overexpressing gonadotrophins and present their possible implications in related human pathologies. In addition, we provide examples of genetic mouse models with secondary effects on gonadotrophin production and, consequently, on gonadal function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16123235&query_hl=1 ER - TY - JFULL T1 - Does variant luteinizing hormone (V-LH) predispose to improper testicular position in late pregnancy? A1 - Kaleva, M A1 - Virtanen, H A1 - Haavisto, AM A1 - Main, K A1 - Skakkebaek, NE A1 - Huhtaniemi, I A1 - Irjala, K A1 - Toppari, J J1 - Pediatr Res Y1 - 2005/09// VL - 58 SN - 0031-3998 SP - 447 EP - 450 N2 - Undescended testes are a common urogenital malformation affecting 2-9% of newborn boys. The etiology of cryptorchidism is probably heterogeneous, but insufficient androgen effect has been recognized as one cause of the condition. A common genetic variant (V) form of LH occurs in apparently healthy individuals universally. Compared with wild-type (WT) LH, the V-LH molecule has increased bioactivity in vitro but shorter half-life in vivo. In the present study, we screened 93 cryptorchid (59 uni- and 34 bilateral) and 211 healthy boys for the occurrence of V-LH to evaluate whether it is related to testicular descent. Two immunofluorometric assays with different combinations of MAb, one detecting WT-LH, the other detecting both WT- and V-LH, were used to measure LH concentrations. The ratio of two LH measurements was used to assess the V-LH status. The prevalence of V-LH was similar in the control and cryptorchid groups, and the total prevalence of V-LH corresponded well to the prevalence of V-LH in general Finnish population. Among cryptorchid boys, the prevalence of V-LH was dependent on gestational age: 6.7% at GA <37, 20.9% at GA 37-39, and 42.9% at GA of 40-42 wk. In contrast, the percentage of V-LH status was similar at different gestational ages in all control groups. We conclude that V-LH is not critical for normal testicular descent but the increased prevalence of V-LH among cryptorchid boys with GA >40, suggests that the lower hormonal efficacy of V-LH predisposes for improper testicular descent in late pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16148055&query_hl=1 ER - TY - JFULL T1 - A randomized trial of amnioreduction versus septostomy in the treatment of twin-twin transfusion syndrome. A1 - Moise, KJ A1 - Dorman, K A1 - Lamvu, G A1 - Saade, GR A1 - Fisk, NM A1 - Dickinson, JE A1 - Wilson, RD A1 - Gagnon, A A1 - Belfort, MA A1 - O'Shaughnessy, RO A1 - Chitkara, U A1 - Hassan, SS A1 - Johnson, A A1 - Sciscione, A A1 - Skupski, D J1 - Am J Obstet Gynecol Y1 - 2005/09// VL - 193 SN - 0002-9378 SP - 701 EP - 707 N2 - OBJECTIVE: Left untreated, severe twin-to-twin transfusion syndrome (TTTS) presenting in the early second trimester of pregnancy is often associated with significant maternal morbidity and almost universal perinatal loss. Removal of excessive amounts of amniotic fluid through serial amniocenteses (amnioreduction) has been the mainstay of therapy. We sought to compare amnioreduction to intentional perforation of the intervening twin membrane (septostomy). STUDY DESIGN: Pregnant women with TTTS before 24 weeks' gestation were randomly assigned to serial amnioreduction or septostomy. A single puncture technique under ultrasound guidance was used for the septostomy. The primary outcome measure was survival to neonatal discharge, and was assessed based on the number of pregnancies or the number of fetuses as appropriate. RESULTS: The study was terminated at the planned interim analysis stage after 73 women were enrolled. This was because the rate of survival of at least 1 infant was similar in the amnioreduction group compared to the septostomy group (78% vs 80% of pregnancies, respectively; RR=0.94, 95%CI 0.55-1.61; P=.82). Patient undergoing septostomy were more likely to require a single procedure for treatment (64% vs 46%; P=.04). CONCLUSION: Although overall perinatal survival is not enhanced, septostomy offers the advantage of often requiring a single procedure compared to serial amnioreduction in the treatment of severe twin-to-twin transfusion syndrome. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16150263&query_hl=1 ER - TY - JFULL T1 - Infection and signalling in the fetal membranes. A1 - Bennett, P J1 - PLACENTA Y1 - 2005/09// VL - 26 SN - 0143-4004 SP - A3 EP - A3 ER - TY - JFULL T1 - Maternal origin of inflammatory leukocytes in preterm fetal membranes, shown by fluorescence in situ hybridisation. A1 - Steel, JH A1 - O'donoghue, K A1 - Kennea, NL A1 - Sullivan, MH A1 - Edwards, AD J1 - Placenta Y1 - 2005/09// VL - 26 SN - 0143-4004 SP - 672 EP - 677 N2 - The aim of this study was to determine the maternal or fetal origin of inflammatory leukocytes in fetal membranes from cases of chorioamnionitis. Fetal membranes were collected from male preterm infants and chorioamnionitis was diagnosed histologically. Fluorescence in situ hybridisation for X and Y chromosomes was used to determine the gender of infiltrating leukocytes in the chorion and amnion. Leukocytes, trophoblast and mesenchymal cells were identified using immunohistochemistry for CD45, cytokeratin-7 and vimentin, respectively. Leukocytes present in the chorion and amnion were labelled XX, indicating maternal origin, and these cells were immunoreactive for the leukocyte marker CD45 but not for vimentin or cytokeratin-7. All other cells in the chorion and amnion were labelled XY and of fetal origin. The results indicated that maternal leukocytes invade the amnion and chorion in chorioamnionitis and we suggest that this is part of the maternal inflammatory response to intrauterine infection. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16085046&query_hl=1 ER - TY - JFULL T1 - Insights into the pathophysiology of twin-twin transfusion syndrome. A1 - Galea, P A1 - Jain, V A1 - Fisk, NM J1 - Prenat Diagn Y1 - 2005/09// VL - 25 SN - 0197-3851 SP - 777 EP - 785 N2 - Twin-twin transfusion syndrome (TTTS) is attributed to trans-anastomotic transfusion between twins. Anastomoses are ubiquitous in monochorionic (MC) placentae, yet TTTS develops in only 15%. Although ex vivo and in vivo studies fail to identify a unique anastomotic signature, TTTS placentae are typically associated with an imbalance in unidirectional arteriovenous anastomoses with absent bidirectional anastomoses. Doppler detection of an artery-artery anastomosis reduces the chance of TTTS, whereas, in those that develop the disease, it improves stage-independent survival. Selective laser is often curative, but an increasingly recognized risk of persistent or reverse TTTS may be attributable to atypical arteriovenous anastomoses not identifiable from the chorionic plate. Simple dysvolaemia fails to explain several phenotypic features, including haematological concordancy, recipient hypertension, and reversibly absent end diastolic flow in the donor. The renin-angiotensin system is upregulated in the donor and downregulated in the recipient's kidneys, while paradoxically raised renin levels in the recipient may contribute to raised afterload along with endothelin. Although research is limited in humans by therapy and the lack of a suitable experimental model, further studies of placental and vascular pathophysiology may not only refine current treatment modalities but may also, in addition, suggest further avenues for downstream management such as genetic predisposition testing or pharmacological intervention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16170838&query_hl=1 ER - TY - JFULL T1 - Focus on gonadotrophin signalling. A1 - Huhtaniemi, I J1 - Reproduction Y1 - 2005/09// VL - 130 SN - 1470-1626 SP - 261 EP - 262 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16123232&query_hl=1 ER - TY - JFULL T1 - Phosphatidylinositol 3-kinase is required for the transcriptional activation of cyclin D2 in BCR activated primary mouse B lymphocytes. A1 - Glassford, J A1 - Vigorito, E A1 - Soeiro, I A1 - Madureira, PA A1 - Zoumpoulidou, G A1 - Brosens, JJ A1 - Turner, M A1 - Lam, EW J1 - Eur J Immunol Y1 - 2005/09// VL - 35 SN - 0014-2980 SP - 2748 EP - 2761 N2 - Induction of cyclin D2 is essential for mediating cell cycle entry in B cells activated by BCR cross-linking. In the present study we show that, like B lymphocytes lacking cyclin D2, the p85alpha subunit of phosphatidylinositol 3-kinase (PI3K) or other components of the B cell signalosome, p110delta-null B cells fail to induce cyclin D2 and enter early G1 but not S phase of the cell cycle. The inhibitors of PI3K activity, LY294002 and Wortmannin, also abrogate cyclin D2 induction by BCR cross-linking, confirming that the class IA PI3K is necessary for cyclin D2 induction in response to BCR stimulation. Furthermore, using both p85alpha-null and p110delta-null B cells and inhibitors of PI3K, this study demonstrates for the first time, that BCR cross-linking induces cyclin D2 mRNA expression via transcriptional activation of the cyclin D2 promoter and that this transcriptional activation of cyclin D2 requires PI3K activity. Moreover, we identify a region between nucleotides -1624 and -1303 of the cyclin D2 promoter containing elements responsive to anti-IgM, which are PI3K dependent. Further characterisation of signalling intermediates downstream of the BCR revealed a perturbation of MAPK signalling pathways in p85alpha-null and p110delta-null B cells, and our data suggests that cross-talk exists between the PI3K and JNK pathways. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16114097&query_hl=1 ER - TY - JFULL T1 - Effect of mechanical stretch on the expression of interleukin-ibetain human uterine myocytes. A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - PLACENTA Y1 - 2005/09// VL - 26 SN - 0143-4004 SP - A44 EP - A44 ER - TY - JFULL T1 - Isatin: Role in stress and anxiety A1 - Medvedev, A A1 - Igosheva, N A1 - Crumeyrolle-Arias, M A1 - Glover, V J1 - STRESS Y1 - 2005/09// VL - 8 SN - 1025-3890 SP - 175 EP - 183 N2 - (Indoledione 2,3) Isatin is an endogenous indole found both in mammalian brain and peripheral tissues. Isatin concentration in blood can exceed 1 mu M and tissue concentrations vary from <0.1 to 10 mu M. Its level in the brain and periphery is increased by stress. Isatin has a wide spectrum of behavioural and metabolic effects. It is anxiogenic at lower doses and sedative at higher doses. Its most potent known in vitro actions are as an antagonist of atrial natriuretic peptide (ANP) function and NO signaling. In this review, we discuss isatin and stress in animal models, the few human studies, and also what it is known to date about the molecular mechanisms of its action. We suggest the possibility that isatin and its analogues may be interesting new pharmacological agents; Isatin antagonists may be anxiolytic, and isatin agonists may activate the HPA axis. ER - TY - JFULL T1 - Expression and potential function of cysteine cathepsins in the human placenta A1 - Varanou, A A1 - Burton, G A1 - Williamson, C A1 - Hemberger, M J1 - PLACENTA Y1 - 2005/09// VL - 26 SN - 0143-4004 SP - A67 EP - A67 ER - TY - JFULL T1 - Multiple signaling defects in the absence of RIP140 impair both cumulus expansion and follicle rupture. A1 - Tullet, JM A1 - Pocock, V A1 - Steel, JH A1 - White, R A1 - Milligan, S A1 - Parker, MG J1 - Endocrinology Y1 - 2005/09// VL - 146 SN - 0013-7227 SP - 4127 EP - 4137 N2 - The nuclear receptor corepressor RIP140 is essential in the ovary for ovulation, but is not required for follicle growth and luteinization. To identify genes that may be subject to regulation by RIP140 or play a role in ovulation, we compared ovarian gene expression profiles in untreated immature wild-type and RIP140 null mice and after treatment with pregnant mare serum gonadotropin and human chorionic gonadotropin. Many genes involved in signaling, extracellular matrix formation, cell-cell attachment, and adhesion were aberrantly regulated in the absence of RIP140, varying according to the hormone status of the mice. Notable among these was the reduced expression of a number of genes that encode components of signaling pathways and matrix proteins required for cumulus expansion, a key remodeling process necessary for ovulation. Histological analysis confirmed that cumulus expansion in RIP140 null mice is reduced, oocyte detachment from the mural cell wall is impaired, and follicles fail to rupture in response to LH. Although the expression of many genes involved in cumulus cell expansion was reduced, there was a subset of genes involved in extracellular matrix formation and cell-cell interactions that was up-regulated and may interfere with ovarian tissue remodeling. We propose that widespread gene dysregulation in ovarian tissues in the absence of RIP140 leads to the anovulatory phenotype. This helps to define an important role for RIP140 in the regulation of multiple processes leading to ovulation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15919748&query_hl=1 ER - TY - JFULL T1 - Placental origin of paradoxical renin angiotensin system activation in recipeient fetuses with twin-twin transfusion syndrome. A1 - Galea, P A1 - Jain, V A1 - Sullivan, M A1 - Fisk, NM J1 - PLACENTA Y1 - 2005/09// VL - 26 SN - 0143-4004 SP - A36 EP - A36 ER - TY - JFULL T1 - Reviving the clinical efficacy of kanamycin-B: Design and synthesis of novel kanamycin analogs and studies of their antibacterial activity against aminoglycoside resistant bacteria A1 - Rai, R A1 - Chang, CWT J1 - ABSTR PAP AM CHEM S Y1 - 2005/08/28/ VL - 230 SP - U2623 EP - U2623 ER - TY - JFULL T1 - Design and synthesis of novel aminoglycosides and their antibacterial studies against aminoglycoside resistant bacteria A1 - Rai, R A1 - Chang, CWT J1 - ABSTR PAP AM CHEM S Y1 - 2005/08/28/ VL - 230 SP - U2623 EP - U2624 ER - TY - JFULL T1 - Non-invasive intrapartum fetal ECG: preliminary report. A1 - Taylor, MJ A1 - Thomas, MJ A1 - Smith, MJ A1 - Oseku-Afful, S A1 - Fisk, NM A1 - Green, AR A1 - Paterson-Brown, S A1 - Gardiner, HM J1 - BJOG Y1 - 2005/08// VL - 112 SN - 1470-0328 SP - 1016 EP - 1021 N2 - OBJECTIVES: To obtain fetal heart rate, detailed fetal electrocardiography (fECG) signals and uterine contractions during labour using a single device. DESIGN: Prospective observational study. SETTING: Delivery suite at a tertiary referral hospital, London, UK. POPULATION: Fifteen patients at median gestation of 39 weeks (range 24-41) were recruited at median cervical dilatation of 4.0 cm (range 0-10) of whom 8/15 (53%) had intact amniotic membranes. METHODS: Using 12 abdominally sited electrodes, we recorded the composite abdominal signal in pregnancies intrapartum. The recorded data were analysed off-line using a blind signal separation technique. MAIN OUTCOME MEASURES: Success of signal separation and fECG time intervals. RESULTS: Successful fECG signal acquisition was achieved in 12/15 (80%) patients and an averaged fECG waveform acquired. In these patients, P and QRS waves were seen in all cases, and T waves in 11/12 (92%). True beat-to-beat heart rate (HR) was displayed and measures of its variability obtained. The mother's ECG and uterine electrical activity, shown to match tocographically recorded uterine contractions, were also separated and displayed. Failure to acquire fECG in three cases was attributed to excessive abdominal muscular activity and electrical interference. CONCLUSIONS: This study demonstrates a non-invasive technique that displays detailed intrapartum fECG waveforms, HR variability, maternal ECG and uterine contractions simultaneously, all in a single device and which avoids the potential risks of invasive monitoring with a fetal scalp electrode. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16045511&query_hl=1 ER - TY - JFULL T1 - Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children. A1 - O'Connor, TG A1 - Ben-Shlomo, Y A1 - Heron, J A1 - Golding, J A1 - Adams, D A1 - Glover, V J1 - Biol Psychiatry Y1 - 2005/08/01/ VL - 58 SN - 0006-3223 SP - 211 EP - 217 N2 - BACKGROUND: Animal studies suggest that prenatal stress is associated with long-term disturbance in hypothalamic-pituitary-adrenal (HPA) axis function, but evidence in humans is lacking. This study examined the long-term association between prenatal anxiety and measures of diurnal cortisol at age 10 years. METHODS: Measures of cortisol were collected at awakening, 30 min after awakening, and at 4 pm and 9 pm on 3 consecutive days in a sample of 10-year-olds (n = 74) from the Avon Longitudinal Study of Parents and Children, a prospective longitudinal cohort study of mothers and children on whom measures of anxiety and depression were collected in pregnancy and the postpartum period. Analyses examined the links between symptoms of prenatal anxiety and multiple indicators of cortisol, an index of HPA axis functioning. RESULTS: Prenatal anxiety was significantly associated with individual differences in awakening and afternoon cortisol after accounting for obstetric and sociodemographic risk (partial correlations were .32 and .25, p < .05). The effect for awakening cortisol remained significant after controlling for multiple postnatal assessments of maternal anxiety and depression. CONCLUSIONS: This study provides the first human evidence that prenatal anxiety might have lasting effects on HPA axis functioning in the child and that prenatal anxiety might constitute a mechanism for an increased vulnerability to psychopathology in children and adolescents. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16084841&query_hl=1 ER - TY - JFULL T1 - Tissue factor is regulated by epidermal growth factor in normal and malignant human endometrial epithelial cells. A1 - Kato, S A1 - Pinto, M A1 - Carvajal, A A1 - Espinoza, N A1 - Monsó, C A1 - Bravo, L A1 - Villalon, M A1 - Cuello, M A1 - Quest, AF A1 - Suenaga, A A1 - Brosens, JJ A1 - Owen, GI J1 - Thromb Haemost Y1 - 2005/08// VL - 94 SN - 0340-6245 SP - 444 EP - 453 N2 - Tissue Factor (TF), the initiator of the extrinsic coagulation cascade, is overexpressed in a variety of cancers. TF is also expressed in normal human endometrium but little is known about its expression or regulation in endometrial cancer. We demonstrate herein that TF is expressed in the endometrial adenocarcinoma cell line Ishikawa. Furthermore, epidermal growth factor (EGF) induces a rapid and sustained increase in TF expression. Estradiol and progesterone had no effect on basal or EGF-induced TF expression in Ishikawa cells. In contrast to the pronounced and sustained upregulation at the protein level, EGF treatment elicited only a modest and transient increase in TF mRNA levels. This activity corresponded to the response observed from an exogenous TF promoter construct. However, the induction of TF was abrogated by cycloheximide as well as actinomycin-D, inhibitors or protein- and mRNA-synthesis, respectively, demonstrating that EGF mediates its effect through activation of the TF gene. Fractionation experiments showed that EGF increases TF presence in caveolin-I containing membrane fractions. Coagulation and invasion assays were used to explore the physiological implications of TF regulation. The results demonstrate that EGF-mediated induction of TF increases the procoagulant activity and invasive potential of Ishikawa cells. Furthermore, immunocytochemistry confirmed that TF is regulated by EGF in primary cultures of normal endometrial epithelial cells and malignant tumor cells. In conclusion, EGF-mediated upregulation of TF results in accumulation of this glycoprotein in caveolae-like membrane fractions and increased coagulative and invasive potential. Our results suggest that TF may play an integral role in endometrial carcinogenesis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16113838&query_hl=1 ER - TY - JFULL T1 - Human FSH beta subunit gene is highly conserved. A1 - Lamminen, T A1 - Jokinen, P A1 - Jiang, M A1 - Pakarinen, P A1 - Simonsen, H A1 - Huhtaniemi, I J1 - Mol Hum Reprod Y1 - 2005/08// VL - 11 SN - 1360-9947 SP - 601 EP - 605 N2 - FSH is a pituitary gonadotropin that along with LH plays a key role in the regulation of gonadal function. The gonadotropic hormones are composed of two subunits, the common alpha subunit and the hormone-specific beta subunit, which determines the binding to specific receptors and induction of biological response. Unlike the LHbeta gene, shown in earlier studies to harbour several amino acid-altering polymorphisms and mutations, information about the eventual sequence variation of the human FSHbeta subunit is not available. In this study, we made sequence analysis and comparison of polymorphisms found in FSHbeta in two Caucasian populations, the Finns and the Danes. It was found that FSHbeta subunit is highly conserved in these populations. Compared with the published sequences, only three silent polymorphisms were detected in the coding regions of the gene, and the promoter sequence was completely identical with the reported sequence. Two of the polymorphisms found were novel, one in the Finnish and one in the Danish population. The results of the sequence analysis show that the human FSHbeta gene is highly conserved and amino acid changing mutations are apparently extremely rare, at least in the samples collected randomly from control populations. This may be due to the crucial role of normal FSH function in the regulation of fertility. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16100240&query_hl=1 ER - TY - JFULL T1 - The effects of chemicals on mammalian fertility. The report and recommendations of ECVAM Workshop 53--the first strategic workshop of the EU ReProTect Project. A1 - Bremer, S A1 - Balduzzi, D A1 - Cortvrindt, R A1 - Daston, G A1 - Eletti, B A1 - Galli, A A1 - Huhtaniemi, I A1 - Laws, S A1 - Lazzari, G A1 - Liminga, U A1 - Smitz, J A1 - Spano, M A1 - Themmen, A A1 - Tilloy, A A1 - Waalkens-Behrends, I J1 - Altern Lab Anim Y1 - 2005/08// VL - 33 SN - 0261-1929 SP - 391 EP - 416 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16185108&query_hl=1 ER - TY - JFULL T1 - Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells. A1 - Igosheva, N A1 - Lorz, C A1 - O'Conner, E A1 - Glover, V A1 - Mehmet, H J1 - Neurochem Int Y1 - 2005/08// VL - 47 SN - 0197-0186 SP - 216 EP - 224 N2 - Isatin is an endogenous indole that is increased in stress, inhibits monoamine oxidase (MAO) B and improves bradykinesia and striatal dopamine levels in rat models of Parkinson's disease. Consequently, it has been suggested that isatin might be a possible treatment for Parkinson's disease although little is known about its effects on neural cell growth and survival. The aim of this study was to investigate the survival of dopaminergic human neuroblastoma (SH-SY5Y) cells following treatment with increasing concentrations of isatin. SH-SY5Y cells were exposed to isatin for defined time points, after which cell survival was determined by MTT assay. A combination of Annexin V binding and propidium iodide (PI) exclusion was used to distinguish apoptosis from necrosis in flow cytometry experiments and FACS profiles of permeabilised PI-labelled cells were employed for the assessment of cell cycle distribution. Isatin treatment (1-400 microM) for 24h induced a significant dose-dependent increase in MTT metabolism by SH-SY5Y cells in culture, but this was not due to an increase in cell division. At the higher concentrations (200-400 microm) isatin triggered cell death, although MTT metabolism was still increased in the culture, suggesting that surviving cells were hypermetabolic. Following a longer (48 h) exposure, isatin was found to cause cell death in a dose-dependent manner; at lower concentrations (50 microM), the predominant mode of cell death was apoptosis while at the highest concentration (400 microm) increasing numbers of necrotic cells were also evident. Thus, in dopaminergic SH-SY5Y cells isatin induces cell death in dose- and time-dependent manner. This death occurred as a continuum of survival, apoptosis and necrosis. Our results re-emphasise that caution should be exercised when considering high doses of isatin as a putative anti-Parkinson's disease therapeutic. