FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Abu Habib, N Wilcox, AJ Daltveit, AK Basso, O Shao, J Oneko, O Lie, RT AF Abu Habib, Ndema Wilcox, Allen J. Daltveit, Anne Kjersti Basso, Olga Shao, John Oneko, Olola Lie, Rolv Terje TI Birthweight, preterm birth and perinatal mortality: a comparison of black babies in Tanzania and the USA SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE Birthweight; developing country; fetal development; perinatal mortality; preterm birth ID UNITED-STATES; RURAL TANZANIA; BELGIUM; INFANTS AB Objectives. Adverse conditions in Africa produce some of the highest rates of infant mortality in the world. Fetal growth restriction and preterm delivery are commonly regarded as major pathways through which conditions in the developing world affect infant survival. The aim of this article was to compare patterns of birthweight, preterm delivery, and perinatal mortality between black people in Tanzania and the USA. Design. Registry-based study. Settings. Referral hospital data from North Eastern Tanzania and US Vital Statistics. Sample. 14 444 singleton babies from a hospital-based registry (1999-2006) and 3 530 335 black singletons from US vital statistics (1995-2000). Main outcome measures. Birthweight, gestational age and perinatal mortality. Methods. Restricting our study to babies born at least 500g, we compared birthweight, gestational age, and perinatal mortality (stillbirths and deaths in the first week) in the two study populations. Results. Perinatal mortality in the Tanzanian sample was 41/1 000, compared with 10/1 000 among USA blacks. Tanzanian babies were slightly smaller on average (43g), but fewer were preterm (<37weeks) (10.0 vs. 16.2%). Applying the USA weight-specific mortality rates to Tanzanian babies born at term suggested that birthweight does not play a role in their increased mortality relative to USA blacks. Conclusions. Higher mortality independent of birthweight and preterm delivery for Tanzanian babies suggests the need to address the contribution of other pathways to further reduce the excess perinatal mortality. C1 [Abu Habib, Ndema] Muhimbili Univ Hlth & Allied Sci, Dept Epidemiol & Biostat, Dar Es Salaam, Tanzania. [Daltveit, Anne Kjersti; Lie, Rolv Terje] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, N-5020 Bergen, Norway. [Daltveit, Anne Kjersti; Lie, Rolv Terje] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [Wilcox, Allen J.; Basso, Olga] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Durham, NC USA. [Shao, John; Oneko, Olola] Kilimanjaro Christian Med Ctr, Dept Obstet & Gynaecol, Moshi, Tanzania. RP Abu Habib, N (reprint author), Muhimbili Univ Hlth & Allied Sci, Dept Epidemiol & Biostat, POB 65015, Dar Es Salaam, Tanzania. EM ndema_h@yahoo.com RI Basso, Olga/E-5384-2010; OI Basso, Olga/0000-0001-9298-4921; Habib, Ndema/0000-0003-4882-1687; Wilcox, Allen/0000-0002-3376-1311 FU Norwegian Council for Higher Education; NIH, National Institute of Environmental Health Sciences FX Funding for this work was provided by the Norwegian Council for Higher Education's Program for Development Research (NUFU) with funds allocated to the Centre for International Health at the University of Bergen under the Health Systems Research and Health Promotion in relation to Reproductive Health in Tanzania project, of which the Medical Birth Registry at Kilimanjaro Christian Medical Center (KCMC) is one element.; Partially supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 22 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-6349 EI 1600-0412 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD OCT PY 2011 VL 90 IS 10 BP 1100 EP 1106 DI 10.1111/j.1600-0412.2011.01195.x PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 829PC UT WOS:000295595100007 PM 21615361 ER PT J AU Andreasen, V AF Andreasen, Viggo TI The Final Size of an Epidemic and Its Relation to the Basic Reproduction Number SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article DE Heterogeneous mixing; Final size relation ID PANDEMIC INFLUENZA; TRANSMISSION DYNAMICS; MODELS; POPULATIONS; NETWORKS; DISEASE; SPREAD; SUSCEPTIBLES; OUTBREAKS; SELECTION AB We study the final size equation for an epidemic in a subdivided population with general mixing patterns among subgroups. The equation is determined by a matrix with the same spectrum as the next generation matrix and it exhibits a threshold controlled by the common dominant eigenvalue, the basic reproduction number R0: There is a unique positive solution giving the size of the epidemic if and only if R0 exceeds unity. When mixing heterogeneities arise only from variation in contact rates and proportionate mixing, the final size of the epidemic in a heterogeneously mixing population is always smaller than that in a homogeneously mixing population with the same basic reproduction number R0. For other mixing patterns, the relation may be reversed. C1 [Andreasen, Viggo] Roskilde Univ Ctr, Dept Sci, DK-4000 Roskilde, Denmark. [Andreasen, Viggo] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Andreasen, V (reprint author), Roskilde Univ Ctr, Dept Sci, DK-4000 Roskilde, Denmark. EM viggo@ruc.dk FU Danish Medical Research Council [271-07-0555]; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX This research was supported in part by a grant 271-07-0555 from the Danish Medical Research Council and by the RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. V.A. thanks Bryan Grenfell for his hospitality during this project. NR 41 TC 20 Z9 20 U1 2 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD OCT PY 2011 VL 73 IS 10 BP 2305 EP 2321 DI 10.1007/s11538-010-9623-3 PG 17 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 844WY UT WOS:000296783600003 PM 21210241 ER PT J AU Berhane, AM Weil, EJ Knowler, WC Nelson, RG Hanson, RL AF Berhane, Abeba M. Weil, E. Jennifer Knowler, William C. Nelson, Robert G. Hanson, Robert L. TI Albuminuria and Estimated Glomerular Filtration Rate as Predictors of Diabetic End-Stage Renal Disease and Death SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PIMA-INDIANS; COLLABORATIVE METAANALYSIS; POPULATION COHORTS; KIDNEY-FUNCTION; HEART-DISEASE; ESTIMATED GFR; PROTEINURIA; RISK; MORTALITY; MELLITUS AB Background and objectives We investigated predictive value of albuminuria and estimated GFR (eGFR) for ESRD in Pima Indians with type 2 diabetes. Design, setting, participants and measurements Beginning in 1982, 2420 diabetic Pima Indians >= 18 years old were followed until they developed ESRD or died or until December 31, 2005. Individuals were classified at baseline by urinary albumin-to-creatinirte ratio (ACR) and by eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Predictors of ESRD and mortality were examined by proportional hazards regression. Results During a mean follow-up of 10.2 years, 287 individuals developed ESRD. Incidence of ESRD among individuals with macroalbuminuria (ACR >= 300 mg/g) was 9.3 times that of those with normoalbuminuria (ACR < 30 mg/g), controlled for age, gender, and duration of diabetes. Incidence among individuals with eGFR 15 to 29 ml/min per 1.73 m(2) was 81.9 times that of those with eGFR 90 to 119 ml/min per 1.73 m(2). Models that combined albuminuria and eGFR added significant predictive information about risk of ESRD or death compared with models containing eGFR or albuminuria alone. The hazard ratio for ESRD associated with a 10-ml/min per 1.73 m(2) lower eGFR was 1.36, whereas that associated with an increase in albuminuria category was 2.69; corresponding hazard ratios for death were 1.15 and 1.37. Conclusions These results suggest that incorporation of quantitative information about albuminuria into staging systems based on eGFR adds significant prognostic information about risk for diabetic ESRD and death. Clin J Am Soc Nephrol 6: 2444-2451, 2011. doi: 10.2215/CJN.00580111 C1 [Berhane, Abeba M.; Weil, E. Jennifer; Knowler, William C.; Nelson, Robert G.; Hanson, Robert L.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@phx.niddk.nih.gov RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The authors thank members of the Gila River Indian Community for participating in this investigation and the staff involved in collecting and processing data. Part of this material was presented at the 69th Annual Scientific Meeting of the American Diabetes Association, June 7, 2009, New Orleans, LA. NR 26 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD OCT PY 2011 VL 6 IS 10 BP 2444 EP 2451 DI 10.2215/CJN.00580111 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 830KX UT WOS:000295657000018 PM 21852671 ER PT J AU Perrone, RD Abebe, KZ Schrier, RW Chapman, AB Torres, VE Bost, J Kaya, D Miskulin, DC Steinman, TI Braun, W Winklhofer, FT Hogan, MC Rahbari-Oskoui, F Kelleher, C Masoumi, A Glockner, J Halin, NJ Martin, D Remer, E Patel, N Pedrosa, I Wetzel, LH Thompson, PA Miller, JP Meyers, CM Bae, KT AF Perrone, Ronald D. Abebe, Kaleab Z. Schrier, Robert W. Chapman, Arlene B. Torres, Vicente E. Bost, James Kaya, Diana Miskulin, Dana C. Steinman, Theodore I. Braun, William Winklhofer, Franz T. Hogan, Marie C. Rahbari-Oskoui, Frederic Kelleher, Cass Masoumi, Amirali Glockner, James Halin, Neil J. Martin, Diego Remer, Erick Patel, Nayana Pedrosa, Ivan Wetzel, Louis H. Thompson, Paul A. Miller, J. Philip Meyers, Catherine M. Bae, K. Ty CA HALT PKD Study Grp TI Cardiac Magnetic Resonance Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GENDER-DIFFERENCES; YOUNG-ADULTS; BODY-SIZE; HYPERTROPHY; HYPERTENSION; SURVIVAL; CHILDREN; MRI; AGE AB Background and objectives Autosomal dominant polycystic kidney disease (ADPKD) is associated with a substantial cardiovascular disease burden including early onset hypertension, intracranial aneurysms, and left ventricular hypertrophy (LVH). A 41% prevalence of LVH has been reported in ADPKD, using echocardiographic assessment of LV mass (LVM). The HALT PKD study was designed to assess the effect of intensive angiotensin blockade on progression of total kidney volume and LVM. Measurements of LVM were performed using cardiac magnetic resonance (MR). Design, setting, participants, & measurements Five hundred forty-three hypertensive patients with GFR >60 ml/min per 1.73 m(2) underwent MR assessment of LVM at baseline. LVM was adjusted for body surface area and expressed as LVM index (LVMI; g/m(2)). Results Baseline BP was 125.1 +/- 14.5/79.3 +/- 11.6 mmHg. Average duration of hypertension was 5.79 years. Prior use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was present in 59.5% of patients. The prevalence of LVH assessed using nonindexed LVM (g) was 3.9% (n = 21, eight men and 13 women) and 0.93% (n = 5, one man and four women) using LVMI (g/m(2)). In exploratory analyses, the prevalence of LVH using LVM indexed to H-2.7, and the allometric index ppLVmass(HW), ranged from 0.74% to 2.23% (n = 4 to 12). Multivariate regression showed significant direct associations of LVMI with systolic BP, serum creatinine, and albuminuria; significant inverse associations with LVMI were found with age and female gender. Conclusions The prevalence of LVH in hypertensive ADPKD patients <50 years of age with short duration of hypertension, and prior use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers is low. Early BP intervention in ADPKD may have decreased LVH and may potentially decrease cardiovascular mortality. Clin J Am Soc Nephrol 6: 2508-2515, 2011. doi: 10.2215/CJN.04610511 C1 [Perrone, Ronald D.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Torres, Vicente E.; Hogan, Marie C.; Glockner, James] Mayo Clin, Coll Med, Rochester, MN USA. [Schrier, Robert W.; Patel, Nayana] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Chapman, Arlene B.; Rahbari-Oskoui, Frederic; Masoumi, Amirali; Martin, Diego] Emory Univ, Sch Med, Atlanta, GA USA. [Abebe, Kaleab Z.; Bost, James; Kaya, Diana; Bae, K. Ty] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Winklhofer, Franz T.; Wetzel, Louis H.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Braun, William; Remer, Erick] Cleveland Clin, Cleveland, OH 44106 USA. [Steinman, Theodore I.; Pedrosa, Ivan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Miller, J. Philip] Washington Univ, St Louis, MO USA. [Meyers, Catherine M.] NIDDK, NIH, Bethesda, MD USA. [Kelleher, Cass] Amgen Inc, Thousand Oaks, CA USA. [Thompson, Paul A.] Sanford Res USD Sioux Falls, Sioux Falls, SD USA. RP Perrone, RD (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Hosp Box 391, Boston, MA 02111 USA. EM rperrone@tuftsmedicalcenter.org OI Abebe, Kaleab/0000-0002-3644-8419 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [DK62408, DK62401, DK62410, DK62402, DK62411]; National Center for Research Resources [RR000039, RR000051, RR00585, RR000054, RR23940, UL1 RR025008, UL1 RR025780, UL1 RR024150, UL1 RR025752, UL1 RR024992]; Polycystic Kidney Disease Foundation FX The HALT-PKD study is supported by cooperative agreements from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (DK62408, DK62401, DK62410, DK62402, and DK62411). The HALT-PKD study and this publication were also supported by Grants from the National Center for Research Resources (RR000039 Emory, RR000051 Colorado, RR00585 Mayo, RR000054 Tufts Medical Center, and RR23940 Kansas and UL1 RR025008 Emory, UL1 RR025780 Colorado, UL1 RR024150 Mayo, UL1 RR025752 Tufts, and UL1 RR024992 Washington University). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR. Study medication for both trials was provided by Boehringer-Ingelheim Pharmaceuticals (telmisartan and matched placebo) and Merck & Co. (lisinopril). The Polycystic Kidney Disease Foundation provided financial support and recruitment assistance for the enrollment phase of HALT PKD. The investigators thank Gigi Flynn and Robin Woltman and all of the clinical coordinators at each clinical site for their perseverance and hard work in implementing HALT PKD. NR 21 TC 14 Z9 16 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD OCT PY 2011 VL 6 IS 10 BP 2508 EP 2515 DI 10.2215/CJN.04610511 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 830KX UT WOS:000295657000026 PM 21903983 ER PT J AU Hanssen-Bauer, A Solvang-Garten, K Sundheim, O Pena-Diaz, J Andersen, S Slupphaug, G Krokan, HE Wilson, DM Akbari, M Otterlei, M AF Hanssen-Bauer, Audun Solvang-Garten, Karin Sundheim, Ottar Pena-Diaz, Javier Andersen, Sonja Slupphaug, Geir Krokan, Hans E. Wilson, David M., III Akbari, Mansour Otterlei, Marit TI XRCC1 Coordinates Disparate Responses and Multiprotein Repair Complexes Depending on the Nature and Context of the DNA Damage SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE base excision repair; micro-irradiation; PARP inhibitors; PCNA; DNA repair complexes ID BASE EXCISION-REPAIR; STRAND BREAK REPAIR; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS; LIGASE-III; IN-VITRO; PARP INHIBITION; LIVING CELLS; PROTEIN; REPLICATION AB XRCC1 is a scaffold protein capable of interacting with several DNA repair proteins. Here we provide evidence for the presence of XRCC1 in different complexes of sizes from 200 to 1500 kDa, and we show that immunoprecipitates using XRCC1 as bait are capable of complete repair of AP sites via both short patch (SP) and long patch (LP) base excision repair (BER). We show that POL beta and PNK colocalize with XRCC1 in replication foci and that POL beta and PNK, but not PCNA, colocalize with constitutively present XRCC1-foci as well as damage-induced foci when low doses of a DNA-damaging agent are applied. We demonstrate that the laser dose used for introducing DNA damage determines the repertoire of DNA repair proteins recruited. Furthermore, we demonstrate that recruitment of POL beta and PNK to regions irradiated with low laser dose requires XRCC1 and that inhibition of PARylation by PARP-inhibitors only slightly reduces the recruitment of XRCC1, PNK, or POL beta to sites of DNA damage. Recruitment of PCNA and FEN-1 requires higher doses of irradiation and is enhanced by XRCC1, as well as by accumulation of PARP-1 at the site of DNA damage. These data improve our understanding of recruitment of BER proteins to sites of DNA damage and provide evidence for a role of XRCC1 in the organization of BER into multiprotein complexes of different sizes. Environ. Mol. Mutagen. 52:623-635, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Hanssen-Bauer, Audun; Solvang-Garten, Karin; Sundheim, Ottar; Pena-Diaz, Javier; Andersen, Sonja; Slupphaug, Geir; Krokan, Hans E.; Akbari, Mansour; Otterlei, Marit] Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, NO-7489 Trondheim, Norway. [Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Otterlei, M (reprint author), Norwegian Univ Sci & Technol, Fac Med, Dept Canc Res & Mol Med, NO-7489 Trondheim, Norway. EM marit.otterlei@ntnu.no RI Pena-Diaz, Javier/M-6232-2016; OI Pena-Diaz, Javier/0000-0002-6316-6011; Akbari, Mansour/0000-0002-6490-7766; Slupphaug, Geir/0000-0002-7498-3500 FU The Research Council of Norway; The National Programme for Research in Functional Genomics in Norway (FUGE) in The Research Council of Norway; St. Olavs. Hospital, Trondheim, Norway; The Norwegian Cancer Society; The Svanhild and Arne Must Fund for Medical Research, Norway; NIH; National Institute on Aging, USA; European Community [LSHG-CT-2005-512113] FX Grant sponsor: The Research Council of Norway; Grant sponsor: The National Programme for Research in Functional Genomics in Norway (FUGE) in The Research Council of Norway; Grant sponsor: The Cancer Fund at St. Olavs. Hospital, Trondheim, Norway; Grant sponsor: The Norwegian Cancer Society; Grant sponsor: The Svanhild and Arne Must Fund for Medical Research, Norway; Grant sponsor: The Intramural Research Program of the NIH; Grant sponsor: National Institute on Aging, USA; Grant sponsor: Integrated Project on DNA Repair Supported by European Community; Grant Number LSHG-CT-2005-512113. NR 54 TC 32 Z9 33 U1 2 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 IS 8 BP 623 EP 635 DI 10.1002/em.20663 PG 13 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 845XQ UT WOS:000296861100004 PM 21786338 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, R. J. Venditti, C. P. TI Demonstration of pre-clinical efficacy of AAV gene therapy for methylmalonic acidemia with a transgene suitable for human clinical trials SO HUMAN GENE THERAPY LA English DT Meeting Abstract C1 [Chandler, R. J.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2011 VL 22 IS 10 BP A47 EP A47 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843WS UT WOS:000296707900149 ER PT J AU Kaler, SG Donsante, A Haddad, MR AF Kaler, Stephen G. Donsante, Anthony Haddad, Marie-Reine TI AAV9 gene therapy rescues a murine model of Menkes disease SO HUMAN GENE THERAPY LA English DT Meeting Abstract C1 [Kaler, Stephen G.; Donsante, Anthony; Haddad, Marie-Reine] NICHD, Program Mol Med, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2011 VL 22 IS 10 BP A77 EP A78 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843WS UT WOS:000296707900248 ER PT J AU Leger, A Le Guiner, C Nickerson, ML Ferry, N Moullier, P Snyder, RO Penaud-Budloo, M AF Leger, A. Le Guiner, C. Nickerson, M. L. Ferry, N. Moullier, P. Snyder, R. O. Penaud-Budloo, M. TI Adeno-Associated Viral Vector DNA is insensitive to de novo CpG methylation but rapidly associated with histone modifications in liver and skeletal muscle SO HUMAN GENE THERAPY LA English DT Meeting Abstract C1 [Leger, A.; Le Guiner, C.; Moullier, P.; Snyder, R. O.; Penaud-Budloo, M.] INSERM, UMR649, Nantes, France. [Le Guiner, C.; Moullier, P.] GENETHON, Evry, France. [Nickerson, M. L.] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. [Ferry, N.] INSERM, UMR948, Nantes, France. [Moullier, P.; Snyder, R. O.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Snyder, R. O.] Univ Florida, CERHB, Alachua, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2011 VL 22 IS 10 BP A103 EP A103 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843WS UT WOS:000296707900330 ER PT J AU Lynn, G Laga, R Fisher, K Seder, R Seymour, L AF Lynn, G. Laga, R. Fisher, K. Seder, R. Seymour, L. TI Polymer conjugates of toll-like receptor ligands as vaccine adjuvants SO HUMAN GENE THERAPY LA English DT Meeting Abstract C1 [Lynn, G.; Laga, R.; Fisher, K.; Seymour, L.] Univ Oxford, Dept Oncol, Oxford OX3 7DQ, England. [Seder, R.] NIH, Dept Cellular Immunol, Vaccine Res Ctr, Bethesda, MD 20814 USA. RI Laga, Richard/G-3627-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2011 VL 22 IS 10 BP A70 EP A70 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843WS UT WOS:000296707900224 ER PT J AU Yu, DY Jin, CJ Leja, JL Majdalani, NM Nilsson, BN Eriksson, FE Essand, ME AF Yu, D. Y. Jin, C. J. Leja, J. L. Majdalani, N. M. Nilsson, B. N. Eriksson, F. E. Essand, M. E. TI Adenovirus with hexon Tat-PTD modification exhibits increased therapeutic effect in experimental neuroblastoma and neuroendocrine tumors SO HUMAN GENE THERAPY LA English DT Meeting Abstract C1 [Yu, D. Y.; Jin, C. J.; Leja, J. L.; Nilsson, B. N.; Eriksson, F. E.; Essand, M. E.] Uppsala Univ, Uppsala, Sweden. [Majdalani, N. M.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2011 VL 22 IS 10 BP A29 EP A29 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843WS UT WOS:000296707900095 ER PT J AU Katsounas, A Schlaak, JF Lempicki, RA AF Katsounas, Antonios Schlaak, Joerg F. Lempicki, Richard A. TI CCL5: A Double-Edged Sword in Host Defense Against the Hepatitis C Virus SO INTERNATIONAL REVIEWS OF IMMUNOLOGY LA English DT Review DE CCL5 (RANTES); Hepatitis C; Liver Fibrosis ID CHEMOKINE GENE-EXPRESSION; T-LYMPHOCYTE RESPONSES; STELLATE CELLS; INTERFERON-ALPHA; CYTOKINE PROFILES; IMMUNE-RESPONSES; CCR5 EXPRESSION; LIVER-DISEASE; IFN-GAMMA; SEMIQUANTITATIVE ANALYSIS AB C-C motif ligand 5 (CCL5) facilitates induction of chemotaxis in immune cells and activation of hepatic stellate cells (HSC) at sites of liver inflammation during chronic hepatitis C virus (HCV) infection. Importantly, CCL5 participates in the establishment of T-helper 1 responses crucial in controlling liver disease and HCV infection outcome and demonstrates distinct gene expression patterns between the blood and the liver, stressing the importance of immunoregulatory networks differentially functioning between these compartments. This review illustrates the significance of CCL5-dependent pathways in HCV-related immunopathogenesis by elaborating on biological mechanisms interconnecting peripheral and tissue immunology, liver pathology, HSC activation, and interferon-a immunotherapy. C1 [Katsounas, Antonios; Schlaak, Joerg F.] Univ Hosp Essen, Dept Gastroenterol & Hepatol, D-45122 Essen, Germany. [Katsounas, Antonios; Lempicki, Richard A.] NCI Frederick, Lab Immunopathogenesis & Bioinformat, SAIC Frederick Inc, Frederick, MD USA. RP Katsounas, A (reprint author), Univ Hosp Essen, Dept Gastroenterol & Hepatol, Hufelandstr 55, D-45122 Essen, Germany. EM antonios.katsounas@uk-essen.de RI Lempicki, Richard/E-1844-2012; OI Lempicki, Richard/0000-0002-7059-409X; Schlaak, Joerg/0000-0002-9499-1014 FU Association for the Promotion of Scientific Research and Science of the Clinic for Gastroenterology and Hepatology at the University Hospital Essen (Essen, NRW, Germany); National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was funded in part with funds from the Association for the Promotion of Scientific Research and Science of the Clinic for Gastroenterology and Hepatology at the University Hospital Essen (Essen, NRW, Germany) and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The illustration is the work of Jiro, Wada from the Scientific Publications, Graphics & Media (SPGM), Information Systems Program, SAIC-Frederick, Inc. National Cancer Institute at Frederick. NR 105 TC 11 Z9 12 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0883-0185 J9 INT REV IMMUNOL JI Int. Rev. Immunol. PD OCT-DEC PY 2011 VL 30 IS 5-6 BP 366 EP 378 DI 10.3109/08830185.2011.593105 PG 13 WC Immunology SC Immunology GA 843GY UT WOS:000296661500008 PM 22053974 ER PT J AU Deater-Deckard, K Lansford, JE Malone, PS Alampay, LP Sorbring, E Bacchini, D Bombi, AS Bornstein, MH Chang, L Di Giunta, L Dodge, KA Oburu, P Pastorelli, C Skinner, AT Tapanya, S Tirado, LMU Zelli, A Al-Hassan, SM AF Deater-Deckard, Kirby Lansford, Jennifer E. Malone, Patrick S. Pena Alampay, Liane Sorbring, Emma Bacchini, Dario Bombi, Anna Silvia Bornstein, Marc H. Chang, Lei Di Giunta, Laura Dodge, Kenneth A. Oburu, Paul Pastorelli, Concetta Skinner, Ann T. Tapanya, Sombat Uribe Tirado, Liliana Maria Zelli, Arnaldo Al-Hassan, Suha M. TI The Association Between Parental Warmth and Control in Thirteen Cultural Groups SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE socialization; parenting; parent-child relations; culture AB The goal of the current study was to investigate potential cross-cultural differences in the covariation between two of the major dimensions of parenting behavior: control and warmth. Participants included 1,421 (51% female) 7- to 10-year-old (M = 8.29, SD = .67 years) children and their mothers and fathers representing 13 cultural groups in nine countries in Africa, Asia, Europe, the Middle East, and North and South America. Children and parents completed questionnaires and interviews regarding mother and father control and warmth. Greater warmth was associated with more control, but this association varied widely between cultural groups. C1 [Deater-Deckard, Kirby] Virginia Tech, Dept Psychol, Blacksburg, VA 24061 USA. [Lansford, Jennifer E.; Dodge, Kenneth A.; Skinner, Ann T.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27706 USA. [Malone, Patrick S.] Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. [Pena Alampay, Liane] Ateneo Manila Univ, Dept Psychol, Manila, Philippines. [Bacchini, Dario] Univ Naples 2, Dept Psychol, Naples, Italy. [Bombi, Anna Silvia; Di Giunta, Laura; Pastorelli, Concetta; Uribe Tirado, Liliana Maria] Sapienza Univ Rome, Dept Psychol, Rome, Italy. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Child & Family Res, Eunice, LA USA. [Chang, Lei] Chinese Univ Hong Kong, Dept Educ Psychol, Hong Kong, Hong Kong, Peoples R China. [Oburu, Paul] Maseno Univ, Dept Educ Psychol, Maseno, Kenya. [Tapanya, Sombat] Chiang Mai Univ, Dept Psychiat, Chiang Mai, Thailand. [Zelli, Arnaldo] Univ Rome Foro Italico Italy, Dept Sports Psychol, Rome, Italy. [Al-Hassan, Suha M.] Hashemite Univ, Dept Child Educ, Zarqa, Jordan. RP Deater-Deckard, K (reprint author), Virginia Tech, Dept Psychol, 109 Williams Hall 0436, Blacksburg, VA 24061 USA. EM kirbydd@vt.edu RI Malone, Patrick/F-6851-2011; Eclevia, Marian/I-6486-2013; ZELLI, ARNALDO/N-2333-2015; OI Malone, Patrick/0000-0002-8364-6987; ZELLI, ARNALDO/0000-0003-4020-8159; Bacchini, Dario/0000-0001-6140-9377 FU FIC NIH HHS [R03 TW008141, R03 TW008141-01]; NICHD NIH HHS [R01 HD054805, R01 HD054805-01A1]; NIDA NIH HHS [K01 DA024116, K01 DA024116-01A1, K05 DA015226, K05 DA015226-01] NR 20 TC 24 Z9 24 U1 2 U2 119 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD OCT PY 2011 VL 25 IS 5 BP 790 EP 794 DI 10.1037/a0025120 PG 5 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 836DA UT WOS:000296087800019 PM 21875202 ER PT J AU Hansson, AC Rimondini, R Heilig, M Mathe, AA Sommer, WH AF Hansson, Anita C. Rimondini, Roberto Heilig, Markus Mathe, Aleksander A. Sommer, Wolfgang H. TI Dissociation of antidepressant-like activity of escitalopram and nortriptyline on behaviour and hippocampal BDNF expression in female rats SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE Depression; forced swim test; PCR; SSRI ID NEUROTROPHIC FACTOR EXPRESSION; NERVE GROWTH-FACTOR; FLINDERS SENSITIVE LINE; TREATMENT-RESISTANT DEPRESSION; MESSENGER-RNA; DIFFERENTIAL REGULATION; ANIMAL-MODEL; ELECTROCONVULSIVE STIMULI; LEARNED HELPLESSNESS; CELL-PROLIFERATION AB A major hypothesis of depression postulates that a dysregulation of the neurotrophin systems is directly involved in the pathophysiology of depression, and that restoration of such deficits may underlie the therapeutic efficacy of antidepressant treatment. One key finding supporting this hypothesis is upregulation of brain derived neurotrophic factor (BDNF) in the hippocampus after antidepressant treatment. Here, we further test the hypothesis of BDNF involvement in antidepressant action in a genetic rat model of depression after chronic oral treatment with escitalopram, nortriptyline or placebo. Active treatments had significant behavioural antidepressant-like actions in female rats of the Flinders Sensitive Line (FSL) and non-selected Sprague Dawley (SD) rats, while Flinders Resistant Line (FRL) rats were unaffected. Escitalopram, but not norbiptyline, markedly reduced BDNF mRNA levels in the dentate gyrus of FSL rats. The BDNF downregulation was common to the four major promoters of the gene. Treatments did not affect BDNF expression in FRL or SD strains. We conclude that the antidepressant effects of escitalopram and nortriptyline, two common drugs with different pharmacological profiles, appear to be unrelated to the regulation of hippocampal BDNF expression in female rats. These results indicate that the tropic hypothesis of depression has limitations and emphasize the need for validated disease models of depression to assess potential treatment targets. C1 [Hansson, Anita C.; Sommer, Wolfgang H.] Cent Inst Mental Hlth, Department Psychopharmacol, D-68159 Mannheim, Germany. [Hansson, Anita C.; Heilig, Markus; Sommer, Wolfgang H.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Rimondini, Roberto] Univ Bologna, Dept Pharmacol, Bologna, Italy. [Mathe, Aleksander A.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. RP Sommer, WH (reprint author), Cent Inst Mental Hlth, Department Psychopharmacol, Sq 35, D-68159 Mannheim, Germany. EM aleksander.mathe@ki.se; wolfgang.sommer@zi-mannheim.de OI roberto, rimondini/0000-0003-4099-513X FU NIAAA; Swedish Medical Research Council [10414]; Karolinska Institute FX This work was supported by the intramural research funds of NIAAA, the Swedish Medical Research Council (grant number 10414 to AAM) and the Karolinska Institute. The sponsors had no further role in study design: in the collection, analysis and interpretation of data; in the writing or the report; and in the decision to submit the paper for publication. NR 78 TC 14 Z9 14 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD OCT PY 2011 VL 25 IS 10 BP 1378 EP 1387 DI 10.1177/0269881110393049 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 846JH UT WOS:000296892800014 PM 21262856 ER PT J AU Saubern, S Guha, R Baell, JB AF Saubern, Simon Guha, Rajarshi Baell, Jonathan B. TI KNIME Workflow to Assess PAINS Filters in SMARTS Format. Comparison of RDKit and Indigo Cheminformatics Libraries SO MOLECULAR INFORMATICS LA English DT Article DE Chemoinformatics; Drug discovery; High-throughput screening; Virtual screening ID SOURCE JAVA LIBRARY; DEVELOPMENT KIT CDK; DRUG DISCOVERY C1 [Saubern, Simon] CSIRO Mat Sci & Engn, Clayton, Vic 3169, Australia. [Guha, Rajarshi] NIH, Ctr Translat Therapeut, Rockville, MD 20850 USA. [Baell, Jonathan B.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia. [Baell, Jonathan B.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia. RP Saubern, S (reprint author), CSIRO Mat Sci & Engn, Bag 10, Clayton, Vic 3169, Australia. EM jbaell@wehi.edu.au RI Saubern, Simon/F-7538-2012; Baell, Jonathan/E-5844-2017 OI Saubern, Simon/0000-0002-1989-4951; Baell, Jonathan/0000-0003-2114-8242 NR 20 TC 28 Z9 28 U1 2 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1868-1743 J9 MOL INFORM JI Mol. Inf. PD OCT PY 2011 VL 30 IS 10 BP 847 EP 850 DI 10.1002/minf.201100076 PG 4 WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Pharmacology & Pharmacy; Computer Science; Mathematical & Computational Biology GA 846LD UT WOS:000296900100002 PM 27468104 ER PT J AU Nahab, FB Wittevrongel, L Ippolito, D Toro, C Grimes, GJ Starling, J Potti, G Haubenberger, D Bowen, D Buchwald, P Dong, CH Kalowitz, D Hallett, M AF Nahab, Fatta B. Wittevrongel, Loretta Ippolito, Dominic Toro, Camilo Grimes, George J. Starling, Judith Potti, Gopal Haubenberger, Dietrich Bowen, Daniel Buchwald, Peter Dong, Chuanhui Kalowitz, Daniel Hallett, Mark TI An Open-Label, Single-Dose, Crossover Study of the Pharmacokinetics and Metabolism of Two Oral Formulations of 1-Octanol in Patients with Essential Tremor SO NEUROTHERAPEUTICS LA English DT Article DE 1-Octanol; Octanoic acid; Essential tremor; Alcohol; Therapeutics; Spirography ID HARMALINE-INDUCED TREMOR; ALCOHOL-DEHYDROGENASE; OCTANOIC-ACID; INTOXICATION AB Existing therapeutic options for management of essential tremor are frequently limited by poor efficacy and adverse effects. Likely the most potent tremor suppressant used is ethanol, although its use is prohibitive due to a brief therapeutic window, and the obvious implications of excessive alcohol use. Longer-chain alcohols have been shown to suppress tremor in harmaline animal models, and appear to be safe and well tolerated in 2 prior studies in humans. Here we report on the findings of a phase I/II study of 1-octanol designed to explore pharmacokinetics, efficacy, and safety. The most significant finding was the identification of octanoic acid as the product of rapid 1-octanol metabolism. Furthermore, the temporal profile of efficacy closely matches the plasma concentration of octanoic acid. Therefore, these findings identify a novel class of compound (e.g., carboxylic acids) with tremor suppressive properties in ET. Administration of 1-octanol also appears to be safe based on various measures collected. Essential tremor (ET) is the most common tremor disorder, with tremors occurring during static posturing or movement. These tremors are known to briefly improve in many cases after alcohol (ethanol) consumption. Two previous studies of a longer chain alcohol, 1-octanol, have demonstrated longer duration tremor-suppressive effects without the occurrence of intoxication. The aim of this study was to characterize the pharmacokinetics of 1-octanol and its primary metabolite octanoic acid using two formulations, along with additional safety and efficacy measures. Participants with proven ethanol-responsive ET were recruited into 1 of 2 parts: (part A) a dose escalation study (1-64 mg/kg; n = 4), and (part B) a fixed dose (64 mg/kg; n = 10) balanced, open-label crossover design. Two participants in part B then completed an exploratory part C evaluating 128 mg/kg.Plasma samples were collected at 10 intervals during a 6-hour period postingestion. Efficacy was assessed using spirography, whereas safety was assessed with electrocardiograms, vital signs, adverse effects surveys, and an intoxication assessment. Plasma concentrations of 1-octanol were detectable at low levels whereas octanoic acid (OA) concentrations were approximately 100-fold higher. The half-life of OA was 87.6minutes. This was matched by a clinical reduction in tremor severity of 32% at 90 minutes, assessed using spirography. The safety profile was favorable, with the most commonly reported adverse effect being dysgeusia (38%). Early detection and higher plasma concentrations of OA are a product of rapid metabolism of 1-octanol.OA pharmacokinetics mirrored the timing of clinical improvement. These findings provide preliminary evidence for a new class of compound that may be effective in the treatment of ET. C1 [Nahab, Fatta B.; Dong, Chuanhui] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Wittevrongel, Loretta; Ippolito, Dominic; Toro, Camilo; Haubenberger, Dietrich; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Grimes, George J.; Starling, Judith; Potti, Gopal] NIH, Pharmaceut Dev Sect, Bethesda, MD 20892 USA. [Haubenberger, Dietrich] Med Univ Vienna, Dept Neurol, Vienna, Austria. [Bowen, Daniel] Wake Forest Univ, Winston Salem, NC 27106 USA. [Buchwald, Peter] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Kalowitz, Daniel] Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Nahab, FB (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. EM fnahab@med.miami.edu OI Buchwald, Peter/0000-0003-2732-8180 FU Intramural division of the National Institute of Neurological Disorders and Stroke; Ariston PharmaceuticalsNational Institute of Neurological Disorders and Stroke (NINDS); Austrian Science Fund FWF (Erwin Schroedinger Fellowship) [J2783-B09]; Neurotoxin Institute; Blackwell Publisher; Cambridge University Press; Springer Verlag; Taylor Francis Group; Oxford University Press; John Wiley Sons; Elsevier; Ariston Pharmaceuticals; National Institutes of Health (NIH)/NINDS; U.S. Department of Defense (Army); NIH (from Brainsway); NIH; U.S. Army via the Henry Jackson Foundation; Ariston Pharmaceutical Company via a Cooperative Research and Development Agreement (CRADA); Kinetics Foundation via a Clinical Trials Agreement (CTA) FX This work was supported by the Intramural division of the National Institute of Neurological Disorders and Stroke and a collaborative research and development agreement with Ariston Pharmaceuticals; Dr. Haubenberger received research support through the National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program and the Austrian Science Fund FWF (Erwin Schroedinger Fellowship, project no. J2783-B09); Dr. Hallett serves as Chair of the Medical Advisory Board and receives funding for travel from the Neurotoxin Institute; serves as Chair of the Medical Advisory Board of the Benign Essential Blepharospasm Foundation and Chair of the Medical Advisory Board of the International Essential Tremor Foundation; Dr. Hallett has received honoraria and/or funding for travel for lectures or educational activities not funded by industry; and serves on Editorial Advisory Boards for Clinical Neurophysiology, Brain, Acta Neurologica Scandinavica, Journal of Clinical Neurophysiology, Italian Journal of Neurological Sciences, Medical Problems of Performing Artists, Annals of Neurology, Neurology and Clinical Neurophysiology, The Cerebellum, NeuroRx, Current Trends in Neurology, Faculty of 1000 Biology, Faculty of 1000 Medicine, Brain Stimulation, Journal of Movement Disorders (Korea), and World Neurology. Dr. Hallett may accrue revenue on U.S. Patent #6,780,413 B2 (issued: August 24, 2004): immunotoxin (MAB-Ricin) for the treatment of focal movement disorders; U. S. Patent #7,407,478 (issued: August 5, 2008): coil for magnetic stimulation and methods for using the same; receives royalties from publishing from Blackwell Publisher, Cambridge University Press, Springer Verlag, Taylor & Francis Group, Oxford University Press, John Wiley & Sons, and Elsevier; Dr. Hallett receives research support from Ariston Pharmaceuticals, National Institutes of Health (NIH)/NINDS (Intramural Program) and the U.S. Department of Defense (Army); Dr. Hallett has received license fee payments from the NIH (from Brainsway) for licensing the patent for the H-coil. Dr. Hallett's research at the NIH is largely supported by the NIH Intramural Program. Supplemental research funds come from the U.S. Army via the Henry Jackson Foundation, Ariston Pharmaceutical Company via a Cooperative Research and Development Agreement (CRADA) with the NIH, and the Kinetics Foundation via a Clinical Trials Agreement (CTA) with the NIH. Dr. Hallett is an inventor for patent applications of 1-octanol and octanoic acid held by NINDS/NIH. NR 21 TC 13 Z9 13 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD OCT PY 2011 VL 8 IS 4 BP 753 EP 762 DI 10.1007/s13311-011-0045-1 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 844FS UT WOS:000296733700019 PM 21594724 ER PT J AU Crocker, MK Yanovski, JA AF Crocker, Melissa K. Yanovski, Jack A. TI Pediatric Obesity: Etiology and Treatment SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Overweight; Differential diagnosis; Pharmacotherapy; Bariatric surgery; Adiposity; Leptin ID EARLY-ONSET OBESITY; BODY-MASS INDEX; GENOME-WIDE ASSOCIATION; CONGENITAL LEPTIN DEFICIENCY; GASTRIC BYPASS-SURGERY; EXPERT COMMITTEE RECOMMENDATIONS; RANDOMIZED CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS; PLACEBO-CONTROLLED TRIAL; GLUCAGON-LIKE PEPTIDE-1 AB This article reviews factors that contribute to excessive weight gain in children and outlines current knowledge regarding approaches for treating pediatric obesity. Most of the known genetic causes of obesity primarily increase energy intake. Genes regulating the leptin signaling pathway are particularly important for human energy homeostasis. Obesity is a chronic disorder that requires long-term strategies for management. The foundation for all treatments for pediatric obesity remains restriction of energy intake with lifestyle modification. There are few long-term studies of pharmacotherapeutic interventions for pediatric obesity. Bariatric surgical approaches are the most efficacious treatment but, because of their potential risks, are reserved for those with the most significant complications of obesity. C1 [Crocker, Melissa K.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH,Dept Hlth & Human Serv,Hatfield Clin Res Ctr, Bethesda, MD USA. RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH,Dept Hlth & Human Serv,Hatfield Clin Res Ctr, Bethesda, MD USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr Yanovski is a Commissioned Officer in the United States Public Health Service, Department of Health and Human Services. Unit on Growth and Obesity, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, 9000 Rockville Pike, Hatfield Clinical Research Center, Room 1-3330, MSC 1103, Bethesda, MD, 20892-1103, USA NR 160 TC 20 Z9 21 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 EI 1557-8240 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 2011 VL 58 IS 5 BP 1217 EP + DI 10.1016/j.pcl.2011.07.004 PG 25 WC Pediatrics SC Pediatrics GA 843NM UT WOS:000296678700010 PM 21981957 ER PT J AU An, P Li, RL Wang, JM Yoshimura, T Takahashi, M Samudralal, R O'Brien, SJ Phair, J Goedert, JJ Kirk, GD Troyer, JL Sezgin, E Buchbinder, SP Donfield, S Nelson, GW Winkler, CA AF An, Ping Li, Rongling Wang, Ji Ming Yoshimura, Teizo Takahashi, Munehisa Samudralal, Ram O'Brien, Stephen J. Phair, John Goedert, James J. Kirk, Gregory D. Troyer, Jennifer L. Sezgin, Efe Buchbinder, Susan P. Donfield, Sharyne Nelson, George W. Winkler, Cheryl A. TI Role of Exonic Variation in Chemokine Receptor Genes on AIDS: CCRL2 F167Y Association with Pneumocystis Pneumonia SO PLOS GENETICS LA English DT Article ID HIV-1 DISEASE PROGRESSION; IMMUNODEFICIENCY-VIRUS TYPE-1; GENOME-WIDE ASSOCIATION; INJECTION-DRUG USERS; AFRICAN-AMERICANS; CORECEPTOR USAGE; INFECTION; CCR5; POLYMORPHISM; INDIVIDUALS AB Chromosome 3p21-22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naive HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28-6.31) among four major AIDS-defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation. C1 [An, Ping; Winkler, Cheryl A.] NCI, Basic Res Lab, SAIC Frederick, Frederick, MD 21701 USA. [Li, Rongling] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA. [Wang, Ji Ming; Yoshimura, Teizo; Takahashi, Munehisa] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. [Samudralal, Ram] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [O'Brien, Stephen J.; Sezgin, Efe] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Phair, John] Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Sch Med, Chicago, IL USA. [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Troyer, Jennifer L.; Nelson, George W.] NCI, BSP CCR Genet Core, SAIC Frederick, Frederick, MD 21701 USA. [Buchbinder, Susan P.] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Donfield, Sharyne] Rho, Chapel Hill, NC USA. RP An, P (reprint author), NCI, Basic Res Lab, SAIC Frederick, Frederick, MD 21701 USA. EM pingan@nih.gov; winklerc@mail.nih.gov RI Troyer, Jennifer/B-8415-2012; Sezgin, Efe/B-8418-2012; OI Sezgin, Efe/0000-0002-8000-7485; O'Brien, Stephen J./0000-0001-7353-8301 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 75 TC 8 Z9 9 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002328 DI 10.1371/journal.pgen.1002328 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400029 PM 22046140 ER PT J AU Avery, CL He, QC North, KE Ambite, JL Boerwinkle, E Fornage, M Hindorff, LA Kooperberg, C Meigs, JB Pankow, JS Pendergrass, SA Psaty, BM Ritchie, MD Rotter, JI Taylor, KD Wilkens, LR Heiss, G Lin, DY AF Avery, Christy L. He, Qianchuan North, Kari E. Ambite, Jose L. Boerwinkle, Eric Fornage, Myriam Hindorff, Lucia A. Kooperberg, Charles Meigs, James B. Pankow, James S. Pendergrass, Sarah A. Psaty, Bruce M. Ritchie, Marylyn D. Rotter, Jerome I. Taylor, Kent D. Wilkens, Lynne R. Heiss, Gerardo Lin, Dan Yu TI A Phenomics-Based Strategy Identifies Loci on APOC1, BRAP, and PLCG1 Associated with Metabolic Syndrome Phenotype Domains SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; GENETIC-LOCI; SIGNAL-TRANSDUCTION; DIABETES RISK; HEART; OBESITY AB Despite evidence of the clustering of metabolic syndrome components, current approaches for identifying unifying genetic mechanisms typically evaluate clinical categories that do not provide adequate etiological information. Here, we used data from 19,486 European American and 6,287 African American Candidate Gene Association Resource Consortium participants to identify loci associated with the clustering of metabolic phenotypes. Six phenotype domains (atherogenic dyslipidemia, vascular dysfunction, vascular inflammation, pro-thrombotic state, central obesity, and elevated plasma glucose) encompassing 19 quantitative traits were examined. Principal components analysis was used to reduce the dimension of each domain such that >55% of the trait variance was represented within each domain. We then applied a statistically efficient and computational feasible multivariate approach that related eight principal components from the six domains to 250,000 imputed SNPs using an additive genetic model and including demographic covariates. In European Americans, we identified 606 genome-wide significant SNPs representing 19 loci. Many of these loci were associated with only one trait domain, were consistent with results in African Americans, and overlapped with published findings, for instance central obesity and FTO. However, our approach, which is applicable to any set of interval scale traits that is heritable and exhibits evidence of phenotypic clustering, identified three new loci in or near APOC1, BRAP, and PLCG1, which were associated with multiple phenotype domains. These pleiotropic loci may help characterize metabolic dysregulation and identify targets for intervention. C1 [Avery, Christy L.; North, Kari E.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [He, Qianchuan; Lin, Dan Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Ambite, Jose L.] Univ So Calif, Inst Informat Sci, Los Angeles, CA USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Div Epidemiol, Houston, TX USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Hindorff, Lucia A.] NHGRI, Off Populat Gen, NIH, Bethesda, MD 20892 USA. [Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Pendergrass, Sarah A.; Ritchie, Marylyn D.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Rotter, Jerome I.; Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Wilkens, Lynne R.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. RP Avery, CL (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. EM christy_avery@unc.edu RI Ritchie, Marylyn/C-1114-2012; OI Pankow, James/0000-0001-7076-483X FU NIH/NHGRI [U01 HG004798]; NIH/NHLBI, U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221, U01 HG004790]; National Cancer Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758]; National Heart, Lung, and Blood Institute; NHLBI [K99-HL-098458]; NIDDK [K24 DK080140, R01 DK078616] FX PAGE: Support for the Genetic Epidemiology of Causal Variants Across the Life Course (CALiCo) was provided through the National Human Genome Research Institute's Population Architecture Using Genomics and Epidemiology (PAGE) network (U01 HG004803). EAGLE work was funded by NIH/NHGRI grant U01 HG004798. The WHI program is funded by NIH/NHLBI, U.S. Department of Health and Human Services, through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221, and U01 HG004790. Funding support for the Multiethnic Cohort study was provided through the National Cancer Institute (R37CA54281, R01 CA63, P01CA33619, U01CA136792, and U01CA98758) and NHGRI (U01 HG004802). CARe: The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff, and study participants in creating this resource for biomedical research. The following five parent studies contributed parent study data, ancillary study data, and DNA samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype data base for wide dissemination to the biomedical research community: Atherosclerosis Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California Davis (N01-HC-85083), University of California Irvine (N01-HC85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California Irvine (N01-HC45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), Harbor-UCLA Research and Education Institute (N01-HC-95169). CLA was supported by grant K99-HL-098458 from the NHLBI. JBM was supported by grants K24 DK080140 and R01 DK078616 from the NIDDK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 40 Z9 43 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002322 DI 10.1371/journal.pgen.1002322 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400023 PM 22022282 ER PT J AU Moore, LE Nickerson, ML Brennan, P Toro, JR Jaeger, E Rinsky, J Han, SS Zaridze, D Matveev, V Janout, V Kollarova, H Bencko, V Navratilova, M Szeszenia-Dabrowska, N Mates, D Schmidt, LS Lenz, P Karami, S Linehan, WM Merino, M Chanock, S Boffetta, P Chow, WH Waldman, FM Rothman, N AF Moore, Lee E. Nickerson, Michael L. Brennan, Paul Toro, Jorge R. Jaeger, Erich Rinsky, Jessica Han, Summer S. Zaridze, David Matveev, Vsevolod Janout, Vladimir Kollarova, Hellena Bencko, Vladimir Navratilova, Marie Szeszenia-Dabrowska, Neonilia Mates, Dana Schmidt, Laura S. Lenz, Petra Karami, Sara Linehan, W. Marston Merino, Maria Chanock, Stephen Boffetta, Paolo Chow, Wong-Ho Waldman, Frederic M. Rothman, Nathaniel TI Von Hippel-Lindau (VHL) Inactivation in Sporadic Clear Cell Renal Cancer: Associations with Germline VHL Polymorphisms and Etiologic Risk Factors SO PLOS GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; KIDNEY CANCER; TRICHLOROETHYLENE EXPOSURE; COLORECTAL-CANCER; SOMATIC MUTATIONS; CENTRAL-EUROPE; POOR SURVIVAL; LINKAGE PHASE; CARCINOMA AB Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC) and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs). VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5). Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31) and current: OR = 0.56 (0.32-0.99); P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation) in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases. C1 [Moore, Lee E.; Toro, Jorge R.; Rinsky, Jessica; Han, Summer S.; Karami, Sara; Chanock, Stephen; Chow, Wong-Ho; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Nickerson, Michael L.; Boffetta, Paolo] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Jaeger, Erich; Waldman, Frederic M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zaridze, David; Matveev, Vsevolod] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Janout, Vladimir; Kollarova, Hellena] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Bencko, Vladimir] Charles Univ Prague, Inst Hyg & Epidemiol, Prague, Czech Republic. [Navratilova, Marie] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Mates, Dana] Inst Publ Hlth, Bucharest, Romania. [Schmidt, Laura S.] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21701 USA. [Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Lenz, Petra; Merino, Maria] NCI, Div Canc Epidemiol & Genet, SAIC Frederick, Frederick, MD 21701 USA. [Chanock, Stephen] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Canc Prevent Res Inst, Lyon, France. RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM moorele@mail.nih.gov RI Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI mates, dana/0000-0002-6219-9807 FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHS261200800001E, CA102600]; European Commission [IC15-CT96-0313] FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHS261200800001E (LS Schmidt, P Lenz) and under contract CA102600 (FM Waldman), and by European Commission INCO-COPERNICUS Grant IC15-CT96-0313. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 62 Z9 63 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002312 DI 10.1371/journal.pgen.1002312 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400013 PM 22022277 ER PT J AU N'Diaye, A Chen, GK Palmer, CD Ge, B Tayo, B Mathias, RA Ding, JZ Nalls, MA Adeyemo, A Adoue, V Ambrosone, CB Atwood, L Bandera, EV Becker, LC Berndt, SI Bernstein, L Blot, WJ Boerwinkle, E Britton, A Casey, G Chanock, SJ Demerath, E Deming, SL Diver, WR Fox, C Harris, TB Hernandez, DG Hu, JJ Ingles, SA John, EM Johnson, C Keating, B Kittles, RA Kolonel, LN Kritchevsky, SB Le Marchand, L Lohman, K Liu, JK Millikan, RC Murphy, A Musani, S Neslund-Dudas, C North, KE Nyante, S Ogunniyi, A Ostrander, EA Papanicolaou, G Patel, S Pettaway, CA Press, MF Redline, S Rodriguez-Gil, JL Rotimi, C Rybicki, BA Salako, B Schreiner, PJ Signorello, LB Singleton, AB Stanford, JL Stram, AH Stram, DO Strom, SS Suktitipat, B Thun, MJ Witte, JS Yanek, LR Ziegler, RG Zheng, W Zhu, XF Zmuda, JM Zonderman, AB Evans, MK Liu, YM Becker, DM Cooper, RS Pastinen, T Henderson, BE Hirschhorn, JN Lettre, G Haiman, CA AF N'Diaye, Amidou Chen, Gary K. Palmer, Cameron D. Ge, Bing Tayo, Bamidele Mathias, Rasika A. Ding, Jingzhong Nalls, Michael A. Adeyemo, Adebowale Adoue, Veronique Ambrosone, Christine B. Atwood, Larry Bandera, Elisa V. Becker, Lewis C. Berndt, Sonja I. Bernstein, Leslie Blot, William J. Boerwinkle, Eric Britton, Angela Casey, Graham Chanock, Stephen J. Demerath, Ellen Deming, Sandra L. Diver, W. Ryan Fox, Caroline Harris, Tamara B. Hernandez, Dena G. Hu, Jennifer J. Ingles, Sue A. John, Esther M. Johnson, Craig Keating, Brendan Kittles, Rick A. Kolonel, Laurence N. Kritchevsky, Stephen B. Le Marchand, Loic Lohman, Kurt Liu, Jiankang Millikan, Robert C. Murphy, Adam Musani, Solomon Neslund-Dudas, Christine North, Kari E. Nyante, Sarah Ogunniyi, Adesola Ostrander, Elaine A. Papanicolaou, George Patel, Sanjay Pettaway, Curtis A. Press, Michael F. Redline, Susan Rodriguez-Gil, Jorge L. Rotimi, Charles Rybicki, Benjamin A. Salako, Babatunde Schreiner, Pamela J. Signorello, Lisa B. Singleton, Andrew B. Stanford, Janet L. Stram, Alex H. Stram, Daniel O. Strom, Sara S. Suktitipat, Bhoom Thun, Michael J. Witte, John S. Yanek, Lisa R. Ziegler, Regina G. Zheng, Wei Zhu, Xiaofeng Zmuda, Joseph M. Zonderman, Alan B. Evans, Michele K. Liu, Yongmei Becker, Diane M. Cooper, Richard S. Pastinen, Tomi Henderson, Brian E. Hirschhorn, Joel N. Lettre, Guillaume Haiman, Christopher A. TI Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HUMAN-POPULATIONS; COMMON; VARIANTS; TRAITS AB Adult height is a classic polygenic trait of high heritability (h(2) similar to 0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain similar to 10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4x10(-12) and 2p14-rs4315565, P = 1.2x10(-8)). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7x10(-4) for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits. C1 [N'Diaye, Amidou; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Chen, Gary K.; Casey, Graham; Ingles, Sue A.; Stram, Alex H.; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Chen, Gary K.; Casey, Graham; Ingles, Sue A.; Press, Michael F.; Stram, Alex H.; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Palmer, Cameron D.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Ge, Bing; Adoue, Veronique; Pastinen, Tomi] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Ge, Bing; Adoue, Veronique; Pastinen, Tomi] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Tayo, Bamidele; Cooper, Richard S.] Loyola Univ, Chicago Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. [Mathias, Rasika A.; Becker, Lewis C.; Suktitipat, Bhoom; Yanek, Lisa R.; Becker, Diane M.] Johns Hopkins Univ, Sch Med, Dept Med, Johns Hopkins GeneSTAR Res Program, Baltimore, MD 21205 USA. [Ding, Jingzhong; Kritchevsky, Stephen B.; Lohman, Kurt; Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Nalls, Michael A.; Britton, Angela; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Adeyemo, Adebowale; Rotimi, Charles] NHGRI, NIH Intramural Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Atwood, Larry] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ USA. [Berndt, Sonja I.; Chanock, Stephen J.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA. [Blot, William J.; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Blot, William J.; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Div Epidemiol, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Demerath, Ellen] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Fox, Caroline] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [John, Esther M.] Stanford Univ, Stanford Canc Ctr, Stanford, CA 94305 USA. [Johnson, Craig] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Keating, Brendan] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Kittles, Rick A.] Univ Illinois, Dept Med, Chicago, IL USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Liu, Jiankang] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Murphy, Adam] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. [Musani, Solomon] Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study,Div Cardiovasc Dis, Jackson, MS 39216 USA. [Neslund-Dudas, Christine; Rybicki, Benjamin A.] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Ogunniyi, Adesola; Salako, Babatunde] Univ Ibadan, Dept Med, Ibadan, Nigeria. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Papanicolaou, George] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Patel, Sanjay; Redline, Susan] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Suktitipat, Bhoom] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94143 USA. [Witte, John S.] Univ Calif San Francisco, Dept Urol, Inst Human Genet, San Francisco, CA USA. [Zhu, Xiaofeng] Case Western Reserve Univ, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA. [Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. [Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP N'Diaye, A (reprint author), Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. EM joelh@broadinstitute.org; guillaume.lettre@umontreal.ca; haiman@usc.edu RI Singleton, Andrew/C-3010-2009; Bandera, Elisa/M-4169-2014; OI Bandera, Elisa/0000-0002-8789-2755; Suktitipat, Bhoom/0000-0001-8034-7757; Kritchevsky, Stephen/0000-0003-3336-6781; Adeyemo, Adebowale/0000-0002-3105-3231; Patel, Sanjay/0000-0002-9142-5172; Zonderman, Alan B/0000-0002-6523-4778; Ostrander, Elaine/0000-0001-6075-9738 FU Department of Defense Breast Cancer Research [BC075007]; NIH/NCI [CA1326792, RC2 CA148085]; Fondation de l'Institut de Cardiologie de Montreal; FRSQ; Canada Research Chair Program; CIHR; March of Dimes [6-FY09-507]; NIH/NIDDK [R01DK075787]; MEC [R01-CA63464, R37-CA54281]; CARE (National Institute for Child Health and Development) [NO1-HD-3-3175]; WCHS (U. S. Army Medical Research and Material Command (USAMRMC) [DAMD-17-01-0-0334]; NIH [CA1326792, R01-CA100598, CA63464, CA54281, CA148085, HG004726, R01 CA056678, R01 CA082664, R01 CA092579, CA092447, HHSN268200782096C, R37-HL045508, R01-HL053353, R01-DK075787, U01-HL054512, R01-HL074166, R01-HL086718, R01-HG003054, NR0224103]; Breast Cancer Research Foundation); SFBCS (NIH) [R01-CA77305]; United States Army Medical Research [DAMD17-96-6071]; NC-BCFR (NIH) [U01-CA69417]; CBCS (NIH) [P50-CA58223]; Center for Environmental Health and Susceptibility, National Institute of Environmental Health Sciences, NIH [P30-ES10126]; PLCO (National Cancer Institute, National Institutes of Health); NHBS (National Institutes of Health) [R01-CA100374]; WFBC (NIH) [R01-CA73629]; National Cancer Institute, NIH [RFA CA-95-011]; Division of Cancer Epidemiology and Genetics, NCI, NIH. LAAPC; Cancer Research Fund [99-00524V-10258, 97-12013]; University of California [98-00924V]; Department of Health Services; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute; Vanderbilt-Ingram Cancer Center [P30 CA68485]; American Cancer Society; NIH, NIA; National Center on Minority Health and Health Disparities [Z01-AG000513, 2009-149]; National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; MISAIC Initiative; [R01CA68578]; [ES007784]; [DAMD W81XWH-07-1-0645]; [P50-CA140388] FX The grants and contracts that have supported CARe are listed at http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx, including HHSN268200625226C (ADB No. N01-HC-65226). AABC was supported by a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to CA Haiman (BC075007) and AAPC was supported by NIH/NCI grants (CA1326792 and RC2 CA148085). Additional support for this work was provided by: the Fondation de l'Institut de Cardiologie de Montreal (G Lettre), FRSQ (G Lettre and T Pastinen), Canada Research Chair Program (G Lettre and T Pastinen), CIHR (T Pastinen), March of Dimes 6-FY09-507 (JN Hirschhorn), and NIH/NIDDK R01DK075787 (JN Hirschhorn). The grants and contracts that have supported CARe are listed at http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx, including HHSN268200625226C (ADB No. N01-HC-65226). Each of the participating AABC studies was supported by the following grants: MEC (NIH grants R01-CA63464 and R37-CA54281), CARE (National Institute for Child Health and Development grant NO1-HD-3-3175), WCHS (U. S. Army Medical Research and Material Command (USAMRMC) grant DAMD-17-01-0-0334, NIH grant R01-CA100598, and the Breast Cancer Research Foundation), SFBCS (NIH grant R01-CA77305 and United States Army Medical Research Program grant DAMD17-96-6071), NC-BCFR (NIH grant U01-CA69417), CBCS (NIH Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA58223, and Center for Environmental Health and Susceptibility, National Institute of Environmental Health Sciences, NIH, grant number P30-ES10126), PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health), NHBS (National Institutes of Health grant R01-CA100374), and WFBC (NIH grant R01-CA73629). The Breast Cancer Family Registry (BCFR) was supported by the National Cancer Institute, NIH, under RFA CA-95-011 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. AAPC was supported by NIH grants CA63464, CA54281, CA1326792, CA148085, and HG004726. Genotyping of the PLCO samples was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH. LAAPC was funded by grant 99-00524V-10258 from the Cancer Research Fund, under Interagency Agreement #97-12013 (University of California contract #98-00924V) with the Department of Health Services Cancer Research Program. KCPCS was supported by NIH grants R01 CA056678, R01 CA082664, R01 CA092579, with additional support from the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute. MDA was support by grants R01CA68578, ES007784, DAMD W81XWH-07-1-0645, and P50-CA140388. GECAP was supported by NIH grant ES011126. CaP Genes was supported by CA88164 and CA127298. DCPC was supported by NIH grant S06GM08016 and DOD grants DAMD W81XWH-07-1-0203 and DAMD W81XWH-06-1-0066. SCCS is funded by NIH grant CA092447, and SCCS sample preparation was conducted at the Epidemiology Biospecimen Core Lab that is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). CPS-II is supported by the American Cancer Society.; HANDLS was supported by the Intramural Research Program of the NIH, NIA, and the NationalCenter on Minority Health and Health Disparities (project #Z01-AG000513 and human subjects protocol #2009-149). Data analyses for the HANDLS study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Md (http://biowulf.nih.gov). The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U. S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf. HABC was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The GWAS was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the NIH to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, NIA. The Nigerian cohort study was supported by NIH grant numbers R37-HL045508, R01-HL053353, R01-DK075787 and U01-HL054512. The authors acknowledge the assistance of the research staff and participants in Igbo-Ora, Oyo State, Nigeria. Maywood cohort study was supported by the NIH grant numbers R37-HL045508, R01-HL074166, R01-HL086718, and R01-HG003054. GeneSTAR was supported by NIH grants NR0224103, HL58625-01A1, HL59684, HL071025-01A1, U01HL72518, and HL087698 and by M01-RR000052 to the Johns Hopkins General Clinical Research Center. RAM was supported in part by the MISAIC Initiative Award at Johns Hopkins University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 40 Z9 40 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002298 DI 10.1371/journal.pgen.1002298 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400007 PM 21998595 ER PT J AU Ohlsson, C Wallaschofski, H Lunetta, KL Stolk, L Perry, JRB Koster, A Petersen, AK Eriksson, J Lehtimaki, T Huhtaniemi, IT Hammond, GL Maggio, M Coviello, AD Ferrucci, L Heier, M Hofman, A Holliday, KL Jansson, JO Kahonen, M Karasik, D Karlsson, MK Kiel, DP Liu, YM Ljunggren, O Lorentzon, M Lyytikainen, LP Meitinger, T Mellstrom, D Melzer, D Miljkovic, I Nauck, M Nilsson, M Penninx, B Pye, SR Vasan, RS Reincke, M Rivadeneira, F Tajar, A Teumer, A Uitterlinden, AG Ulloor, J Viikari, J Volker, U Volzke, H Wichmann, HE Wu, TS Zhuang, WV Ziv, E Wu, FCW Raitakari, O Eriksson, A Bidlingmaier, M Harris, TB Murray, A De Jong, FH Murabito, JM Bhasin, S Vandenput, L Haring, R AF Ohlsson, Claes Wallaschofski, Henri Lunetta, Kathryn L. Stolk, Lisette Perry, John R. B. Koster, Annemarie Petersen, Ann-Kristin Eriksson, Joel Lehtimaki, Terho Huhtaniemi, Ilpo T. Hammond, Geoffrey L. Maggio, Marcello Coviello, Andrea D. Ferrucci, Luigi Heier, Margit Hofman, Albert Holliday, Kate L. Jansson, John-Olov Kahonen, Mika Karasik, David Karlsson, Magnus K. Kiel, Douglas P. Liu, Yongmei Ljunggren, Osten Lorentzon, Mattias Lyytikainen, Leo-Pekka Meitinger, Thomas Mellstrom, Dan Melzer, David Miljkovic, Iva Nauck, Matthias Nilsson, Maria Penninx, Brenda Pye, Stephen R. Vasan, Ramachandran S. Reincke, Martin Rivadeneira, Fernando Tajar, Abdelouahid Teumer, Alexander Uitterlinden, Andre G. Ulloor, Jagadish Viikari, Jorma Voelker, Uwe Voelzke, Henry Wichmann, H. Erich Wu, Tsung-Sheng Zhuang, Wei Vivian Ziv, Elad Wu, Frederick C. W. Raitakari, Olli Eriksson, Anna Bidlingmaier, Martin Harris, Tamara B. Murray, Anna De Jong, Frank H. Murabito, Joanne M. Bhasin, Shalender Vandenput, Liesbeth Haring, Robin CA EMAS Study Grp TI Genetic Determinants of Serum Testosterone Concentrations in Men SO PLOS GENETICS LA English DT Article ID HORMONE-BINDING GLOBULIN; POPULATION-BASED COHORT; ELDERLY-MEN; OLDER MEN; ANDROGEN DEFICIENCY; METABOLIC SYNDROME; RISK-FACTORS; SHBG GENE; MORTALITY; HEALTH AB Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as,300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2x10(-41) and rs6258, p = 2.3x10(-22)). Subjects with >= 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6610216). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. C1 [Ohlsson, Claes; Eriksson, Joel; Lorentzon, Mattias; Mellstrom, Dan; Nilsson, Maria; Eriksson, Anna; Vandenput, Liesbeth] Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Internal Med,Inst Med, Gothenburg, Sweden. [Wallaschofski, Henri; Nauck, Matthias; Haring, Robin] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Lunetta, Kathryn L.; Coviello, Andrea D.; Kiel, Douglas P.; Vasan, Ramachandran S.; De Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender] NHLBI, Framingham Heart Study, Framingham, MA USA. [Lunetta, Kathryn L.; Zhuang, Wei Vivian] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Stolk, Lisette; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Perry, John R. B.; Murray, Anna] Univ Exeter, Peninsula Med Sch, Exeter, Devon, England. [Stolk, Lisette; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Hlth Ageing, Rotterdam, Netherlands. [Perry, John R. B.; Murray, Anna] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Petersen, Ann-Kristin] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Lehtimaki, Terho; Lyytikainen, Leo-Pekka] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, Terho; Kahonen, Mika; Lyytikainen, Leo-Pekka] Tampere Univ Hosp, Tampere, Finland. [Huhtaniemi, Ilpo T.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England. [Hammond, Geoffrey L.; Wu, Tsung-Sheng] Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC V5Z 1M9, Canada. [Hammond, Geoffrey L.; Wu, Tsung-Sheng] Univ British Columbia, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada. [Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Internal Med, I-43100 Parma, Italy. [Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Biomed Sci, I-43100 Parma, Italy. [Coviello, Andrea D.; Vasan, Ramachandran S.; Ulloor, Jagadish; De Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Coviello, Andrea D.; Vasan, Ramachandran S.; Ulloor, Jagadish; De Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Coviello, Andrea D.; Vasan, Ramachandran S.; Ulloor, Jagadish; De Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Coviello, Andrea D.; Vasan, Ramachandran S.; Ulloor, Jagadish; De Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender] Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [EMAS Study Grp] Univ Manchester, European Male Ageing Study, Manchester, Lancs, England. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Heier, Margit] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Holliday, Kate L.; Pye, Stephen R.; Tajar, Abdelouahid] Univ Manchester, Arthrit Res UK Epidemiol Unit, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Jansson, John-Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Karlsson, Magnus K.] Lund Univ, Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden. [Karlsson, Magnus K.] Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden. [Liu, Yongmei] Wake Forest Univ Hlth Sci, Dept Epidemiol & Biostat, Winston Salem, NC USA. [Ljunggren, Osten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany. [Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Melzer, David] Univ Exeter, Peninsula Med Sch, Exeter, Devon, England. [Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Penninx, Brenda] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Penninx, Brenda] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Reincke, Martin; Bidlingmaier, Martin] Univ Munich, Med Klin Innenstadt, D-8000 Munich, Germany. [Teumer, Alexander; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H. Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Wichmann, H. Erich] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Ziv, Elad] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Ziv, Elad] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94143 USA. [Wu, Frederick C. W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Androl Res Unit,Dev & Regenerat Biomed Res Grp, Manchester M13 9WL, Lancs, England. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, SF-20500 Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. RP Ohlsson, C (reprint author), Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Dept Internal Med,Inst Med, Gothenburg, Sweden. EM claes.ohlsson@medic.gu.se RI Koster, Annemarie/E-7438-2010; Pye, Stephen/D-9236-2011; Ziv, Elad/L-5396-2014; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Lyytikainen, Leo-Pekka/C-8544-2016; OI Ramachandran, Vasan/0000-0001-7357-5970; Kiel, Douglas/0000-0001-8474-0310; Melzer, David/0000-0002-0170-3838; Karasik, David/0000-0002-8826-0530; Vandenput, Liesbeth/0000-0002-1712-6131; Pye, Stephen/0000-0002-7263-2897; Rivadeneira, Fernando/0000-0001-9435-9441; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Murabito, Joanne/0000-0002-0192-7516; Bidlingmaier, Martin/0000-0002-4681-6668; Lunetta, Kathryn/0000-0002-9268-810X; Murray, Anna/0000-0002-2351-2522; Miljkovic, Iva/0000-0002-3155-9777 FU National Institute of Aging (Genetics of Reproductive Life Period and Health Outcomes) [R21AG032598]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]; National Institute on Aging (NIA) [1RO1AG31206, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, 1R01AG032098-01A1]; Boston Claude D. Pepper Older Americans Independence Center [5P30AG031679]; National Institute on Aging and the National Institute of Arthritis Musculoskeletal and Skin Diseases [R01 AR/AG 41398]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities [h1231]; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg - West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg West Pomerania; Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg - West Pomerania [03IS2061A]; Siemens Healthcare Diagnostics, Eschborn, formerly DPC Biermann GmbH, Bad Nauheim, Germany; Swedish Research Council [K2010-54X-09894-19-3, 2006-3832, K2010-52X-20229-05-3]; Swedish Foundation for Strategic Research [K2010-54X-09894-19-3, 2006-3832]; ALF/LUA in Gothenburg; Lundberg Foundation; Torsten and Ragnar Soderberg's Foundation; Petrus and Augusta Hedlunds Foundation; Vastra Gotaland Foundation; Goteborg Medical Society; Novo Nordisk foundation; Canadian Institutes of Health Research [MOP-15261]; European Commission [HEALTH-F2-2008-201865-GEFOS]; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015]; Helmholtz Center Munich, German Research Center for Environmental Health; German Federal Ministry of Education and Research (BMBF); State of Bavaria; German National Genome Research Network [NGFN-2, NGFNPlus:01GS0823]; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; National Institutes of Health [HHSN268200782096C]; NIH, National Institute on Aging; Netherlands Organisation of Scientific Research NWO [175.010.2005.011, 911-03-012]; Institute for Diseases in the Elderly [014-93-015;RIDE2]; Netherlands Genomics Initiative (NGI) - Netherlands Consortiumof Healthy Aging (NCHA) [050-060-810]; European Commision [HEALTH-F2-2008-201865, HEALTH-F2-2008-35627]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organisation for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture, and Science; Ministry for Health, Welfare, and Sports; the European Commission (DG XII); Municipality of Rotterdam; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institute on Aging, National Institutes of Health, Baltimore, Maryland; Commission of the European Community [QLK6-CT-2001-00258]; UK Arthritis Research Campaign; University Hospitals Leuven, Belgium; Academy of Finland [117797, 121584, 126925]; Social Insurance Institution of Finland; Turku University Foundation; Tampere and Turku University Hospital; Emil Aaltonen Foundation; Juho Vainio Foundation; Paavo Nurmi Foundation; Tampere Tubeculosis Foundation; Orion-Farmos Research Foundation; Finnish Foundation of Cardiovascular Research; Finnish Cultural Foundation FX Framingham Heart Study (FHS): The FHS phenotype-genotype analyses for this work were supported by the National Institute of Aging (Genetics of Reproductive Life Period and Health Outcomes, R21AG032598; JM Murabito, KL Lunetta, D Karasik, DP Kiel, WV Zhuang). The Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine is supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study Contract No. N01-HC-25195 and its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278). Sex hormone measurements were funded primarily by National Institute on Aging grant 1RO1AG31206 (PIs: S Bhasin and RS Vasan); additional support was provided by the Boston Claude D. Pepper Older Americans Independence Center (5P30AG031679) and a grant from the National Institute on Aging and the National Institute of Arthritis Musculoskeletal and Skin Diseases to DP Kiel (R01 AR/AG 41398). Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II), funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Study of Health in Pomerania (SHIP): Computing resources have been made available by the Leibniz Supercomputing Centre of the Bavarian Academy of Sciences and Humanities (HLRB project h1231). SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg - West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg West Pomerania. The University of Greifswald is a member of the "Center of Knowledge Interchange'' program of the Siemens AG. This work is also part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg - West Pomerania (03IS2061A). The testosterone reagents used were sponsored by Siemens Healthcare Diagnostics, Eschborn, formerly DPC Biermann GmbH, Bad Nauheim, Germany. Novo Nordisc provided partial grant support for the determination of serum samples and data analysis. Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study: Financial support was received from the Swedish Research Council (K2010-54X-09894-19-3, 2006-3832, and K2010-52X-20229-05-3), the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Soderberg's Foundation, Petrus and Augusta Hedlunds Foundation, the Vastra Gotaland Foundation, the Goteborg Medical Society, the Novo Nordisk foundation, the Canadian Institutes of Health Research (MOP-15261), and the European Commission grant HEALTH-F2-2008-201865-GEFOS. We would like to acknowledge Maria Nethander at the genomics core facility at University of Gothenburg for statistical analyses. We would also like to thank Dr. Tobias A. Knoch, Luc V.; de Zeeuw,Anis Abuseiris, and Rob de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministerium fuer Forschung und Technology under grants #01 AK 803 A-H and #01 IG 07015 G for access to their grid resources. Cooperative Research in the Region of Augsburg (KORA): The KORA research platform was initiated and financed by the Helmholtz Center Munich, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN-2 and NGFNPlus:01GS0823). Our research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. This study was in part supported by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e. V.). Health, Aging, and Body Composition (Health ABC) Study: This study was supported by National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported (in part) by the Intramural Research Program of the NIH, National Institute on Aging. Rotterdam study (RS1): The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr.175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015;RIDE2), the Netherlands Genomics Initiative (NGI) - Netherlands Consortiumof Healthy Aging (NCHA) project nr.050-060-810, and funding from the European Commision (HEALTH-F2-2008-201865, GEFOS; HEALTH-F2-2008-35627, TREAT-OA). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University Rotterdam; Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture, and Science; the Ministry for Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. We thank Pascal Arp, Mila Jhamai, Dr. Michael Moorhouse, Marijn Verkerk, and Sander Bervoets for their help in creating the GWAS database. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practioners and pharmacists. We would like to thank Dr. Tobias A. Knoch, Luc V. de Zeeuw, Anis Abuseiris, and Rob de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministerium fuer Forschung und Technology under grants # 01 AK 803 A-H and # 01 IG 07015 G for access to their grid resources. Invecchiare in Chianti (InCHIANTI): The InCHIANTI study baseline (1998-2000) was supported as a "targeted project'' (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S.; National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 82336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002); supported in part by the Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. European Male Ageing Study (EMAS): The EMAS is funded by the Commission of the European Communities Fifth Framework Programme "Quality of Life and Management of Living Resources'' Grant QLK6-CT-2001-00258 and supported by funding from the UK Arthritis Research Campaign. The EMAS Principal Investigator is Professor Frederick Wu, MD; Dept of Endocrinology, Manchester Royal Infirmary, UK. The "EMAS Study Group'' consists of the following people:Gyorgy Bartfai, Steven Boonen, Felipe Casanueva, Joseph D Finn, Gianni Forti, Aleksander Giwercman, Thang S Han, Kate L Holliday, Ilpo T Huhtaniemi, Krzysztof Kula, Michael EJ Lean, David M Lee, Terence W O'Neill, Neil Pendleton, Margus Punab, Stephen R Pye, Alan J Silman, Abdelouahid Tajar, Wendy Thomson, Dirk Vanderschueren, and Frederick CW Wu. The authors wish to thank the men who participated in the eight countries and the research/nursing staff in the eight centres: C Pott, Manchester, E Wouters, Leuven, M Nilsson, Malmo, M del Mar Fernandez, Santiago de Compostela, M Jedrzejowska, Lodz, H-M Tabo, Tartu, A Heredi, Szeged for their data collection and C Moseley, Manchester for data entry and project coordination. Dr. Vanderschueren is a senior clinical investigator supported by the Clinical Research Fund of the University Hospitals Leuven, Belgium. Dr. Boonen is a senior clinical investigator of the Fund for Scientific Research-Flanders, Belgium(F.W.O.-Vlaanderen). Dr. Boonen is holder of the Leuven University Chair in Metabolic Bone Diseases. The Osteoporotic Fractures in Men Study - Sweden (MrOS Sweden): Financial support was received from the Swedish Research Council (K2010-54X-09894-19-3, 2006-3832), the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Soderberg's Foundation, Petrus and Augusta Hedlunds Foundation, the Vastra Gotaland Foundation, the Goteborg Medical Society, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS. The Cardiovascular Risk in Young Finns Study (YFS): YFS has been financially supported by the Academy of Finland (grant no. 117797, 121584, and 126925), the Social Insurance Institution of Finland, Turku University Foundation, Tampere and Turku University Hospital Medical Funds, Emil Aaltonen Foundation (T. L), Juho Vainio Foundation, Paavo Nurmi Foundation, the Tampere Tubeculosis Foundation, the Orion-Farmos Research Foundation, Finnish Foundation of Cardiovascular Research, and Finnish Cultural Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 65 Z9 65 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002313 DI 10.1371/journal.pgen.1002313 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400014 PM 21998597 ER PT J AU Pierson, TM Adams, D Bonn, F Martinelli, P Cherukuri, PF Teer, JK Hansen, NF Cruz, P Mullikin, JC Blakesley, RW Golas, G Kwan, J Sandler, A Fajardo, KF Markello, T Tifft, C Blackstone, C Rugarli, EI Langer, T Gahl, WA Toro, C AF Pierson, Tyler Mark Adams, David Bonn, Florian Martinelli, Paola Cherukuri, Praveen F. Teer, Jamie K. Hansen, Nancy F. Cruz, Pedro Mullikin, James C. Blakesley, Robert W. Golas, Gretchen Kwan, Justin Sandler, Anthony Fajardo, Karin Fuentes Markello, Thomas Tifft, Cynthia Blackstone, Craig Rugarli, Elena I. Langer, Thomas Gahl, William A. Toro, Camilo CA NISC Comparative Sequencing TI Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases SO PLOS GENETICS LA English DT Article ID DIMETHYLGLYCINE DEHYDROGENASE; INBORN ERROR; PARAPLEGIA; DEGENERATION; SCA28; GENE; METALLOPROTEASE; IMPAIRMENT; DEFICIENCY; METABOLISM AB We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C) gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C) complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other "mitochondrial'' features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias. C1 [Pierson, Tyler Mark; Adams, David; Golas, Gretchen; Fajardo, Karin Fuentes; Markello, Thomas; Tifft, Cynthia; Gahl, William A.; Toro, Camilo] Natl Inst Hlth Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA. [Adams, David; Golas, Gretchen; Markello, Thomas; Tifft, Cynthia; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Pierson, Tyler Mark; Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD USA. [Martinelli, Paola; Rugarli, Elena I.] Univ Cologne, Bioctr, Cologne, Germany. [Cherukuri, Praveen F.; Hansen, Nancy F.; Cruz, Pedro; Mullikin, James C.; Blakesley, Robert W.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Teer, Jamie K.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Mullikin, James C.; NISC Comparative Sequencing] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Kwan, Justin] Natl Inst Neurol Disorders & Stroke, EMG Sect, NIH, Bethesda, MD USA. [Sandler, Anthony] Childrens Natl Med Ctr, Div Surg, Washington, DC 20010 USA. [Langer, Thomas] Univ Cologne, Inst Genet, Ctr Mol Med CMMC, Cologne Excellence Cluster Cellular Stress Respon, D-5000 Cologne, Germany. [Langer, Thomas] Max Planck Inst Biol Aging, Cologne, Germany. RP Pierson, TM (reprint author), Natl Inst Hlth Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA. EM piersonty@ninds.nih.gov FU National Human Genome Research Institute or National Institutes of Health; NIH, National Institutes of Health; Deutsche Forschungsgemeinschaft [SFB635]; European Research Council FX This work and D Adams, G Golas, K Fuentes Fajardo, T Markello, C Tifft, WA Gahl, and C Toro were supported by the Intramural Research Program of the National Human Genome Research Institute or National Institutes of Health; this work and TM Pierson, D Adams, G Golas, K Fuente Fajardo, C Tifft, WA Gahl, and C Toro were also supported by the NIH Undiagnosed Diseases Program, National Institutes of Health. In addition, work was also supported by grants from the Deutsche Forschungsgemeinschaft (SFB635) and the European Research Council to T Langer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 73 Z9 75 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002325 DI 10.1371/journal.pgen.1002325 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400026 PM 22022284 ER PT J AU Giannelli, SV Graf, CE Herrmann, FR Michel, JP Patel, KV Pizzarelli, F Ferrucci, L Guralnik, J AF Giannelli, Sandra V. Graf, Christophe E. Herrmann, Francois R. Michel, Jean-Pierre Patel, Kushang V. Pizzarelli, Francesco Ferrucci, Luigi Guralnik, Jack TI Natural History of Older Adults with Impaired Kidney Function: The InCHIANTI Study SO REJUVENATION RESEARCH LA English DT Article ID GLOMERULAR-FILTRATION-RATE; NORMAL SERUM CREATININE; CHRONIC RENAL-INSUFFICIENCY; CYSTATIN-C; FUNCTION DECLINE; UNITED-STATES; DISEASE; PROGRESSION; AGE; POPULATION AB The aim of this study was to assess the kidney function of an older community-dwelling population at baseline and appraise its evolution after 3 years of follow-up in terms of chronic kidney disease (CKD) stage progression, magnitude of glomerular filtration rate (GFR) changes, and value of serum creatinine. This was a prospective population-based study of 676 Italian participants, aged 65 years and older. GFR was estimated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease Study equation. Using the Cockcroft-Gault equation. A total of 33% of participants had criteria of CKD (GFR < 60 mL/min) at baseline; among them, the majority remained stable, 10% improved, and 7% progressed to more severe CKD stages at follow-up. Loss of GFR in participants with GFR < 60 mL/min was significantly lower (1.4 mL/min per year) than in participants with GFR >= 60 mL/min (3.3 mL/min per year) at baseline. Most participants classified with CKD stage 2 (GFR 60-89 mL/min) or stage 3 (GFR 30-59 mL/min) at baseline did not change stage, whereas 55% of people with CKD stage 1 (GFR > 90 mL/min) at baseline worsened to stage 2 and 10% worsened to stage 3. An abnormal high level of serum creatinine at baseline did not help to predict who might worsen at follow-up. Older people with CKD displayed a low progression of renal disease and therefore are at higher risk for comorbidities related to CKD than for progression to end-stage renal disease. C1 [Giannelli, Sandra V.; Graf, Christophe E.; Herrmann, Francois R.; Michel, Jean-Pierre] Univ Hosp Geneva, Dept Internal Med Rehabil & Geriatr, Geneva, Switzerland. [Patel, Kushang V.; Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Pizzarelli, Francesco] SM Annunziata Hosp, Div Nephrol, Florence, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Giannelli, SV (reprint author), Univ Hosp Geneva, Dept Internal Med Rehabil & Geriatr, Rue Pont Bochet 3, CH-1226 Thonex, Switzerland. EM sandra.giannelli@hcuge.ch RI Giannelli, Sandra/E-8637-2011; HERRMANN, Francois/B-6710-2011; Graf, Christophe/E-8635-2011 OI HERRMANN, Francois/0000-0003-1312-1517; FU Italian Ministry of Health [ICS 100.1\RS97.71]; National Institute on Aging, National Institutes of Health (NIH); Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland FX This study was supported as a "targeted project" (ICS 100.1\RS97.71) by the Italian Ministry of Health, and in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH). Sandra V. Giannelli was supported by funds from the Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland. The granting institutions named did not interfere in any way with the design, methods, subjects recruitment, data collections, analysis, and preparation of paper. NR 42 TC 7 Z9 7 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD OCT PY 2011 VL 14 IS 5 BP 513 EP 523 DI 10.1089/rej.2011.1179 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 839OA UT WOS:000296375900006 PM 21954982 ER PT J AU Dutta, A Henley, W Lang, IA Murray, A Guralnik, J Wallace, RB Melzer, D AF Dutta, Ambarish Henley, William Lang, Iain A. Murray, Anna Guralnik, Jack Wallace, Robert B. Melzer, David TI The Coronary Artery Disease-Associated 9p21 Variant and Later Life 20-Year Survival to Cohort Extinction SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE coronary artery disease; genetic variation; myocardial infarction; survival; Framingham Risk Score ID CHROMOSOME 9P21.3; HEART-DISEASE; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; GENETIC ASSOCIATION; ISCHEMIC-STROKE; LOCUS; POPULATION; DEATH; SUSCEPTIBILITY AB Background-Common variation at chromosome 9p21 (marked by rs10757278 or rs1333049) is associated with coronary artery disease (CAD) and peripheral vascular disease. A decreasing effect at older age was suggested, and effects on long-term mortality are unclear. We estimated 9p21 associations with CAD and all-cause mortality in a CAD diagnosis-free older population. We also estimated classification gains on adding the variant to the Framingham Risk Score (FRS) for CAD. Methods and Results-DNA was from an Established Populations for Epidemiological Study of the Elderly-Iowa cohort from 1988 (participants >71 years), with death certificates obtained to 2008 for 92% of participants. Cox regression models were adjusted for confounders and CAD risk factors. Of 1095 CAD diagnosis-free participants, 52% were heterozygous (CG) and 22% were homozygous (CC) for the risk C allele rs1333049. Unadjusted CAD-attributed death rates in the CC group were 30 vs 22 per 1000 person-years for the GG group. The C allele was associated with all-cause (hazard ratio, 1.19; 95% CI, 1.08-1.30) and CAD (hazard ratio, 1.29; 95% CI, 1.08-1.56) mortality, independent of CAD risk factors. There was no association with stroke deaths. Variant associations with CAD mortality were attenuated after the age of 80 years (age-interaction term P = 0.05). In age group 71 to 80 years, FRS classified as high risk 21% of respondents who died of CAD within 10 years; adding 9p21 identified 27% of respondents. Conclusions-In 71- to 80-year-old subjects free of CAD diagnoses, 9p21 is associated with excess mortality, mainly attributed to CAD mortality. Adding 9p21 to the FRS may improve the targeting of CAD prevention in older people, but validation in independent samples is needed for confirmation. (Circ Cardiovasc Genet. 2011; 4:542-548.) C1 [Dutta, Ambarish; Henley, William; Lang, Iain A.; Melzer, David] Univ Exeter, Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Exeter EX2 5DW, Devon, England. [Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Ctr Aging, Iowa City, IA USA. [Guralnik, Jack] NIA, NIH, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Univ Exeter, Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk RI Lang, Iain/B-8255-2008; OI Murray, Anna/0000-0002-2351-2522; Lang, Iain/0000-0002-8473-2350; Melzer, David/0000-0002-0170-3838; Dutta, Ambarish/0000-0002-4019-7472 FU National Institutes of Health/National Institute on Aging [R01 AG024233]; Dunhill Trust UK; National Institute for Health Research; Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD FX This study was supported by grant R01 AG024233 and the Intramural Research Program, National Institutes of Health/National Institute on Aging; an unrestricted research grant from the Dunhill Trust UK; and funding from the National Institute for Health Research (Dr Henley).; We thank the many people who contributed to the EPESE-Iowa study, especially the respondents; and the support received from the Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD. NR 33 TC 11 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2011 VL 4 IS 5 BP 542 EP 548 DI 10.1161/CIRCGENETICS.111.960146 PG 7 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 841RB UT WOS:000296529200015 PM 21852414 ER PT J AU Schnabel, RB Kerr, KF Lubitz, SA Alkylbekova, EL Marcus, GM Sinner, MF Magnani, JW Wolf, PA Deo, R Lloyd-Jones, DM Lunetta, KL Mehra, R Levy, D Fox, ER Arking, DE Mosley, TH Muller-Nurasyid, M Young, TR Wichmann, HE Seshadri, S Farlow, DN Rotter, JI Soliman, EZ Glazer, NL Wilson, JG Breteler, MMB Sotoodehnia, N Newton-Cheh, C Kaab, S Ellinor, PT Alonso, A Benjamin, EJ Heckbert, SR AF Schnabel, Renate B. Kerr, Kathleen F. Lubitz, Steven A. Alkylbekova, Ermeg L. Marcus, Gregory M. Sinner, Moritz F. Magnani, Jared W. Wolf, Philip A. Deo, Rajat Lloyd-Jones, Donald M. Lunetta, Kathryn L. Mehra, Reena Levy, Daniel Fox, Ervin R. Arking, Dan E. Mosley, Thomas H. Mueller-Nurasyid, Martina Young, Taylor R. Wichmann, H. -Erich Seshadri, Sudha Farlow, Deborah N. Rotter, Jerome I. Soliman, Elsayed Z. Glazer, Nicole L. Wilson, James G. Breteler, Monique M. B. Sotoodehnia, Nona Newton-Cheh, Christopher Kaeaeb, Stefan Ellinor, Patrick T. Alonso, Alvaro Benjamin, Emelia J. Heckbert, Susan R. CA Candidate Gene Assoc Resource CARe TI Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6R Polymorphism in Relation to Atrial Fibrillation The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) Project SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE atrial fibrillation; single nucleotide polymorphism; epidemiology; cohort study; race/ethnicity ID C-REACTIVE PROTEIN; CHROMOSOME 4Q25; ATHEROSCLEROSIS RISK; EUROPEAN ANCESTRY; ISCHEMIC-STROKE; INFLAMMATION; VARIANTS; INTERLEUKIN-6; DISEASE; DESIGN AB Background-The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated. Methods and Results-We examined a panel of approximately 50 000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n = 18 524; 2260 cases) or African American descent (n = 3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n = 906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n = 19 602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85-0.95; P = 0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72-1.03; P = 0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57-0.89; P = 0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16-1.69; P = 0.0005). Conclusions-In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans. (Circ Cardiovasc Genet. 2011; 4: 557-564.) C1 [Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98101 USA. [Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Schnabel, Renate B.; Sinner, Moritz F.; Magnani, Jared W.; Wolf, Philip A.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Schnabel, Renate B.] Univ Med Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Kerr, Kathleen F.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98101 USA. [Lubitz, Steven A.; Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Alkylbekova, Ermeg L.; Fox, Ervin R.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Marcus, Gregory M.] Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, San Francisco, CA USA. [Sinner, Moritz F.; Mueller-Nurasyid, Martina; Kaeaeb, Stefan] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Wolf, Philip A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Deo, Rajat] Univ Penn, Div Cardiol, Electrophysiol Sect, Philadelphia, PA 19104 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Mehra, Reena] Case Sch Med, Dept Med, Cleveland, OH USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA. [Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Mueller-Nurasyid, Martina; Wichmann, H. -Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Young, Taylor R.; Farlow, Deborah N.; Newton-Cheh, Christopher] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA. [Glazer, Nicole L.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Breteler, Monique M. B.] Univ Med Ctr, Erasmus MC, Rotterdam, Netherlands. [Sotoodehnia, Nona; Heckbert, Susan R.] Univ Washington, Sch Med, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Sotoodehnia, Nona] Univ Washington, Sch Med, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Ctr Human Genet Res, Boston, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Dept Cardiol, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Prevent Med, Boston, MA 02215 USA. RP Heckbert, SR (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Sch Publ Hlth, Dept Epidemiol, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM schnabelr@gmx.de; emelia@bu.edu; heckbert@u.washington.edu RI Alonso, Alvaro/A-4917-2010; Lloyd-Jones, Donald/C-5899-2009; Kerr, Kathleen/A-2893-2013; Schnabel, Renate/F-6527-2014; Breteler, Monique /J-5058-2014; OI Alonso, Alvaro/0000-0002-2225-8323; Lunetta, Kathryn/0000-0002-9268-810X; Seshadri, Sudha/0000-0001-6135-2622; Mehra, Reena/0000-0002-6222-2675; Benjamin, Emelia/0000-0003-4076-2336 FU NIH/NHLBI [RC1HL099452]; American Heart Association [09SDG2280087, 09FTF2190028]; CHS (Cardiovascular Health Study); National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, HHSN268200625226C, HHSN268200900055C, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022 R01HL087641, R01HL59367, R01HL086694, R01HL093029]; FHS (Framingham Heart Study) [R01-HL080295]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; NIH [HHSN268200625226C, 1R01HL092577, RC1HL101056, AG028321, T32 HL007575, DA027021, HL104156, HL105780]; Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-1]; FHS [SCHN 1149/3-1]; German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung); German National Genome Research Network (NGFN); German National Competence Network on Atrial Fibrillation (AFNET); Leducq Foundation [07-CVD 03]; German Heart Foundation; Helmholtz Zentrum Munchen; State of Bavaria; German National Genome Research Network; LMUinnovativ; National Human Genome Research Institute [U01HG004402]; NIH Roadmap for Medical Research [UL1RR025005]; National Institute on Aging [R01AG027002]; National Center for Research Resources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Affymetrix [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; NINDS [NS17950]; National Institute of Aging [AG08122, AG031287, AG033193]; Netherlands Organization of Scientific Research [175.010.2005.011]; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Ageing [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture, and Science; Ministry for Health, Welfare, and Sports; European Commission; Municipality of Rotterdam to the Rotterdam Study; [01GS0499]; [01GI0204]; [01GS0838] FX We acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the all research institutions, study investigators, field staff, and study participants in creating the Candidate Gene Association Resource for Biomedical Research (CARe). The following 3 parent studies have specifically contributed phenotype data and DNA samples through the Massachusetts Institute of Technology, Broad Institute (N01-HC-65226) to create this genotype/phenotype database that will become publically available: ARIC (Atherosclerosis Risk in Communities), University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55022), and University of North Carolina, Forsyth County (N01-HC-55018). This study was additionally supported by grants RC1HL099452 (NIH/NHLBI) and 09SDG2280087 (American Heart Association); CHS (Cardiovascular Health Study). This research was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, HHSN268200625226C, and HHSN268200900055C from the National Heart, Lung, and Blood Institute, and by grant R01-HL080295; FHS (Framingham Heart Study). This research was conducted using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The Framingham Heart Study research was supported by NIH grants 1R01HL092577 (P.T.E., E.J.B.); RC1HL101056 (E.J.B., A.A.); AG028321 (E.J.B.); T32 HL007575 (S.A.L.); DA027021, HL104156, and HL105780 (P.T.E.); The Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-1 and Emmy Noether Program SCHN 1149/3-1 supported FHS research (R. B. S.). JWM was supported by American Heart Association award No. 09FTF2190028; AFNET/KORA S4: The study was also supported by the German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung) in the context of the German National Genome Research Network (NGFN), the German National Competence Network on Atrial Fibrillation (AFNET), the Leducq Foundation (07-CVD 03) by grants to Dr Kaab (01GS0499, 01GI0204, and 01GS0838). Dr Sinner is supported by the German Heart Foundation.; KORA S4: The KORA platform is funded by the Helmholtz Zentrum Munchen, the BMBF partly in the context of the German National Genome Research Network, and the State of Bavaria, and as part of LMUinnovativ; CHARGE Stroke Consortium: Supported by grants or contracts from the National Heart, Lung, and Blood Institute (N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022 R01HL087641, R01HL59367, and R01HL086694, R01HL093029), the National Human Genome Research Institute (U01HG004402), and NIH (HHSN268200625226C) and the NIH Roadmap for Medical Research (UL1R025005) to the Atherosclerosis Risk in Communities study; contracts and grants from the National Heart, Lung, and Blood Institute (N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01HL080295, and R01HL087652), the National Institute on Aging (R01AG027002), the National Center for Research Resources (M01RR00069, that partially supported the genotyping), and the National Institute of Diabetes and Digestive and Kidney Diseases (DK063491) to the Cardiovascular Health Study; grants from the National Heart, Lung, and Blood Institute (N01-HC-25195) and its contract with Affymetrix for genotyping services (N02-HL-6-4278), the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center for the use of the Linux Cluster for Genetic Analysis; and by grants from the NINDS (NS17950) and the National Institute of Aging (AG08122, AG031287, and AG033193 to the Framingham Heart Study), the Netherlands Organization of Scientific Research (175.010.2005.011), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Ageing (050-060-810), the Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture, and Science, the Ministry for Health, Welfare, and Sports, the European Commission, and the Municipality of Rotterdam to the Rotterdam Study. We thank the staff and participants of the above-mentioned studies for their important contributions. NR 45 TC 27 Z9 29 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2011 VL 4 IS 5 BP 557 EP U188 DI 10.1161/CIRCGENETICS.110.959197 PG 28 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 841RB UT WOS:000296529200017 PM 21846873 ER PT J AU Saunier, B Triyatni, M Berger, EA AF Saunier, Bertrand Triyatni, Miriam Berger, Edward A. TI Culturing HCV: challenges and progress SO FUTURE VIROLOGY LA English DT Article DE adaptive mutations; cell culture; deterministic approaches; HCV; human hepatocytes; RNA replication ID HEPATITIS-C-VIRUS; CELL-CULTURE; IN-VIVO; EFFICIENT REPLICATION; STRUCTURAL PROTEINS; ACTING ANTIVIRALS; RNA REPLICATION; INFECTION; PARTICLES; GENOTYPE AB Hepatocellular carcinoma cell lines supporting HCV replication in culture produce infectious particles (cell culture-derived HCV) for only a limited number of strains. Mutations in the viral genome resulting from the combined effects of the error-prone HCV RNA polymerase coupled with selection of the best-adapted viral variants generate a drift in cell culture-derived HCV properties, which can result in a total loss of in vivo infectivity in the chimpanzee model. Other systems for producing HCV or HCV-related particles, some of which bypass HCV RNA replication, have been developed to study the biology of this virus, with limitations of their own. This review briefly analyzes the pros and cons of these in vitro models, focusing on recent advances. C1 [Saunier, Bertrand] Inst Cochin, F-75014 Paris, France. [Saunier, Bertrand] INSERM, U1016, Paris, France. [Saunier, Bertrand] CNRS, UMR8104, Paris, France. [Saunier, Bertrand] Univ Paris 05, Fac Med, F-75006 Paris, France. [Triyatni, Miriam] Hoffmann La Roche Inc, Virol Discovery, Nutley, NJ 07110 USA. [Berger, Edward A.] NIAID, Mol Struct Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Saunier, B (reprint author), Inst Cochin, 27 Rue Fg St Jacques, F-75014 Paris, France. EM bertrand.saunier@inserm.fr NR 78 TC 0 Z9 0 U1 3 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 J9 FUTURE VIROL JI Future Virol. PD OCT PY 2011 VL 6 IS 10 BP 1169 EP 1178 DI 10.2217/FVL.11.95 PG 10 WC Virology SC Virology GA 841FA UT WOS:000296496700010 ER PT J AU Shriner, D AF Shriner, D. TI Investigating population stratification and admixture using eigenanalysis of dense genotypes SO HEREDITY LA English DT Article DE admixture; population stratification; principal components; stopping rule; vicariance ID PRINCIPAL-COMPONENTS; NUMBER; ASSOCIATION; MAP AB Principal components analysis of genetic data is used to avoid inflation in type I error rates in association testing due to population stratification by covariate adjustment using the top eigenvectors and to estimate cluster or group membership independent of self-reported or ethnic identities. Eigendecomposition transforms correlated variables into an equal number of uncorrelated variables. Numerous stopping rules have been developed to identify which principal components should be retained. Recent developments in random matrix theory have led to a formal hypothesis test of the top eigenvalue, providing another way to achieve dimension reduction. In this study, I compare Velicer's minimum average partial test to a test on the basis of Tracy-Widom distribution as implemented in EIGENSOFT, the most widely used implementation of principal components analysis in genome-wide association analysis. By computer simulation of vicariance on the basis of coalescent theory, EIGENSOFT systematically overestimates the number of significant principal components. Furthermore, this overestimation is larger for samples of admixed individuals than for samples of unadmixed individuals. Overestimating the number of significant principal components can potentially lead to a loss of power in association testing by adjusting for unnecessary covariates and may lead to incorrect inferences about group differentiation. Velicer's minimum average partial test is shown to have both smaller bias and smaller variance, often with a mean squared error of 0, in estimating the number of principal components to retain. Velicer's minimum average partial test is implemented in R code and is suitable for genome-wide genotype data with or without population labels. Heredity (2011) 107, 413-420; doi:10.1038/hdy.2011.26; published online 30 March 2011 C1 NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. RP Shriner, D (reprint author), NHGRI, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA. EM shrinerda@mail.nih.gov FU National Institutes of Health [S06GM008016-320107, S06GM008016-380111, 2M01RR010284]; Center for Research on Genomics and Global Health (CRGGH); National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; Office of the Director at the National Institutes of Health [Z01HG200362] FX I thank Gil McVean for sharing R code to perform simulations of coalescent vicariance for two populations. The contents of this publication are solely the responsibility of the author and do not necessarily represent the official view of the National Institutes of Health. The Howard University Family Study was supported by National Institutes of Health grants S06GM008016-320107 to Charles Rotimi and S06GM008016-380111 to Adebowale Adeyemo. Participant enrollment was carried out at the Howard University General Clinical Research Center, supported by National Institutes of Health grant 2M01RR010284. Genotyping support was provided by the Coriell Institute for Medical Research. This research was supported by the Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362). NR 19 TC 17 Z9 17 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0018-067X J9 HEREDITY JI Heredity PD OCT PY 2011 VL 107 IS 5 BP 413 EP 420 DI 10.1038/hdy.2011.26 PG 8 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 842BE UT WOS:000296560300005 PM 21448230 ER PT J AU Ji, HF Ren, W Wang, LY Shi, P Chen, XF Wu, XQ Yao, X Lau, ST Zhou, QF Shung, KK AF Ji, Hongfen Ren, Wei Wang, Lingyan Shi, Peng Chen, Xiaofeng Wu, Xiaoqing Yao, Xi Lau, Sien-Ting Zhou, Qifa Shung, K. Kirk TI Structure and Electrical Properties of Na0.5Bi0.5TiO3 Ferroelectric Thick Films Derived From a Polymer Modified Sol-Gel Method SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID PULSED-LASER DEPOSITION; PIEZOELECTRIC PROPERTIES; MU-M; DEPENDENCE; POLYVINYLPYRROLIDONE; FABRICATION; STRESS; MODEL AB Lead-free Na0.5Bi0.5TiO3 (NBT) ferroelectric thick films were prepared by a poly(vinylpyrrolidone) (PVP) modified sol-gel method. The NBT thick films annealed from 500 degrees C to 750 degrees C exhibit a perovskite structure. The relationship between annealing temperature, thickness, and electrical properties of the thick films has been investigated. The dielectric constants and remnant polarizations of the thick films increase with annealing temperature. The electrical properties of the NBT films show strong thickness dependence. As thickness increases from 1.0 to 4.8 mu m, the dielectric constant of the NBT films increases from 620 to 848, whereas the dielectric loss is nearly independent of the thickness. The remnant polarization of the NBT thick films also increases with increasing thickness. The leakage current density first decreases and then increases with film thickness. C1 [Ji, Hongfen; Ren, Wei; Wang, Lingyan; Shi, Peng; Chen, Xiaofeng; Wu, Xiaoqing; Yao, Xi] Xi An Jiao Tong Univ, Elect Mat Res Lab, Key Lab, Minist Educ, Xian, Peoples R China. [Ji, Hongfen; Ren, Wei; Wang, Lingyan; Shi, Peng; Chen, Xiaofeng; Wu, Xiaoqing; Yao, Xi] Xi An Jiao Tong Univ, Int Ctr Dielect Res, Xian, Peoples R China. [Lau, Sien-Ting; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA USA. [Lau, Sien-Ting; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. RP Ji, HF (reprint author), Xi An Jiao Tong Univ, Elect Mat Res Lab, Key Lab, Minist Educ, Xian, Peoples R China. EM wren@mail.xtju.edu.cn RI Lau, Sien-Ting/B-6091-2013; shi, peng/C-8551-2011 OI shi, peng/0000-0003-2217-8486 FU National Natural Science Foundation of China [90923001, U0634006]; International Science & Technology Cooperation Program of China [2010DFB13640]; Shaanxi Province International Collaboration Program [2009KW-12, 2010KW-09]; NIH [P41-EB2182] FX Manuscript received December 31, 2010; accepted July 8, 2011. This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 90923001 and U0634006), by the International Science & Technology Cooperation Program of China (Grant No. 2010DFB13640), by the Shaanxi Province International Collaboration Program (Grant Nos. 2009KW-12 and 2010KW-09), and by NIH Grant P41-EB2182. NR 36 TC 18 Z9 18 U1 3 U2 25 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD OCT PY 2011 VL 58 IS 10 BP 2042 EP 2049 DI 10.1109/TUFFC.2011.2054 PG 8 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 847XI UT WOS:000297007300003 PM 21989868 ER PT J AU Wang, E Marincola, FM AF Wang, Ena Marincola, Francesco M. TI Applying the uncertainty principle to immunology FOREWORD SO IMMUNOTHERAPY LA English DT Editorial Material ID CANCER PATIENTS; T-CELLS; TUMOR; IMMUNITY C1 [Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis Immunogenet Sect IDIS, Dept Transfus Med, Clin Ctr trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Infect Dis Immunogenet Sect IDIS, Dept Transfus Med, Clin Ctr trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA. EM fmarincola@mail.cc.nih.gov FU Intramural NIH HHS [ZIA CL002118-03] NR 20 TC 1 Z9 1 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD OCT PY 2011 VL 3 IS 10 BP 1127 EP 1128 DI 10.2217/IMT.11.125 PG 2 WC Immunology SC Immunology GA 843XX UT WOS:000296711800001 PM 21995565 ER PT J AU Kotlan, B Umansky, V Malyguine, AM Marincola, FM Shurin, MR AF Kotlan, Beatrix Umansky, Viktor Malyguine, Anatoli M. Marincola, Francesco M. Shurin, Michael R. TI Immunotherapy reaches new milestones in cancer eradication SO IMMUNOTHERAPY LA English DT News Item ID ADOPTIVE IMMUNOTHERAPY; T-CELLS; THERAPY; LYMPHOCYTES C1 [Kotlan, Beatrix] Natl Inst Oncol, Ctr Surg & Mol Tumor Pathol, Dept Mol Immunol & Toxicol, Budapest, Hungary. [Umansky, Viktor] German Canc Res Ctr, Clin Cooperat Unit, D-69120 Heidelberg, Germany. [Malyguine, Anatoli M.] NCI, Lab Cell Mediated Immun, SAIC Frederick, Frederick, MD 21702 USA. [Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Translat Med, Ctr Clin, Bethesda, MD 20892 USA. [Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Shurin, Michael R.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA 15213 USA. [Shurin, Michael R.] Univ Pittsburgh, Dept Immunol, Med Ctr, Pittsburgh, PA 15213 USA. RP Kotlan, B (reprint author), Natl Inst Oncol, Ctr Surg & Mol Tumor Pathol, Dept Mol Immunol & Toxicol, 1122 Rath Gy St 7-9, Budapest, Hungary. EM kotlanb@netscape.net NR 21 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD OCT PY 2011 VL 3 IS 10 BP 1131 EP 1137 DI 10.2217/IMT.11.114 PG 7 WC Immunology SC Immunology GA 843XX UT WOS:000296711800004 PM 21995567 ER PT J AU Subleski, JJ Jiang, Q Weiss, JM Wiltrout, RH AF Subleski, Jeff J. Jiang, Qun Weiss, Jonathan M. Wiltrout, Robert H. TI The split personality of NKT cells in malignancy, autoimmune and allergic disorders SO IMMUNOTHERAPY LA English DT Review DE autoimmunity; cancer; inflammation; NAFLD; type I NKT cells; type II NKT cells ID KILLER T-CELLS; FATTY LIVER-DISEASE; INDUCED JOINT INFLAMMATION; NONOBESE DIABETIC MICE; INNATE IMMUNE-SYSTEM; INDUCED AIRWAY HYPERREACTIVITY; ANTIGEN-PRESENTING CELLS; PHASE I/II TRIAL; NATURAL-KILLER; DENDRITIC CELLS AB NKT cells are a heterogeneous subset of specialized, self-reactive T cells, with innate and adaptive immune properties, which allow them to bridge innate and adaptive immunity and profoundly influence autoimmune and malignant disease outcomes. NKT cells mediate these activities through their ability to rapidly express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. Not only do NKT cells regulate the functions of other cell types, but experimental evidence has found NKT cell subsets can modulate the functions of other NKT subsets. Depending on underlying mechanisms, NKT cells can inhibit or exacerbate autoimmunity and malignancy, making them potential targets for disease intervention. NKT cells can respond to foreign and endogenous antigenic glycolipid signals that are expressed during pathogenic invasion or ongoing inflammation, respectively, allowing them to rapidly react to and influence a broad array of diseases. In this article we review the unique development and activation pathways of NKT cells and focus on how these attributes augment or exacerbate autoimmune disorders and malignancy. We also examine the growing evidence that NKT cells are involved in liver inflammatory conditions that can contribute to the development of malignancy. C1 [Subleski, Jeff J.; Jiang, Qun; Weiss, Jonathan M.; Wiltrout, Robert H.] NCI, Lab Expt Immunol, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Wiltrout, RH (reprint author), NCI, Lab Expt Immunol, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. EM wiltrour@mail.nih.gov RI Jiang, Qun/A-1358-2014 FU National Cancer Institute (NCI)/NIH FX This work was supported by the Intramural Research Program of the National Cancer Institute (NCI)/NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 211 TC 17 Z9 20 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD OCT PY 2011 VL 3 IS 10 BP 1167 EP 1184 DI 10.2217/IMT.11.117 PG 18 WC Immunology SC Immunology GA 843XX UT WOS:000296711800007 PM 21995570 ER PT J AU Schauberger, EM Ewart, SL Arshad, SH Huebner, M Karmaus, W Holloway, JW Friderici, KH Ziegler, JT Zhang, HM Rose-Zerilli, MJ Barton, SJ Holgate, ST Kilpatrick, JR Harley, JB Lajoie-Kadoch, S Harley, ITW Hamid, Q Kurukulaaratchy, RJ Seibold, MA Avila, PC Rodriguez-Cintron, W Rodriguez-Santana, JR Hu, DL Gignoux, C Romieu, I London, SJ Burchard, EG Langefeld, CD Wills-Karp, M AF Schauberger, Eric M. Ewart, Susan L. Arshad, Syed H. Huebner, Marianne Karmaus, Wilfried Holloway, John W. Friderici, Karen H. Ziegler, Julie T. Zhang, Hongmei Rose-Zerilli, Matthew J. Barton, Sheila J. Holgate, Stephen T. Kilpatrick, Jeffrey R. Harley, John B. Lajoie-Kadoch, Stephane Harley, Isaac T. W. Hamid, Qutayba Kurukulaaratchy, Ramesh J. Seibold, Max A. Avila, Pedro C. Rodriguez-Cintron, William Rodriguez-Santana, Jose R. Hu, Donglei Gignoux, Christopher Romieu, Isabelle London, Stephanie J. Burchard, Esteban G. Langefeld, Carl D. Wills-Karp, Marsha TI Identification of ATPAF1 as a novel candidate gene for asthma in children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; ATPAF1; children; gene; genetic; genome-wide association; purinergic; respiratory; single nucleotide polymorphism; SNP ID GENOME-WIDE ASSOCIATION; CHILDHOOD ASTHMA; PUERTO-RICAN; SUSCEPTIBILITY GENES; EXTRACELLULAR ATP; ASSEMBLY FACTORS; LINKAGE ANALYSES; DENDRITIC CELLS; FRENCH EGEA; PHENOTYPES AB Background: Asthma is a common disease of children with a complex genetic origin. Understanding the genetic basis of asthma susceptibility will allow disease prediction and risk stratification. Objective: We sought to identify asthma susceptibility genes in children. Methods: A nested case-control genetic association study of children of Caucasian European ancestry from a birth cohort was conducted. Single nucleotide polymorphisms (SNPs, n = 116,024) were genotyped in pools of DNA samples from cohort children with physician-diagnosed asthma (n = 112) and normal controls (n = 165). A genomic region containing the ATPAF1 gene was found to be significantly associated with asthma. Additional SNPs within this region were genotyped in individual samples from the same children and in 8 independent study populations of Caucasian, African American, Hispanic, or other ancestries. SNPs were also genotyped or imputed in 2 consortia control populations. ATPAF1 expression was measured in bronchial biopsies from asthmatic patients and controls. Results: Asthma was found to be associated with a cluster of SNPs and SNP haplotypes containing the ATPAF1 gene, with 2 SNPs achieving significance at a genome-wide level (P = 2.26 x 10(-5) to 2.2 x 10(-8)). Asthma severity was also found to be associated with SNPs and SNP haplotypes in the primary population. SNP and/or gene-level associations were confirmed in the 4 non-Hispanic populations. Haplotype associations were also confirmed in the non-Hispanic populations (P = .045-.0009). ATPAF1 total RNA expression was significantly (P < .01) higher in bronchial biopsies from asthmatic patients than from controls. Conclusion: Genetic variation in the ATPAF1 gene predisposes children of different ancestries to asthma. (J Allergy Clin Immunol 2011;128:753-60.) C1 [Ewart, Susan L.] Michigan State Univ, Vet Med Ctr G100, E Lansing, MI 48824 USA. [Arshad, Syed H.; Kurukulaaratchy, Ramesh J.] David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England. [Arshad, Syed H.; Holloway, John W.; Rose-Zerilli, Matthew J.; Barton, Sheila J.; Holgate, Stephen T.; Kurukulaaratchy, Ramesh J.] Univ Southampton, Sch Med, Southampton SO9 5NH, Hants, England. [Karmaus, Wilfried; Zhang, Hongmei] Univ S Carolina, Columbia, SC 29208 USA. [Ziegler, Julie T.; Langefeld, Carl D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Kilpatrick, Jeffrey R.; Harley, John B.] JKA Genom, Oklahoma City, OK USA. [Harley, John B.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Lajoie-Kadoch, Stephane; Harley, Isaac T. W.; Wills-Karp, Marsha] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Hamid, Qutayba] McGill Univ, Meakins Christie Lab, Montreal, PQ, Canada. [Seibold, Max A.] Natl Jewish Hlth, Denver, CO USA. [Avila, Pedro C.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Rodriguez-Cintron, William] Vet Affairs Med Ctr, San Juan, PR USA. [Rodriguez-Santana, Jose R.] CSP, Ctr Neumol Pediatr, San Juan, PR USA. [Hu, Donglei; Gignoux, Christopher; Burchard, Esteban G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Romieu, Isabelle] Natl Inst Publ Hlth, Cuernevaca, Mexico. [London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Ewart, SL (reprint author), Michigan State Univ, Vet Med Ctr G100, E Lansing, MI 48824 USA. EM ewart@cvm.msu.edu RI Holloway, John/B-5424-2009; Schauberger, Eric/A-9213-2008; OI Holloway, John/0000-0001-9998-0464; Schauberger, Eric/0000-0001-5069-7190; Barton, Sheila/0000-0003-4963-4242; London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health [R01 AI061471, R01 HL67736, P01 HL076383, T32GM063483]; Asthma UK [364]; Asthma, Allergy and Inflammation Research Charity; Richard and Edith Strauss Foundation of Canada; Robert Wood Johnson Foundation Amos Medical Faculty [HL078885, HL088133, AI077439, ES015794]; Flight Attendant Medical Research Institute (FAMRI); National Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES49019]; National Council of Science and Technology, Mexico [26206-M]; National Center for Environmental Health at the Centers for Disease Control and Prevention; National Heart, Lung, and Blood Institute [NO1-HR-16044, NO1-HR-16045, NO1-HR-16046, NO1-HR-16047, NO1-HR-16048, NO1-HR-16049, NO1-HR-16050, NO1-HR-16051, NO1-HR-16052, HL071742-01, HL004519-04, 5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, 5U10HL064313]; General Clinical Research Center; National Center for Research Resources [M01RR00051, M01RR0099718-24, M01RR02719-14, RR00036]; National Institutes of Health and the National Jewish Medical and Research Center [M01 RR00036, M01 RR00051] FX This study was funded by the National Institutes of Health, grants R01 AI061471, R01 HL67736, P01 HL076383, and T32GM063483, Asthma UK (364), and the Asthma, Allergy and Inflammation Research Charity. The Wessex Family Cohort was originally recruited in collaboration with Genome Therapeutics Corporation and Schering-Plough. The Richard and Edith Strauss Foundation of Canada and Dr Ron Olivenstein supported the severe asthma program and collection of bronchial biopsies. The GALA studies were supported by grants HL078885, HL088133, AI077439, and ES015794, Robert Wood Johnson Foundation Amos Medical Faculty Development Program, Flight Attendant Medical Research Institute (FAMRI). The Mexico Childhood Asthma Study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01 ES49019). Subject enrollment was also supported in part by the National Council of Science and Technology (grant 26206-M), Mexico. I. Romieu was supported in part by the National Center for Environmental Health at the Centers for Disease Control and Prevention. The CAMP study was supported by contracts with the National Heart, Lung, and Blood Institute (NO1-HR-16044, NO1-HR-16045, NO1-HR-16046, NO1-HR-16047, NO1-HR-16048, NO1-HR-16049, NO1-HR-16050, NO1-HR-16051, and NO1-HR-16052) and by General Clinical Research Center grants from the National Center for Research Resources (M01RR00051, M01RR0099718-24, M01RR02719-14, and RR00036). The CARE study was supported by grants (HL071742-01, HL004519-04, 5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, and 5U10HL064313) from the National Heart, Lung, and Blood Institute. This study was carried out in part in the General Clinical Research Centers at Washington University School of Medicine (M01 RR00036) sponsored by the National Institutes of Health and the National Jewish Medical and Research Center (M01 RR00051). The data analyses for the CAMP, CARE, Wellcome Trust Case Control Consortium, and the Consortium for Systemic Lupus Erythematosus Genetics populations were supported by the Wake Forest School of Medicine Center for Public Health Genomics. NR 65 TC 14 Z9 14 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2011 VL 128 IS 4 BP 753 EP U415 DI 10.1016/j.jaci.2011.04.058 PG 19 WC Allergy; Immunology SC Allergy; Immunology GA 841UA UT WOS:000296538100008 PM 21696813 ER PT J AU White, SS Fenton, SE Hines, EP AF White, Sally S. Fenton, Suzanne E. Hines, Erin P. TI Endocrine disrupting properties of perfluorooctanoic acid SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE PFOA; Mammary gland; PPAR; Exposure; Developmental effects ID MAMMARY-GLAND DEVELOPMENT; ACTIVATED RECEPTOR-ALPHA; NATIONAL BIRTH COHORT; HUMAN BREAST-MILK; PERFLUORINATED COMPOUNDS; PEROXISOME PROLIFERATOR; POLYFLUOROALKYL CHEMICALS; SULFONATE PFOS; AMMONIUM PERFLUOROOCTANOATE; PRENATAL EXPOSURE AB Perfluoroallcyl acids (PFAAs) have attracted attention in recent years for their environmental ubiquity, as well as their toxicity. Several PFAAs are found in human tissues globally, as humans are exposed on a daily basis through intake of contaminated food, water, and air, irrespective of proximity to industry. Perfluorooctanoic acid (PFOA) is a PFAA shown to be developmentally toxic in mice, with broad and varied health consequences that may include long-lasting effects in reproductive tissues and metabolic reprogramming. To date, the only demonstrated mode of action by which the health effects of PFOA are mediated is via the activation of the peroxisome proliferator-activated receptor alpha (PPAR alpha). The endogenous roles for this receptor, as well as the adverse outcomes of activation by exogenous agents during development, are currently under investigation. Recent studies suggest that PFOA may alter steroid hormone production or act indirectly, via ovarian effects, as a novel means of endocrine disruption. Here we review the existing literature on the known health effects of PFOA in animal models, focusing on sensitive developmental periods. To complement this, we also present epidemiologic health data, with the caveat that these studies largely address only associations between adult exposures and outcomes, rarely focusing on endocrine-specific endpoints, susceptible subpopulations, or windows of sensitivity. Further research in these areas is needed. Published by Elsevier C1 [White, Sally S.; Fenton, Suzanne E.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Hines, Erin P.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27711 USA. RP Fenton, SE (reprint author), NIEHS, Natl Toxicol Program, NIH, POB 12233,Bldg 101,MD E1-08, Res Triangle Pk, NC 27709 USA. EM fentonse@niehs.nih.gov OI Hines, Erin Pias/0000-0002-2458-6267 FU Intramural NIH HHS [ZIA ES102785-01, ZIA ES102785-02] NR 99 TC 83 Z9 85 U1 6 U2 76 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 2011 VL 127 IS 1-2 SI SI BP 16 EP 26 DI 10.1016/j.jsbmb.2011.03.011 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 841WV UT WOS:000296546800004 PM 21397692 ER PT J AU Liu, XD Xu, LQ Sun, LG Liu, F Wang, YH Yan, H Liu, Y Luo, YH Huang, J AF Liu Xiaodong Xu Liqiang Sun Liguang Liu Fei Wang Yuhong Yan Hong Liu Yi Luo Yuhan Huang Jing TI A 400-year record of black carbon flux in the Xisha archipelago, South China Sea and its implication SO MARINE POLLUTION BULLETIN LA English DT Article DE Xisha Archipelago; Ornithogenic sediments; Black carbon; Deposition flux; Energy structure ID POLYCYCLIC AROMATIC-HYDROCARBONS; LAKE-SEDIMENTS; DONGDAO ISLAND; GEOCHEMICAL EVIDENCE; SURFACE SEDIMENTS; ORGANIC-MATTER; SOILS; EMISSIONS; RADIONUCLIDES; OXIDATION AB We reconstructed the first long-term (similar to 400 years) records of black carbon (BC) deposition flux from three ornithogenic sediment profiles, which were collected from three remote, isolated islets of the Xisha archipelago, South China Sea. The significant correlations between black carbon, organic matter and excess Pb-210 suggested that black carbon was mainly derived from atmospheric deposition, and further enriched by plant-derived organic matter in sediments. During the past 400 years, the BC flux remained relatively low before the onset of 20th century; it started to increase from approximately 1900 AD, and peaked around the 1970s. In the recent 30 years, the BC flux seemed to display decreasing trend, very likely due to the change of energy structure and development of pollution control techniques. In comparison with marginal sea regions that are greatly impacted by anthropogenic activities, these pristine Xisha islands were not significantly influenced by black carbon of anthropogenic origin. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Liu Xiaodong; Xu Liqiang; Sun Liguang; Liu Fei; Yan Hong; Liu Yi; Luo Yuhan; Huang Jing] Univ Sci & Technol China, Inst Polar Environm, Sch Earth & Space Sci, Hefei 230026, Anhui, Peoples R China. [Wang Yuhong] NIH, Bethesda, MD 20892 USA. RP Liu, XD (reprint author), Univ Sci & Technol China, Inst Polar Environm, Sch Earth & Space Sci, Hefei 230026, Anhui, Peoples R China. EM ycx@ustc.edu.cn; slg@ustc.edu.cn RI Yan, Hong/I-8970-2014 FU National Natural Science Foundation of China [40730107]; National Basic Research Program of China (973 Program) [2010CB428902]; CAS [KZCX2-EW-QN50]; Ministry of Education of China's Ph.D. Programs Foundation for the new teachers [20093402120004]; Fundamental Research Funds for the Central Universities [WK2060190007] FX This work was funded by the National Natural Science Foundation of China (No. 40730107), the National Basic Research Program of China (973 Program, No. 2010CB428902), Knowledge Innovation Program of CAS (KZCX2-EW-QN50), the Ministry of Education of China's Ph.D. Programs Foundation for the new teachers (20093402120004) and the Fundamental Research Funds for the Central Universities (No. WK2060190007). All members of field study team, including the Chinese People's Liberation Army, are acknowledged for their help in sample collection. NR 52 TC 10 Z9 13 U1 5 U2 36 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0025-326X EI 1879-3363 J9 MAR POLLUT BULL JI Mar. Pollut. Bull. PD OCT PY 2011 VL 62 IS 10 BP 2205 EP 2212 DI 10.1016/j.marpolbul.2011.06.027 PG 8 WC Environmental Sciences; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA 834IX UT WOS:000295954100033 PM 21840551 ER PT J AU Englund, EE Neumann, S Eliseeva, E McCoy, JG Titus, S Zheng, W Southall, N Shinn, P Leister, W Thomas, CJ Inglese, J Austin, CP Gershengorn, MC Huang, WW AF Englund, Erika E. Neumann, Susanne Eliseeva, Elena McCoy, Joshua G. Titus, Steven Zheng, Wei Southall, Noel Shinn, Paul Leister, William Thomas, Craig J. Inglese, James Austin, Christopher P. Gershengorn, Marvin C. Huang, Wenwei TI The synthesis and evaluation of dihydroquinazolin-4-ones and quinazolin-4-ones as thyroid stimulating hormone receptor agonists SO MEDCHEMCOMM LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; SMALL-MOLECULE AGONISTS; INVERSE AGONIST; TSH RECEPTOR; BINDING; ANTAGONIST AB We herein describe the rapid synthesis of a diverse set of dihydroquinazolin-4-ones and quinazolin-4-ones, their biological evaluation as thyroid stimulating hormone receptor (TSHR) agonists, and SAR analysis. Among the compounds screened, 8b was 60-fold more potent than the hit compound la, which was identified from a high throughput screen of over 73,000 compounds. C1 [Englund, Erika E.; McCoy, Joshua G.; Titus, Steven; Zheng, Wei; Southall, Noel; Shinn, Paul; Leister, William; Thomas, Craig J.; Inglese, James; Austin, Christopher P.; Huang, Wenwei] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Neumann, Susanne; Eliseeva, Elena; Gershengorn, Marvin C.] NIDDK, Bethesda, MD 20892 USA. RP Huang, WW (reprint author), NIH, Chem Genom Ctr, 9800 Med Ctr Dr,Bldg B, Bethesda, MD 20892 USA. RI Southall, Noel/H-8991-2012; OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU National Institute of Diabetes and Digestive and Kidney Diseases; Molecular Libraries Initiative of the Roadmap for Medical Research, National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the Molecular Libraries Initiative of the Roadmap for Medical Research, National Institutes of Health. We thank Chris LeClair, Jim Bougie, Danielle VanLeer and Thomas Daniel for compound management and analytical support. NR 26 TC 5 Z9 5 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 J9 MEDCHEMCOMM JI MedChemComm PD OCT PY 2011 VL 2 IS 10 BP 1016 EP 1020 DI 10.1039/c1md00145k PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 840AS UT WOS:000296411200014 PM 22408719 ER PT J AU Devine, MJ Gwinn, K Singleton, A Hardy, J AF Devine, Michael J. Gwinn, Katrina Singleton, Andrew Hardy, John TI Parkinson's Disease and alpha-Synuclein Expression SO MOVEMENT DISORDERS LA English DT Review DE Parkinsonism; genetics; alpha-synuclein ID MULTIPLE SYSTEM ATROPHY; LEWY BODY; IN-VIVO; SNCA DUPLICATION; GENE DUPLICATION; MOUSE MODEL; NEURODEGENERATIVE DISEASE; DOPAMINERGIC-NEURONS; LOCUS TRIPLICATION; MESSENGER-RNA AB Genetic studies of Parkinson's disease over the last decade or more have revolutionized our understanding of this condition. alpha-Synuclein was the first gene to be linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease. Intriguingly, duplications and triplications of the locus, as well as point mutations, cause familial disease. Therefore, subtle alterations of alpha-synuclein expression can manifest with a dramatic phenotype. We outline the clinical impact of alpha-synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis. Finally, we discuss potential strategies for disease-modifying therapies for this currently incurable disorder. (C) 2011 Movement Disorder Society C1 [Devine, Michael J.; Hardy, John] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Gwinn, Katrina] Baylor Coll Med, Houston, TX 77030 USA. [Singleton, Andrew] NIA, NIH, Bethesda, MD 20892 USA. RP Devine, MJ (reprint author), UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM m.devine@ion.ucl.ac.uk RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009 FU Medical Research Council [G0800437, G0701075, MC_G1000735]; Parkinson's UK [G-0907]; Wellcome Trust [089698] NR 98 TC 64 Z9 65 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2011 VL 26 IS 12 BP 2160 EP 2168 DI 10.1002/mds.23948 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 842PH UT WOS:000296610900004 PM 21887711 ER PT J AU Bratslavsky, G Linehan, WM AF Bratslavsky, Gennady Linehan, W. Marston TI SURGERY Routine adrenalectomy in renal cancer-an antiquated practice SO NATURE REVIEWS UROLOGY LA English DT Editorial Material ID RADICAL NEPHRECTOMY; INSUFFICIENCY; COMPONENT; GLAND AB For decades, complete removal of the kidney with all the contents of the Gerota's fascia (including the adrenal gland) has been a standard procedure for treating renal cell carcinoma (RCC). Two recent articles argue against routine adrenalectomy, and encourage adrenal preservation for the vast majority of patients with RCC. C1 [Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bratslavsky, Gennady] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,Room 1-5940, Bethesda, MD 20892 USA. EM wml@nih.gov FU Intramural NIH HHS [Z01 BC011023-01]; NCI NIH HHS [Z01 BC011092-01, Z01 BC011028-01, Z01 BC011023-01, Z01 BC011089-01] NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 J9 NAT REV UROL JI Nat. Rev. Urol. PD OCT PY 2011 VL 8 IS 10 BP 534 EP 536 DI 10.1038/nrurol.2011.136 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 838CT UT WOS:000296265100002 PM 21931345 ER PT J AU Steeg, PS Zollo, M Wieland, T AF Steeg, Patricia S. Zollo, Massimo Wieland, Thomas TI A critical evaluation of biochemical activities reported for the nucleoside diphosphate kinase/Nm23/Awd family proteins: opportunities and missteps in understanding their biological functions SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Editorial Material ID X-RAY-STRUCTURE; HETEROTRIMERIC G-PROTEINS; ENERGY PHOSPHATE TRANSFER; SUPPRESS CELL-MIGRATION; GTP-BINDING-PROTEIN; BETA-GAMMA DIMERS; ATP-CITRATE LYASE; KINASE NDPK B; TUMOR-METASTASIS; ESCHERICHIA-COLI C1 [Wieland, Thomas] Univ Heidelberg, Mannheim Med Fac, Inst Expt & Clin Pharmacol & Toxicol, D-68169 Mannheim, Germany. [Zollo, Massimo] Univ Naples Federico 2, Dipartimento Biochim & Biotecnol Avanzate, DBBM, Ctr Ingn Genet Biotecnol Avanzate,CEINGE, I-80131 Naples, Italy. [Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Wieland, T (reprint author), Univ Heidelberg, Mannheim Med Fac, Inst Expt & Clin Pharmacol & Toxicol, Maybachstr 14, D-68169 Mannheim, Germany. EM steegp@mail.nih.gov; massimo.zollo@unina.it; thomas.wieland@urz.uni-heidelberg.de RI Wieland, Thomas/G-1772-2012; Zollo, Massimo/K-5857-2016 OI Zollo, Massimo/0000-0002-0970-7243 NR 101 TC 20 Z9 20 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD OCT PY 2011 VL 384 IS 4-5 BP 331 EP 339 DI 10.1007/s00210-011-0651-9 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 842YT UT WOS:000296639000001 PM 21611737 ER PT J AU Marino, N Marshall, JC Steeg, PS AF Marino, Natascia Marshall, Jean-Claude Steeg, Patricia S. TI Protein-protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1 SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Review DE Nm23-H1; Protein interactions; Metastasis ID NUCLEOSIDE DIPHOSPHATE KINASE; METASTASIS SUPPRESSOR NM23-H2; BREAST-CARCINOMA CELLS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; TUMOR-METASTASIS; ADHERENS JUNCTIONS; CANCER-CELLS; H-PRUNE; SIGNAL-TRANSDUCTION; COMPLEX-FORMATION AB Nm23-H1, also known as NDPK-A, was the first of a class of metastasis suppressor genes to be identified. Overexpression of Nm23-H1 in metastatic cell lines (melanoma, breast carcinoma, prostate, colon, hepatocellular, and oral squamous cell carcinoma) reduced cell motility in in vitro assays and metastatic potential in xenograft models, without a significant effect on primary tumor size. The mechanism of Nm23-H1 suppression of metastasis, however, is incompletely understood. Nm23-H1 has been reported to bind proteins, including those in small G-protein complexes, transcriptional complexes, the Map kinase, the TGF-beta signaling pathways and the cytoskeleton. Evidence supporting these associations is presented together with evidence of resultant biochemical and phenotypic consequences of association. Cumulatively, the data suggest that part of the anti-metastatic function of Nm23-H1 lies in pathways that it interrupts via binding and inactivation of proteins. C1 [Marino, Natascia; Marshall, Jean-Claude] NIH, Bethesda, MD 20892 USA. [Marino, Natascia; Marshall, Jean-Claude; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Marino, N (reprint author), NIH, Bldg 37,Room 1122, Bethesda, MD 20892 USA. EM Marinon@mail.nih.gov; Marshallje@mail.nih.gov FU National Cancer Institute FX This research was supported by the Intramural program of the National Cancer Institute. NR 101 TC 22 Z9 26 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD OCT PY 2011 VL 384 IS 4-5 BP 351 EP 362 DI 10.1007/s00210-011-0646-6 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 842YT UT WOS:000296639000003 PM 21713383 ER PT J AU Younes, SA Punkosdy, G Caucheteux, S Chen, T Grossman, Z Paul, WE AF Younes, Souheil-Antoine Punkosdy, George Caucheteux, Stephane Chen, Tao Grossman, Zvi Paul, William E. TI Memory Phenotype CD4 T Cells Undergoing Rapid, Nonburst-Like, Cytokine-Driven Proliferation Can Be Distinguished from Antigen-Experienced Memory Cells SO PLOS BIOLOGY LA English DT Article ID HOMEOSTATIC PROLIFERATION; NAIVE; LYMPHOCYTES; INFECTION; REPERTOIRE; EXPANSION; EFFECTORS; SURVIVAL; OPINION AB Memory phenotype (CD44(bright), CD25(negative)) CD4 spleen and lymph node T cells (MP cells) proliferate rapidly in normal or germ-free donors, with BrdU uptake rates of 6% to 10% per day and Ki-67 positivity of 18% to 35%. The rapid proliferation of MP cells stands in contrast to the much slower proliferation of lymphocytic choriomeningitis virus (LCMV)-specific memory cells that divide at rates ranging from <1% to 2% per day over the period from 15 to 60 days after LCMV infection. Anti-MHC class II antibodies fail to inhibit the in situ proliferation of MP cells, implying a non-T-cell receptor (TCR)-driven proliferation. Such proliferation is partially inhibited by anti-IL-7R alpha antibody. The sequence diversity of TCR beta CDR3 gene segments is comparable among the proliferating and quiescent MP cells from conventional and germ-free mice, implying that the majority of proliferating MP cells have not recently derived from a small cohort of cells that expand through multiple continuous rounds of cell division. We propose that MP cells constitute a diverse cell population, containing a subpopulation of slowly dividing authentic antigen-primed memory cells and a majority population of rapidly proliferating cells that did not arise from naive cells through conventional antigen-driven clonal expansion. C1 [Younes, Souheil-Antoine; Punkosdy, George; Caucheteux, Stephane; Chen, Tao; Grossman, Zvi; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Younes, SA (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov RI younes, souheil-antoine/G-4503-2014 OI younes, souheil-antoine/0000-0003-2186-7140 FU Division of Intramural Research National Institute of Allergy and Infectious Diseases FX This research is funded by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 18 Z9 18 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD OCT PY 2011 VL 9 IS 10 AR e1001171 DI 10.1371/journal.pbio.1001171 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 844GJ UT WOS:000296735400004 PM 22022231 ER PT J AU Chi, BH Yiannoutsos, CT Westfall, AO Newman, JE Zhou, JL Cesar, C Brinkhof, MWG Mwango, A Balestre, E Carriquiry, G Sirisanthana, T Mukumbi, H Martin, JN Grimsrud, A Bacon, M Thiebaut, R AF Chi, Benjamin H. Yiannoutsos, Constantin T. Westfall, Andrew O. Newman, Jamie E. Zhou, Jialun Cesar, Carina Brinkhof, Martin W. G. Mwango, Albert Balestre, Eric Carriquiry, Gabriela Sirisanthana, Thira Mukumbi, Henri Martin, Jeffrey N. Grimsrud, Anna Bacon, Melanie Thiebaut, Rodolphe CA Int Epidemiologic Databases TI Universal Definition of Loss to Follow-Up in HIV Treatment Programs: A Statistical Analysis of 111 Facilities in Africa, Asia, and Latin America SO PLOS MEDICINE LA English DT Article ID ANTIRETROVIRAL TREATMENT PROGRAMS; LOWER-INCOME COUNTRIES; SUB-SAHARAN AFRICA; WESTERN KENYA; HIV-1-INFECTED PATIENTS; INFECTED PATIENTS; THERAPY PROGRAMS; COHORT PROFILE; SCALE-UP; 1ST YEAR AB Background: Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition. Methods and Findings: At a set "status classification" date, patients were categorized as either "active" or "LTFU" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173-181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean = 150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean = 1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean = 19.9%, 95% CI: 19.1%-21.7%). Conclusions: Based on this evaluation, we recommend the adoption of >= 180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. C1 [Chi, Benjamin H.; Westfall, Andrew O.] Univ Alabama, Birmingham, AL USA. [Chi, Benjamin H.; Westfall, Andrew O.] Ctr Infect Dis Res Zambia, Lusaka, Zambia. [Yiannoutsos, Constantin T.] Indiana Univ, Indianapolis, IN 46204 USA. [Newman, Jamie E.] RTI Int, Res Triangle Pk, NC USA. [Zhou, Jialun] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia. [Cesar, Carina] Fdn Huesped, Buenos Aires, DF, Argentina. [Brinkhof, Martin W. G.] Univ Bern, Bern, Switzerland. [Mwango, Albert] Zambian Minist Hlth, Lusaka, Zambia. [Balestre, Eric; Thiebaut, Rodolphe] Bordeaux Segalen Univ ISPED, INSERM, U897, Bordeaux, France. [Carriquiry, Gabriela] Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. [Sirisanthana, Thira] Chiang Mai Univ, Chiang Mai 50000, Thailand. [Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mukumbi, Henri] Amo Congo, Kinshasa, Zaire. [Grimsrud, Anna] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Bacon, Melanie] NIH, Bethesda, MD 20892 USA. RP Chi, BH (reprint author), Univ Alabama, Birmingham, AL USA. EM bchi@cidrz.org OI Westfall, Andrew/0000-0002-0468-4695; Brinkhof, Martin/0000-0002-9319-665X; MASKEW, MHAIRI/0000-0003-4238-0200 FU National Institute of Allergy and Infectious Diseases; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01AI069927, U01AI069919, U01AI069924, U01AI069907, U01AI069923]; Foundation for AIDS Research (amfAR); Dutch Ministry of Foreign Affairs; Stichting Aids Fonds; US National Institutes of Health [D43-TW001035, P30-AI027767]; Doris Duke Charitable Foundation [2007061] FX The International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration is funded jointly by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the following grants: Central African region (U01AI069927), Eastern African region (U01AI069919), Southern African region (U01AI069924), Western African region (U01AI069919), Asia/Pacific region (U01AI069907), and Caribbean, Central American, and South American region (U01AI069923). The TREAT Asia HIV Observation Database, a contributor to the Asia/Pacific IeDEA region, is jointly supported by the Foundation for AIDS Research (amfAR), the Dutch Ministry of Foreign Affairs, and Stichting Aids Fonds. Additional salary and trainee support was provided by the US National Institutes of Health (D43-TW001035; P30-AI027767) and the Doris Duke Charitable Foundation (2007061). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 57 Z9 57 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD OCT PY 2011 VL 8 IS 10 AR e1001111 DI 10.1371/journal.pmed.1001111 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 841YZ UT WOS:000296552400012 PM 22039357 ER PT J AU Lessler, J Metcalf, CJE Grais, RF Luquero, FJ Cummings, DAT Grenfell, BT AF Lessler, Justin Metcalf, C. Jessica E. Grais, Rebecca F. Luquero, Francisco J. Cummings, Derek A. T. Grenfell, Bryan T. TI Measuring the Performance of Vaccination Programs Using Cross-Sectional Surveys: A Likelihood Framework and Retrospective Analysis SO PLOS MEDICINE LA English DT Article ID COVERAGE AB Background: The performance of routine and supplemental immunization activities is usually measured by the administrative method: dividing the number of doses distributed by the size of the target population. This method leads to coverage estimates that are sometimes impossible (e. g., vaccination of 102% of the target population), and are generally inconsistent with the proportion found to be vaccinated in Demographic and Health Surveys (DHS). We describe a method that estimates the fraction of the population accessible to vaccination activities, as well as within-campaign inefficiencies, thus providing a consistent estimate of vaccination coverage. Methods and Findings: We developed a likelihood framework for estimating the effective coverage of vaccination programs using cross-sectional surveys of vaccine coverage combined with administrative data. We applied our method to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone, using data from each country's most recent DHS survey and administrative coverage data reported to the World Health Organization. We estimate that 93% (95% CI: 91, 94) of the population in Ghana was ever covered by any measles vaccination activity, 77% (95% CI: 78, 81) in Madagascar, and 69% (95% CI: 67, 70) in Sierra Leone. "Within-activity" inefficiencies were estimated to be low in Ghana, and higher in Sierra Leone and Madagascar. Our model successfully fits age-specific vaccination coverage levels seen in DHS data, which differ markedly from those predicted by naive extrapolation from country-reported and World Health Organization-adjusted vaccination coverage. Conclusions: Combining administrative data with survey data substantially improves estimates of vaccination coverage. Estimates of the inefficiency of past vaccination activities and the proportion not covered by any activity allow us to more accurately predict the results of future activities and provide insight into the ways in which vaccination programs are failing to meet their goals. C1 [Lessler, Justin; Cummings, Derek A. T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Metcalf, C. Jessica E.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Grais, Rebecca F.] Harvard Univ, Harvard Humanitarian Initiat, Cambridge, MA 02138 USA. [Grais, Rebecca F.; Luquero, Francisco J.] Epicentre, Paris, France. [Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Grenfell, Bryan T.] NIH, Forgarty Int Ctr, Bethesda, MD 20892 USA. RP Lessler, J (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. EM jlessler@jhsph.edu OI Lessler, Justin/0000-0002-9741-8109 FU Bill & Melinda Gates Foundation (Vaccine Modeling Initiative) [705580-3]; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, US National Institutes of Health; Scientific Interface from the Burroughs Welcome Fund; Royal Society; [NIH R01 GM083983-01] FX The work of JL, CJEM, DATC, and BTG on this project was funded by a grant from the Bill & Melinda Gates Foundation (Vaccine Modeling Initiative, 705580-3). BTG and DATC were also supported by the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, US National Institutes of Health, and by grant NIH R01 GM083983-01. DATC holds a Career Award at the Scientific Interface from the Burroughs Welcome Fund. CJEM is funded by the Royal Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 16 TC 18 Z9 18 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD OCT PY 2011 VL 8 IS 10 AR e1001110 DI 10.1371/journal.pmed.1001110 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 841YZ UT WOS:000296552400011 PM 22039353 ER PT J AU Durbin, AP Whitehead, SS AF Durbin, Anna P. Whitehead, Stephen S. TI Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development SO VIRUSES-BASEL LA English DT Review DE Dengue vaccine; DNA vaccine; vectored-vaccine; sub-unit protein vaccine ID NEUTRALIZING ANTIBODY-RESPONSE; GLYCOPROTEIN PROTECT MICE; TETRAVALENT DNA VACCINE; FLAVIVIRUS-NAIVE ADULTS; VIRUS E-GLYCOPROTEIN; IMMUNE-RESPONSES; MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES; ADENOVIRUS VECTOR; SUBUNIT VACCINE AB Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed. C1 [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. [Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, 624 N Broadway,Room 251, Baltimore, MD 21205 USA. EM adurbin@jhsph.edu; swhitehead@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA FX Support for A. P. D. (in part) and S. S. W. is provided by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. NR 65 TC 31 Z9 31 U1 0 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD OCT PY 2011 VL 3 IS 10 BP 1800 EP 1814 DI 10.3390/v3101800 PG 15 WC Virology SC Virology GA 842GY UT WOS:000296585100001 PM 22069516 ER PT J AU Edwards, DC McKinnon, KM Fenizia, C Jung, KJ Brady, JN Pise-Masison, CA AF Edwards, Dustin C. McKinnon, Katherine M. Fenizia, Claudio Jung, Kyung-Jin Brady, John N. Pise-Masison, Cynthia A. TI Inhibition of Geranylgeranyl Transferase-I Decreases Cell Viability of HTLV-1-Transformed Cells SO VIRUSES-BASEL LA English DT Article DE human T-cell leukemia virus type-1; HTLV-1; Tax; long terminal repeat; LTR; geranylgeranyltransferase; GGTI-298; small GTPase; NF-kappa B; p53; cell cycle ID VIRUS TYPE-I; PROTEIN GERANYLGERANYLATION; LEUKEMIA-CELLS; HTLV-I; 1-TRANSFORMED CELLS; TUMOR-CELLS; TAX PROTEIN; RHO-GTPASES; KAPPA-B; APOPTOSIS AB Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), an aggressive and highly chemoresistant malignancy. Rho family GTPases regulate multiple signaling pathways in tumorigenesis: cytoskeletal organization, transcription, cell cycle progression, and cell proliferation. Geranylgeranylation of Rho family GTPases is essential for cell membrane localization and activation of these proteins. It is currently unknown whether HTLV-1-transformed cells are preferentially sensitive to geranylgeranylation inhibitors, such as GGTI-298. In this report, we demonstrate that GGTI-298 decreased cell viability and induced G(2)/M phase accumulation of HTLV-1-transformed cells, independent of p53 reactivation. HTLV-1-LTR transcriptional activity was inhibited and Tax protein levels decreased following treatment with GGTI-298. Furthermore, GGTI-298 decreased activation of NF-kappa B, a downstream target of Rho family GTPases. These studies suggest that protein geranylgeranylation contributes to dysregulation of cell survival pathways in HTLV-1-transformed cells. C1 [Edwards, Dustin C.; Jung, Kyung-Jin; Brady, John N.; Pise-Masison, Cynthia A.] NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [McKinnon, Katherine M.; Fenizia, Claudio] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pise-Masison, CA (reprint author), NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM edwardsd2@mail.nih.gov; mckinnonkm@mail.nih.gov; feniziac@mail.nih.gov; jungk@kitox.re.kr; masisonc@mail.nih.gov FU National Institute of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute, Center for Cancer Research. We would like to thank the Brady lab for thoughtful discussion. NR 52 TC 2 Z9 2 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD OCT PY 2011 VL 3 IS 10 BP 1815 EP 1835 DI 10.3390/v3101815 PG 21 WC Virology SC Virology GA 842GY UT WOS:000296585100002 PM 22069517 ER PT J AU Parry, M AF Parry, Manon TI RETHINKING DR. SPOCK RESPONSE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID INFANT-DEATH-SYNDROME; SIDS RATES; POSITION C1 Natl Lib Med, Exhibit Program, Bethesda, MD 20894 USA. RP Parry, M (reprint author), Natl Lib Med, Exhibit Program, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA. EM parrym@mail.nlm.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2011 VL 101 IS 10 BP 1812 EP 1813 DI 10.2105/AJPH.2011.300337 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 830LB UT WOS:000295657400002 ER PT J AU Frankel, LK AF Frankel, Lee K. TI The Relation of Life Insurance to Public Hygiene SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Lib Med, Div Hist Med, Bethesda, MD 20894 USA. RP Frankel, LK (reprint author), Natl Lib Med, Div Hist Med, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2011 VL 101 IS 10 BP 1868 EP 1869 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 830LB UT WOS:000295657400020 PM 21917618 ER PT J AU Fee, E AF Fee, Elizabeth TI Lee K. Frankel (1867-1931): Public Health Leader and Life Insurance Executive SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM feee@nlm.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2011 VL 101 IS 10 BP 1870 EP 1870 DI 10.2105/AJPH.2009.191072 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 830LB UT WOS:000295657400021 ER PT J AU de Heer, HD Koehly, L Pederson, R Morera, O AF de Heer, Hendrik D. Koehly, Laura Pederson, Rockie Morera, Osvaldo TI Effectiveness and Spillover of an After-School Health Promotion Program for Hispanic Elementary School Children SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID GEORGIA FITKID PROJECT; PHYSICAL-ACTIVITY PROGRAM; OBESITY PREVENTION; MEDICAL-COLLEGE; CARDIOVASCULAR HEALTH; ADOLESCENT TRIAL; RISK BEHAVIOR; INTERVENTION; YOUTH; CHILDHOOD AB Objectives. We evaluated the effectiveness and spillover of an after-school health education and physical activity program among Hispanic elementary school children. Methods. In fall 2008, students in third through fifth grades in 6 schools in El Paso, Texas (n=901), were randomized to intervention (n=292 participants) or control (n=354) classrooms (4 unknown). Intervention classrooms also contained a spillover group (n=251) that did not join the after-school program but that completed measurements and surveys. The intervention was a 12-week culturally tailored after-school program meeting twice a week. Four-month outcomes were body mass index, aerobic capacity, and dietary intentions and knowledge. We calculated intervention exposure as the proportion of after-school participants per classroom. Results. Intervention exposure predicted lower body mass index (P=.045), higher aerobic capacity (P=.012), and greater intentions to eat healthy (P=.046) for the classroom at follow-up. Intervention effectiveness increased with increasing proportions of intervention participants in a classroom. Nonparticipants who had classroom contact with program participants experienced health improvements that could reduce their risk of obesity. Conclusions. Spillover of beneficial intervention effects to nonparticipants is a valuable public health benefit and should be part of program impact assessments. (Am J Public Health. 2011;101:1907-1913. doi:10.2105/AJPH.2011.300177) C1 [de Heer, Hendrik D.; Morera, Osvaldo] Univ Texas El Paso, Dept Psychol, El Paso, TX 79968 USA. [Pederson, Rockie] Univ Texas El Paso, Dept Kinesiol, El Paso, TX 79968 USA. [de Heer, Hendrik D.; Koehly, Laura] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. RP de Heer, HD (reprint author), No Arizona Univ, Dept Phys Therapy & Athlet Training, POB 15105,Bldg 66,Rm 102, Flagstaff, AZ 86011 USA. EM dirkdeheer@hotmail.com RI de Heer, Hendrik/D-3192-2013 OI de Heer, Hendrik/0000-0002-9241-5021 FU Center for Border Health Research through the Paso del Norte Health Foundation; National Institutes of Health Hispanic Health Disparities Research Center [P20MD002287-01] FX This project was supported by pilot research grants from the Center for Border Health Research through the Paso del Norte Health Foundation and by the National Institutes of Health Hispanic Health Disparities Research Center (grant P20MD002287-01). NR 42 TC 12 Z9 12 U1 1 U2 14 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2011 VL 101 IS 10 BP 1907 EP 1913 DI 10.2105/AJPH.2011.300177 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 830LB UT WOS:000295657400029 PM 21852659 ER PT J AU Wolf, R Ruzicka, T Yuspa, SH AF Wolf, Ronald Ruzicka, Thomas Yuspa, Stuart H. TI Novel S100A7 (psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function SO AMINO ACIDS LA English DT Review DE Calcium-binding protein; S100; Koebnerisin; Psoriasin; Evolution; Paralogs; RAGE; Innate immunity; Inflammation; Cancer ID GLYCATION END-PRODUCTS; EPIDERMAL DIFFERENTIATION COMPLEX; HUMAN-CHROMOSOME 1Q21; PSORIASIN S100A7; CORNIFIED ENVELOPE; ATOPIC-DERMATITIS; BREAST-CANCER; SUBCELLULAR-LOCALIZATION; MOLECULAR-CLONING; PROTEIN PSORIASIN AB S100A7 (psoriasin) and S100A15 (koebnerisin) were first identified in inflamed psoriatic skin. They are of major interest because of their putative functional roles in innate immunity, epidermal cell maturation, and epithelial tumorigenesis. Human S100A7 and S100A15 have lately evolved by gene duplications within the epidermal differentiation complex (chromosome 1q21) during primate evolution forming a novel S100 subfamily. Therefore, S100A7 and S100A15 are almost identical in sequence (> 90%) and are difficult to discriminate. Despite their high homology, S100A7 and S100A15 are distinct in tissue distribution, regulation, and function, and thus, exemplary for the diversity within the S100 family. Their different properties are compelling reasons to discriminate S100A7 (psoriasin) and S100A15 (koebnerisin) in epithelial homeostasis, inflammation, and cancer. C1 [Wolf, Ronald; Ruzicka, Thomas] Univ Munich, Dept Dermatol, D-80337 Munich, Germany. [Wolf, Ronald; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wolf, R (reprint author), Univ Munich, Dept Dermatol, Frauenlobstr 9-11, D-80337 Munich, Germany. EM Ronald.Wolf@med.uni-muenchen.de FU NIH, National Cancer Institute, Center for Cancer Research; German Research Foundation (DFG) FX This work was supported by grants from the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the German Research Foundation (DFG). NR 54 TC 24 Z9 24 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD OCT PY 2011 VL 41 IS 4 BP 789 EP 796 DI 10.1007/s00726-010-0666-4 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 840VE UT WOS:000296468600005 PM 20596736 ER PT J AU Gaitan, MI Shea, CD Evangelou, IE Stone, RD Fenton, KM Bielekova, B Massacesi, L Reich, DS AF Gaitan, Maria I. Shea, Colin D. Evangelou, Iordanis E. Stone, Roger D. Fenton, Kaylan M. Bielekova, Bibiana Massacesi, Luca Reich, Daniel S. TI Heterogeneity in Longitudinal Evolution of Ring-Enhancing Multiple Sclerosis Lesions Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 [Gaitan, Maria I.; Shea, Colin D.; Evangelou, Iordanis E.; Stone, Roger D.; Fenton, Kaylan M.; Bielekova, Bibiana; Massacesi, Luca; Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Massacesi, Luca] Univ Florence, Dept Neurol & Psychiat Sci, Florence, Italy. RP Gaitan, MI (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 2 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2011 VL 70 IS 4 BP 669 EP 670 DI 10.1002/ana.22589 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839VD UT WOS:000296396700026 ER PT J AU Hirtz, DG AF Hirtz, D. G. TI Effect of prenatal MgSO4 on head ultrasound imaging in preterm infants SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 136th Annual Meeting of the American-Neurological-Association (ANA) CY SEP 25-27, 2011 CL San Diego, CA SP Amer Neurol Assoc (ANA) C1 [Hirtz, D. G.] Eunice Kennedy Shriver Natl Inst, Child Hlth & Human Dev Maternal Fetal Med Units N, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2011 VL 70 SU 15 BP S110 EP S111 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 840DW UT WOS:000296419500357 ER PT J AU Han, Q Robinson, H Cai, T Tagle, DA Li, JY AF Han, Qian Robinson, Howard Cai, Tao Tagle, Danilo A. Li, Jianyong TI Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV SO BIOSCIENCE REPORTS LA English DT Article DE aspartate aminotransferase; crystal structure; oxo acid; kynurenic acid; kynurenine; kynurenine aminotransferase ID ACID-BINDING-PROTEIN; GLUTAMINE TRANSAMINASE-K; RAT-BRAIN ASTROCYTES; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; GLUTAMATERGIC NEURONS; SYNAPTIC-TRANSMISSION; OXIDATIVE-METABOLISM; NICOTINIC RECEPTORS AB Mammalian mAspAT (mitochondrial aspartate aminotransferase) is recently reported to have RAT (kynurenine aminotransferase) activity and plays a role in the biosynthesis of KYNA (kynurenic acid) in rat, mouse and human brains. This study concerns the biochemical and structural characterization of mouse mAspAT. In this study, mouse mAspAT cDNA was amplified from mouse brain first stand cDNA and its recombinant protein was expressed in an Escherichia coli expression system. Sixteen oxo acids were tested for the co-substrate specificity of mouse mAspAT and 14 of them were shown to be capable of serving as co-substrates for the enzyme. Structural analysis of mAspAT by macromolecular crystallography revealed that the cofactor-binding residues of mAspAT are similar to those of other KATs. The substrate-binding residues of mAspAT are slightly different from those of other KATs. Our results provide a biochemical and structural basis towards understanding the overall physiological role of mAspAT in vivo and insight into controlling the levels of endogenous KYNA through modulation of the enzyme in the mouse brain. C1 [Han, Qian; Li, Jianyong] Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. [Robinson, Howard] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. [Cai, Tao] NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. [Tagle, Danilo A.] NINDS, Ctr Neurosci, NIH, Bethesda, MD USA. RP Li, JY (reprint author), Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. EM lij@vt.edu RI Han, Qian/J-8696-2014 OI Han, Qian/0000-0001-6245-5252 FU NINDS [NS062836]; NIDCR; NINDS at National Institutes of Health FX This work was supported by a grant from NINDS [NS062836] and by Intramural Research Programs of NIDCR and NINDS at National Institutes of Health. The present study was carried out in part at the National Synchrotron Light Source, Brookhaven National Laboratory. NR 73 TC 12 Z9 13 U1 1 U2 11 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0144-8463 EI 1573-4935 J9 BIOSCIENCE REP JI Biosci. Rep. PD OCT PY 2011 VL 31 IS 5 BP 323 EP 332 DI 10.1042/BSR20100117 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 841AA UT WOS:000296482900004 PM 20977429 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI Breastfeeding Is a Dynamic Biological Process-Not Simply a Meal at the Breast SO BREASTFEEDING MEDICINE LA English DT Editorial Material ID COGNITIVE-DEVELOPMENT; MILK FORMULA; BRAIN; INFANTS; VOICE; TRIAL; IQ C1 [Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD USA. RP Raju, TNK (reprint author), NICHHD, NIH, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 21 TC 6 Z9 7 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1556-8253 J9 BREASTFEED MED JI Breastfeed. Med. PD OCT PY 2011 VL 6 IS 5 BP 257 EP 259 DI 10.1089/bfm.2011.0081 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 839QD UT WOS:000296382300005 PM 22007804 ER PT J AU Parry, C Kent, EE Mariotto, AB Alfano, CM Rowland, JH AF Parry, Carla Kent, Erin E. Mariotto, Angela B. Alfano, Catherine M. Rowland, Julia H. TI Cancer Survivors: A Booming Population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; OLDER-ADULTS; UNITED-STATES; PREVALENCE; CHALLENGES; AGE; COMORBIDITY; REGISTRIES; CHILDHOOD; VARIANCE AB Background: In this first article of what is planned to be an annual series, we examine the history of cancer prevalence reporting and the role that these annual figures play in guiding the direction of cancer control research, and specifically the science of cancer survivorship. For this inaugural year, we focus on the confluence of the growing number of survivors and population aging, and the impact these combined trends will have on cancer survivorship in the future. Methods: State or metro area-level cancer incidence and prevalence data were collected from 9 registries via the Surveillance, Epidemiology, and End Results Program. The complete prevalence method was used to estimate prevalence for 2008 and the Prevalence, Incidence Approach Model method was used to project prevalence data through 2020, assuming flat cancer incidence and survival trends but dynamic U. S. population projections. Results: As of January 2008, the number of cancer survivors is estimated at 11.9 million. Approximately 60% of cancer survivors are age 65 or older, and by the year 2020, it is estimated that 63% of cancer survivors will be age 65 or older. Conclusions: Improved survival and population aging converge to generate a booming population of older adult cancer survivors, many of whom have multiple complex health conditions and unique survivorship needs. This demographic shift has important implications for future health care needs and costs of the U. S. population. Impact: The findings provide information critical for guiding cancer prevention and control research and service provision. Cancer Epidemiol Biomarkers Prev; 20(10); 1996-2005. (C) 2011 AACR. C1 [Rowland, Julia H.] NCI, NIH, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kent, Erin E.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Mariotto, Angela B.] NCI, Surveillance Res Program, Bethesda, MD 20892 USA. RP Rowland, JH (reprint author), NCI, NIH, Off Canc Survivorship, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 404, Bethesda, MD 20892 USA. EM rowlandj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 43 TC 136 Z9 137 U1 2 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2011 VL 20 IS 10 BP 1996 EP 2005 DI 10.1158/1055-9965.EPI-11-0729 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900002 PM 21980007 ER PT J AU Yabroff, KR Lund, J Kepka, D Mariotto, A AF Yabroff, K. Robin Lund, Jennifer Kepka, Deanna Mariotto, Angela TI Economic Burden of Cancer in the United States: Estimates, Projections, and Future Research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID METASTATIC COLORECTAL-CANCER; POTENTIAL LIFE LOST; HEALTH-CARE COSTS; BREAST-CANCER; LUNG-CANCER; PRODUCTIVITY COSTS; TUMOR-REGISTRY; MEDICAL COSTS; TIME; SURVIVORS AB The economic burden of cancer in the United States is substantial and expected to increase significantly in the future because of expected growth and aging of the population and improvements in survival as well as trends in treatment patterns and costs of care following cancer diagnosis. In this article, we describe measures of the economic burden of cancer and present current estimates and projections of the national burden of cancer in the United States. We discuss ongoing efforts to characterize the economic burden of cancer in the United States and identify key areas for future work including developing and enhancing research resources, improving estimates and projections of economic burden, evaluating targeted therapies, and assessing the financial burden for patients and their families. This work will inform efforts by health care policy makers, health care systems, providers, and employers to improve the cancer survivorship experience in the United States. Cancer Epidemiol Biomarkers Prev; 20(10); 2006-14. (C) 2011 AACR. C1 [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Lund, Jennifer] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov RI Lund, Jennifer/G-9420-2012; OI Yabroff, K. Robin/0000-0003-0644-5572 FU Intramural NIH HHS [Z99 CA999999] NR 65 TC 68 Z9 68 U1 1 U2 25 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2011 VL 20 IS 10 BP 2006 EP 2014 DI 10.1158/1055-9965.EPI-11-0650 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900003 PM 21980008 ER PT J AU Khoury, MJ Clauser, SB Freedman, AN Gillanders, EM Glasgow, RE Klein, WMP Schully, SD AF Khoury, Muin J. Clauser, Steven B. Freedman, Andrew N. Gillanders, Elizabeth M. Glasgow, Russ E. Klein, William M. P. Schully, Sheri D. TI Population Sciences, Translational Research, and the Opportunities and Challenges for Genomics to Reduce the Burden of Cancer in the 21st Century SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID EGAPP WORKING GROUP; GENETIC TESTING STRATEGIES; WIDE ASSOCIATION; COLORECTAL-CANCER; BREAST-CANCER; LYNCH SYNDROME; MOLECULAR EPIDEMIOLOGY; PERSONALIZED MEDICINE; MUTATION CARRIERS; RESEARCH AGENDA AB Advances in genomics and related fields are promising tools for risk assessment, early detection, and targeted therapies across the entire cancer care continuum. In this commentary, we submit that this promise cannot be fulfilled without an enhanced translational genomics research agenda firmly rooted in the population sciences. Population sciences include multiple disciplines that are needed throughout the translational research continuum. For example, epidemiologic studies are needed not only to accelerate genomic discoveries and new biological insights into cancer etiology and pathogenesis, but to characterize and critically evaluate these discoveries in well-defined populations for their potential for cancer prediction, prevention and response to treatment. Behavioral, social, and communication sciences are needed to explore genomic-modulated responses to old and new behavioral interventions, adherence to therapies, decision making across the continuum, and effective use in health care. Implementation science, health services, outcomes research, comparative effectiveness research, and regulatory science are needed for moving validated genomic applications into practice and for measuring their effectiveness, cost-effectiveness, and unintended consequences. Knowledge synthesis, evidence reviews, and economic modeling of the effects of promising genomic applications will facilitate policy decisions and evidence-based recommendations. Several independent and multidisciplinary panels have recently made specific recommendations for enhanced research and policy infrastructure to inform clinical and population research for moving genomic innovations into the cancer care continuum. An enhanced translational genomics and population sciences agenda is urgently needed to fulfill the promise of genomics in reducing the burden of cancer. Cancer Epidemiol Biomarkers Prev; 20(10); 2105-14. (C)2011 AACR. C1 [Khoury, Muin J.] Ctr Dis Control & Prevent, Office Publ Hlth Genom, Atlanta, GA USA. [Khoury, Muin J.; Clauser, Steven B.; Freedman, Andrew N.; Gillanders, Elizabeth M.; Glasgow, Russ E.; Klein, William M. P.; Schully, Sheri D.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Khoury, MJ (reprint author), CDC, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM muk1@CDC.GOV FU Intramural NIH HHS [Z99 CA999999] NR 74 TC 23 Z9 23 U1 3 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2011 VL 20 IS 10 BP 2105 EP 2114 DI 10.1158/1055-9965.EPI-11-0481 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900014 PM 21795499 ER PT J AU Milne, RL Goode, EL Garca-Closas, M Couch, FJ Severi, G Hein, R Fredericksen, Z Malats, N Zamora, MP Perez, JIA Benitez, J Dork, T Schurmann, P Karstens, JH Hillemanns, P Cox, A Brock, IW Elliot, G Cross, SS Seal, S Turnbull, C Renwick, A Rahman, N Shen, CY Yu, JC Huang, CS Hou, MF Nordestgaard, BG Bojesen, SE Lanng, C Alnaes, GG Kristensen, V Borrensen-Dale, AL Hopper, JL Dite, GS Apicella, C Southey, MC Lambrechts, D Yesilyurt, BT Floris, G Leunen, K Sangrajrang, S Gaborieau, V Brennan, P McKay, J Chang-Claude, J Wang-Gohrke, S Radice, P Peterlongo, P Manoukian, S Barile, M Giles, GG Baglietto, L John, EM Miron, A Chanock, SJ Lissowska, J Sherman, ME Figueroa, JD Bogdanova, NV Antonenkova, NN Zalutsky, IV Rogov, YI Fasching, PA Bayer, CM Ekici, AB Beckmann, MW Brenner, H Muller, H Arndt, V Stegmaier, C Andrulis, IL Knight, JA Glendon, G Mulligan, AM Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Meindl, A Heil, J Bartram, CR Schmutzler, RK Thomas, GD Hoover, RN Fletcher, O Gibson, LJ Silva, ID Peto, J Nickels, S Flesch-Janys, D Anton-Culver, H Ziogas, A Sawyer, E Tomlinson, I Kerin, M Miller, N Schmidt, MK Broeks, A Van't Veer, LJ Tollenaar, RAEM Pharoah, PDP Dunning, AM Pooley, KA Marme, F Schneeweiss, A Sohn, C Burwinkel, B Jakubowska, A Lubinski, J Jaworska, K Durda, K Kang, D Yoo, KY Noh, DY Ahn, SH Hunter, DJ Hankinson, SE Kraft, P Lindstrom, S Chen, XQ Beesley, J Hamann, U Harth, V Justenhoven, C Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Hooning, M Hollestelle, A Oldenburg, RA Tilanus-Linthorst, M Khusnutdinova, E Bermisheva, M Prokofieva, D Farahtdinova, A Olson, JE Wang, XS Humphreys, MK Wang, Q Chenevix-Trench, G Easton, DF AF Milne, Roger L. Goode, Ellen L. Garca-Closas, Montserrat Couch, Fergus J. Severi, Gianluca Hein, Rebecca Fredericksen, Zachary Malats, Nuria Pilar Zamora, M. Arias Perez, Jose Ignacio Benitez, Javier Doerk, Thilo Schuermann, Peter Karstens, Johann H. Hillemanns, Peter Cox, Angela Brock, Ian W. Elliot, Graeme Cross, Simon S. Seal, Sheila Turnbull, Clare Renwick, Anthony Rahman, Nazneen Shen, Chen-Yang Yu, Jyh-Cherng Huang, Chiun-Sheng Hou, Ming-Feng Nordestgaard, Borge G. Bojesen, Stig E. Lanng, Charlotte Alnaes, Grethe Grenaker Kristensen, Vessela Borrensen-Dale, Anne-Lise Hopper, John L. Dite, Gillian S. Apicella, Carmel Southey, Melissa C. Lambrechts, Diether Yesilyurt, Betul T. Floris, Giuseppe Leunen, Karin Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul McKay, James Chang-Claude, Jenny Wang-Gohrke, Shan Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Giles, Graham G. Baglietto, Laura John, Esther M. Miron, Alexander Chanock, Stephen J. Lissowska, Jolanta Sherman, Mark E. Figueroa, Jonine D. Bogdanova, Natalia V. Antonenkova, Natalia N. Zalutsky, Iosif V. Rogov, Yuri I. Fasching, Peter A. Bayer, Christian M. Ekici, Arif B. Beckmann, Matthias W. Brenner, Hermann Mueller, Heiko Arndt, Volker Stegmaier, Christa Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Meindl, Alfons Heil, Joerg Bartram, Claus R. Schmutzler, Rita K. Thomas, Gilles D. Hoover, Robert N. Fletcher, Olivia Gibson, Lorna J. Silva, Isabel dos Santos Peto, Julian Nickels, Stefan Flesch-Janys, Dieter Anton-Culver, Hoda Ziogas, Argyrios Sawyer, Elinor Tomlinson, Ian Kerin, Michael Miller, Nicola Schmidt, Marjanka K. Broeks, Annegien Van't Veer, Laura J. Tollenaar, Rob A. E. M. Pharoah, Paul D. P. Dunning, Alison M. Pooley, Karen A. Marme, Frederik Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Jakubowska, Anna Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Ahn, Sei-Hyun Hunter, David J. Hankinson, Susan E. Kraft, Peter Lindstrom, Sara Chen, Xiaoqing Beesley, Jonathan Hamann, Ute Harth, Volker Justenhoven, Christina Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Hooning, Maartje Hollestelle, Antoinette Oldenburg, Rogier A. Tilanus-Linthorst, Madeleine Khusnutdinova, Elza Bermisheva, Marina Prokofieva, Darya Farahtdinova, Albina Olson, Janet E. Wang, Xianshu Humphreys, Manjeet K. Wang, Qin Chenevix-Trench, Georgia Easton, Douglas F. CA GENICA Network KConFab Investigators AOCS Grp TI Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS; SUBTYPES; ALLELES; RISK AB Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 x 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR 1.07, 95% CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 x 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) 2 x 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; Ptrend 5 x 10(-7)]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222-31. (C) 2011 AACR. C1 [Milne, Roger L.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain. [Pilar Zamora, M.] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain. [Milne, Roger L.; Severi, Gianluca; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Giles, Graham G.; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Severi, Gianluca; Giles, Graham G.; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Goode, Ellen L.; Fredericksen, Zachary; Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Gibson, Lorna J.; Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, London, England. [Sawyer, Elinor] Guys & St Thomas NHS Fdn Trust Partnership Kings, Div Canc Studies, NIHR Comprehens Biomed Res Ctr, London, England. [Hein, Rebecca; Chang-Claude, Jenny; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Unit, Heidelberg, Germany. [Heil, Joerg; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara] Univ Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Marme, Frederik; Schneeweiss, Andreas] Univ Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany. [Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain. [Doerk, Thilo; Schuermann, Peter; Hillemanns, Peter; Bogdanova, Natalia V.] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany. [Karstens, Johann H.; Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany. [Cox, Angela; Brock, Ian W.; Elliot, Graeme] Univ Sheffield, Dept Oncol, Inst Canc Studies, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England. [Elliot, Graeme] Univ Manchester, Manchester, Lancs, England. [Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Rahman, Nazneen] Inst Canc Res, Sect Canc Genet, Surrey, England. [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Yu, Jyh-Cherng] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan. [Huang, Chiun-Sheng] Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ Chung Ho Mem Hosp, Ctr Canc, Kaohsiung, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ Chung Ho Mem Hosp, Dept Surg, Kaohsiung, Taiwan. [Nordestgaard, Borge G.; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark. [Nordestgaard, Borge G.; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Lanng, Charlotte] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark. [Alnaes, Grethe Grenaker; Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, Oslo, Norway. [Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Fac Med, Fac Div Ahus, Uio, Norway. [Floris, Giuseppe; Leunen, Karin] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand. [Gaborieau, Valerie; Brennan, Paul; McKay, James] Int Agcy Res Canc, F-69372 Lyon, France. [Chang-Claude, Jenny; Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany. [Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Tumori, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Tumori, Italy. [Barile, Monica] IEO, Div Canc Prevent & Genet, Milan, Italy. [John, Esther M.] Fremont & Stanford Univ, Sch Med, Canc Prevent Inst Calif, Stanford, CA USA. [Miron, Alexander] Dana Farber Canc Inst, Boston, MA USA. [Hunter, David J.; Kraft, Peter; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA. [Hunter, David J.; Hankinson, Susan E.; Kraft, Peter; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Chanock, Stephen J.; Sherman, Mark E.; Figueroa, Jonine D.; Thomas, Gilles D.; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Jaworska, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland. [Antonenkova, Natalia N.; Zalutsky, Iosif V.; Rogov, Yuri I.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus. [Fasching, Peter A.; Bayer, Christian M.; Beckmann, Matthias W.] Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen Nuremberg, Dept Gynecol & Obstet, Univ Breast Ctr Franconia, Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [Andrulis, Irene L.; Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, New York, NY USA. [Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, New York, NY USA. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Dept Lab Med, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Helsinki, Finland. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Bioctr Kuopio, Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Obstet & Gynecol, D-8000 Munich, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, CMMC, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Tomlinson, Ian] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX1 2JD, England. [Kerin, Michael; Miller, Nicola] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland. [Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Pharoah, Paul D. P.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England. [Pharoah, Paul D. P.; Pooley, Karen A.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Pharoah, Paul D. P.; Dunning, Alison M.; Pooley, Karen A.; Humphreys, Manjeet K.; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge, England. [Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Seoul 151, South Korea. [Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Seoul, South Korea. [Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Harth, Volker] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany. [Justenhoven, Christina] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Justenhoven, Christina] Univ Tubingen, Tubingen, Germany. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Canc Genet Lab, Dept Clin Genet, Oulu, Finland. [Winqvist, Robert; Pylkas, Katri; GENICA Network] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland. [Grip, Mervi] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland. [Hooning, Maartje] Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Oldenburg, Rogier A.] Family Canc Clin, Dept Clin Genet, Rotterdam, Netherlands. [Tilanus-Linthorst, Madeleine] Family Canc Clin, Dept Surg Oncol, Rotterdam, Netherlands. [Hollestelle, Antoinette] Erasmus Univ, Med Ctr, Dept Med Oncol, Josephine Nefkens Inst, Rotterdam, Netherlands. [Khusnutdinova, Elza; Bermisheva, Marina; Prokofieva, Darya; Farahtdinova, Albina] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450001, Russia. RP Milne, RL (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM rmilne@cnio.es RI Jakubowska, Anna/O-8050-2014; Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Hartikainen, Jaana/E-6256-2015; Bowtell, David/H-1007-2016; Khusnutdinova, Elza/A-4810-2013; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Rahman, Nazneen/D-2802-2013; Radice, Paolo/O-3119-2013; Rahman, Nazneen/B-8890-2012; Dork, Thilo/J-8620-2012; Noh, Dong-Young/G-5531-2011; Knight, Julia/A-6843-2012; Shen, CY/F-6271-2010; Verdrengh, Evelien/H-4571-2012; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Kerin, Michael/D-6748-2013; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013 OI Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684; Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Bowtell, David/0000-0001-9089-7525; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Hollestelle, Antoinette/0000-0003-1166-1966; Rahman, Nazneen/0000-0003-4376-0440; Dite, Gillian/0000-0002-2448-2548; Huang, Chiun-Sheng/0000-0002-6557-211X; Cross, Simon/0000-0003-2044-1754; FU European Community [223175, HEALTH-F2-2009-223175]; CR-UK [C1287/A10118, C1287/A12014]; European Union COST [BM0606]; Dutch Cancer Society [NKI 2001-2423, 2007-3839, DDHK 2004-3124, DDHK 2009-4318]; Dutch National Genomics Initiative; United States National Cancer Institute, NIH [RFA-CA-06-503]; Breast Cancer Family Registry (BCFR); Cancer Care Ontario [U01 CA69467]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of Tasmania; Cancer Foundation of Western Australia; NHMRC [199600, 145684, 288704, 454508]; ELAN-Fond of the University Hospital of Erlangen; Cancer Research UK [C1287/A10118, C8620/A8372, C8620/A8857, C490/A10124, C8197/A10123]; Breakthrough Breast Cancer; NHS; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research Center (DKFZ); Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Herlev Hospital; Genome Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120]; Baden Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid (Deutsche Krebshilfe); US Military Acquisition (ACQ)Activity, Era of Hope Award [W81XWH-05-1-0204]; Institute of Cancer Research (UK); Medical Research Council (UK); Deutsche Krebshilfe [107054]; German Cancer Research Centre (DKFZ); Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany; Deutsche Krebshilfe e. V. [70492, 70-2892-BR I]; Hannover Medical School; German Academic Exchange Program; German Federal Ministry of Research and Education [RUS08/017]; Kuopio University Hospital; Cancer Fund of North Savo; Finnish Cancer Organizations; Academy of Finland; University of Eastern Finland; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales; Cancer Councils of Victoria; Cancer Councils of Tasmania; Cancer Councils of South Australia; Stichting tegen Kanker [232-2008, 196-2010]; Hamburg Cancer Society; German Cancer Research Center; Ministero della Salute; Ministero dell'Universita' e Ricerca [RBLAO3-BETH]; Fondazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Ricerca sul Cancro [4017]; Fondazione IRCCS Istituto Nazionale Tumori [5 x 1000]; NIH [CA122340, CA128978, CA87969, CA58860, CA92044]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; VicHealth; Cancer Council Victoria; Australian NHMRC [209057, 251553, 504711]; Norwegian Research council [155218/V40, 175240/S10]; Borrensen-Dale; FUGE-NFR [181600/V11]; Swizz Bridge Award; Finnish Cancer Foundation; Sigrid Juselius Foundation; University of Oulu; Oulu University Hospital; National Cancer Institute, Department of Health and Human Services, USA; Yorkshire Cancer Research; Breast Cancer Campaign; Ministry of Health and Welfare, Republic of Korea [AO30001]; Polish Foundation of Science; National Cancer Institute Thailand; Institute of Biomedical Sciences, Academia Sinica, Taiwan; Lon V Smith Foundation [LVS39420]; NIHR Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation; King's College London, United Kingdom; Oxford Biomedical Research Centre; [PBZ_KBN_122/P05/2004] FX Part of this work was supported by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175; COGS). The BCAC is funded by CR-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST Programme (BM0606). D.F. Easton is a Principal Research Fellow of CR-UK. The ABCS was supported by the Dutch Cancer Society (grants NKI 2001-2423, 2007-3839) and the Dutch National Genomics Initiative. The ABCFS, NC-BCFR, and OFBCR work was supported by the United States National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and principal investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638). The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L. Hopper is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M.C. Southey is an NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC (199600). G. Chenevix-Trench is supported by the NHMRC. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev Hospital. The CNIO-BCS was supported by the Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer, and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI081583 and PI081120). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The FBCS is supported by funds from Cancer Research UK (C8620/A8372 and C8620/A8857), a US Military Acquisition (ACQ) Activity, Era of Hope Award (W81XWH-05-1-0204), and the Institute of Cancer Research (UK). C. Turnbull is funded by a Medical Research Council (UK) Clinical Research Fellowship. The FBCS acknowledges NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical Research Centre. The GC-HBOC was supported by Deutsche Krebshilfe (107054), the Dietmar-Hopp Foundation, the Helmholtz society, and the German Cancer Research Centre (DKFZ).; The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Isurance (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e. V. (70492) and genotyping in part by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm (P.685). The HABCS study was supported by an intramural grant from Hannover Medical School. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (to N.V. Bogdanova), and the Friends of Hannover Medical School (to N.V. Bogdanova). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017). The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, The Academy of Finland, and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC (145684, 288704, 454508). LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). The MARIE study was supported by the Deutsche Krebshilfe e. V. (70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research Center, and the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). MBCSG was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro", and "Progetto Tumori Femminili" to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to PR), Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"), Associazione Italiana per la Ricerca sul Cancro (4017 to P. Peterlongo), and by funds from Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). The MCBCS was supported by the NIH grants (CA122340, CA128978) and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. SEE ABCFS. The NBCS was supported by grants from the Norwegian Research council, 155218/V40, 175240/S10 to A.-L. Borrensen-Dale, FUGE-NFR 181600/V11 to V.-M. Kosma, and a Swizz Bridge Award to A.-L. Borrensen-Dale. The NHS was funded by NIH grant CA87969. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital. The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318).; The SBCS was suppoted by Yorkshire Cancer Research and the Breast Cancer Campaign. SEARCH is funded by program grants from Cancer Research UK (C490/A10124, C8197/A10123, C1287/A10118). The SEBCS was supported by the Korea Health 21 R&D Project (AO30001), Ministry of Health and Welfare, Republic of Korea. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004; K. Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The TBCS was funded by The National Cancer Institute Thailand. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH (CA58860, CA92044) and the Lon V Smith Foundation (LVS39420). E. Sawyer is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. I. Tomlinson is supported by the Oxford Biomedical Research Centre. NR 14 TC 23 Z9 23 U1 1 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2011 VL 20 IS 10 BP 2222 EP 2231 DI 10.1158/1055-9965.EPI-11-0569 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900028 PM 21795498 ER PT J AU Shiels, MS Chaturvedi, AK Katki, HA Gochuico, BR Caporaso, NE Engels, EA AF Shiels, Meredith S. Chaturvedi, Anil K. Katki, Hormuzd A. Gochuico, Bernadette R. Caporaso, Neil E. Engels, Eric A. TI Circulating Markers of Interstitial Lung Disease and Subsequent Risk of Lung Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SURFACTANT PROTEIN-D; IDIOPATHIC PULMONARY-FIBROSIS; EPIDEMIOLOGIC EVIDENCE; SCREENING TRIAL; SERUM; TUBERCULOSIS; BIOMARKERS; CHINA; CELL; ADENOCARCINOMA AB Background: Inflammation and pulmonary diseases, including interstitial lung diseases, are associated with increased lung cancer risk. Circulating levels of surfactant protein-D (SP-D) and Krebs von Lungren-6 (KL-6) are elevated in interstitial lung disease patients and may be useful markers of processes contributing to lung cancer. Methods: We conducted a nested case-control study, including 532 lung cancer cases, 582 matched controls, and 150 additional controls with chest X-ray (CXR) evidence of pulmonary scarring, in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serum SP-D and KL-6 levels were measured using enzyme immunoassay. Logistic regression was used to estimate the associations of SP-D and KL-6 with lung cancer and CXR scarring. Results: Cases had higher levels than controls for SP-D (median 118.7 vs. 105.4 ng/mL, P = 0.008) and KL-6 (372.0 vs. 325.8 mu g/mL, P = 0.001). Lung cancer risk increased with SP-D (P(trend) = 0.0003) and KL-6 levels (P(trend) = 0.005). Compared with the lowest quartile, lung cancer risk was elevated among those with the highest quartiles of SP-D (OR = 1.87, 95% CI: 1.32-2.64) or KL-6 (OR = 1.58, 95% CI: 1.11-2.25). Among controls, participants with CXR scarring were more likely than those without scarring to have elevated levels of SP-D (quartile 4 vs. quartile 1: OR = 1.67, 95% CI: 1.04-2.70, P(trend) = 0.05) but not of KL-6 (OR = 1.04, 95% CI: 0.64-1.68, P(trend) = 0.99). Conclusion: Circulating levels of SP-D and KL-6 are associated with subsequent lung cancer risk. Impact: Our findings support a potential role for interstitial lung disease in lung cancer etiology or early detection, but additional research is needed. Cancer Epidemiol Biomarkers Prev; 20(10); 2262-72. (C) 2011 AACR. C1 [Shiels, Meredith S.] NCI, Infect & Immunoepidemiol Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Gochuico, Bernadette R.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20852 USA. EM shielsms@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU National Human Genome Research Institute; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute and of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. NR 38 TC 15 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2011 VL 20 IS 10 BP 2262 EP 2272 DI 10.1158/1055-9965.EPI-11-0326 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900032 PM 21828236 ER PT J AU Campo, RA Rowland, JH Irwin, ML Nathan, PC Gritz, ER Kinney, AY AF Campo, Rebecca A. Rowland, Julia H. Irwin, Melinda L. Nathan, Paul C. Gritz, Ellen R. Kinney, Anita Y. TI Cancer Prevention after Cancer: Changing the Paradigm-a Report from the American Society of Preventive Oncology SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; LONG-TERM SURVIVORS; BREAST-CANCER; CHILDHOOD-CANCER; PHYSICAL-ACTIVITY; 5-YEAR SURVIVORS; SUBSEQUENT NEOPLASMS; TEACHABLE MOMENT; ADULT SURVIVORS; LATE MORTALITY C1 [Kinney, Anita Y.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Campo, Rebecca A.; Kinney, Anita Y.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH DHHS, Bethesda, MD 20892 USA. [Irwin, Melinda L.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Nathan, Paul C.] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Gritz, Ellen R.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. RP Kinney, AY (reprint author), Univ Utah, Dept Internal Med, 2000 Circle Hope,Rm 4160, Salt Lake City, UT 84112 USA. EM anita.kinney@hci.utah.edu FU Office of Cancer Survivorship, Division of Cancer Control and Population Sciences, National Cancer Institute FX The 2011 annual American Society of Preventive Oncology Survivorship Special Interest Group was partially supported by the Office of Cancer Survivorship, Division of Cancer Control and Population Sciences, National Cancer Institute. NR 47 TC 10 Z9 10 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2011 VL 20 IS 10 BP 2317 EP 2324 DI 10.1158/1055-9965.EPI-11-0728 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900039 PM 21908726 ER PT J AU Sissung, TM Pressler, H Price, DK Figg, WD AF Sissung, T. M. Pressler, H. Price, D. K. Figg, W. D. TI SLCO Transport Genes in Prostate Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID TESTOSTERONE C1 [Sissung, T. M.; Figg, W. D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Pressler, H.; Price, D. K.; Figg, W. D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA. [Pressler, H.] Johns Hopkins Univ, Baltimore, MD USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wf13e@nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [Z01 BC010453-06] NR 5 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2011 VL 20 IS 10 BP 2325 EP 2325 DI 10.1158/1055-9965.EPI-11-0606 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900040 PM 21896883 ER PT J AU Peters, JM Gonzalez, FJ AF Peters, Jeffrey M. Gonzalez, Frank J. TI Why Toxic Equivalency Factors Are Not Suitable for Perfluoroalkyl Chemicals SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ACTIVATED-RECEPTOR-ALPHA; ARYL-HYDROCARBON RECEPTOR; MAMMARY-GLAND DEVELOPMENT; SPRAGUE-DAWLEY RATS; PPAR-ALPHA; PERFLUOROOCTANOIC ACID; AMMONIUM PERFLUOROOCTANOATE; NUCLEAR RECEPTORS; HUMAN RELEVANCE; IN-VITRO AB The pervasive nature of perfluoroalkyl chemicals in the environment has generated considerable interest for developing new strategies for risk assessment. In experimental animal models, exposure to perfluoroalkyl chemicals can cause developmental toxicity and hepatotoxicity. Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is required to mediate some but not all of these effects. Since PPARa has a role in mediating some of these effects, and there is some overlap in the type of toxicities elicited by perfluoroalkyl chemicals, it has been suggested that a scaling system analogous to the toxic equivalency factor (TEF) system used for polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), and polychlorinated biphenyls (PCB) could be used for perfluoroalkyl chemicals. However, evidence suggests that perfluoroalkyl chemicals can activate/interfere with other receptors, and there is reason to suggest the possibility of species differences in the response mediated by different receptors as well as qualitative differences in toxicities elicited by perfluoroalkyl chemicals. These differences and other data gaps preclude the development of a TEF approach for perfluoroalkyl chemicals. C1 [Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu NR 68 TC 20 Z9 21 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2011 VL 24 IS 10 BP 1601 EP 1609 DI 10.1021/tx200316x PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 832PP UT WOS:000295817800001 PM 21913657 ER PT J AU Mi, LX Hood, BL Stewart, NA Xiao, Z Govind, S Wang, XT Conrads, TP Veenstra, TD Chung, FL AF Mi, Lixin Hood, Brian L. Stewart, Nicolas A. Xiao, Zhen Govind, Sudha Wang, Xiantao Conrads, Thomas P. Veenstra, Timothy D. Chung, Fung-Lung TI Identification of Potential Protein Targets of Isothiocyanates by Proteomics SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PROSTATE-CANCER CELLS; PHENETHYL ISOTHIOCYANATE; INDUCED APOPTOSIS; LUNG-CANCER; EXPRESSION LEVEL; PHASE-2 ENZYMES; S-NITROSYLATION; A/J MICE; SULFORAPHANE; PHOSPHORYLATION AB Isothiocyanates (ITCs), such as phenethyl isothiocyanate (PEITC) and sulforaphane (SFN), are effective cancer chemopreventive compounds. It is believed that the major mechanism for the cancer preventive activity of ITCs is through the induction of cell cycle arrest and apoptosis. However, the upstream molecular targets of ITCs have been underexplored until recently. To identify proteins that are covalently modified by ITCs, human non-small cell lung cancer A549 cells were treated with (14)C-PEITC and (14)C-SFN, and the cell lysates were extracted for analysis by 2-D gel electrophoresis and mass spectrometry. After superimposing the colloidal Coomassie blue protein staining pattern with the pattern of radioactivity obtained from X-ray films, it was clear that only a small fraction of cellular proteins contained radioactivity, presumably resulting from selective binding with PEITC or SFN via thiocarbamation. More than 30 proteins with a variety of biological functions were identified with high confidence. Here, we report the identities of these potential ITC target proteins and discuss their biological relevance. The discovery of the protein targets may facilitate studies of the mechanisms by which ITCs exert their cancer preventive activity and provide the molecular basis for designing more efficacious ITC compounds. C1 [Mi, Lixin; Govind, Sudha; Wang, Xiantao; Chung, Fung-Lung] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Hood, Brian L.; Stewart, Nicolas A.; Xiao, Zhen; Conrads, Thomas P.; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Chung, FL (reprint author), Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd,LL 128A,Box 571465, Washington, DC 20057 USA. EM flc6@georgetown.edu FU NIH [CA-100853] FX This study was supported by NIH grant CA-100853. NR 52 TC 37 Z9 38 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2011 VL 24 IS 10 BP 1735 EP 1743 DI 10.1021/tx2002806 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 832PP UT WOS:000295817800016 PM 21838287 ER PT J AU Hazard, M Steele, S Wang, DW Pearson, T Scheideler, M Dewhurst, S AF Hazard, Mike Steele, Scott Wang, Dongwen Pearson, Thomas Scheideler, Mark Dewhurst, Steve TI CTSA-IP: A Solution to Identifying and Aggregating Intellectual Property across the NIH Clinical Translational Science Award (CTSA) Consortium of Biomedical Research Institutes SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE intellectual property; informatics; research partnerships AB One of the objectives of the Consortium of Institutions with Clinical and Translational Science Awards (CTSAs) is to enhance technology transfer among the CTSAs and with public and private sector partners. Clinical and Translational Sciences Award Intellectual Property (CTSA-IP; http://www.CTSAIP.org) is a web-based, open access IP search tool that aggregates and promotes technologies from member institutions of the National Institutes of Health's (NIH) CTSAs consortium. Its ultimate aim is to stimulate collaborative research activity by encouraging the formation of public-private partnerships with CTSA institutions and the NIH. First launched in 2009, CTSA-IP has grown rapidly and met its first objectives of developing wide member institution participation and site usage. This communication will discuss the strategy employed in the initiative of aggregating IP across institutional boundaries, the promise that lies therein, as well as the challenges encountered and lessons learned in promoting CTSA-wide engagement. Clin Trans Sci 2011; Volume 4: 328-331 C1 [Steele, Scott] Univ Rochester, Med Ctr, Clin & Translat Sci Inst, Off Res Alliances & Publ Private Partnerships Key, Rochester, NY 14642 USA. [Hazard, Mike; Wang, Dongwen] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Steele, Scott; Pearson, Thomas] Univ Rochester, Sch Med & Dent, Dept Community & Prevent Med, Rochester, NY 14642 USA. [Scheideler, Mark] NINDS, Off Translat Res, NIH, Bethesda, MD 20892 USA. [Dewhurst, Steve] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. RP Steele, S (reprint author), Univ Rochester, Med Ctr, Clin & Translat Sci Inst, Off Res Alliances & Publ Private Partnerships Key, Rochester, NY 14642 USA. EM scott.steele@rochester.edu FU National Center for Research Resources, NIH, CTSA, part of the Roadmap Initiative, Re-engineering the Clinical Research Enterprise FX The authors gratefully thank Dr. Bonnie Harbinger of NIH for assistance and advice throughout the development of this project. This project was supported by a Supplement to Award Number UL1 RR024160 from the National Center for Research Resources, NIH, CTSA program, part of the Roadmap Initiative, Re-engineering the Clinical Research Enterprise. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 8 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD OCT PY 2011 VL 4 IS 5 BP 328 EP 331 DI 10.1111/j.1752-8062.2011.00308.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 840ER UT WOS:000296421600010 PM 22029803 ER PT J AU Kunkel, TA AF Kunkel, Thomas A. TI Balancing eukaryotic replication asymmetry with replication fidelity SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID DNA-POLYMERASE-DELTA; UNIQUE ERROR SIGNATURE; IMBALANCED DNTP POOLS; MISMATCH REPAIR; SACCHAROMYCES-CEREVISIAE; RIBONUCLEOTIDE INCORPORATION; S-PHASE; YEAST; EPSILON; FORK AB Coordinated replication of eukaryotic nuclear genomes is asymmetric, with copying of a leading strand template preceding discontinuous copying of the lagging strand template. Replication is catalyzed by DNA polymerases alpha, delta and epsilon, enzymes that are related yet differ in physical and biochemical properties, including fidelity. Recent studies suggest that Pol epsilon is normally the primary leading strand replicase, whereas most synthesis by Pol delta occurs during lagging strand replication. New studies show that replication asymmetry can generate strand-specific genome instability resulting from biased deoxynucleotide pools and unrepaired ribonucleotides incorporated into DNA during replication, and that the eukaryotic replication machinery has evolved to most efficiently correct those replication errors that are made at the highest rates. C1 [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Division of Intramural Research, NIEHS, NIH [Z01 ES065070, Z01 ES065089] FX To the many scientists whose work contributed to the topics considered here but whose publications were not cited due to space limitations, I thank them for their understanding. Interested readers arc encouraged to consult the recent articles that are cited, where citations to many other important studies can be found. I also thank Peter Burgers and Andrei Chabes for thoughtful comments on this article. Research performed in my laboratory is supported by Projects Z01 ES065070 and Z01 ES065089 from the Division of Intramural Research, NIEHS, NIH. NR 51 TC 24 Z9 24 U1 3 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD OCT PY 2011 VL 15 IS 5 BP 620 EP 626 DI 10.1016/j.cbpa.2011.07.025 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 840AL UT WOS:000296410500007 PM 21862387 ER PT J AU Dainiak, N Gent, RN Carr, Z Schneider, R Bader, J Buglova, E Chao, N Coleman, CN Ganser, A Gorin, C Hauer-Jensen, M Huff, LA Lillis-Hearne, P Maekawa, K Nemhauser, J Powles, R Schunemann, H Shapiro, A Stenke, L Valverde, N Weinstock, D White, D Albanese, J Meineke, V AF Dainiak, Nicholas Gent, Robert Nicolas Carr, Zhanat Schneider, Rita Bader, Judith Buglova, Elena Chao, Nelson Coleman, C. Norman Ganser, Arnold Gorin, Claude Hauer-Jensen, Martin Huff, L. Andrew Lillis-Hearne, Patricia Maekawa, Kazuhiko Nemhauser, Jeffrey Powles, Ray Schuenemann, Holger Shapiro, Alla Stenke, Leif Valverde, Nelson Weinstock, David White, Douglas Albanese, Joseph Meineke, Viktor TI Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE countermeasures for ARS; acute radiation syndrome management; treatment of ARS; narrative review of countermeasures for ARS ID MESENCHYMAL STEM-CELLS; RESPIRATORY-DISTRESS-SYNDROME; MEDICAL-MANAGEMENT; CRITICALLY-ILL; GLUCOSE CONTROL; PUBLIC-HEALTH; CRITICAL-CARE; SEPTIC SHOCK; DOUBLE-BLIND; LUNG INJURY AB Objectives: The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results: No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. Conclusions: High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future. C1 [Meineke, Viktor] Bundeswehr Inst Radiobiol, D-80937 Munich, Germany. [Dainiak, Nicholas] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Dainiak, Nicholas] Yale New Haven Hlth Bridgeport Hosp, New Haven, CT USA. [Carr, Zhanat] World Hlth Org, Geneva, Switzerland. [Schneider, Rita] Univ Wurzburg, Dept Nucl Med, D-97070 Wurzburg, Germany. [Bader, Judith; Coleman, C. Norman] Natl Canc Inst, Bethesda, MD 20892 USA. [Chao, Nelson] Duke Univ, Durham, NC 27706 USA. [Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [Gorin, Claude] Hosp St Antoine, St Antoine, France. [Hauer-Jensen, Martin] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Huff, L. Andrew; Lillis-Hearne, Patricia] Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Maekawa, Kazuhiko] Kanto Cent Hosp, Tokyo, Japan. [Nemhauser, Jeffrey] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Schuenemann, Holger] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Shapiro, Alla] US FDA, Rockville, MD 20857 USA. [Stenke, Leif] Karolinska Inst, S-10401 Stockholm, Sweden. [Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Douglas] Univ Pittsburgh, Program Eth & Crit Care Med, Pittsburgh, PA 15260 USA. [Albanese, Joseph] Yale New Haven Hlth Ctr Emergency Preparedness &, New Haven, CT USA. RP Meineke, V (reprint author), Bundeswehr Inst Radiobiol, Neuherbergstr 11, D-80937 Munich, Germany. EM ViktorMeineke@bundeswehr.org FU National Institute of Allergy and Infectious Diseases FX Owing to their seminal contributions in the field of radiation biology and their pioneering approaches to treatment of victims of radiation injury, this consultancy report is dedicated to Theodor M. Fliedner and Angelina Guskova. The authors thank Makoto Akashi, Axel Bottger, Thierry de Revel, Patrick Gourmelon, Richard Hatchett, Mikhail Konchalovski, Ying Liu, Maria Julia Marinissen, Hilary Walker, Helmut Walerius, and Wei Zhang for participating in the consultancy and contributing to consensus building. The authors are grateful to Richard Hatchett and the National Institute of Allergy and Infectious Diseases for providing financial support for this consultancy. NR 181 TC 28 Z9 28 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD OCT PY 2011 VL 5 IS 3 BP 183 EP 201 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 839JU UT WOS:000296362300007 PM 21986999 ER PT J AU Dainiak, N Gent, RN Carr, Z Schneider, R Bader, J Buglova, E Chao, N Coleman, CN Ganser, A Gorin, C Hauer-Jensen, M Huff, LA Lillis-Hearne, P Maekawa, K Nemhauser, J Powles, R Schunemann, H Shapiro, A Stenke, L Valverde, N Weinstock, D White, D Albanese, J Meineke, V AF Dainiak, Nicholas Gent, Robert Nicolas Carr, Zhanat Schneider, Rita Bader, Judith Buglova, Elena Chao, Nelson Coleman, C. Norman Ganser, Arnold Gorin, Claude Hauer-Jensen, Martin Huff, L. Andrew Lillis-Hearne, Patricia Maekawa, Kazuhiko Nemhauser, Jeffrey Powles, Ray Schuenemann, Holger Shapiro, Alla Stenke, Leif Valverde, Nelson Weinstock, David White, Douglas Albanese, Joseph Meineke, Viktor TI First Global Consensus for Evidence-Based Management of the Hematopoietic Syndrome Resulting From Exposure to Ionizing Radiation SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE countermeasures for ARS; cytokines and radiation injury; transplantation for ARS; acute radiation syndrome management; hematopoietic syndrome management ID COLONY-STIMULATING FACTOR; MEDICAL-MANAGEMENT; PROGENITOR CELLS; RHESUS-MONKEYS; RECOMMENDATIONS; ACCIDENT; MYELOSUPPRESSION; RADIOSENSITIVITY; TRANSPLANTATION; GROWTH AB Objective: Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with >1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence. Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to panel members before the meeting and updated during the meeting. Published case series and case reports of individuals with HS, published randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with radiation-associated HS. The use of GRADE analysis of countermeasures for injury to hematopoietic tissue was restricted by the lack of comparator groups in humans. Reliance on data generated in nonirradiated humans and experimental animals was necessary. Results: Based upon GRADE analysis and narrative review, a strong recommendation was made for the administration of granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor and a weak recommendation was made for the use of erythropoiesis-stimulating agents or hematopoietic stem cell transplantation. Conclusions: Assessment of therapeutic interventions for HS in humans exposed to nontherapeutic radiation is difficult because of the limits of the evidence. (Disaster Med Public Health Preparedness. 2011;5:202-212) C1 [Meineke, Viktor] Bundeswehr Inst Radiobiol, D-80937 Munich, Germany. [Dainiak, Nicholas] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Dainiak, Nicholas] Yale New Haven Hlth Bridgeport Hosp, New Haven, CT USA. [Carr, Zhanat] World Hlth Org, Geneva, Switzerland. [Schneider, Rita] Univ Wurzburg, Dept Nucl Med, D-97070 Wurzburg, Germany. [Bader, Judith; Coleman, C. Norman] Natl Canc Inst, Bethesda, MD 20892 USA. [Chao, Nelson] Duke Univ, Durham, NC 27706 USA. [Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [Gorin, Claude] Hosp St Antoine, St Antoine, France. [Hauer-Jensen, Martin] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Huff, L. Andrew; Lillis-Hearne, Patricia] Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Maekawa, Kazuhiko] Kanto Cent Hosp, Tokyo, Japan. [Nemhauser, Jeffrey] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Schuenemann, Holger] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Shapiro, Alla] US FDA, Rockville, MD 20857 USA. [Stenke, Leif] Karolinska Inst, S-10401 Stockholm, Sweden. [Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Douglas] Univ Pittsburgh, Program Eth & Crit Care Med, Pittsburgh, PA 15260 USA. [Albanese, Joseph] Yale New Haven Hlth Ctr Emergency Preparedness &, New Haven, CT USA. RP Meineke, V (reprint author), Bundeswehr Inst Radiobiol, Neuherbergstr 11, D-80937 Munich, Germany. EM ViktorMeineke@bundeswehr.org FU National Institute of Allergy and Infectious Diseases FX Owing to their seminal contributions in the field of radiation biology and their pioneering approaches to treatment of victims of radiation injury, this consultancy report is dedicated to Theodor M. Fliedner and Angelina Guskova. The authors thank Makoto Akashi, Axel Bottger, Thierry de Revel, Patrick Gourmelon, Richard Hatchett, Mikhail Konchalovski, Ying Liu, Maria Julia Marinissen, Hilary Walker, Helmut Walerius, and Wei Zhang for participating in the consultancy and contributing to consensus building. The authors are grateful to the National Institute of Allergy and Infectious Diseases for providing financial support for this consultancy. NR 44 TC 32 Z9 34 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD OCT PY 2011 VL 5 IS 3 BP 202 EP 212 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 839JU UT WOS:000296362300008 PM 21987000 ER PT J AU Davidson, TS Shevach, EM AF Davidson, Todd S. Shevach, Ethan M. TI Polyclonal Treg cells modulate T effector cell trafficking SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE EAE; Immunosuppression; Trafficking; Treg cells ID DENDRITIC CELLS; AUTOIMMUNE-DISEASE; CUTTING EDGE; IN-VITRO; INHIBIT; DIFFERENTIATION; RESPONSES; PREVENT; MICE; VIVO AB In this study, we have analyzed the in vivo dynamics of the interaction between polyclonal Foxp3(+) Treg cells, effector T (Teff) cells, and DCs in order to further our understanding of the mechanisms of Treg cell-mediated suppression. Cotransfer of polyclonal activated Treg cells into healthy mice attenuated the induction of EAE. Suppression of disease strongly correlated with a reduced number of Teff cells in the spinal cord, but not with Treg cell-mediated inhibition of Th1/Th17 differentiation. Cotransfer of Treg cells with TCR-Tg Teff cells followed by immunization by multiple routes resulted in an enhanced number of Teff cells in the lymph nodes draining the site of immunization without an inhibition of Teff-cell differentiation. Fewer Teff cells could be detected in the blood in the presence of Treg cells and fewer T cells could access a site of antigen exposure in a modified delayed-type hypersensitivity assay. Teff cells recovered from LNs in the presence of Treg cells expressed decreased levels of CXCR4, syndecan, and the sphingosine phosphate receptor, S1P1 (sphingosine 1-phosphate receptor 1). Thus, polyclonal Treg cells influence Teff-cell responses by targeting trafficking pathways, thus allowing immunity to develop in lymphoid organs, but limiting the number of potentially auto-aggressive cells that are allowed to enter the tissues. C1 [Davidson, Todd S.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases FX These studies were supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. NR 23 TC 25 Z9 25 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2011 VL 41 IS 10 BP 2862 EP 2870 DI 10.1002/eji.201141503 PG 9 WC Immunology SC Immunology GA 837KB UT WOS:000296199000009 PM 21728170 ER PT J AU Mkrtichyan, M Najjar, YG Raulfs, EC Abdalla, MY Samara, R Rotem-Yehudar, R Cook, L Khleif, SN AF Mkrtichyan, Mikayel Najjar, Yana G. Raulfs, Estella C. Abdalla, Maher Y. Samara, Raed Rotem-Yehudar, Rinat Cook, Larry Khleif, Samir N. TI Anti-PD-1 synergizes with cyclophosphamide to induce potent anti-tumor vaccine effects through novel mechanisms SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Cancer immunotherapy; Programmed death-1 receptor; Vaccine ID REGULATORY T-CELLS; IMMUNOLOGICAL SELF-TOLERANCE; FACILITATED ADOPTIVE IMMUNOTHERAPY; TUMOR-INFILTRATING LYMPHOCYTES; INCREASED POPULATIONS; PERIPHERAL-BLOOD; CLINICAL-SIGNIFICANCE; CARCINOMA PATIENTS; PROGNOSTIC-FACTORS; PANCREATIC-CANCER AB Programmed death-1 receptor (PD-1) is expressed on T cells following TCR activation. Binding of this receptor to its cognate ligands, programmed death ligand (PDL)-1 and PDL-2, down-regulates signals by the TCR, promoting T-cell anergy and apoptosis, thus leading to immune suppression. Here, we find that using an anti-PD-1 antibody (CT-011) with Treg-cell depletion by low-dose cyclophosphamide (CPM), combined with a tumor vaccine, induces synergistic antigen-specific immune responses and reveals novel activities of each agent in this combination. This strategy led to complete regression of established tumors in a significant percentage of treated animals, with survival prolongation. We show for the first time that combining CT-011 and CPM significantly increases the number of vaccine-induced tumor-infiltrating CD8(+) T cells, with simultaneous decrease in infiltrating Treg cells. Interestingly, we find that CT-011 prolongs Treg-cell inhibition induced by CPM, leading to a sustainable significant synergistic decrease of splenic and tumor-infiltrated Treg cells. Surprisingly, we find that the anti-tumor effect elicited by the combination of CT-011 and CPM is dependent on both CD8(+) and CD4(+) T-cell responses, although the antigen we used is a class I MHC-restricted peptide. Thus, we describe a novel and effective therapeutic approach by combining multiple strategies to target several tumor-mediated immune inhibitory mechanisms. C1 [Mkrtichyan, Mikayel; Najjar, Yana G.; Raulfs, Estella C.; Abdalla, Maher Y.; Samara, Raed; Khleif, Samir N.] NCI, Canc Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Rotem-Yehudar, Rinat] CureTech Ltd, Yavne, Israel. [Cook, Larry] NIH, Lab Anim Sci Program, Bethesda, MD 20892 USA. RP Khleif, SN (reprint author), NCI, Canc Vaccine Sect, NIH, Bldg 41,Room B900, Bethesda, MD 20892 USA. EM khleif@nih.gov FU Center for Cancer Research, NCI, NIH FX The authors thank Daniel O'Mard, Ashley Reynolds and Gail McMullen from the NIH animal facility for their technical assistance with animal injections. This work was supported by the Intramural Research Program of the Center for Cancer Research, NCI, NIH. NR 46 TC 55 Z9 56 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2011 VL 41 IS 10 BP 2977 EP 2986 DI 10.1002/eji.201141639 PG 10 WC Immunology SC Immunology GA 837KB UT WOS:000296199000020 PM 21710477 ER PT J AU Faupel-Badger, JM Staff, AC Thadhani, R Powe, CE Potischman, N Hoover, RN Troisi, R AF Faupel-Badger, Jessica M. Staff, Anne Cathrine Thadhani, Ravi Powe, Camille E. Potischman, Nancy Hoover, Robert N. Troisi, Rebecca TI Maternal angiogenic profile in pregnancies that remain normotensive SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE Pregnancy; Angiogenic factors; sFlt1; PlGF; Soluble endoglin; Maternal ID PLACENTAL GROWTH-FACTOR; SOLUBLE ENDOGLIN; HYPERTENSIVE DISORDERS; ANTIANGIOGENIC FACTORS; TYROSINE KINASE-1; PREECLAMPSIA; RISK; SFLT1; VASCULOGENESIS; PATHOGENESIS AB Objective: We sought to determine if maternal characteristics are associated with angiogenic profile in the first and second trimester of normotensive pregnancies. Study design: Circulating levels of maternal placental like growth factor (PIGF), soluble fms-like tyrosine kinase receptor (sFlt1), and soluble endoglin (sEng) were measured in serum samples collected during the first (median 11.3 weeks) and second trimester (median 17.1 weeks) of 182 normotensive pregnancies. Diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) were measured at the same visits when samples were collected to measure angiogenic factors. Linear regression analysis was used to examine associations of the angiogenic measures with maternal characteristics. The association between blood pressure measures and concentrations of angiogenic factors was evaluated using Spearman correlation and linear regression analysis. Results: In adjusted analyses, nulliparous women had higher sFlt1 concentrations in both first (p = 0.06) and second (p = 0.001) trimester. Higher BMI was associated with greater sFlt1 concentrations in both the first (p = 0.004) and second trimester (p = 0.008), but significantly lower sEng concentrations in both trimesters (p = 0.002 for first trimester and p = 0.0009 for second). Nulliparity and higher BMI also were associated with higher sFlt1/PLGF anti-angiogenic ratios in both first (p = 0.05 and p = 0.007, respectively) and second trimesters (p = 0.003 and p = 0.02, respectively). First trimester sFlt1 levels were weakly correlated with first trimester SBP (r(s) = 0.18, p = 0.03) and MAP (r(s) = 0.16, p = 0.04). Second trimester sEng levels were inversely associated with second trimester MAP (r(s) = -0.17, p = 0.05). Including blood pressure measures in the linear regression models did not change the reported associations of angiogenic factors with maternal characteristics. Conclusions: These results demonstrate that even early in normotensive pregnancies maternal characteristics are associated with variations in angiogenic profile across this population. Published by Elsevier Ireland Ltd. C1 [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD USA. [Faupel-Badger, Jessica M.; Hoover, Robert N.; Troisi, Rebecca] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Rockville, MD USA. [Staff, Anne Cathrine] Oslo Univ Hosp, Dept Obstet & Gynaecol, Ulleval, Norway. [Staff, Anne Cathrine] Univ Oslo, Fac Med, Oslo, Norway. [Thadhani, Ravi; Powe, Camille E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thadhani, Ravi; Powe, Camille E.] Harvard Univ, Sch Med, Boston, MA USA. [Potischman, Nancy] NCI, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Troisi, Rebecca] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. RP Faupel-Badger, JM (reprint author), NIH, 6120 Execut Blvd,Suite 150E,MSC 7105, Bethesda, MD 20892 USA. EM badgerje@mail.nih.gov FU NIH; National Cancer Institute; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services; Division Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services; [HD 39223] FX Funding support: This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. The Divisions of Cancer Epidemiology and Genetics and Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services provided funding for the data analysis and manuscript preparation. HD 39223 provided funding for the collection of original data and laboratory assays. NR 25 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD OCT PY 2011 VL 158 IS 2 BP 189 EP 193 DI 10.1016/j.ejogrb.2011.05.001 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 838OK UT WOS:000296301900012 PM 21641103 ER PT J AU Ko, SU Stenholm, S Chia, CW Simonsick, EM Ferrucci, L AF Ko, Seung-uk Stenholm, Sari Chia, Chee W. Simonsick, Eleanor M. Ferrucci, Luigi TI Gait pattern alterations in older adults associated with type 2 diabetes in the absence of peripheral neuropathy-Results from the Baltimore Longitudinal Study of Aging SO GAIT & POSTURE LA English DT Article DE Type 2 diabetes; Aging; Gait; Mobility limitation; Peripheral neuropathy; Mechanical work expenditure ID JOINT KINEMATICS; CENTER LOCATION; WALKING; MELLITUS; ACCURACY AB Diabetes may impact gait mechanics before onset of frank neuropathies and other associated threats to mobility. This study aims to characterize gait pattern alterations of type 2 diabetic adults without peripheral neuropathy during walking at maximum speed (fast-walking) as well as at self-selected speed (usual-walking). One-hundred and eighty-six participants aged 60-87 from the Baltimore Longitudinal Study of Aging (BLSA) able to walk unassisted and without peripheral neuropathy were classified as nondiabetic (N = 160) or having type 2 diabetes (N = 26). Gait parameters from the fast-walking and usual-walking tests were compared between participants with and without type 2 diabetes. Participants with diabetes had a shorter stride length for fast-walking (p = 0.033) and a longer percentage of the gait cycle with the knee in 1st flexion for both fast- and usual-walking (p = 0.033, and 0.040, respectively) than non-diabetic participants. Participants with diabetes exhibited a smaller hip range of motion in the sagittal plane during usual-walking compared to non-diabetics (p = 0.049). During fast-walking, participants with diabetes used lower ankle generative mechanical work expenditure (MWE) and higher knee absorptive MWE compared to non-diabetic persons (p = 0.021, and 0.018, respectively). These findings suggest that individuals with type 2 diabetes without overt peripheral neuropathy exhibit altered and less efficient gait patterns than non-diabetic persons. These alterations are more apparent during walking at a maximum speed indicating that maximum gait testing may be useful for identifying early threats to mobility limitations in older adults with type 2 diabetes. (C) 2011 Elsevier B.V. All rights reserved. C1 [Ko, Seung-uk] Chonnam Natl Univ, Dept Mech Engn, Yeosu 550749, Jeonnam, South Korea. [Chia, Chee W.; Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Stenholm, Sari] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Turku, Finland. RP Ko, SU (reprint author), Chonnam Natl Univ, Dept Mech Engn, 50 Daehak Ro, Yeosu 550749, Jeonnam, South Korea. EM seunguk.ko@gmail.com RI Stenholm, Sari/G-6940-2011 FU NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. Data for these analyses were obtained from the Baltimore Longitudinal Study of Aging, a study performed by the National Institute on Aging. NR 23 TC 26 Z9 27 U1 3 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD OCT PY 2011 VL 34 IS 4 BP 548 EP 552 DI 10.1016/j.gaitpost.2011.07.014 PG 5 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 841AQ UT WOS:000296484800020 PM 21873064 ER PT J AU Felizardo, T Wang, JCM McGray, RAJ Evelegh, C Spaner, DE Fowler, DH Bramson, JL Medin, JA AF Felizardo, T. C. Wang, J. C. M. McGray, R. A. J. Evelegh, C. Spaner, D. E. Fowler, D. H. Bramson, J. L. Medin, J. A. TI Differential immune responses mediated by adenovirus- and lentivirus-transduced DCs in a HER-2/neu overexpressing tumor model SO GENE THERAPY LA English DT Article DE HER-2/neu; adenovirus; lentivirus; dendritic cells vaccine ID PLASMACYTOID DENDRITIC CELLS; RECOMBINANT ADENOVIRUS; IN-VIVO; ANTITUMOR IMMUNITY; CLINICAL-TRIALS; GENE DELIVERY; T-CELLS; ANTIGEN; VECTOR; CANCER AB Recent investigations have demonstrated that adenoviral and lentiviral vectors encoding HER-2 can be utilized in cancer immunotherapy. However, it is not known whether both viral systems elicit a similar immune response. Here, we compare the immune response in mice induced by dendritic cells (DCs) infected with either recombinant adenovirus or lentivirus encoding rat HER-2 (rHER-2). Both vaccine types yielded similar control of tumor growth, but we found clear differences in their immune responses 10 days after DC immunization. Adenovirus rHER-2-transduced DCs elicited locally and systemically high frequencies of CD4+ and CD8+ T cells, while lentivirus rHER-2-transduced DCs predominantly led to CD4+ T-cell infiltration at the tumor site. Splenocytes from mice immunized with lentivirus rHER-2-transduced DCs secreted higher levels of interferon (IFN)-gamma, mainly by CD4+ T cells, following stimulation by RM-1-mHER-2 tumors. In contrast, the adenovirus vaccinated group exhibited CD4+ and CD8+ T cells that both contributed to IFN-gamma production. Besides an established cellular immune response, the rHER-2/DC vaccine elicited a significant humoral response that was highest in the adenovirus group. DC subsets and regulatory T cells in the spleen were also differentially modulated in the two vaccine systems. Finally, adoptive transfer of splenocytes from both groups of immunized mice strongly inhibited in vivo tumor growth. Our results suggest that not only the target antigen but also the virus system may determine the nature and magnitude of antitumor immunity by DC vaccination. Gene Therapy (2011) 18, 986-995; doi:10.1038/gt.2011.53; published online 14 April 2011 C1 [Felizardo, T. C.; Medin, J. A.] Univ Hlth Network, Campbell Family Canc Res Inst, Toronto, ON M5G 2M1, Canada. [Felizardo, T. C.; Medin, J. A.] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M1, Canada. [Wang, J. C. M.; Medin, J. A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Spaner, D. E.; Medin, J. A.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Spaner, D. E.] Sunnybrook Odette Canc Ctr, Dept Med Oncol, Toronto, ON, Canada. [McGray, R. A. J.; Evelegh, C.; Bramson, J. L.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Fowler, D. H.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Medin, JA (reprint author), Univ Hlth Network, Campbell Family Canc Res Inst, Room 456,67 Coll St, Toronto, ON M5G 2M1, Canada. EM jmedin@uhnres.utoronto.ca FU Ontario Ministry of Health and Long-Term Care; Terry Fox Foundation Canada FX We thank Cindy Guo and Kenneth Zhang for their technical assistance in the preparation of plasmids and vectors used in these experiments. We also would like to thank Dr Natalia Pacienza for helping with the processing of samples. This research was funded in part by the Ontario Ministry of Health and Long-Term Care. The views expressed do not necessarily reflect those of the OMOHLTC. Funding was also provided in part by a program project grant from The Terry Fox Foundation Canada to JAM, JLB and DES. NR 36 TC 6 Z9 8 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2011 VL 18 IS 10 BP 986 EP 995 DI 10.1038/gt.2011.53 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 836VS UT WOS:000296145300007 PM 21490686 ER PT J AU Pagani, JH Lee, HJ Young, WS AF Pagani, J. H. Lee, H. -J. Young, W. S., III TI Postweaning, forebrain-specific perturbation of the oxytocin system impairs fear conditioning SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Central amygdala; conditional knockout; oxytocin receptor; vasopressin 1a receptor ID DIFFERENTIAL CONTRIBUTION; BASOLATERAL AMYGDALA; POTENTIATED STARTLE; SOCIAL RECOGNITION; PERIRHINAL CORTEX; EXTENDED AMYGDALA; BINDING-SITES; C57BL/6 MICE; RAT-BRAIN; VASOPRESSIN AB Oxytocin (Oxt) and vasopressin (Avp) are important for a wide variety of behaviors and the use of transgenic mice lacking the peptides or their receptors, particularly when their loss is spatially and temporally manipulated, offers an opportunity to closely examine their role in a particular behavior. We used a cued fear conditioning paradigm to examine associative learning in three lines of transgenic mice: mice that constitutively lack vasopressin 1a (Avpr1a(-/-)) or Oxt receptors (Oxtr(-/-)) and mice that have Oxt receptor loss restricted to the forebrain that begins postweaning (OxtrFB/FB). Oxtr(-/-) and Avpr1a(-/-) mice have normal conditioned freezing. OxtrFB/FB mice have a reduction in freezing behavior during acquisition, as well as during context and cue retention. In addition to reduction of Oxtr in the central nucleus of the amygdala, in vitro receptor autoradiography showed that the OxtrFB/FB mice have significantly reduced levels of Avpr1a only in that structure. Our results show that postweaning alteration of the distribution of Oxtr receptors is critically important for fear behavior, an effect mirrored in the neural structures that mediate it. While constitutive knockouts of Oxtr and Avpr1a are useful for identifying the neural underpinnings of some behaviors, compensatory mechanisms within some circuits may obscure other behavioral roles. C1 [Pagani, J. H.; Young, W. S., III] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. [Lee, H. -J.] Kyungpook Natl Univ, Sch Dent, Dept Dent Microbiol, Taegu, South Korea. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, 9000 Rockville Pike,Bldg 49,Room 5A56, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009; OI Young, W Scott/0000-0001-6614-5112; , Heon-Jin/0000-0002-1911-5014 FU NIMH [Z01-MH-002498-22] FX The authors would like to thank Kevin Brown, Michael Burman and Michael Lehmann for their comments on the original document and Emily Shepard and June Song for their technical assistance. This research was supported by the NIMH Intramural Research Program (Z01-MH-002498-22). The authors state that they have no conflicts of interest. NR 57 TC 14 Z9 14 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD OCT PY 2011 VL 10 IS 7 BP 710 EP 719 DI 10.1111/j.1601-183X.2011.00709.x PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 837WD UT WOS:000296238100003 PM 21668734 ER PT J AU Cole, J Weinberger, DR Mattay, VS Cheng, X Toga, AW Thompson, PM Powell-Smith, G Cohen-Woods, S Simmons, A McGuffin, P Fu, CHY AF Cole, J. Weinberger, D. R. Mattay, V. S. Cheng, X. Toga, A. W. Thompson, P. M. Powell-Smith, G. Cohen-Woods, S. Simmons, A. McGuffin, P. Fu, C. H. Y. TI No effect of 5HTTLPR or BDNF Val66Met polymorphism on hippocampal morphology in major depression SO GENES BRAIN AND BEHAVIOR LA English DT Article DE BDNF; 5HTTLPR; hippocampus; major depressive disorder; MRI; shape mapping ID SEROTONIN TRANSPORTER GENE; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; 5-HTTLPR POLYMORPHISM; BRAIN STRUCTURE; LONG VARIANT; VOLUME; DISORDER; ASSOCIATION; MEMORY AB Neuroimaging research implicates the hippocampus in the aetiology of major depressive disorder (MDD). Imaging genetics studies have investigated the influence of the serotonin transporter-linked polymorphic region (5HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on the hippocampus in healthy individuals and patients with depression (MDD). However, conflicting results have led to inconclusive evidence about the effect of 5HTTLPR or BDNF on hippocampal volume (HCV). We hypothesized that analysis methods based on three-dimensional (3D) hippocampal shape mapping could offer improved sensitivity to clarify these effects. Magnetic resonance imaging data were collected in parallel samples of 111 healthy individuals and 84 MDD patients. Manual hippocampal segmentation was conducted and the resulting data used to investigate the influence of 5HTTLPR and BDNF Val66Met genotypes on HCV and 3D shape within each sample. Hippocampal volume normalized by intracranial volume (ICV) showed no significant difference between 5HTTLPR S allele carriers and L/L homozygotes or between BDNF Met allele carriers and Val/Val homozygotes in the group of healthy individuals. Moreover, there was no significant difference in normalized HCV between 5HTTLPR diallelic and triallelic classifications or between the BDNF Val66Met genotypes in MDD patients, although there was a relationship between BDNF Val66Met and ICV. Shape analysis detected dispersed between-group differences, but these effects did not survive multiple testing correction. In this study, there was no evidence of a genetic effect for 5HTTLPR or BDNF Val66Met on hippocampal morphology in either healthy individuals or MDD patients despite the relatively large sample sizes and sensitive methodology. C1 [Cole, J.; Powell-Smith, G.; Cohen-Woods, S.; McGuffin, P.; Fu, C. H. Y.] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Res Ctr, London SE5 8AF, England. [Weinberger, D. R.; Mattay, V. S.; Cheng, X.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Toga, A. W.; Thompson, P. M.] Univ Calif Los Angeles, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA. [Simmons, A.; McGuffin, P.; Fu, C. H. Y.] Kings Coll London, S London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, London WC2R 2LS, England. [Simmons, A.] Kings Coll London, MRC Ctr Neurodegenerat Res, London WC2R 2LS, England. [Simmons, A.] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. RP Cole, J (reprint author), Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Res Ctr, POB 80, London SE5 8AF, England. EM james.h.cole@kcl.ac.uk RI Cole, James/G-8045-2011; Simmons, Andrew/B-8848-2008; McGuffin, Peter/A-1565-2012; Cohen-Woods, Sarah/F-8674-2014; OI Simmons, Andrew/0000-0003-2306-5811; McGuffin, Peter/0000-0002-9888-2907; Cohen-Woods, Sarah/0000-0003-2199-6129; Fu, Cynthia/0000-0003-4313-3500 FU Medical Research Council; Wellcome Trust; GlaxoSmithKline, UK; National Institute of Health Research Biomedical Research Centre for Mental Health at the South London; Maudsley NHS Foundation Trust; Institute of Psychiatry King's College London; NARSAD; NH [R01 EB008281, P41 RR013642] FX J. C. was funded by a Medical Research Council studentship and a Wellcome Trust Value in People award for the duration of this work. The study was funded in part by GlaxoSmithKline, UK, and the National Institute of Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry King's College London, as well as a NARSAD Young Investigator Award to C. H. Y. F. Additional support for algorithm development was provided by NH grants R01 EB008281 to P. M. T. and P41 RR013642 to A. W. T. NR 58 TC 32 Z9 33 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD OCT PY 2011 VL 10 IS 7 BP 756 EP 764 DI 10.1111/j.1601-183X.2011.00714.x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 837WD UT WOS:000296238100008 PM 21692988 ER PT J AU Pidala, J Kurland, BF Chai, XY Vogelsang, G Weisdorf, DJ Pavletic, S Cutler, C Majhail, N Lee, SJ AF Pidala, Joseph Kurland, Brenda F. Chai, Xiaoyu Vogelsang, Georgia Weisdorf, Daniel J. Pavletic, Steven Cutler, Corey Majhail, Navneet Lee, Stephanie J. TI Sensitivity of changes in chronic graft-versus-host disease activity to changes in patient-reported quality of life: results from the Chronic Graft-versus-Host Disease Consortium SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE chronic graft versus host disease; quality of life; sensitivity to change ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; FORM HEALTH SURVEY; RECOMMENDATIONS; RELIABILITY; SURVIVORS; RECOVERY; VALIDITY; TRIALS; TESTS AB Background The 2005 National Institute of Health Chronic Graft-versus-Host Disease Consensus Conference recommended collection of patient-reported outcomes in clinical trials on chronic graft-versus-host disease. We assessed whether changes in chronic graft-versus-host disease severity, determined using National Institute of Health criteria, clinicians' assessment or patients' self-evaluation, correlated with patient-reported quality of life as measured by the Short Form-36 and Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) instruments. Design and Methods Three-hundred and thirty-six adult patients (median age 52 years; range, 19 - 79) with chronic graft-versus-host disease from six transplant centers contributed baseline and follow-up data (from 936 visits overall). Results While the majority of the patients had stable chronic graft-versus-host disease, improvement or worsening was noted in approximately 40% of follow-up visits. Multivariable analysis demonstrated no association between change in chronic graft-versus-host disease severity evaluated by National Institute of Health criteria and change in quality of life, while clinician-reported changes in severity were associated with changes in some quality of life measures. Patient-reported changes in the severity of chronic graft-versus-host disease were associated with changes in all quality of life measures. Comparison of the Short Form-36 and the FACT-BMT suggested that the data collected in the Functional Assessment of Cancer Therapy - General (FACT-G) core survey are sufficient without the need for the Short Form-36 or the FACT-BMT subscale. Conclusions We conclude that serial National Institute of Health and clinician-reported chronic graft-versus-host disease severity assessments cannot substitute for patient-reported outcomes in clinical trials. Collection of just the FACT-G instead of the Short Form-36 and the full FACT-BMT will decrease respondent burden without compromising quality of life assessment. C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Kurland, Brenda F.; Chai, Xiaoyu; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Vogelsang, Georgia] Johns Hopkins Univ, Baltimore, MD USA. [Weisdorf, Daniel J.; Majhail, Navneet] Univ Minnesota, Minneapolis, MN USA. [Pavletic, Steven] NCI, Bethesda, MD 20892 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pidala, J (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr,FOB 3308, Tampa, FL 33612 USA. EM joseph.pidala@moffitt.org OI Kurland, Brenda/0000-0002-5669-0595 NR 26 TC 20 Z9 21 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD OCT PY 2011 VL 96 IS 10 BP 1528 EP 1535 DI 10.3324/haematol.2011.046367 PG 8 WC Hematology SC Hematology GA 837XR UT WOS:000296245000020 PM 21685473 ER PT J AU Kelley, MW Mann, ZF AF Kelley, Matthew W. Mann, Zoe F. TI Response to a Letter to the Editor SO HEARING RESEARCH LA English DT Letter ID COCHLEAR HAIR-CELLS; MAMMALIAN COCHLEA; BASILAR PAPILLA; ONTOGENETIC CHANGES; FREQUENCY MAP; EXPRESSION; CHICKEN; INNERVATION; PATTERN; GERBIL C1 [Kelley, Matthew W.; Mann, Zoe F.] Natl Inst Deafness & Commun Disorders, Lab Cochlear Dev, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Kelley, MW (reprint author), Natl Inst Deafness & Commun Disorders, Lab Cochlear Dev, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. EM kelleymt@nidcd.nih.gov NR 20 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 2011 VL 280 IS 1-2 BP 1 EP 2 DI 10.1016/j.heares.2011.04.009 PG 2 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 834XG UT WOS:000295997200001 PM 21600274 ER PT J AU Bastian, H Scheibler, F Knelangen, M Zschorlich, B Nasser, M Waltering, A AF Bastian, Hilda Scheibler, Fueloep Knelangen, Marco Zschorlich, Beate Nasser, Mona Waltering, Andreas TI Choosing health technology assessment and systematic review topics: The development of priority-setting criteria for patients' and consumers' interests SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE `Priority setting; Disinvestments; Patient and consumer interests; Patient participation ID INVOLVEMENT; CARE AB Background: The Institute for Quality and Efficiency in Health Care (IQWiG) was established in 2003 by the German parliament. Its legislative responsibilities are health technology assessment, mostly to support policy making and reimbursement decisions. It also has a mandate to serve patients' interests directly, by assessing and communicating evidence for the general public. Objectives: To develop a priority-setting framework based on the interests of patients and the general public. Methods: A theoretical framework for priority setting from a patient/consumer perspective was developed. The process of development began with a poll to determine level of lay and health professional interest in the conclusions of 124 systematic reviews (194 responses). Data sources to identify patients' and consumers' information needs and interests were identified. Results: IQWiG's theoretical framework encompasses criteria for quality of evidence and interest, as well as being explicit about editorial considerations, including potential for harm. Dimensions of "patient interest" were identified, such as patients' concerns, information seeking, and use. Rather than being a single item capable of measurement by one means, the concept of "patients' interests" requires consideration of data and opinions from various sources. Conclusions: The best evidence to communicate to patients/consumers is right, relevant and likely to be considered interesting and/or important to the people affected. What is likely to be interesting for the community generally is sufficient evidence for a concrete conclusion, in a common condition. More research is needed on characteristics of information that interest patients and consumers, methods of evaluating the effectiveness of priority setting, and methods to determine priorities for disinvestment. C1 [Bastian, Hilda] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Scheibler, Fueloep; Knelangen, Marco; Zschorlich, Beate; Waltering, Andreas] Inst Qual & Efficiency Hlth Care, D-51105 Cologne, Germany. [Nasser, Mona] Univ Exeter, Peninsula Coll Med & Dent, Plymouth PL6 8BU, Devon, England. [Nasser, Mona] Univ Plymouth, Peninsula Coll Med & Dent, Plymouth PL6 8BU, Devon, England. RP Bastian, H (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM hilda.bastian@nih.gov; fueloep.scheibler@iqwig.de; beate.zschorlich@iqwig.de; andreas.waltering@iqwig.de RI Nasser, Mona/J-3601-2013; Embrett, Mark/H-4466-2014; OI Embrett, Mark/0000-0002-3969-0219; Bastian, Hilda/0000-0001-8544-7386 NR 20 TC 1 Z9 1 U1 0 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD OCT PY 2011 VL 27 IS 4 BP 348 EP 356 DI 10.1017/S0266462311000547 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 840EH UT WOS:000296420600013 PM 22004776 ER PT J AU Danner, M Hummel, JM Volz, F van Manen, JG Wiegard, B Dintsios, CM Bastian, H Gerber, A IJzerman, MJ AF Danner, Marion Hummel, J. Marjan Volz, Fabian van Manen, Jeannette G. Wiegard, Beate Dintsios, Charalabos-Markos Bastian, Hilda Gerber, Andreas IJzerman, Maarten J. TI Integrating patients' views into health technology assessment: Analytic hierarchy process (AHP) as a method to elicit patient preferences SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE Patient involvement; Patient preferences; Analytic hierarchy process (AHP); Health technology assessment (HTA); Medical decision making; Multi-criteria decision analysis (MCDA) ID DECISION-MAKING; CONJOINT-ANALYSIS; PRIORITIES; CARE AB Background: Patient involvement is widely acknowledged to be a valuable component in health technology assessment (HTA) and healthcare decision making. However, quantitative approaches to ascertain patients' preferences for treatment endpoints are not yet established. The objective of this study is to introduce the analytic hierarchy process (AHP) as a preference elicitation method in HTA. Based on a systematic literature review on the use of AHP in health care in 2009, the German Institute for Quality and Efficiency in Health Care (IQWiG) initiated an AHP study related to its HTA work in 2010. Methods: The AHP study included two AHP workshops, one with twelve patients and one with seven healthcare professionals. In these workshops, both patients and professionals rated their preferences with respect to the importance of different endpoints of antidepressant treatment by a pairwise comparison of individual endpoints. These comparisons were performed and evaluated by the AHP method and relative weights were generated for each endpoint. Results: The AHP study indicates that AHP is a well-structured technique whose cognitive demands were well handled by patients and professionals. The two groups rated some of the included endpoints of antidepressant treatment differently. For both groups, however, the same six of the eleven endpoints analyzed accounted for more than 80 percent of the total weight. Conclusions: AHP can be used in HTA to give a quantitative dimension to patients' preferences for treatment endpoints. Preference elicitation could provide important information at various stages of HTA and challenge opinions on the importance of endpoints. C1 [Hummel, J. Marjan; van Manen, Jeannette G.; IJzerman, Maarten J.] Univ Twente, Dept Hlth Technol & Serv Res, NL-7500 AE Enschede, Netherlands. [Bastian, Hilda] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Danner, M (reprint author), Inst Qual & Efficiency Hlth Care IQWiG, Hlth Econ Dept, D-51105 Cologne, Germany. EM marion.danner@iqwig.de; j.m.hummel@utwente.nl; Fabian.volz@iqwig.de; j.g.vanmanen@utwente.nl; beate.wiegard@iqwig.de; charalabos-markos@iqwig.de; Hilda.bastian@nih.gov; andreas.gerger@iqwig.de; m.j.ijzerman@utwente.nl RI IJzerman, Maarten/Q-8963-2016; OI IJzerman, Maarten/0000-0001-5788-5805; Bastian, Hilda/0000-0001-8544-7386 FU IGWIG FX The authors report that this work has been partly funded by IGWIG. NR 25 TC 35 Z9 35 U1 1 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD OCT PY 2011 VL 27 IS 4 BP 369 EP 375 DI 10.1017/S0266462311000523 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 840EH UT WOS:000296420600016 PM 22004779 ER PT J AU Woo, JM Gibbons, RD Qin, P Komarow, H Kim, JB Rogers, CA Mann, JJ Postolache, TT AF Woo, Jong-Min Gibbons, Robert D. Qin, Ping Komarow, Hirsh Kim, Jong Bae Rogers, Christine A. Mann, J. John Postolache, Teodor T. TI Suicide and Prescription Rates of Intranasal Corticosteroids and Nonsedating Antihistamines for Allergic Rhinitis: An Ecological Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; NASAL CORTICOSTEROIDS; CYTOKINE EXPRESSION; MAJOR DEPRESSION; SLEEP; BEHAVIOR; BRAIN; DISTURBANCES; NEUROBIOLOGY; INFLAMMATION AB Objective: To estimate the relationship between antiallergy drug prescription rates and suicide across the United States and over time. The relationship between allergy, allergens, and suicidal behavior and suggestions of a possible immune mediation led us to hypothesize that intranasal corticosteroids, known to reduce local airway production of T-helper cell type 2 cytokines, may be associated with reduced risk of suicide relative to antihistamines, which only secondarily affect cytokine production. Method: The authors evaluated the relationship of suicide rates at the county level in the United States (N=120,076 suicides) with prescriptions for intranasal corticosteroids and nonsedating antihistamines, in interaction with antidepressant prescriptions and other socioeconomic variables, for the period from 1999 to 2002. Suicide rate data were derived from state vital record systems based on local death certificate registries, and county-level allergy and antidepressant prescription data were obtained from IMS Health Incorporated (Plymouth Meeting, Pennsylvania). Results: The prescription volume of intranasal corticosteroids was associated with a lower suicide risk (P=.0004), while that of antihistamines was associated with a modestly greater suicide risk (P=.0001). Adjustment for antidepressant prescriptions did not affect these relationships. Conclusions:This is the first study, to our knowledge, to find a possible association between completed suicide and medications for allergic rhinitis and also the first report of an association of intranasal corticosteroid use with a lower suicide rate. This association should be considered preliminary and deserving of further investigation. C1 [Woo, Jong-Min; Postolache, Teodor T.] Univ Maryland, Sch Med, Mood & Anxiety Program, Dept Psychiat, Baltimore, MD 21201 USA. [Woo, Jong-Min] Seoul Paik Hosp, Dept Psychiat, Seoul, South Korea. [Woo, Jong-Min] Inje Univ, Sch Med, Seoul, South Korea. [Woo, Jong-Min] Inje Univ, Stress Res Inst, Seoul, South Korea. [Gibbons, Robert D.; Kim, Jong Bae] Univ Illinois, Ctr Hlth Stat, Chicago, IL USA. [Qin, Ping] Univ Aarhus, Natl Ctr Register Based Res, Aarhus, Denmark. [Komarow, Hirsh] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Rogers, Christine A.] Univ Massachusetts, Amherst, MA 01003 USA. [Mann, J. John] New York State Psychiat Inst & Hosp, Dept Mol Imaging & Neuropathol, New York, NY 10032 USA. [Mann, J. John] Columbia Univ, New York, NY USA. RP Postolache, TT (reprint author), Univ Maryland, Sch Med, Mood & Anxiety Program, Dept Psychiat, 685 W Baltimore St,MSTF Bldg,Room 930, Baltimore, MD 21201 USA. EM teopostolache@gmail.com RI Rogers, Christine/A-2189-2008 OI Rogers, Christine/0000-0003-0887-9606 FU National Institutes of Health [R01MH074891]; Inje Research and Scholarship Foundation FX Financial support was provided by the National Institutes of Health (R01MH074891; principal investigator: Dr Postolache). Dr Woo was also supported by the Inje Research and Scholarship Foundation from 2007 to 2009. NR 47 TC 10 Z9 10 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2011 VL 72 IS 10 BP 1423 EP 1428 DI 10.4088/JCP.10m06765 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 839XL UT WOS:000296402700018 PM 22075102 ER PT J AU Corsini, E Oukka, M Pieters, R Kerkvliet, NI Ponce, R Germolec, DR AF Corsini, Emanuela Oukka, Mohamed Pieters, Raymond Kerkvliet, Nancy I. Ponce, Rafael Germolec, Dori R. TI Alterations in regulatory T-cells: Rediscovered pathways in immunotoxicology SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Review DE Regulatory T-cells; immunosuppression; allergy; autoimmunity ID ARYL-HYDROCARBON RECEPTOR; MERCURY-INDUCED AUTOIMMUNITY; BROWN-NORWAY RATS; TRANSCRIPTION FACTOR; DENDRITIC CELLS; D-PENICILLAMINE; ORAL TOLERANCE; CUTTING EDGE; TGF-BETA; IN-VIVO AB In addition to the effector T-cells subsets, T-cells can also differentiate into cells that play a suppressive or regulatory role in adaptive immune responses. The cell types currently identified as regulatory T-cells (T-regs) include natural or thymic-derived T-regs, T-cells which express Foxp3(+)CD25(+)CD4(+) and can suppress immune responses to autoreactive T-cells, as well as inducible T-regs, that are generated from naive T-cells in the periphery after interaction with antigens presented by dendritic cells. Inducible T-regs include T(H)3 cells, T(r)1 cells, and Foxp3(+)-inducible T-regs. T-regs have been shown to be critical in the maintenance of immune responses and T-cell homeostasis. These cells play an important role in suppressing responses to self-antigens and in controlling inappropriate responses to non-self-antigens, such as commensal bacteria or food in the gut. For example, depletion of CD4(+)CD25(+) T-regs from mice resulted in the development of multi-organ autoimmune diseases. CD4(+)CD25(+) T-regs and/or IL-10-producing T(r)1 cells are capable of suppressing or attenuating T(H)2 responses to allergens. Moreover, adoptive transfer of CD4(+)CD25(+) T-regs from healthy to diseased animals resulted in the prevention or cure of certain autoimmune diseases, and was able to induce transplantation tolerance. Clinical improvement seen after allergen immunotherapy for allergic diseases such as rhinitis and asthma is associated with the induction of IL-10- and TGF beta-producing T(r)1 cells as well as FoxP3-expressing IL-10 T-cells, with resulting suppression of the T(H)2 cytokine milieu. Activation, expansion, or suppression of CD4(+)CD25(+) T-regs in vivo by xenobiotics, including drugs, may therefore represent a relevant mechanism underlying immunotoxicity, including immunosuppression, allergic asthma, and autoimmune diseases. C1 [Corsini, Emanuela] Univ Milan, Dept Pharmacol Sci, Toxicol Lab, I-20133 Milan, Italy. [Oukka, Mohamed] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA USA. [Pieters, Raymond] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Pieters, Raymond] Utrecht Univ Appl Sci, Res Ctr Technol & Innovat, Utrecht, Netherlands. [Kerkvliet, Nancy I.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Ponce, Rafael] Amgen Inc, Seattle, WA USA. [Germolec, Dori R.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. RP Corsini, E (reprint author), Univ Milan, Dept Pharmacol Sci, Toxicol Lab, Via Balzaretti 9, I-20133 Milan, Italy. EM emanuela.corsini@unimi.it FU Intramural NIH HHS [Z99 ES999999] NR 67 TC 11 Z9 12 U1 0 U2 9 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PD OCT-DEC PY 2011 VL 8 IS 4 BP 251 EP 257 DI 10.3109/1547691X.2011.598885 PG 7 WC Toxicology SC Toxicology GA 840SI UT WOS:000296461200001 PM 21848365 ER PT J AU Guo, TL Germolec, DR Collins, BJ Luebke, RW Auttachoat, W Smith, MJ White, KL AF Guo, Tai L. Germolec, Dori R. Collins, Bradley J. Luebke, Robert W. Auttachoat, Wimolnut Smith, Matthew J. White, Kimber L., Jr. TI Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Article DE Chloramine; monochloramine; immunotoxicity; drinking water disinfection ID CHEMICAL-INDUCED IMMUNOTOXICITY; SWIMMING POOLS; EXPOSURE; MONOCHLORAMINE; DISINFECTANT; PREVALENCE; RAT AB Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B6C3F1 mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days. No statistically significant differences in drinking water consumption, body weight, body weight gain, organ weights, or hematological parameters between the exposed and control animals were noted during the experimental period. There were no changes in the percentages and numbers of total B-lymphocytes, T-lymphocytes, CD4(+) and CD8(+) T-lymphocytes, natural killer (NK) cells, and macrophages in the spleen. Exposure to chloramine did not affect the IgM antibody-forming cell response to sheep red blood cells (SRBC) or anti-SRBC IgM antibody production. Minimal effects, judged to be biologically insignificant, were observed in the mixed-leukocyte response and NK activity. In conclusion, chloramine produced no toxicological and immunotoxic effects in female B6C3F1 mice when administered for 28 days in the drinking water at concentrations ranging from 2-200 ppm. C1 [Guo, Tai L.; Auttachoat, Wimolnut; Smith, Matthew J.; White, Kimber L., Jr.