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15876476&query_hl=1 ER - TY - JFULL T1 - Novel concepts of human chorionic gonadotropin: reproductive system interactions and potential in the management of infertility. A1 - Filicori, M A1 - Fazleabas, AT A1 - Huhtaniemi, I A1 - Licht, P A1 - Rao, ChV A1 - Tesarik, J A1 - Zygmunt, M J1 - Fertil Steril Y1 - 2005/08// VL - 84 SN - 1556-5653 SP - 275 EP - 284 N2 - OBJECTIVE: To extensively review the scientific literature on the potential sites of hCG action and the role of this hormone on reproductive processes not necessarily related to the classic hCG functions of supporting early pregnancy. DESIGN: Review of the international scientific literature and the authors' personal research experience in this area. RESULT(S): The LH/hCG receptor has an almost ubiquitous distribution in reproductive organs, thus suggesting that the actions of hCG might be more extensive than previously thought. Independently of FSH, low-dose hCG can support development and maturation of larger ovarian follicles that have acquired granulosa cells LH/hCG receptors, potentially providing effective and safer ovulation induction regimens. Human chorionic gonadotropin seems to be capable of improving uterine receptivity by enhancing endometrial quality and stromal fibroblast function. Furthermore, through its actions on insulin-like growth factor binding protein-1 and vascular endothelial growth factor, hCG might stimulate endometrial angiogenesis and growth and extend the implantation window, thus making pregnancy more likely. CONCLUSION(S): Mounting evidence indicates that hCG could be mediating relevant actions enhancing fertility and the efficacy of therapeutic procedures used in the management of infertility. Greater understanding of the physiologic roles that hCG plays in human reproduction might suggest novel clinical applications for this traditional hormone of pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16084861&query_hl=1 ER - TY - JFULL T1 - Discovery and characterization of new epididymis-specific beta-defensins in mice. A1 - Jalkanen, J A1 - Huhtaniemi, I A1 - Poutanen, M J1 - Biochim Biophys Acta Y1 - 2005/07/25/ VL - 1730 SN - 0006-3002 SP - 22 EP - 30 N2 - The male urogenital tract epithelium is exposed to several pathogens, but only a few are potent enough to cause infection in a healthy individual. The exact mechanisms that protect the male reproductive tract from ascending pathogenic micro-organisms are still poorly characterized. We recently reported a method to identify novel epididymis-specific genes by analyzing the expressed sequence tags (ESTs) present in the mouse epididymal cDNA library of the UniGene collection at National Center for Biotechnology Information (NCBI). In the present study, we discovered in silico two novel epididymal genes: the beta-defensins Defb41 and Defb42. The full-length cDNAs for the genes were acquired by the RT-PCR and 5'-RACE approaches and were subsequently sequenced. Q-RT-PCR and in situ hybridization revealed Defb41 and Defb42 to be expressed mainly in the proximal caput. The expression of both defensins was found to be regulated by androgens. Based on their structure and expression pattern, Defb41 and Defb42 are suggested to have a role in the antimicrobial protection of sperm and urogenital tract epithelia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16023745&query_hl=1 ER - TY - JFULL T1 - Increased latency of absent end-diastolic flow in the umbilical artery of monochorionic twin fetuses. A1 - Vanderheyden, TM A1 - Fichera, A A1 - Pasquini, L A1 - Tan, TY A1 - Wee, LY A1 - Frusca, T A1 - Fisk, NM J1 - Ultrasound Obstet Gynecol Y1 - 2005/07// VL - 26 SN - 0960-7692 SP - 44 EP - 49 N2 - OBJECTIVE: To determine if absent end-diastolic flow (AEDF) in the umbilical artery (UA) has a longer latency in monochorionic (MC) twin fetuses compared to singleton or dichorionic twin (DC) fetuses. METHODS: One hundred and eight pregnancies with a fetus with AEDF were reviewed: 47 MC and 17 DC twin pregnancies and 44 singletons. Because twin-twin transfusion syndrome (TTTS) is a potential confounder when determining latency, subgroup analysis was also performed on the 21 MC affected pregnancies without TTTS. Latency of AEDF (in days) was defined as the difference between the gestational age at diagnosis of AEDF and gestational age at delivery or intrauterine death. RESULTS: Latency was similar in MC twins (median, 39 days) and DC twins (30 days) but longer compared to singletons (11 days; P = 0.0001). After excluding pregnancies with TTTS, latency in non-TTTS MC twins (54 days) was longer than in both singletons and DC twins. This was due to an earlier gestational age at AEDF in non-TTTS MC twins of 20 weeks compared to 27 weeks in both singleton and DC twins because median gestational age at delivery was similar in MC twins, DC twins and singletons. CONCLUSIONS: The latency period of UA AEDF is longer in MC twins than in singletons. Our data suggest that in MC twin fetuses without TTTS, AEDF begins earlier and lasts about twice as long as in DC twin fetuses, which is consistent with placental insufficiency not being the sole factor mediating abnormal UA waveforms in MC placentation. This observation is important in counseling and managing twin pregnancies discordant for AEDF. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15971285&query_hl=1 ER - TY - JFULL T1 - Disentangling fetal and maternal susceptibility for pre-eclampsia: a British multicenter candidate-gene study. A1 - GOPEC Consortium J1 - Am J Hum Genet Y1 - 2005/07// VL - 77 SN - 0002-9297 SP - 127 EP - 131 N2 - The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNFalpha. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70-1.16; GRRs associated with fetal genotypes had a range of 0.72-1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of false-positive results is to be avoided. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15889386&query_hl=1 ER - TY - JFULL T1 - Standardization of power Doppler quantification of blood flow in the human fetus using the aorta and inferior vena cava. A1 - Welsh, AW A1 - Rubin, JM A1 - Fowlkes, JB A1 - Fisk, NM J1 - Ultrasound Obstet Gynecol Y1 - 2005/07// VL - 26 SN - 0960-7692 SP - 33 EP - 43 N2 - OBJECTIVE: This study aimed to test the applicability to the fetus of mathematical techniques developed to standardize power Doppler indices of adult regional perfusion. METHOD: Fetal power Doppler imaging was performed on 14 fetuses (25-37 weeks' gestation) using a standardized parasagittal plane, examining renal and aortic blood flow, and additionally inferior vena caval (IVC) flow in one fetus. Images were stored and transferred for off-line computer analysis using purpose-designed software. We first tested the need for techniques to remove the effects of red blood cell clumping on power Doppler amplitude, then performed further analyses to: (1) investigate cardiac cycle effects on aortic amplitude; (2) determine the spatial consistency of, and influence of angle of insonation on, maximal pixel value; (3) quantify temporal consistency; and (4) compare peak pixel values in the fetal aorta and IVC. RESULTS: No rouleaux effect on the vascular profile was detectable, in contrast to that identified in the adult. Within each fetus a consistent value was seen in the center of the aorta corresponding to 100% vascular amplitude, which was unaltered by the phase of the cardiac cycle, with a coefficient of variation of 28.9% at 89 degrees and 6.5% at 73 degrees . This value was constant in the aorta and IVC. CONCLUSION: Fetal blood does not appear to form rouleaux to any significant degree, so there is no artificially elevated maximal value for power Doppler amplitude as seen in the adult. We propose that the value representing 100% amplitude may be consistently measured in the center of large fetal vessels such as the aorta, allowing the direct measurement of fractional moving blood volumes in the human fetus. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15971284&query_hl=1 ER - TY - JFULL T1 - Circulating first trimester human fetal mesenchymal stem cells; Biology and potential clinical application A1 - Fisk, NM J1 - EXP HEMATOL Y1 - 2005/07// VL - 33 SN - 0301-472X SP - 39 EP - 39 ER - TY - JFULL T1 - Fertility in luteinizing hormone receptor-knockout mice after wild-type ovary transplantation demonstrates redundancy of extragonadal luteinizing hormone action. A1 - Pakarainen, T A1 - Zhang, FP A1 - Poutanen, M A1 - Huhtaniemi, I J1 - J Clin Invest Y1 - 2005/07// VL - 115 SN - 0021-9738 SP - 1862 EP - 1868 N2 - The luteinizing hormone receptor (LHR), mainly expressed in gonads, is essential for normal reproduction. However, numerous recent studies have also demonstrated LHR expression in multiple extragonadal reproductive and nonreproductive tissues. Although some effects of luteinizing hormone (LH) or its agonist, human chorionic gonadotropin, have been shown in extragonadal sites, their physiological significance remains open. In the present study, we have addressed the function of the extragonadal LHR using LHR-KO mice (LuRKO mice), in which the ovaries of prepubertal mice were orthotopically replaced with pieces of WT ovary using similarly transplanted WT mice as controls. Most ovarian transplants attained normal endocrine function in both groups of mice, as demonstrated by normal age at vaginal opening, estrous cycles, and sexual behavior. Both the LuRKO and WT mice repeatedly became pregnant (9/16 vs. 16/20 after first mating; difference not significant) and delivered similarly sized litters, which grew normally after birth, indicating normal lactation. In conclusion, fertility is restored in LuRKO mice by transplantation of WT ovarian tissue. This is achieved in the absence of extragonadal LHR expression, which indicates physiological redundancy for such receptor sites. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15951841&query_hl=1 ER - TY - JFULL T1 - Stress responses at birth: determinants of cord arterial cortisol and links with cortisol response in infancy. A1 - Miller, NM A1 - Fisk, NM A1 - Modi, N A1 - Glover, V J1 - BJOG Y1 - 2005/07// VL - 112 SN - 1470-0328 SP - 921 EP - 926 N2 - OBJECTIVE: To investigate (A) the determinants of infant stress response at delivery and (B) test the hypothesis that stress at birth, as reflected by cord arterial cortisol, influences cortisol response to vaccination at two months. DESIGN: Prospective observational study. SETTING: Tertiary referral maternity hospital. POPULATION: One hundred and seventy-two primiparous women with uncomplicated singleton pregnancies. METHODS: Women were recruited antenatally. At birth, cord arterial blood and obstetric data were collected. Saliva was collected from infants immediately before and after vaccination at two months. Cortisol was analysed from cord blood and saliva by radio-immunoassay. MAIN OUTCOME MEASURES: Stress response at birth, as demonstrated by cord arterial cortisol; association with saliva cortisol response to vaccination at two months. RESULTS: Cord arterial cortisol varied with mode of delivery, combined spinal/epidural use and pH. Salivary cortisol response at two months correlated with cord arterial cortisol (r= 0.24, P < 0.05). Infants with the highest and lowest cord arterial cortisol had markedly different cortisol responses at two months (P= 0.017). These groups had different modes of delivery with caesarean rates of <8% in the high cortisol response group and 83% in the low cortisol response group (P < 0.0001). CONCLUSION: Babies born vaginally mount greater cortisol responses at birth than those delivered by caesarean section. Stress at delivery may influence the infant HPA axis response for up to two months. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15957993&query_hl=1 ER - TY - JFULL T1 - Inhibition of Stat3 activation in the endometrium prevents implantation: a nonsteroidal approach to contraception. A1 - Catalano, RD A1 - Johnson, MH A1 - Campbell, EA A1 - Charnock-Jones, DS A1 - Smith, SK A1 - Sharkey, AM J1 - Proc Natl Acad Sci U S A Y1 - 2005/06/14/ VL - 102 SN - 0027-8424 SP - 8585 EP - 8590 N2 - Activation of the receptors for leukemia inhibitory factor (LIF) and IL-11 is essential for embryo attachment and decidualization in mice. Both receptors induce activation of the Stat family of signal transducers via the Jak/Stat pathway. Here, we aimed to establish whether activation of Stat3 in maternal endometrium is essential for successful implantation. Functional blockade of Stat3 before implantation, by injection into the uterine lumen of a cell-permeable Stat3 peptide inhibitor, reduced embryo implantation specifically by 70% (P < 0.001). Stat3 is phosphorylated in the luminal epithelium (LE) in response to LIF, and this phosphorylation was significantly reduced both in vitro and in vivo by the Stat3 inhibitor. The inhibitor also blocked induction by LIF of several LIF-regulated genes in the LE including Irg1, which has been shown previously to be essential for implantation. Successful implantation is therefore dependent on phosphorylation and activation of Stat3 in the endometrium before implantation. This finding provides a target for contraceptive development, based on selective blockade of signal transduction pathways essential for implantation. This study demonstrates that cell-permeable peptide inhibitors can be used effectively to target intracellular signaling pathways in the uterine LE. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15937114&query_hl=1 ER - TY - JFULL T1 - Targeted ablation of prostate carcinoma cells through LH receptor using Hecate-CGbeta conjugate: functional characteristic and molecular mechanism of cell death pathway. A1 - Bodek, G A1 - Kowalczyk, A A1 - Waclawik, A A1 - Huhtaniemi, I A1 - Ziecik, AJ J1 - Exp Biol Med (Maywood) Y1 - 2005/06// VL - 230 SN - 1535-3702 SP - 421 EP - 428 N2 - A Hecate-CGbeta conjugate (lytic peptide and beta-chorionic gonadotropin) selectively destroyed cells possessing LH receptors. This study described functional characteristics of the conjugate and the molecular mechanism of the cell death pathway in prostate cancer cells. Based on in vitro studies, we conclude that the conjugate kills cells possessing luteinizing hormone receptors (LHR) faster than Hecate alone. Competitive studies have shown that blocking of LHR by preincubation with chorionic gonadotropin (100 ng/ml) reduced toxicity of the conjugate in low concentrations. Further studies have also shown that the conjugate in treated cells both did not induce internucleosomal DNA fragmentation and did not induce morphological changes in cells characterized as having apoptotic features. These results proved that cells died by necrosis rather than apoptosis after the conjugate treatment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15956772&query_hl=1 ER - TY - JFULL T1 - High risk of unexpected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study. A1 - Barigye, O A1 - Pasquini, L A1 - Galea, P A1 - Chambers, H A1 - Chappell, L A1 - Fisk, NM J1 - PLoS Med Y1 - 2005/06// VL - 2 SN - 1549-1676 SP - e172 EP - e172 N2 - BACKGROUND: The rationale for fetal surveillance in monochorionic twin pregnancies is timely intervention to prevent the increased fetal/perinatal morbidity and mortality attributed to twin-twin transfusion syndrome and intrauterine growth restriction. We investigated the residual risk of fetal death after viability in otherwise uncomplicated monochorionic diamniotic twin pregnancies. METHODS AND FINDINGS: We searched an electronic database of 480 completed monochorionic pregnancies that underwent fortnightly ultrasound surveillance in our tertiary referral fetal medicine service between 1992 and 2004. After excluding pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence, and monoamniotic and high-order multiple pregnancies, we identified 151 uncomplicated monochorionic diamniotic twin pregnancies with normal growth, normal liquor volume, and normal Doppler studies on fortnightly ultrasound scans. Ten unexpected intrauterine deaths occurred in seven (4.6%) of 151 previously uncomplicated monochorionic diamniotic pregnancies, within 2 wk of a normal scan, at a median gestational age of 34(+1) wk (weeks(+days); range 28(+0) to 36(+3)). Two of the five cases that underwent autopsy had features suggestive of acute late onset twin-twin transfusion syndrome, but no antenatal indicators of transfusional imbalance or growth restriction, either empirically or in a 1:3 gestation-matched case-control comparison. The prospective risk of unexpected antepartum stillbirth after 32 wk was 1/23 monochorionic diamniotic pregnancies (95% confidence interval 1/11 to 1/63). CONCLUSION: Despite intensive fetal surveillance, structurally normal monochorionic diamniotic twin pregnancies without TTTS or IUGR are complicated by a high rate of unexpected intrauterine death. This prospective risk of fetal death in otherwise uncomplicated monochorionic diamniotic pregnancies after 32 wk of gestation might be obviated by a policy of elective preterm delivery, which now warrants evaluation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15971947&query_hl=1 ER - TY - JFULL T1 - The mitogen-activated protein kinase dependent expression of prostaglandin H synthase-2 and interleukin-8 messenger ribonucleic acid by myometrial cells: the differential effect of stretch and interleukin-1{beta}. A1 - Sooranna, SR A1 - Engineer, N A1 - Loudon, JA A1 - Terzidou, V A1 - Bennett, PR A1 - Johnson, MR J1 - J Clin Endocrinol Metab Y1 - 2005/06// VL - 90 SN - 0021-972X SP - 3517 EP - 3527 N2 - Infection and uterine stretch are the common causes of preterm labor. IL-1beta plays a key role in infection-induced preterm labor and increases prostaglandin H synthase 2 (PGHS-2) and IL-8 expression. We have shown that mechanical stretch of uterine myocytes in vitro up-regulates the expression of PGHS-2 and IL-8. In this study, we tested the hypotheses that both IL-1beta and mechanical stretch increase the myometrial expression of PGHS-2 and IL-8 via MAPK activation and that their effects are synergistic. MAPK activation was assessed in myocytes obtained from pregnant women undergoing cesarean section before the onset of labor after exposure to IL-1beta and stretch either alone or in combination. Specific inhibitors of ERK, p38, and c-Jun N-terminal kinase were used to define the role of each in the increased expression of PGHS-2 and IL-8 mRNA. We found that both IL-1beta and stretch activated all three MAPK subtypes but that they had no synergistic effect. The inhibitor studies showed that stretch-induced increases in both PGHS-2 and IL-8 mRNA expression were ERK1/2 and p38 dependent and that IL-1beta-induced increases of PGHS-2 mRNA expression were also ERK1/2 and p38 dependent, but those of IL-8 were dependent only on ERK1/2 activation. These data show that exposure of human uterine myocytes to both stretch and IL-1beta activates the MAPK system, which is responsible for the increase in PGHS-2 and IL-8 mRNA expression. We found no evidence of a synergistic effect of IL-1beta and stretch on myometrial expression of PGHS-2 and IL-8 mRNA. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15784717&query_hl=1 ER - TY - JFULL T1 - ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy. A1 - Müllenbach, R A1 - Bennett, A A1 - Tetlow, N A1 - Patel, N A1 - Hamilton, G A1 - Cheng, F A1 - Chambers, J A1 - Howard, R A1 - Taylor-Robinson, SD A1 - Williamson, C J1 - Gut Y1 - 2005/06// VL - 54 SN - 0017-5749 SP - 829 EP - 834 N2 - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). AIMS: To establish whether mutations in ATP8B1 are associated with ICP in British cases PATIENTS: Sixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. METHODS: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P magnetic resonance spectroscopy (MRS) RESULTS: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls. CONCLUSIONS: We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15888793&query_hl=1 ER - TY - JFULL T1 - The utility of TIPS in the management of Budd-Chiari syndrome. A1 - Molmenti, EP A1 - Segev, DL A1 - Arepally, A A1 - Hong, J A1 - Thuluvath, PJ A1 - Rai, R A1 - Klein, AS J1 - Ann Surg Y1 - 2005/06// VL - 241 SN - 0003-4932 N2 - BACKGROUND AND AIM: Budd-Chiari syndrome (BCS) is a rare condition associated with hepatic venous outflow obstruction classically treated with portosystemic shunts or liver transplantation. Recent reports indicate promising results with the use of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of these patients. PATIENTS AND METHODS: We reviewed a 10-year single-institution experience with TIPS in patients diagnosed with BCS. RESULTS: Eleven patients with BCS underwent TIPS procedures, 3 of whom carried a diagnosis of paroxysmal nocturnal hemoglobinuria, a relative contraindication for liver transplantation. One TIPS procedure was unsuccessful for technical reasons. No patient suffered mortality or major morbidity related to the TIPS procedure. The mean reduction of portal venous pressures was 43.7%, with a mean decrease of 73% in the pressure gradient. Of the 7 patients where long-term follow-up was available, 57% had shunts which remained patent but required several nonsurgical revisions for occlusion, with an average assisted patency of 37.5 months. CONCLUSIONS: TIPS is an effective modality in the treatment of patients with BCS, especially for those who are not candidates for liver transplantation. TIPS can be successfully used as a bridge to surgical portosystemic shunting, as well as liver transplantation, but may cause technical difficulties when performing transplantation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15912047&query_hl=1 ER - TY - JFULL T1 - TOCOX--a randomised, double-blind, placebo-controlled trial of rofecoxib (a COX-2-specific prostaglandin inhibitor) for the prevention of preterm delivery in women at high risk. A1 - Groom, KM A1 - Shennan, AH A1 - Jones, BA A1 - Seed, P A1 - Bennett, PR J1 - BJOG Y1 - 2005/06// VL - 112 SN - 1470-0328 SP - 725 EP - 730 N2 - OBJECTIVE: To assess the safety and efficacy of the long term prophylactic use of rofecoxib (a COX-2-specific inhibitor) in women at high risk of preterm delivery. DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Queen Charlotte's and Chelsea Hospital, London and Guys and St Thomas' Hospitals, London. POPULATION: Ninety-eight singleton pregnancies at high risk of preterm labour. METHODS: Treatment from 16 to 32 weeks. Weekly ultrasound surveillance. MAIN OUTCOME MEASURES: Fetal renal function and ductus arteriosus blood flow changes. Preterm delivery rates and neonatal outcome. RESULTS: Rofecoxib caused a reduction in hourly fetal urine production rates (-34%, 95% CI -13 to -50%, P = 0.004) and amniotic fluid index (-2.2, 95% CI -3.2 to -1.2, P < 0.001). This effect did not increase with time on treatment and reversed in all cases on discontinuation of treatment. Rofecoxib had an effect on the ductus arteriosus, increasing maximum systolic velocity (0.1 m/s, 95% CI 0.03-0.16, P = 0.02) and minimum diastolic velocity (0.007 m/s, 95% CI 0.0007-0.013, P= 0.03). This effect increased with time on treatment but was reversed with discontinuation of treatment and had no long term clinical sequelae. There was no difference in preterm delivery rates <30 weeks (28% on placebo vs 33% on rofecoxib, Mantel-Haensel [M-H]-adjusted risk 1.11, 95% CI 0.67-1.87). There were more deliveries <37 weeks in those on rofecoxib (40%vs 67%, M-H-adjusted risk 1.59, 95% CI 1.09-2.32). Rates of preterm prelabour rupture of membranes (PPROM) were higher in those on rofecoxib (RR 2.5, 95% CI 1.3-4.7). CONCLUSION: Rofecoxib has a significant but reversible effect on fetal renal function and the ductus arteriosus. It does not reduce the incidence of early preterm delivery <30 weeks and is associated with an increased risk of delivery before 37 weeks in women at high risk. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15924527&query_hl=1 ER - TY - JFULL T1 - 15-Deoxy-{delta}12,14-prostaglandin j2 inhibits interleukin-1{beta}-induced nuclear factor-{kappa}b in human amnion and myometrial cells: mechanisms and implications. A1 - Lindström, TM A1 - Bennett, PR J1 - J Clin Endocrinol Metab Y1 - 2005/06// VL - 90 SN - 0021-972X SP - 3534 EP - 3543 N2 - Proinflammatory cytokines and prostaglandins play key roles in term and preterm human labor. The expression of the prostaglandin synthetic enzyme cyclooxygenase (COX)-2 and cytokines IL-1beta and IL-8 increases within the uterus at the time of labor, and each is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB). In addition to its role in driving inflammation, COX-2 may also synthesize 15-deoxy-Delta (12, 14)-prostaglandin J(2) (15d-PGJ(2)), an antiinflammatory cyclopentenone prostaglandin (cyPG), which acts in some cells as an agonist of peroxisome proliferator-activated receptors (PPARs). We found that PPARalpha and -gamma proteins are expressed in both amnion epithelial and myometrial cells, but synthetic PPAR agonists could not inhibit NF-kappaB activity or COX-2 expression. 15d-PGJ(2) inhibited NF-kappaB activity and COX-2 expression in both cell types. This was unaffected by a PPAR antagonist and could be mimicked by the cyPG PGA(1) but not 9,10-dihydro-15d-PGJ(2) in which the cyclopentenone ring is disrupted. This shows that, in amnion and myometrium, inhibition of NF-kappaB activity and COX-2 expression by 15d-PGJ(2) is independent of PPARs and requires the cyclopentenone ring. We further show that 15d-PGJ(2) acts at multiple levels in the NF-kappaB pathway: blocking inhibitor of kappaBalpha degradation by repressing inhibitor of kappaB kinase activation and the 26S proteasome and also repressing NF-kappaB DNA binding and phosphorylation. Our data suggest that PPARs are unlikely to play a role in the regulation of either NF-kappaB or COX-2 in human amnion and myometrium. Targeting of NF-kappaB is a potential therapeutic strategy in preterm labor. PPAR agonists are unlikely to be effective in this context, but cyPGs may have potential. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15755849&query_hl=1 ER - TY - JFULL T1 - Endometrial dating--still room for controversy. A1 - Koninckx, P A1 - Brosens, JJ A1 - Brosens, I J1 - Fertil Steril Y1 - 2005/06// VL - 83 SN - 1556-5653 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15950681&query_hl=1 ER - TY - JFULL T1 - Increased carotid atherosclerosis in andropausal middle-aged men. A1 - Mäkinen, J A1 - Järvisalo, MJ A1 - Pöllänen, P A1 - Perheentupa, A A1 - Irjala, K A1 - Koskenvuo, M A1 - Mäkinen, J A1 - Huhtaniemi, I A1 - Raitakari, OT J1 - J Am Coll Cardiol Y1 - 2005/05/17/ VL - 45 SN - 0735-1097 SP - 1603 EP - 1608 N2 - OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. METHODS: We studied 239 40- to 70-year-old men (mean +/- SD: 57 +/- 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 +/- 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 +/- 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E2), LH, and sex hormone-binding globulin were measured using standard immunoassays. RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 +/- 0.34 vs. 1.00 +/- 0.23, p < 0.05) and in the carotid bulb (1.44 +/- 0.48 vs. 1.27 +/- 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking. CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15893174&query_hl=1 ER - TY - JFULL T1 - Natriuretic peptide interaction with [H-3]isatin binding sites in rat brain A1 - Medvedev, A A1 - Crumeyrolle-Arias, M A1 - Cardona, A A1 - Sandler, M A1 - Glover, V J1 - BRAIN RES Y1 - 2005/05/03/ VL - 1042 SN - 0006-8993 SP - 119 EP - 124 N2 - Isatin is an endogenous indole, which has a distinct and discontinuous distribution in the brain and exhibits a wide range of physiological and pharmacological effects.In the present study, we have demonstrated that atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) inhibited [H-3]isatin binding to rat brain sections and isolated membrane fractions. Isatin itself antagonised not only natriuretic peptide receptor type A (NPR-A) (ANP-stimulation, of guanylyl cyclase) but also NPR-C (ANP and CNP mediated inhibition of adenylyl cyclase) signalling. These results suggest that some [H-3]isatin binding in the brain may be to NPR-A and NPR-C. Competitive interactions between isatin and natriuretic peptides and their receptors give a possible explanation of the known anxiogenic effect of low doses of isatin, interacting at NPR-A, and the sedative effects of higher doses, antagonising respectively the anxiolytic effect of ANP and the anxiogenic effect of CNP. © 2005 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - Bone involvement in sickle cell disease. A1 - Almeida, A A1 - Roberts, I J1 - Br J Haematol Y1 - 2005/05// VL - 129 SN - 0007-1048 SP - 482 EP - 490 N2 - Bone involvement is the commonest clinical manifestation of sickle cell disease both in the acute setting such as painful vaso-occlusive crises, and as a source of chronic, progressive disability such as avascular necrosis. Management of these problems is often difficult because of the diagnostic imprecision of most laboratory and imaging investigations and because of the lack of evidence for most surgical procedures in sickle cell disease. This review first discusses the acute problems related to bone involvement in sickle cell disease, with particular reference to differentiating infection from infarction, and then describes the long-term effects of sickle cell disease on bone mineral density, growth, and chronic bone and joint damage. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15877730&query_hl=1 ER - TY - JFULL T1 - Mouse cysteine-rich secretory protein 4 (CRISP4): a member of the Crisp family exclusively expressed in the epididymis in an androgen-dependent manner. A1 - Jalkanen, J A1 - Huhtaniemi, I A1 - Poutanen, M J1 - Biol Reprod Y1 - 2005/05// VL - 72 SN - 0006-3363 SP - 1268 EP - 1274 N2 - The final maturation of spermatozoa produced in the testis takes place during their passage through the epididymis. In this process, the proteins secreted into the epididymal lumen along with changes in the pH and salt composition of the epididymal fluid cause several biochemical changes and remodeling of the sperm plasma membrane. The Crisp family is a group of cysteine-rich secretory proteins that previously consisted of three members, one of which-CRISP1-is an epididymal protein shown to attach to the sperm surface in the epididymal lumen and to inhibit gamete membrane fusion. In the present paper, we introduce a new member of the Crisp protein family, CRISP4. The new gene was discovered through in silico analysis of the epididymal expressed sequence tag library deposited in the UniGene database. The peptide sequence of CRISP4 has a signal sequence suggesting that it is secreted into the epididymal lumen and might thus interact with sperm. Unlike the other members of the family, Crisp4 is located on chromosome 1 in a cluster of genes encoding for cysteine-rich proteins. Crisp4 is expressed in the mouse exclusively in epithelial cells of the epididymis in an androgen-dependent manner, and the expression of the gene starts at puberty along with the onset of sperm maturation. The identified murine CRISP4 peptide has high homology with human CRISP1, and the homology is higher than that between murine and human CRISP1, suggesting that CRISP4 represents the mouse counterpart of human CRISP1 and could have similar effects on sperm membrane as mouse and human CRISP1. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15673606&query_hl=1 ER - TY - JFULL T1 - Natural killer cells and reproductive failure--theory, practice and prejudice. A1 - Rai, R A1 - Sacks, G A1 - Trew, G J1 - Hum Reprod Y1 - 2005/05// VL - 20 SN - 0268-1161 SP - 1123 EP - 1126 N2 - The relationship between peripheral blood natural killer (NK) cells and reproductive failure is one of the most controversial areas in reproductive medicine. Amidst much publicity, peripheral blood NK cell testing is being promoted as a useful diagnostic test to guide the initiation of a variety of immunosuppressive therapies amongst patients with either recurrent miscarriage or infertility. We contend (i) that at present there is no scientific basis for the introduction of NK cell testing into routine clinical practice, and (ii) that the use of immunosuppressant agents based on the results of such testing may potentially be harmful. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15760961&query_hl=1 ER - TY - JFULL T1 - Age-related androgen receptor polymorphisms and responsiveness - Response to the letter-to-editor of R.D. Dickerman et al. A1 - Jiang, M A1 - Huhtaniemi, I J1 - EXP GERONTOL Y1 - 2005/05// VL - 40 SN - 0531-5565 SP - 361 EP - 362 ER - TY - JFULL T1 - A novel targeted therapy of Leydig and granulosa cell tumors through the luteinizing hormone receptor using a hecate-chorionic gonadotropin beta conjugate in transgenic mice. A1 - Bodek, G A1 - Vierre, S A1 - Rivero-Müller, A A1 - Huhtaniemi, I A1 - Ziecik, AJ A1 - Rahman, NA J1 - Neoplasia Y1 - 2005/05// VL - 7 SN - 1522-8002 SP - 497 EP - 508 N2 - We investigated the antitumoral efficacy, endocrine consequences, and molecular mechanisms underlying cell death induced by the Hecate-chorionic gonadotropin (CG)beta conjugate, a fusion protein of a 23-amino acid lytic peptide Hecate with a 15-amino acid (81-95) fragment of the human CGbeta chain. Transgenic (TG) mice expressing the inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T-antigen (Tag) transgene, developing luteinizing hormone (LH) receptor (R) expressing Leydig and granulosa cell tumors, and wild-type control littermates were treated either with vehicle, Hecate, or Hecate-CGbeta conjugate for 3 weeks. Hecate-CGbeta conjugate treatment reduced the testicular and ovarian tumor burden (P < .05), whereas a concomitant increase (testis; P < .05) or no change (ovary) in tumor volumes occured with Hectate treatment. A drop in serum progesterone, produced by the tumors, and an increase in LH levels occured in Hecate-CGbeta treated mice, in comparison with vehicle and Hecate groups, providing further support for the positive treatment response. Hecate-CGbeta conjugate induced a rapid and cell-specific membrane permeabilization of LHR-expressing cells in vitro, suggesting a necrotic mode of cell death without activation of apoptosis. These results prove the principle that the Hecate-CGbeta conjugate provides a novel specific lead into gonadal somatic cell cancer therapy by targeted destruction of LHR-expressing tumor cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15967102&query_hl=1 ER - TY - JFULL T1 - A new Mother-to-Infant Bonding Scale: links with early maternal mood A1 - Taylor, A A1 - Atkins, R A1 - Kumar, R A1 - Adams, D A1 - Glover, V J1 - ARCH WOMEN MENT HLTH Y1 - 2005/05// VL - 8 SP - 45 EP - 51 N2 - Some mothers find it hard to relate to their new baby, and such failure may have long-term effects on the infant. This has been a neglected area of research. A new simple 8 item self-rating mother-to-infant bonding questionnaire has been designed to assess the feelings of a mother towards her new baby. A principal components and reliability analysis demonstrated in alpha score of 0.71. One hundred and sixty two women filled in the Kennerley Blues Scale, the Edinburgh postnatal Depression Scale (EPDS) the Highs Scale and the new Mother to Infant Bonding Scale on day 3 postpartum. Twelve weeks later they were sent the EPDS and the Bonding scales again. One hundred and forty four returned all questionnaires. There was a strong correlation between the Bonding scores at 3 days and at 12 weeks (r(s)=0.54 p < 0.001). Multiple regression analysis showed that those with raised Blues scores had worse, and those with raised Highs scores had better bonding at 3 days. Those with raised EPDS scores at 3 days (13 and over) had worse bonding scores in the "first few weeks" (median 4 versus 1, p=0.028), as recalled at 12 weeks. This simple questionnaire is acceptable for use with mothers and gives significant correlations with their early mood. ER - TY - JFULL T1 - Multiple sites of tumorigenesis in transgenic mice overproducing hCG. A1 - Huhtaniemi, I A1 - Rulli, S A1 - Ahtiainen, P A1 - Poutanen, M J1 - Mol Cell Endocrinol Y1 - 2005/04/29/ VL - 234 SN - 0303-7207 SP - 117 EP - 126 N2 - We have produced transgenic (TG) mice expressing under the ubiquitin C promoter either the glycoprotein hormone common alpha-subunit (C(alpha)) or human chorionic gonadotropin (hCG) beta-subunit. C(alpha) overexpression alone had no phenotypic effect, but the hCG(beta) expressing females, presenting with moderately elevated levels of bioactive LH/hCG, due to dimerization of the TG hCG(beta) with endogenous C(alpha), developed multiple gonadal and extragonadal neoplasias. Crosses of the C(alpha) and hCG(beta) mice (hCG(alpha)beta) had >1000-fold elevated hCG levels, due to ubiquitous transgene expression, and presented with more aggressive tumour formation. The ovaries displayed initially strong luteinisation of all somatic cell types, leading to formation of luteomas, and subsequently to germ cell tumours (teratomas). The pituitary glands of TG females were massively enlarged, up to >100 mg, developing macroprolactinomas with very high prolactin (PRL) production. This endocrine response probably induced breast cancers in the mice. In contrast to the females, similar high levels of hCG in male mice had only marginal effects in adulthood, with slight Leydig cell hyperplasia and atrophy in the seminiferous epithelium. However, clear Leydig cell adenomas were observed in postnatal mice, apparently originating from fetal Leydig cells. In conclusion, these studies demonstrate marked tumorigenic effects of supraphysiological hCG levels in female mice, but clear resistance to similar changes in males. The extragonadal tumours were induced by hCG stimulated aberrant ovarian endocrine function, rather than by direct hCG action, because gonadectomy prevented all extragonadal phenotypes despite persistent hCG elevation. The phenotypes of the TG mice apparently represent exaggerated responses to hCG/LH and/or gonadal steroids. It remains to be explored to what extent they simulate respective responses in humans to pathophysiological elevation of the same hormones. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15836960&query_hl=1 ER - TY - JFULL T1 - Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. A1 - Van den Bergh, BR A1 - Mulder, EJ A1 - Mennes, M A1 - Glover, V J1 - Neurosci Biobehav Rev Y1 - 2005/04// VL - 29 SN - 0149-7634 SP - 237 EP - 258 N2 - A direct link between antenatal maternal mood and fetal behaviour, as observed by ultrasound from 27 to 28 weeks of gestation onwards, is well established. Moreover, 14 independent prospective studies have shown a link between antenatal maternal anxiety/stress and cognitive, behavioural, and emotional problems in the child. This link generally persisted after controlling for post-natal maternal mood and other relevant confounders in the pre- and post-natal periods. Although some inconsistencies remain, the results in general support a fetal programming hypothesis. Several gestational ages have been reported to be vulnerable to the long-term effects of antenatal anxiety/stress and different mechanisms are likely to operate at different stages. Possible underlying mechanisms are just starting to be explored. Cortisol appears to cross the placenta and thus may affect the fetus and disturb ongoing developmental processes. The development of the HPA-axis, limbic system, and the prefrontal cortex are likely to be affected by antenatal maternal stress and anxiety. The magnitude of the long-term effects of antenatal maternal anxiety/stress on the child is substantial. Programs to reduce maternal stress in pregnancy are therefore warranted. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15811496&query_hl=1 ER - TY - JFULL T1 - Mutations in human gonadotropin and gonadotropin-receptor genes. A1 - Huhtaniemi, IT A1 - Themmen, AP J1 - Endocrine Y1 - 2005/04// VL - 26 SN - 0969-711X SP - 207 EP - 217 N2 - This short review provides an update on the new information that has become available in the recent years about mutations and polymorphisms in the genes for gonadotropins and their receptors. Combining the types and locations of the mutations, their phenotypic effects, and the recently emerged information about the crystal structure of these molecules is providing us with increasingly detailed picture about the structure-function relationships of gonadotropin action. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16034174&query_hl=1 ER - TY - JFULL T1 - Role of genetic predisposition in multiple primary neoplasia - a study in Indian population A1 - Kotnis, A A1 - Rai, R A1 - Sarin, R A1 - Mulherkar, R J1 - ORAL ONCOL Y1 - 2005/04// VL - 1 SN - 1368-8375 SP - 103 EP - 103 ER - TY - JFULL T1 - Intraovarian actions of anti-angiogenic agents disrupt periovulatory events during the menstrual cycle in monkeys A1 - Xu, FH A1 - Hazzard, TM A1 - Evans, A A1 - Charnock-Jones, S A1 - Smith, S A1 - Stouffer, RL J1 - CONTRACEPTION Y1 - 2005/04// VL - 71 SN - 0010-7824 SP - 239 EP - 248 N2 - To determine if anti-angiogenic agents disrupt primate ovarian function, vehicle or a general angiostatic compound (TNP-470), specific antagonists of vascular endothelial growth factor (soluble VEGF receptor-1, sVEGFR-1; anti-VEGF monoclonal antibody, VEGF Ab) and/or an angiopoietin antagonist (Ang-2) were administered to rhesus monkeys: (1) locally via injection into the preovulatory follicle at midcycle or the developing corpus luteum at the midluteal phase; or (2) systemically via subcutaneous injection in the early follicular phase or at midcycle during the natural menstrual cycle. Compared to controls, intrafollicular injection of TNP-470 or sVEGFR-1 decreased circulating progesterone (P) levels in the subsequent luteal phase. Treatment with sVEGFR-1, but not TNP-470, also decreased the incidence of ovulation. Intrafollicular injection of Ang-2 also prevented ovulation, as well as any functional luteal phase. In the absence of elevated P, serum estradiol levels rose to peak levels 11-12 days post-Ang-2 treatment, at which time another large antral follicle was observed on the contralateral (noninjected) ovary. Intraluteal and systemic injection of VEGF antagonists alone or with Ang-2 had minimal effects. Thus, antiangiogenic factors can act locally in the primate follicle to disrupt the gametogenic (oocyte release) and endocrine (steroid) functions of the ovary. However, further studies are needed to optimize delivery of angiogenic agents before they can be meaningfully evaluated as possible contraceptive agents. (c) 2005 Elsevier Inc. All rights reserved. ER - TY - JFULL T1 - Role of the RIP140 corepressor in ovulation and adipose biology. A1 - Steel, JH A1 - White, R A1 - Parker, MG J1 - J Endocrinol Y1 - 2005/04// VL - 185 SN - 0022-0795 SP - 1 EP - 9 N2 - RIP140 is a ligand-dependent corepressor for most, if not all, nuclear receptors. It is expressed widely in many different tissues, but the phenotype of mice devoid of RIP140 indicates that it plays a crucial role in the ovary and in adipose biology. Ovarian expression of RIP140 is cell-type-specific during follicular development and it is essential for oocyte release during ovulation, but not for luteinization of mature ovarian follicles. In adipose tissue, RIP140 is essential for normal fat accumulation and RIP140-null mice show decreased lipid storage even on a high-fat diet, with upregulation of mitochondrial uncoupling protein (UCP1) in some fat depots. Thus RIP140 plays a crucial role in female fertility and in energy homeostasis, and could be a target for infertility treatment, new contraceptive strategies or prevention of obesity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15817822&query_hl=1 ER - TY - JFULL T1 - Novel antiangiogenic agents for use in contraception. A1 - Sharkey, AM A1 - Catalano, R A1 - Evans, A A1 - Charnock-Jones, DS A1 - Smith, SK J1 - Contraception Y1 - 2005/04// VL - 71 SN - 0010-7824 SP - 263 EP - 271 N2 - Angiogenesis and vascular development are fundamental to the development of a receptive endometrium that permits implantation. The underlying hypothesis of this project is that implantation in primates and in humans is dependent on vascular remodeling in the endometrium and that the identification of agents that can disrupt this process prior to embryo attachment will lead to the development of new post coital contraceptives. To identify suitable targets for postcoital contraception, we studied the expression in endometrium of the vascular endothelial growth factor (VEGF) and angiopoietin families of angiogenic regulators. We produced a neutralizing antibody to VEGF-A, and this was shown to inhibit implantation in rhesus monkeys, apparently through direct antagonism of the action of VEGF-A in the endometrium. This demonstrated 'proof of principle' that agents antagonizing molecules that regulate angiogenesis can be developed as contraceptive agents. A second objective was to identify new contraceptive targets. We have developed microarrays to compare receptive endometrium with endometrium-rendered nonreceptive by a number of experimental strategies. We have identified over 100 RNA transcripts that are acutely regulated by administration of the antiprogestin RU486 to women, and 20 transcripts altered by antagonizing the action of VEGF-A in endometrium. These transcripts represent new potential targets for development of novel postcoital contraceptives. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15792645&query_hl=1 ER - TY - JFULL T1 - A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception. A1 - Hay, CJ A1 - Brady, BM A1 - Zitzmann, M A1 - Osmanagaoglu, K A1 - Pollanen, P A1 - Apter, D A1 - Wu, FC A1 - Anderson, RA A1 - Nieschlag, E A1 - Devroey, P A1 - Huhtaniemi, I A1 - Kersemaekers, WM J1 - J Clin Endocrinol Metab Y1 - 2005/04// VL - 90 SN - 0021-972X SP - 2042 EP - 2049 N2 - The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15671109&query_hl=1 ER - TY - JFULL T1 - Development of factor VIIa inhibitors: Selectivity in trypsin family proteases A1 - Shrader, WD A1 - Costerison, J A1 - Hendrix, J A1 - Hu, HY A1 - Kolesnikov, A A1 - Kumar, V A1 - Leahy, E A1 - Rai, R A1 - Shaghafi, M A1 - Ton, T A1 - Torkelson, S A1 - Wesson, K A1 - Young, WB A1 - Katz, BA A1 - Sprengeler, PA A1 - Yu, C A1 - Cabuslay, R A1 - Gjerstad, E A1 - Janc, J A1 - Sanford, E J1 - ABSTR PAP AM CHEM S Y1 - 2005/03/13/ VL - 229 SP - U153 EP - U153 ER - TY - JFULL T1 - Development of factor VIIa inhibitors: Addressing pharmacokinetic parameters A1 - Kolesnikov, A A1 - Rai, R A1 - Young, WB A1 - Torkelson, S A1 - Shrader, WD A1 - Leahy, EM A1 - Katz, BA A1 - Sprengeler, PA A1 - Liu, L A1 - Mordenti, J A1 - Gjerstad, E A1 - Janc, J J1 - ABSTR PAP AM CHEM S Y1 - 2005/03/13/ VL - 229 SP - U153 EP - U153 ER - TY - JFULL T1 - Fetal plasma testosterone correlates positively with cortisol. A1 - Gitau, R A1 - Adams, D A1 - Fisk, NM A1 - Glover, V J1 - Arch Dis Child Fetal Neonatal Ed Y1 - 2005/03// VL - 90 SN - 1359-2998 SP - F166 EP - F169 N2 - BACKGROUND: Fetal exposure to testosterone has been implicated in programming childhood behaviour, but little is known about the determinants of fetal testosterone concentrations. AIMS: To investigate the relation between fetal testosterone and maternal and fetal cortisol. METHODS: Clinically indicated blood samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15-38), together with paired maternal samples, were analysed for testosterone and cortisol concentrations. RESULTS: Male fetuses had significantly higher concentrations of testosterone than females. Female but not male fetal concentrations rose significantly with gestational age. Fetal testosterone correlated positively with both fetal cortisol and maternal testosterone concentrations. Multiple regression showed that maternal testosterone and fetal cortisol were independently correlated with fetal plasma testosterone in both sexes. CONCLUSION: Unlike the norm in the adult, where testosterone production is often inhibited by cortisol, in the fetus there is a positive link between the two. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15724043&query_hl=1 ER - TY - JFULL T1 - Association of raised titres of antibodies to Chlamydia pneumoniae with a history of pre-eclampsia. A1 - Goulis, DG A1 - Chappell, L A1 - Gibbs, RG A1 - Williams, D A1 - Dave, JR A1 - Taylor, P A1 - de Swiet, M A1 - Poston, L A1 - Williamson, C J1 - BJOG Y1 - 2005/03// VL - 112 SN - 1470-0328 SP - 299 EP - 305 N2 - OBJECTIVE: To establish the prevalence of Chlamydia pneumoniae (C. pneumoniae) infection in a pregnant UK population and to investigate whether C. pneumoniae infection is more common in women with a previous history of pre-eclampsia. DESIGN: Prospective study. SETTING: Academic Hospital. POPULATION: Ninety-one pregnant women (54 parous and 37 nulliparous) at 16-22 weeks of gestation were studied. Of the parous women, 32 had a previous history of pre-eclampsia. METHODS: Peripheral blood was drawn for C. pneumoniae antibodies between 16-22 and 28-40 weeks of gestation. C. pneumoniae antibodies were measured using a solid-phase enzyme immunoassay. According to pregnancy outcome, women were categorised into normal, gestational hypertension and pre-eclampsia groups. MAIN OUTCOME MEASURES: Serum levels of IgG, IgA and IgM C. pneumoniae antibodies. RESULTS: Prevalence of seropositivity to C. pneumoniae was 77%. Parous women had significantly higher levels of IgA and IgM C. pneumoniae antibodies than nulliparous women (P < 0.04). Parous women with previous pre-eclampsia were found to have higher levels of antibodies than parous women with a normal obstetric history (P< or = 0.003). There was no difference in the antibody levels in women with different pregnancy outcomes. CONCLUSIONS: The longitudinal data do not indicate an association between C. pneumoniae infection and pre-eclampsia. However, the subgroup analysis of parous women demonstrated raised C. pneumoniae antibodies in the women with previous pre-eclampsia, and therefore suggests that there may be an association between C. pneumoniae and the disease in this group. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15713143&query_hl=1 ER - TY - JFULL T1 - Obstetric complications due to autoantibodies A1 - Lakasing, L A1 - Williamson, C J1 - BEST PRACT RES CL EN Y1 - 2005/03// VL - 19 SN - 1521-690X SP - 149 EP - 175 N2 - Autoimmune diseases are most common and most active in young women; it is therefore not uncommon for obstetricians and physicians to encounter pregnant women with these conditions, and knowledge of the potential maternal, foetal and neonatal complications is essential for good clinical management. The most common maternal autoimmune endocrine conditions in pregnancy are insulin-dependent diabetes mellitus and thyroid disease. Other relatively common non-endocrine autoimmune conditions include systemic lupus erythematosus and antiphospholipid syndrome. Much rarer autoimmune conditions include autoimmune thrombocytopenia, rheumatoid arthritis, myasthenia gravis and Addison's disease. In this chapter, we discuss autoimmune endocrine conditions and briefly mention some non-endocrine conditions of particular importance. ER - TY - JFULL T1 - Fetal plasma testosterone correlates positively with cortisol A1 - Gitau, R A1 - Adams, D A1 - Fisk, NM A1 - Glover, V J1 - ARCH DIS CHILD-FETAL Y1 - 2005/03// VL - 90 SN - 1359-2998 SP - 166 EP - 169 N2 - Background: Fetal exposure to testosterone has been implicated in programming childhood behaviour, but little is known about the determinants of Fetal testosterone concentrations.Aims: To investigate the relation between fetal testosterone and maternal and fetal cortisol.Methods: Clinically indicated blood samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15-38), together with paired maternal samples, were analysed for testosterone and cortisol concentrations.Results: Male fetuses had significantly higher concentrations of testosterone than females. Female but not male fetal concentrations rose significantly with gestational age. Fetal testosterone correlated positively with both fetal cortisol and maternal testosterone concentrations. Multiple regression showed that maternal testosterone and fetal cortisol were independently correlated with fetal plasma testosterone in both sexes.Conclusion: Unlike the norm in the adult, where testosterone production is often inhibited by cortisol, in the fetus there is a positive link between the two. ER - TY - JFULL T1 - Novel method for the synthesis of 3 ',4 '-dideoxygenated pyranmycin and kanamycin compounds, and studies of their antibacterial activity against aminoglycoside-resistant bacteria A1 - Rai, R A1 - Chen, HN A1 - Chang, H A1 - Chang, CWT J1 - J CARBOHYD CHEM Y1 - 2005/03// VL - 24 SN - 0732-8303 SP - 131 EP - 143 N2 - A novel protocol for converting a trans-diol to an alkene under mild conditions was developed. This method let to the synthesis of a 3',4'-dideoxykanamycin (dibekacin) analog and a 3',4'-dideoxypyranmycin that were found to be active against aminoglycoside-resistant bacteria. ER - TY - JFULL T1 - Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. A1 - Steel, JH A1 - Malatos, S A1 - Kennea, N A1 - Edwards, AD A1 - Miles, L A1 - Duggan, P A1 - Reynolds, PR A1 - Feldman, RG A1 - Sullivan, MH J1 - Pediatr Res Y1 - 2005/03// VL - 57 SN - 0031-3998 SP - 404 EP - 411 N2 - Intrauterine infection has been frequently linked with preterm labor before 30 wk of human pregnancy. Many different species of organisms have been detected, leading to the suggestion that infection-induced preterm labor is a generic inflammatory response to organisms rather than a specific response to a limited number of pathogens. The detection of organisms by microbiological culture is a laborious and unreliable process, so the aim of this study was to harness modern molecular techniques to detect organisms in tissues from human pregnancy. A DNA probe specific for conserved regions of bacterial 16S ribosomal RNA sequence was designed and labeled with fluorescein for fluorescence in situ hybridization. Organisms were detected in the great majority (>80%) of fetal membranes after prolonged premature rupture of the fetal membranes and after preterm labor, which was consistent with previous data. Organisms were also detected in fetal membranes after preterm delivery without labor and in term deliveries (with or without labour). Inflammatory cells were found frequently in the amnion or chorion of preterm fetal membranes but not in term tissues. Our primary finding is that fluorescence in situ hybridization is an appropriate method to detect organisms in human fetal membranes. In addition, our data show that bacteria may be present in fetal membranes without necessarily causing an inflammatory response, so the mere presence of bacteria may not be sufficient to cause preterm labor. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15659699&query_hl=1 ER - TY - JFULL T1 - Interaction between platelets and cytokines - A possible role in the pathogenesis of preeclampsia A1 - Bar, J A1 - Ben-Haroush, A A1 - Feldberg, D A1 - Hod, M A1 - Lahav, J A1 - Sullivan, MH J1 - THROMB RES Y1 - 2005/02// VL - 115 SN - 0049-3848 SP - 110 EP - 110 ER - TY - JFULL T1 - Polycystic ovaries, insulin resistance, hypofibrinolysis and recurrent miscarriage. A1 - Regan, L A1 - Carrington, B A1 - Rasul, S A1 - Lawn, A A1 - Rai, R J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 91A EP - 92A ER - TY - JFULL T1 - Identification of novel progesterone receptor regulated pathways in the endometrium. A1 - Catalano, RD A1 - Critchley, HO A1 - Heikinheimo, O A1 - Smith, SK A1 - Sharkey, AM J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 209A EP - 210A ER - TY - JFULL T1 - Mechanical stretch in human amnion cells activates both NF kappa B and AP-1. A1 - Mohan, AR A1 - Sooranna, SR A1 - Johnson, MR A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 85A EP - 85A ER - TY - JFULL T1 - Can routine commercial cord blood banking be scientifically and ethically justified? A1 - Fisk, NM A1 - Roberts, IA A1 - Markwald, R A1 - Mironov, V J1 - PLoS Med Y1 - 2005/02// VL - 2 SN - 1549-1676 SP - e44 EP - e44 N2 - BACKGROUND TO THE DEBATE: Umbilical cord blood--the blood that remains in the placenta after birth--can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation). L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15737000&query_hl=1 ER - TY - JFULL T1 - Term preeclampsia is associated with minimal histopathological placental features regardless of clinical severity. A1 - Sebire, NJ A1 - Goldin, RD A1 - Regan, L J1 - J Obstet Gynaecol Y1 - 2005/02// VL - 25 SN - 0144-3615 SP - 117 EP - 118 N2 - Preeclampsia (PET) is a serious complication of pregnancy, which is associated with uteroplacental disease and reduced uteroplacental perfusion. One of the histological features in placentas from pregnancies complicated by PET is infarction, representing focal severe uteroplacental ischaemia. This study examines the relationship between gestation at induced delivery and the prevalence of placental infarction using a placental pathology database to identify induced or operative deliveries on the basis of severe PET. The clinical and pathological findings were reviewed. Thirty-seven cases were identified, (4.9% of all placentas submitted). In 16 (43%), non-peripheral significant infarcts were identified histologically, including 13/20 (65%) requiring delivery before 34 weeks' compared to 3/17 (17%) requiring delivery > or = 34 weeks (z=2.9, P<0.01). Histological infarction is common in placentas from pregnancies complicated by severe PET but the prevalence is significantly greater in cases requiring delivery at earlier gestations, even when similar clinical indications for delivery are applied. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15814385&query_hl=1 ER - TY - JFULL T1 - Functional role of integrins in primary culures of uterine myometrial cells. A1 - Engineer, N A1 - Chakravarti, S A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 348A EP - 348A ER - TY - JFULL T1 - Rapid activation of heat shock protein 27 via P38MAPK and MAPKAPK-2 by mechanical stretch and interleukin-1beta in human uterine smooth muscle cells. A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 262A EP - 262A ER - TY - JFULL T1 - Progesterone increases tissue factor gene expression, procoagulant activity, and invasion in the breast cancer cell line ZR-75-1. A1 - Kato, S A1 - Pinto, M A1 - Carvajal, A A1 - Espinoza, N A1 - Monso, C A1 - Sadarangani, A A1 - Villalon, M A1 - Brosens, JJ A1 - White, JO A1 - Richer, JK A1 - Horwitz, KB A1 - Owen, GI J1 - J Clin Endocrinol Metab Y1 - 2005/02// VL - 90 SN - 0021-972X SP - 1181 EP - 1188 N2 - Progesterone in hormonal preparations increases the incidence of breast cancer. Tissue factor (TF), the initiator of the extrinsic coagulation pathway, is associated with metastasis in a wide variety of cancers. We demonstrate herein that TF mRNA and protein are up-regulated by progesterone in the breast cancer cell line ZR-75. Epidermal growth factor, also associated with increased breast cancer risk, did not regulate TF. The increase in TF is both rapid and transient; increasing after 6 h, reaching a maximum at 24 h, before decreasing to basal levels at 72 h. Sucrose gradient experiments demonstrated that TF is located in the heavy fraction of the plasma membrane, although caveolin-1 is not expressed in ZR-75. To understand the physiological implications of an increase in TF, we performed coagulation and invasion assays. An increase in TF corresponded to an increase in procoagulant activity. Furthermore, progesterone increased the invasion of ZR-75 cells through a matrigel, an effect that was blocked by an antibody against TF. Because TF expression is associated with an enhanced risk of metastasis, we postulate that the progesterone-dependent up-regulation of TF provides a survival advantage to burgeoning breast cancer cells and may contribute to the increased risk of cancer associated with combined hormone replacement therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15562024&query_hl=1 ER - TY - JFULL T1 - Impaired insulin-dependent glucose metabolism in granulosa-lutein cells from anovulatory women with polycystic ovaries. A1 - Rice, S A1 - Christoforidis, N A1 - Gadd, C A1 - Nikolaou, D A1 - Seyani, L A1 - Donaldson, A A1 - Margara, R A1 - Hardy, K A1 - Franks, S J1 - Hum Reprod Y1 - 2005/02// VL - 20 SN - 0268-1161 SP - 373 EP - 381 N2 - BACKGROUND: Insulin resistance and hyperinsulinaemia are well-recognized characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study is that insulin resistance in the ovary is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism), whereas the steroidogenic action of insulin remains intact. METHODS: Granulosa-lutein cells were obtained during IVF cycles from seven women with normal ovaries, six ovulatory women with PCO (ovPCO) and seven anovulatory women with PCO (anovPCO). Mean body mass index was in the normal range in all three groups. Granulosa-lutein cells were cultured with insulin (1, 10, 100 and 1000 ng/ml) and LH (1, 2.5 and 5 ng/ml). Media were sampled at 24 and 48 h and analysed for glucose uptake, lactate production and (48 h only) progesterone production. RESULTS: Insulin-stimulated glucose uptake by cells from anovPCO was attenuated at higher doses of insulin (100 and 1000 ng/ml) compared with that by cells from either ovPCO (P=0.02) or controls (P=0.02). Insulin and LH stimulated lactate production in a dose-dependent manner, but insulin-dependent lactate production was markedly impaired in granulosa-lutein cells from anovPCO compared with either normal (P=0.002) or ovPCO (P<0.0001). By contrast, there was no difference in insulin-stimulated progesterone production between granulosa-lutein cells from the three ovarian types. CONCLUSIONS: Granulosa-lutein cells from women with anovPCOS are relatively resistant to the effects of insulin-stimulated glucose uptake and utilization compared with those from normal and ovPCO, whilst maintaining normal steroidogenic output in response to physiological doses of insulin. These studies support the probability of a post-receptor, signalling pathway-specific impairment of insulin action in PCOS. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15539436&query_hl=1 ER - TY - JFULL T1 - ABO incompatibility due to immunoglobulin G anti-B antibodies presenting with severe fetal anaemia. A1 - Ziprin, JH A1 - Payne, E A1 - Hamidi, L A1 - Roberts, I A1 - Regan, F J1 - Transfus Med Y1 - 2005/02// VL - 15 SN - 0958-7578 SP - 57 EP - 60 N2 - ABO incompatibility is a common haematological problem affecting the newborn. The haemolysis is widely accepted to follow a relatively benign course rarely causing the escalating levels of hyperbilirubinaemia and significant anaemia associated with Rh haemolytic disease of the newborn. Case reports of fetal hydrops secondary to ABO incompatibility are particularly rare. We describe two cases, first that of a twin pregnancy with both fetuses developing severe anaemia at 20 weeks gestation, and then a second case of a preterm baby demonstrating aggressive haemolysis and anaemia within hours of delivery. Both mothers were of black Africian origin and both were identified to have elevated titres of IgG anti-B antibodies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15713130&query_hl=1 ER - TY - JFULL T1 - Micro-array classification of endometrial cDNAs from fertile and infertile patients. A1 - Sherwin, JRA A1 - Catalano, RD A1 - Zaidi, F A1 - Smith, SK A1 - Edassery, S A1 - Sharkey, AM J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 204A EP - 204A ER - TY - JFULL T1 - Effect of protein kinase inhibitors apigenin, D-erythro-sphingosine and rottlerin on interleukin-8 and PGHS-2 expression in cultured human uterine myocytes. A1 - Sooranna, SR A1 - Chakravarti, S A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 262A EP - 262A ER - TY - JFULL T1 - Preterm rupture of membranes is associated with increased cytokine concentrations, infection and NF kappa B activity but occurs independently of nuclear PR A1 - Loudon, JAZ A1 - Terzidou, V A1 - Kandola, M A1 - Sullivan, MHF A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 254A EP - 254A ER - TY - JFULL T1 - The expression of different progesterone receptor isoforms in human myometrium. A1 - Lee, YS A1 - Kanola, M A1 - Soorana, SR A1 - Johnson, MR A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 135A EP - 135A ER - TY - JFULL T1 - In vivo effects of isatin on rat platelet eicosanoids A1 - Pataki, I A1 - Mezei, Z A1 - Adamik, A A1 - Glover, V A1 - Gecse, A A1 - Telegdy, G J1 - PLATELETS Y1 - 2005/02// VL - 16 SN - 0953-7104 SP - 39 EP - 43 N2 - To establish the possible influence of isatin (2,3-dioxo-indole) on the activity of platelets, the effects of isatin on platelet eicosanoid synthesis were studied in rats. Different doses (12.5-50 mg/kg) of isatin were injected intraperitoneally (i.p.) and the effects on the arachiclonate cascade of isolated platelets were investigated. Cells were labeled with [C-14] arachiclonic acid, then the eicosanoids were separated with overpressure thin-layer chromatography and were quantitatively determined with a liquid scintillation analyzer. The lipoxygenase pathway was significantly inhibited by isatin (50 mg/kg) treatment and also the overall activity of the arachiclonate cascade was diminished; however, the cyclooxygenase system was significantly stimulated. A 50-mg/kg i.p. dose of isatin significantly increased the production of vasoconstrictor cyclooxygenase metabolites. Among the vasodilator cyclooxygenase products, the synthesis of PGE2 and PGD2 were significantly decreased while that of 12-hydroxyheptadecatrienoic acid (HHT) increased upon isatin (50mg/kg) administration. Our results provide further evidence on the peripheral actions of isatin and suggest that this endogenous indole may induce significant changes in the production of blood platelet arachidonic acid metabolites, which are important regulatory substances, thus isatin may potentially affect an even broader range of ftinctions than was previously assumed. ER - TY - JFULL T1 - Anisomycin upregulates oxytocin receptor expression in human uterine myocytes. A1 - Sooranna, SR A1 - Engineer, N A1 - Terzidou, V A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 353A EP - 353A ER - TY - JFULL T1 - Hey1, a mediator of notch signaling, is an androgen receptor corepressor. A1 - Belandia, B A1 - Powell, SM A1 - García-Pedrero, JM A1 - Walker, MM A1 - Bevan, CL A1 - Parker, MG J1 - Mol Cell Biol Y1 - 2005/02// VL - 25 SN - 0270-7306 SP - 1425 EP - 1436 N2 - Hey1 is a member of the basic helix-loop-helix-Orange family of transcriptional repressors that mediate Notch signaling. Here we show that transcription from androgen-dependent target genes is inhibited by Hey1 and that expression of a constitutively active form of Notch is capable of repressing transactivation by the endogenous androgen receptor (AR). Our results indicate that Hey1 functions as a corepressor for AF1 in the AR, providing a mechanism for cross talk between Notch and androgen-signaling pathways. Hey1 colocalizes with AR in the epithelia of patients with benign prostatic hyperplasia, where it is found in both the cytoplasm and the nucleus. In marked contrast, we demonstrate that Hey1 is excluded from the nucleus in most human prostate cancers, raising the possibility that an abnormal Hey1 subcellular distribution may have a role in the aberrant hormonal responses observed in prostate cancer. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15684393&query_hl=1 ER - TY - JFULL T1 - Progesterone receptor isoforms PR-A and NF kappa B subunit rela inhibits PR-B-mediated transactivation in human amnion and myometrial cells. A1 - Lee, YS A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 135A EP - 135A ER - TY - JFULL T1 - GATA1 mutation and trisomy 21 are required only in haematopoietic cells for development of transient myeloproliferative disorder A1 - Carpenter, E A1 - Valverde-Garduno, V A1 - Sternberg, A A1 - Mitchell, C A1 - Roberts, I A1 - Vyas, P A1 - Vora, A J1 - BRIT J HAEMATOL Y1 - 2005/02// VL - 128 SN - 0007-1048 SP - 548 EP - 551 N2 - Trisomy 21 [Down's syndrome (DS)] and mutations in transcription factor GATA1 predispose neonates to a transient myeloproliferative disorder (TMD) and/or acute megakaryocytic leukaemia (AMKL). The role of trisomy 21 in their pathogenesis is unclear. We previously reported two rare neonates without DS who had TMD, one of whom progressed to AMKL. Trisomy 21 was detected only in blood cells at presentation with TMD/AMKL and disappeared with disease resolution. We now show that the blood cells at presentation of TMD harboured GATA1 genomic DNA mutations, suggesting a requirement for trisomy 21 in haematopoietic cells, rather than other cell types, for development of TMD/AMKL. ER - TY - JFULL T1 - The role of prostaglandin E2 and inflammatory cytokines in the regulation of progesterone receptor expression in human myometrium. A1 - Chakravarti, S A1 - Engineer, N A1 - Sooranna, SR A1 - Bennett, PR A1 - Johmson, MR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 288A EP - 288A ER - TY - JFULL T1 - Inflammatory cytokine-induced expression of COX-2and IL-8 in primary human myometrial cells. A1 - Sooranna, R A1 - Bennett, PR A1 - Johnson, MR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 251A EP - 252A ER - TY - JFULL T1 - Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis. A1 - Hull, ML A1 - Prentice, A A1 - Wang, DY A1 - Butt, RP A1 - Phillips, SC A1 - Smith, SK A1 - Charnock-Jones, DS J1 - Hum Reprod Y1 - 2005/02// VL - 20 SN - 0268-1161 SP - 350 EP - 358 N2 - BACKGROUND: Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2 inhibition would reduce the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. METHODS: The selective COX-2 inhibitor, nimesulide, was administered to estrogen-supplemented nude mice implanted with human endometrial tissue. Ten days after implantation, the number and size of ectopic endometrial lesions were evaluated and compared with lesions from a control group. Immunohistochemical assessment of vascular development and macrophage and myofibroblast infiltration in control and treated lesions was performed. RESULTS: There was no difference in the number or size of ectopic endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did not induce a visually identifiable difference in blood vessel development or macrophage or myofibroblast infiltration in nude mouse explants. CONCLUSION: The hypothesized biological properties of COX-2 inhibition did not influence lesion number or size in the nude mouse model of endometriosis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15567877&query_hl=1 ER - TY - JFULL T1 - Effects of vasoactive agents on intracellular calcium and force in myometrial and subcutaneous resistance arteries isolated from preeclamptic, pregnant, and nonpregnant woman. A1 - Wimalasundera, RC A1 - Thom, SA A1 - Regan, L A1 - Hughes, AD J1 - Am J Obstet Gynecol Y1 - 2005/02// VL - 192 SN - 0002-9378 SP - 625 EP - 632 N2 - OBJECTIVE: Preeclampsia is a common and serious complication of pregnancy, characterized by maternal hypertension and proteinuria, placental insufficiency, and fetal growth restriction. The purpose of this study was to investigate whether intracellular Ca 2+ ([Ca 2+ ] i ) and contractile responses of vascular smooth muscle to vasoactive agents are altered in preeclampsia compared with normal pregnancy and the nonpregnant state. STUDY DESIGN: Subcutaneous and myometrial resistance arteries from women who had preeclampsia, normal pregnancy, and nonpregnant women were obtained at the time of cesarean section or hysterectomy. Arteries were mounted on an isometric myograph and loaded with the Ca 2+ indicator, fura-2AM, to permit simultaneous measurement of force and [Ca 2+ ] i . Reponses to endothelium-dependent relaxants (acetylcholine and substance P) and vasoconstrictors (depolarizing potassium solution, phenylephrine, and angiotensin II) were examined. RESULTS: The fall in [Ca 2+ ] i and relaxation in response to acetylcholine was significantly inhibited in both myometrial and subcutaneous arteries from preeclamptic women compared with arteries from nonpregnant or normal pregnant women. However, responses to substance P did not differ between the 3 groups. There were no significant differences in [Ca 2+ ] i or force responses to high potassium, phenylephrine, or angiotensin II in myometrial and subcutaneous resistance vessels in women with preeclampsia compared with normal pregnant women. However, force, but not [Ca 2+ ] i responses to angiotensin II, in subcutaneous vessels from normal pregnant and preeclamptic women were reduced compared with subcutaneous arteries from nonpregnant women, indicating that pregnancy is associated with a reduction in Ca 2+ sensitization in this tissue. A similar effect was not seen in myometrial arteries. CONCLUSION: Endothelial function is altered in preeclampsia, with loss of effect of acetylcholine, but not substance P. Vasoconstrictor reactivity is not increased in preeclampsia compared with uncomplicated normal pregnancy, and this is unlikely to be an explanation for the increased peripheral vascular resistance seen in preeclampsia. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15696013&query_hl=1 ER - TY - JFULL T1 - The development of a mouse model to study the effect of uterine infection on preterm labour and fetal outcome. A1 - Themis, M A1 - Bennett, PR A1 - Mehmet, H A1 - Waddington, SN A1 - Buckley, SM J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 259A EP - 259A ER - TY - JFULL T1 - Accurate and robust quantification of circulating fetal and total DNA in maternal plasma from 5 to 41 weeks of gestation. A1 - Birch, L A1 - English, CA A1 - O'Donoghue, K A1 - Barigye, O A1 - Fisk, NM A1 - Keer, JT J1 - Clin Chem Y1 - 2005/02// VL - 51 SN - 0009-9147 SP - 312 EP - 320 N2 - BACKGROUND: Detection of fetal DNA in maternal plasma is achievable at 5 weeks of gestation, but few large-scale studies have reported circulating fetal and maternal DNA across all trimesters. METHODS: Blood samples were collected from 201 women between 5 and 41 weeks of pregnancy. Quantitative PCR was used to assess total and fetal DNA concentrations, and allelic discrimination analysis was investigated as a route to detecting specifically fetal DNA. RESULTS: Male fetuses were detectable from 5 weeks amenorrhea with increasing fetal DNA concentrations across gestation. The sensitivity of fetal male gender determination in pregnancies with live birth confirmation was 99%, with 100% specificity. Total DNA concentrations did not correlate with gestational age, but appeared slightly higher in the first and third trimesters than in mid-pregnancy. Analysis of short tandem repeats demonstrated that significant improvements in the detection limit are required for specific detection of fetal DNA. CONCLUSIONS: The high sensitivity of PCR-based detection, together with quantification provided by real-time DNA analysis, has clear potential for clinical application in noninvasive prenatal diagnosis. However, accurate quantification using best-fit data analysis, standardization of methods, and performance control indicators are necessary for robust routine noninvasive diagnostics. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15608152&query_hl=1 ER - TY - JFULL T1 - Testosterone replacement therapy induces spermatogenesis and partially restores fertility in luteinizing hormone receptor knockout mice. A1 - Pakarainen, T A1 - Zhang, FP A1 - Mäkelä, S A1 - Poutanen, M A1 - Huhtaniemi, I J1 - Endocrinology Y1 - 2005/02// VL - 146 SN - 0013-7227 SP - 596 EP - 606 N2 - Testosterone (T) is essential for spermatogenesis, fertility, and maintenance of the male phenotype. We analyzed in hypogonadal LH receptor knockout (LuRKO) male mice whether T treatment can restore their phenotype, spermatogenesis, and fertility. In LuRKO mice, spermatogenesis is arrested at round spermatids, adult-type Leydig cells are absent, T production is dramatically decreased, the animals are cryptorchid, and their accessory sex organs are atrophic. T replacement therapy from 21 d of life for 60 or 120 d in LuRKO mice induced a male phenotype macroscopically indistinguishable from that of wild-type littermates as well as full spermatogenesis and testicular descent. Thus, the absence of LH-dependent prepubertal androgen priming is not necessary for subsequent maturation of the male phenotype. Conspicuously, some abnormalities remained in epididymal histology after T treatment despite normal expression of several epididymis-specific genes in caput epididymis. The mice displayed normal mating behavior, although at lower frequency than wild-type controls. The spermatozoa were able to fertilize oocytes, but their impaired passage from epididymis to uterus was apparent. The mice remained subfertile, because only 9% of all breedings resulted in pregnancy, and only two of 13 mice (15%) were fertile. Moreover, inflammation in epididymides and prostate was found in many T-treated LuRKO mice, which probably impaired sperm transport and contributed to their high rate of subfertility. In conclusion, T replacement initiated prepubertally only partially restores the fertility of LuRKO mice, even though most features of the male phenotype recover. Full fertility may require higher and/or earlier postnatal T exposure or production of other Leydig cell factors lacking in this model. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15514086&query_hl=1 ER - TY - JFULL T1 - Nuclear factor kappa B (NFkappaB) and inhibitory kappa B alpha (IkappaBa) activity in the labouring and non-labouring human myometrium. A1 - Kandola, M A1 - Lindstrom, TM A1 - Bennett, PR J1 - J SOC GYNECOL INVEST Y1 - 2005/02// VL - 12 SN - 1071-5576 SP - 254A EP - 254A ER - TY - JFULL T1 - T:G mismatch-specific thymine-DNA glycosylase (TDG) as a coregulator of transcription interacts with SRC1 family members through a novel tyrosine repeat motif. A1 - Lucey, MJ A1 - Chen, D A1 - Lopez-Garcia, J A1 - Hart, SM A1 - Phoenix, F A1 - Al-Jehani, R A1 - Alao, JP A1 - White, R A1 - Kindle, KB A1 - Losson, R A1 - Chambon, P A1 - Parker, MG A1 - Schär, P A1 - Heery, DM A1 - Buluwela, L A1 - Ali, S J1 - Nucleic Acids Res Y1 - 2005/// VL - 33 SN - 1362-4962 SP - 6393 EP - 6404 N2 - Gene activation involves protein complexes with diverse enzymatic activities, some of which are involved in chromatin modification. We have shown previously that the base excision repair enzyme thymine DNA glycosylase (TDG) acts as a potent coactivator for estrogen receptor-alpha. To further understand how TDG acts in this context, we studied its interaction with known coactivators of nuclear receptors. We find that TDG interacts in vitro and in vivo with the p160 coactivator SRC1, with the interaction being mediated by a previously undescribed motif encoding four equally spaced tyrosine residues in TDG, each tyrosine being separated by three amino acids. This is found to interact with two motifs in SRC1 also containing tyrosine residues separated by three amino acids. Site-directed mutagenesis shows that the tyrosines encoded in these motifs are critical for the interaction. The related p160 protein TIF2 does not interact with TDG and has the altered sequence, F-X-X-X-Y, at the equivalent positions relative to SRC1. Substitution of the phenylalanines to tyrosines is sufficient to bring about interaction of TIF2 with TDG. These findings highlight a new protein-protein interaction motif based on Y-X-X-X-Y and provide new insight into the interaction of diverse proteins in coactivator complexes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16282588&query_hl=1 ER - TY - JFULL T1 - Heparin and aspirin attenuate placental apoptosis in vitro: Implications for early pregnancy failure A1 - Bose, P A1 - Black, S A1 - Kadyrov, M A1 - Weissenborn, U A1 - Neuten, J A1 - Regan, L A1 - Huppertz, B J1 - AM J OBSTET GYNECOL Y1 - 2005/01// VL - 192 SN - 0002-9378 SP - 23 EP - 30 N2 - Objective: Live birth rates are increased by treatment with heparin and aspirin in cases of poor pregnancy outcome such as antiphospholipid syndrome. Both drugs may attenuate miscarriage by inhibiting aberrant coagulation or by modulating trophoblast apoptosis. Here we assessed their roles in trophoblast apoptosis in vitro.Study design: BeWo cells and placental villi were cultured in sera from women with successful or failing in vitro fertilization, with and without heparin or aspirin. Apoptosis was assessed by using DNA laddering, cytokeratin 18 neoepitope formation. Bcl-2, and caspase 7 expression.Results: In BeWo cells, sera from in vitro fertilization failure increased trophoblast apoptosis. whereas heparin and aspirin reversed these effects. In villous trophoblast, heparin increased Bel-2 and cytokeratin IS protein expression. Heparin and aspirin inhibited DNA laddering.Conclusion: Heparin and aspirin modulate trophoblast apoptosis suggesting a direct impact on trophoblast biology, thus providing an additional mechanism to explain the clinical benefits of heparin and aspirin on recurrent pregnancy loss. (C) 2005 Elsevier Inc. All rights reserved. ER - TY - JFULL T1 - Follicle-stimulating hormone affects metaphase I chromosome alignment and increases aneuploidy in mouse oocytes matured in vitro. A1 - Roberts, R A1 - Iatropoulou, A A1 - Ciantar, D A1 - Stark, J A1 - Becker, DL A1 - Franks, S A1 - Hardy, K J1 - Biol Reprod Y1 - 2005/01// VL - 72 SN - 0006-3363 SP - 107 EP - 118 N2 - Follicle-Stimulating Hormone (FSH) at a wide range of doses is routinely added to culture media during in vitro maturation (IVM) of oocytes, but the effects on oocyte health are unclear. The suggestion that superovulation may cause aneuploidy and fetal abnormalities prompted us to study the potential role of FSH in the genesis of chromosomal abnormalities during meiosis I. Mouse cumulus-oocyte complexes (COCs) isolated from the antral follicles of unprimed, sexually immature B6CBF1 mice were cultured in increasing concentrations of FSH. Following culture, matured oocytes were isolated, spread, stained with DAPI, and the numbers of chromosomes counted. Significantly increased aneuploidy, arising during the first meiotic division, was observed in metaphase II oocytes matured in higher concentrations of FSH (> or =20 ng/ml). The effect of FSH on spindle morphology and chromosome alignment during metaphase I was then explored using immunocytochemistry and three-dimensional reconstruction of confocal sections. High FSH had no effect on gross spindle morphology but did alter chromosome congression during prometaphase and metaphase, with the spread of chromosomes across the spindle at this time being significantly greater in oocytes cultured in 2000 ng/ml compared with 2 ng/ml FSH. Analysis of three-dimensional reconstructions of spindles in oocytes matured in 2000 ng/ml FSH shows that chromosomes are more scattered and farther apart than they are following maturation in 2 ng/ml FSH. These results demonstrate that exposure to high levels of FSH during IVM can accelerate nuclear maturation and induce chromosomal abnormalities and highlights the importance of the judicious use of FSH during IVM. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15371272&query_hl=1 ER - TY - JFULL T1 - Ontology aided query expansion for retrieving relevant texts A1 - Dey, L A1 - Singh, S A1 - Rai, R A1 - Gupta, S J1 - LECT NOTES COMPUT SC Y1 - 2005/// VL - 3528 SN - 0302-9743 SP - 126 EP - 132 N2 - Knowledge based approaches to text information retrieval are aimed at increasing the precision of retrieval. In this paper we show that query enhancement through the use of domain ontological structures can enhance the quality of retrieval to a large extent. We have presented a formal framework for extending user queries with domain ontological structures. The query-expansion mechanism has been implemented as a client-side query processor which can use any efficient search engine like Google or Alta Vista at the back end. The approach offers substantial performance gains. We have established the effectiveness of the approach experimentally through the use of single and multiple ontologies. ER - TY - JFULL T1 - Mechanical stretch up-regulates the human oxytocin receptor in primary human uterine myocytes. A1 - Terzidou, V A1 - Sooranna, SR A1 - Kim, LU A1 - Thornton, S A1 - Bennett, PR A1 - Johnson, MR J1 - J Clin Endocrinol Metab Y1 - 2005/01// VL - 90 SN - 0021-972X SP - 237 EP - 246 N2 - Oxytocin receptor (OTR) expression is increased before the onset of labor in all models of parturition. However, the mechanisms responsible for the increase in OTR expression are uncertain. Animal data suggest that uterine stretch increases OTR mRNA expression. In primary cultures of human uterine smooth muscle cells obtained from nonpregnant (NP) women and pregnant women before (NL) and after (L) the onset of labor, we investigated the effect of stretch on the expression of OTR mRNA and DNA binding of activator protein-1 (AP-1), CCAAT/enhancer binding protein (C/EBP)beta, and nuclear factor-kappaB transcription factors. OTR expression was least in NL, intermediate in NP, and greatest in L cells. Stretch of NL cells resulted in up-regulation of OTR mRNA expression associated with increased OTR gene promoter activity. Stretch of NP and L cells did not affect OTR mRNA expression. The increased promoter activity was associated with increased DNA binding of C/EBP and AP-1 but not nuclear factor-kappaB transcription factors. Overexpression of C/EBP, but not AP-1, increased OTR promoter activity. We conclude that stretch of NL cells results in increased OTR mRNA expression probably through increased C/EBPbeta DNA binding. These data suggest that stretch contributes to the massive increase in OTR expression before the onset of human labor. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15494465&query_hl=1 ER - TY - JFULL T1 - Human fetal mesenchymal stem cells as vehicles for gene delivery. A1 - Chan, J A1 - O'Donoghue, K A1 - de la Fuente, J A1 - Roberts, IA A1 - Kumar, S A1 - Morgan, JE A1 - Fisk, NM J1 - Stem Cells Y1 - 2005/// VL - 23 SN - 1066-5099 SP - 93 EP - 102 N2 - First-trimester fetal blood contains a readily expandable population of stem cells, human fetal mesenchymal stem cells (hfMSCs), which might be exploited for autologous intrauterine gene therapy. We investigated the self-renewal and differentiation of hfMSCs after transduction with onco-retroviral and lentiviral vectors. After transduction with either a MoMuLV retrovirus or an HIV-1-based lentiviral vector carrying the ss-galactosidase and green fluorescent reporter gene, respectively, transgene expression, self-renewal, and differentiation capabilities were assessed 2 and 14 weeks later. Transduction with the lentiviral vector resulted in higher efficiencies than with the MoMuLV-based vector (mean, 97.7 +/- 1.4% versus 80.2 +/- 5.4%; p = .02). Transgene expression was maintained with lentiviral-transduced cells (94.6 +/- 2.6%) but decreased over 14 weeks in culture with onco-retroviral-transduced cells (48.3 +/- 3.9%). The self-renewal capability of these cells and their ability to undergo osteogenic, adipogenic, and myogenic differentiation was unimpaired after transduction with either vector. Finally, clonal expansion of lentivirally modified cells was expanded over 20 population doublings with maintenance of multiline age differentiation capacity. These results suggest that hfMSCs may be suitable targets for ex vivo genetic manipulation with onco-retroviral or lentiviral vectors without affecting their stem cell properties. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15625126&query_hl=1 ER - TY - JFULL T1 - Gonadotrophin-releasing hormone analogues for pain associated with endometriosis (Withdrawn Paper. 1999, art. no. CD000346.pub2) A1 - Prentice, A A1 - Deary, AJ A1 - Goldbeck-Wood, S A1 - Farquhar, C A1 - Smith, SK J1 - COCHRANE DB SYST REV Y1 - 2005/// ER - TY - JFULL T1 - Timing of mid-trimester sacral ossification. A1 - Fisk, NM A1 - Shirley, I J1 - Prenat Diagn Y1 - 2005/01// VL - 25 SN - 0197-3851 SP - 91; author reply 92 EP - 91; author reply 92 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15662712&query_hl=1 ER - TY - JFULL T1 - Gonadotrophin-releasing hormone analogues for pain associated with endometriosis (Withdrawn Paper. 1999, art. no. CD000346.pub2) A1 - Prentice, A A1 - Deary, AJ A1 - Goldbeck-Wood, S A1 - Farquhar, C A1 - Smith, SK J1 - COCHRANE DB SYST REV Y1 - 2005/// ER - TY - JFULL T1 - Gonadotrophin-releasing hormone analogues for pain associated with endometriosis (Withdrawn Paper. 1999, art no. CD000346) A1 - Prentice, A A1 - Deary, AJ A1 - Goldbeck-Wood, S A1 - Farquhar, C A1 - Smith, SK J1 - COCHRANE DB SYST REV Y1 - 2005/// ER - TY - JFULL T1 - Neonatal thrombocytopenia A1 - Chakravorty, S A1 - Murray, N A1 - Roberts, I J1 - EARLY HUM DEV Y1 - 2005/01// VL - 81 SN - 0378-3782 SP - 35 EP - 41 N2 - Thrombocytopenia occurs in up to a third of preterm neonates admitted to intensive care units. In these babies, thrombocytopenia typically presents in one of two patterns: earty-onset thrombocytopenia occurring within 72 h of birth and late-onset thrombocytopenia which develops after 72 h. Early-onset thrombocytopenia is most commonly caused by disorders associated with placental insufficiency (e.g. maternal hypertension), is mild-moderate, self-limiting and requires no treatment; it is caused by reduced platelet production. Late-onset thrombocytopenia is usually due to bacterial sepsis or necrotising enterocolitis; it is often severe (platelets < 50 x 10(9)/l), prolonged and requires treatment with platelet transfusions. In term babies, neonatal thrombocytopenia is usually severe and most commonly caused by bacterial sepsis, perinatal asphyxia or neonatal alloimmune thrombocytopenia. There is a lack of evidence-based guidelines for treatment of neonatal thrombocytopenia. The most important future developments wilt depend upon studies aimed at determining optimal platelet transfusion schedules for term and preterm neonates. (C) 2004 Elsevier Ireland Ltd. ALL rights reserved. ER - TY - JFULL T1 - Characterisation of deep arterio-venous anastomoses within monochorionic placentae by vascular casting. A1 - Wee, LY A1 - Taylor, M A1 - Watkins, N A1 - Franke, V A1 - Parker, K A1 - Fisk, NM J1 - Placenta Y1 - 2005/01// VL - 26 SN - 0143-4004 SP - 19 EP - 24 N2 - OBJECTIVE: To characterise arterio-venous anastomoses (AVA) in monochorionic (MC) placentae and determine (i) whether shared cotyledons lie beneath the co-termination of an artery from one twin and a vein to the contralateral twin and (ii) whether all AVA can be detected by visual inspection of the chorionic plate. METHODS: Vascular casts were made of 15 MC placentae. The number of typical AVAs suspected visually before digestion was compared with the number of AVAs identified after acid digestion. RESULTS: Thirty-three of 67 (49%) suspected typical AVAs were confirmed as typical after casting. There were five false positives and no false negatives. The remainder were classified as atypical AVAs, found in > or =90% of MC placentae. Type I (small vascular connections between two apparently normal cotyledons not seen before casting) and Type II (shared cotyledons arising within larger apparently normal cotyledons) atypical AVAs were found in 53% and 73% of placentae, respectively. CONCLUSIONS: Only half the shared cotyledons in MC placentae are characterised by co-termination of an artery and vein on the chorionic plate. We report the existence of deep anastomoses beneath the chorionic plate that cannot be visualised by chorionic plate inspection. These findings have implications for laser treatment of twin-twin transfusion syndrome. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15664407&query_hl=1 ER - TY - JFULL T1 - Testicular cell lines. A1 - Rahman, NA A1 - Huhtaniemi, IT J1 - Mol Cell Endocrinol Y1 - 2004/12/30/ VL - 228 SN - 0303-7207 SP - 53 EP - 65 N2 - The range of in vivo or in vitro immortalized cell lines currently available provides a variety of model systems for studies of normal and pathological cell functions. The cell lines have been derived from spontaneous or experimentally induced tumors, or through in vitro immortalization. The transgenic (TG) techniques provide a powerful approach, allowing the production of in vivo animal models for a variety of diseases, including malignant tumors, through tissue-specific expression of oncogenes or other tumor-promoting genes. The TG techniques also enable the production of cell lines with specific characteristics, through insertion of desired genes into specific cell types, which can then be immortalized upon cell culture. The use of temperature-sensitive immortalizing genes offers an additional advantage of controlling gene expression, including the proliferation and differentiation of the cells to be immortalized. As regards the male reproductive system, a number of cell lines of testicular somatic cells are currently available. This review covers mainly the immortalized cell lines of testicular Leydig and Sertoli cells, with special reference to murine cell lines for the study of testicular endocrine function and tumorigenesis. These cell lines also provide useful tools to investigate the molecular basis of hormone actions and testicular cell interactions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15541572&query_hl=1 ER - TY - JFULL T1 - Endocrine cell lines from the placenta. A1 - Sullivan, MH J1 - Mol Cell Endocrinol Y1 - 2004/12/30/ VL - 228 SN - 0303-7207 SP - 103 EP - 119 N2 - Cell-lines derived from human placenta and chorion have been used extensively to model the endocrine functions of human trophoblast. In general terms, the endocrine functions of the primary cells and tissues are at least partially replicated within the cell-lines, suggesting that they may be used as appropriate models. There are, however, two major provisos that compromise this generalisation. Firstly, the endocrine function of placenta represents a complex interaction between cytotrophoblast, syncytiotrophoblast and multiple regulators, so a single cell population digested from the normal environment is unlikely to represent this. Secondly, the characterisation of primary trophoblast populations and of cell-lines is incomplete, complicating the assignment of functions to trophoblast populations. Despite these difficulties, useful information has been obtained from the available cell-lines, regardless of whether they have arisen spontaneously, been transformed in vitro, or derived from cancers in vivo. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15541575&query_hl=1 ER - TY - JFULL T1 - Molecular and biochemical mechanisms of preterm labour. A1 - Mohan, AR A1 - Loudon, JA A1 - Bennett, PR J1 - Semin Fetal Neonatal Med Y1 - 2004/12// VL - 9 SN - 1744-165X SP - 437 EP - 444 N2 - Parturition involves the synchronization of myometrial activity and structural changes of the cervix, leading to regular co-ordinated uterine contractions and cervical dilatation and effacement. The biochemical events involved in parturition resemble an inflammatory reaction, with growing evidence pointing to a crucial role for pro-inflammatory cytokines and prostaglandins in labour. There is accumulating evidence that there are common mediators involved in the regulation of 'labour-associated proteins', and that, in each case, an increase or decrease in gene expression mediates changes in their concentration. It is possible, therefore, that targeting these common mediators may represent newer strategies for the prevention of preterm labour. Our aim is to review the mechanical and biochemical mechanisms that may be involved in the processes of term and preterm labour. Specifically, we will consider the regulation of some of the 'labour-associated proteins', chemotactic cytokines, prostaglandins and enzymes of the prostaglandin biosynthetic pathway and the oxytocin receptor. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15691781&query_hl=1 ER - TY - JFULL T1 - Fetal stem cells. A1 - O'Donoghue, K A1 - Fisk, NM J1 - Best Pract Res Clin Obstet Gynaecol Y1 - 2004/12// VL - 18 SN - 1521-6934 SP - 853 EP - 875 N2 - Fetal stem cells can be isolated from fetal blood and bone marrow as well as from other fetal tissues, including liver and kidney. Fetal blood is a rich source of haemopoietic stem cells (HSC), which proliferate more rapidly than those in cord blood or adult bone marrow. First trimester fetal blood also contains a population of non-haemopoietic mesenchymal stem cells (MSC), which support haemopoiesis and can differentiate along multiple lineages. In terms of eventual downstream application, both fetal HSC and MSC have advantages over their adult counterparts, including better intrinsic homing and engraftment, greater multipotentiality and lower immunogenicity. Fetal stem cells are less ethically contentious than embryonic stem cells and their differentiation potential appears greater than adult stem cells. Fetal stem cells represent powerful tools for exploring many aspects of cell biology and hold considerable promise as therapeutic tools for cell transplantation and ex vivo gene therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15582543&query_hl=1 ER - TY - JFULL T1 - Pregnancy following monofollicular ovulation induction with recombinant FSH, recombinant LH and timed coitus in an amenorrheic woman with long-standing hypogonadotrophic hypogonadism. A1 - El-Shawarby, SA A1 - Turner, CF A1 - Reddy, N A1 - Margara, RA A1 - Trew, GH A1 - Lavery, SA J1 - BJOG Y1 - 2004/12// VL - 111 SN - 1470-0328 SP - 1481 EP - 1484 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15663144&query_hl=1 ER - TY - JFULL T1 - Mechanical stretch of human uterine smooth muscle cells increases IL-8 mRNA expression and peptide synthesis. A1 - Loudon, JA A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - Mol Hum Reprod Y1 - 2004/12// VL - 10 SN - 1360-9947 SP - 895 EP - 899 N2 - Labour is associated with increased synthesis of interleukin-8 (IL-8) by the fetal membranes and myometrium, which leads to an inflammatory infiltrate. Stretch has been shown to increase the expression of contraction-associated proteins in animal models of labour and in human myocytes in vitro. In this study, we tested the hypothesis that mechanical stretch of human myometrial cells increases IL-8 messenger ribonucleic acid (mRNA) expression. We isolated myocytes from non-pregnant women undergoing hysterectomy and pregnant women undergoing Caesarean section before and after the onset of labour. Myocytes in culture were subjected to stretch of varying intensity (6-16%) and duration (1 or 6 h) using the Flexercell system. IL-8 mRNA expression was lowest in myocytes from pregnant women not in labour, intermediate in those from non-pregnant women and greatest in those from pregnant women in labour. Stretch increased IL-8 mRNA expression independent of reproductive state. The stretch-induced increase in IL-8 mRNA expression was associated with higher IL-8 levels in the culture supernatant and enhanced promoter activity. These data suggest that stretch contributes to the increase in myometrial IL-8 synthesis associated with the onset of labour in humans. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15489245&query_hl=1 ER - TY - JFULL T1 - MRI guidance of focused ultrasound therapy of uterine fibroids: early results. A1 - Hindley, J A1 - Gedroyc, WM A1 - Regan, L A1 - Stewart, E A1 - Tempany, C A1 - Hynyen, K A1 - Hynnen, K A1 - Mcdannold, N A1 - Macdanold, N A1 - Inbar, Y A1 - Itzchak, Y A1 - Rabinovici, J A1 - Kim, HS A1 - Kim, K A1 - Geschwind, JF A1 - Hesley, G A1 - Gostout, B A1 - Gostout, B A1 - Ehrenstein, T A1 - Hengst, S A1 - Sklair-Levy, M A1 - Shushan, A A1 - Jolesz, F J1 - AJR Am J Roentgenol Y1 - 2004/12// VL - 183 SN - 0361-803X SP - 1713 EP - 1719 N2 - OBJECTIVE: The purpose of this study was to explore our hypothesis that MRI-guided focused ultrasound therapy for the treatment of uterine fibroids will lead to a significant reduction in symptoms and improvement in quality of life. We describe focused ultrasound therapy applications and the method for monitoring the thermal energy deposited in the fibroids, including the MRI parameters required, in a prospective review of 108 treatments. MATERIALS AND METHODS: Patients presenting with symptomatic uterine fibroids who attained a minimal symptom severity score and who would otherwise have been offered a hysterectomy were recruited. Thermal lesions were created within target fibroids using an MRI-guided focused ultrasound therapy system. The developing lesion was monitored using real-time MR thermometry, which was used to assess treatment outcome in real time to change treatment parameters and achieve the desired outcome. Fibroid volume, fibroid symptoms, and quality-of-life scores were measured before treatment and 6 months after treatment. Adverse events were actively monitored and recorded. RESULTS: In this study, 79.3% of women who had been treated reported a significant improvement in their uterine fibroid symptoms on follow-up health-related quality-of-life questionnaires, which supports our hypothesis. The mean reduction in fibroid volume at 6 months was 13.5%, but nonenhancing volume (mean, 51 cm(3)) remained within the treated fibroid at 6 months. CONCLUSION: This early description of MRI-guided focused ultrasound therapy treatment of fibroids includes follow-up data and shows that, although the volume reduction is moderate, it correlates with treatment volume and the symptomatic response to this treatment is encouraging. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15547216&query_hl=1 ER - TY - JFULL T1 - Infant cortisol response after prolonged antenatal prednisolone treatment. A1 - Miller, NM A1 - Williamson, C A1 - Fisk, NM A1 - Glover, V J1 - BJOG Y1 - 2004/12// VL - 111 SN - 1470-0328 SP - 1471 EP - 1474 N2 - Prednisolone is widely used to treat medical conditions in pregnancy, despite the lack of long-term safety studies on infants. Animal studies have shown that antenatal glucocorticoid treatment can cause in utero growth restriction and up-regulation of the offsprings' hypathalamic-pituitary-adrenal axis. We recruited women treated antenatally with prednisolone, and followed 12 of the infants up to four months, using routine infant vaccinations as a stressor. Birthweights were similar to controls (n = 289, uncomplicated, singleton term pregnancies), as were infants' baseline and stress-induced cortisol levels. Mothers rated their infants as less difficult and more adaptable than controls. This study provides initial reassurance about the safety of prednisolone in pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15663140&query_hl=1 ER - TY - JFULL T1 - Localization of the VEGF and angiopoietin genes in uterine carcinosarcoma. A1 - Emoto, M A1 - Charnock-Jones, DS A1 - Licence, DR A1 - Ishiguro, M A1 - Kawai, M A1 - Yanaihara, A A1 - Saito, T A1 - Hachisuga, T A1 - Iwasaki, H A1 - Kawarabayashi, T A1 - Smith, SK J1 - Gynecol Oncol Y1 - 2004/12// VL - 95 SN - 0090-8258 SP - 474 EP - 482 N2 - OBJECTIVE: Carcinosarcoma of the uterus is a highly aggressive tumor. However, the angiogenesis in this tumor remains unclear. This is the first study to examine the characteristics of angiogenesis in this tumor at the molecular level while also comparing the findings with those of high-grade endometrial carcinoma. METHODS: The expression of vascular endothelial growth factors (VEGF) and angiopoietins (Ang) genes were examined in 35 primary uterine carcinosarcomas as well as in 12 high-grade endometrial carcinomas by in situ hybridization. RESULTS: A strong expression of VEGF-A mRNA was significantly seen in carcinosarcomas compared to high-grade endometrial carcinomas. Interestingly, in uterine carcinosarcoma, VEGF-A mRNA was more strongly expressed in the carcinoma cells than in the sarcoma cells. In addition, a decrease in the VEGF-A mRNA expression was found in the transitional areas between carcinomatous and sarcomatous elements in most carcinosarcomas evaluated. Moreover, the Ang-2 mRNA expression was significantly seen in the vasculature adjacent to the periphery of the carcinoma cells in most carcinosarcomas, in comparison to that of endometrial carcinomas. CONCLUSIONS: A high angiogenic activity in uterine carcinosarcoma was shown, in comparison to that of endometrial carcinoma. Tumor angiogenesis in uterine carcinosarcoma might be chiefly influenced by VEGF-A in the carcinoma cells, in cooperation with Ang-2 in the surrounding microvessels, however, this is not fully usually the case in sarcoma cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15581949&query_hl=1 ER - TY - JFULL T1 - Regulation of human villous trophoblast by insulin-like growth factors and insulin-like growth factor-binding protein-1. A1 - Hills, FA A1 - Elder, MG A1 - Chard, T A1 - Sullivan, MH J1 - J Endocrinol Y1 - 2004/12// VL - 183 SN - 0022-0795 SP - 487 EP - 496 N2 - Many studies have implicated the insulin-like growth factors (IGFs) and insulin-like growth factor-binding protein-1 (IGFBP-1) in the control of the feto-maternal interface of human pregnancy, but many of the data are from cell lines derived from primary trophoblast or from extravillous trophoblast. We have obtained highly enriched villous cytotrophoblast (VCT) from first trimester and term human placentae, and investigated the effects of IGF-I, IGF-II and phosphoisoforms of IGFBP-1. First trimester villous trophoblast cells were regulated by all these factors. IGF-II increased cell numbers 3.5-fold after 96 h in culture, and IGF-I had less effect (1.5-fold increase) (both P<0.05). IGF-II also had a greater effect on the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Phosphorylated and non-phosphorylated iso-forms of IGFBP-1 added alone increased cell numbers and MMP levels (P<0.05). IGFBP-1 did not modify the effects of IGF-II on cell numbers or on MMP production. Term VCT numbers and MMP production in vitro were unaffected by IGFs (P>0.05). Cell numbers were increased only by 100 nM IGFBP-1 isoforms (P<0.05), whereas MMP levels released from term cells were optimally increased by 1-10 nM IGFBP-1. Overall, our data show that IGFs regulate only first trimester, but not term, VCT. IGFBP-1 regulates VCT from both gestations, but the effects are concentration and end-point specific. In particular, first trimester cell numbers are more affected by low levels of IGFBP-1, whereas high levels of IGFBP-1 are needed to increase MMP and the converse applies to term VCT; low levels of IGFBP-1 have more effect on MMP levels. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15590975&query_hl=1 ER - TY - JFULL T1 - Circulating human fetal mesenchymal stem cells support LTC-IC and express a cytokine profile to maintain quiescence of co-circulating hemopoietic stem cells. A1 - de la Fuente, J A1 - Chan, J A1 - O'Donoghue, K A1 - Kaeda, J A1 - Kumar, S A1 - Fisk, NM A1 - Roberts, IAG J1 - BLOOD Y1 - 2004/11/16/ VL - 104 SN - 0006-4971 SP - 640A EP - 641A ER - TY - JFULL T1 - Polymorphisms in androgen and estrogen receptor genes: effects on male aging. A1 - Jiang, M A1 - Huhtaniemi, I J1 - Exp Gerontol Y1 - 2004/11// VL - 39 SN - 0531-5565 SP - 1603 EP - 1611 N2 - Besides lifestyle and environmental factors, the life-long exposure to the endocrine milieu of gonadal steroids is a determining factor to gender specific features of aging. In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, cross-sectional and longitudinal population studies demonstrate that the hormones with anabolic actions (e.g. testosterone [T], growth hormone, insulin-like growth factor [IGF]-1, dehydroepiandrosterone) do decrease progressively with aging in healthy men, and chronic systemic illnesses accelerate this process. In addition, estrogen has recently been established to be essential for normal physiology of the male. The slow progressive decline of the hypothalamic-pituitary-gonadal (HPG) function is thought to be responsible for many common signs and symptoms of aging men, such as general weakness, sexual dysfunction, and increased fat mass. There is a large inter-individual variation in sex hormone levels cross-sectionally within given age groups as well as longitudinally with aging. A contributing factor to this variability are the numerous functionally significant polymorphisms that have been detected in the receptors for androgen and estrogen. In this review, we summarize the recent information on some common polymorphisms in androgen and estrogen receptor genes and their effect on gender specific and aging-related symptoms and diseases of men. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15582276&query_hl=1 ER - TY - JFULL T1 - FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism. A1 - Fernández de Mattos, S A1 - Essafi, A A1 - Soeiro, I A1 - Pietersen, AM A1 - Birkenkamp, KU A1 - Edwards, CS A1 - Martino, A A1 - Nelson, BH A1 - Francis, JM A1 - Jones, MC A1 - Brosens, JJ A1 - Coffer, PJ A1 - Lam, EW J1 - Mol Cell Biol Y1 - 2004/11// VL - 24 SN - 0270-7306 SP - 10058 EP - 10071 N2 - Cell cycle arrest by FoxO transcription factors involves transcriptional repression of cyclin D, although the exact mechanism remains unclear. In this study, we used the BCR-ABL-expressing cell line BV173 as a model system to investigate the mechanisms whereby FoxO3a regulates cyclin D2 expression. Inhibition of BCR-ABL by STI571 results in down-regulation of cyclin D2 expression, activation of FoxO3a activity, and up-regulation of BCL6 expression. Using reporter gene assays, we demonstrate that STI571, FoxO3a, and BCL6 can repress cyclin D2 transcription through a STAT5/BCL6 site located within the cyclin D2 promoter. We propose that BCR-ABL inhibition leads to FoxO3a activation, which in turn induces the expression of BCL6, culminating in the repression of cyclin D2 transcription through this STAT5/BCL6 site. This process was verified by mobility shift and chromatin immunoprecipitation analyses. We find that conditional activation of FoxO3a leads to accumulation of BCL6 and down-regulation of cyclin D2 at protein and mRNA levels. Furthermore, silencing of FoxO3a and BCL6 in BCR-ABL-expressing cells abolishes STI571-mediated effects on cyclin D2. This report establishes the signaling events whereby BCR-ABL signals are relayed to cyclin D2 to mediate cell cycle progression and defines a potential mechanism by which FoxO proteins regulate cyclin D2 expression. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15509806&query_hl=1 ER - TY - JFULL T1 - Labour is associated with increased expression of type-IIA secretory phospholipase A(2) but not type-IV cytosolic phospholipase A(2) in human myometrium A1 - Slater, DM A1 - Astle, S A1 - Bennett, PR A1 - Thornton, S J1 - MOL HUM REPROD Y1 - 2004/11/01/ VL - 10 SN - 1360-9947 SP - 799 EP - 805 N2 - Human labour is associated with increased prostaglandin synthesis within the uterus. The aim of this study was to examine the expression of the type-IV cytosolic phospholipase A(2) (cPLA(2)-IV) and the type IIA secretory phospholipase A(2) (sPLA(2)-IIA) in myometrium in association with labour onset at term and preterm deliveries. These enzymes are important for the release of the prostaglandin precursor, arachidonic acid, from phospholipid membrane stores. RT-PCR was used to determine differences in gene expression between non-labour and labour groups. Expression of sPLA(2)-IIA in human myometrium was significantly increased with pregnancy, and with labour, both at term and preterm. Expression of cPLA(2)-IV in myometrium was not significantly altered with respect to pregnancy or labour. Immunohistochemical analysis demonstrated differences in the spatial localization of cPLA(2)-IV and sPLA(2)-IIA protein in upper and lower segment myometrium. cPLA(2)-IV was predominantly in vascular endothelial cells, while sPLA(2)-IIA was observed in vascular, endothelial and smooth muscle cells. In addition, sPLA(2)-IIA showed a distinct nuclear or perinuclear localization in myometrial smooth muscle cells of the lower segment. We postulate that the increased expression of sPLA(2)-IIA rather than cPLA(2)-IV in the myometrium may play a role in the onset and/or maintenance of human parturition. ER - TY - JFULL T1 - Postiranslational protein arginylation: Identification and characterization of novel arginylation enzymes A1 - Rai, R A1 - Kashina, A J1 - MOL BIOL CELL Y1 - 2004/11// VL - 15 SN - 1059-1524 SP - 457A EP - 457A ER - TY - JFULL T1 - Indirect Sertoli cell-mediated ablation of germ cells in mice expressing the inhibin-alpha promoter/herpes simplex virus thymidine kinase transgene. A1 - Ahtiainen, M A1 - Toppari, J A1 - Poutanen, M A1 - Huhtaniemi, I J1 - Biol Reprod Y1 - 2004/11// VL - 71 SN - 0006-3363 SP - 1545 EP - 1550 N2 - In the present study, we describe a novel mouse model for inducible germ cell ablation. The mice express herpes simplex virus thymidine kinase (HSV-TK) under the inhibin-alpha subunit promoter (Inhalpha). When adult transgenic (TG) mice were treated with famciclovir (FCV) for 4 wk, their spermatogenesis was totally abolished, with only Sertoli cells and few spermatids remaining in the seminiferous tubules. However, testicular steroidogenesis was not affected. Shorter treatment periods allowed us to follow up the progression of germ cell death: After 3 days, spermatogonia and preleptotene spermatocytes were no longer present. After a 1-wk treatment, spermatogonia, preleptotene, and zygotene spermatocytes were missing and the amount of pachytene spermatocytes was decreased. After a 2-wk treatment, round and elongating spermatids were present. During the third week, round spermatids were lost and, finally, after a 4-wk treatment, only Sertoli cells and few spermatids were present. Interestingly, the transgene is detected in Leydig and Sertoli cells but not in spermatogonia. This suggests that FCV is phosphorylated in Sertoli cells, and thereafter, leaks to neighboring spermatogonia, apparently through cell-cell junctions present, enabling trafficking of phosphorylated FCV. Because of the many mitotic divisions they pass through, the spermatogonia are very sensitive to toxins interfering with DNA replication, while nondividing Sertoli cells are protected. Using transillumination-assisted microdissection of the seminiferous tubules, the gene-expression patterns analyzed corresponded closely to the histologically observed progression of cell death. Thus, the model offers a new tool for studies on germ cell-Sertoli cell interactions by accurate alteration of the germ cell composition in seminiferous tubules. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15240419&query_hl=1 ER - TY - JFULL T1 - Cervical cerclage for prevention of preterm delivery in women with short cervix A1 - Simcox, R A1 - Bennett, PR A1 - Shennan, AH J1 - LANCET Y1 - 2004/11// VL - 364 SN - 0140-6736 SP - 1934 EP - 1935 ER - TY - JFULL T1 - [Study of the profile of gene expression in the endometrium] A1 - Smith, SK J1 - J Gynecol Obstet Biol Reprod (Paris) Y1 - 2004/10// VL - 33 SN - 0368-2315 SP - 3S15 EP - 8S15 N2 - Implantation in humans is a complex process that is temporally and spatially restricted. Over the past decade, using a one-by-one approach, several genes and gene products that may participate in this process have been identified in secretory phase endometrium. In order to understand this critical aspect of endometrial physiology, Smith group undertook a genome-wide analysis of transcript abundance and changes in transcript level between normal endometrium in the proliferative and secretory phases of the menstrual cycle, between normal and ectopic endometrium (endometriosis) and between normal and RU486-exposed endometrium. A high-density, oligonucleotide gene array was used to define the gene expression profiles of endometrium. Results from the arrays were verified using real-time PCR. Several gene products, known to be differentially expressed in the implantation window or in secretory endometrium, were identified. High density oligonucleotide microarray technology is a valid technique to investigate global changes in gene expression in human endometrium. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15643679&query_hl=1 ER - TY - JFULL T1 - Adrenocortical tumorigenesis in transgenic mice expressing the inhibin alpha-subunit promoter/simian virus 40 T-antigen transgene: relationship between ectopic expression of luteinizing hormone receptor and transcription factor GATA-4. A1 - Rahman, NA A1 - Kiiveri, S A1 - Rivero-Müller, A A1 - Levallet, J A1 - Vierre, S A1 - Kero, J A1 - Wilson, DB A1 - Heikinheimo, M A1 - Huhtaniemi, I J1 - Mol Endocrinol Y1 - 2004/10// VL - 18 SN - 0888-8809 SP - 2553 EP - 2569 N2 - We have analyzed the ontogeny and putative mechanisms of transregulation of LH receptor (LHR) and transcription factor GATA-4, coexpressed during the adrenocortical tumorigenesis of prepubertally gonadectomized transgenic (TG) mice expressing the inhibin alpha-subunit promoter/simian virus 40 T-antigen (inhalpha/Tag) transgene. The onset of adrenal LHR mRNA and protein expression coincided with that of GATA-4 at the age of 4 months and preceded the appearance of discernible adrenal tumors at about 6 months. In situ hybridization and double-immunohistochemistry demonstrated colocalization of the LHR and GATA-4 messages and proteins in the adrenal cortex. A GATA-4 expression plasmid cotransfected with a murine LHR promoter-driven luciferase reporter plasmid, containing a consensus GATA-binding site, induced a dose-dependent significant transactivation of the LHR promoter in nonsteroidogenic human embryonic kidney 293, steroidogenic murine mLTC-1 Leydig cells and in murine adrenal Y-1 cells. The Calpha1 cells derived from an Inhalpha/Tag adrenal tumor did not show this response, apparently due to their high endogenous GATA-4 expression. However, an additional link between GATA-4 and LHR in Calpha1 cells was provided upon the LH/human chorionic gonadotropin stimulation of LHR promoter activity; mutations or deletion of the consensus GATA-4 binding site of the LHR promoter abolished this transactivation. EMSAs further proved GATA-4 binding to the putative consensus GATA recognition site. Our results demonstrate direct interrelationship between LHR and GATA-4 expression during adrenocortical tumorigenesis of the inhalpha/Tag mice. There is apparently a positive and reciprocal feed-forward amplification link between LHR and GATA-4 expression. This mechanism gradually and in synergy with Tag expression leads to formation of the LH-dependent adrenocortical tumors. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15256532&query_hl=1 ER - TY - JFULL T1 - Assessment of cell-mediated immunity in patients with chronic hepatitis C infection: Initial experience with 103 patients at Johns Hopkins Hospital. A1 - Rai, R A1 - Jing, T A1 - Dunbar, K A1 - Post, D A1 - Kowalski, R J1 - HEPATOLOGY Y1 - 2004/10// VL - 40 SN - 0270-9139 SP - 684A EP - 684A ER - TY - JFULL T1 - Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats. A1 - Shetty, G A1 - Weng, CC A1 - Bolden-Tiller, OU A1 - Huhtaniemi, I A1 - Handelsman, DJ A1 - Meistrich, ML J1 - Endocrinology Y1 - 2004/10// VL - 145 SN - 0013-7227 SP - 4461 EP - 4469 N2 - Suppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3-7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2-4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA's function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15205377&query_hl=1 ER - TY - JFULL T1 - Soluble factors from human endometrium promote angiogenesis and regulate the endothelial cell transcriptome. A1 - Print, C A1 - Valtola, R A1 - Evans, A A1 - Lessan, K A1 - Malik, S A1 - Smith, S J1 - Hum Reprod Y1 - 2004/10// VL - 19 SN - 0268-1161 SP - 2356 EP - 2366 N2 - BACKGROUND: Angiogenesis and vascular remodeling play critical roles in the cyclical growth and regression of endometrium. They also appear to play roles in the pathogenesis of endometriosis. METHODS AND RESULTS: Supernatants were collected from cultured endometrium isolated from women with and without endometriosis. These supernatants induced endothelial cell proliferation and angiogenesis in vitro. They contained vascular endothelial growth factor (VEGF)-A, and their proliferative effects on endothelial cells were partially abrogated by a blocking anti-VEGF-A antibody. Gene array analysis showed that culture supernatants from proliferative phase endometrium, and to a lesser extent secretory phase endometrium, induced significant changes in the transcriptome of endothelial cells. We could not detect any association between endometriosis and the ability of endometrial-derived soluble factors to promote angiogenesis or to regulate the endothelial transcriptome. In addition, we could not detect any association between endometriosis and the concentration of VEGF-A in supernatants from cultured endometrium or in menstrual effluent. CONCLUSIONS: We have shown that endometrium cultured in vitro produced soluble factors, including VEGF-A, that promoted angiogenesis. Proliferative phase endometrium promoted significant endothelial cell transcriptome changes that appear overall to be pro-angiogenic. These transcriptome changes provide insight into the dynamic control of vessel structure on which both eutopic endometrium and endometriotic lesions depend. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15242995&query_hl=1 ER - TY - JFULL T1 - Absence of the genetic variant Val79Met in human chorionic gonadotropin-beta gene 5 in five European populations. A1 - Jiang, M A1 - Savontaus, ML A1 - Simonsen, H A1 - Williamson, C A1 - Müllenbach, R A1 - Gromoll, J A1 - Terwort, N A1 - Alevizaki, M A1 - Huhtaniemi, I J1 - Mol Hum Reprod Y1 - 2004/10// VL - 10 SN - 1360-9947 SP - 763 EP - 766 N2 - Chorionic gonadotropin (CG) is an essential signal in establishment and maintenance of pregnancy in humans and higher primates. A G-to-A transition in exon 3 of human CGbeta gene 5, changing the naturally occurring valine residue to methionine in codon 79 (Val(79)Met) has been reported at carrier frequency 4.2% in a random population from the Midwest of the United States. The biological activity of the variant hCG was similar to that of wild-type (WT) hCG. However, the Val(79)Met beta-subunit displayed impaired ability to assemble with alpha-subunit, and the amount of hCG alpha/beta heterodimers formed and secreted by transfected cells was seriously impaired in the previous study. Because of these functional implications we found it important to study the occurrence of the Val(79)Met hCGbeta variant in other populations. By using a PCR-RFLP method, a search for the Val(79)Met hCGbeta variant was carried out on a total of 580 DNA samples from five European populations (Finland, Denmark, Greece, Germany and the UK). The results demonstrated an absence of the polymorphism in these populations. Hence, the naturally occurring variant (Val(79)Met) of the hCGbeta gene 5, found previously at high frequency in the US, is clearly less common, or absent, in the European populations studied. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15299093&query_hl=1 ER - TY - JFULL T1 - Wild-type p53 protein is up-regulated upon cyclic adenosine monophosphate-induced differentiation of human endometrial stromal cells. A1 - Pohnke, Y A1 - Schneider-Merck, T A1 - Fahnenstich, J A1 - Kempf, R A1 - Christian, M A1 - Milde-Langosch, K A1 - Brosens, JJ A1 - Gellersen, B J1 - J Clin Endocrinol Metab Y1 - 2004/10// VL - 89 SN - 0021-972X SP - 5233 EP - 5244 N2 - Decidualization of the endometrial stromal compartment is critical for embryo implantation. Initiation of this differentiation process requires elevated intracellular cAMP levels. We now report a massive and sustained up-regulation of p53 tumor suppressor protein during cAMP-induced decidualization of cultured endometrial stromal cells. Nuclear accumulation of p53 was not accompanied by increased mRNA expression, suggesting stabilization of the protein as the underlying mechanism. Proteasomal degradation of p53 is known to be mediated by nuclear Mdm2. Nuclear translocation of Mdm2, in turn, is dependent on phosphorylation by protein kinase B/Akt (PKB/Akt). In cAMP-treated decidualized cells, p53 accumulation was associated with decreased nuclear Mdm2 and cytoplasmic PKB/Akt levels. Conversely, withdrawal of the decidualization stimulus resulted in morphological and biochemical dedifferentiation, disappearance of p53, but increased abundance of PKB/Akt. Furthermore, Western blot and immunohistochemical analyses of endometrial biopsies confirmed that p53 is expressed in vivo in the stromal compartment during the late secretory phase of the cycle. The observation that p53 protein expression is closely associated with decidual transformation indicates a novel role for this tumor suppressor in regulating human endometrial function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15472230&query_hl=1 ER - TY - JFULL T1 - Identification of genes regulated by leukemia-inhibitory factor in the mouse uterus at the time of implantation. A1 - Sherwin, JR A1 - Freeman, TC A1 - Stephens, RJ A1 - Kimber, S A1 - Smith, AG A1 - Chambers, I A1 - Smith, SK A1 - Sharkey, AM J1 - Mol Endocrinol Y1 - 2004/09// VL - 18 SN - 0888-8809 SP - 2185 EP - 2195 N2 - The endometrium is prepared for implantation by the actions of estradiol (E2) and progesterone (P4). In mice the luminal epithelium (LE) only becomes fully receptive to the attaching blastocyst in response to the nidatory estrogen surge on d 4 of pregnancy. The cytokine leukemia-inhibitory factor (LIF) is rapidly induced by nidatory estrogen and has been shown to be the primary mediator of its action. Implantation fails in the absence of LIF, and injection of LIF on d 4 of pregnancy can substitute for the nidatory estrogen. In this study, we sought to identify genes regulated by LIF in the uterine epithelium. We used oligonucleotide microarrays to compare the transcript profiles of paired uterine horns from LIF-deficient MF1 mice after intraluminal injection of LIF or PBS on d 4 of pseudopregnancy. IGF-binding protein 3 was identified as a gene up-regulated by LIF; this was confirmed by RT-PCR. In situ hybridization showed that the primary site of IGF-binding protein 3 expression is the luminal epithelium (LE), the known site of LIF action in the uterus. We identified two other genes: amphiregulin and immune response gene-1, the expression of which were also up-regulated by LIF. Immune response gene 1 has recently been shown to be essential for implantation. Expression of all three of these genes in the LE is known to be regulated by P4. The expression of osteoblast-specific factor 2 and leukocyte 12/15 lipoxygenase, which are also expressed in LE under the control of P4, were not increased by LIF. This suggests that one of the actions of LIF on LE may be to enhance the expression of a subset of P4-regulated genes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15178747&query_hl=1 ER - TY - JFULL T1 - Activation of intracellular signalling pathways in response to mechanical stretch of human myometrium A1 - Sooranna, SR A1 - Bennett, PR A1 - Johnson, MR J1 - PLACENTA Y1 - 2004/09// VL - 25 SN - 0143-4004 SP - A16 EP - A16 ER - TY - JFULL T1 - Switching on kinases: oncogenic activation of BRAF and the PDGFR family. A1 - Dibb, NJ A1 - Dilworth, SM A1 - Mol, CD J1 - Nat Rev Cancer Y1 - 2004/09// VL - 4 SN - 1474-175X SP - 718 EP - 727 N2 - The cytoplasmic serine/threonine kinase BRAF and receptor tyrosine kinases of the platelet-derived growth factor receptor (PDGFR) family are frequently activated in cancer by mutations of an equivalent amino acid. Structural studies have provided important insights into why these very different kinases share similar oncogenic hot spots and why the PDGFR juxtamembrane region is also a frequent oncogenic target. This research has implications for other kinases that are mutated in human tumours and for the treatment of cancer using kinase inhibitors. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15343278&query_hl=1 ER - TY - JFULL T1 - Expression of prostanoid receptors in human myometrium A1 - Sooranna, SR A1 - Sun, K A1 - Myatt, L A1 - Bennett, PR A1 - Johnson, MR J1 - PLACENTA Y1 - 2004/09// VL - 25 SN - 0143-4004 SP - A16 EP - A16 ER - TY - JFULL T1 - Antenatal maternal anxiety is linked with atypical handedness in the child. A1 - Glover, V A1 - O'Connor, TG A1 - Heron, J A1 - Golding, J A1 - ALSPAC Study team J1 - Early Hum Dev Y1 - 2004/09// VL - 79 SN - 0378-3782 SP - 107 EP - 118 N2 - BACKGROUND: Animal studies have shown that prenatal stress is linked with altered laterality in the offspring. AIMS: The aim of this study was to test the hypothesis that antenatal maternal anxiety was associated with altered lateralisation in children, as demonstrated by mixed handedness. STUDY DESIGN AND SUBJECTS: We used the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective longitudinal study that has followed women since pregnancy. The final analysis included data on 7431 mother-child pairs. Maternal anxiety was measured at 18- and 32-week gestation and 8 weeks postnatally using a self-report inventory. Child handedness was assessed at 42 months using an established maternal report scale. Information on maternal and paternal handedness, as well as data on possible confounding variables such as obstetric and antenatal risks, were also assessed. RESULTS: Univariable analysis showed that antenatal anxiety at 18 weeks was associated with mixed-handedness in the child, OR=1.28 (95% CI 1.09-1.50, p<0.01). Although boys were more likely than girls to be mixed handed, the link with antenatal anxiety was similar. There was no significant association with antenatal anxiety at 32 weeks. Multivariable analyses indicated that maternal anxiety at 18 weeks of pregnancy predicted an increased likelihood of mixed-handedness in the child (OR=1.23, 95% CI 1.02-1.48, p<0.05), independently of parental handedness, obstetric and other antenatal risks, and postnatal anxiety. CONCLUSION: This result provides further evidence for a link between antenatal anxiety and fetal programming in humans. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15324991&query_hl=1 ER - TY - JFULL T1 - Thrombocythemia and hemoperitoneum after transvaginal oocyte retrieval for in vitro fertilization. A1 - El-Shawarby, SA A1 - Margara, RA A1 - Trew, GH A1 - Laffan, MA A1 - Lavery, SA J1 - Fertil Steril Y1 - 2004/09// VL - 82 SN - 0015-0282 SP - 735 EP - 737 N2 - OBJECTIVE: To present the first report of massive hemoperitoneum in a case of essential thrombocythemia after transvaginal oocyte retrieval for IVF and review the relevant literature related to the management of patients with this condition. DESIGN: Case report. SETTING: Assisted conception unit of a tertiary care university hospital in the United Kingdom. PATIENT(S): A 37-year-old woman with essential thrombocythemia who developed massive intra-abdominal bleeding after transvaginal oocyte retrieval for IVF. INTERVENTION(S): Emergency laparotomy and right salpingoophorectomy. RESULT(S): Resuscitation of the patient. MAIN OUTCOME MEASURE(S): Overall management of the patient is discussed. CONCLUSION(S): The management of patients with essential thrombocythemia at the childbearing period poses a difficult problem. Fertility may be reduced, and an adverse outcome of pregnancy due to thrombotic or bleeding complications is a matter of concern. A multidisciplinary approach with close and early cooperation with the hematologists before initiation of IVF therapy for patients with essential thrombocythemia is essential. Efforts should be made to reduce the platelet count and assess the platelet function before embarking on IVF, keeping in mind the double jeopardy from bleeding and thrombosis in these cases. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15374723&query_hl=1 ER - TY - JFULL T1 - Identification of genes regulated by leukaemia inhibitory factor in the mouse uterus at the time of implantation. A1 - Sherwin, JR A1 - Smith, SK A1 - Sharkey, AM J1 - FERTIL STERIL Y1 - 2004/09// VL - 82 SN - 0015-0282 SP - S271 EP - S271 ER - TY - JFULL T1 - Pseudo-arterio-arterial anastomoses in twin-twin transfusion syndrome. A1 - Taylor, MJ A1 - Talbert, D A1 - Fisk, NM J1 - Placenta Y1 - 2004/09// VL - 25 SN - 0143-4004 N2 - OBJECTIVE: It has recently been claimed that fetoscopic recognition of a haemodynamic equator within an arterio-arterial anastomosis (AAA) suggests minimal net intertwin flow. This was based on blood from one fetus being dark and from the other bright red, the boundary between them reciprocating with the fetal heart beats. However, bright red indicates that the blood had passed through a cotyledon and been freshly oxygenated, which should be impossible in an AAA. We applied a computer model of chorionic vessels to determine a configuration that reproduced this phenomenon. METHODS: A previously published TTTS model was extended to provide placental detail in a segment containing four cotyledons of each placenta supplied by three generations of placental arteries and veins. RESULTS: Reciprocating flow is not unique to AAAs. It also occurs in the chorionic arteries of any cotyledon deprived of its venous outflow, in a similar manner to that in which reverse end-diastolic flow occurs in umbilical arteries when whole placental resistance is high. If venous return from the common chorionic vein in the recipient (draining the venous end of an AVA) is blocked as might happen after laser, there can be bidirectional flow from one umbilical artery insertion, through two cotyledons to the other insertion. We define this phenomenon as a pseudo-AAA (PAAA). The inclusion of two cotyledons in this path means that its resistance cannot match the low flow resistance of a true AAA, and transmission of the contralateral pulsatile pattern is absorbed in the cotyledons. Thus, PAAA Doppler patterns differ from true AAA patterns in that two sets of systolic peaks, one forward and one reverse, can be discerned in true AAAs but only one in PAAAs. CONCLUSIONS: We demonstrate how venous occlusion of an arterio-venous anastomosis may produce a pseudo-AAA colour equator at endoscopy. However, visual observation of reciprocating flow is not sufficient to define a vessel as a true AAA which instead requires ultrasonical identification of two systolic patterns. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15450393&query_hl=1 ER - TY - JFULL T1 - Human fetal mesenchymal stem cells for intrauterine cellular therapy A1 - Chan, J A1 - O'Donoghue, K A1 - Kennea, N A1 - de la Fuente, J A1 - Waddington, S A1 - Themis, M A1 - Mehmet, H A1 - Watt, D A1 - Morgan, J A1 - Fisk, N J1 - J GENE MED Y1 - 2004/09// VL - 6 SN - 1099-498X SP - S17 EP - S17 ER - TY - JFULL T1 - Re: Intra-amniotic Doppler measurement of blood flow in placental vascular anastomoses in twin-twin transfusion syndrome. A1 - Taylor, MJ A1 - Wee, LY A1 - Denbow, ML A1 - Fisk, NM J1 - Ultrasound Obstet Gynecol Y1 - 2004/09// VL - 24 SN - 0960-7692 SP - 479; author reply 479 EP - 481; author reply 481 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15343610&query_hl=1 ER - TY - JFULL T1 - Independent component analysis of microarray data in the study of endometrial cancer. A1 - Saidi, SA A1 - Holland, CM A1 - Kreil, DP A1 - MacKay, DJ A1 - Charnock-Jones, DS A1 - Print, CG A1 - Smith, SK J1 - Oncogene Y1 - 2004/08/26/ VL - 23 SN - 0950-9232 SP - 6677 EP - 6683 N2 - Gene microarray technology is highly effective in screening for differential gene expression and has hence become a popular tool in the molecular investigation of cancer. When applied to tumours, molecular characteristics may be correlated with clinical features such as response to chemotherapy. Exploitation of the huge amount of data generated by microarrays is difficult, however, and constitutes a major challenge in the advancement of this methodology. Independent component analysis (ICA), a modern statistical method, allows us to better understand data in such complex and noisy measurement environments. The technique has the potential to significantly increase the quality of the resulting data and improve the biological validity of subsequent analysis. We performed microarray experiments on 31 postmenopausal endometrial biopsies, comprising 11 benign and 20 malignant samples. We compared ICA to the established methods of principal component analysis (PCA), Cyber-T, and SAM. We show that ICA generated patterns that clearly characterized the malignant samples studied, in contrast to PCA. Moreover, ICA improved the biological validity of the genes identified as differentially expressed in endometrial carcinoma, compared to those found by Cyber-T and SAM. In particular, several genes involved in lipid metabolism that are differentially expressed in endometrial carcinoma were only found using this method. This report highlights the potential of ICA in the analysis of microarray data. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15247901&query_hl=1 ER - TY - JFULL T1 - Glycodiversification and new drug development. A1 - Chang, CWT A1 - Wang, JH A1 - Li, J A1 - Rai, R A1 - Chang, HW A1 - Wennergren, J A1 - Czyryca, PG J1 - ABSTR PAP AM CHEM S Y1 - 2004/08/22/ VL - 228 SP - U220 EP - U220 ER - TY - JFULL T1 - Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. A1 - Thornton, JG A1 - Hornbuckle, J A1 - Vail, A A1 - Spiegelhalter, DJ A1 - Levene, M A1 - GRIT study group J1 - Lancet Y1 - 2004/08/07/ VL - 364 SN - 1474-547X SP - 513 EP - 520 N2 - BACKGROUND: Although delivery is widely used for preterm babies failing to thrive in utero, the effect of altering delivery timing has never been assessed in a randomised controlled trial. We aimed to compare the effect of delivering early with delaying birth for as long as possible. METHODS: 548 pregnant women were recruited by 69 hospitals in 13 European countries. Participants had fetal compromise between 24 and 36 weeks, an umbilical-artery doppler waveform recorded, and clinical uncertainty about whether immediate delivery was indicated. Before birth, 588 babies were randomly assigned to immediate delivery (n=296) or delayed delivery until the obstetrician was no longer uncertain (n=292). The main outcome was death or disability at or beyond 2 years of age. Disability was defined as a Griffiths developmental quotient of 70 or less or the presence of motor or perceptual severe disability. Analysis was by intention-to-treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN41358726. FINDINGS: Primary outcomes were available on 290 (98%) immediate and 283 (97%) deferred deliveries. Overall rate of death or severe disability at 2 years was 55 (19%) of 290 immediate births, and 44 (16%) of 283 delayed births. With adjustment for gestational age and umbilical-artery doppler category, the odds ratio (95% CrI) was 1.1 (0.7-1.8). Most of the observed difference was in disability in babies younger than 31 weeks of gestation at randomisation: 14 (13%) immediate versus five (5%) delayed deliveries. No important differences in the median Griffiths developmental quotient in survivors was seen. INTERPRETATION: The lack of difference in mortality suggests that obstetricians are delivering sick preterm babies at about the correct moment to minimise mortality. However, they could be delivering too early to minimise brain damage. These results do not lend support to the idea that obstetricians can deliver before terminal hypoxaemia to improve brain development. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15302194&query_hl=1 ER - TY - JFULL T1 - Transcriptome analysis of endometrial cancer identifies peroxisome proliferator-activated receptors as potential therapeutic targets. A1 - Holland, CM A1 - Saidi, SA A1 - Evans, AL A1 - Sharkey, AM A1 - Latimer, JA A1 - Crawford, RA A1 - Charnock-Jones, DS A1 - Print, CG A1 - Smith, SK J1 - Mol Cancer Ther Y1 - 2004/08// VL - 3 SN - 1535-7163 SP - 993 EP - 1001 N2 - Endometrial cancer is the most common gynecologic malignancy, frequently arising in association with obesity and diabetes mellitus. To identify gene pathways contributing to endometrial cancer development, we studied the transcriptome of 20 endometrial cancers and 11 benign endometrial tissues using cDNA microarrays. Among the transcript changes identified in endometrial cancer were up-regulation of the nuclear hormone receptors peroxisome proliferator-activated receptors (PPAR) alpha and gamma, whereas retinoid X receptor beta was down-regulated. To clarify the contribution of PPARalpha to endometrial carcinogenesis, we did experiments on cultured endometrial carcinoma cells expressing this transcript. Treatment with fenofibrate, an activating ligand for PPARalpha, significantly reduced proliferation and increased cell death, suggesting that altered expression of nuclear hormone receptors involved with fatty acid metabolism leads to deregulated cellular proliferation and apoptosis. These results support further investigation of members of the PPAR/retinoid X receptor pathway as novel therapeutic targets in endometrial cancer. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15299082&query_hl=1 ER - TY - JFULL T1 - Antenatal stress and anxiety and child behavioural problems: links and mechanisms A1 - Glover, V J1 - J REPROD INFANT PSYC Y1 - 2004/08// VL - 22 SP - 229 EP - 229 ER - TY - JFULL T1 - Comparison of the arrhythmogenic effects of tauro- and glycoconjugates of cholic acid in an in vitro study of rat cardiomyocytes. A1 - Gorelik, J A1 - Shevchuk, A A1 - de Swiet, M A1 - Lab, M A1 - Korchev, Y A1 - Williamson, C J1 - BJOG Y1 - 2004/08// VL - 111 SN - 1470-0328 SP - 867 EP - 870 N2 - Obstetric cholestasis is associated with intrauterine death. In obstetric cholestasis, primary bile acids are more commonly conjugated with taurine than glycine, while glycoconjugates predominate in normal pregnancy. Using an in vitro model of rat cardiomyocytes, we compared the effect of tauro- and glycoconjugated cholate on cardiomyocyte rhythm, contraction amplitude and network integrity. We demonstrated that taurocholate had a more marked effect on all of these parameters, and the effects of the glycoconjugates were fully reversible while those of tauroconjugates were not. The increased proportion of tauroconjugated bile acids in obstetric cholestasis may contribute to the aetiology of the intrauterine death associated with the condition. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15270939&query_hl=1 ER - TY - JFULL T1 - Convergence of interferon-gamma and progesterone signaling pathways in human endometrium: role of PIASy (protein inhibitor of activated signal transducer and activator of transcription-y). A1 - Zoumpoulidou, G A1 - Jones, MC A1 - Fernandez de Mattos, S A1 - Francis, JM A1 - Fusi, L A1 - Lee, YS A1 - Christian, M A1 - Varshochi, R A1 - Lam, EW A1 - Brosens, JJ J1 - Mol Endocrinol Y1 - 2004/08// VL - 18 SN - 0888-8809 SP - 1988 EP - 1999 N2 - All cardinal events during the reproductive cycle, including ovulation, implantation, and menstruation, are characterized by a profound tissue remodeling and an associated local inflammatory response. The ovarian hormone progesterone is a key modulator of inflammatory signals in reproductive tissues, but the underlying mechanisms are not well understood. In this study, we report that differentiating human endometrial stromal cells (ESCs) acquire resistance to interferon-gamma (IFNgamma)-dependent signal transducers and activators of transcription (STAT) 1 signaling, although phosphorylation, nuclear translocation, and binding of STAT1 to DNA, are unaffected. These observations prompted an investigation into the role of nuclear repressors of STAT1 signaling. We demonstrate that protein inhibitor of activated STAT-y is complexed to the progesterone receptor (PR) in human ESCs and that its ability to repress STAT1 signaling is dependent upon activation of PR in response to hormone binding. Conversely, IFNgamma and protein inhibitor of activated STAT-y synergistically inhibited PR-dependent transcription, demonstrating that the progesterone and IFNgamma signaling pathways engage in reciprocal transcriptional antagonism in human endometrium. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15155784&query_hl=1 ER - TY - JFULL T1 - Derivation of rate of arterio-arterial anastomotic transfusion between monochorionic twin fetuses by Doppler waveform analysis. A1 - Denbow, ML A1 - Taylor, M A1 - Cox, P A1 - Fisk, NM J1 - Placenta Y1 - 2004/08// VL - 25 SN - 0143-4004 SP - 664 EP - 670 N2 - We aimed to determine rates of interfetal transfusion along arterio-arterial (AA) anastomoses in monochorionic twins in vivo from analysis of Doppler waveform patterns. Twenty-one monochorionic twin pregnancies in which an AA anastomosis was identified antenatally underwent serial Doppler velocimetry. Unidirectional AA anastomotic flow rates increased with increasing gestational age (log y = 8 x 10(-9)x - 5 x 10(-8); p = 0.0002). The mean net rate of flow through an AA anastomosis at 28 weeks gestation was 7.6 x 10(-8) l/s (SD = 4.9 x 10(-8) l/s). This flow was significantly related to the distribution of arterio-venous (AV) anastomoses (p = 0.009) and birthweight discordancy (p = 0.006). We derived estimates of flow along individual AV anastomoses by assuming that net AA countertransfusion is shared equally among uncompensated AV anastomoses, and speculate that the median AV flow rate at 28 weeks is in the order of 6 x 10(-8) l/s. In conclusion, this study demonstrates that flow rates along AA anastomoses can be quantified antenatally. These are the first estimates of flow rates in vivo along placental anastomoses. Although AA net flows are modest, chronic unbalanced counterflow of this magnitude in the absence of compensatory superficial anastomoses could lead to significant haemodynamic compromise. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15193874&query_hl=1 ER - TY - JFULL T1 - Management of other complications specific to monochorionic twin pregnancies. A1 - Pasquini, L A1 - Wimalasundera, RC A1 - Fisk, NM J1 - Best Pract Res Clin Obstet Gynaecol Y1 - 2004/08// VL - 18 SN - 1521-6934 SP - 577 EP - 599 N2 - Monochorionic (MC) twins have a 3-10-fold higher perinatal mortality and morbidity than dichorionic twins. This is largely attributable to their common vascular architecture and the high rate of discordant fetal growth, growth restriction and congenital abnormalities. In the event of a single intrauterine death (IUD), intertwin agonal transfusion results in up to a 38% risk of death and a 46% risk of neurological injury to the co-twin. This chapter addresses the management of complications unique to MC twins. The primary aim of management is to prevent single IUD or, if inevitable, prevent agonal transfusion occurring by vascular occlusive selective feticide. Older fetoscopic techniques have been replaced by the simpler ultrasound-guided techniques of interstitial laser and bipolar cord occlusion. Their application in twin reversed-arterial perfusion sequence has been associated with a 50% reduction of perinatal mortality in the pump twin. Moreover, prophylactic interstitial laser therapy in early pregnancy might obviate the technical and clinical difficulties in the presence of fetal decompensation in later pregnancy. Recent strategies to reduce the high perinatal mortality due to cord entanglement in antenatally diagnosed monoamniotic twins including medical amnioreduction and elective caesarean delivery at 32 weeks, are also discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15279818&query_hl=1 ER - TY - JFULL T1 - Blood and urine proteomic profiles of BK virus associated nephropathy (BKVAN) in renal transplantation. A1 - Vats, AN A1 - Randhawa, PS A1 - Singla, I A1 - Rai, R A1 - Dhar, CP A1 - Shapiro, R J1 - AM J TRANSPLANT Y1 - 2004/08// VL - 4 SN - 1600-6135 SP - 200 EP - 200 ER - TY - JFULL T1 - Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. A1 - O'Donoghue, K A1 - Chan, J A1 - de la Fuente, J A1 - Kennea, N A1 - Sandison, A A1 - Anderson, JR A1 - Roberts, IA A1 - Fisk, NM J1 - Lancet Y1 - 2004/07/10/ VL - 364 SN - 1474-547X SP - 179 EP - 182 N2 - Fetal cells enter maternal blood during pregnancy and persist in women with autoimmune disease. The frequency of subsequent fetomaternal microchimerism in healthy women and its cell type is unknown. To test the hypothesis that fetal mesenchymal stem cells persist in maternal organs, we studied female bone marrow and ribs. Male cells were identified by XY fluorescence in-situ hybridisation in marrow-derived mesenchymal stem cells and in rib sections from all women with male pregnancies, but not in controls (9/9 vs 0/5, p=0.0005). We conclude that fetal stem cells transferred into maternal blood engraft in marrow, where they remain throughout life. This finding has implications for normal pregnancy, for obstetric complications that increase fetomaternal trafficking, and for graft survival after transplantation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15246731&query_hl=1 ER - TY - JFULL T1 - Twin-twin transfusion--as good as it gets? A1 - Fisk, NM A1 - Galea, P J1 - N Engl J Med Y1 - 2004/07/08/ VL - 351 SN - 1533-4406 SP - 182 EP - 184 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15238623&query_hl=1 ER - TY - JFULL T1 - Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. A1 - Williamson, C A1 - Hems, LM A1 - Goulis, DG A1 - Walker, I A1 - Chambers, J A1 - Donaldson, O A1 - Swiet, M A1 - Johnston, DG J1 - BJOG Y1 - 2004/07// VL - 111 SN - 1470-0328 SP - 676 EP - 681 N2 - OBJECTIVE: To explore the clinical features of obstetric cholestasis pregnancies in UK white Caucasians. DESIGN: A questionnaire survey. SETTING: Study coordinated at Queen Charlotte's Hospital. POPULATION: Clinical features of 352 affected pregnancies in 227 Caucasian women identified via a patient support group. METHODS: Evaluation of the gestation at which prematurity and intrauterine death occur, and recording of additional clinical features in pregnancies complicated by obstetric cholestasis. MAIN OUTCOME MEASURES: The timing of pregnancies complicated by intrauterine death and prematurity. RESULTS: Among the affected pregnancies, 23 (7%) were complicated by intrauterine death (20 singletons and 3 twins) and 133 (38%) were delivered prematurely (56 spontaneous and 77 iatrogenic). Eighteen of the 20 singleton intrauterine deaths occurred after 37 weeks. All three intrauterine deaths in twin pregnancies occurred before 37 weeks. Pruritus started earlier in pregnancies complicated by spontaneous prematurity, but not in those complicated by intrauterine death. CONCLUSIONS: Intrauterine death in singleton pregnancies complicated by obstetric cholestasis death mainly occurs after 37 weeks. The gestation at which pruritus is first reported may help to predict spontaneous prematurity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15198757&query_hl=1 ER - TY - JFULL T1 - Influence of mutations affecting gonadotropin production or responsiveness on expression of inhibin subunit mRNA and protein in the mouse ovary. A1 - Hirst, RC A1 - Abel, MH A1 - Wilkins, V A1 - Simpson, C A1 - Knight, PG A1 - Zhang, FP A1 - Huhtaniemi, I A1 - Kumar, TR A1 - Charlton, HM J1 - Reproduction Y1 - 2004/07// VL - 128 SN - 1470-1626 SP - 43 EP - 52 N2 - Measurement of inhibins A and B in the serum of normal cyclic rodents has implicated FSH in the regulation of these peptides within the ovary. To extend these observations we have used a panel of mutant mice carrying mutations which affect either the production of, or the ability to respond to, FSH and LH. As a consequence, the females are infertile and show different degrees of follicular development. The aim of this study was to measure inhibin gene transcription in the ovaries of these mutant females together with inhibin protein levels in ovaries and serum and to relate these to follicular development within the ovary. Comparison was made with a pool of normal/heterozygous females. In hpg females where lack of GnRH production results in the absence of gonadotropin synthesis, in FSHbeta knockout (FSHbetaKO) females where disruption of the gene encoding FSHbeta results in the absence of FSH production, and in FSH receptor knockout (FSHRKO) females which are unable to respond to circulating FSH, follicular development remains at the pre-antral stage in these three mutants. Only in the hpg females were common inhibin alpha subunit mRNA levels significantly lower than normal. In these three mutants, however, mRNA levels for both the betaA and betaB subunits were extremely low compared with normal mice. At the protein level, neither inhibin A nor B was detected in the serum of these three mutants; however inhibin B, albeit at very low levels, was detectable within the ovaries. These observations confirm a major role for FSH in the control of transcription of the betaA and betaB genes but suggest that the constitutive transcription of the alpha subunit is less dependent on FSH. In contrast, in LH receptor knockout (LuRKO) female mice inhibin betaA subunit mRNA levels were similar to those measured in normal/heterozygous females but levels of inhibin alpha and betaB subunit mRNAs were significantly higher than in the normal group. This was reflected in significantly higher inhibin B protein levels in ovaries and serum. An inability to respond to LH combined with high circulating levels of FSH leads to a high proportion of antral follicles in LuRKO females, with granulosa cells constituting the major cell type within the ovary. The high percentage of antral granulosa cells is likely to account for the significantly higher levels of inhibin B production in these ovaries. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15232063&query_hl=1 ER - TY - JFULL T1 - Film properties of ALD HfO2 and La2O3 gate dielectrics grown on Si with various pre-deposition treatments A1 - Triyoso, DH A1 - Hegde, RI A1 - Grant, J A1 - Fejes, P A1 - Liu, R A1 - Roan, D A1 - Ramon, M A1 - Werho, D A1 - Rai, R A1 - La, LB A1 - Baker, J A1 - Garza, C A1 - Guenther, T A1 - White, BE A1 - Tobin, PJ J1 - J VAC SCI TECHNOL B Y1 - 2004/07// VL - 22 SN - 1071-1023 SP - 2121 EP - 2127 N2 - In this article, we report film properties of HfO2 and La2O3 gate dielectrics grown on Si(100) substrate using atomic layer deposition (ALD) with various surfaces modified before film growth. The precursors used for HfO2 and La2O3 films are hafnium tetrachloride (HfCl4), lanthanum tris[bis(trimethylsilyl)amide] (C18H54N3LaSi6) and water. Pre-deposition treatments examined for HfO2 dielectric films include (1) surface nitridation using NH3, N2O, or NO, (2) substrate annealing in an oxidizing or reducing ambient, and (3) surface fluorination. These results were compared to those obtained using established approaches of growing HfO2 on an OH terminated surface produced chemically. Linear film growth was observed for the HfO2 with all pre-deposition treatments. Time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and transmission electron microscopy (TEM) analysis indicated that all pre-treatments result in good film coverage with no interaction between HfO2 and silicon at the silicon substrate. The as deposited ALD HfO2 film is mainly amorphous, continuous, and relatively smooth on all pretreated Si surface. The thickness of a thin interfacial layer varies depending on the particular pre-treatments. Similar studies were also conducted for the growth of ALD La2O3. In this case, a significant interaction between La2O3 and silicon substrate was observed on films grown directly on chemical oxide. A rough interface between La2O3 and the silicon substrate is clearly seen in XTEM results. This interaction is more significant when the film is deposited at higher temperature. The XTEM images showed that the ALD La2O3 films are mostly amorphous. Results show that independent of surface pre-treatments, interactions between La2O3 and the silicon substrate occur for the deposition conditions explored here. Electrical characterization using evaporated platinum electrodes and mercury probe of the high-k film stacks have been carried out to determine the impact of the pre-treatments on the electrical properties of the films. Results indicated that ALD HfO2 films have higher dielectric constant, lower leakage and better flatband voltage stability during post deposition annealing compared to ALD La2O3 films. These results indicate that ALD HfO2 is a more promising candidate than ALD La2O3 due to superior thermal stability in contact with silicon. (C) 2004 American Vacuum Society. ER - TY - JFULL T1 - Preconception transabdominal cervicoisthmic cerclage. A1 - Groom, KM A1 - Jones, BA A1 - Edmonds, DK A1 - Bennett, PR J1 - Am J Obstet Gynecol Y1 - 2004/07// VL - 191 SN - 0002-9378 SP - 230 EP - 234 N2 - OBJECTIVE: The purpose of this study was to report pregnancy outcome and complication rates for women with recurrent late pregnancy loss who were treated with preconception transabdominal cervicoisthmic cerclage. STUDY DESIGN: This was a case note review of 19 women at high risk for second trimester loss and early preterm delivery who were treated with preconception transabdominal cervicoisthmic cerclage at Queen Charlotte's and Chelsea Hospital from 1994 to 2003. RESULTS: Preconception transabdominal cervicoisthmic cerclage was associated with a postoperative fetal survival rate of 100% for pregnancies that reached >12 weeks of gestation, compared with a preoperative fetal survival rate of 12%. There were no significant intraoperative, antenatal, intrapartum or neonatal complications. CONCLUSION: Within this case series, preconception transabdominal cervicoisthmic cerclage was a safe alternative to transabdominal cervicoisthmic cerclage that was performed in pregnancy with no risk to a fetus. It should be considered in appropriate cases in women seen for prepregnancy counseling. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15295371&query_hl=1 ER - TY - JFULL T1 - Energy substrate metabolism of mouse cumulus-oocyte complexes: response to follicle-stimulating hormone is mediated by the phosphatidylinositol 3-kinase pathway and is associated with oocyte maturation. A1 - Roberts, R A1 - Stark, J A1 - Iatropoulou, A A1 - Becker, DL A1 - Franks, S A1 - Hardy, K J1 - Biol Reprod Y1 - 2004/07// VL - 71 SN - 0006-3363 SP - 199 EP - 209 N2 - Successful in vitro maturation (IVM) of oocytes obtained from medium-sized antral follicles could avoid the need for superovulation for in vitro fertilization. The wide range of doses of FSH used in IVM prompted us to study the effect of varying concentrations of FSH on the dynamics of nutrient uptake and production by individual maturing mouse cumulus-oocyte complexes (COCs). COCs isolated from the antral follicles of unprimed, prepubertal B6CBF(1) mice were cultured individually in increasing concentrations of FSH (0-2000 ng/ml). Following culture, pyruvate, glucose, and lactate uptake or production by individual complexes were noninvasively assessed and compared with the stage of nuclear maturation of the enclosed oocyte. FSH significantly increased oocyte maturation and produced a two- to threefold increase in glucose uptake and lactate production by COCs in which the enclosed oocyte completed maturation. In these COCs, pyruvate was taken up under control conditions but was produced in progressively higher quantities in increasing concentrations of FSH. In COCs where the oocyte failed to complete maturation, pyruvate was taken up (rather than produced) and glucose uptake and lactate production were lower and unaffected by the presence or absence of FSH. This suggests that there is dialogue between cumulus cells and the maturing oocyte that influences FSH responsiveness and substrate metabolism of the whole COC. Finally, inhibition of FSH-stimulated glucose uptake by the PI3-kinase inhibitor LY294002 and the finding of GLUT4 protein in granulosa cells suggest that FSH increases glucose uptake by PI3-kinase-mediated translocation of GLUT4 to the granulosa cell membrane. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15028625&query_hl=1 ER - TY - JFULL T1 - Nuclear receptor corepressor RIP140 regulates fat accumulation. A1 - Leonardsson, G A1 - Steel, JH A1 - Christian, M A1 - Pocock, V A1 - Milligan, S A1 - Bell, J A1 - So, PW A1 - Medina-Gomez, G A1 - Vidal-Puig, A A1 - White, R A1 - Parker, MG J1 - Proc Natl Acad Sci U S A Y1 - 2004/06/01/ VL - 101 SN - 0027-8424 SP - 8437 EP - 8442 N2 - Nuclear receptors and their coactivators have been shown to function as key regulators of adipose tissue biology. Here we show that a ligand-dependent transcriptional repressor for nuclear receptors plays a crucial role in regulating the balance between energy storage and energy expenditure. Mice devoid of the corepressor protein RIP140 are lean, show resistance to high-fat diet-induced obesity and hepatic steatosis, and have increased oxygen consumption. Although the process of adipogenesis is unaffected, expression of certain lipogenic enzymes is reduced. In contrast, genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1, are markedly increased. Therefore, the maintenance of energy homeostasis requires the action of a transcriptional repressor in white adipose tissue, and ligand-dependent recruitment of RIP140 to nuclear receptors may provide a therapeutic target in the treatment of obesity and related disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15155905&query_hl=1 ER - TY - JFULL T1 - Re: Stage-based treatment of twin-twin transfusion syndrome. A1 - Fisk, NM A1 - Tan, TY A1 - Taylor, MJ J1 - Am J Obstet Gynecol Y1 - 2004/06// VL - 190 SN - 0002-9378 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15290827&query_hl=1 ER - TY - JFULL T1 - Doppler for artery-artery anastomosis and stage-independent survival in twin-twin transfusion. A1 - Tan, TY A1 - Taylor, MJ A1 - Wee, LY A1 - Vanderheyden, T A1 - Wimalasundera, R A1 - Fisk, NM J1 - Obstet Gynecol Y1 - 2004/06// VL - 103 SN - 0029-7844 SP - 1174 EP - 1180 N2 - OBJECTIVE: Treatment selection in twin-twin transfusion syndrome is increasingly determined by disease severity. We investigated whether detection of arterio-arterial anastomoses predicts perinatal survival. METHODS: An artery-artery anastomosis was sought by Doppler and disease stage was determined in 105 cases of twin-twin transfusion syndrome at presentation, first treatment, and worst stage. Outcome measures were perinatal, double, and any (1 or more babies) survival rates. RESULTS: After exclusion of 10 noninformative pregnancies, perinatal, double, and any survival rates were 61%, 44%, and 77%, respectively. When an anastomosis was detected at each of the 3 time points, perinatal and double survival rates were higher than when one was not (at first treatment, perinatal survival 83% versus 53%, respectively, P =.003; double survival 78% versus 33%, P <.001). Perinatal and double survival (P < or =.01) were poorer with more advanced stage, but any survival rates were not influenced by stage or anastomosis detection. Multiple logistic regression demonstrated that anastomosis detection at treatment increased the chance of perinatal (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.6, 15.9) and double survival (OR 19.3, 95% CI 2.7, 138), independently of stage. For stages I-III at treatment, anastomosis detection predicted better perinatal (100% versus 63%, 100% versus 59%, and 83% versus 44%, respectively) and double survival rates (100% versus 52%, 100% versus 46%, and 78% versus 26%). Stage III, with anastomoses detected, had better perinatal (83% versus 63%) and double survival (78% versus 52%) than did stage I without detection. CONCLUSION: Antenatal detection of artery-to-artery anastomosis predicts higher perinatal and double survival in twin-twin transfusion syndrome, independently of disease stage. LEVEL OF EVIDENCE: II-3 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15172849&query_hl=1 ER - TY - JFULL T1 - Prenatal stress alters cardiovascular responses in adult rats. A1 - Igosheva, N A1 - Klimova, O A1 - Anishchenko, T A1 - Glover, V J1 - J Physiol Y1 - 2004/05/15/ VL - 557 SN - 0022-3751 SP - 273 EP - 285 N2 - Environmental factors in early life are clearly established risk factors for cardiovascular disease in later life. Most studies have focused on nutritional programming and analysed basal cardiovascular parameters rather than responses. In the present study we have investigated whether prenatal stress has long-term effects on cardiovascular responses in adult offspring. Female pregnant Sprague-Dawley rats were subjected to stress three times daily from day 15 to day 21 of gestation. Litters from stressed and control females were cross-fostered at birth to control for mothering effects. When the offspring were 6 months old, blood pressure was measured in the conscious rats through implanted catheters at rest, during restraint stress and during recovery. Basal haemodynamic parameters were similar in the different groups but the pattern of cardiovascular responses during stress and recovery differed markedly between prenatally stressed (PS) and control animals. PS rats had higher and longer-lasting systolic arterial pressure elevations to restraint stress than control animals. They also showed elevated systolic and diastolic blood pressure values during the recovery phase. PS rats demonstrated a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, and showed more prolonged heart rate responses to acute stress and delayed recovery than controls. There was no effect of prenatal stress on baroreflex regulation of heart rate. PS females showed a greater increase in systolic arterial pressure and blood pressure variability and delayed heart rate recovery following return to the home cage then did PS males. These findings demonstrate for the first time that prenatal stress can induce long-term, sex-related changes in the sensitivity of the cardiovascular system to subsequent stress. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15034122&query_hl=1 ER - TY - JFULL T1 - Stage-based treatment of twin-twin transfusion syndrome. A1 - Fisk, NM A1 - Tan, TY A1 - Taylor, MJ J1 - Am J Obstet Gynecol Y1 - 2004/05// VL - 190 SN - 0002-9378 SP - 1491 EP - 1492 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15198096&query_hl=1 ER - TY - JFULL T1 - Orexin A and B levels in the hypothalamus of female rats: the effects of the estrous cycle and age. A1 - Porkka-Heiskanen, T A1 - Kalinchuk, A A1 - Alanko, L A1 - Huhtaniemi, I A1 - Stenberg, D J1 - Eur J Endocrinol Y1 - 2004/05// VL - 150 SN - 0804-4643 SP - 737 EP - 742 N2 - OBJECTIVE: Orexins have been implicated in the regulation of several physiological functions including reproduction, energy balance and vigilance state. For successful reproduction, the precisely timed hormonal secretions of the estrous cycle must be combined with appropriate nutritional and vigilance states. The steroid- and nutritional state-dependent modulation of LH release by orexins, as well as an increase of vigilance, suggest that orexins may co-ordinate these functions in the course of the estrous cycle. DESIGN: We studied the brain tissue levels of orexins in the course of the estrous cycle in young and middle-aged rats. Young cycling rats (3 months old) and irregularly/non-cycling (7-9 months old) female rats were inspected for vaginal smears and serum hormone levels. METHODS: Tissue concentrations of orexin A and B were measured in the hypothalamus and lateral hypothalamus on different days of the estrous cycle. RESULTS: Orexin A concentration in the hypothalamus of young cycling rats was higher on the day of proestrus 5-6 h after the lights were switched on than on the other days of the estrous cycle at the same circadian time. Orexin B concentration was higher on both the day of proestrus and the day of estrus as compared with the days of diestrus. The hypothalamic concentrations of both orexin A and B in the non-cycling middle-aged rats were lower than those in cycling rats on the days of proestrus and estrus. CONCLUSIONS: We have concluded that the high hypothalamic concentration of orexins on the day of proestrus may contribute to the LH and prolactin surges. High orexin A levels may also contribute to the decreased amount of sleep on the day of proestrus. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15132733&query_hl=1 ER - TY - JFULL T1 - The course of anxiety and depression through pregnancy and the postpartum in a community sample. A1 - Heron, J A1 - O'Connor, TG A1 - Evans, J A1 - Golding, J A1 - Glover, V A1 - The ALSPAC Study Team J1 - J Affect Disord Y1 - 2004/05// VL - 80 SN - 0165-0327 SP - 65 EP - 73 N2 - BACKGROUND: Postnatal and antenatal depression are a focus of considerable clinical and research attention, but little is known about the patterns of anxiety across this period. METHODS: Self-reported anxiety and depression were assessed at 18 and 32 weeks gestation and 8 weeks and 8 months postnatally in a prospective longitudinal study of a community sample of women in England (n=8323). RESULTS: The majority of cases of postnatal depression were preceded by antenatal depression; similarly, postnatal anxiety was preceded by antenatal anxiety. Despite the stability of anxiety and depression across this period, there was a mean decrease in both anxiety and depression. Finally, antenatal anxiety predicted postnatal depression at 8 weeks and 8 months, even after controlling for antenatal depression (OR=3.22, p<0.001). Limitations: Data were based on self-report only and there was evidence of selective attrition. CONCLUSION: The findings confirm that antenatal anxiety occurs frequently, overlaps with depression and increases the likelihood of postnatal depression. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15094259&query_hl=1 ER - TY - JFULL T1 - Characterization of four autonomous repression domains in the corepressor receptor interacting protein 140. A1 - Christian, M A1 - Tullet, JM A1 - Parker, MG J1 - J Biol