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Germolec, Dori R.; Collins, Bradley J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Luebke, Robert W.] US EPA, Cardiopulm & Immunotoxicol Branch, Environm Publ Hlth Div, NHEERL, Res Triangle Pk, NC USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. EM klwhite@vcu.edu FU EPA [DW75937992]; Division of Intramural Research at the NIEHS [ES55538]; National Institute of Environmental Health Sciences [ES55538] FX This work was supported in part by EPA Interagency Agreement DW75937992 and the Division of Intramural Research at the NIEHS through Contract ES55538. The authors thank D. L. Musgrove and R. D. Brown for their technical assistance, and Dr Michelle Hooth and Dr Marsha Ward for their comments and review of the manuscript.; Dr Kimber L. White, Jr. is the owner of a company, ImmunoTox (R), Inc., that conducts immunotoxicological studies under Good Laboratory Practices (GLP). This work was supported by the National Institute of Environmental Health Sciences [ES55538]. This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), however, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the US government. This report has been reviewed by the Environmental Protection Agency's Office of Research and Development and approved for publication. Approval does not signify that the contents necessarily reflect the views of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. NR 29 TC 0 Z9 0 U1 3 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PD OCT-DEC PY 2011 VL 8 IS 4 BP 381 EP 388 DI 10.3109/1547691X.2011.622317 PG 8 WC Toxicology SC Toxicology GA 840SI UT WOS:000296461200015 PM 22017662 ER PT J AU Wang, C Henkes, LM Doughty, LB He, M Wang, DF Meyer-Almes, FJ Cheng, YQ AF Wang, Cheng Henkes, Leonhard M. Doughty, Leah B. He, Min Wang, Difei Meyer-Almes, Franz-Josef Cheng, Yi-Qiang TI Thailandepsins: Bacterial Products with Potent Histone Deacetylase Inhibitory Activities and Broad-Spectrum Antiproliferative Activities SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID TUMOR-CELL-LINES; NATURAL-PRODUCTS; NONRIBOSOMAL PEPTIDES; ANTICANCER AGENTS; BIOSYNTHESIS; DEPSIPEPTIDE; CANCER; FK228; POLYKETIDE; MECHANISMS AB Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer drugs, with one synthetic compound, SAHA (vorinostat, Zolinza; 1), and one natural product, FK228 (depsipeptide, romidepsin, Istodax; 2), approved by FDA for clinical use. Our studies of FK228 biosynthesis in Chromobacterium violaceum no. 968 led to the identification of a cryptic biosynthetic gene cluster in the genome of Burkholderia thailandensis E264. Genome mining and genetic manipulation of this gene cluster further led to the discovery of two new products, thailandepsin A (6) and thailandepsin B (7). HDAC inhibition assays showed that thailandepsins have selective inhibition profiles different from that of FK228, with comparable inhibitory activities to those of FK228 toward human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC9 but weaker inhibitory activities than FK228 toward HDAC4 and HDAC8, the latter of which could be beneficial. NCI-60 anticancer screening assays showed that thailandepsins possess broad-spectrum antiproliferative activities with GI(50) for over 90% of the tested cell lines at low nanomolar concentrations and potent cytotoxic activities toward certain types of cell lines, particularly for those derived from colon, melanoma, ovarian, and renal cancers. Thailandepsins thus represent new naturally produced HDAC inhibitors that are promising for anticancer drug development. C1 [Wang, Cheng; Doughty, Leah B.; Cheng, Yi-Qiang] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53201 USA. [Henkes, Leonhard M.; Meyer-Almes, Franz-Josef] Univ Appl Sci Darmstadt, Dept Chem Engn & Biotechnol, D-64287 Darmstadt, Germany. [He, Min] US Natl Canc Inst, Dev Therapeut Program, Frederick, MD 21701 USA. [Wang, Difei] US Natl Canc Inst, Cell Biol Lab, Bethesda, MD 20892 USA. [Cheng, Yi-Qiang] Wuhan Univ, Sch Pharmaceut Sci, MoE Key Lab Combinatorial Biosynth & Drug Dis, Wuhan 430071, Peoples R China. RP Cheng, YQ (reprint author), Univ Wisconsin, Dept Biol Sci, POB 413, Milwaukee, WI 53201 USA. EM ycheng@uwm.edu RI Wang, Difei/E-7066-2010 FU Research Growth Initiative from University of Wisconsin-Milwaukee; NIH/NCI [R01 CA152212]; NIH/NCI of the Center for Cancer Research FX We thank D. DeShazer (Walter Reed Army Medical Center) and H. Schweizer (Colorado State University) for providing vector tools, K. Nithipatikom (Medical College of Wisconsin) for assistance with HR-MS analysis, H. Foersterling (University of Wisconsin-Milwaukee) for assistance with NMR analysis, the NCI Developmental Therapeutics Program for conducting NCI-60 anticancer screening, M. Kunkel (NCI-DTP) for assistance with the COMPARE analysis of NCI-60 data, and D. Newman (NCI-DTP) for critical reading of this manuscript. This work was supported by a Research Growth Initiative Award from the University of Wisconsin-Milwaukee and an NIH/NCI grant R01 CA152212 (both to Y.-Q.C). D.W. also acknowledges the NIH/NCI Intramural Research Program of the Center for Cancer Research for a fellowship support. NR 49 TC 43 Z9 44 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 2011 VL 74 IS 10 BP 2031 EP 2038 DI 10.1021/np200324x PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 837LZ UT WOS:000296206500001 PM 21793558 ER PT J AU Klausmeyer, P Shipley, SM Zuck, KM McCloud, TG AF Klausmeyer, Paul Shipley, Suzanne M. Zuck, Karina M. McCloud, Thomas G. TI Histone Deacetylase Inhibitors from Burkholderia thailandensis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CYSTEINE RESIDUES; DEPSIPEPTIDE; FR901228; GROWTH; CANCER; FK228; PEPTIDES; CELLS AB Bioactivity-guided fractionation of an extract of Burkholderia thailandensis led to the isolation and identification of a new cytotoxic depsipeptide and its dimer. Both compounds potently inhibited the function of histone deacetylases 1 and 4. The monomer, spiruchostatin C (2), was tested side by side with the clinical depsipeptide FK228 (1, Istodax, romidepsin) in a murine hollow fiber assay consisting of 12 implanted tumor cell lines. Spiruchostatin C (2) showed good activity toward LOX IMVI melanoma cells and NCI-H522 non small cell lung cancer cells. Overall, however, FK228 (1) showed a superior in vivo antitumor profile in comparison to the new compound. C1 [Klausmeyer, Paul; Shipley, Suzanne M.; Zuck, Karina M.; McCloud, Thomas G.] NCI Frederick, Nat Prod Support Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Klausmeyer, P (reprint author), NCI Frederick, Nat Prod Support Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. EM klausmeyerp@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. This research was supported (in part) by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. We gratefully acknowledge Q Van for NMR experiments, the NCI 60 team for in vitro biological assay results, M. Hollingshead, M. Ahalt-Gottholm, and V. Brinsfield for the murine hollow fiber assay results, and J. Britt for robotics and computer support. NR 20 TC 13 Z9 13 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 2011 VL 74 IS 10 BP 2039 EP 2044 DI 10.1021/np200532d PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 837LZ UT WOS:000296206500002 PM 21967146 ER PT J AU Garg, PK Liu, K Ferrucci, L Guralnik, JM Criqui, MH Tian, L Sufit, R Nishida, T Tao, HM Liao, YH McDermott, MM AF Garg, Parveen K. Liu, Kiang Ferrucci, Luigi Guralnik, Jack M. Criqui, Michael H. Tian, Lu Sufit, Robert Nishida, Takashi Tao, Huimin Liao, Yihua McDermott, Mary M. TI Lower Extremity Nerve Function, Calf Skeletal Muscle Characteristics, and Functional Performance in Peripheral Arterial Disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE claudication; muscles; peripheral nervous system; peripheral vascular disease; physical functioning ID ANKLE BRACHIAL INDEX; PHYSICAL-ACTIVITY; WOMENS HEALTH; 6-MINUTE WALK; LEG SYMPTOMS; CLASSIFICATION; OSTEOARTHRITIS; ASSOCIATIONS; PREVALENCE; DISABILITY AB OBJECTIVES: To determine whether poor lower extremity nerve function is associated with less-favorable calf muscle characteristics and greater functional impairment in people with and without peripheral arterial disease (PAD). DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: Four hundred thirteen participants with PAD (ankle-brachial index (ABI) < 0.90) and 255 without. MEASUREMENTS: Electrodiagnostic testing of the peroneal nerve was performed. Calf muscle cross-sectional area and percentage fat were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Six-minute walk performance was measured. RESULTS: Adjusting for age, sex, race, ABI, leg symptoms, smoking, physical activity, comorbidities, and other covariates, lower peroneal nerve conduction velocity (NCV) was associated with lower calf muscle area (first quartile 4,770.3 mm(2), fourth quartile 5,571 mm(2), P < .001) and poorer 6-minute walk distance (first quartile 989.2 feet, fourth quartile 1,210.8 feet, P < .001) in participants without diabetes mellitus with PAD. Lower peroneal NCV was associated with lower calf muscle area (first quartile 5,166.0 mm(2), fourth quartile 6,003.8 mm(2), P = .01) and poorer 6-minute walk distance (first quartile 866.4 feet, fourth quartile 1,082.5 feet, P = .01) in participants with diabetes mellitus and PAD as well. In participants without PAD, lower peroneal NCV was not associated with lower calf muscle area but was associated with poorer 6-minute walk distance only in participants without diabetes mellitus (first quartile 1,317.0 feet, fourth quartile 1,570.4 feet, P-trend < .001). CONCLUSION: Lower peroneal nerve function is associated with smaller calf muscle area and greater functional impairment in individuals with PAD. Future study is needed to determine whether improving peroneal NCV prevents loss of calf muscle and functional decline in people with PAD. J Am Geriatr Soc 59:1855-1863, 2011. C1 [Garg, Parveen K.; McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Liu, Kiang; Tao, Huimin; Liao, Yihua; McDermott, Mary M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Sufit, Robert; Nishida, Takashi] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. [Ferrucci, Luigi] NIA, Lab Clin Epidemiol, Bethesda, MD 20892 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Tian, Lu] Stanford Univ, Palo Alto, CA 94304 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU National Heart Lung and Blood Institute [K12-HL083790, R01-HL58099, R01-HL64739, R01-HL71223, R01-HL076298]; National Center for Research Resources, National Institutes of Health [RR-00048] FX Conflict of Interest: This study was supported by grants K12-HL083790, R01-HL58099, R01-HL64739, and R01-HL71223, and R01-HL076298 from the National Heart Lung and Blood Institute and grant RR-00048 from the National Center for Research Resources, National Institutes of Health. NR 28 TC 8 Z9 8 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2011 VL 59 IS 10 BP 1855 EP 1863 DI 10.1111/j.1532-5415.2011.03600.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 840OE UT WOS:000296449300010 PM 22091499 ER PT J AU Hohman, TJ Beason-Held, LL Resnick, SM AF Hohman, Timothy J. Beason-Held, Lori L. Resnick, Susan M. TI Cognitive Complaints, Depressive Symptoms, and Cognitive Impairment: Are They Related? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive complaints; depression; aging ID SUBJECTIVE MEMORY COMPLAINTS; OLDER-PEOPLE; ALZHEIMERS-DISEASE; DEMENTIA; RISK; POPULATION; FAILURES; DECLINE; ADULTS AB OBJECTIVES: To examine whether concurrent depressive symptoms and self-and informant-reported cognitive impairments are related to cognitive complaints. DESIGN: Longitudinal aging study of the relationship between depressive symptoms, reported cognitive impairments, and cognitive complaints. Mixed-effects regression models were used to determine whether scores on the Center for Epidemiologic Studies Depression Scale (CES-D) and Clinical Dementia Rating Scale (CDR) predicted cognitive complaints. The Cognitive Failures Questionnaire (CFQ) assessed cognitive complaints. SETTING: A community-dwelling sample in Baltimore, Maryland. PARTICIPANTS: One hundred five cognitively normal older individuals with a mean baseline age of 75 followed for an average of 4 years. MEASUREMENTS: The CES-D measured depressive symptoms. The CDR Sum of Boxes (CDR-SB) measured self-and informant-reported impairment, and the CFQ measured cognitive complaints. RESULTS: Greater depressive symptoms and reported impairments are associated with higher CFQ scores. In addition, there was a significant interaction between depressive symptoms and reported impairment. Specifically, individuals without reported cognitive impairment had the strongest association between depressive symptoms and cognitive complaints. Finally, reported impairments interact with baseline age, suggesting that the relationship between reported impairments and cognitive complaints is strongest in individuals younger than 80. CONCLUSION: These findings confirm a relationship between reported cognitive impairment and cognitive complaints in older individuals and highlight the extent to which age and depressive symptoms account for variation in complaints. These factors should be considered when interpreting cognitive complaints in a clinical setting. J Am Geriatr Soc 59:1908-1912, 2011. C1 [Hohman, Timothy J.] American Univ, Dept Psychol, Washington, DC 20016 USA. [Hohman, Timothy J.; Beason-Held, Lori L.; Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. RP Hohman, TJ (reprint author), American Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM timothyjhohman@gmail.com OI Hohman, Timothy/0000-0002-3377-7014 FU National Institutes of Health, NIA; [N01-AG-3-2124] FX Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. This research was supported in part by the Intramural Research Program of the National Institutes of Health, NIA and by Research and Development Contract N01-AG-3-2124. NR 30 TC 12 Z9 12 U1 0 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2011 VL 59 IS 10 BP 1908 EP 1912 DI 10.1111/j.1532-5415.2011.03589.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 840OE UT WOS:000296449300016 PM 22091504 ER PT J AU Clarke, JL Ennis, MM Yung, WKA Chang, SM Wen, PY Cloughesy, TF DeAngelis, LM Robins, HI Lieberman, FS Fine, HA Abrey, L Gilbert, MR Mehta, M Kuhn, JG Aldape, KD Lamborn, KR Prados, MD AF Clarke, Jennifer L. Ennis, Michele M. Yung, W. K. Alfred Chang, Susan M. Wen, Patrick Y. Cloughesy, Timothy F. DeAngelis, Lisa M. Robins, H. Ian Lieberman, Frank S. Fine, Howard A. Abrey, Lauren Gilbert, Mark R. Mehta, Minesh Kuhn, John G. Aldape, Kenneth D. Lamborn, Kathleen R. Prados, Michael D. CA N Amer Brain Tumor Consortium TI Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; PFS6; prognosis; recurrence; surgery ID II CLINICAL-TRIALS; PHASE-II; GLIOMA; THERAPY AB Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998-2005, 105 of whom had surgery (excluding biopsies) during the study or <= 30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005-2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. C1 [Clarke, Jennifer L.; Chang, Susan M.; Lamborn, Kathleen R.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Yung, W. K. Alfred; Gilbert, Mark R.; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeAngelis, Lisa M.; Abrey, Lauren] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Robins, H. Ian] Univ Wisconsin Hosp, Madison, WI USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr Canc Pavil, Div Neurooncol, Pittsburgh, PA USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Mehta, Minesh] Northwestern Univ, Dept Radiat Oncol, Chicago, IL 60611 USA. RP Clarke, JL (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,A-808, San Francisco, CA 94143 USA. EM clarkej@neurosurg.ucsf.edu RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU North American Brain Tumor Consortium [CA62399] FX This work was supported by the North American Brain Tumor Consortium [CA62399]. NR 5 TC 30 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2011 VL 13 IS 10 BP 1118 EP 1124 DI 10.1093/neuonc/nor110 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 835YB UT WOS:000296071900007 PM 21813511 ER PT J AU Kreisl, TN Zhang, WT Odia, Y Shih, JH Butman, JA Hammoud, D Iwamoto, FM Sul, J Fine, HA AF Kreisl, Teri N. Zhang, Weiting Odia, Yazmin Shih, Joanna H. Butman, John A. Hammoud, Dima Iwamoto, Fabio M. Sul, Joohee Fine, Howard A. TI A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma SO NEURO-ONCOLOGY LA English DT Article DE anaplastic glioma; bevacizumab; FDG; perfusion MRI ID HIGH-GRADE GLIOMAS; MALIGNANT BRAIN-TUMORS; PLUS IRINOTECAN; GLIOBLASTOMA; SURVIVAL; CRITERIA; THERAPY; PROGRESSION AB The purpose of this study was to evaluate the activity of single-agent bevacizumab in patients with recurrent anaplastic glioma and assess correlative advanced imaging parameters. Patients with recurrent anaplastic glioma were treated with bevacizumab 10 mg/kg every 2 weeks. Complete patient evaluations were repeated every 4 weeks. Correlative dynamic contrast-enhanced MR and (18)fluorodeoxyglucose PET imaging studies were obtained to evaluate physiologic changes in tumor and tumor vasculature at time points including baseline, 96 h after the first dose, and after the first 4 weeks of therapy. Median overall survival was 12 months (95% confidence interval [CI]: 6.08-22.8). Median progression-free survival was 2.93 months (95% CI: 2.01-4.93), and 6-month progression-free survival was 20.9% (95% CI: 10.3%-42.5%). Thirteen (43%) patients achieved a partial response. The most common grade >= 3 treatment-related toxicities were hypertension, hypophosphatemia, and thromboembolism. Single-agent bevacizumab produces significant radiographic response in patients with recurrent anaplastic glioma but did not meet the 6-month progression-free survival endpoint. Early change in enhancing tumor volume at 4 days after start of therapy was the most significant prognostic factor for overall and progression-free survival. C1 [Kreisl, Teri N.; Zhang, Weiting; Odia, Yazmin; Iwamoto, Fabio M.; Sul, Joohee; Fine, Howard A.] NCI, Neurooncol Branch, Ctr Canc Res, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Rockville, MD USA. [Butman, John A.; Hammoud, Dima] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Kreisl, TN (reprint author), NCI, Neurooncol Branch, Ctr Canc Res, Natl Inst Neurol Disorders & Stroke, 9030 Old Georgetown Rd,Rm 225, Bethesda, MD 20892 USA. EM kreislt@mail.nih.gov RI Hammoud, Dima/C-2286-2015; Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU National Cancer Institute FX National Cancer Institute Intramural Research Program. NR 21 TC 48 Z9 53 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2011 VL 13 IS 10 BP 1143 EP 1150 DI 10.1093/neuonc/nor091 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 835YB UT WOS:000296071900010 PM 21865400 ER PT J AU Dietz, J Bradley, MM Okun, MS Bowers, D AF Dietz, J. Bradley, M. M. Okun, M. S. Bowers, D. TI Emotion and ocular responses in Parkinson's disease SO NEUROPSYCHOLOGIA LA English DT Article DE Emotion; Arousal; Parkinson's disease; Pupil; Eye movement ID PUPILLARY LIGHT REFLEX; BASAL GANGLIA; DOPAMINERGIC MODULATION; CLINICAL-DIAGNOSIS; APATHY; AMYGDALA; RECOGNITION; PATHOLOGY; VOLUNTEERS; INSTRUMENT AB Parkinson's disease (PD) is a neurodegenerative disease that affects motor, cognitive, and emotional functioning. Previous studies reported reduced skin conductance responses in PD patients, compared to healthy older adults when viewing emotionally arousing pictures. Attenuated skin conductance changes in PD may reflect peripheral autonomic dysfunction (e.g., reduced nerve endings at the sweat gland) or, alternatively, a more central emotional deficit. The aim of the current study was to investigate a second measure of sympathetic arousal-change in pupil dilation. Eye movements, a motor-based correlate of emotional processing, were also assessed. Results indicated that pupil dilation was significantly greater when viewing emotional, compared to neutral pictures for both PD patients and controls. On the other hand, PD patients made fewer fixations with shorter scan paths, particularly when viewing pleasant pictures. These results suggest that PD patients show normal sympathetic arousal to affective stimuli (indexed by pupil diameter), but differences in motor correlates of emotion (eye movements). (C) 2011 Elsevier Ltd. All rights reserved. C1 [Dietz, J.; Bowers, D.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32610 USA. [Dietz, J.; Bradley, M. M.] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL 32610 USA. [Okun, M. S.] Univ Florida, Ctr Movement Disorders & Neurorestorat, Dept Neurol, Gainesville, FL 32610 USA. [Okun, M. S.] Univ Florida, Ctr Movement Disorders & Neurorestorat, Dept Neurosurg, Gainesville, FL 32610 USA. RP Dietz, J (reprint author), Univ Florida, Dept Clin & Hlth Psychol, POB 100165, Gainesville, FL 32610 USA. EM jdietz@phhp.ufl.edu OI Okun, Michael/0000-0002-6247-9358 FU National Institute of Mental Health [P50 MH72850]; Center for the Study of Emotion and Attention (CSEA) at the University of Florida; National Institute of Neurological Disorders and Stroke [RO1-NS05063, K23-NS044997]; UF National Parkinson Foundation Center of Excellence FX This project was completed as part of a master's thesis (J. Dietz) at the University of Florida. The research was supported in part by a grant from the National Institute of Mental Health (P50 MH72850) to PJ Lang & MM Bradley at the Center for the Study of Emotion and Attention (CSEA) at the University of Florida. Support was also provided by the National Institute of Neurological Disorders and Stroke (RO1-NS05063 to D. Bowers, K23-NS044997 to M.S. Okun) and the UF National Parkinson Foundation Center of Excellence. NR 54 TC 13 Z9 13 U1 2 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD OCT PY 2011 VL 49 IS 12 BP 3247 EP 3253 DI 10.1016/j.neuropsychologia.2011.07.029 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 839WP UT WOS:000296400500009 PM 21839756 ER PT J AU Pitcher, D Duchaine, B Walsh, V Yovel, G Kanwisher, N AF Pitcher, David Duchaine, Bradley Walsh, Vincent Yovel, Galit Kanwisher, Nancy TI The role of lateral occipital face and object areas in the face inversion effect SO NEUROPSYCHOLOGIA LA English DT Article DE Face perception; Object recognition; Transcranial magnetic stimulation; Occipital face area; Lateral occipital area ID HUMAN OCCIPITOTEMPORAL CORTEX; SURFACE-BASED ANALYSIS; EXTRASTRIATE CORTEX; FACIAL IDENTITY; PERCEPTION; RECOGNITION; PROSOPAGNOSIA; DISSOCIATION; DISRUPTS; FEATURES AB Stimulus inversion impairs face discrimination to a greater extent than discrimination of other non-face object categories. This finding has led to suggestions that upright faces are represented by mechanisms specialized for upright faces whereas inverted face representation depends on more general object recognition mechanisms. In the present study we tested the causal role of face-selective and object-selective cortical areas for upright and inverted face discrimination by transiently disrupting neural processing using transcranial magnetic stimulation (TMS). Participants matched upright and inverted faces while TMS was delivered over each participant's functionally localized right occipital face area (rOFA) or right lateral occipital area (rLO). TMS delivered over rOFA disrupted the discrimination of upright and inverted faces while TMS delivered over rLO impaired inverted face discrimination only. These results provide causal evidence that upright faces are represented by face-specific mechanisms whereas inverted faces are represented by both face-specific and object-specific mechanisms. The similar sensitivity of the OFA to upright and inverted faces is consistent with the hypothesis that the OFA processes facial features at an early stage of face processing. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Pitcher, David; Kanwisher, Nancy] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Pitcher, David; Walsh, Vincent] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Duchaine, Bradley] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA. [Yovel, Galit] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. RP Pitcher, D (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM pitcherdj@mail.nih.gov FU BBSRC [BB/F022875/1]; [EY13455] FX Thanks to Tanya Goldhaber. This work was partially supported by BBSRC grant BB/F022875/1 to BD & VW and by EY13455 to NK. NR 44 TC 22 Z9 22 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD OCT PY 2011 VL 49 IS 12 BP 3448 EP 3453 DI 10.1016/j.neuropsychologia.2011.08.020 PG 6 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 839WP UT WOS:000296400500032 PM 21896279 ER PT J AU Singh, CR Watanabe, R Zhou, DH Jennings, MD Fukao, A Lee, B Ikeda, Y Chiorini, JA Campbell, SG Ashe, MP Fujiwara, T Wek, RC Pavitt, GD Asano, K AF Singh, Chingakham Ranjit Watanabe, Ryosuke Zhou, Donghui Jennings, Martin D. Fukao, Akira Lee, Bumjun Ikeda, Yuka Chiorini, John A. Campbell, Susan G. Ashe, Mark P. Fujiwara, Toshinobu Wek, Ronald C. Pavitt, Graham D. Asano, Katsura TI Mechanisms of translational regulation by a human eIF5-mimic protein SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; IN-VIVO; SACCHAROMYCES-CEREVISIAE; P-BODIES; INITIATION; EIF2; COMPLEX; DOMAIN; PHOSPHORYLATION; COMMON AB The translation factor eIF5 is an important partner of eIF2, directly modulating its function in several critical steps. First, eIF5 binds eIF2/GTP/Met-tRNA(i)(Met) ternary complex (TC), promoting its recruitment to 40S ribosomal subunits. Secondly, its GTPase activating function promotes eIF2 dissociation for ribosomal subunit joining. Finally, eIF5 GDP dissociation inhibition (GDI) activity can antagonize eIF2 reactivation by competing with the eIF2 guanine exchange factor (GEF), eIF2B. The C-terminal domain (CTD) of eIF5, a W2-type HEAT domain, mediates its interaction with eIF2. Here, we characterize a related human protein containing MA3- and W2-type HEAT domains, previously termed BZW2 and renamed here as eIF5-mimic protein 1 (5MP1). Human 5MP1 interacts with eIF2 and eIF3 and inhibits general and gene-specific translation in mammalian systems. We further test whether 5MP1 is a mimic or competitor of the GEF catalytic subunit eIF2B epsilon or eIF5, using yeast as a model. Our results suggest that 5MP1 interacts with yeast eIF2 and promotes TC formation, but inhibits TC binding to the ribosome. Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function. C1 [Singh, Chingakham Ranjit; Watanabe, Ryosuke; Lee, Bumjun; Ikeda, Yuka; Asano, Katsura] Kansas State Univ, Div Biol, Mol Cellular & Dev Biol Program, Manhattan, KS 66506 USA. [Zhou, Donghui; Wek, Ronald C.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Jennings, Martin D.; Campbell, Susan G.; Ashe, Mark P.; Pavitt, Graham D.] Univ Manchester, Fac Life Sci, Manchester M31 9PT, Lancs, England. [Fukao, Akira; Fujiwara, Toshinobu] Kobe Univ, Grad Sch Engn, Dept Chem Sci & Engn, Kobe, Hyogo 6578501, Japan. [Chiorini, John A.] NIDCR, NIH, Bethesda, MD 20892 USA. RP Asano, K (reprint author), Kansas State Univ, Div Biol, Mol Cellular & Dev Biol Program, Ackert Hall, Manhattan, KS 66506 USA. EM kasano@ksu.edu RI Jennings, martin/E-5240-2010; Pavitt, Graham/A-1363-2010 OI Pavitt, Graham/0000-0002-8593-2418 FU National Institutes of Health [GM64781]; NCRR [P20 RR016475]; K-state Terry Johnson Cancer Center; NIDCR; BBSRC [BB/E002005/1, BB/H010599/1]; [GM49164] FX National Institutes of Health GM64781, NCRR K-INBRE Pilot Grant P20 RR016475; K-state Terry Johnson Cancer Center (to K. A.); NIDCR intramural grant (to J.A.C.); GM49164 (to R.C.W.); BBSRC grants BB/E002005/1 and BB/H010599/1 (to G.D.P.); and short-term fellowship for his sabbatical to Manchester, UK in Feb-Mar, 2008 (to K. A.). Funding for open access charge: K-state Terry Johnson Cancer Center. NR 41 TC 9 Z9 11 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 19 BP 8314 EP 8328 DI 10.1093/nar/gkr339 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 839CB UT WOS:000296341100012 PM 21745818 ER PT J AU Kodama, S Hosseinpour, F Goldstein, JA Negishi, M AF Kodama, Susumu Hosseinpour, Fardin Goldstein, Joyce A. Negishi, Masahiko TI Liganded pregnane X receptor represses the human sulfotransferase SULT1E1 promoter through disrupting its chromatin structure SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESTROGEN SULFOTRANSFERASE; BREAST-CANCER; CROSS-TALK; ANDROSTANE-RECEPTOR; GENE-EXPRESSION; ENHANCER MODULE; CYP2B6 GENE; CAR; ACTIVATION; LIVER AB Pregnane X receptor (PXR), acting as a xenobiotic-activated transcription factor, regulates the hepatic metabolism of therapeutics as well as endobiotics such as steroid hormones. Given our finding that PXR activation by rifampicin (RIF) represses the estrogen sulfotransferase (SULT1E1) gene in human primary hepatocytes and hepatocellular carcinoma Huh7 cells, here we have investigated the molecular mechanism of this repression. First the PXR-responsive enhancer was delineated to a 100 bp sequence (-1000/-901), which contains three half sites that constitute the overlapping direct repeat 1 (DR1) and direct repeat 2 (DR2) motifs and two forkhead factor binding sites. siRNA knockdown, chromatin immunoprecipitation and chromatin conformation capture assays were employed to demonstrate that hepatocyte nuclear factor 4 alpha (HNF4 alpha) bound to the PXR-responsive enhancer, and activated the enhancer by looping its position close to the proximal promoter. Upon activation by RIF, PXR indirectly interacted with the enhancer, decreasing the interaction with HNF4 alpha and dissolving the looped SULT1E1 promoter with deacetylation of histone 3. Removal of the DR sites from the enhancer hampers the ability of HNF4 alpha to loop the promoter and that of PXR to repress the promoter activity. Thus, PXR represses human SULT1E1, possibly attenuating the inactivation of estrogen. C1 [Kodama, Susumu; Hosseinpour, Fardin; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Goldstein, Joyce A.] NIEHS, Human Metab Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012 FU National Institutes of Health; National Institute of Environmental Health Sciences [Z01ES1005-01] FX Intramutal Research Program of the National Institutes of Health and National Institute of Environmental Health Sciences: Z01ES1005-01. Funding for open access charge: NIH. NR 30 TC 16 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 19 BP 8392 EP 8403 DI 10.1093/nar/gkr458 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 839CB UT WOS:000296341100018 PM 21764778 ER PT J AU Yu, TX Wang, PY Rao, JN Zou, TT Liu, L Xiao, L Gorospe, M Wang, JY AF Yu, Ting-Xi Wang, Peng-Yuan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Xiao, Lan Gorospe, Myriam Wang, Jian-Ying TI Chk2-dependent HuR phosphorylation regulates occludin mRNA translation and epithelial barrier function SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BINDING PROTEIN HUR; POSTTRANSCRIPTIONAL GENE-REGULATION; TIGHT JUNCTION PROTEIN; POLYAMINE DEPLETION; IN-VIVO; STABILIZATION; CELLS; STABILITY; EXPRESSION; STRESS AB Occludin is a transmembrane tight junction (TJ) protein that plays an important role in TJ assembly and regulation of the epithelial barrier function, but the mechanisms underlying its post-transcriptional regulation are unknown. The RNA-binding protein HuR modulates the stability and translation of many target mRNAs. Here, we investigated the role of HuR in the regulation of occludin expression and therefore in the intestinal epithelial barrier function. HuR bound the 3'-untranslated region of the occludin mRNA and enhanced occludin translation. HuR association with the occludin mRNA depended on Chk2-dependent HuR phosphorylation. Reduced HuR phosphorylation by Chk2 silencing or by reduction of Chk2 through polyamine depletion decreased HuR-binding to the occludin mRNA and repressed occludin translation, whereas Chk2 overexpression enhanced (HuR/occludin mRNA) association and stimulated occludin expression. In mice exposed to septic stress induced by cecal ligation and puncture, Chk2 levels in the intestinal mucosa decreased, associated with an inhibition of occludin expression and gut barrier dysfunction. These results indicate that HuR regulates occludin mRNA translation through Chk2-dependent HuR phosphorylation and that this influence is crucial for maintenance of the epithelial barrier integrity in the intestinal tract. C1 [Yu, Ting-Xi; Wang, Peng-Yuan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Xiao, Lan; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA. [Yu, Ting-Xi; Wang, Peng-Yuan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Xiao, Lan; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Gorospe, Myriam] Natl Inst Aging IRP, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore St, Baltimore, MD 21201 USA. EM jwang@smail.umaryland.edu FU US Department of Veterans Affairs; National Institutes of Health [DK57819, DK61972, DK68491]; National Institute on Aging, National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX Merit Review Grants to J.-Y.W. and J.N.R.) from US Department of Veterans Affairs and by National Institutes of Health DK57819, DK61972, DK68491 to J.-Y.W.). National Institute on Aging-Intramural Research Program, National Institutes of Health to M.G.). Funding for open access charge: National Institute of Diabetes and Digestive and Kidney Diseases. NR 64 TC 25 Z9 25 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 19 BP 8472 EP 8487 DI 10.1093/nar/gkr567 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 839CB UT WOS:000296341100024 PM 21745814 ER PT J AU He, SS Hickman, AB Dyda, F Johnson, NP Chandler, M Ton-Hoang, B AF He, Susu Hickman, Alison B. Dyda, Fred Johnson, Neil P. Chandler, Michael Ton-Hoang, Bao TI Reconstitution of a functional IS608 single-strand transpososome: role of non-canonical base pairing SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA TRANSPOSASES; TRANSPOSITION; INSERTION; RECOGNITION; INTERMEDIATE; REPLICATION; INTEGRATION; MECHANISM; CATALYSIS; COMPLEX AB Single-stranded (ss) transposition, a recently identified mechanism adopted by members of the widespread IS200/IS605 family of insertion sequences (IS), is catalysed by the transposase, TnpA. The transposase of IS608, recognizes subterminal imperfect palindromes (IP) at both IS ends and cleaves at sites located at some distance. The cleavage sites, C, are not recognized directly by the protein but by short sequences 5' to the foot of each IP, guide (G) sequences, using a network of canonical ('Watson-Crick') base interactions. In addition a set of non-canonical base interactions similar to those found in RNA structures are also involved. We have reconstituted a biologically relevant complex, the transpososome, including both left and right ends and TnpA, which catalyses excision of a ss DNA circle intermediate. We provide a detailed picture of the way in which the IS608 transpososome is assembled and demonstrate that both C and G sequences are essential for forming a robust transpososome detectable by EMSA. We also address several questions central to the organization and function of the ss transpososome and demonstrate the essential role of non-canonical base interactions in the IS608 ends for its stability by using point mutations which destroy individual non-canonical base interactions. C1 [He, Susu; Chandler, Michael; Ton-Hoang, Bao] CNRS, Lab Microbiol & Genet Mol, UMR 5100, F-31062 Toulouse, France. [Hickman, Alison B.; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Johnson, Neil P.] CNRS, Inst Pharmacol & Biol Struct, UMR 5089, F-31077 Toulouse, France. RP Chandler, M (reprint author), CNRS, Lab Microbiol & Genet Mol, UMR 5100, 118 Rte Narbonne, F-31062 Toulouse, France. EM mike@ibcg.biotoul.fr; tonhoang@ibcg.biotoul.fr OI Chandler, Michael/0000-0002-0292-6662 FU Centre National de la Recherche Scientifique (France), by Agence National de Recherche (France); National Institute of Diabetes and Digestive and Kidney Diseases; Agence National de Recherche (France) FX Centre National de la Recherche Scientifique (France), by Agence National de Recherche (France) grant Mobigen (M.C. and N.P.J.); the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases (F.D.). Funding for open access charge: Agence National de Recherche (France) (Grant MOBIGEN to M.C. and N.P.J.). NR 27 TC 12 Z9 12 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 19 BP 8503 EP 8512 DI 10.1093/nar/gkr566 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 839CB UT WOS:000296341100026 PM 21745812 ER PT J AU Abdelmohsen, K Tominaga, K Lee, EK Srikantan, S Kang, MJ Kim, MM Selimyan, R Martindale, JL Yang, XL Carrier, F Zhan, M Becker, KG Gorospe, M AF Abdelmohsen, Kotb Tominaga, Kumiko Lee, Eun Kyung Srikantan, Subramanya Kang, Min-Ju Kim, Mihee M. Selimyan, Roza Martindale, Jennifer L. Yang, Xiaoling Carrier, France Zhan, Ming Becker, Kevin G. Gorospe, Myriam TI Enhanced translation by Nucleolin via G-rich elements in coding and non-coding regions of target mRNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POSTTRANSCRIPTIONAL GENE-REGULATION; SURFACE-EXPRESSED NUCLEOLIN; INHIBITS HIV-INFECTION; PRE-RIBOSOMAL-RNA; BINDING-PROTEIN; CELL-PROLIFERATION; GENOTOXIC STRESS; SIGNATURE MOTIF; HEAT-SHOCK; IN-VIVO AB RNA-binding proteins (RBPs) regulate gene expression at many post-transcriptional levels, including mRNA stability and translation. The RBP nucleolin, with four RNA-recognition motifs, has been implicated in cell proliferation, carcinogenesis and viral infection. However, the subset of nucleolin target mRNAs and the influence of nucleolin on their expression had not been studied at a transcriptome-wide level. Here, we globally identified nucleolin target transcripts, many of which encoded cell growth- and cancer-related proteins, and used them to find a signature motif on nucleolin target mRNAs. Surprisingly, this motif was very rich in G residues and was not only found in the 3'-untranslated region (UTR), but also in the coding region (CR) and 5'-UTR. Nucleolin enhanced the translation of mRNAs bearing the G-rich motif, since silencing nucleolin did not change target mRNA stability, but decreased the size of polysomes forming on target transcripts and lowered the abundance of the encoded proteins. In summary, nucleolin binds G-rich sequences in the CR and UTRs of target mRNAs, many of which encode cancer proteins, and enhances their translation. C1 [Abdelmohsen, Kotb; Tominaga, Kumiko; Lee, Eun Kyung; Srikantan, Subramanya; Kang, Min-Ju; Kim, Mihee M.; Selimyan, Roza; Martindale, Jennifer L.; Yang, Xiaoling; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Carrier, France] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Zhan, Ming; Becker, Kevin G.] NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810; Becker, Kevin/0000-0002-6794-6656 FU National Institute on Aging of the National Institutes of Health; NIH [RO1 1CA116491-01] FX National Institute on Aging-Intramural Research Program of the National Institutes of Health; NIH (RO1 1CA116491-01 to F.C.). Funding for open access charge: National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 71 TC 40 Z9 40 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 19 BP 8513 EP 8530 DI 10.1093/nar/gkr488 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 839CB UT WOS:000296341100027 PM 21737422 ER PT J AU Huang, WC Umbach, DM Jordan, NV Abell, AN Johnson, GL Li, LP AF Huang, Weichun Umbach, David M. Jordan, Nicole Vincent Abell, Amy N. Johnson, Gary L. Li, Leping TI Efficiently identifying genome-wide changes with next-generation sequencing data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CHIP-SEQ DATA; DIFFERENTIAL EXPRESSION ANALYSIS; FACTOR-BINDING SITES; RNA-SEQ; TRANSCRIPTOMES; IDENTIFICATION; PACKAGE; MODEL; CELL; TOOL AB We propose a new and effective statistical framework for identifying genome-wide differential changes in epigenetic marks with ChIP-seq data or gene expression with mRNA-seq data, and we develop a new software tool EpiCenter that can efficiently perform data analysis. The key features of our framework are: (i) providing multiple normalization methods to achieve appropriate normalization under different scenarios, (ii) using a sequence of three statistical tests to eliminate background regions and to account for different sources of variation and (iii) allowing adjustment for multiple testing to control false discovery rate (FDR) or family-wise type I error. Our software EpiCenter can perform multiple analytic tasks including: (i) identifying genome-wide epigenetic changes or differentially expressed genes, (ii) finding transcription factor binding sites and (iii) converting multiple-sample sequencing data into a single read-count data matrix. By simulation, we show that our framework achieves a low FDR consistently over a broad range of read coverage and biological variation. Through two real examples, we demonstrate the effectiveness of our framework and the usages of our tool. In particular, we show that our novel and robust 'parsimony' normalization method is superior to the widely-used 'tagRatio' method. Our software EpiCenter is freely available to the public. C1 [Huang, Weichun; Umbach, David M.; Li, Leping] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Jordan, Nicole Vincent; Abell, Amy N.; Johnson, Gary L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Jordan, Nicole Vincent; Abell, Amy N.; Johnson, Gary L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Huang, WC (reprint author), NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM weichun.huang@nih.gov; li3@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [ES101765-05]; National Institutes of Health [GM30324, DK37871, GM007040]; UNC Cancer Research Fund FX Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ES101765-05); National Institutes of Health (GM30324, DK37871 to G.L.J., GM007040 to N.V.J.); UNC Cancer Research Fund (to G.L.J.). Funding for open access charge: Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences. NR 35 TC 17 Z9 17 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 19 AR e130 DI 10.1093/nar/gkr592 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 839CB UT WOS:000296341100005 PM 21803788 ER PT J AU Saji, M Narahara, K McCarty, SK Vasko, VV La Perle, KM Porter, K Jarjoura, D Lu, C Cheng, SY Ringel, MD AF Saji, M. Narahara, K. McCarty, S. K. Vasko, V. V. La Perle, K. M. Porter, K. Jarjoura, D. Lu, C. Cheng, S-Y Ringel, M. D. TI Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer SO ONCOGENE LA English DT Article DE PI3 kinase; thyroid hormone receptor beta; thyrotropin; p27; gelsolin ID EPITHELIAL-MESENCHYMAL TRANSITION; MOUSE MODEL; CELL-MIGRATION; BREAST-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; DISTINCT ROLES; BETA-RECEPTOR; P27(KIP1); GROWTH; MICE AB Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis in vivo in several model systems. In contrast, clinical and in vitro studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression in vivo using thyroid hormone receptor (TR) beta(PV/PV) knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1(-/-) and PV mice and compared tumor development, local progression, metastasis and histology in TR beta(PV/PV)/Akt1(+/+) (PVPV-Akt1WT) and TR beta(PV/PV)/Akt1(-/-) (PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice (P<0.001). In comparison with PVPV-Akt1WT mice, thyroid cancer development was delayed in the PVPV-Akt1KO mice (P = 0.003) and the degree of tumor invasiveness was reduced. The PVPV-Akt1WT mice displayed pulmonary metastases at 12 and 15 months of age, by contrast PVPV-Akt1KO mice did not develop distant metastases at 15 months of age. Despite continued expression of Akt2 or Akt3, pAkt levels were decreased and there was evidence of reduced Akt effect on p27 in the PVPV-Akt1KO thyroids. TSH levels were similarly elevated in PV mice regardless of Akt1 expression. In conclusion, thyroid cancer development and progression in TR beta(PV/PV) mice are Akt1-dependent, consistent with a tumor progression-promoting role in this murine thyroid cancer model. Oncogene (2011) 30, 4307-4315; doi: 10.1038/onc.2011.136; published online 2 May 2011 C1 [Saji, M.; Narahara, K.; McCarty, S. K.; Ringel, M. D.] Ohio State Univ, Coll Med, Div Endocrinol, Columbus, OH 43210 USA. [Saji, M.; Narahara, K.; McCarty, S. K.; Ringel, M. D.] Ohio State Univ, Coll Med, Div Diabet, Columbus, OH 43210 USA. [Saji, M.; Narahara, K.; McCarty, S. K.; Ringel, M. D.] Ohio State Univ, Coll Med, Div Metab, Columbus, OH 43210 USA. [Saji, M.; Narahara, K.; McCarty, S. K.; Porter, K.; Jarjoura, D.; Ringel, M. D.] Arthur G James Comprehens Canc Ctr, Columbus, OH USA. [Ringel, M. D.] Ohio State Univ, Coll Med, Div Oncol, Columbus, OH 43210 USA. [Porter, K.; Jarjoura, D.] Ohio State Univ, Coll Med, Ctr Biostat, Columbus, OH 43210 USA. [Vasko, V. V.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [La Perle, K. M.] Ohio State Univ, Coll Vet Med, Columbus, OH 43210 USA. [Lu, C.; Cheng, S-Y] NCI, NIH, Bethesda, MD 20892 USA. RP Ringel, MD (reprint author), Ohio State Univ, Coll Med, Div Endocrinol, 445D McCampbell Hall,1581 Dodd Dr, Columbus, OH 43210 USA. EM matthew.ringel@osumc.edu RI Saji, Motoyasu/E-4007-2011; La Perle, Krista/B-3099-2015 FU NIH [P01CA124570, R01CA102572] FX Funding for the work is from NIH grants (P01CA124570 and R01CA102572) to MDR. We appreciate the technical assistance of Michael Ostrowski, John Thompson and Jun Liu. NR 50 TC 24 Z9 24 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2011 VL 30 IS 42 BP 4307 EP 4315 DI 10.1038/onc.2011.136 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 839HP UT WOS:000296356400002 PM 21532616 ER PT J AU Liu, PC Barb, J Woodhouse, K Taylor, JG Munson, PJ Raghavachari, N AF Liu, Poching Barb, Jennifer Woodhouse, Kimberly Taylor, James G. Munson, Peter J. Raghavachari, Nalini TI Transcriptome profiling and sequencing of differentiated human hematopoietic stem cells reveal lineage-specific expression and alternative splicing of genes SO PHYSIOLOGICAL GENOMICS LA English DT Article DE hematopoiesis; differentiation; microarrays; gene expression; splicing; qPCR; RNAseq ID ERYTHROPOIESIS; LEUKEMOGENESIS; CATENIN; GTPASES; FAMILY; FATE AB Liu P, Barb J, Woodhouse K, Taylor JG VI, Munson PJ, Raghavachari N. Transcriptome profiling and sequencing of differentiated human hematopoietic stem cells reveal lineage-specific expression and alternative splicing of genes. Physiol Genomics 43: 1117-1134, 2011. First published August 9, 2011; doi:10.1152/physiolgenomics.00099.2011.-Hematopoietic differentiation is strictly regulated by complex network of transcription factors that are controlled by ligands binding to cell surface receptors. Disruptions of the intricate sequences of transcriptional activation and suppression of multiple genes cause hematological diseases, such as leukemias, myelodysplastic syndromes, or myeloproliferative syndromes. From a clinical standpoint, deciphering the pattern of gene expression during hematopoiesis may help unravel disease-specific mechanisms in hematopoietic malignancies. Herein, we describe a human in vitro hematopoietic model system where lineage-specific differentiation of CD34(+) cells was accomplished using specific cytokines. Microarray and RNAseq-based whole transcriptome and exome analysis was performed on the differentiated erythropoietic, granulopoietic, and megakaryopoietic cells to delineate changes in expression of whole transcripts and exons. Analysis on the Human 1.0 ST exon arrays indicated differential expression of 172 genes (P < 0.0000001) and significant alternate splicing of 86 genes during differentiation. Pathway analysis identified these genes to be involved in Rac/RhoA signaling, Wnt/B-catenin signaling and alanine/aspartate metabolism. Comparison of the microarray data to next generation RNAseq analysis during erythroid differentiation demonstrated a high degree of correlation in gene (R = 0.72) and exon (R = 0.62) expression. Our data provide a molecular portrait of events that regulate differentiation of hematopoietic cells. Knowledge of molecular processes by which the cells acquire their cell-specific fate would be beneficial in developing cell-based therapies for human diseases. C1 [Raghavachari, Nalini] NHLBI, Genom Core Facil, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Barb, Jennifer; Munson, Peter J.] NHLBI, Math & Stat Comp Lab, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. [Taylor, James G.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RP Raghavachari, N (reprint author), NHLBI, Genom Core Facil, Genet & Dev Biol Ctr, NIH, 10 Ctr Dr,Bldg 10,8C 103B, Bethesda, MD 20892 USA. EM nraghavachari@nhlbi.nih.gov OI Taylor, James/0000-0002-4421-1809 FU Intramural Research, NHLBI; CIT, NIH FX We acknowledge Intramural Research, NHLBI, for the funding and Edge Biosciences and Applied Biosystems for generous help in RNAseq analysis using the SOLiD platform. We appreciate the help of Drs. Harry L. Malech and Uimook Choi, in the Genetic Immunotherapy Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, for providing the CD34+ cells. We acknowledge Dr. Phil Mccoy and Ms. Leigh Samsel in the NHLBI Flow Cytometry Core for help with the flow characterization of cells. We gratefully acknowledge the help of Dr. Zu Xi Yu in the Pathology Core Facility-NHLBI for help in the staining of cells.; Funding by Intramural Research, NHLBI and CIT, NIH. NR 38 TC 7 Z9 7 U1 0 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD OCT PY 2011 VL 43 IS 20 BP 1117 EP 1134 DI 10.1152/physiolgenomics.00099.2011 PG 18 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 841ZJ UT WOS:000296553500001 PM 21828245 ER PT J AU Moore, RA Timmes, AG Wilmarth, PA Safronetz, D Priola, SA AF Moore, Roger A. Timmes, Andrew G. Wilmarth, Phillip A. Safronetz, David Priola, Suzette A. TI Identification and removal of proteins that co-purify with infectious prion protein improves the analysis of its secondary structure SO PROTEOMICS LA English DT Article DE Animal proteomics; Apolipoprotein E; Ferritin; infrared spectroscopy; Prion protein purification; Prion strains ID TRANSFORM INFRARED-SPECTROSCOPY; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; SCRAPIE PRION; APOLIPOPROTEIN-E; DIFFERENT STRAINS; MOUSE SCRAPIE; DISEASE; CONFORMATIONS; PURIFICATION; HAMSTERS AB Prion diseases are neurodegenerative disorders associated with the accumulation of an abnormal isoform of the mammalian prion protein (PrP). Fourier transform infrared spectroscopy (FTIR) has previously been used to show that the conformation of aggregated, infectious PrP (PrP(Sc)) varies between prion strains and these unique conformations may determine strain-specific disease phenotypes. However, the relative amounts of alpha-helix, beta-sheet and other secondary structures have not always been consistent between studies, suggesting that other proteins might be confounding the analysis of PrP(Sc) secondary structure. We have used FTIR and LC-MS/MS to analyze enriched PrP(Sc) from mouse and hamster prion strains both before and after the removal of protein contaminants that commonly co-purify with PrP(Sc). Our data show that non-PrP proteins do contribute to absorbances that have been associated with alpha-helical, loop, turn and beta-sheet structures attributed to PrP(Sc). The major contaminant, the alpha-helical protein ferritin, absorbs strongly at 1652 cm(-1) in the FTIR spectrum associated with PrP(Sc). However, even the removal of more than 99% of the ferritin from PrP(Sc) did not completely abolish absorbance at 1652 cm(-1). Our results show that contaminating proteins alter the FTIR spectrum attributed to PrP(Sc) and suggest that the alpha-helical, loop/turn and beta-sheet secondary structure that remains following their removal are derived from PrP(Sc) itself. C1 [Moore, Roger A.; Timmes, Andrew G.; Safronetz, David; Priola, Suzette A.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. [Wilmarth, Phillip A.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Sch Med, Portland, OR 97201 USA. RP Moore, RA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th Str, Hamilton, MT 59840 USA. EM rmoore@niaid.nih.gov FU National Institute of Allergy and Infectious Disease, National Institutes of Health [AI000752-16]; National Institutes of Health [EY007755] FX The authors thank Dr. Bruce Chesebro, Dr. Gerald Baron and Dr. Byron Caughey for critically evaluating the manuscript. Anita Mora and Austin Athman provided technical assistance in preparation of the figures. The authors thank Craig Martens, Kimmo Virtaneva and Steve Porcella from the Rocky Mountain Research Technologies Branch for the extraction of tissue used for obtaining hamster DNA sequencing data. The authors also thank Brent Weatherly from NuSep, Inc. for helpful discussions with ProteoIQ software. This research was supported by intramural research program of the National Institute of Allergy and Infectious Disease, National Institutes of Health (AI000752-16). P. A. W. was supported by National Institutes of Health grant EY007755. NR 55 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD OCT PY 2011 VL 11 IS 19 SI SI BP 3853 EP 3865 DI 10.1002/pmic.201100253 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 836VF UT WOS:000296142100012 PM 21805638 ER PT J AU Gundry, RL Burridge, PW Boheler, KR AF Gundry, Rebekah L. Burridge, Paul W. Boheler, Kenneth R. TI Pluripotent stem cell heterogeneity and the evolving role of proteomic technologies in stem cell biology SO PROTEOMICS LA English DT Review DE Cell biology; Cell surface; Heterogeneity; Pluripotent stem cell ID MOUSE EMBRYONIC STEM; PLASMA-MEMBRANE PROTEOMICS; TANDEM MASS-SPECTROMETRY; HUMAN SOMATIC-CELLS; HEMATOPOIETIC STEM; CARCINOMA-CELLS; HUMAN FIBROBLASTS; PROGENITOR CELLS; SURFACE MARKERS; DEFINED FACTORS AB Stem cells represent obvious choices for regenerative medicine and are invaluable for studies of human development and drug testing. The proteomic landscape of pluripotent stem cells (PSCs), in particular, is not yet clearly defined; consequently, this field of research would greatly benefit from concerted efforts designed to better characterize these cells. In this concise review, we provide an overview of stem cell potency, highlight the types and practical implications of heterogeneity in PSCs and provide a detailed analysis of the current view of the pluripotent proteome in a unique resource for this rapidly evolving field. Our goal in this review is to provide specific insights into the current status of the known proteome of both mouse and human PSCs. This has been accomplished by integrating published data into a unified PSC proteome to facilitate the identification of proteins, which may be informative for the stem cell state as well as to reveal areas where our current view is limited. These analyses provide insight into the challenges faced in the proteomic analysis of PSCs and reveal one area - the cell surface subproteome - that would especially benefit from enhanced research efforts. C1 [Gundry, Rebekah L.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. [Gundry, Rebekah L.] Med Coll Wisconsin, Dept Biotechnol, Milwaukee, WI 53226 USA. [Gundry, Rebekah L.] Med Coll Wisconsin, Ctr Bioengn, Milwaukee, WI 53226 USA. [Burridge, Paul W.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA. [Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, NIH, Baltimore, MD USA. RP Gundry, RL (reprint author), Med Coll Wisconsin, Dept Biochem, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM rgundry@mcw.edu FU Innovation Center at the Medical College of Wisconsin; Maryland Stem Cell Research Fund; NIH, National Institute on Aging; NIH Induced Pluripotent Stem Cell Center (NiPSCC); [4R00HL094708-03] FX The authors are supported by 4R00HL094708-03 (R.L.G.), the Innovation Center at the Medical College of Wisconsin (R.L.G.), Maryland Stem Cell Research Fund Postdoctoral Fellowship (P.W.B.), the Intramural Research Program of the NIH, National Institute on Aging (K.R.B.), and NIH Induced Pluripotent Stem Cell Center (NiPSCC) Pilot Study Award (K.R.B.). NR 104 TC 11 Z9 11 U1 1 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD OCT PY 2011 VL 11 IS 20 SI SI BP 3947 EP 3961 DI 10.1002/pmic.201100100 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 841DD UT WOS:000296491800002 PM 21834136 ER PT J AU Mercer, BM Spong, CY AF Mercer, Brian M. Spong, Catherine Y. TI Indicated Late Preterm and Early-Term Births Introduction SO SEMINARS IN PERINATOLOGY LA English DT Editorial Material C1 [Mercer, Brian M.] Soc Maternal Fetal Med, Washington, DC 20024 USA. [Mercer, Brian M.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH 44109 USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Mercer, BM (reprint author), Soc Maternal Fetal Med, Washington, DC 20024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2011 VL 35 IS 5 BP 245 EP 245 DI 10.1053/j.semperi.2011.05.001 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 834KC UT WOS:000295957200001 PM 21962620 ER PT J AU Acharya, P Dogo-Isonagie, C LaLonde, JM Lam, SN Leslie, GJ Louder, MK Frye, LL Debnath, AK Greenwood, JR Luongo, TS Martin, L Watts, KS Hoxie, JA Mascola, JR Bewley, CA Kwong, PD AF Acharya, Priyamvada Dogo-Isonagie, Cajetan LaLonde, Judith M. Lam, Son N. Leslie, George J. Louder, Mark K. Frye, Leah L. Debnath, Asim K. Greenwood, Jeremy R. Luongo, Timothy S. Martin, Loic Watts, K. Shawn Hoxie, James A. Mascola, John R. Bewley, Carole A. Kwong, Peter D. TI Structure-Based Identification and Neutralization Mechanism of Tyrosine Sulfate Mimetics That Inhibit HIV-1 Entry SO ACS CHEMICAL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CORECEPTOR-BINDING-SITE; PROTEIN-PROTEIN INTERACTIONS; GP120 ENVELOPE GLYCOPROTEIN; SMALL-MOLECULE INHIBITOR; CCR5 N-TERMINUS; RECEPTOR-BINDING; LINKED GLYCAN; CD4; ANTIBODY AB Tyrosine sulfate-mediated interactions play an important role in HIV-1 entry. After engaging the CD4 receptor at the cell surface, the HIV-1 gp120 glycoprotein binds to the CCR5 co-receptor via an interaction that requires two tyrosine sulfates, at positions 10 and 14 in the CCRS-N terminus. Building on previous structure determinations of this interaction, here we report the targeting of these tyrosine sulfate binding sites for drug design through in silica screening of Small molecule libraries, identification of lead compounds, and characterization of biological activity. A class of tyrosine sulfonate-mimicking small molecules containing a "phenyl sulfonate-linker-aromatic" motif was identified that specifically inhibited binding of gp120 to the CCRS-N terminus as well as to sulfated antibodies that recognize the co-receptor binding region on gp120. The most potent of these compounds bound gp120 with low micromolar affinity and its CD4-induced conformation with K(D)'s as tight as similar to 50 nM. Neutralization experiments suggested the targeted site to be conformationally inaccessible prior to CD4 engagement. Primary HIV-1 isolates were weakly neutralized, preincubation with soluble CD4 enhanced neutralization, and engineered isolates with increased dependence on the N terminus of CCR5 or with reduced, conformational barriers were neutralized with IC(50) values as low as similar to 1 mu M. These results reveal the potential of targeting the tyrosine sulfate interactions of HIV-1 and provide insight into how mechanistic barriers, evolved by HIV-1 to evade antibody recognition, also restrict small-molecule-mediated neutralization. C1 [Dogo-Isonagie, Cajetan; Lam, Son N.; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Acharya, Priyamvada; Louder, Mark K.; Luongo, Timothy S.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Leslie, George J.; Hoxie, James A.] Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Frye, Leah L.; Greenwood, Jeremy R.; Watts, K. Shawn] Schrodinger LLC, Portland, OR 97204 USA. [Debnath, Asim K.] New York Blood Ctr, Lab Mol Modeling & Drug Design, Lindsley F Kimball Res Inst, New York, NY 10021 USA. [Martin, Loic] CEA, iBiTecS, Serv Ingn Mol Prot, F-91191 Gif Sur Yvette, France. RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov; pdkwong@nih.gov FU NIH (NIDDK); NIH (NIAID); European Community [LSHP-2003-503558]; French National Agency of Research [ANR-07-EMPB-019-01]; NIH [GM 56550]; Intramural AIDS Research Fellowship FX We thank J. Lloyd for HR-MS data, members of the Structural Biology Section and Structural Bioinformatics Core at the NIH Vaccine Research Center for comments on the manuscript, J. Stuckey for assistance with figures, and I. Georgiev for discussions on statistical methods. sCD4 and Cf2Th cells stably expressing human CD4 and CCR5 were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. Support for this work was provided by the Intramural AIDS Targeted Antiviral Program (CAB. and P.D.K.), by the Intramural Research Program of the NIH (NIDDK and NIAID), by grants from the European Community's Sixth Framework programme (EMPRO) under grant agreement no. LSHP-2003-503558, by a grant from the French National Agency of Research (ANR-07-EMPB-019-01) (L.M.) and by a grant from the NIH (GM 56550) (J.M.L.). C.D.-I. was supported by an Intramural AIDS Research Fellowship. NR 42 TC 20 Z9 20 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD OCT PY 2011 VL 6 IS 10 BP 1069 EP 1077 DI 10.1021/cb200068b PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 837MO UT WOS:000296208100013 PM 21793507 ER PT J AU Phan, VTM Rabaa, MA Vinh, H Holmes, EC Nguyen, VMH Vinh, NT Phuong, LT Tham, NT Phan, VBB Campbell, JI Farrar, J Baker, S AF Phan Vu Tra My Rabaa, Maia A. Ha Vinh Holmes, Edward C. Nguyen Van Minh Hoang Nguyen Thanh Vinh Lei Thi Phuong Nguyen Thi Tham Phan Van Be Bay Campbell, James I. Farrar, Jeremy Baker, Stephen TI The Emergence of Rotavirus G12 and the Prevalence of Enteric Viruses in Hospitalized Pediatric Diarrheal Patients in Southern Vietnam SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID SPATIOTEMPORAL DYNAMICS; DEMOGRAPHIC-VARIABILITY; MOLECULAR EPIDEMIOLOGY; ACUTE GASTROENTERITIS; SEQUENCE-ANALYSIS; CHILDREN; SURVEILLANCE; HANOI; VACCINATION; INFECTIONS AB Diarrhea is a major cause of childhood morbidity and mortality in developing countries, and the majority of infections are of viral etiology. We aimed to compare the etiological prevalence of the major enteric viruses in an urban and a rural setting in southern Vietnam. We simultaneously screened fecal specimens from 362 children in Ho Chi Minh City and Dong Thap province that were hospitalized with acute diarrhea over a 1-month-long period for four viral gastrointestinal pathogens. Rotavirus was the most common pathogen identified, but there was a differential prevalence of rotavirus and norovirus between the urban and rural locations. Furthermore, rotavirus genotyping and phylogenetic analysis again differentiated the genotypes by the sampling location. Our data show a disproportional distribution of enteric viral pathogens in urban and rural locations, and we provide evidence of continual importation of new rotavirus strains into southern Vietnam and report the emergence of rotavirus genotype G12. C1 [Phan Vu Tra My; Nguyen Van Minh Hoang; Nguyen Thanh Vinh; Campbell, James I.; Farrar, Jeremy; Baker, Stephen] Univ Oxford, Enter Infect Grp, Wellcome Trust Major Overseas Programme, Hosp Trop Dis,Clin Res Unit, Ho Chi Minh City, Vietnam. [Rabaa, Maia A.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Lei Thi Phuong; Nguyen Thi Tham; Phan Van Be Bay] Dong Thap Prov Hosp, Infect Ward, Dong Thap, Vietnam. Univ Oxford, Ctr Trop Dis, Oxford, England. [Ha Vinh] Hosp Trop Dis, Pediat Ward B, Ho Chi Minh City, Vietnam. RP Baker, S (reprint author), Univ Oxford, Enter Infect Grp, Wellcome Trust Major Overseas Programme, Hosp Trop Dis,Clin Res Unit, 190 Ben Ham Tu,Dist 5, Ho Chi Minh City, Vietnam. EM mypvt@oucru.org; maia.rabaa@gmail.com; vinhh@oucru.org; ech15@psu.edu; hoangnvm@oucru.org; vinhnt@oucru.org; jcampbell@oucru.org; jfarrar@oucru.org; sbaker@oucru.org OI Rabaa, Maia/0000-0003-0529-2228; Farrar, Jeremy/0000-0002-2700-623X; Holmes, Edward/0000-0001-9596-3552 FU Wellcome Trust, Euston Road, London, United Kingdom; Oak Foundation through Oxford University; National Science Foundation FX This work is supported by The Wellcome Trust, Euston Road, London, United Kingdom. S.B. is supported by an Oak Foundation Fellowship through Oxford University. M.A.R. is supported by a National Science Foundation Graduate Research Fellowship. NR 37 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2011 VL 85 IS 4 BP 768 EP 775 DI 10.4269/ajtmh.2011.11-0364 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 833QB UT WOS:000295898900033 ER PT J AU Kemp, CD Ripley, RT Mathur, A Steinberg, SM Nguyen, DM Fojo, T Schrump, DS AF Kemp, Clinton D. Ripley, R. Taylor Mathur, Aarti Steinberg, Seth M. Nguyen, Dao M. Fojo, Tito Schrump, David S. TI Pulmonary Resection for Metastatic Adrenocortical Carcinoma: The National Cancer Institute Experience SO ANNALS OF THORACIC SURGERY LA English DT Article ID ADRENAL-CORTICAL CARCINOMA; SERIES AB Background. Adrenocortical carcinoma (ACC) is a rare neoplasm with a high propensity for locoregional recurrences and distant metastases for which there are no effective systemic therapies. This study was undertaken to determine outcomes of patients undergoing pulmonary metastasectomy for ACC. Methods. A single-institution retrospective review was performed of patients undergoing pulmonary metastasectomy for ACC from 1979 to 2010. Results. Twenty-six patients underwent 60 pulmonary metastasectomies. Fifteen patients (58%) underwent unilateral thoracotomy, 6 (23%) had staged thoracotomies, and 5 (19%) underwent median sternotomy as the initial thoracic procedure. Median number and size of lesions were 6 and 2 cm, respectively. Twenty-three patients (88%) were rendered free of disease in the lung, and 14 (54%) were rendered completely free of disease. Median overall and 5-year actuarial survivals from initial pulmonary metastasectomy were 40 months and 41%, respectively, with a median potential follow-up of 120 months. Median recurrence-free survival (RFS) and 5-year RFS for ipsilateral thoracic recurrences were 6 months, and 25%, respectively. The median RFS in the contralateral thorax was 5 months. Time to first recurrence after adrenalectomy and T stage of the primary tumor, but not adjuvant or neoadjuvant chemotherapy, were associated with increased overall survival after pulmonary metastasectomy. Conclusions. This study represents the most comprehensive review of outcomes of patients undergoing pulmonary metastasectomy for ACC. Given the lack of effective systemic therapies, pulmonary metastasectomy may be beneficial in properly selected patients. (Ann Thorac Surg 2011;92:1195-201) (C) 2011 by The Society of Thoracic Surgeons C1 [Schrump, David S.] NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Rm 4-3942,MSC 1201, Bethesda, MD 20892 USA. EM david_schrump@nih.gov NR 17 TC 14 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2011 VL 92 IS 4 BP 1195 EP 1200 DI 10.1016/j.athoracsur.2011.05.013 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 833ZI UT WOS:000295924400016 PM 21958764 ER PT J AU Amirghofran, AA Karimi, A Emaminia, A Sharifkazemi, MB Salaminia, S AF Amirghofran, Ahmad Ali Karimi, Ashkan Emaminia, Abbas Sharifkazemi, Mohammad Bagher Salaminia, Shirvan TI Brucellosis Relapse Causing Prosthetic Valve Endocarditis and Aortic Root Infective Pseudoaneurysm SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID ABSCESS AB We report a previously treated case of brucellosis and aortic root replacement, which became complicated by prosthetic valve endocarditis and a massive aortic root pseudoaneurysm. Preoperative blood and intraoperative pseudoaneurysm wall cultures were positive for Brucella, and the patient was managed successfully with a combination of surgical and medical treatment. Brucella endocarditis is further discussed. (Ann Thorac Surg 2011;92:e77-9) (C) 2011 by The Society of Thoracic Surgeons C1 [Karimi, Ashkan] Univ Florida, Div Thorac & Cardiovasc Surg, Gainesville, FL 32610 USA. Shiraz Univ Med Sci, Div Cardiothorac Surg, Shiraz, Iran. NIH, Cardiothorac Surg Res Program, Ctr Heart, Bethesda, MD 20892 USA. Shiraz Univ Med Sci, Div Cardiol, Dept Med, Shiraz, Iran. RP Karimi, A (reprint author), Univ Florida, Div Thorac & Cardiovasc Surg, 1600 Archer Rd,Room NG-32, Gainesville, FL 32610 USA. EM ashkan.karimi@surgery.ufl.edu NR 10 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2011 VL 92 IS 4 BP E77 EP E79 DI 10.1016/j.athoracsur.2011.03.144 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 833ZI UT WOS:000295924400004 PM 21958835 ER PT J AU Remaley, AT AF Remaley, A. T. TI "Who's on First": Determining the roster for the key players in the reverse cholesterol transport pathway SO ATHEROSCLEROSIS LA English DT Editorial Material DE ABCA1; SR-BI; Atherosclerosis; Cholesterol efflux; High density lipoproteins ID DENSITY-LIPOPROTEIN CHOLESTEROL; SCAVENGER RECEPTOR BI; IN-VIVO; SR-BI; ABCA1; HDL; DEFICIENT; SECRETION; DISEASE; ABCG1 C1 NHLBI, Lipoprot Metab Sect, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NHLBI, Lipoprot Metab Sect, Cardiopulm Branch, NIH, Bldg 10,Room 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley1@cc.nih.gov FU Intramural NIH HHS [Z01 CL010303-07] NR 18 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2011 VL 218 IS 2 BP 287 EP 289 DI 10.1016/j.atherosclerosis.2011.06.037 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 836WJ UT WOS:000296147600041 PM 21798543 ER PT J AU Polak, JF Wong, Q Johnson, WC Bluemke, DA Harrington, A O'Leary, DH Yanez, ND AF Polak, Joseph F. Wong, Quenna Johnson, W. Craig Bluemke, David A. Harrington, Anita O'Leary, Daniel H. Yanez, N. David TI Associations of cardiovascular risk factors, carotid intima-media thickness and left ventricular mass with inter-adventitial diameters of the common carotid artery: The Multi-Ethnic Study of Atherosclerosis (MESA) SO ATHEROSCLEROSIS LA English DT Article DE Carotid arteries; Ultrasonics; Hypertrophy; Magnetic resonance imaging; Remodeling; Risk factors; Left ventricle ID BLOOD-PRESSURE; OLDER-ADULTS; ENLARGEMENT; POPULATION; QUANTITATION; COMMUNITIES; DISEASE; HEALTH AB Background: Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors. Methods: IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis ( MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass. Results: Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a 1 mm difference in IMT was associated with a 1.802 mm (95% CI: 1.553, 2.051) higher mean IAD. A 1 g difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.007) higher mean IAD. After adjusting for cardiovascular risk factors and IMT, a 1 g difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.008) higher mean IAD for women and 0.004 mm (95% CI: 0.003, 0.005) higher IAD for men. Conclusions: Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Polak, Joseph F.; Harrington, Anita; O'Leary, Daniel H.] Tufts Med Ctr, Dept Radiol, Boston, MA 02111 USA. [Wong, Quenna; Johnson, W. Craig; Yanez, N. David] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98115 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RP Polak, JF (reprint author), Tufts Med Ctr, Dept Radiol, 800 Washington St,Box 299, Boston, MA 02111 USA. EM jpolak@tuftsmedicalcenter.org OI Bluemke, David/0000-0002-8323-8086 FU [N01-HC-95159]; [N01-HC-95165]; [N01-HC-95167]; [R01 HL069003]; [R01 HL081352] FX The authors would like to thank the investigators, the staff, and the participants of the Multi-Ethnic Study of Atherosclerosis, MESA for their valuable contributions. This research was supported by Contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95167 as well as R01 HL069003 and R01 HL081352. NR 22 TC 15 Z9 17 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2011 VL 218 IS 2 BP 344 EP 349 DI 10.1016/j.atherosclerosis.2011.05.033 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 836WJ UT WOS:000296147600050 PM 21726862 ER PT J AU Xu, P Alam, MM Kalsy, A Charles, RC Calderwood, SB Qadri, F Ryan, ET Kovac, P AF Xu, Peng Alam, Mohammad Murshid Kalsy, Anuj Charles, Richelle C. Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. Kovac, Pavol TI Simple, Direct Conjugation of Bacterial O-SP-Core Antigens to Proteins: Development of Cholera Conjugate Vaccines SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SQUARIC ACID DIESTER; VIBRIO-CHOLERAE; SEROTYPE INABA; DETOXIFIED LIPOPOLYSACCHARIDE; ANTIBODY-RESPONSE; DIETHYL SQUARATE; SIDE-CHAIN; POLYSACCHARIDE; INFECTION; CARRIER AB Bacterial O-SP core antigens can be conjugated to proteins in the same, simple way as synthetic, linker-equipped carbohydrates by applying squaric acid chemistry. Introduction of spacers (linkers) to either O-SP core antigens or protein carriers, which is involved in commonly applied protocols, is not required. The newly developed method described here consists of preparation of a squaric acid monoester derivative of O-SP core antigen, utilizing the amino group inherent in the core, and reaction of the monoester with the carrier protein. The intermediate monoester can be easily purified; its conjugation can be monitored by SELDI-TOF mass spectrometry and, thus, readily controlled, since the conjugation can be terminated when the desired carbohydrate protein ratio is reached. Here, we describe production of conjugates containing the O-SP core antigen of Vibrio cholerae 01, the major cause of cholera, a severe dehydrating diarrheal disease of humans. The resultant products are recognized by convalescent phase sera from patients recovering from cholera in Bangladesh, and anti-O-SP-core-protein responses correlate with plasma antilipopolysaccharide and vibriocidal responses, which are the primary markers of protection from cholera. The results suggest that such conjugates have potential as vaccines for cholera and other bacterial diseases. C1 [Alam, Mohammad Murshid; Kalsy, Anuj; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Alam, Mohammad Murshid; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org; kpn@helix.nih.gov RI Xu, Peng/K-7036-2012; Kovac, Pavol/B-8813-2008 OI Kovac, Pavol/0000-0001-5044-3449 FU NIH, NIDDK; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (ICDDR, B); Fogarty International Center (FIC) [TW05572] FX This research was supported by the Intramural Research Program of the NIH, NIDDK, as well the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (ICDDR, B), and NIAID AI077883 (ETR), AI058935 (SBC, FQ), AI089721 (RCC), and the Fogarty International Center (FIC) TW05572 (MMA, FQ). NR 35 TC 18 Z9 18 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD OCT PY 2011 VL 22 IS 10 BP 2179 EP 2185 DI 10.1021/bc2001984 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 833WE UT WOS:000295915100034 PM 21899371 ER PT J AU Hildebrandt, GC Fazekas, T Lawitschka, A Bertz, H Greinix, H Halter, J Pavletic, SZ Holler, E Wolff, D AF Hildebrandt, G. C. Fazekas, T. Lawitschka, A. Bertz, H. Greinix, H. Halter, J. Pavletic, S. Z. Holler, E. Wolff, D. TI Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD SO BONE MARROW TRANSPLANTATION LA English DT Review DE chronic GVHD; allo-SCT; lung; obliterative bronchiolitis; treatment ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; BRONCHIOLITIS OBLITERANS SYNDROME; TOTAL LYMPHOID IRRADIATION; HIGH-RESOLUTION CT; WORKING GROUP-REPORT; LONG-TERM SURVIVORS; IDIOPATHIC PNEUMONIA SYNDROME; OBSTRUCTIVE AIRWAY DISEASE AB This consensus statement established under the auspices of the German working group on BM and blood stem cell transplantation (DAG-KBT), the German Society of Hematology and Oncology (DGHO), the Austrian Stem Cell Transplant Working Group, the Swiss Blood Stem Cell Transplantation Group (SBST) and the German-Austrian Pediatric Working Group on SCT (Pad-Ag-KBT) summarizes current evidence for diagnosis, immunosuppressive and supportive therapy to provide practical guidelines for the care and treatment of patients with pulmonary manifestations of chronic GVHD (cGVHD). Pulmonary cGVHD can present with obstructive and/or restrictive changes. Disease severity ranges from subclinical pulmonary function test (PFT) impairment to respiratory insufficiency with bronchiolitis obliterans being the only pulmonary complication currently considered diagnostic of cGVHD. Early diagnosis may improve clinical outcome, and regular post-transplant follow-up PFTs are recommended. Diagnostic work-up includes high-resolution computed tomography, bronchoalveolar lavage and histology. Topical treatment is based on inhalative steroids plus beta-agonists. Early addition of azithromycin is suggested. Systemic first-line treatment consists of corticosteroids plus, if any, continuation of other immunosuppressive therapy. Second-line therapy and beyond includes extracorporeal photopheresis, mammalian target of rapamycin inhibitors, mycophenolate, etanercept, imatinib and TLI, but efficacy is limited. Clinical trials are urgently needed to improve understanding and treatment of this deleterious complication. Bone Marrow Transplantation (2011) 46, 1283-1295; doi: 10.1038/bmt.2011.35; published online 28 March 2011 C1 [Hildebrandt, G. C.] LSUHSC Shreveport, Feist Weiller Canc Ctr, Blood & Marrow Transplant Program, Shreveport, LA 71130 USA. [Hildebrandt, G. C.; Holler, E.; Wolff, D.] Univ Regensburg, Med Ctr, Dept Hematol & Oncol, Regensburg, Germany. [Fazekas, T.; Lawitschka, A.] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. [Bertz, H.] Univ Freiburg, Med Ctr, Dept Haematol & Oncol, D-7800 Freiburg, Germany. [Greinix, H.] Med Univ Vienna, Dept Internal Med 1, Vienna, Austria. [Halter, J.] Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland. [Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hildebrandt, GC (reprint author), LSUHSC Shreveport, Feist Weiller Canc Ctr, Blood & Marrow Transplant Program, 1501 Kings Highway, Shreveport, LA 71130 USA. EM ghilde@lsuhsc.edu RI Halter, Joerg/C-9487-2012 FU Jose Carreras Foundation 'Competence center GVHD Regensburg' FX We thank all participating centers of conferences and surveys, which included participants from the transplant centers in Augsburg, Basel, Berlin, Cologne, Dresden, Duesseldorf, Erlangen, Essen, Freiburg, Greifswald, Hamburg, Hannover, Heidelberg, Jena, Kiel, Leipzig, Linz, Mainz, Munster, Munich, Nantes, Nuernberg, Oldenburg, Paris, Regensburg, Rostock, Tuebingen, Ulm, Vienna, Wiesbaden and Wuerzburg. We thank Anna Hackl for evaluating the survey on treatment of cGVHD. The conference was supported by the Jose Carreras Foundation project 'Competence center GVHD Regensburg'. We convey our special thanks to Dr Nicolai Kittan for his critical review of the manuscript and figure design. NR 127 TC 62 Z9 63 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 2011 VL 46 IS 10 BP 1283 EP 1295 DI 10.1038/bmt.2011.35 PG 13 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 838HR UT WOS:000296279000001 PM 21441964 ER PT J AU Norman, BC Jacobsohn, DA Williams, KM Au, BKC Au, MA Lee, SJ Moravec, CK Chien, JW AF Norman, B. C. Jacobsohn, D. A. Williams, K. M. Au, B. K. C. Au, M. A. Lee, S. J. Moravec, C. K. Chien, J. W. TI Fluticasone, azithromycin and montelukast therapy in reducing corticosteroid exposure in bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: a case series of eight patients SO BONE MARROW TRANSPLANTATION LA English DT Article DE bronchiolitis obliterans syndrome; corticosteroids; steroid sparing; FAM ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; OBSTRUCTIVE LUNG-DISEASE; ADVERSE EVENTS; RISK-FACTORS; EPIDEMIOLOGY; ADULTS AB Bronchiolitis obliterans syndrome (BOS) is a devastating pulmonary complication affecting long-term survivors of allogeneic hematopoietic cell transplantation. Treatment of BOS with prolonged courses of high dose corticosteroids is often associated with significant morbidity. Reducing the exposure to corticosteroids may reduce treatment-related morbidity. Our institution has recently begun to treat patients with emerging therapies in an effort to diminish corticosteroid exposure. We retrospectively reviewed the 6-month corticosteroid exposure, lung function and failure rates in eight patients with newly diagnosed BOS who were treated with a combination of fluticasone, azithromycin and montelukast (FAM) and a rapid corticosteroid taper. These patients were compared with 14 matched historical patients who received high-dose corticosteroids, followed by a standard taper. The median 6-month prednisone exposure in FAM-treated patients was 1819 mg (0-4036 mg) compared with 7163 mg (6551-7829 mg) in the control group (P = 0.002). The median forced expiratory volume in 1s (FEV(1)) change in FAM-treated patients was 2% (-3 to 4%] compared with 1% (-4 to 5%) in the control group (P = 1.0). Prednisone exposure in FAM patients was one quarter that of a retrospective-matched group of patients, with minimal change in median FEV(1), suggesting that BOS may be spared of the morbidities associated with long-term corticosteroid use by using alternative agents with less side effects. Bone Marrow Transplantation (2011) 46, 1369-1373; doi: 10.1038/bmt.2010.311; published online 6 December 2010 C1 [Lee, S. J.; Moravec, C. K.; Chien, J. W.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Norman, B. C.] Univ Washington, Dept Med, Affiliated Hosp, Seattle, WA USA. [Jacobsohn, D. A.] Northwestern Univ, Sch Med, Stem Cell Transplant Program, Chicago, IL USA. [Williams, K. M.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Au, B. K. C.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Au, M. A.] Univ Hawaii, Canc Res Ctr, Dept Epidemiol, Honolulu, HI 96813 USA. RP Chien, JW (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-280, Seattle, WA 98109 USA. EM jchien@fhcrc.org FU National Institutes of Health [HL088201, AI083028] FX Financial disclosure: This work was supported in part by the National Institutes of Health Grants HL088201 and AI083028. NR 23 TC 29 Z9 31 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 2011 VL 46 IS 10 BP 1369 EP 1373 DI 10.1038/bmt.2010.311 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 838HR UT WOS:000296279000014 PM 21132024 ER PT J AU Ghanima, W Junker, P Hasselbalch, HC Boiocchi, L Geyer, JT Feng, XM Gudbrandsdottir, S Orazi, A Bussel, JB AF Ghanima, Waleed Junker, Peter Hasselbalch, Hans Carl Boiocchi, Leonardo Geyer, Julia T. Feng, Xingmin Gudbrandsdottir, Sif Orazi, Attilio Bussel, James B. TI Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE platelets; myelofibrosis; transforming growth factor beta (TGF-beta); hepatocyte growth factor; procollagen ID HEPATOCYTE GROWTH-FACTOR; BONE-MARROW RETICULIN; CHRONIC MYELOPROLIFERATIVE DISORDERS; CONTROLLED-TRIAL; DOUBLE-BLIND; FACTOR-BETA; PURPURA; ROMIPLOSTIM; ELTROMBOPAG; FIBROSIS AB This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen-III formation and fibrosis-related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo-RA) who had at least one BM biopsy. Assessment of 8 pre- and on-treatment BM biopsies revealed statistically significant increases in reticulin. Reticulin in biopsies performed after a median of 1.4 years of treatment was graded: MF-0 in 3 (12%), MF-1 in 19 (76%), MF-2 in 2 (8%) and MF-3 in 1 (4%). No cytogenetic or flow-cytometric abnormalities were detected. Median pretreatment Procollagen III N-propeptide (PIIINP) (6.6 mu g/l) was significantly higher than on-treatment levels (5.6 mu g/l); both were higher than controls (3.4 mu g/l; P < 0.001). PIIINP was negatively correlated with treatment duration (r = -0.49) suggesting a decelerated reticulin production over time. There was a trend towards an association between grade of reticulin and PIIINP. Transforming growth factor (GF)-beta and basic-Fibroblast GF were not different between patients and controls but Hepatocyte GF (HGF), an anti-fibrotic cytokine, was significantly elevated in patients. In conclusion, low-grade BM reticulin fibrosis is seen in most ITP patients on Tpo-RA. The novel findings of decreasing PIIINP and elevated HGF need further investigation to explore their significance in BM fibrogenesis. C1 [Ghanima, Waleed; Bussel, James B.] Cornell Univ, Weill Med Coll, Dept Pediat Hematol Oncol, New York, NY 10065 USA. [Ghanima, Waleed] Ostfold Hosp Trust Fredrikstad, Dept Med, Fredrikstad, Norway. [Junker, Peter] Odense Univ Hosp, Dept Rheumatol C, DK-5000 Odense, Denmark. [Hasselbalch, Hans Carl; Gudbrandsdottir, Sif] Roskilde Hosp, Dept Hematol Oncol, Roskilde, Denmark. [Boiocchi, Leonardo; Geyer, Julia T.; Orazi, Attilio] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Boiocchi, Leonardo] Univ Milan, Sch Med, Dept Med,Pathol Unit, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy. [Feng, Xingmin] NHLBI, NIH, Bethesda, MD 20892 USA. [Gudbrandsdottir, Sif] Rigshosp, Copenhagen Univ Hosp, Dept Rheumatol, Inst Inflammat Res, DK-2100 Copenhagen, Denmark. RP Ghanima, W (reprint author), Cornell Univ, Weill Med Coll, Dept Pediat Hematol Oncol, New York, NY 10065 USA. EM wghanima@c2i.net OI Boiocchi, Leonardo/0000-0001-5188-6217 FU Amgen; GSK; Eisai; Shionogi FX W.G has received research grants from Amgen, and received honorariums for from Amgen and GlaxoSmithKline (GSK) whose products were studied in the present report. S.G. has received research funding from GSK and Amgen. J.B.B currently receives clinical research support from the following companies: Amgen, GSK, Eisai, and Shionogi and has participated in Advisory Boards for Amgen, GSK, and Eisai. His family owns stock in Amgen and GSK. NR 35 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2011 VL 155 IS 2 BP 248 EP 255 DI 10.1111/j.1365-2141.2011.08845.x PG 8 WC Hematology SC Hematology GA 835VD UT WOS:000296063400011 PM 21902682 ER PT J AU Herrero, R Wacholder, S Rodriguez, AC Solomon, D Gonzalez, P Kreimer, AR Porras, C Schussler, J Jimenez, S Sherman, ME Quint, W Schiller, JT Lowy, DR Schiffman, M Hildesheim, A AF Herrero, Rolando Wacholder, Sholom Rodriguez, Ana C. Solomon, Diane Gonzalez, Paula Kreimer, Aimee R. Porras, Carolina Schussler, John Jimenez, Silvia Sherman, Mark E. Quint, Wim Schiller, John T. Lowy, Douglas R. Schiffman, Mark Hildesheim, Allan CA Costa Rica Vaccine Trial Grp TI Prevention of Persistent Human Papillomavirus Infection by an HPV16/18 Vaccine: A Community-Based Randomized Clinical Trial in Guanacaste, Costa Rica SO CANCER DISCOVERY LA English DT Article ID CERVICAL-CANCER VACCINE; YOUNG-WOMEN; PARTICLE VACCINE; HPV TYPES; CROSS-PROTECTION; BROAD-SPECTRUM; DOUBLE-BLIND; RISK; PCR; IMPACT AB Target groups for human papillomavirus (HPV) vaccination are controversial. We evaluated vaccine efficacy (VE) against 1-year persistent infection, stratified by age and sexual behavior, among young women in Costa Rica. We randomized 7,466 healthy women 18 to 25 years of age to HPV16/18 or hepatitis A vaccine (follow-up, 50.4 months). According-to-protocol (ATP) cohorts included compliant HPV-negative women; intention-to-treat (ITT) included all randomized women. ATP VE was 90.9% (95% CI, 82.0-95.9) against HPV16/18 infections, 44.5% against HPV31/33/45 (95% CI, 17.5-63.1), and 12.4% (95% CI, -3.2 to 25.6) against any oncogenic infection. Overall ITT VE against HPV16/18 infections was 49.0%, but ATP and ITT VE almost reached 100% in year 4 of follow-up. ATP efficacy against HPV16/18 was similar by age, but ITT VE was greatest among youngest women (68.9% among those 18-19 years of age; 21.8% among those 24-25 years of age) and 79.8% among virgins. Among previously unexposed women, vaccination is highly efficacious against HPV16/18 and partially against HPV31/33/45. Vaccination is most effective in women and girls before they initiate sexual activity, with programmatic and individual decision implications. SIGNIFICANCE: In an independent trial of the bivalent ASO4-adjuvanted HPV16/18 vaccine (Cervarix) conducted among young women in Costa Rica, we confirmed the high efficacy against HPV16/18 persistent infection and partial cross-protection against HPV31/33/45. Furthermore, efficacy data suggest that the benefit of HPV vaccination is maximal when the vaccine is given to young women before they initiate sexual activity. Cancer Discovery;1(5):408-19. (C) 2011 AACR. C1 [Herrero, Rolando] Int Agcy Res Canc, Early Detect & Prevent Sect, F-69372 Lyon, France. [Herrero, Rolando; Rodriguez, Ana C.; Gonzalez, Paula; Porras, Carolina; Jimenez, Silvia] Fdn Inst Costarricense Invest & Ensenanza Nutr &, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Wacholder, Sholom; Kreimer, Aimee R.; Sherman, Mark E.; Schiffman, Mark; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Solomon, Diane] NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. [Schiller, John T.; Lowy, Douglas R.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Schussler, John] Informat Management Syst IMS, Beltsville, MD USA. [Quint, Wim] DDL Diagnost Lab, Voorburg, Netherlands. RP Herrero, R (reprint author), Int Agcy Res Canc, Early Detect & Prevent Sect, 150 Cours Albert Thomas, F-69372 Lyon, France. EM herreror@iarc.fr RI Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015 OI Hildesheim, Allan/0000-0003-0257-2363; FU NCI [N01-CP-11005]; NIH Office of Research on Women's Health FX The Costa Rican Vaccine Trial is a longstanding collaboration between investigators in Costa Rica and NCI. The trial is sponsored and funded by NCI (N01-CP-11005) with support from the NIH Office of Research on Women's Health and conducted in agreement with the Ministry of Health of Costa Rica. The NCI and Costa Rica investigators are responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript. Vaccine was provided for our trial by GSK Biologicals, under a Clinical Trials Agreement with NCI. GSK also provided support for aspects of the trial associated with regulatory submission needs of the company under FDA BB-IND 7920. D. R. Lowy and J.T. Schiller are named inventors on U. S. government-owned HPV vaccine patents that are licensed to GSK and Merck, and so are entitled to limited royalties as specified by federal law. None of the other coauthors have any potential conflicts of interest to report. NR 32 TC 59 Z9 61 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD OCT PY 2011 VL 1 IS 5 BP 408 EP 419 DI 10.1158/2159-8290.CD-11-0131 PG 12 WC Oncology SC Oncology GA 836UX UT WOS:000296140600019 PM 22586631 ER PT J AU Hsiao, YH Deng, CX Mason, JT Chou, MC Man, YG AF Hsiao, Yi-Hsuan Deng, Chuxia Mason, Jeffrey T. Chou, Ming-Chih Man, Yan-gao TI Hidden malignant cells within leukocyte aggregates: Seeds for invasive and metastatic cancer? SO CANCER EPIDEMIOLOGY LA English DT Article DE Leukocyte aggregate; Myoepithelial cell; Pregnancy-associated breast cancer; Tumor invasion; Tumor metastasis ID BREAST-TUMOR INVASION; MAMMARY-TUMORS; MACROPHAGES; PROGRESSION; HYPOTHESIS; PREGNANCY; TRIGGER; LAYERS AB Background: Our previous studies revealed that leukocyte infiltration into aged or injured myoepithelial cell layers is a key trigger for breast tumor invasion and metastasis. Our current study further assessed the possibility that leukocyte aggregates may harbor detached individual tumor cell or clusters of tumor cells. Materials and methods: Tissue sections from patients with pregnancy-associated breast cancer (PABC) and controls were subjected to morphological and immunohistochemical assessment with a panel of leukocyte and tumor cell related markers. Results: A total of 63 leukocyte aggregates were detected in the 20 PABC cases studied. Of these, 55 (87%) were distributed within normal or hyperplastic lobules adjacent to invasive lesions. Over 70% of these leukocyte aggregates harbored detached individual tumor cell or cell clusters with malignant properties, including strong p53 positivity, elevated proliferation, reduced cell surface adhesion molecules, and cytological resemblance to adjacent invasive cancer cells. A significant number of these tumor cells or condensed chromosomes of mitotic tumor cells were observed to conjoin with the plasma membrane of leukocytes. Similar alterations were seen in leukocyte aggregates within the inter-lobular space and in non-PABC with a lower frequency. Conclusions: These findings suggest that leukocyte infiltration may trigger dissemination of tumor cells from their primary site, and that leukocyte aggregates may serve as a reservoir for disseminated tumor cells that may be physically dragged to distant sites by leukocytes during their migration. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Hsiao, Yi-Hsuan; Chou, Ming-Chih] Chung Shan Med Univ, Inst Med, Taichung, Taiwan. [Hsiao, Yi-Hsuan] Changhua Christian Hosp, Dept Obstet & Gynecol, Changhua, Taiwan. [Deng, Chuxia] NIDDK, Mammalian Genet Sect, GDDB, NIH, Bethesda, MD USA. [Mason, Jeffrey T.; Man, Yan-gao] Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Washington, DC 20306 USA. [Man, Yan-gao] Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. RP Chou, MC (reprint author), Chung Shan Med Univ, Inst Med, Taichung, Taiwan. EM graduate@csmu.edu.tw; man@afip.osd.mil RI deng, chuxia/N-6713-2016 FU Susan G. Komen Breast Cancer Foundation [BCTR 0706983]; US Military Cancer Institute [2008-02]; Henry M. Jackson Foundation; Ministry of Chinese Science and Technology Department [2006CB910505] FX This study was supported in part by research grants BCTR 0706983 from The Susan G. Komen Breast Cancer Foundation, 2008-02 from the US Military Cancer Institute and Henry M. Jackson Foundation, and 2006CB910505 from the Ministry of Chinese Science and Technology Department to Dr. Yan-gao Man. NR 20 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD OCT PY 2011 VL 35 IS 5 BP 475 EP 479 DI 10.1016/j.canep.2010.11.010 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 837CB UT WOS:000296167600014 PM 21292584 ER PT J AU Yao, XL Remaley, AT Levine, SJ AF Yao, Xianglan Remaley, Alan T. Levine, Stewart J. TI New Kids on the Block The Emerging Role of Apolipoproteins in the Pathogenesis and Treatment of Asthma SO CHEST LA English DT Article ID MIMETIC PEPTIDE; A-I; REDUCES ATHEROSCLEROSIS; AIRWAY INFLAMMATION; DENSITY-LIPOPROTEIN; ALZHEIMERS-DISEASE; CHOLESTEROL EFFLUX; MOUSE MODEL; APOA-I; MICE AB New treatments are needed for patients with severe asthma. We hypothesized that a clinically relevant experimental model of house dust mite (HDM)-induced murine asthma could be used to discover new pathways that regulate disease severity. In HDM-challenged mice, genome-wide expression profiling of the asthmatic lung transcriptome identified apolipoprotein E (apoE) as a steroid-unresponsive gene with persistently upregulated expression despite dexamethasone treatment. ApoE and low-density lipoprotein receptor (LDLR) knockout mice were used to demonstrate that apoE, which is produced by lung macrophages, functions in a paracrine fashion by binding to LDLRs expressed on ciliated airway epithelial cells, to negatively modulate airway hyperreactivity, mucin gene expression, and goblet cell hyperplasia. Furthermore, administration of an apoE mimetic peptide, which corresponded to the LDLR-binding domain of apoE, prevented the induction of airway inflammation, airway hyperreactivity, and goblet cell hyperplasia in HDM-challenged apoE knockout mice. This suggests that therapeutic strategies that activate the apoE-LDLR pathway, such as apoE mimetic peptides, may represent a novel treatment approach for patients with asthma. Similarly, we showed that administration of a 5A apolipoprotein A-I mimetic peptide attenuated the induction of HDM-mediated asthma in mice. These preclinical data suggest that apoE and apoA-I mimetic peptides might be developed into alternative treatments for patients with severe asthma. Future clinical trials will be required to determine whether inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides are effective for the treatment of severe asthma, including patients with phenotypes that lack effective therapeutic options. CHEST 2011; 140(4):1048-1054 C1 [Yao, Xianglan; Remaley, Alan T.; Levine, Stewart J.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health FX This study was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 50 TC 13 Z9 13 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2011 VL 140 IS 4 BP 1048 EP 1054 DI 10.1378/chest.11-0158 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 833QP UT WOS:000295900300032 PM 21972383 ER PT J AU Sheydina, A Riordon, DR Boheler, KR AF Sheydina, Anna Riordon, Daniel R. Boheler, Kenneth R. TI Molecular mechanisms of cardiomyocyte aging SO CLINICAL SCIENCE LA English DT Article DE aging; apoptosis; cardiomyocyte; cardiovascular disease ID APOPTOSIS-INDUCING FACTOR; MITOCHONDRIAL-DNA MUTATIONS; PERMEABILITY TRANSITION PORE; FAILING HUMAN HEART; AGE-RELATED-CHANGES; RAT LEFT-VENTRICLE; MYOCYTE CELL LOSS; GENE-EXPRESSION; CARDIAC-HYPERTROPHY; CARDIOVASCULAR-DISEASE AB Western societies are rapidly aging, and cardiovascular diseases are the leading cause of death. In fact, age and cardiovascular diseases are positively correlated, and disease syndromes affecting the heart reach epidemic proportions in the very old. Genetic variations and molecular adaptations are the primary contributors to the onset of cardiovascular disease; however, molecular links between age and heart syndromes are complex and involve much more than the passage of time. Changes in CM (cardiomyocyte) structure and function occur with age and precede anatomical and functional changes in the heart. Concomitant with or preceding some of these cellular changes are alterations in gene expression often linked to signalling cascades that may lead to a loss of CMs or reduced function. An understanding of the intrinsic molecular mechanisms underlying these cascading events has been instrumental in forming our current understanding of how CMs adapt with age. In the present review, we describe the molecular mechanisms underlying CM aging and how these changes may contribute to the development of cardiovascular diseases. C1 [Sheydina, Anna; Riordon, Daniel R.; Boheler, Kenneth R.] NIA, Cardiovasc Sci Lab, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Boheler, KR (reprint author), NIA, Cardiovasc Sci Lab, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov FU National Institutes of Health National Institute on Aging FX Our own work was supported entirely by the Intramural Research Program of the National Institutes of Health National Institute on Aging. NR 151 TC 19 Z9 22 U1 2 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD OCT PY 2011 VL 121 IS 7-8 BP 315 EP 329 DI 10.1042/CS20110115 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 836OG UT WOS:000296120400005 PM 21699498 ER PT J AU Conlon, ASC Taylor, JMG Sargent, DJ Yothers, G AF Conlon, Anna S. C. Taylor, Jeremy M. G. Sargent, Daniel J. Yothers, Greg TI Using cure models and multiple imputation to utilize recurrence as an auxiliary variable for overall survival SO CLINICAL TRIALS LA English DT Article ID INDIVIDUAL PATIENT DATA; SURROGATE END-POINTS; 18 RANDOMIZED-TRIALS; CLINICAL-TRIALS; MIXTURE MODEL; COLON-CANCER; MARKER; TIME AB Background Intermediate outcome variables can often be used as auxiliary variables for the true outcome of interest in randomized clinical trials. For many cancers, time to recurrence is an informative marker in predicting a patient's overall survival outcome and could provide auxiliary information for the analysis of survival times. Purpose To investigate whether models linking recurrence and death combined with a multiple imputation procedure for censored observations can result in efficiency gains in the estimation of treatment effects and be used to shorten trial lengths. Methods Recurrence and death times are modeled using data from 12 trials in colorectal cancer. Multiple imputation is used as a strategy for handling missing values arising from censoring. The imputation procedure uses a cure model for time to recurrence and a time-dependent Weibull proportional hazards model for time to death. Recurrence times are imputed, and then death times are imputed conditionally on recurrence times. To illustrate these methods, trials are artificially censored 2 years after the last accrual, the imputation procedure implemented, and a log-rank test and Cox model used to analyze and compare these new data with the original data. Results The results show modest, but consistent gains in efficiency in the analysis using the auxiliary information in recurrence times. Comparison of analyses show the treatment effect estimates and log-rank test results from the 2-year censored imputed data to be in between the estimates from the original data and the artificially censored data, indicating that the procedure was able to recover some of the lost information due to censoring. Limitations The models used are all fully parametric, requiring distributional assumptions of the data. Conclusions The proposed models may be useful in improving the efficiency in estimation of treatment effects in cancer trials and shortening trial length. Clinical Trials 2011; 8: 581-590. http://ctj.sagepub.com C1 [Conlon, Anna S. C.; Taylor, Jeremy M. G.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Sargent, Daniel J.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Mayo Clin, Rochester, MN USA. [Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Yothers, Greg] Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Dept Biostat, Pittsburgh, PA 15261 USA. RP Taylor, JMG (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, 1420 Washington Hts, Ann Arbor, MI 48109 USA. EM jmgt@umich.edu OI Yothers, Greg/0000-0002-7965-7333; Sargent, Daniel/0000-0002-2684-4741 FU NIH [CA129102, CA083654, GM74910] FX This research was partially supported by NIH grants CA129102, CA083654 and GM74910. NR 21 TC 4 Z9 4 U1 0 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2011 VL 8 IS 5 BP 581 EP 590 DI 10.1177/1740774511414741 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 835FI UT WOS:000296020500004 PM 21921063 ER PT J AU Kernan, W Viscoli, C Brass, L Amatangelo, M Birch, A Clark, W Conwit, R Furie, K Gorman, M Pesapane, B Kleindorfer, D Lovejoy, A Osborne, J Silliman, S Zweifler, R Horwitz, R AF Kernan, W. Viscoli, C. Brass, L. Amatangelo, M. Birch, A. Clark, W. Conwit, R. Furie, K. Gorman, M. Pesapane, B. Kleindorfer, D. Lovejoy, A. Osborne, J. Silliman, S. Zweifler, R. Horwitz, R. TI Boosting enrolment in clinical trials: validation of a regional network model SO CLINICAL TRIALS LA English DT Article ID STROKE; RECRUITMENT; SYSTEM AB Background Clinical trials of stroke therapy have been hampered by slow rates of enrolment. Purpose Our purpose is to validate a previously developed model for accelerating enrolment in clinical trials by replicating it at new locations. The model employs coordinators who travel from a host institution to enrol participants from a network of participating hospitals. Active surveillance assures identification of all eligible patients. Methods Among 70 U. S. investigators participating in National Institutes of Health-funded trial of stroke prevention, five investigators were invited to develop local identification and outreach networks (LIONs). Each LION comprised a LION coordinating centre servicing multiple hospitals. Hospitals provided names of patients with stroke or transient ischaemic attack to researchers at the LION coordinating centre who initiated contact; patients were offered home visits for consent and randomization. Outcomes were feasibility, enrolment, data quality, and cost. Results Five LIONs varied in size from two to eight hospitals. All 24 hospitals we approached agreed to participate. The average monthly rate of enrolment at the research sites increased from 1.4 participants to 3.5 after expanding from a single institution model to the LION format (mean change = 2.1, range 0.9-3.7). Monthly performance improved over time. Data quality was similar for LIONs and non-LION sites, except for drug adherence which was lower at LIONs. The average cost to randomize and follow one participant during the study interval was 2.4 times the cost under the per-patient, cost-reimbursement strategy at non-LION sites. The cost ratio declined from 3.4 in year one to 1.8 in year two. Limitations The LION strategy requires unprecedented collaboration and trust among institutions. Applicability beyond stroke requires confirmation. Conclusion LIONs are a practical, reproducible method to increase enrolment in trial research. Twelve months were required for the average site to reach its potential. The per-participant cost at LIONs was higher than conventional sites but declined over time. Clinical Trials 2011; 8: 645-653. http://ctj.sagepub.com C1 [Kernan, W.] IRIS Coordinating Ctr, New Haven, CT USA. [Viscoli, C.; Brass, L.; Pesapane, B.; Lovejoy, A.] Yale Univ, Sch Med, New Haven, CT USA. [Amatangelo, M.; Birch, A.; Furie, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, W.] Oregon Hlth & Sci Univ, Portland, OR USA. [Conwit, R.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Gorman, M.] Univ Vermont, Burlington, VT USA. [Kleindorfer, D.; Osborne, J.] Univ Cinncinati, Cinncinati, OH USA. [Silliman, S.] Univ Florida, Coll Medicine Jacksonville, Jacksonville, FL USA. [Zweifler, R.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Horwitz, R.] Glaxo Smithkline, Philadelphia, PA USA. RP Kernan, W (reprint author), IRIS Coordinating Ctr, Suite 515 2 Church St S, New Haven, CT USA. EM walter.kernan@yale.edu RI Zweifler, Richard/K-1314-2015 FU National Institutes of Neurological Disorders and Stroke (NINDS) [U01 NS044876] FX This work was supported by the National Institutes of Neurological Disorders and Stroke (NINDS) (U01 NS044876). Placebo and pioglitazone tablets were supplied by Takeda Pharmaceuticals North America, Inc. NR 14 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2011 VL 8 IS 5 BP 645 EP 653 DI 10.1177/1740774511414925 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 835FI UT WOS:000296020500011 PM 21824978 ER PT J AU Jiang, CT Qu, AJ Matsubara, T Chanturiya, T Jou, W Gavrilova, O Shah, YM Gonzalez, FJ AF Jiang, Changtao Qu, Aijuan Matsubara, Tsutomu Chanturiya, Tatyana Jou, William Gavrilova, Oksana Shah, Yatrik M. Gonzalez, Frank J. TI Disruption of Hypoxia-Inducible Factor 1 in Adipocytes Improves Insulin Sensitivity and Decreases Adiposity in High-Fat Diet-Fed Mice SO DIABETES LA English DT Article ID OBESE MICE; LIPID-METABOLISM; CYTOKINE SIGNALING-3; TISSUE HYPOXIA; ACID OXIDATION; FACTOR 1-ALPHA; RESISTANCE; ADIPONECTIN; DIFFERENTIATION; SUPPRESSOR AB OBJECTIVE-Obesity, insulin resistance, and type 2 diabetes form a tightly correlated cluster of metabolic disorders in which adipose is one of the first affected tissues. The role of hypoxia and hypoxia-inducible factor 1 (HIF1) in the development of high-fat diet (HFD)-induced obesity and insulin resistance was investigated using animal models. RESEARCH DESIGN AND METHODS-Mice with adipocyte-specific targeted disruption of the genes encoding the HIFI obligatory subunits Hif1 alpha or Arnt (Hif1 beta) were generated using an aP2-Cre transgene with the Cre/LoxP system. The mice were fed an HFD for 12 weeks and their metabolic phenotypes were determined. Gene expression patterns in adipose tissues were also determined by microarray and quantitative PCR. RESULTS-On an HFD, adipocyte-specific ARNT knockout mice and adipocyte-specific HIF1 alpha knockout mice exhibit similar metabolic phenotypes, including reduced fat formation, protection from HFD-induced obesity, and insulin resistance compared with similarly fed wild-type controls. The cumulative food intake remained similar; however, the metabolic efficiency was lower in adipocyte-specific HIF1 alpha knockout mice. Moreover, indirect calorimetry revealed respiratory exchange ratios were reduced in adipocyte-specific HIF1 alpha knockout mice. Hyperinsulinemic-euglycemic clamp studies demonstrated that targeted disruption of HIF1 alpha in adipocytes enhanced whole-body insulin sensitivity. The improvement of insulin resistance is associated with decreased expression of Socs3 and induction of adiponectin. CONCLUSIONS-Inhibition of HIF1 in adipose tissue ameliorates obesity and insulin resistance. This study reveals that HIF1 could provide a novel potential therapeutic target for obesity and type 2 diabetes. Diabetes 60:2484-2495, 2011 C1 [Jiang, Changtao; Qu, Aijuan; Matsubara, Tsutomu; Shah, Yatrik M.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Chanturiya, Tatyana; Jou, William; Gavrilova, Oksana] Natl Inst Diabet & Digest & Kidney Dis, Mouse Metab Core Lab, NIH, Bethesda, MD USA. [Shah, Yatrik M.] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol & Internal Med, Div Gastroenterol, Ann Arbor, MI USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov FU National Cancer Institute; National Institute of Diabetes; Digestive and Kidney Diseases Intramural Research Programs; National Institutes of Health [CA-148828] FX This study was supported by the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Programs and National Institutes of Health Grant CA-148828 (to Y.M.S.). NR 41 TC 91 Z9 94 U1 2 U2 19 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2011 VL 60 IS 10 BP 2484 EP 2495 DI 10.2337/db11-0174 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834XV UT WOS:000295998700007 PM 21873554 ER PT J AU Faulhaber-Walter, R Jou, W Mizel, D Li, LL Zhang, JD Kim, SM Huang, YN Chen, M Briggs, JP Gavrilova, O Schnermann, JB AF Faulhaber-Walter, Robert Jou, William Mizel, Diane Li, Lingli Zhang, Jiandi Kim, Soo Mi Huang, Yuning Chen, Min Briggs, Josephine P. Gavrilova, Oksana Schnermann, Jurgen B. TI Impaired Glucose Tolerance in the Absence of Adenosine A1 Receptor Signaling SO DIABETES LA English DT Article ID RAT SKELETAL-MUSCLE; IMPROVES INSULIN-RESISTANCE; A(1) ADENOSINE RECEPTORS; A1 RECEPTOR; LATERAL HYPOTHALAMUS; SLEEP-WAKEFULNESS; WHITE ADIPOCYTES; BODY-COMPOSITION; GROWTH-HORMONE; ADIPOSE-TISSUE AB OBJECTIVE-The role of adenosine (ADO) in the regulation of glucose homeostasis is not clear. In the current study, we used A1-ADO receptor (A1AR)-deficient mice to investigate the role of ADO/A1AR signaling for glucose homeostasis. RESEARCH DESIGN AND METHODS-After weaning, A1AR(-/-) and wild-type mice received either a standard diet (12 kcal% fat) or high-fat diet (HFD; 45 kcal% fat). Body weight, fasting plasma glucose, plasma insulin, and intraperitoneal glucose tolerance tests were performed in 8-week-old mice and again after 12-20 weeks of subsequent observation. Body composition was quantified by magnetic resonance imaging and epididymal fat-pad weights. Glucose metabolism was investigated by hyperinsulinemic-euglycemic clamp studies. To describe pathophysiological mechanisms, adipokines and Akt phosphorylation were measured. RESULTS-A1AR(-/-) mice were significantly heavier than wild-type mice because of an increased fat mass. Fasting plasma glucose and insulin were significantly higher in A1AR(-/-) mice after weaning and remained higher in adulthood. An intraperitoneal glucose challenge disclosed a significantly slower glucose clearance in A1AR(-/-) mice. An HFD enhanced this phenotype in A1AR(-/-) mice and unmasked a dysfunctional insulin secretory mechanism. Insulin sensitivity was significantly impaired in A1AR(-/-) mice on the standard diet shortly after weaning. Clamp studies detected a significant decrease of net glucose uptake in A1AR(-/-) mice and a reduced glucose uptake in muscle and white adipose tissue. Effects were not triggered by leptin deficiency but involved a decreased Akt phosphorylation. CONCLUSIONS-ADO/A1AR signaling contributes importantly to insulin-controlled glucose homeostasis and insulin sensitivity in C57BL/6 mice and is involved in the metabolic regulation of adipose tissue. Diabetes 60:2578-2587, 2011 C1 [Faulhaber-Walter, Robert; Jou, William; Mizel, Diane; Li, Lingli; Zhang, Jiandi; Kim, Soo Mi; Huang, Yuning; Chen, Min; Gavrilova, Oksana; Schnermann, Jurgen B.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. [Briggs, Josephine P.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Faulhaber-Walter, R (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. EM rofaulhaber@web.de RI Briggs, Josephine/B-9394-2009; OI Briggs, Josephine/0000-0003-0798-1190; Faulhaber-Walter, Robert/0000-0002-7769-9652 FU National Institutes of Health (NIH) FX This work was funded by a postdoctoral fellowship award of the National Institutes of Health (NIH) (to R.F.-W.). NR 47 TC 23 Z9 24 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2011 VL 60 IS 10 BP 2578 EP 2587 DI 10.2337/db11-0058 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834XV UT WOS:000295998700017 PM 21831968 ER PT J AU Strawbridge, RJ Dupuis, J Prokopenko, I Barker, A Ahlqvist, E Rybin, D Petrie, JR Travers, ME Bouatia-Naji, N Dimas, AS Nica, A Wheeler, E Chen, H Voight, BF Taneera, J Kanoni, S Peden, JF Turrini, F Gustafsson, S Zabena, C Almgren, P Barker, DJP Barnes, D Dennison, EM Eriksson, JG Eriksson, P Eury, E Folkersen, L Fox, CS Frayling, TM Goel, A Gu, HF Horikoshi, M Isomaa, B Jackson, AU Jameson, KA Kajantie, E Kerr-Conte, J Kuulasmaa, T Kuusisto, J Loos, RJF Luan, JA Makrilakis, K Manning, AK Martinez-Larrad, MT Narisu, N Mannila, MN Ohrvik, J Osmond, C Pascoe, L Payne, F Sayer, AA Sennblad, B Silveira, A Stancakova, A Stirrups, K Swift, AJ Syvanen, AC Tuomi, T van 't Hooft, FM Walker, M Weedon, MN Xie, WJ Zethelius, B Ongen, H Malarstig, A Hopewell, JC Saleheen, D Chambers, J Parish, S Danesh, J Kooner, J Ostenson, CG Lind, L Cooper, CC Serrano-Rios, M Ferrannini, E Forsen, TJ Clarke, R Franzosi, MG Seedorf, U Watkins, H Froguel, P Johnson, P Deloukas, P Collins, FS Laakso, M Dermitzakis, ET Boehnke, M McCarthy, MI Wareham, NJ Groop, L Pattou, F Gloyn, AL Dedoussis, GV Lyssenko, V Meigs, JB Barroso, I Watanabe, RM Ingelsson, E Langenberg, C Hamsten, A Florez, JC AF Strawbridge, Rona J. Dupuis, Josee Prokopenko, Inga Barker, Adam Ahlqvist, Emma Rybin, Denis Petrie, John R. Travers, Mary E. Bouatia-Naji, Nabila Dimas, Antigone S. Nica, Alexandra Wheeler, Eleanor Chen, Han Voight, Benjamin F. Taneera, Jalal Kanoni, Stavroula Peden, John F. Turrini, Fabiola Gustafsson, Stefan Zabena, Carina Almgren, Peter Barker, David J. P. Barnes, Daniel Dennison, Elaine M. Eriksson, Johan G. Eriksson, Per Eury, Elodie Folkersen, Lasse Fox, Caroline S. Frayling, Timothy M. Goel, Anuj Gu, Harvest F. Horikoshi, Momoko Isomaa, Bo Jackson, Anne U. Jameson, Karen A. Kajantie, Eero Kerr-Conte, Julie Kuulasmaa, Teemu Kuusisto, Johanna Loos, Ruth J. F. Luan, Jian'an Makrilakis, Konstantinos Manning, Alisa K. Teresa Martinez-Larrad, Maria Narisu, Narisu Mannila, Maria Nastase Ohrvik, John Osmond, Clive Pascoe, Laura Payne, Felicity Sayer, Avan A. Sennblad, Bengt Silveira, Angela Stancakova, Alena Stirrups, Kathy Swift, Amy J. Syvanen, Ann-Christine Tuomi, Tiinamaija van 't Hooft, Ferdinand M. Walker, Mark Weedon, Michael N. Xie, Weijia Zethelius, Bjorn Ongen, Halit Malarstig, Anders Hopewell, Jemma C. Saleheen, Danish Chambers, John Parish, Sarah Danesh, John Kooner, Jaspal Ostenson, Claes-Goran Lind, Lars Cooper, Cyrus C. Serrano-Rios, Manuel Ferrannini, Ele Forsen, Tom J. Clarke, Robert Franzosi, Maria Grazia Seedorf, Udo Watkins, Hugh Froguel, Philippe Johnson, Paul Deloukas, Panos Collins, Francis S. Laakso, Markku Dermitzakis, Emmanouil T. Boehnke, Michael McCarthy, Mark I. Wareham, Nicholas J. Groop, Leif Pattou, Francois Gloyn, Anna L. Dedoussis, George V. Lyssenko, Valeriya Meigs, James B. Barroso, Ines Watanabe, Richard M. Ingelsson, Erik Langenberg, Claudia Hamsten, Anders Florez, Jose C. CA DIAGRAM Consortium GIANT Consortium MuTHER Consortium CARDIoGRAM Consortium C4D Consortium TI Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes SO DIABETES LA English DT Article ID CORONARY HEART-DISEASE; BETA-CELL FUNCTION; SUSCEPTIBILITY LOCI; GLUCOSE-HOMEOSTASIS; INSULIN SENSITIVITY; POPULATION; TCF7L2; RISK; OBESITY; METAANALYSIS AB OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS-We have conducted a meta-analysis of genome-wide association tests of similar to 2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS-Nine SNPs at eight loci were associated with proinsulin levels (P < 5 x 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC3OA8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 x 10(-4)), improved beta-cell function (P = 1.1 x 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 x 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS-We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis. Diabetes 60:2624-2634, 2011 C1 [Voight, Benjamin F.; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Strawbridge, Rona J.; Eriksson, Per; Mannila, Maria Nastase; Ohrvik, John; Sennblad, Bengt; Silveira, Angela; van 't Hooft, Ferdinand M.; Malarstig, Anders; Hamsten, Anders] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden. [Dupuis, Josee; Chen, Han; Manning, Alisa K.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Prokopenko, Inga; Travers, Mary E.; Horikoshi, Momoko; Johnson, Paul; McCarthy, Mark I.; Gloyn, Anna L.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Prokopenko, Inga; Dimas, Antigone S.; Peden, John F.; Goel, Anuj; Horikoshi, Momoko; Ongen, Halit; Watkins, Hugh; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Barker, Adam; Barnes, Daniel; Loos, Ruth J. F.; Luan, Jian'an; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Ahlqvist, Emma; Taneera, Jalal; Turrini, Fabiola; Almgren, Peter; Groop, Leif; Lyssenko, Valeriya] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Univ Hosp & Malmo, Malmo, Sweden. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Petrie, John R.] Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Bouatia-Naji, Nabila; Eury, Elodie; Kerr-Conte, Julie; Froguel, Philippe; Pattou, Francois] Univ Lille Nord France, Lille, France. [Bouatia-Naji, Nabila; Eury, Elodie; Froguel, Philippe] Inst Pasteur, CNRS UMR 8199, Lille, France. [Dimas, Antigone S.; Nica, Alexandra; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Wheeler, Eleanor; Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton, England. [Voight, Benjamin F.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Voight, Benjamin F.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Kanoni, Stavroula; Dedoussis, George V.] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Peden, John F.; Goel, Anuj; Ongen, Halit; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Turrini, Fabiola] Univ Verona, Dept Med, I-37100 Verona, Italy. [Gustafsson, Stefan; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Zabena, Carina; Teresa Martinez-Larrad, Maria; Serrano-Rios, Manuel] CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid, Spain. [Zabena, Carina; Teresa Martinez-Larrad, Maria; Serrano-Rios, Manuel] Hosp Clin San Carlos, Fdn Invest Biomed, Madrid, Spain. [Barker, David J. P.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. [Dennison, Elaine M.; Jameson, Karen A.; Osmond, Clive; Sayer, Avan A.; Cooper, Cyrus C.] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Eriksson, Johan G.; Kajantie, Eero] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.] Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.; Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.; Forsen, Tom J.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Folkersen, Lasse] Karolinska Inst, Dept Med Solna, Expt Cardiovasc Res Unit, Stockholm, Sweden. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Frayling, Timothy M.; Weedon, Michael N.; Xie, Weijia] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Gu, Harvest F.; Ostenson, Claes-Goran] Karolinska Inst, Endocrinol & Diabet Unit, Dept Mol Med & Surg, Stockholm, Sweden. [Isomaa, Bo] Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland. [Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Kajantie, Eero] Helsinki Univ Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. [Kerr-Conte, Julie; Pattou, Francois] INSERM, UMR 859, F-59045 Lille, France. [Kuulasmaa, Teemu; Kuusisto, Johanna; Stancakova, Alena; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuulasmaa, Teemu; Kuusisto, Johanna; Stancakova, Alena; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Makrilakis, Konstantinos] Univ Athens, Sch Med, Laiko Gen Hosp, Dept Propaedeut Med 1, GR-11527 Athens, Greece. [Narisu, Narisu; Swift, Amy J.] Natl Human Genome Res Inst, NIH, Bethesda, MD USA. [Pascoe, Laura] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Syvanen, Ann-Christine; Lind, Lars] Uppsala Univ, Sci Life Lab, Dept Med Sci, Uppsala, Sweden. [Tuomi, Tiinamaija] Helsinki Univ Cent Hosp, Dept Med, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Zethelius, Bjorn] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Ongen, Halit] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Hopewell, Jemma C.; Parish, Sarah; Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Saleheen, Danish; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Saleheen, Danish] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan. [Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Chambers, John; Kooner, Jaspal] Ealing Hosp NHS Trust, Middlesex, England. [Ferrannini, Ele] Univ Pisa, Sch Med, Dept Internal Med, I-56100 Pisa, Italy. [Ferrannini, Ele] Univ Pisa, Sch Med, CNR Inst Clin Physiol, I-56100 Pisa, Italy. [Forsen, Tom J.] Vaasa Hlth Care Ctr, Vaasa, Finland. [Franzosi, Maria Grazia] Mario Negri Inst Pharmacol Res, Dept Cardiovasc Res, Milan, Italy. [Seedorf, Udo] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Hammersmith Hosp, Dept Genom Common Dis, London, England. [Johnson, Paul] Univ Oxford, DRWF Human Islet Isolat Facil, Oxford, England. [Johnson, Paul] Univ Oxford, Oxford Islet Transplant Programme, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Florez, JC (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. EM claudia.langenberg@mrc-epid.cam.ac.uk; anders.hamsten@ki.se; jcflorez@partners.org RI Smith, Albert Vernon/K-5150-2015; Erdmann, Jeanette/P-7513-2014; Aulchenko, Yurii/M-8270-2013; Visvikis-Siest, Sophie/H-2324-2014; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Schwarz, Peter/B-5127-2013; Leander, Karin/C-7261-2017; Feitosa, Mary/K-8044-2012; Zondervan, Krina/M-1143-2013; Cooper, Matthew/J-4420-2014; Strawbridge, Rona/H-5422-2012; Palmer, Lyle/K-3196-2014; Witte, Daniel/C-1722-2008; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Prokopenko, Inga/H-3241-2014; Aben, Katja/G-9686-2016; Stark, Klaus/D-3813-2009; Kiemeney, Lambertus/D-3357-2009; Aihie Sayer, Avan/A-4359-2012; Willenborg, Christina/D-2668-2012; Ridderstrale, Martin/F-7678-2012; Elliott, Amanda/G-5120-2012; Rudan, Igor/I-1467-2012; Barker, David/A-5671-2013; Deloukas, Panos/B-2922-2013; Dermitzakis, Emmanouil/B-7687-2013; 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Palmer, Colin/0000-0002-6415-6560; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Aihie Sayer, Avan/0000-0003-1283-6457; Esko, Tonu/0000-0003-1982-6569; Smith, Albert Vernon/0000-0003-1942-5845; Stewart, Alexandre/0000-0003-2673-9164; Manunta, Paolo/0000-0003-3976-9696; Zeggini, Eleftheria/0000-0003-4238-659X; Erdmann, Jeanette/0000-0002-4486-6231; Dupuis, Josee/0000-0003-2871-3603; Peyvandi, Flora/0000-0001-7423-9864; Luben, Robert/0000-0002-5088-6343; van Dam, Rob/0000-0002-7354-8734; Sijbrands, Eric/0000-0001-8857-7389; Goddard, Michael/0000-0001-9917-7946; Griffin, Simon/0000-0002-2157-4797; Marre, Michel/0000-0002-3071-1837; Barnes, Daniel/0000-0002-3781-7570; Johnson, Toby/0000-0002-5998-3270; Cappuccio, Francesco Paolo/0000-0002-7842-5493; Macciardi, Fabio/0000-0003-0537-4266; Lango Allen, Hana/0000-0002-7803-8688; Bouatia-Naji, Nabila/0000-0001-5424-2134; Magi, Reedik/0000-0002-2964-6011; Zgaga, Lina/0000-0003-4089-9703; Rybin, Denis/0000-0002-3657-4829; Willer, Cristen/0000-0001-5645-4966; Meisinger, Christa/0000-0002-9026-6544; Beckmann, Jacques S /0000-0002-9741-1900; Pichler, Irene/0000-0001-8251-0757; ELOSUA, ROBERTO/0000-0001-8235-0095; Aulchenko, Yurii/0000-0002-7899-1575; Visvikis-Siest, Sophie/0000-0001-8104-8425; Hayward, Caroline/0000-0002-9405-9550; Schwarz, Peter/0000-0001-6317-7880; Leander, Karin/0000-0002-1404-9222; Feitosa, Mary/0000-0002-0933-2410; Seedorf, Udo/0000-0003-4652-5358; Thiering, Elisabeth/0000-0002-5429-9584; Kaakinen, Marika/0000-0002-9228-0462; Zondervan, Krina/0000-0002-0275-9905; Cooper, Matthew/0000-0003-1139-3682; Strawbridge, Rona/0000-0001-8506-3585; Palmer, Lyle/0000-0002-1628-3055; Witte, Daniel/0000-0002-0769-2922; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862; Prokopenko, Inga/0000-0003-1624-7457; Aben, Katja/0000-0002-0214-2147; Stark, Klaus/0000-0002-7832-1942; Kiemeney, Lambertus/0000-0002-2368-1326; Willenborg, Christina/0000-0001-5217-6882; Rudan, Igor/0000-0001-6993-6884; Deloukas, Panos/0000-0001-9251-070X; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X FU British Heart Foundation [RG/08/014/24067]; Diabetes UK [08/0003775]; Medical Research Council [MC_UP_A620_1014, 81696, G0601261, G0601966, G0700222, G0700222(81696), G0700931, G0801056, MC_PC_U127561128, MC_PC_U127592696, MC_U106188470, MC_U127561128, MC_U137686857, MC_UP_A620_1015]; NHLBI NIH HHS [R01 HL087647, U01 HL054527]; NIDDK NIH HHS [DK062370, K24 DK080140, R01 DK078616]; Wellcome Trust [077016/Z/05/Z, 083270/Z/07/Z, 090532] NR 47 TC 128 Z9 134 U1 3 U2 50 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2011 VL 60 IS 10 BP 2624 EP 2634 DI 10.2337/db11-0415 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834XV UT WOS:000295998700022 PM 21873549 ER PT J AU Park, BJ Pappas, PG Wannemuehler, KA Alexander, BD Anaissie, EJ Andes, DR Baddley, JW Brown, JM Brumble, LM Freifeld, AG Hadley, S Herwaldt, L Ito, JI Kauffman, CA Lyon, GM Marr, KA Morrison, VA Papanicolaou, G Patterson, TF Perl, TM Schuster, MG Walker, R Wingard, JR Walsh, TJ Kontoyiannis, DP AF Park, Benjamin J. Pappas, Peter G. Wannemuehler, Kathleen A. Alexander, Barbara D. Anaissie, Elias J. Andes, David R. Baddley, John W. Brown, Janice M. Brumble, Lisa M. Freifeld, Alison G. Hadley, Susan Herwaldt, Loreen Ito, James I. Kauffman, Carol A. Lyon, G. Marshall Marr, Kieren A. Morrison, Vicki A. Papanicolaou, Genovefa Patterson, Thomas F. Perl, Trish M. Schuster, Mindy G. Walker, Randall Wingard, John R. Walsh, Thomas J. Kontoyiannis, Dimitrios P. TI Invasive Non-Aspergillus Mold Infections in Transplant Recipients, United States, 2001-2006 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HEMATOPOIETIC STEM-CELL; CARE CANCER CENTER; SURVEILLANCE NETWORK TRANSNET; FUNGAL-INFECTIONS; HEMATOLOGIC MALIGNANCIES; BREAKTHROUGH ZYGOMYCOSIS; SCEDOSPORIUM-PROLIFICANS; RECEIVING VORICONAZOLE; ANTIFUNGAL THERAPY; EPIDEMIOLOGY AB Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HOT recipients increased substantially during the surveillance period. C1 [Park, Benjamin J.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Pappas, Peter G.; Baddley, John W.] Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. [Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA. [Anaissie, Elias J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Andes, David R.] Univ Wisconsin, Madison, WI USA. [Brown, Janice M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA. [Freifeld, Alison G.] Univ Nebraska Med Ctr, Omaha, NE USA. [Hadley, Susan] Tufts Med Ctr, Boston, MA USA. [Herwaldt, Loreen] Univ Iowa Hosp, Iowa City, IA USA. [Ito, James I.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst Med, Ann Arbor, MI USA. [Lyon, G. Marshall] Emory Univ, Sch Med, Atlanta, GA USA. [Marr, Kieren A.; Perl, Trish M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA. [Morrison, Vicki A.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Papanicolaou, Genovefa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Schuster, Mindy G.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Walker, Randall] Mayo Clin, Rochester, MN USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Walsh, Thomas J.] NIH, Bethesda, MD 20892 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Park, BJ (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd NE,Mailstop C09, Atlanta, GA 30333 USA. EM bpark1@cdc.gov OI Papanicolaou, Genovefa/0000-0002-2891-079X; Patterson, Thomas /0000-0002-9513-7127 FU Centers for Disease Control and Prevention [5U01CI000286-05]; Merck Co., Inc.; Astellas U.S., Inc.; Pfizer, Inc.; Schering-Plough Research Institute; Enzon Pharmaceuticals, Inc. FX This study was supported through Centers for Disease Control and Prevention Grant 5U01CI000286-05 and grants from Merck & Co., Inc.; Astellas U.S., Inc.; Pfizer, Inc.; Schering-Plough Research Institute; and Enzon Pharmaceuticals, Inc. NR 35 TC 74 Z9 74 U1 0 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT PY 2011 VL 17 IS 10 BP 1855 EP 1864 DI 10.3201/eid1710.110087 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 833PL UT WOS:000295897300009 PM 22000355 ER PT J AU Silbergleit, R Lowenstein, D Durkalski, V Conwit, R AF Silbergleit, Robert Lowenstein, Daniel Durkalski, Valerie Conwit, Robin CA Neurological Emergency Treatment TI RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): A double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics SO EPILEPSIA LA English DT Article DE Binary outcome; Intravenous; Intramuscular; Lorazepam; Midazolam; Placebo; Seizure termination ID DIAZEPAM AB Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting has been shown to be associated with improved outcomes. However, an increasing number of Emergency Medical System (EMS) protocols use an intramuscular (IM) route because it is faster and consistently achievable. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) is a double-blind randomized clinical trial to determine if the efficacy of IM midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). Children and adults with >5 min of convulsions who are still seizing after paramedic arrival are administered study medication by IM autoinjector or IV infusion. The primary efficacy outcome is absence of seizures at emergency department (ED) arrival, without EMS rescue therapy. Safety outcomes include acute endotracheal intubation and recurrent seizures. Secondary outcomes include timing of treatment and initial seizure cessation. At the time of writing this communication, enrollment of all subjects is near completion and the study data will soon be analyzed. C1 [Lowenstein, Daniel] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Silbergleit, Robert] Univ Michigan Hlth Syst, Dept Emergency Med, Ann Arbor, MI USA. [Durkalski, Valerie] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Conwit, Robin] NINDS, Div Extramural Res, Bethesda, MD 20892 USA. RP Lowenstein, D (reprint author), Univ Calif San Francisco, Dept Neurol, 505 Parnussus Ave,Room M-794, San Francisco, CA 94143 USA. EM lowenstein@medsch.ucsf.edu FU National Institute of Neurological Disorders and Stroke (NINDS) [5U01NS056975-04]; Office of the Director, National Institutes of Health (OD); BARDA; NIH FX This work is supported by award 5U01NS056975-04 from the National Institute of Neurological Disorders and Stroke (NINDS), the Office of the Director, National Institutes of Health (OD), BARDA, and the NIH CounterACT program. This trial is registered with Clinical Trials.gov (NCT00809146). NR 4 TC 26 Z9 27 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2011 VL 52 SU 8 SI SI BP 45 EP 47 DI 10.1111/j.1528-1167.2011.03235.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 835VR UT WOS:000296065200015 PM 21967361 ER PT J AU Propst, AM Hill, MJ Bates, GW Palumbo, M Van Horne, AK Retzloff, MG AF Propst, Anthony M. Hill, Micah J. Bates, Gordon Wright Palumbo, Michelle Van Horne, Anne K. Retzloff, Matthew G. TI Low-dose human chorionic gonadotropin may improve in vitro fertilization cycle outcomes in patients with low luteinizing hormone levels after gonadotropin-releasing hormone antagonist administration SO FERTILITY AND STERILITY LA English DT Article DE GnRH antagonist; IVF; low-dose uhCG; luteinizing hormone ID FOLLICLE-STIMULATING-HORMONE; CONTROLLED OVARIAN STIMULATION; HUMAN MENOPAUSAL GONADOTROPIN; RECOMBINANT HUMAN FSH; HIGHLY PURIFIED HMG; INTRACYTOPLASMIC SPERM INJECTION; HUMAN LH SUPPLEMENTATION; EARLY-PREGNANCY LOSS; NORMOGONADOTROPHIC WOMEN; ASSISTED REPRODUCTION AB Objective: To evaluate the effect of low levels of endogenous luteinizing hormone (LH) and low-dose human chorionic gonadotropin (hCG) supplementation on in vitro fertilization (IVF) cycle outcomes in a gonadotropin-releasing hormone (GnRH) antagonist protocol. Design: Retrospective study. Setting: Military medical center. Patient(s): General in vitro fertilization/embryo transfer (IVF-ET) population. Intervention(s): Addition of low-dose urinary hCG to IVF stimulations using a recombinant follicle-stimulating hormone (FSH) and GnRH antagonist protocol. Main Outcome Measure(s): Implantation and live-birth rates. Result(s): As part of a larger cohort of 239 patients, 42 patients with LH levels <= 0.5 mIU/mL were evaluated. In the larger cohort, there were no differences in implantation and pregnancy rates between the recombinant FSH only (n = 113) and the recombinant FSH with low-dose hCG supplementation (n = 126) groups. In the FSH-only group, patients with LH levels <= 0.5 mIU/mL had decreased implantation rates (19% vs. 42%) and live-birth rates (25% vs. 54%) as compared with patients with LH levels >0.5 mIU/mL. Low LH patients in the recombinant FSH with low-dose urinary hCG group had statistically significantly higher implantation rates (54% vs. 19%) and live-birth rates (64% vs. 25%) as compared with patients with similar low LH levels in the recombinant FSH-only group. Conclusion(s): Endogenous LH levels <= 0.5 mIU/mL after GnRH antagonist treatment are associated with statistically significantly lower implantation and pregnancy rates in recombinant FSH-only cycles. The addition of low-dose urinary hCG results in improved implantation and live-birth rates in patients with low LH levels. (Fertil Steril (R) 2011; 96: 898-904. (C) 2011 by American Society for Reproductive Medicine.) C1 [Propst, Anthony M.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Propst, Anthony M.; Hill, Micah J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Propst, Anthony M.; Bates, Gordon Wright; Palumbo, Michelle; Van Horne, Anne K.; Retzloff, Matthew G.] San Antonio Uniformed Serv Hlth Educ Consortium, Div Reprod Endocrinol, Wilford Hall Med Ctr, San Antonio, TX USA. RP Propst, AM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM anthony.propst@usuhs.mil FU Ferring; Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX A.M.P. has received consulting fees from Ferring. M.J.H. has nothing to disclose. G.W.B. has nothing to disclose. M.P. has nothing to disclose. A.K.V.H. has nothing to disclose. M.G.R. has nothing to disclose.; Supported in part by the Intramural research program of the Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The opinions and conclusions in this paper are those of the authors and are not intended to represent the official position of the Department of Defense, United States Air Force, United States Army or any other government agency. NR 69 TC 5 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2011 VL 96 IS 4 BP 898 EP 904 DI 10.1016/j.fertnstert.2011.06.069 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 834DF UT WOS:000295938800030 PM 21839437 ER PT J AU Achyut, BR Yang, L AF Achyut, Bhagelu Ram Yang, Li TI Transforming Growth Factor-beta in the Gastrointestinal and Hepatic Tumor Microenvironment SO GASTROENTEROLOGY LA English DT Review DE Cancer Cell Signaling; Proliferation; T beta R; Apoptosis ID SQUAMOUS-CELL CARCINOMA; EPITHELIAL-MESENCHYMAL TRANSITION; GR-1+CD11B+ MYELOID CELLS; SMAD4 GENE-MUTATIONS; HUMAN BREAST-CANCER; AUTOCRINE TGF-BETA; HEPATOCELLULAR-CARCINOMA; PANCREATIC-CANCER; COLON-CANCER; IMMUNE CELLS AB Transforming growth factor (TGF)-beta is a multifunctional cytokine that has important roles in tumor formation, progression, and metastasis. TGF-beta is overproduced, and its signaling is deregulated, in a variety of human tumors, including colorectal, gastric, pancreatic, and liver. Therapeutics are being developed to block TGF-beta signaling. However, TGF-beta also functions as a tumor suppressor in premalignant cells. It is not clear how its function changes from that of a tumor suppressor to a tumor promoter; improvements are needed in our understanding of TGF-beta functions in tumor development before we can design inhibitors for use as anticancer therapies. TGF-beta regulates not only different tumor-cell autonomous signaling pathways, but also interactions between tumor and host cells, through paracrine mechanisms. We review recent findings about how TGF-beta is regulated and its roles in the tumor microenvironment and metastasis, with a focus on gastrointestinal cancers. Improved understanding of TGF-beta regulation and how it mediates interaction between cancer epithelial cells, immune cells, and fibroblasts will provide important insights into tumor development and progression. C1 [Yang, Li] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA. RP Yang, L (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bldg 37,Room 3134C,37 Convent Dr,MSC 4258, Bethesda, MD 20876 USA. EM yangl3@mail.nih.gov NR 147 TC 76 Z9 80 U1 1 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2011 VL 141 IS 4 BP 1167 EP 1178 DI 10.1053/j.gastro.2011.07.048 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829OQ UT WOS:000295593700023 PM 21839702 ER PT J AU Sandler, NG Koh, C Roque, A Eccleston, JL Siegel, RB Demino, M Kleiner, DE Deeks, SG Liang, TJ Heller, T Douek, DC AF Sandler, Netanya G. Koh, Christopher Roque, Annelys Eccleston, Jason L. Siegel, Rebecca B. Demino, Mary Kleiner, David E. Deeks, Steven G. Liang, T. Jake Heller, Theo Douek, Daniel C. TI Host Response to Translocated Microbial Products Predicts Outcomes of Patients With HBV or HCV Infection SO GASTROENTEROLOGY LA English DT Article DE Microbial Translocation; Soluble CD14; Hepatitis; Intestinal Fatty Acid Binding Protein ID ACID-BINDING-PROTEIN; C VIRUS-INFECTION; HEPATITIS-C; LIVER-DISEASE; SOLUBLE CD14; BACTEROIDES-FRAGILIS; LIPOPOLYSACCHARIDE; CELLS; EXPRESSION; ENDOTOXIN AB BACKGROUND & AIMS: Chronic infection with hepatitis B or C virus (HBV or HCV) is a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation of gut microbial products into the systemic circulation might increase because of increased intestinal permeability, bacterial overgrowth, or impaired clearance of microbial products by Kupffer cells. We investigated whether the extent and progression of liver disease in patients with chronic HBV or HCV infection are associated with microbial translocation and subsequent activation of monocytes. METHODS: In a retrospective study, we analyzed data from 16 patients with minimal fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) by the limulus amebocyte lysate assay, at presentation and after antiviral treatment. RESULTS: Compared with uninfected individuals, HCV- and HBV-infected individuals had higher plasma levels of LPS, intestinal fatty acid binding protein (indicating enterocyte death), sCD14 (produced upon LPS activation of monocytes), and interleukin-6. Portal hypertension, indicated by low platelet counts, was associated with enterocyte death (P = .045 at presentation, P < .0001 after therapy). Levels of sCD14 correlated with markers of hepatic inflammation (P = .02 for aspartate aminotransferase, P = .002 for ferritin) and fibrosis (P < .0001 for gamma-glutamyl transpeptidase, P = .01 for alkaline phosphatase, P < .0001 for alpha-fetoprotein). Compared to subjects with minimal fibrosis, subjects with severe fibrosis at presentation had higher plasma levels of sCD14 (P = .01) and more hepatic CD14(+) cells (P = .0002); each increased risk for disease progression (P = .0009 and P = .005, respectively). CONCLUSIONS: LPS-induced local and systemic inflammation is associated with cirrhosis and predicts progression to end-stage liver disease in patients with HBV or HCV infection. C1 [Sandler, Netanya G.; Roque, Annelys; Siegel, Rebecca B.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Koh, Christopher; Eccleston, Jason L.; Demino, Mary; Liang, T. Jake; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, Dept Med, San Francisco, CA USA. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 3509, Bethesda, MD 20892 USA. EM theoh@intra.niddk.nih.gov; ddouek@mail.nih.gov OI Utay, Netanya/0000-0002-6407-8670; Kleiner, David/0000-0003-3442-4453 FU National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute (National Institutes of Health); National Institutes of Health [AI-76174] FX Grant support received from the intramural programs of National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, and National Cancer Institute (National Institutes of Health) and National Institutes of Health grant AI-76174. NR 56 TC 105 Z9 109 U1 1 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2011 VL 141 IS 4 BP 1220 EP U640 DI 10.1053/j.gastro.2011.06.063 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829OQ UT WOS:000295593700029 PM 21726511 ER PT J AU Ahlenstiel, G Edlich, B Hogdal, LJ Rotman, Y Noureddin, M Feld, JJ Holz, LE Titerence, RH Liang, TJ Rehermann, B AF Ahlenstiel, Golo Edlich, Birgit Hogdal, Leah J. Rotman, Yaron Noureddin, Mazen Feld, Jordan J. Holz, Lauren E. Titerence, Rachel H. Liang, T. Jake Rehermann, Barbara TI Early Changes in Natural Killer Cell Function Indicate Virologic Response to Interferon Therapy for Hepatitis C SO GASTROENTEROLOGY LA English DT Article DE Liver Disease; HCV Treatment; Response to Therapy; Cell Death ID VIRUS-INFECTION; NK CELLS; RECEPTOR EXPRESSION; INNATE; HCV; CYTOTOXICITY; CYTOKINES; SUBSET; ALPHA; RIBAVIRIN AB BACKGROUND & AIMS: Mathematical modeling of hepatitis C virus (HCV) kinetics indicated that cellular immune responses contribute to interferon (IFN)-induced clearance of HCV. We investigated a potential role of natural killer (NK) cells in this process. METHODS: Phenotype and function of blood and liver NK cells were studied during the first 12 weeks of treatment with pegylated IFN-alfa and ribavirin, the time period used to define the early virological response. RESULTS: Within hours of treatment initiation, NK cells of patients that had an early virological response increased expression of activating receptors NKG2D, NKp30, and CD16 and decreased expression of NKG2C and 2B4, along with inhibitory receptors SIGLEC7 and NKG2A, resulting in NK cell activation. NK cell cytotoxicity, measured by degranulation and tumor necrosis factor-related apoptosis-inducing ligand production, peaked after 24 hours (P < .01), concomitant with an increase in alanine aminotransferase levels (P < .05), whereas IFN-gamma production decreased within 6 hours and did not recover for more than 4 weeks (P < .05). NK cells from liver biopsies taken 6 hours after treatment initiation had increased numbers of cytotoxic CD16(+)NK cells (P < .05) and a trend toward increased production of tumor necrosis factor-related apoptosis-inducing ligand. Degranulation of peripheral blood NK cells correlated with treatment-induced, first-phase decreases in viral load (P < .05) and remained higher in early virological responders than in nonresponders for weeks. CONCLUSIONS: IFN activates NK cells early after treatment is initiated. Their cytotoxic function, in particular, is strongly induced, which correlates to virologic response. Therefore, NK cell activation indicates responsiveness to IFN-alpha-based treatment and suggests the involvement of the innate immune cells in viral clearance. C1 [Ahlenstiel, Golo; Edlich, Birgit; Hogdal, Leah J.; Holz, Lauren E.; Titerence, Rachel H.; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov OI Rotman, Yaron/0000-0002-7549-8216; Ahlenstiel, Golo/0000-0003-0026-1457 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health intramural research program. NR 30 TC 82 Z9 85 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2011 VL 141 IS 4 BP 1231 EP U651 DI 10.1053/j.gastro.2011.06.069 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829OQ UT WOS:000295593700030 PM 21741920 ER PT J AU Grandemange, S Aksentijevich, I Jeru, I Gul, A Touitou, I AF Grandemange, S. Aksentijevich, I. Jeru, I. Gul, A. Touitou, I. TI The regulation of MEFV expression and its role in health and familial Mediterranean fever SO GENES AND IMMUNITY LA English DT Review DE expression; MEFV; FMF ID NF-KAPPA-B; PRIMARY FIBROBLAST-CULTURES; MESSENGER-RNA; SUBCELLULAR-LOCALIZATION; C5A INHIBITOR; PYRIN DOMAIN; SPRY DOMAIN; GENE; PROTEIN; ASC AB Familial Mediterranean fever (FMF) is a hereditary recurrent fever associated with mutations in the gene MEFV encoding pyrin. It is expressed mainly in neutrophils and macrophages, and modulates the production of the potent pro-inflammatory cytokine interleukin-1 beta through regulation of nuclear factor-kappa B and caspase-1. The MEFV gene expression depends on multiple levels of regulation. Sequence variants located in the promoter and at the 3'-untranslated region of the gene modulate this expression. Two studies demonstrated decreased mRNA levels in FMF patients compared with healthy subjects, whereas two others found no significant differences. The diverse experimental settings may have resulted in variable quantification of the 15 splice variants that have been identified recently. Some of these isoforms are regulated by nonsense-mediated decay in both cell-and transcript-specific manner, and may be differentially translated in THP1 cells. In addition, pyrin may be cleaved by caspase 1. The full-length pyrin was less abundant than the cleaved fragment in mononuclear cells from FMF patients than in controls, whereas the opposite was observed in granulocytes. Altogether, the regulation of MEFV expression is more complex than anticipated in both physiological and pathological conditions. Its deregulation is likely to alter the inflammasome function and subsequently result in uncontrolled inflammation as seen in FMF. Genes and Immunity (2011) 12, 497-503; doi:10.1038/gene.2011.53; published online 21 July 2011 C1 [Grandemange, S.; Touitou, I.] Hop Arnaud de Villeneuve, Unite Med Malad Autoinflammatoires, CHRU Montpellier, INSERM,U844,UM1, F-34295 Montpellier 5, France. [Aksentijevich, I.] NHGRI, Bethesda, MD 20892 USA. [Jeru, I.] Univ Paris 06, INSERM, U933, UMR S933, Paris, France. [Gul, A.] Istanbul Univ, Istanbul Fac Med, Div Rheumatol, Dept Internal Med, Istanbul, Turkey. RP Touitou, I (reprint author), Hop Arnaud de Villeneuve, Unite Med Malad Autoinflammatoires, CHRU Montpellier, INSERM,U844,UM1, 371 Ave Doyen Giraud, F-34295 Montpellier 5, France. EM isabelle.touitou@inserm.fr FU CHRU of Montpellier [PHRC2005]; National Human Genome Research Institute; INSERM; Istanbul Faculty of Medicine FX This work was supported by the CHRU of Montpellier (PHRC2005), the National Human Genome Research Institute, INSERM and Istanbul Faculty of Medicine. We thank the clinicians for providing patient samples, J Tazy for helpful discussion and M Vittal for English editing of the manuscript. NR 39 TC 10 Z9 11 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2011 VL 12 IS 7 BP 497 EP 503 DI 10.1038/gene.2011.53 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 838ZI UT WOS:000296332900001 PM 21776013 ER PT J AU Shakes, DC Allen, AK Albert, KM Golden, A AF Shakes, Diane C. Allen, Anna K. Albert, Kelsey M. Golden, Andy TI emb-1 Encodes the APC16 Subunit of the Caenorhabditis elegans Anaphase-Promoting Complex SO GENETICS LA English DT Article ID CHROMOSOME SEGREGATION; SACCHAROMYCES-CEREVISIAE; DEVELOPMENTAL DEFECTS; GENETIC INTERFERENCE; PROTEIN COMPLEXES; MEIOSIS-I; C-ELEGANS; YEAST; COMPLEX/CYCLOSOME; MUTANTS AB In the nematode Caenorhabditis elegans, temperature-sensitive mutants of emb-1 arrest as one-cell embryos in metaphase of meiosis I in a manner that is indistinguishable from embryos that have been depleted of known subunits of the anaphase-promoting complex or cyclosome (APC/C). Here we show that the emb-1 phenotype is enhanced in double mutant combinations with known APC/C subunits and suppressed in double mutant combinations with known APC/C suppressors. In addition to its meiotic function, emb-1 is required for mitotic proliferation of the germline. These studies reveal that emb-1 encodes K10D2.4, a homolog of the small, recently discovered APC/C subunit, APC16. C1 [Allen, Anna K.; Golden, Andy] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. [Shakes, Diane C.; Albert, Kelsey M.] Coll William & Mary, Dept Biol, Williamsburg, VA 23185 USA. RP Golden, A (reprint author), 8 Ctr Dr,Bldg 8,Room 323, Bethesda, MD 20892 USA. EM andyg@mail.nih.gov FU National Institutes of Health (NIH) [R15GM60359]; Jeffress Memorial Trust [J-840]; NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX We acknowledge Yuji Kohara (National Institute of Genetics, Mishima, Japan) for generously providing us with the cDNA clone for emb-1. We are also grateful to Shohei Mitani (Tokyo Women's Medical University School of Medicine) for generating the cid-1 deletion alleles, the C. elegans Gene Knockout Consortium (Oklahoma Medical Research Foundation), and the C. elegans Reverse Genetics Core Facility (Vancouver) for isolating the ok2757 and ok2759 deletion alleles of emb-1. We thank Colin Thacker (University of Utah) for generating our transgenic lines, the Caenorhabditis Genetics Center for providing numerous strains for mapping, James LaRue (College of William and Mary) for preliminary studies of emb-1 doubles, and Kevin O'Connell for critical comments on this manuscript. We are also grateful for the discussions and suggestions from members of our laboratories and the Baltimore Worm Club. This research was supported, in part, by National Institutes of Health (NIH) grant R15GM60359 (D.C.S.), Jeffress Memorial Trust Grant (J-840; D.C.S.), and the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (A.G.). NR 55 TC 8 Z9 12 U1 0 U2 1 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2011 VL 189 IS 2 BP 549 EP 560 DI 10.1534/genetics.111.131714 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 836ZH UT WOS:000296158500012 PM 21775471 ER PT J AU Saghir, SA Ghanayem, BI Schultz, IR AF Saghir, Shakil A. Ghanayem, Burhan I. Schultz, Irvin R. TI Kinetics of Trihalogenated Acetic Acid Metabolism and Isoform Specificity in Liver Microsomes SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE bromodichloroacetic acid; chlorodibromoacetic acid; tribromoacetic acid; microsomal metabolism; rat; mouse; human ID B6C3F1 MICE; ORAL BIOAVAILABILITY; DIBROMOACETIC ACID; HALOACETIC ACIDS; DRINKING-WATER; DEPLETED RATS; DICHLOROACETATE; TOXICOKINETICS; BROMODICHLOROACETATE; TRICHLOROACETATE AB This study determined the metabolism of 3 drinking water disinfection by-products (halogenated acetic acids [HAAs]), bromodichloroacetic acid (BDCAA), chlorodibromoacetic acid (CDBAA), and tribromoacetic acid (TBAA), using rat, mouse, human liver microsomes, and recombinant P450. Metabolism proceeded by reductive debromination forming a di-HAA; the highest under nitrogen >>2% oxygen > atmospheric headspaces. V(max) for the loss of tri-HAA was 4 to 5 times higher under nitrogen than atmospheric headspace. Intrinsic metabolic clearance was TBAA>CDBAA>>BDCAA. At the high substrate concentrations, tri-HAA consumption rate was 2 to 3 times higher than the formation of di-HAA. Liberation of Br(-) from TBAA corresponded to the expected amount produced after DBAA formation, indicating retention of Br(-) by additional metabolite/metabolites. Subsequent experiments with CDBAA detected negligible formation of chlorodibromomethane (CDBM) and failed to account for the missing tri-HAA. Carbon monoxide and especially diphenyleneiodonium ([DPI] P450 reductase inhibitor) blocked CDBAA metabolism. Other chemical inhibitors were only partially able to block CDBAA metabolism. Most effective were inhibitors of CYP 2E1 and CYP 3A4. Immunoinhibition studies using human liver microsomes and anti-human CYP 2E1 antibodies were successful in reducing CDBAA metabolism. However, CDBAA metabolism in wild-type (WT) and CYP 2E1 knockout (KO) mouse liver microsomes was similar, suggesting significant interspecies differences in CYP isoform in tri-HAA metabolism. Additional assessment of CYP isoform involvement was complicated by the finding that recombinantly expressed rat and human P450 reductase was able to metabolize CDBAA, which may be a contributing factor in interspecies differences in tri-HAA metabolism. C1 [Saghir, Shakil A.] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. [Saghir, Shakil A.] Aga Khan Univ, Dept Biol & Biomed Sci, Karachi, Pakistan. [Ghanayem, Burhan I.] NIEHS, Environm Toxicol Program, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. [Schultz, Irvin R.] Pacific NW Natl Lab, Sequim, WA USA. RP Saghir, SA (reprint author), Dow Chem Co USA, Toxicol & Environm Res & Consulting, 1803 Bldg, Midland, MI 48674 USA. EM ssaghir@dow.com FU U.S. Environmental Protection Agency [R828044, R82594] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: U.S. Environmental Protection Agency Grants R828044, R82594. NR 30 TC 1 Z9 1 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD OCT PY 2011 VL 30 IS 5 BP 551 EP 561 DI 10.1177/1091581811414213 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 835GJ UT WOS:000296023600011 PM 21933969 ER PT J AU Sun, HM Veith, H Xia, MH Austin, CP Huang, RL AF Sun, Hongmao Veith, Henrike Xia, Menghang Austin, Christopher P. Huang, Ruili TI Predictive Models for Cytochrome P450 Isozymes Based on Quantitative High Throughput Screening Data SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID MACHINE-LEARNING TECHNIQUES; CHEMICAL LIBRARIES; CRYSTAL-STRUCTURE; DRUG-METABOLISM; CYP3A4; SELECTIVITY; BINDING; P450S; 3A4 AB The human cytochrome P450 (CYP450) isozymes are the most important enzymes in the body to metabolize many endogenous and exogenous substances including environmental toxins and therapeutic drugs. Any unnecessary interactions between a small molecule and CYP450 isozymes may raise a potential to disarm the integrity of the protection. Accurately predicting the potential interactions between a small molecule and CYP450 isozymes is highly desirable for assessing the metabolic stability and toxicity of the molecule. The National Institutes of Health Chemical Genomics Center (NCGC) has screened a collection of over 17,000 compounds against the five major isozymes of CYP450 (1A2, 2C9, 2C19, 2D6, and 3A4) in a quantitative high throughput screening (qHTS) format. In this study, we developed support vector classification (SVC) models for these five isozymes using a set of customized generic atom types. The CYP450 data sets were randomly split into equal-sized training and test sets. The optimized SVC models exhibited high predictive power against the test sets for all five CYP450 isozymes with accuracies of 0.93, 0.89, 0.89, 0.85, and 0.87 for 1A2, 2C9, 2C19, 2D6, and 3A4, respectively, as measured by the area under the receiver operating characteristic (ROC) curves. The important atom types and features extracted from the five models are consistent with the structural preferences for different CYP450 substrates reported in the literature. We also identified novel features with significant discerning power to separate CYP450 actives from inactives. These models can be useful in prioritizing compounds in a drug discovery pipeline or recognizing the toxic potential of environmental chemicals. C1 [Sun, Hongmao; Veith, Henrike; Xia, Menghang; Austin, Christopher P.; Huang, Ruili] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Sun, HM (reprint author), NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM sunh7@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Human Genome Research Institute, National Institutes of Health. We thank in particular Rena Zheng for helpful comments and suggestions during the preparation of this manuscript. NR 35 TC 25 Z9 27 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD OCT PY 2011 VL 51 IS 10 BP 2474 EP 2481 DI 10.1021/ci200311w PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 835NX UT WOS:000296044200004 PM 21905670 ER PT J AU da Silva, SP Resnick, E Lucas, M Lortan, J Patel, S Cunningham-Rundles, C Gatter, K Liu, QY Jaffe, ES Chapel, H AF da Silva, Sara Pereira Resnick, Elena Lucas, Mary Lortan, Jennifer Patel, Smita Cunningham-Rundles, Charlotte Gatter, Kevin Liu, Qingyan Jaffe, Elaine S. Chapel, Helen TI Lymphoid Proliferations of Indeterminate Malignant Potential arising in Adults with Common Variable Immunodeficiency Disorders: Unusual Case Studies and Immunohistological Review in the Light of Possible Causative Events SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Common variable immunodeficiency disorders; lymphoid proliferation; lymphoma; infection ID HELICOBACTER-PYLORI ERADICATION; T-CELL RESPONSE; ANTIBODY DEFICIENCY; MALT LYMPHOMA; LONG-TERM; DISEASE; TISSUE; CLASSIFICATION; ASPERGILLOSIS; INFECTION AB Patients with common variable immunodeficiency disorders (CVIDs) who developed B cell lymphoproliferation of indeterminate malignant potential are described in order to raise a discussion of the relationship between infection and lymphoproliferation in infection prone patients. Those with CVID are at risk of developing either polyclonal or monoclonal lymphoproliferation in part due to the dysregulation of their adaptive immune systems. The aetiologies of the lymphoproliferations are unknown but intriguing; the relevance of infection being particularly problematic. The patients described here demonstrate variability in preceding infection, age at presentation, response to antibiotics and other types of therapy as well as outcome. The question of treatment is also controversial; issues include whether antibiotics or chemotherapy are the first line of therapy in all patients and whether transformation to aggressive B cell malignancy is inevitable or depends on other factors and if so, the length of time for such progression. C1 [Lucas, Mary; Lortan, Jennifer; Patel, Smita; Chapel, Helen] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Clin Immunol Unit, Oxford OX3 9DU, England. [da Silva, Sara Pereira] Hosp Santa Maria, Immunoallergol Dept, Lisbon, Portugal. [Resnick, Elena; Cunningham-Rundles, Charlotte] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. [Resnick, Elena; Cunningham-Rundles, Charlotte] Mt Sinai Med Ctr, Inst Immunol, New York, NY 10029 USA. [Lortan, Jennifer; Gatter, Kevin] Univ Oxford, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England. [Liu, Qingyan; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Chapel, H (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Clin Immunol Unit, Level 7,Headley Way, Oxford OX3 9DU, England. EM helen.chapel@ndm.ox.ac.uk OI Jaffe, Elaine/0000-0003-4632-0301 FU NIHR Oxford Biomedical Centre; EU; Primary Immunodeficiency Association; Baxter Healthcare; Jeffrey Modell Foundation; Sociedade Portuguesa de Alergologia e Imunologia Clinica; National Institutes of Health [AI 101093, AI-467320, AI-48693]; NIAID [03-22]; David S Gottesman Immunology Chair FX We are grateful to the following funding bodies for their financial support: NIHR Oxford Biomedical Centre Programme, EU 7th Framework Programme (PADnet), the Primary Immunodeficiency Association, Baxter Healthcare, the Jeffrey Modell Foundation (HC, CCR) and to Sociedade Portuguesa de Alergologia e Imunologia Clinica, for the scholarship programme that allowed a training period in the Oxford Centre for Clinical Immunology, Oxford Radcliffe Hospitals. This work was also supported by grants from the National Institutes of Health, AI 101093, AI-467320, AI-48693, NIAID contract 03-22 and the David S Gottesman Immunology Chair (CCR.) NR 34 TC 16 Z9 16 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD OCT PY 2011 VL 31 IS 5 BP 784 EP 791 DI 10.1007/s10875-011-9565-z PG 8 WC Immunology SC Immunology GA 835CT UT WOS:000296012300007 PM 21744182 ER PT J AU Woodson, SE Holbrook, MR AF Woodson, Sara E. Holbrook, Michael R. TI Infection of hepatocytes with 17-D vaccine-strain yellow fever virus induces a strong pro-inflammatory host response SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID ACUTE-PHASE RESPONSE; IN-VIVO SYNTHESIS; VISCEROTROPIC DISEASE; IMMUNE-RESPONSE; ADVERSE EVENTS; TGF-BETA; ACTIVATION; LIVER; APOPTOSIS; PROTEIN AB Yellow fever virus (YFV) causes serious disease in endemic areas of South America and Africa, even though a very well tolerated vaccine is available. YFV primarily targets the liver where as many as 80% of hepatocytes may be involved during infection. The objective of this project was to compare and contrast the cytokine response from hepatocytes infected with either wild-type (Asibi) or vaccine (17-D-204) strains of YFV, with the goal of identifying responses that might be correlated with disease severity or vaccine efficacy. We report here that PH5CH8 hepatocytes support a productive infection with both wild-type and vaccine-strain YFV. Infection with either virus resulted in elevated expression of several pro- and anti-inflammatory cytokines [interleukin (IL)-1 beta, IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-alpha) with a corresponding increase in transcription. Hepatocytes infected with vaccine virus had a more profound response than did cells infected with wild-type virus. Pre-stimulation of hepatocytes with IL-6 resulted in reduced viral titres, elevated concentrations of cytokines released from Asibi virus-infected cells and improved cell viability in cells infected with 17-D virus. Data reported here suggest that 17-D virus stimulates an appropriate antiviral inflammatory response in hepatocytes, while Asibi virus can attenuate the host response. These data identify potential mechanisms that are associated with increased virulence in wild-type virus infections and also provide clues towards potential immune-response limitations that may be associated with vaccine-related adverse events. C1 Univ Texas Med Branch, Dept Pathol, Galveston, TX 77550 USA. Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77550 USA. RP Holbrook, MR (reprint author), NIAID Integrated Res Facil, 8200 Res Plaza, Frederick, MD 21702 USA. EM michael.holbrook@nih.gov NR 45 TC 3 Z9 3 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 2011 VL 92 BP 2262 EP 2271 DI 10.1099/vir.0.031617-0 PN 10 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 833BE UT WOS:000295856000004 PM 21697351 ER PT J AU Cruz, AV Mallet, N Magill, PJ Brown, P Averbeck, BB AF Cruz, Ana V. Mallet, Nicolas Magill, Peter J. Brown, Peter Averbeck, Bruno B. TI Effects of dopamine depletion on information flow between the subthalamic nucleus and external globus pallidus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE maximum entropy; Parkinson's disease; coding capacity ID TONICALLY ACTIVE NEURONS; PARKINSONS-DISEASE; BASAL GANGLIA; BETA-OSCILLATIONS; CEREBRAL-CORTEX; NEURAL OSCILLATIONS; FIELD POTENTIALS; SYNCHRONIZATION; NETWORK; MODEL AB Cruz AV, Mallet N, Magill PJ, Brown P, Averbeck BB. Effects of dopamine depletion on information flow between the subthalamic nucleus and external globus pallidus. J Neurophysiol 106: 2012-2023, 2011. First published August 3, 2011; doi: 10.1152/jn.00094.2011.-Abnormal oscillatory synchrony is increasingly acknowledged as a pathophysiological hallmark of Parkinson's disease, but what promotes such activity remains unclear. We used novel, nonlinear time series analyses and information theory to capture the effects of dopamine depletion on directed information flow within and between the subthalamic nucleus (STN) and external globus pallidus (GPe). We compared neuronal activity recorded simultaneously from these nuclei in 6-hydroxydopamine-lesioned Parkinsonian rats with that in dopamine-intact control rats. After lesioning, both nuclei displayed pronounced augmentations of beta-frequency (similar to 20 Hz) oscillations and, critically, information transfer between STN and GPe neurons was increased. Furthermore, temporal profiles of the directed information transfer agreed with the neurochemistry of these nuclei, being "excitatory" from STN to GPe and "inhibitory" from GPe to STN. Separation of the GPe population in lesioned animals into "type-inactive" (GP-TI) and "type-active" (GP-TA) neurons, according to definitive firing preferences, revealed distinct temporal profiles of interaction with STN and each other. The profile of GP-TI neurons suggested their output is of greater causal significance than that of GP-TA neurons for the reduced activity that periodically punctuates the spiking of STN neurons during beta oscillations. Moreover, STN was identified as a key candidate driver for recruiting ensembles of GP-TI neurons but not GP-TA neurons. Short-latency interactions between GP-TI and GP-TA neurons suggested mutual inhibition, which could rhythmically dampen activity and promote anti-phase firing across the two subpopulations. Results thus indicate that information flow around the STN-GPe circuit is exaggerated in Parkinsonism and further define the temporal interactions underpinning this. C1 [Cruz, Ana V.; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Cruz, Ana V.; Brown, Peter; Averbeck, Bruno B.] UCL, Sobell Dept Motor Neurosci & Movement Disorders, Inst Neurol, London, England. [Cruz, Ana V.] Inst Gulbenkian Ciencias, Oeiras, Portugal. [Mallet, Nicolas; Magill, Peter J.] Univ Oxford, MRC, Anat Neuropharmacol Unit, Oxford, England. [Mallet, Nicolas; Magill, Peter J.] Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford, England. [Brown, Peter] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Rm 1B-80, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov RI Brown, Peter/J-4307-2016; OI Brown, Peter/0000-0002-5201-3044; Magill, Peter/0000-0001-7141-7071 FU Fundacao para a Ciencia e Tecnologia [SFRH/BD/33201/2007]; Fundacao Gulbenkian; Medical Research Council UK; Dana Foundation USA; Parkinson's UK Grant [G-0806]; Oxford National Institute for Health Research Biomedical Centre; Wellcome Trust; National Institute of Mental Health FX A. V. Cruz was supported by Fundacao para a Ciencia e Tecnologia Grant SFRH/BD/33201/2007 and Fundacao Gulbenkian. N. Mallet and P. J. Magill were supported by the Medical Research Council UK, The Dana Foundation USA, and Parkinson's UK Grant G-0806. P. Brown was supported by the Medical Research Council UK and the Oxford National Institute for Health Research Biomedical Centre. B. B. Averbeck was supported by the Wellcome Trust and the National Institute of Mental Health Intramural Research Program. NR 56 TC 23 Z9 24 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2011 VL 106 IS 4 BP 2012 EP 2023 DI 10.1152/jn.00094.2011 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 836EJ UT WOS:000296092000035 PM 21813748 ER PT J AU Zanarini, MC Horwood, J Wolke, D Waylen, A Fitzmaurice, G Grant, BF AF Zanarini, Mary C. Horwood, Jeremy Wolke, Dieter Waylen, Andrea Fitzmaurice, Garrett Grant, Bridget F. TI PREVALENCE OF DSM-IV BORDERLINE PERSONALITY DISORDER IN TWO COMMUNITY SAMPLES: 6,330 ENGLISH 11-YEAR-OLDS AND 34,653 AMERICAN ADULTS SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; RANDOMIZED CONTROLLED-TRIAL; RISK-FACTORS; FOLLOW-UP; AXIS-I; CHILDREN; RELIABILITY; PSYCHOPATHOLOGY; ALCOHOL; ADOLESCENTS AB This study had two main objectives. The first was to assess the prevalence of DSM-IV borderline personality disorder and its constituent symptoms in a community sample of late-latency children. The second was to compare these rates to those found in a community sample of American adults. A birth cohort of 6,330 11-year-old children in Bristol, England, was interviewed concerning borderline psychopathology in 2002-2004. A community sample of 34,653 American adults was interviewed about borderline psychopathology in 2004-2005. Rates of chronic emptiness, physically self-damaging acts, and stormy relationships were very similar in both samples (<2% difference). However, a significantly higher percentage of children than adults reported being angry and moody. In contrast, a significantly higher percentage of adults than children reported being paranoid/dissociated, having a serious identity disturbance, being impulsive, and making frantic efforts to avoid abandonment. In addition, a significantly higher percentage of adults than children met DSM-IV criteria for BPD (5.9% vs. 3.2%). Statistically significant but clinically minor gender differences were also found between girls and boys as well as men and women. Taken together, the results of this study suggest that late-latency children are about half as likely as adults to meet DSM-IV criteria for BPD. They also suggest that gender does not play a defining role in symptom expression. C1 [Zanarini, Mary C.; Fitzmaurice, Garrett] McLean Hosp, Belmont, MA 02478 USA. [Zanarini, Mary C.; Fitzmaurice, Garrett] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Horwood, Jeremy; Waylen, Andrea] Univ Bristol, Bristol BS8 1TH, Avon, England. [Wolke, Dieter] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Grant, Bridget F.] NIAAA, Bethesda, MD USA. RP Zanarini, MC (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM zanarini@mclean.harvard.edu RI Waylen, Andrea/H-7332-2014; Wolke, Dieter/C-5372-2008 OI Wolke, Dieter/0000-0003-0304-268X FU Intramural NIH HHS [Z99 AA999999]; Wellcome Trust [092731] NR 35 TC 35 Z9 35 U1 3 U2 16 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD OCT PY 2011 VL 25 IS 5 BP 607 EP 619 PG 13 WC Psychiatry SC Psychiatry GA 836AB UT WOS:000296077300004 PM 22023298 ER PT J AU Cao, XE Pei, HR Huo, LS Hu, GH Ito, Y AF Cao, Xueli Pei, Hairun Huo, Liangsheng Hu, Guanghui Ito, Yoichiro TI Development and evaluation of a spiral tube column for counter-current chromatography SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Anthocyanins; Counter-current chromatography; Peptides; Proteins; Spiral tube column ID STATIONARY-PHASE RETENTION; SPEED; SEPARATION; CCC AB An improved type-J counter-current chromatography (CCC) planet centrifuge with two spiral tube columns (volume 2 x 15 mL, beta value 0.3-0.7, tubing 0.8 mm id) was developed and evaluated for its retention ability of four typical different solvent systems including heptane-methanol (1:1, v/v) (A), hexane-ethyl acetate-methanol-water (1:1:1:1, v/v) (B), n-butanol-acetic acid-water (4:1:5, v/v) (C), PEG1000-K(2)HPO(4)-water (12.5:12.5:75, w/w) (D) under eight different operation modes. The results indicated that the spiral tube column could significantly increase the retention of four typical solvent systems compared with a traditional multilayer coil column with similar parameters (volume 35 mL, beta value 0.3-0.7, tubing 0.8 mm id). The retention of stationary phase (S(f)) for the less polar system (A) and moderately polar solvent system (B) can be increased by about 10%, and for the polar system (C) and aqueous two-phase system (ATPS) (D) by 30-40%. The preliminary applications of this spiral tube column to the separation of small molecular compounds such as moderately polar theaflavins, polar anthocyanins and dipeptides were successful. Acceptable resolution can be obtained between cytochrome c and myoglobin, lysozyme and myoglobin when it was applied on protein separation; however, it still needs to be improved with regard to its column efficiency. C1 [Cao, Xueli; Pei, Hairun; Huo, Liangsheng; Hu, Guanghui] Beijing Technol & Business Univ, Dept Bioengn, Beijing 100048, Peoples R China. [Ito, Yoichiro] NHLBI, NIH, Biochem & Biophys Ctr, Bioseparat Technol Lab, Bethesda, MD 20892 USA. RP Cao, XE (reprint author), Beijing Technol & Business Univ, Dept Bioengn, 33 Fucheng Rd, Beijing 100048, Peoples R China. EM caoxl@th.btbu.edu.cn FU National Natural Science Foundation of China [20877005]; National High Technology Research and Development Program ("863" Program) [2007AA061601]; Beijing Natural Science Foundation [2102016] FX The authors acknowledge financial support of this work by the National Natural Science Foundation of China (No. 20877005) the National High Technology Research and Development Program ("863" Program No. 2007AA061601), and Beijing Natural Science Foundation (No. 2102016). NR 14 TC 9 Z9 9 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD OCT PY 2011 VL 34 IS 19 BP 2611 EP 2617 DI 10.1002/jssc.201100205 PG 7 WC Chemistry, Analytical SC Chemistry GA 836VA UT WOS:000296141200008 PM 21898798 ER PT J AU Ji, HF Ren, W Wang, LY Shi, P Chen, XF Wu, XQ Yao, X Lau, ST Zhou, QF Shung, KK AF Ji, Hongfen Ren, Wei Wang, Lingyan Shi, Peng Chen, Xiaofeng Wu, Xiaoqing Yao, Xi Lau, Sien-Ting Zhou, Qifa Shung, K. Kirk TI Enhanced Structures and Electrical Properties of Lead-Free K0.5Na0.5NbO3-Bi0.5Na0.5TiO3 0-3 Composite Ferroelectric Thick Films SO JOURNAL OF THE AMERICAN CERAMIC SOCIETY LA English DT Article ID PIEZOELECTRIC PROPERTIES; DIELECTRIC-PROPERTIES; TRANSDUCERS; FABRICATION AB Lead-free K0.5Na0.5NbO3-Bi0.5Na0.5TiO3 (KNN-BNT) 0-3 composite ferroelectric thick films have been successfully prepared by a modified composite sol-gel process. The KNN fine ceramic powders were dispersed in the BNT precursor solution to form the uniform slurry that was spin coated on (111) Pt/TiO2/SiO2/Si substrates. The buffer layers and vacuum infiltration were used during the deposition process to improve the structure and density of the composite films. Influence of the annealing temperature and weight ratio of the powder-to-solution on the structures and electrical properties of KNN-BNT composite thick films has been investigated. X-ray diffraction analysis indicates that the composite thick films possess pure perovskite structures composed by KNN and BNT phases. The dielectric constant and remnant polarization of the composite thick films increase with increasing annealing temperature and decreasing powder-to-solution weight ratio due to reduction of pores and improvement of film density. The composite thick films with the powder-to-solution weight ratio of 0.40 and annealed at 750 degrees C have a dielectric constant of 848 and a remnant polarization of 23.6 mu C/cm(2). The KNN-BNT composite thick films obtained are a promising candidate for transducer applications. C1 [Ji, Hongfen; Ren, Wei; Wang, Lingyan; Shi, Peng; Chen, Xiaofeng; Wu, Xiaoqing; Yao, Xi] Xi An Jiao Tong Univ, Elect Mat Res Lab, Key Lab, Minist Educ, Xian 710049, Peoples R China. [Ji, Hongfen; Ren, Wei; Wang, Lingyan; Shi, Peng; Chen, Xiaofeng; Wu, Xiaoqing; Yao, Xi] Xi An Jiao Tong Univ, Int Ctr Dielect Res, Xian 710049, Peoples R China. [Lau, Sien-Ting; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. RP Ren, W (reprint author), Xi An Jiao Tong Univ, Elect Mat Res Lab, Key Lab, Minist Educ, Xian 710049, Peoples R China. EM wren@mail.xjtu.edu.cn RI shi, peng/C-8551-2011; Lau, Sien-Ting/B-6091-2013; Wang, Lingyan/K-7687-2013 OI shi, peng/0000-0003-2217-8486; FU Natural Science Foundation of China [90923001]; International Science & Technology Cooperation Program of China [2010DFB13640]; Shaanxi Province International Collaboration Program [2009KW-12, 2010KW-09]; NIH [P41-EB2182] FX This work was financially supported by the Natural Science Foundation of China (Grant No. 90923001), International Science & Technology Cooperation Program of China (Grant No. 2010DFB13640), the Shaanxi Province International Collaboration Program (Grant Nos. 2009KW-12 and 2010KW-09), and the NIH Grant P41-EB2182. NR 26 TC 7 Z9 7 U1 3 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-7820 EI 1551-2916 J9 J AM CERAM SOC JI J. Am. Ceram. Soc. PD OCT PY 2011 VL 94 IS 10 BP 3425 EP 3430 DI 10.1111/j.1551-2916.2011.04524.x PG 6 WC Materials Science, Ceramics SC Materials Science GA 828SY UT WOS:000295524300050 ER PT J AU Yothers, G Sargent, DJ Wolmark, N Goldberg, RM O'Connell, MJ Benedetti, JK Saltz, LB Dignam, JJ Blackstock, AW AF Yothers, Greg Sargent, Daniel J. Wolmark, Norman Goldberg, Richard M. O'Connell, Michael J. Benedetti, Jacqueline K. Saltz, Leonard B. Dignam, James J. Blackstock, A. William CA ACCENT Collaborative Grp TI Outcomes Among Black Patients With Stage II and III Colon Cancer Receiving Chemotherapy: An Analysis of ACCENT Adjuvant Trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; BOWEL PROJECT; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; COLORECTAL-CANCER; PLUS LEUCOVORIN; FLUOROURACIL; BREAST; CARCINOMA; SURVIVAL AB Background Among patients with resected colon cancer, black patients have worse survival than whites. We investigated whether disparities in survival and related endpoints would persist when patients were treated with identical therapies in controlled clinical trials. Methods We assessed 14 611 patients (1218 black and 13 393 white) who received standardized adjuvant treatment in 12 randomized controlled clinical trials conducted in North America for resected stage II and stage III colon cancer between 1977 and 2002. Individual patient data on covariates and outcomes were extracted from the Adjuvant Colon Cancer ENdpoinTs (ACCENT) database. The endpoints examined in this meta-analysis were overall survival (time to death), recurrence-free survival (time to recurrence or death), and recurrence-free interval (time to recurrence). Cox models were stratified by study and controlled for sex, stage, age, and treatment to determine the effect of race. Kaplan-Meier estimates were adjusted for similar covariates to control for confounding. All statistical tests were two-sided. Results Black patients were younger than whites (median age, 58 vs 61 years, respectively; P < .001) and more likely to be female (55% vs 45%, respectively; P < .001). Overall survival was worse in black patients than whites (hazard ratio [HR] of death = 1.22, 95% confidence interval [CI] = 1.11 to 1.34, P < .001). Five-year overall survival rates for blacks and whites were 68.2% and 72.8%, respectively. When subsets defined by sex, stage, and age were analyzed, overall survival was consistently worse in black patients. Recurrence-free survival was worse in black patients than whites (HR of recurrence or death = 1.14, 95% CI = 1.04 to 1.24, P = .0045). Three-year recurrence-free survival rates in blacks and whites were 68.4% and 72.1%, respectively. In contrast, recurrence-free interval was similar in black and white patients (HR of recurrence = 1.08, 95% CI = 0.97 to 1.19, P = .15). Three-year recurrence-free interval rates in blacks and whites were 71.3% and 74.2%, respectively. Conclusions Black patients with resected stage II and stage III colon cancer who were treated with the same therapy as white patients experienced worse overall and recurrence-free survival, but similar recurrence-free interval, compared with white patients. The differences in survival may be mostly because of factors unrelated to the patients' adjuvant colon cancer treatment. J Natl Cancer Inst 2011; 103: 1498-1506 C1 [Yothers, Greg; Wolmark, Norman; O'Connell, Michael J.; Dignam, James J.] Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA 15213 USA. [Yothers, Greg; Wolmark, Norman; O'Connell, Michael J.; Dignam, James J.] Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA 15213 USA. [Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sargent, Daniel J.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Wolmark, Norman] Drexel Univ, Dept Human Oncol, Allegheny Gen Hosp, Coll Med, Pittsburgh, PA USA. [Goldberg, Richard M.] Univ N Carolina, Chapel Hill Sch Med, Chapel Hill, NC USA. [Benedetti, Jacqueline K.] Univ Washington, Seattle, WA 98195 USA. [Benedetti, Jacqueline K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Dignam, James J.] Univ Chicago, Chicago, IL 60637 USA. [Blackstock, A. William] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Goldberg, Richard M.; Saltz, Leonard B.; Blackstock, A. William] Canc & Leukemia Grp B, Chicago, IL USA. [Benedetti, Jacqueline K.] SW Oncol Grp, Ann Arbor, MI USA. [Dignam, James J.] Radiat Therapy Oncol Grp, Philadelphia, PA USA. RP Yothers, G (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, 1 Sterling Plaza,Ste 350,201 N Craig St, Pittsburgh, PA 15213 USA. EM yothers@nsabp.pitt.edu RI Goldberg , Richard/M-1311-2013; OI Bot, Brian/0000-0002-2412-6826; Sargent, Daniel/0000-0002-2684-4741; Yothers, Greg/0000-0002-7965-7333; Saltz, Leonard/0000-0001-8353-4670 FU National Surgical Adjuvant Breast and Bowel Project [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651, U24-CA-114732]; National Cancer Institute, Department of Health and Human Services (North Central Cancer Treatment Group) [CA 25224]; sanofi-aventis [C-07] FX Public Health Service Grants U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651, and U24-CA-114732 (National Surgical Adjuvant Breast and Bowel Project); CA 25224 (North Central Cancer Treatment Group) from the National Cancer Institute, Department of Health and Human Services.; NW declares funding from sanofi-aventis to NSABP through a business contract for C-07 only, for certain costs not covered by the NCI, for non-standard-of-care procedures required for the study. Also, consultancy from sanofi-aventis (C-07 only), honoraria to the NSABP for NW's participation on the advisory board, and reasonable travel and accommodations for the sanofi-aventis board meeting. There are no other potential conflicts. NR 30 TC 24 Z9 25 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT PY 2011 VL 103 IS 20 BP 1498 EP 1506 DI 10.1093/jnci/djr310 PG 9 WC Oncology SC Oncology GA 836JJ UT WOS:000296107700007 PM 21997132 ER PT J AU Bedognetti, D Sertoli, MR Pronzato, P Del Mastro, L Venturini, M Taveggia, P Zanardi, E Siffredi, G Pastorino, S Queirolo, P Gardin, G Wang, E Monzeglio, C Boccardo, F Bruzzi, P AF Bedognetti, Davide Sertoli, Mario Roberto Pronzato, Paolo Del Mastro, Lucia Venturini, Marco Taveggia, Paola Zanardi, Elisa Siffredi, Guido Pastorino, Simona Queirolo, Paola Gardin, Giovanni Wang, Ena Monzeglio, Clara Boccardo, Francesco Bruzzi, Paolo TI Concurrent vs Sequential Adjuvant Chemotherapy and Hormone Therapy in Breast Cancer: A Multicenter Randomized Phase III Trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TAMOXIFEN; SURVIVAL; CELLS; WOMEN; 5-FLUOROURACIL; DISEASE; DRUGS AB Background The most appropriate timing of chemotherapy and hormone therapy administration is a critical issue in early breast cancer patients. The purpose of our study was to compare the efficacy of concurrent vs sequential administration of adjuvant chemotherapy and tamoxifen. Methods Women with node-positive primary breast cancer were randomly assigned to receive tamoxifen (20 mg/d for 5 years) during (concurrent arm) or after (sequential arm) adjuvant chemotherapy. Chemotherapy consisted of alternating regimens of cyclophosphamide, epidoxorubicin, and 5-fluorouracil and cyclophosphamide, methotrexate, and 5-fluorouracil every 21 days for a total of 12 cycles. The primary endpoint was overall survival (OS), and secondary endpoints were toxic effects and disease-free survival (DFS). No provision for interim analyses was made in the original study protocol. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models, adjusted for age, menopausal status, tumor stage, and lymph node and hormone receptor status, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results From 1985 to 1992, 431 patients were randomly assigned and studied according to the intention-to-treat principle. After a maximum of 15.4 years of follow-up (median 12.3 years), the estimated actuarial 10-year OS was equivalent for the two study arms (concurrent arm: 111 patients, 66%, 95% CI = 59% to 72%; sequential arm: 114 patients, 65%, 95% CI = 59% to 72%, P = .86). No differences in DFS and toxic effects were evident. Four interim analyses were performed, but no alpha error adjustment was necessary because of the largely negative results of this final analysis (sequential vs concurrent arm: HR of death = 1.06, 95% CI = 0.78 to 1.44, P = .76; HR of relapse = 1.16, 95% CI = 0.88 to 1.52, P = .36). Conclusions No statistically significant differences in OS, DFS, and toxic effects between concurrent and sequential adjuvant chemo-and hormone therapies were observed. Our study does not support the superiority of one schedule of chemo-and hormone-therapy administration over the other. However, because of the limited statistical power of the study, these results must be considered with caution. J Natl Cancer Inst 2011; 103: 1529-1539 C1 [Bedognetti, Davide; Wang, Ena] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Bedognetti, Davide; Wang, Ena] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA. [Bedognetti, Davide; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia; Venturini, Marco; Taveggia, Paola; Zanardi, Elisa; Pastorino, Simona; Queirolo, Paola; Gardin, Giovanni; Boccardo, Francesco] Natl Inst Canc Res, Dept Med Oncol, I-16132 Genoa, Italy. [Bruzzi, Paolo] Natl Inst Canc Res, Dept Epidemiol, I-16132 Genoa, Italy. [Bedognetti, Davide; Sertoli, Mario Roberto; Zanardi, Elisa; Siffredi, Guido; Boccardo, Francesco] Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. [Venturini, Marco] Sacro Cuore Don Calabria Hosp, Dept Oncol, Verona, Italy. [Monzeglio, Clara] St Anna Univ Hosp, Dept Obstet & Gynecol, Turin, Italy. RP Bedognetti, D (reprint author), NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM bedodav@yahoo.it; marioroberto.sertoli@istge.it RI Bedognetti, Davide/A-9090-2012; Queirolo, Paola/K-6778-2016; OI Queirolo, Paola/0000-0002-9917-6633; Bedognetti, Davide/0000-0002-5857-773X; Bruzzi, Paolo/0000-0002-7874-2077; Del Mastro, Lucia/0000-0002-9546-5841 FU Italian National Research Council, Rome [8800601.44]; Conquer Cancer Foundation of the American Society of Clinical Oncology FX This study was supported by a grant from the Italian National Research Council, Rome [Special Project Oncology (8800601.44)].; The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the article. The random allocation sequence was generated at the National Cancer Research Institute of Genoa under the supervision of PB. The authors have no affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article. The following centers and investigators also contributed to patient accrual: Dr Pier Franco Conte (Department of Medical Oncology, S. Chiara Hospital, Pisa), Dr Elio Paganini (Medical Oncology Unit, Villa Scassi Hospital, Genoa, Italy); Dr Fulvio Brema (Department of Oncology, S. Paolo Hospital, Savona, Italy), Dr Pietro Gallotti (Clinical Oncology, Beato Matteo Clinical Institute, Vigevano, Italy). DB thanks Dr Francesco Barone-Adesi (Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, University of Turin, Turin, Italy) and Dr Pietro Blandini (U. C. Sampdoria, Genoa, Italy) for their useful statistical advice. The authors thank Ms. Shari Lama (National Institutes of Health Library, Bethesda, MD, USA) for help in editing for the English format. Davide Bedognetti is a participant in the NIH Graduate Partnership Program and a graduate student at University of Genoa. Davide Bedognetti's scholarship is partially supported by the Conquer Cancer Foundation of the American Society of Clinical Oncology (2011 Young Investigator Award). NR 38 TC 9 Z9 10 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT PY 2011 VL 103 IS 20 BP 1529 EP 1539 DI 10.1093/jnci/djr351 PG 11 WC Oncology SC Oncology GA 836JJ UT WOS:000296107700010 PM 21921285 ER PT J AU Simon, RM Paik, S Hayes, DF AF Simon, Richard M. Paik, Soonmyung Hayes, Daniel F. TI Re: Use of Archived Specimens in Evaluation of Prognostic and Predictive Biomarkers Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Simon, Richard M.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Paik, Soonmyung] Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA USA. [Hayes, Daniel F.] Univ Michigan, Breast Oncol Program, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Simon, RM (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT PY 2011 VL 103 IS 20 BP 1559 EP U85 DI 10.1093/jnci/djr332 PG 2 WC Oncology SC Oncology GA 836JJ UT WOS:000296107700016 ER PT J AU Shingai, M Yoshida, T Martin, MA Strebel, K AF Shingai, Masashi Yoshida, Takeshi Martin, Malcolm A. Strebel, Klaus TI Some Human Immunodeficiency Virus Type 1 Vpu Proteins Are Able To Antagonize Macaque BST-2 In Vitro and In Vivo: Vpu-Negative Simian-Human Immunodeficiency Viruses Are Attenuated In Vivo SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; HIV-1 VPU; ENVELOPE GLYCOPROTEIN; PARTICLE RELEASE; DOWN-MODULATION; BETA-TRCP; TRANSMEMBRANE DOMAIN; RESTRICTION FACTOR; CLINICAL-OUTCOMES; MOLECULAR CLONE AB Human immunodeficiency virus type 1 (HIV-1) Vpu enhances the release of viral particles from infected cells by targeting BST-2/tetherin, a cellular protein inhibiting virus release. The widely used HIV-1(NL4-3) Vpu functionally inactivates human BST-2 but not murine or monkey BST-2, leading to the notion that Vpu antagonism is species specific. Here we investigated the properties of the CXCR4-tropic simian-human immunodeficiency virus DH12 (SHIV(DH12)) and the CCR5-tropic SHIV(AD8), each of which carries vpu genes derived from different primary HIV-1 isolates. We found that virion release from infected rhesus peripheral blood mononuclear cells was enhanced to various degrees by the Vpu present in both SHIVs. Transfer of the SHIV(DH12) Vpu transmembrane domain to the HIV-1(NL4-3) Vpu conferred antagonizing activity against macaque BST-2. Inactivation of the SHIV(DH12) and SHIV(AD8) vpu genes impaired virus replication in 6 of 8 inoculated rhesus macaques, resulting in lower plasma viral RNA loads, slower losses of CD4(+) T cells, and delayed disease progression. The expanded host range of the SHIV(DH12) Vpu was not due to adaptation during passage in macaques but was an intrinsic property of the parental HIV-1(DH12) Vpu protein. These results demonstrate that the species-specific inhibition of BST-2 by HIV-1(NL4-3) Vpu is not characteristic of all HIV-1 Vpu proteins; some HIV-1 isolates encode a Vpu with a broader host range. C1 [Shingai, Masashi; Yoshida, Takeshi; Martin, Malcolm A.; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM mmartin@nih.gov; kstrebel@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 63 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 9708 EP 9715 DI 10.1128/JVI.00626-11 PG 8 WC Virology SC Virology GA 837ZH UT WOS:000296253900006 PM 21775449 ER PT J AU Hogue, IB Grover, JR Soheilian, F Nagashima, K Ono, A AF Hogue, Ian B. Grover, Jonathan R. Soheilian, Ferri Nagashima, Kunio Ono, Akira TI Gag Induces the Coalescence of Clustered Lipid Rafts and Tetraspanin-Enriched Microdomains at HIV-1 Assembly Sites on the Plasma Membrane SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 MATRIX PROTEIN; TO-CELL TRANSMISSION; MURINE LEUKEMIA-VIRUS; CAPSID PROTEIN; ELECTRON-MICROSCOPY; PRIMARY MACROPHAGES; PARTICLE-PRODUCTION; ADHESION RECEPTORS; INFECTIOUS HIV-1 AB The HIV-1 structural protein Gag associates with two types of plasma membrane microdomains, lipid rafts and tetraspanin-enriched microdomains (TEMs), both of which have been proposed to be platforms for HIV-1 assembly. However, a variety of studies have demonstrated that lipid rafts and TEMs are distinct microdomains in the absence of HIV-1 infection. To measure the impact of Gag on microdomain behaviors, we took advantage of two assays: an antibody-mediated copatching assay and a Forster resonance energy transfer (FRET) assay that measures the clustering of microdomain markers in live cells without antibody-mediated patching. We found that lipid rafts and TEMs copatched and clustered to a greater extent in the presence of membrane-bound Gag in both assays, suggesting that Gag induces the coalescence of lipid rafts and TEMs. Substitutions in membrane binding motifs of Gag revealed that, while Gag membrane binding is necessary to induce coalescence of lipid rafts and TEMs, either acylation of Gag or binding of phosphatidylinositol-(4,5)-bisphosphate is sufficient. Finally, a Gag derivative that is defective in inducing membrane curvature appeared less able to induce lipid raft and TEM coalescence. A higher-resolution analysis of assembly sites by correlative fluorescence and scanning electron microscopy showed that coalescence of clustered lipid rafts and TEMs occurs predominately at completed cell surface virus-like particles, whereas a transmembrane raft marker protein appeared to associate with punctate Gag fluorescence even in the absence of cell surface particles. Together, these results suggest that different membrane microdomain components are recruited in a stepwise manner during assembly. C1 [Hogue, Ian B.; Grover, Jonathan R.; Ono, Akira] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Soheilian, Ferri; Nagashima, Kunio] NCI, Electron Microscopy Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Ono, A (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, 5736 Med Sci Bldg 2,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM akiraono@umich.edu OI Ono, Akira/0000-0001-7841-851X FU NIH [R01 AI071727, R56 089282, T32 GM007544]; amfAR [107449-45-RGHF]; University of Michigan FX This work was supported by NIH grant R01 AI071727 and R56 089282 (A.O.), amfAR research grant 107449-45-RGHF (A.O.), NIH training grant T32 GM007544 (I.B.H.), and a University of Michigan Rackham Predoctoral Fellowship (I.B.H.). NR 146 TC 50 Z9 51 U1 0 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 9749 EP 9766 DI 10.1128/JVI.00743-11 PG 18 WC Virology SC Virology GA 837ZH UT WOS:000296253900010 PM 21813604 ER PT J AU Yang, ZL Reynolds, SE Martens, CA Bruno, DP Porcella, SF Moss, B AF Yang, Zhilong Reynolds, Sara E. Martens, Craig A. Bruno, Daniel P. Porcella, Stephen F. Moss, Bernard TI Expression Profiling of the Intermediate and Late Stages of Poxvirus Replication SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINIA VIRUS INTERMEDIATE; MUTATIONAL ANALYSIS; TEMPORAL REGULATION; DNA-REPLICATION; LATE PROMOTERS; GENES; TRANSCRIPTION; COMPLEX; GENOME; PROTEIN AB The double-stranded DNA genome of vaccinia virus (VACV), the prototype poxvirus, contains approximately 200 open reading frames (ORFs) that are transcribed at early, intermediate, and late stages of infection. Previous high-throughput deep RNA sequencing allowed us to map 118 VACV early genes that are expressed before viral DNA replication and 93 postreplicative genes. However, the intermediate-and late-stage postreplicative genes could not be differentiated. Here, we synchronized infections with a reversible inhibitor of DNA replication and used a VACV mutant that conditionally transcribes late genes to sequence the two classes of mRNAs. In addition, each postreplicative ORF was individually expressed under conditions that distinguished intermediate and late classes. We identified 38 VACV genes that belong to the late class and 53 that belong to the intermediate class, with some of the latter continuing to be expressed late. These data allowed us to prepare a genome-wide early, intermediate, and late transcription map. Inspection of sequences upstream of these ORFs revealed distinctive characteristics of intermediate and late promoters and suggested that some promoters have intermediate and late elements. The intermediate genes encoded many DNA binding/packaging and core-associated proteins in addition to late transcription factors; the late genes encoded many morphogenesis and mature virion membrane proteins, including those involved in entry, in addition to early transcription factors. The top-ranked antigens for CD4(+) T cells and B cells were mainly intermediate rather than late gene products. The differentiation of intermediate and late genes may enhance understanding of poxvirus replication and lead to improvements in expression vectors and recombinant vaccines. C1 [Yang, Zhilong; Reynolds, Sara E.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Reynolds, Sara E.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Martens, Craig A.; Bruno, Daniel P.; Porcella, Stephen F.] NIAID, Res Technol Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The study was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 25 TC 36 Z9 36 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 9899 EP 9908 DI 10.1128/JVI.05446-11 PG 10 WC Virology SC Virology GA 837ZH UT WOS:000296253900023 PM 21795349 ER PT J AU Lin, J Cheng, NQ Chow, M Filman, DJ Steven, AC Hogle, JM Belnap, DM AF Lin, Jun Cheng, Naiqian Chow, Marie Filman, David J. Steven, Alasdair C. Hogle, James M. Belnap, David M. TI An Externalized Polypeptide Partitions between Two Distinct Sites on Genome-Released Poliovirus Particles SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-B-VIRUS; CRYOELECTRON MICROSCOPY; CELLULAR RECEPTOR; CAPSID PROTEIN; 3-DIMENSIONAL STRUCTURE; ENTRY-INTERMEDIATE; STRUCTURAL-CHANGES; CRYSTAL-STRUCTURE; CORE ANTIGEN; VP1 AB During cell entry, native poliovirus (160S) converts to a cell-entry intermediate (135S) particle, resulting in the externalization of capsid proteins VP4 and the amino terminus of VP1 (residues 1 to 53). Externalization of these entities is followed by release of the RNA genome (uncoating), leaving an empty (80S) particle. The antigen-binding fragment (Fab) of a monospecific peptide 1 (P1) antibody, which was raised against a peptide corresponding to amino-terminal residues 24 to 40 of VP1, was utilized to track the location of the amino terminus of VP1 in the 135S and 80S states of poliovirus particles via cryogenic electron microscopy (cryo-EM) and three-dimensional image reconstruction. On 135S, P1 Fabs bind to a prominent feature on the external surface known as the "propeller tip." In contrast, our initial 80S-P1 reconstruction showed P1 Fabs also binding to a second site, at least 50 angstrom distant, at the icosahedral 2-fold axes. Further analysis showed that the overall population of 80S-P1 particles consisted of three kinds of capsids: those with P1 Fabs bound only at the propeller tips, P1 Fabs bound only at the 2-fold axes, or P1 Fabs simultaneously bound at both positions. Our results indicate that, in 80S particles, a significant fraction of VP1 can deviate from icosahedral symmetry. Hence, this portion of VP1 does not change conformation synchronously when switching from the 135S state. These conclusions are compatible with previous observations of multiple conformations of the 80S state and suggest that movement of the amino terminus of VP1 has a role in uncoating. Similar deviations from icosahedral symmetry may be biologically significant during other viral transitions. C1 [Lin, Jun; Belnap, David M.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. [Cheng, Naiqian; Steven, Alasdair C.; Belnap, David M.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Chow, Marie] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [Filman, David J.; Hogle, James M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Belnap, DM (reprint author), Brigham Young Univ, Dept Chem & Biochem, C100 BNSN, Provo, UT 84602 USA. EM David.Belnap@byu.edu OI Hogle, James/0000-0002-3655-1504 FU BYU; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health; National Institute of Allergy and Infectious Diseases [R15AI084085]; BYU Department of Chemistry and Biochemistry; NIH [R01AI020566, R01 AI022627, AI042390] FX This work was supported by BYU institutional funds (to D.M.B.) and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (to D.M.B., N.C., and A.C.S.). Jun Lin was partially supported by grant R15AI084085 from the National Institute of Allergy and Infectious Diseases (to D.M.B.) and a fellowship from the BYU Department of Chemistry and Biochemistry. This work was also supported by NIH grant R01AI020566 (to J.M.H.) and grants R01 AI022627 and AI042390 (to M.C.). NR 50 TC 24 Z9 26 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 9974 EP 9983 DI 10.1128/JVI.05013-11 PG 10 WC Virology SC Virology GA 837ZH UT WOS:000296253900030 PM 21775460 ER PT J AU Bonsignori, M Hwang, KK Chen, X Tsao, CY Morris, L Gray, E Marshall, DJ Crump, JA Kapiga, SH Sam, NE Sinangil, F Pancera, M Yang, YP Zhang, BS Zhu, J Kwong, PD O'Dell, S Mascola, JR Wu, L Nabel, GJ Phogat, S Seaman, MS Whitesides, JF Moody, MA Kelsoe, G Yang, XZ Sodroski, J Shaw, GM Montefiori, DC Kepler, TB Tomaras, GD Alam, SM Liao, HX Haynes, BF AF Bonsignori, Mattia Hwang, Kwan-Ki Chen, Xi Tsao, Chun-Yen Morris, Lynn Gray, Elin Marshall, Dawn J. Crump, John A. Kapiga, Saidi H. Sam, Noel E. Sinangil, Faruk Pancera, Marie Yang Yongping Zhang, Baoshan Zhu, Jiang Kwong, Peter D. O'Dell, Sijy Mascola, John R. Wu, Lan Nabel, Gary J. Phogat, Sanjay Seaman, Michael S. Whitesides, John F. Moody, M. Anthony Kelsoe, Garnett Yang, Xinzhen Sodroski, Joseph Shaw, George M. Montefiori, David C. Kepler, Thomas B. Tomaras, Georgia D. Alam, S. Munir Liao, Hua-Xin Haynes, Barton F. TI Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; EPSTEIN-BARR-VIRUS; B-CELL RESPONSES; CRYSTAL-STRUCTURE; PG16; PG9; INDIVIDUALS; DIVERSITY; INFECTION AB V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B. 9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies. C1 [Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Crump, John A.] Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA. [Montefiori, David C.; Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Kelsoe, Garnett] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Kepler, Thomas B.] Duke Univ, Med Ctr, Ctr Computat Immunol, Durham, NC 27710 USA. [Morris, Lynn; Gray, Elin] Natl Inst Communicable Dis, Johannesburg, South Africa. [Crump, John A.] Duke Univ, Duke Global Hlth Inst, Durham, NC 27710 USA. [Crump, John A.; Sam, Noel E.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania. [Crump, John A.] Tumaini Univ, Kilimanjaro Christian Med Coll, Moshi, Tanzania. [Kapiga, Saidi H.] London Sch Hyg & Trop Med, London WC1, England. [Sinangil, Faruk] Global Solut Infect Dis, San Francisco, CA USA. [Pancera, Marie; Yang Yongping; Zhang, Baoshan; Zhu, Jiang; Kwong, Peter D.; O'Dell, Sijy; Mascola, John R.; Wu, Lan; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Phogat, Sanjay] IAVI, AIDS Vaccine Design & Dev Lab, Brooklyn, NY USA. [Seaman, Michael S.; Yang, Xinzhen] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Sodroski, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Shaw, George M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Bonsignori, M (reprint author), Duke Univ, Med Ctr, Dept Med, Duke Human Vaccine Inst, MSRB 2,POB 103020,2 Genome Court, Durham, NC 27710 USA. EM mattia.bonsignori@duke.edu; barton.haynes@duke.edu RI Tomaras, Georgia/J-5041-2016; OI Kepler, Thomas/0000-0002-1383-6865; Moody, Tony/0000-0002-3890-5855; Gray, Elin/0000-0002-8613-3570 FU NIH [AI64518]; NIH, NIAID, the Division of AIDS with the Center for HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]; Bill and Melinda Gates Foundation; Vaccine Research Center, NIAID, NIH; International AIDS Vaccine Initiative FX Single-cell sorting was performed in the Research Flow Cytometry Core Facility at the Duke Human Vaccine Institute, partly supported by the NIH-funded Duke Center for AIDS Research (CFAR) (grant AI64518), and directed by J.F.W. This work was supported by the NIH, NIAID, the Division of AIDS with the Center for HIV/AIDS Vaccine Immunology (CHAVI) (grant U19 AI067854); by a Collaboration for AIDS Vaccine Discovery grant to B.F.H. from the Bill and Melinda Gates Foundation; in part by a grant from the intramural research program of the Vaccine Research Center, NIAID, NIH, to J.R.M., P.D.K., and G.J.N.; and by a grant from the International AIDS Vaccine Initiative to J.R.M., P.D.K., and S.P. NR 63 TC 216 Z9 219 U1 0 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 9998 EP 10009 DI 10.1128/JVI.05045-11 PG 12 WC Virology SC Virology GA 837ZH UT WOS:000296253900032 PM 21795340 ER PT J AU Koh, Y Aoki, M Danish, ML Aoki-Ogata, H Amano, M Das, D Shafer, RW Ghosh, AK Mitsuya, H AF Koh, Yasuhiro Aoki, Manabu Danish, Matthew L. Aoki-Ogata, Hiromi Amano, Masayuki Das, Debananda Shafer, Robert W. Ghosh, Arun K. Mitsuya, Hiroaki TI Loss of Protease Dimerization Inhibition Activity of Darunavir Is Associated with the Acquisition of Resistance to Darunavir by HIV-1 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 PROTEASE; IN-VITRO; ANTIRETROVIRAL THERAPY; CRYSTAL-STRUCTURE; DRUG-RESISTANCE; ANTIVIRAL ACTIVITY; POTENT; PI; SITE AB Dimerization of HIV protease is essential for the acquisition of protease's proteolytic activity. We previously identified a group of HIV protease dimerization inhibitors, including darunavir (DRV). In the present work, we examine whether loss of DRV's protease dimerization inhibition activity is associated with HIV development of DRV resistance. Single amino acid substitutions, including I3A, L5A, R8A/Q, L24A, T26A, D29N, R87K, T96A, L97A, and F99A, disrupted protease dimerization, as examined using an intermolecular fluorescence resonance energy transfer (FRET)-based HIV expression assay. All recombinant HIV(NL4-3)-based clones with such a protease dimerization-disrupting substitution failed to replicate. A highly DRV-resistant in vitro-selected HIV variant and clinical HIV strains isolated from AIDS patients failing to respond to DRV-containing antiviral regimens typically had the V32I, L33F, I54M, and I84V substitutions in common in protease. None of up to 3 of the 4 substitutions affected DRV's protease dimerization inhibition, which was significantly compromised by the four combined substitutions. Recombinant infectious clones containing up to 3 of the 4 substitutions remained sensitive to DRV, while a clonal HIV variant with all 4 substitutions proved highly resistant to DRV with a 205-fold 50% effective concentration (EC(50)) difference compared to HIV(NL4-3). The present data suggest that the loss of DRV activity to inhibit protease dimerization represents a novel mechanism contributing to HIV resistance to DRV. The finding that 4 substitutions in PR are required for significant loss of DRV's protease dimerization inhibition should at least partially explain the reason DRV has a high genetic barrier against HIV's acquisition of DRV resistance. C1 [Koh, Yasuhiro; Aoki, Manabu; Danish, Matthew L.; Aoki-Ogata, Hiromi; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto 8608556, Japan. [Koh, Yasuhiro; Aoki, Manabu; Danish, Matthew L.; Aoki-Ogata, Hiromi; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto 8608556, Japan. [Aoki, Manabu] Kumamoto Hlth Sci Univ, Dept Med Technol, Kumamoto 8615598, Japan. [Das, Debananda; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Shafer, Robert W.] Stanford Univ, Med Ctr, Div Infect Dis, Stanford, CA 94305 USA. [Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hmitsuya@helix.nih.gov RI Amano, Masayuki/N-7407-2016 OI Amano, Masayuki/0000-0003-0516-9502 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; Ministry of Health, Welfare, and Labor of Japan; Kumamoto University [78]; National Institutes of Health [GM53386] FX This work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, in part by a grant for global education and research centers aimed at the control of AIDS (Global Center of Excellence supported by Monbu-Kagakusho), Promotion of AIDS Research from the Ministry of Health, Welfare, and Labor of Japan, by a grant to the Cooperative Research Project on Clinical and Epidemiological Studies of Emerging and Reemerging Infectious Diseases (Renkei Jigyo no. 78, Kumamoto University) of Monbu-Kagakusho, and by a grant from the National Institutes of Health (GM53386 to A.K.G.). NR 42 TC 16 Z9 16 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 10079 EP 10089 DI 10.1128/JVI.05121-11 PG 11 WC Virology SC Virology GA 837ZH UT WOS:000296253900040 PM 21813613 ER PT J AU Lam, TTY Zhu, HC Wang, J Smith, DK Holmes, EC Webster, RG Webby, R Peiris, JM Guan, Y AF Lam, Tommy Tsan-Yuk Zhu, Huachen Wang, Jia Smith, David K. Holmes, Edward C. Webster, Robert G. Webby, Richard Peiris, Joseph M. Guan, Yi TI Reassortment Events among Swine Influenza A Viruses in China: Implications for the Origin of the 2009 Influenza Pandemic SO JOURNAL OF VIROLOGY LA English DT Article ID GENETIC REASSORTMENT; H1N1; PIGS; EVOLUTION; TRANSMISSION; MODELS AB That pigs may play a pivotal role in the emergence of pandemic influenza was indicated by the recent H1N1/2009 human pandemic, likely caused by a reassortant between viruses of the American triple-reassortant (TR) and Eurasian avian-like (EA) swine influenza lineages. As China has the largest human and pig populations in the world and is the only place where both TR and EA viruses have been reported to cocirculate, it is potentially the source of the H1N1/2009 pandemic virus. To examine this, the genome sequences of 405 swine influenza viruses from China were analyzed. Thirty-six TR and EA reassortant viruses were identified before and after the occurrence of the pandemic. Several of these TR-EA reassortant viruses had genotypes with most segments having the same lineage origin as the segments of the H1N1/2009 pandemic virus. However, these viruses were generated from independent reassortment events throughout our survey period and were not associated with the current pandemic. One TR-EA reassortant, which is least similar to the pandemic virus, has persisted since 2007, while all the other variants appear to be transient. Despite frequent reassortment events between TR and EA lineage viruses in China, evidence for the genesis of the 2009 pandemic virus in pigs in this region is still absent. C1 [Lam, Tommy Tsan-Yuk; Zhu, Huachen; Smith, David K.; Peiris, Joseph M.; Guan, Yi] Univ Hong Kong, State Key Lab Emerging Infect Dis, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China. [Lam, Tommy Tsan-Yuk; Zhu, Huachen; Wang, Jia; Smith, David K.; Guan, Yi] Shantou Univ, Int Inst Infect & Immun, Coll Med, Shantou, Guangdong, Peoples R China. [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Webster, Robert G.; Webby, Richard] St Jude Childrens Hosp, Div Virol, Dept Infect Dis, Memphis, TN 38105 USA. RP Guan, Y (reprint author), Univ Hong Kong, State Key Lab Emerging Infect Dis, Li Ka Shing Fac Med, 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China. EM yguan@hku.hk RI Lam, Tommy Tsan-Yuk/D-4837-2012; Zhu, Huachen/A-8252-2017; OI Zhu, Huachen/0000-0003-2711-0501; Holmes, Edward/0000-0001-9596-3552 FU National Institutes of Health (National Institute of Allergy and Infectious Diseases) [HSN266200700005C]; Li Ka Shing Foundation; Area of Excellence Scheme of the UGC of the Hong Kong SAR [AoE/M-12/06]; Computer Centre of The University of Hong Kong FX We acknowledge the National Institutes of Health (National Institute of Allergy and Infectious Diseases contract HSN266200700005C), the Li Ka Shing Foundation, and the Area of Excellence Scheme of the UGC of the Hong Kong SAR (grant AoE/M-12/06) for financial support.; We thank the staff from the International Institute of Infection and Immunity (Shantou, China) and the State Key Laboratory of Emerging Infectious Diseases (Shenzhen and Hong Kong SAR, China) for technical assistance. We acknowledge the support of HPCPower projects for bioinformatics and computational services from the Computer Centre of The University of Hong Kong. We also thank W. K. Kwan and Frankie Cheung for technical assistance. NR 27 TC 26 Z9 28 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 10279 EP 10285 DI 10.1128/JVI.05262-11 PG 7 WC Virology SC Virology GA 837ZH UT WOS:000296253900060 PM 21795347 ER PT J AU Yeh, WW Rao, SS Lim, SY Zhang, JR Hraber, PT Brassard, LM Luedemann, C Todd, JP Dodson, A Shen, L Buzby, AP Whitney, JB Korber, BT Nabel, GJ Mascola, JR Letvin, NL AF Yeh, Wendy W. Rao, Srinivas S. Lim, So-Yon Zhang, Jinrong Hraber, Peter T. Brassard, Laura M. Luedemann, Corinne Todd, John Paul Dodson, Alan Shen, Ling Buzby, Adam P. Whitney, James B. Korber, Bette T. Nabel, Gary J. Mascola, John R. Letvin, Norman L. TI The TRIM5 Gene Modulates Penile Mucosal Acquisition of Simian Immunodeficiency Virus in Rhesus Monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID VIVO VIRAL REPLICATION; HIV-1 INFECTION; MALE CIRCUMCISION; TRIM5-ALPHA; MACAQUES; CELLS; SIV; PROGRESSION; DETERMINANTS; RESTRICTION AB There is considerable variability in host susceptibility to human immunodeficiency virus type 1 (HIV-1) infection, but the host genetic determinants of that variability are not well understood. In addition to serving as a block for cross-species retroviral infection, TRIM5 was recently shown to play a central role in limiting primate immunodeficiency virus replication. We hypothesized that TRIM5 may also contribute to susceptibility to mucosal acquisition of simian immunodeficiency virus (SIV) in rhesus monkeys. We explored this hypothesis by establishing 3 cohorts of Indian-origin rhesus monkeys with different TRIM5 genotypes: homozygous restrictive, heterozygous permissive, and homozygous permissive. We then evaluated the effect of TRIM5 genotype on the penile transmission of SIVsmE660. We observed a significant effect of TRIM5 genotype on mucosal SIVsmE660 acquisition in that no SIV transmission occurred in monkeys with only restrictive TRIM5 alleles. In contrast, systemic SIV infections were initiated after preputial pocket exposures in monkeys that had at least one permissive TRIM5 allele. These data demonstrate that host genetic factors can play a critical role in restricting mucosal transmission of a primate immunodeficiency virus. In addition, we used our understanding of TRIM5 to establish a novel nonhuman primate penile transmission model for AIDS mucosal pathogenesis and vaccine research. C1 [Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Div Viral Pathogensis, Boston, MA 02215 USA. [Rao, Srinivas S.; Todd, John Paul; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hraber, Peter T.; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Dodson, Alan] Bioqual, Rockville, MD 20850 USA. RP Letvin, NL (reprint author), Beth Israel Deaconess Med Ctr, Div Viral Pathogensis, 330 Brookline Ave,E-CLS 1043, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu RI Lujan Center, LANL/G-4896-2012; OI Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897 FU NIAID [K08 AI069995, R21 AI093199]; Vaccine Research Center, NIAID, NIH, Center for HIV/AIDS Vaccine Immunology [U19 AI067854]; Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard Medical School; Infectious Diseases Society of America; Harvard University Center for AIDS Research [P30AI060354] FX This work was supported by NIAID grants K08 AI069995 and R21 AI093199 (W.W.Y.), the intramural research program of the Vaccine Research Center, NIAID, NIH, Center for HIV/AIDS Vaccine Immunology (grant U19 AI067854), Harvard Clinical and Translational Science Center grant UL1 RR 025758 (W.W.Y.), a Shore Fellowship from Harvard Medical School (W.W.Y.), the Pfizer Young Investigator Award in Vaccine Development from the Infectious Diseases Society of America (W.W.Y.), and Harvard University Center for AIDS Research grant P30AI060354 (W.W.Y.). NR 41 TC 30 Z9 30 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 19 BP 10389 EP 10398 DI 10.1128/JVI.00854-11 PG 10 WC Virology SC Virology GA 837ZH UT WOS:000296253900070 PM 21775457 ER PT J AU Dilley, KA Ni, N Nikolaitchik, OA Chen, JB Galli, A Hu, WS AF Dilley, Kari A. Ni, Na Nikolaitchik, Olga A. Chen, Jianbo Galli, Andrea Hu, Wei-Shau TI Determining the Frequency and Mechanisms of HIV-1 and HIV-2 RNA Copackaging by Single-Virion Analysis SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; INTERSUBTYPE RECOMBINATION; GENETIC-RECOMBINATION; INITIATION SIGNAL; COTE-DIVOIRE; INFECTION; ORIGIN; GENOME; GAG AB HIV-1 and HIV-2 are derived from two distinct primate viruses and share only limited sequence identity. Despite this, HIV-1 and HIV-2 Gag polyproteins can coassemble into the same particle and their genomes can undergo recombination, albeit at an extremely low frequency, implying that HIV-1 and HIV-2 RNA can be copackaged into the same particle. To determine the frequency of HIV-1 and HIV-2 RNA copackaging and to dissect the mechanisms that allow the heterologous RNA copackaging, we directly visualized the RNA content of each particle by using RNA-binding proteins tagged with fluorescent proteins to label the viral genomes. We found that when HIV-1 and HIV-2 RNA are present in viral particles at similar ratios, similar to 10% of the viral particles encapsidate both HIV-1 and HIV-2 RNAs. Furthermore, heterologous RNA copackaging can be promoted by mutating the 6-nucleotide (6-nt) dimer initiation signal (DIS) to discourage RNA homodimerization or to encourage RNA heterodimerization, indicating that HIV-1 and HIV-2 RNA can heterodimerize prior to packaging using the DIS sequences. We also observed that the coassembly of HIV-1 and HIV-2 Gag proteins is not required for the heterologous RNA copackaging; HIV-1 Gag proteins are capable of mediating HIV-1 and HIV-2 RNA copackaging. These results define the cis- and trans-acting elements required for and affecting the heterologous RNA copackaging, a prerequisite for the generation of chimeric viruses by recombination, and also shed light on the mechanisms of RNA-Gag recognition essential for RNA encapsidation. C1 [Dilley, Kari A.; Ni, Na; Nikolaitchik, Olga A.; Chen, Jianbo; Galli, Andrea; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM Wei-Shau.Hu@nih.gov RI Chen, Jianbo/N-3737-2014; OI Chen, Jianbo/0000-0001-6491-6577; Galli, Andrea/0000-0002-4404-430X FU NIH, National Cancer Institute, Center for Cancer Research; IATAP, NIH FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; IATAP funding, NIH. NR 35 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 20 BP 10499 EP 10508 DI 10.1128/JVI.05147-11 PG 10 WC Virology SC Virology GA 837ZJ UT WOS:000296254100007 PM 21849448 ER PT J AU Khattar, SK Samal, S DeVico, AL Collins, PL Samal, SK AF Khattar, Sunil K. Samal, Sweety DeVico, Anthony L. Collins, Peter L. Samal, Siba K. TI Newcastle Disease Virus Expressing Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Induces Strong Mucosal and Serum Antibody Responses in Guinea Pigs SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPH-NODE IMMUNIZATION; NEUTRALIZING ANTIBODIES; VACCINE DEVELOPMENT; IMMUNE-RESPONSES; INTRANASAL IMMUNIZATION; MONOCLONAL-ANTIBODIES; OLIGOMERIC STRUCTURE; RESPIRATORY-TRACT; ATTENUATED SIV; HIV-1 VACCINE AB Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly through mucosal sites. Optimum strategies to elicit both systemic and mucosal immunity are critical for the development of vaccines against HIV-1. We therefore sought to evaluate the induction of systemic and mucosal immune responses by the use of Newcastle disease virus (NDV) as a vaccine vector. We generated a recombinant NDV, designated rLaSota/gp160, expressing the gp160 envelope (Env) protein of HIV-1 from an added gene. The gp160 protein expressed by rLaSota/gp160 virus was detected on an infected cell surface and was incorporated into the NDV virion. Biochemical studies showed that gp160 present in infected cells and in the virion formed a higher-order oligomer that retained recognition by conformationally sensitive monoclonal antibodies. Expression of gp160 did not increase the virulence of recombinant NDV (rNDV) strain LaSota. Guinea pigs were administered rLaSota/gp160 via the intranasal (i.n.) or intramuscular (i.m.) route in different prime-boost combinations. Systemic and mucosal antibody responses specific to the HIV-1 envelope protein were assessed in serum and vaginal washes, respectively. Two or three immunizations via the i.n. or i.m. route induced a more potent systemic and mucosal immune response than a single immunization by either route. Priming by the i.n. route was more immunogenic than by the i.m. route, and the same was true for the boosts. Furthermore, immunization with rLaSota/gp160 by any route or combination of routes induced a Th1-type response, as reflected by the induction of stronger antigen-specific IgG2a than IgG1 antibody responses. Additionally, i.n. immunization elicited a stronger neutralizing serum antibody response to laboratory-adapted HIV-1 strain MN.3. These data illustrate that it is feasible to use NDV as a vaccine vector to elicit potent humoral and mucosal responses to the HIV-1 envelope protein. C1 [Khattar, Sunil K.; Samal, Sweety; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. [DeVico, Anthony L.] Univ Maryland, Sch Med, Inst Human Virol, Div Basic Sci, Baltimore, MD 21201 USA. [Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. EM ssamal@umd.edu FU NIAID [N01A060009]; NIAID, NIH FX This research was supported in part by NIAID contract no. N01A060009. P. L. C. was supported by the NIAID, NIH Intramural Research Program. NR 73 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 20 BP 10529 EP 10541 DI 10.1128/JVI.05050-11 PG 13 WC Virology SC Virology GA 837ZJ UT WOS:000296254100010 PM 21849467 ER PT J AU Blaney, JE Wirblich, C Papaneri, AB Johnson, RF Myers, CJ Juelich, TL Holbrook, MR Freiberg, AN Bernbaum, JG Jahrling, PB Paragas, J Schnell, MJ AF Blaney, Joseph E. Wirblich, Christoph Papaneri, Amy B. Johnson, Reed F. Myers, Carey J. Juelich, Terry L. Holbrook, Michael R. Freiberg, Alexander N. Bernbaum, John G. Jahrling, Peter B. Paragas, Jason Schnell, Matthias J. TI Inactivated or Live-Attenuated Bivalent Vaccines That Confer Protection against Rabies and Ebola Viruses SO JOURNAL OF VIROLOGY LA English DT Article ID NONHUMAN-PRIMATES; HEMORRHAGIC-FEVER; RESPIRATORY-TRACT; VECTORED VACCINE; TYPE-1 GAG; SAD B19; GLYCOPROTEIN; RHABDOVIRUS; INFECTION; PROTEIN AB The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas. C1 [Schnell, Matthias J.] Thomas Jefferson Univ, Jefferson Vaccine Ctr, Dept Microbiol & Immunol, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Blaney, Joseph E.; Papaneri, Amy B.; Johnson, Reed F.; Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Bethesda, MD 20892 USA. [Holbrook, Michael R.; Bernbaum, John G.; Jahrling, Peter B.; Paragas, Jason] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD 21702 USA. [Juelich, Terry L.; Holbrook, Michael R.; Freiberg, Alexander N.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Juelich, Terry L.; Freiberg, Alexander N.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. RP Schnell, MJ (reprint author), Thomas Jefferson Univ, Jefferson Vaccine Ctr, Dept Microbiol & Immunol, Jefferson Med Coll, 531 BLSB,233 S 10th St, Philadelphia, PA 19107 USA. EM jblaney@niaid.nih.gov; Matthias.schnell@jefferson.edu OI Papaneri, Amy/0000-0003-2144-2441 FU NIAID Division of Intramural Research; Jefferson Vaccine Center, TJU FX These studies were supported, in part, by the NIAID Division of Intramural Research and internal funds of the Jefferson Vaccine Center, TJU, to M.J.S. NR 54 TC 33 Z9 38 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 20 BP 10605 EP 10616 DI 10.1128/JVI.00558-11 PG 12 WC Virology SC Virology GA 837ZJ UT WOS:000296254100017 PM 21849459 ER PT J AU Nishimura, Y Shingai, M Lee, WR Sadjadpour, R Donau, OK Willey, R Brenchley, JM Iyengar, R Buckler-White, A Igarashi, T Martin, MA AF Nishimura, Yoshiaki Shingai, Masashi Lee, Wendy R. Sadjadpour, Reza Donau, Olivia K. Willey, Ronald Brenchley, Jason M. Iyengar, Ranjini Buckler-White, Alicia Igarashi, Tatsuhiko Martin, Malcolm A. TI Recombination-Mediated Changes in Coreceptor Usage Confer an Augmented Pathogenic Phenotype in a Nonhuman Primate Model of HIV-1-Induced AIDS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; HIV-1 INFECTION; T-CELL; RHESUS MACAQUE; DISEASE PROGRESSION; BIOLOGICAL PHENOTYPE; CHEMOKINE RECEPTORS; CLINICAL-OUTCOMES; TYPE-1 INFECTION AB Evolution of the env gene in transmitted R5-tropic human immunodeficiency virus type 1 (HIV-1) strains is the most widely accepted mechanism driving coreceptor switching. In some infected individuals, however, a shift in coreceptor utilization can occur as a result of the reemergence of a cotransmitted, but rapidly controlled, X4 virus. The latter possibility was studied by dually infecting rhesus macaques with X4 and R5 chimeric simian simian/human immunodeficiency viruses (SHIVs) and monitoring the replication status of each virus using specific primer pairs. In one of the infected monkeys, both SHIVs were potently suppressed by week 12 postinoculation, but a burst of viremia at week 51 was accompanied by an unrelenting loss of total CD4(+) T cells and the development of clinical disease. PCR analyses of plasma viral RNA indicated an env gene segment containing the V3 region from the inoculated X4 SHIV had been transferred into the genetic background of the input R5 SHIV by intergenomic recombination, creating an X4 virus with novel replicative, serological, and pathogenic properties. These results indicate that the effects of retrovirus recombination in vivo can be functionally profound and may even occur when one of the recombination participants is undetectable in the circulation as cell-free virus. C1 [Nishimura, Yoshiaki; Shingai, Masashi; Lee, Wendy R.; Sadjadpour, Reza; Donau, Olivia K.; Willey, Ronald; Brenchley, Jason M.; Iyengar, Ranjini; Buckler-White, Alicia; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Igarashi, Tatsuhiko] Kyoto Univ, Inst Virus Res, Lab Primate Models, Sakyo Ku, Kyoto 6068507, Japan. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 315A,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM malm@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 60 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 20 BP 10617 EP 10626 DI 10.1128/JVI.05010-11 PG 10 WC Virology SC Virology GA 837ZJ UT WOS:000296254100018 PM 21813599 ER PT J AU Tosi, G Forlani, G Andresen, V Turci, M Bertazzoni, U Franchini, G Poli, G Accolla, RS AF Tosi, Giovanna Forlani, Greta Andresen, Vibeke Turci, Marco Bertazzoni, Umberto Franchini, Genoveffa Poli, Guido Accolla, Roberto S. TI Major Histocompatibility Complex Class II Transactivator CIITA Is a Viral Restriction Factor That Targets Human T-Cell Lymphotropic Virus Type 1 Tax-1 Function and Inhibits Viral Replication SO JOURNAL OF VIROLOGY LA English DT Article ID BARE LYMPHOCYTE SYNDROME; ELEMENT-BINDING PROTEIN; COACTIVATOR CBP; HIV-1 INFECTION; IN-VITRO; HTLV-I; LEUKEMIA; PROMOTERS; GENES; CREB AB Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4(+) T lymphocytes. Since the viral transactivator Tax-1 is a major player in T-cell transformation, targeting Tax-1 protein is regarded as a possible strategy to arrest viral replication and to counteract neoplastic transformation. We demonstrate that CIITA, the master regulator of major histocompatibility complex class II gene transcription, inhibits HTLV-1 replication by blocking the transactivating function of Tax-1 both when exogenously transfected in 293T cells and when endogenously expressed by a subset of U937 promonocytic cells. Tax-1 and CIITA physically interact in vivo via the first 108 amino acids of Tax-1 and two CIITA adjacent regions (amino acids 1 to 252 and 253 to 410). Interestingly, only CIITA 1-252 mediated Tax-1 inhibition, in agreement with the fact that CIITA residues from positions 64 to 124 were required to block Tax-1 transactivation. CIITA inhibitory action on Tax-1 correlated with the nuclear localization of CIITA and was independent of the transcription factor NF-YB, previously involved in CIITA-mediated inhibition of Tax-2 of HTLV-2. Instead, CIITA severely impaired the physical and functional interaction of Tax-1 with the cellular coactivators p300/CBP-associated factor (PCAF), cyclic AMP-responsive element binding protein (CREB), and activating transcription factor 1 (ATF1), which are required for the optimal activation of HTLV-1 promoter. Accordingly, the overexpression of PCAF, CREB, and ATF1 restored Tax-1-dependent transactivation of the viral long-terminal-repeat promoter inhibited by CIITA. These findings strongly support our original observation that CIITA, beside increasing the antigen-presenting function for pathogen antigens, acts as an endogenous restriction factor against human retroviruses by blocking virus replication and spreading. C1 [Tosi, Giovanna; Forlani, Greta; Accolla, Roberto S.] Univ Insubria, Dept Expt Med, I-21100 Varese, Italy. [Andresen, Vibeke; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Turci, Marco; Bertazzoni, Umberto] Univ Verona, Dept Life & Reprod Sci, Sect Biol & Genet, I-37100 Verona, Italy. [Poli, Guido] Ist Sci San Raffaele, AIDS Immunopathogenesis Unit, Div Immunol Transplantat & Infect Dis, Milan, Italy. RP Accolla, RS (reprint author), Univ Insubria, Dept Expt Med, Via O Rossi 9, I-21100 Varese, Italy. EM roberto.accolla@uninsubria.it OI Accolla, Roberto/0000-0003-2493-7378; FORLANI, GRETA/0000-0003-1987-7761 FU Fondazione Cariplo [A.I.R.C IG 8862]; MIUR [2008-WXF7KK]; University of Insubria; Associazione Italiana per la Ricerca sul Cancro FX This study was supported by the grants to R.S.A. (Fondazione Cariplo 2008-2230, Cellular and Molecular Basis of Human Retroviral-Dependent Pathology; A.I.R.C IG 8862, New Strategies of Tumor Vaccination and Immunotherapy Based on Optimized Triggering of Anti-Tumor CD4+ T Cells; MIUR-PRIN project 2008-WXF7KK, New Strategies of Immunointervention against Tumors), University of Insubria grants FAR 2009 and FAR 2010 to G. T., and grant Miur PRIN 2007 and AIRC 2008 regional grant to U. B. NR 54 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 20 BP 10719 EP 10729 DI 10.1128/JVI.00813-11 PG 11 WC Virology SC Virology GA 837ZJ UT WOS:000296254100028 PM 21813598 ER PT J AU Kuniholm, MH Gao, XJ Xue, XN Kovacs, A Anastos, K Marti, D Greenblatt, RM Cohen, MH Minkoff, H Gange, SJ Fazzari, M Young, MA Strickler, HD Carrington, M AF Kuniholm, Mark H. Gao, Xiaojiang Xue, Xiaonan Kovacs, Andrea Anastos, Kathryn Marti, Darlene Greenblatt, Ruth M. Cohen, Mardge H. Minkoff, Howard Gange, Stephen J. Fazzari, Melissa Young, Mary A. Strickler, Howard D. Carrington, Mary TI Human Leukocyte Antigen Genotype and Risk of HIV Disease Progression before and after Initiation of Antiretroviral Therapy SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE GENITAL-TRACT; CLASS-I; HLA-BW4 HOMOZYGOSITY; DRUG-RESISTANCE; HLA-B; INFECTION; AIDS; WOMEN; RECOVERY AB While the human leukocyte antigen (HLA) genotype has been associated with the rate of HIV disease progression in untreated patients, little is known regarding these relationships in patients using highly active antiretroviral therapy (HAART). The limited data reported to date identified few HLA-HIV disease associations in patients using HAART and even occasional associations that were opposite of those found in untreated patients. We conducted high-resolution HLA class I and II genotyping in a random sample (n = 860) of HIV-seropositive women enrolled in a long-term cohort initiated in 1994. HLA-HIV disease associations before and after initiation of HAART were examined using multivariate analyses. In untreated HIV-seropositive patients, we observed many of the predicted associations, consistent with prior studies. For example, HLA-B*57 (beta = -0.7; 95% confidence interval [CI] = -0.9 to -0.5; P = 5 x 10(-11)) and Bw4 (beta = -0.2; 95% CI = -0.4 to -0.1; P = 0.009) were inversely associated with baseline HIV viral load, and B*57 was associated with a low risk of rapid CD4(+) decline (odds ratio [OR] = 0.2; 95% CI = 0.1 to 0.6; P = 0.002). Conversely, in treated patients, the odds of a virological response to HAART were lower for B*57: 01 (OR = 0.2; 95% CI = 0.0 to 0.9; P = 0.03), and Bw4 (OR = 0.4; 95% CI = 0.1 to 1.0; P = 0.04) was associated with low odds of an immunological response. The associations of HLA genotype with HIV disease are different and sometimes even opposite in treated and untreated patients. C1 [Kuniholm, Mark H.; Xue, Xiaonan; Anastos, Kathryn; Fazzari, Melissa; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] SAIC Frederick Inc, NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Kovacs, Andrea] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Cohen, Mardge H.] CORE Ctr, Cook Cty Bur Hlth Serv, Chicago, IL USA. [Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. [Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Young, Mary A.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. RP Kuniholm, MH (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Belfer Bldg,Room 1308,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM mark.kuniholm@einstein.yu.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases [5R01AI057006, R01A1052065, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH; Center for Cancer Research; Einstein-Montefiore Center for AIDS Research [5P30AI051519-08] FX Funding for this project was provided in part by grants from the National Institute of Allergy and Infectious Diseases (5R01AI057006 to H.D.S. and R01A1052065 to A.K.). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding was also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). This project has also been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by the Einstein-Montefiore Center for AIDS Research (grant 5P30AI051519-08). NR 40 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 20 BP 10826 EP 10833 DI 10.1128/JVI.00804-11 PG 8 WC Virology SC Virology GA 837ZJ UT WOS:000296254100038 PM 21849458 ER PT J AU Nagel, JD Rudick, J AF Nagel, Joan Davis Rudick, Joyce TI Eighth Annual NIH Interdisciplinary Women's Health Research Symposium November 17, 2011 Introduction SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 [Rudick, Joyce] NIH, Programs & Management Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Rudick, J (reprint author), NIH, Programs & Management Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA. EM orwh-research@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2011 VL 20 IS 10 BP 1384 EP 1385 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 833IQ UT WOS:000295877900001 ER PT J AU Alley, D Yerges, L Shardell, M Metter, EJ Simonsick, E Snitker, S Stenholm, S Shuldiner, AR Mitchell, B Ferrucci, L AF Alley, Dawn Yerges, Laura Shardell, Michelle Metter, E. Jeffrey Simonsick, Eleanor Snitker, Soren Stenholm, Sari Shuldiner, Alan R. Mitchell, Braxton Ferrucci, Luigi TI Cohort differences in Body Composition in Women: A Comparison of the Baltimore Longitudinal Study of Aging and Old Order Amish SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Alley, Dawn; Yerges, Laura; Shardell, Michelle; Snitker, Soren; Shuldiner, Alan R.; Mitchell, Braxton] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Metter, E. Jeffrey; Simonsick, Eleanor; Stenholm, Sari; Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. RI Stenholm, Sari/G-6940-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2011 VL 20 IS 10 BP 1387 EP 1387 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 833IQ UT WOS:000295877900005 ER PT J AU Foulkes, MA Grady, C Spong, CY Bates, A Clayton, JA AF Foulkes, Mary A. Grady, Christine Spong, Catherine Y. Bates, Angela Clayton, Janine A. TI Clinical Research Enrolling Pregnant Women: A Workshop Summary SO JOURNAL OF WOMENS HEALTH LA English DT Article ID DRUG-USE; PRESCRIPTION AB Clinical research investigates mechanisms of human disease, interventions, or new technologies, but pregnant women are often excluded from clinical studies. Few studies, beyond research on pregnancy, are designed to address questions relevant to pregnant women. A recent National Institutes of Health workshop considered the barriers and opportunities in conducting clinical research studies enrolling pregnant women. C1 [Foulkes, Mary A.] George Washington Univ, Ctr Biostat, Dept Hlth Policy, Rockville, MD 20852 USA. [Foulkes, Mary A.] George Washington Univ, Ctr Biostat, Dept Epidemiol & Biostat, Rockville, MD 20852 USA. [Grady, Christine] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA. [Bates, Angela; Clayton, Janine A.] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Foulkes, MA (reprint author), George Washington Univ, Ctr Biostat, Dept Hlth Policy, 6110 Executive Blvd,Suite 750, Rockville, MD 20852 USA. EM mfoulkes@bsc.gwu.edu FU U.S. Public Health Service; NIH Office of Research on Women's Health; Food and Drug Administration Office of Women's Health; Centers for Disease Control and Prevention; Health Resources and Services Administration; Eunice Kennedy Shriver National Institute of Child Health and Development; National Institute of Allergy and Infectious Diseases; National Institute of Drug Abuse; NIH Office of AIDS Research; NIH Office of Behavioral and Social Sciences Research FX The workshop summarized here was cosponsored by agencies of the U.S. Public Health Service, including the NIH Office of Research on Women's Health, the Food and Drug Administration Office of Women's Health, the Centers for Disease Control and Prevention, the Health Resources and Services Administration, the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Drug Abuse, the NIH Office of AIDS Research, and the NIH Office of Behavioral and Social Sciences Research. The authors acknowledge the vision, support, and encouragement of Dr. Vivian W. Pinn, Director, NIH Office of Research on Women's Health, without whom this meeting and discussions would not have occurred. A videocast of this meeting is available at videocast.nih.gov/summary.asp?Live=9616. NR 24 TC 8 Z9 8 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2011 VL 20 IS 10 BP 1429 EP 1432 DI 10.1089/jwh.2011.3118 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 833IQ UT WOS:000295877900086 PM 21819233 ER PT J AU Espeland, MA Miller, ME Goveas, JS Hogan, PE Coker, LH Williamson, J Naughton, M Resnick, SM AF Espeland, Mark A. Miller, Michael E. Goveas, Joseph S. Hogan, Patricia E. Coker, Laura H. Williamson, Jeff Naughton, Michelle Resnick, Susan M. CA Whisca Study Grp TI Cognitive Function and Fine Motor Speed in Older Women with Diabetes Mellitus: Results from the Women's Health Initiative Study of Cognitive Aging SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ALZHEIMERS-DISEASE; INSULIN-RESISTANCE; POSTMENOPAUSAL WOMEN; IMPAIRMENT; DECLINE; MEMORY; COHORT; ADULTS; RISK; HIPPOCAMPUS AB Background: We sought to determine if type 2 diabetes mellitus (T2DM) was associated with accelerated decline in domain-specific measures of cognitive function and fine motor speed. Methods: Women aged 65-80 years who were enrolled in a clinical trial of postmenopausal hormone therapy were grouped as having T2DM (n = 179) or not (n = 1984) and followed for an average of 5 years with annual standardized assessments of domain-specific cognitive function. Mean patterns of cognitive measures over time were contrasted between groups using general linear models and Wald tests, with varying levels of covariate adjustment. The influences of age at onset, use of oral medications, and use of insulin were also examined. Results: T2DM was associated with mean deficits of 0.2-0.4 standard deviations (SD) across follow-up in most cognitive domains. Consistent evidence that rates of decline were accelerated among women with T2DM was evident only for verbal knowledge and verbal memory (p < 0.05). Decrements in fine motor speed, but no measure of cognitive function, were greater for women with earlier onset T2DM. Use of oral diabetes medications was associated with better relative cognitive function. Conclusions: In these women, T2DM was associated with cognitive deficits in most domains. Relative deficits in verbal knowledge and verbal memory may continue to increase after deficits in other domains have stabilized. Relative deficits in fine motor speed may be greater among women with earlier onsets of T2DM. Use of insulin, which may reflect greater T2DM severity, was associated with relatively greater cognitive deficits. C1 [Espeland, Mark A.; Miller, Michael E.; Hogan, Patricia E.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Coker, Laura H.; Naughton, Michelle] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC USA. [Williamson, Jeff] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Resnick, Susan M.] NIH, Intramural Res Program, Natl Inst Aging, Baltimore, MD USA. RP Espeland, MA (reprint author), Wake Forest Hlth Sci, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mespelan@wfubme.edu FU Department of Health and Human Services; National Institute on Aging [NO1-AG-1-2106]; National Heart, Lung, and Blood Institute; Wyeth Pharmaceuticals; Wake Forest University; National Institutes of Health FX The Women's Health Initiative Study of Cognitive Aging was supported by the Department of Health and Human Services and the National Institute on Aging (NO1-AG-1-2106). The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute. Wyeth Pharmaceuticals provided the study drug and the placebo to the WHI trial. The Women's Health Initiative Memory Study was funded by Wyeth Pharmaceuticals, Wake Forest University, and the National Heart, Lung, and Blood Institute. S. M. R. is supported by the Intramural Research Program, National Institute on Aging, and National Institutes of Health. NR 45 TC 17 Z9 18 U1 2 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2011 VL 20 IS 10 BP 1435 EP 1443 DI 10.1089/jwh.2011.2812 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 833IQ UT WOS:000295877900088 PM 21819251 ER PT J AU Benard, VB Saraiya, MS Soman, A Roland, KB Yabroff, KR Miller, J AF Benard, Vicki B. Saraiya, Mona S. Soman, Ashwini Roland, Katherine B. Yabroff, K. Robin Miller, Jackie TI Cancer Screening Practices Among Physicians in the National Breast and Cervical Cancer Early Detection Program SO JOURNAL OF WOMENS HEALTH LA English DT Article ID HUMAN-PAPILLOMAVIRUS; SOCIETY GUIDELINES; UNITED-STATES; MANAGEMENT; WOMEN; AREAS; PAP AB Background: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides low-income, uninsured women with screening and diagnostic services for breast and cervical cancer. Our study was conducted to describe the demographic and practice characteristics of participating and nonparticipating physicians, as well as their beliefs, adoption of new screening technologies, and recommendations for breast and cervical cancer screening. Methods: From a 2006-2007 nationally representative survey, we identified 1,111 practicing primary care physicians who provide breast and cervical cancer screenings and assessed their recommendations using clinical vignettes related to screening initiation, frequency, and cessation. Responses of physicians participating in the NBCCEDP were compared with those from nonparticipating physicians. Results: Of the physicians surveyed, 15% reported participation in the NBCCEDP, 65% were not participants, and 20% were not sure or did not respond to this question. Program physicians were significantly more likely to practice in multispecialty settings, in a rural location, and in a hospital or clinic setting and had more patients who were female and insured by Medicaid or uninsured compared with nonprogram physicians. Beliefs about the effectiveness of screening tools or procedures in reducing breast or cervical cancer mortality were similar by program participation. Adoption of new technologies, including digital mammography and human papillomavirus (HPV) testing, and making guideline-consistent recommendations for screening initiation, frequency, and cessation did not differ significantly by program participation. Conclusions: Although there may be differences in physician characteristics and practice settings, the beliefs and screening practices for both breast and cervical cancer are similar between program and nonprogram providers. C1 [Benard, Vicki B.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Epidemiol & Appl Res Branch, Atlanta, GA 30341 USA. [Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Benard, VB (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Epidemiol & Appl Res Branch, 4770 Buford Highway,Mailstop K-55, Atlanta, GA 30341 USA. EM vbenard@cdc.gov OI Yabroff, K. Robin/0000-0003-0644-5572 FU NCI [N02-PC-51308]; CDC [Y3-PC-6017-01]; AHRQ [Y3-PC-5019-01, Y3-PC-5019-02] FX Funding for this study was provided by NCI (contract N02-PC-51308), CDC (interagency agreement Y3-PC-6017-01) and AHRQ (interagency agreements Y3-PC-5019-01 and Y3-PC-5019-02). NR 21 TC 12 Z9 12 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2011 VL 20 IS 10 BP 1479 EP 1484 DI 10.1089/jwh.2010.2530 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 833IQ UT WOS:000295877900092 PM 21774673 ER PT J AU Clark, C AF Clark, Cindy TI The 2011 Guide to Free or Nearly-Free e-Books SO LEARNED PUBLISHING LA English DT Book Review C1 [Clark, Cindy] Natl Inst Hlth Lib, Off Res Serv, NIH, Bethesda, MD 20892 USA. RP Clark, C (reprint author), Natl Inst Hlth Lib, Off Res Serv, NIH, Bethesda, MD 20892 USA. EM clarkc@ors.od.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ASSOC LEARNED PROFESSIONAL SOC PUBL PI W SUSSEX PA SOUTH HOUSE, THE STREET WORTHING, W SUSSEX BN13 3UU, ENGLAND SN 0953-1513 J9 LEARN PUBL JI Learn. Publ. PD OCT PY 2011 VL 24 IS 4 BP 332 EP 334 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA 833SU UT WOS:000295906000013 ER PT J AU Clark, C AF Clark, Cindy TI E-books in Libraries: A Practical Guide SO LEARNED PUBLISHING LA English DT Book Review C1 [Clark, Cindy] Natl Inst Hlth Lib, Off Res Serv, NIH, Bethesda, MD 20892 USA. RP Clark, C (reprint author), Natl Inst Hlth Lib, Off Res Serv, NIH, Bethesda, MD 20892 USA. EM clarkc@ors.od.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ASSOC LEARNED PROFESSIONAL SOC PUBL PI W SUSSEX PA SOUTH HOUSE, THE STREET WORTHING, W SUSSEX BN13 3UU, ENGLAND SN 0953-1513 J9 LEARN PUBL JI Learn. Publ. PD OCT PY 2011 VL 24 IS 4 BP 332 EP 334 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA 833SU UT WOS:000295906000012 ER PT J AU Kirschbaum, MH Synold, T Stein, AS Tuscano, J Zain, JM Popplewell, L Karanes, C O'Donnell, MR Pulone, B Rincon, A Wright, J Frankel, P Forman, SJ Newman, EM AF Kirschbaum, M. H. Synold, T. Stein, A. S. Tuscano, J. Zain, J. M. Popplewell, L. Karanes, C. O'Donnell, M. R. Pulone, B. Rincon, A. Wright, J. Frankel, P. Forman, S. J. Newman, E. M. TI A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia SO LEUKEMIA LA English DT Article DE farnesyltransferase; tipifarnib; Zarnestra; AML; acute myelogenous leukemia; phase 1 trial ID FARNESYLTRANSFERASE INHIBITOR TIPIFARNIB; ADVANCED CANCER; R115777; RAS AB Inhibition of farnesyltransferase (FT) activity has been associated with in vitro and in vivo anti-leukemia activity. We report the results of a phase 1 dose-escalation study of tipifarnib, an oral FT inhibitor, in patients with relapsed, refractory or newly diagnosed (if over age 70) acute myelogenous leukemia (AML), on a week-on, week-off schedule. Forty-four patients were enrolled, two patients were newly diagnosed, and the rest were relapsed or refractory to previous treatment, with a median age of 61 (range 33-79). The maximum tolerated dose was determined to be 1200 mg given orally twice daily (b.i.d.) on this schedule. Cycle 1 dose-limiting toxicities were hepatic and renal. There were three complete remissions seen, two at the 1200 mg b.i.d. dose and one at the 1000 mg b.i.d. dose, with minor responses seen at the 1400 mg b.i.d. dose level. Pharmacokinetic studies performed at doses of 1400 mg b. i. d. showed linear behavior with minimal accumulation between days 1-5. Tipifarnib administered on a week-on, week-off schedule shows activity at higher doses, and represents an option for future clinical trials in AML. Leukemia (2011) 25, 1543-1547; doi: 10.1038/leu.2011.124; published online 31 May 2011 C1 [Kirschbaum, M. H.; Stein, A. S.; Zain, J. M.; Popplewell, L.; Karanes, C.; O'Donnell, M. R.; Pulone, B.; Forman, S. J.] City Hope Natl Med Ctr, HCT, Dept Hematol, Duarte, CA USA. [Synold, T.; Newman, E. M.] City Hope Natl Med Ctr, Dept Mol Pharmacol, Duarte, CA USA. [Tuscano, J.] Calif State Univ Sacramento, Div Hematol & Oncol, Davis Sch Med, Sacramento, CA 95819 USA. [Rincon, A.; Frankel, P.] City Hope Natl Med Ctr, Dept Biostat, Duarte, CA USA. [Wright, J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kirschbaum, MH (reprint author), Nevada Canc Inst, Dept Med Oncol, 1 Breakthrough Way, Las Vegas, NV 89135 USA. EM mkirschb@yahoo.com FU NCI Cancer Therapy Evaluation Program [U01-CA-62505, N01-CM-62209]; [P30-CA-033572] FX We thank the City of Hope medical, nursing and administrative staff for their dedication and support for this study. We also thank Sandra Thomas for assistance with editing and review of the manuscript. This work was supported by grant nos. U01-CA-62505 and N01-CM-62209 (NCI Cancer Therapy Evaluation Program) and P30-CA-033572 (City of Hope). NR 15 TC 11 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2011 VL 25 IS 10 BP 1543 EP 1547 DI 10.1038/leu.2011.124 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 836WG UT WOS:000296147300003 PM 21625235 ER PT J AU Jewett, MW Jain, S Linowski, AK Sarkar, A Rosa, PA AF Jewett, Mollie W. Jain, Sunny Linowski, Angelika K. Sarkar, Amit Rosa, Patricia A. TI Molecular characterization of the Borrelia burgdorferi in vivo-essential protein PncA SO MICROBIOLOGY-SGM LA English DT Article ID LYME-DISEASE SPIROCHETE; LIFE-SPAN EXTENSION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; NICOTINAMIDASE PNCA; CALORIE RESTRICTION; INITIATION CODON; INFECTIOUS CYCLE; GENE; IDENTIFICATION AB The conversion of nicotinamide to nicotinic acid by nicotinamidase enzymes is a critical step in maintaining NAD(+) homeostasis and contributes to numerous important biological processes in diverse organisms. In Borrelia burgdorferi, the nicotinamidase enzyme, PncA, is required for spirochaete survival throughout the infectious cycle. Mammals lack nicotinamidases and therefore PncA may serve as a therapeutic target for Lyme disease. Contrary to the in vivo importance of PncA, the current annotation for the pncA ORF suggests that the encoded protein may be inactive due to the absence of an N-terminal aspartic acid residue that is a conserved member of the catalytic triad of characterized PncA proteins. Herein, we have used genetic and biochemical strategies to determine the N-terminal sequence of B. burgdorferi PncA. Our data demonstrate that the PncA protein is 24 aa longer than the currently annotated sequence and that pncA translation is initiated from the rare, non-canonical initiation codon AUU. These findings are an important first step in understanding the catalytic function of this in vivo-essential protein. C1 [Jewett, Mollie W.; Sarkar, Amit; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Jewett, Mollie W.; Jain, Sunny; Linowski, Angelika K.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32827 USA. RP Jewett, MW (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM Mollie.Jewett@ucf.edu FU NIH, NIAID [5K22AI081730] FX Many thanks to S. J. Norris, University of Texas Health Science Center at Houston, TX, USA, for giving us the Salmonella strains and to M. K. Garfield in the Protein Chemistry Section of the Research Technologies Branch, NIAID, NIH, Rockville, MD, USA, for N-terminal sequence analysis. Thank you to T. J. Jewett for critical reading of this manuscript. This research was supported, in part, by NIH, NIAID grant 5K22AI081730 to M. W. J. and the Intramural Research Program of the NIH, NIAID. NR 52 TC 11 Z9 11 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD OCT PY 2011 VL 157 BP 2831 EP 2840 DI 10.1099/mic.0.051706-0 PN 10 PG 10 WC Microbiology SC Microbiology GA 837FU UT WOS:000296177300009 PM 21778210 ER PT J AU Gallin, JI AF Gallin, John I. TI The NIH Clinical Center and the future of clinical research SO NATURE MEDICINE LA English DT Article ID COMBINATION CHEMOTHERAPY; DOUBLE-BLIND; THERAPY; DISEASE; AIDS C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Gallin, JI (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM jig@nih.gov NR 24 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2011 VL 17 IS 10 BP 1221 EP 1223 DI 10.1038/nm.2466 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 835FW UT WOS:000296022100037 PM 21989014 ER PT J AU Bollee, G Flamant, M Schordan, S Fligny, C Rumpel, E Milon, M Schordan, E Sabaa, N Vandermeersch, S Galaup, A Rodenas, A Casal, I Sunnarborg, SW Salant, DJ Kopp, JB Threadgill, DW Quaggin, SE Dussaule, JC Germain, S Mesnard, L Endlich, K Boucheix, C Belenfant, X Callard, P Endlich, N Tharaux, PL AF Bollee, Guillaume Flamant, Martin Schordan, Sandra Fligny, Cecile Rumpel, Elisabeth Milon, Marine Schordan, Eric Sabaa, Nathalie Vandermeersch, Sophie Galaup, Ariane Rodenas, Anita Casal, Ibrahim Sunnarborg, Susan W. Salant, David J. Kopp, Jeffrey B. Threadgill, David W. Quaggin, Susan E. Dussaule, Jean-Claude Germain, Stephane Mesnard, Laurent Endlich, Karlhans Boucheix, Claude Belenfant, Xavier Callard, Patrice Endlich, Nicole Tharaux, Pierre-Louis TI Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis SO NATURE MEDICINE LA English DT Article ID PARIETAL EPITHELIAL-CELLS; GENE-EXPRESSION; CELLULAR CRESCENTS; ENDOTHELIAL-CELLS; NEPHROTOXIC SERUM; MEDIATED-IMMUNITY; BOWMANS CAPSULE; TRANSGENIC MICE; MESANGIAL CELLS; T-LYMPHOCYTES AB Rapidly progressive glomerulonephritis (RPGN) is a life-threatening clinical syndrome and a morphological manifestation of severe glomerular injury that is marked by a proliferative histological pattern ('crescents') with accumulation of T cells and macrophages and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the epidermal growth factor receptor (EGFR, also known as ErbB1) in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Likewise, pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 d after the induction of experimental RPGN. This suggests that targeting the HB-EGF-EGFR pathway could also be beneficial in treatment of human RPGN. C1 [Bollee, Guillaume; Fligny, Cecile; Milon, Marine; Tharaux, Pierre-Louis] INSERM, Unite Mixte Rech UMR 970, Paris Cardiovasc Res Ctr, Paris, France. [Bollee, Guillaume; Fligny, Cecile; Milon, Marine; Tharaux, Pierre-Louis] Univ Paris 05, Paris, France. [Flamant, Martin; Sabaa, Nathalie] Univ Paris Diderot, Paris, France. [Flamant, Martin; Sabaa, Nathalie] Hop Bichat Claude Bernard, AP HP, Serv Physiol Explorat Fonct, F-75877 Paris, France. [Schordan, Sandra; Rumpel, Elisabeth; Schordan, Eric; Endlich, Karlhans; Endlich, Nicole] Univ Med Greifswald, Inst Anat & Zellbiol, Greifswald, Germany. [Vandermeersch, Sophie; Dussaule, Jean-Claude; Mesnard, Laurent] Hop Tenon, INSERM, UMR702, F-75970 Paris, France. [Vandermeersch, Sophie; Dussaule, Jean-Claude; Mesnard, Laurent; Callard, Patrice] Sorbonne Univ, Univ Paris 06, Paris, France. [Galaup, Ariane; Germain, Stephane] INSERM, Ctr Interdisciplinary Res Biol, Ctr Natl Rech Sci, UMR 7241,U1050, Paris, France. [Galaup, Ariane; Germain, Stephane] Coll France, Chaire Med Expt, F-75231 Paris, France. [Rodenas, Anita; Callard, Patrice] Hop Tenon, AP HP, Serv Anat & Cytol Pathol, F-75970 Paris, France. [Casal, Ibrahim; Boucheix, Claude] Hop Paul Brousse, INSERM, UMR 1004, Inst Andre Lwoff, Villejuif, France. [Casal, Ibrahim; Boucheix, Claude] Univ Paris 11, Villejuif, France. [Sunnarborg, Susan W.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. [Salant, David J.] Boston Univ, Med Ctr, Renal Sect, Boston, MA USA. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, Bethesda, MD USA. [Threadgill, David W.] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. [Quaggin, Susan E.] Univ Toronto, Mt Sinai Hosp, St Michaels Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Dussaule, Jean-Claude] Hop St Antoine, AP HP, Serv Physiol Explorat Fonct, F-75571 Paris, France. [Belenfant, Xavier] Ctr Hosp Intercommunal Andre Gregoire, Serv Nephrol & Dialyse, Montreuil, France. [Tharaux, Pierre-Louis] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Serv Nephrol, Paris, France. RP Tharaux, PL (reprint author), INSERM, Unite Mixte Rech UMR 970, Paris Cardiovasc Res Ctr, Paris, France. EM pierre-louis.tharaux@inserm.fr RI Endlich, Karlhans/G-5485-2013; Germain, Stephane/E-2301-2016; Tharaux, Pierre-Louis/A-9155-2009; Threadgill, David/N-4425-2013; OI Germain, Stephane/0000-0001-5992-1275; Tharaux, Pierre-Louis/0000-0002-6062-5905; Threadgill, David/0000-0003-3538-1635; Salant, David/0000-0002-3866-3120; Kopp, Jeffrey/0000-0001-9052-186X FU INSERM; l'Agence Nationale de la Recherche of France [ANR-08-EBIO-003]; German Federal Ministry of Education and Research (BMBF) [01GN0805, 03IP612]; US National Institutes of Health [CA43793, DK30932]; la Fondation pour la Recherche Medicale; la Fondation Lefoulon-Delalande FX This work was supported by INSERM, grant ANR-08-EBIO-003 (P.-L. T.) from l'Agence Nationale de la Recherche of France, grant 01GN0805 (K.E.) from the German Federal Ministry of Education and Research (BMBF) and grants CA43793 (S.W.S.) and DK30932 (D.S.) from the US National Institutes of Health. We are grateful to la Fondation pour la Recherche Medicale and la Fondation Lefoulon-Delalande for supporting G.B. and C.F., respectively. We thank L.B. Holzman (Perelman School of Medicine, University of Pennsylvania) for the use of podocin-Cre mice crossed with Z/EGFP mice. We also thank X. Biolchini, C. Kitou, C. Martin, E. Huc and the ERI970 team for assistance in animal care and handling, H. Wegner, R. Maciejewski and T. Felix for technical assistance and J. Peters for help with fluorescence-activated cell sorting (FACS; supported by InnoProfile grant 03IP612 of the BMBF). We acknowledge administrative support from M.-C. Poeuf, V. Oberweiss, A. De Rueda, M. Autran and P. Coudol. NR 56 TC 87 Z9 88 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2011 VL 17 IS 10 BP 1242 EP U272 DI 10.1038/nm.2491 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 835FW UT WOS:000296022100042 PM 21946538 ER PT J AU Chang, SH Wang, RH Akagi, K Kim, KA Martin, BK Cavallone, L Haines, DC Basik, M Mai, P Poggi, E Isaacs, C Looi, LM Mun, KS Greene, MH Byers, SW Teo, SH Deng, CX Sharan, SK AF Chang, Suhwan Wang, Rui-Hong Akagi, Keiko Kim, Kyung-Ae Martin, Betty K. Cavallone, Luca Haines, Diana C. Basik, Mark Mai, Phuong Poggi, Elizabeth Isaacs, Claudine Looi, Lai M. Mun, Kein S. Greene, Mark H. Byers, Stephen W. Teo, Soo H. Deng, Chu-Xia Sharan, Shyam K. CA Kathleen Cuningham Fdn Consortium TI Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155 SO NATURE MEDICINE LA English DT Article ID CELL-CYCLE CHECKPOINT; DNA-DAMAGE RESPONSE; BREAST-CANCER; LIGASE ACTIVITY; HIGH EXPRESSION; STEM-CELLS; IN-VIVO; C-MYC; PROTEIN; GENE AB BRCA1, a well-known tumor suppressor with multiple interacting partners, is predicted to have diverse biological functions. However, so far its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low-penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate-risk variant, and found that it does not impair DNA damage repair but abrogates the repression of microRNA-155 (miR-155), a bona fide oncomir. Mechanistically, we found that BRCA1 epigenetically represses miR-155 expression via its association with HDAC2, which deacetylates histones H2A and H3 on the miR-155 promoter. We show that overexpression of miR-155 accelerates but the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Our findings demonstrate a new mode of tumor suppression by BRCA1 and suggest that miR-155 is a potential therapeutic target for BRCA1-deficient tumors. C1 [Sharan, Shyam K.; Kathleen Cuningham Fdn Consortium] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Chang, Suhwan; Kim, Kyung-Ae] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. [Wang, Rui-Hong; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, Bethesda, MD USA. [Akagi, Keiko] Ohio State Univ, Human Canc Genet Program, Dept Mol Virol, Columbus, OH 43210 USA. [Akagi, Keiko] Ohio State Univ, Human Canc Genet Program, Dept Immunol, Columbus, OH 43210 USA. [Akagi, Keiko] Ohio State Univ, Human Canc Genet Program, Dept Med Genet, Columbus, OH 43210 USA. [Martin, Betty K.] NCI, Sci Applicat Int Corp SAIC Frederick, Frederick, MD 21701 USA. [Cavallone, Luca; Basik, Mark] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Cavallone, Luca] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada. [Cavallone, Luca] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ, Canada. [Haines, Diana C.] NCI, Pathol Histotechnol Lab, SAIC Frederick, Frederick, MD 21701 USA. [Mai, Phuong; Greene, Mark H.] NCI, Clin Genet Branch, Rockville, MD USA. [Poggi, Elizabeth; Isaacs, Claudine; Byers, Stephen W.] Georgetown Univ, Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Looi, Lai M.; Mun, Kein S.] Univ Malaya, Dept Pathol, Med Ctr, Kuala Lumpur, Malaysia. [Teo, Soo H.] Univ Malaya, Med Ctr, Dept Surg, Univ Malaya Canc Res Inst, Kuala Lumpur, Malaysia. [Teo, Soo H.] Sime Darby Med Ctr, Canc Res Initiat Fdn, Kuala Lumpur, Malaysia. RP Sharan, SK (reprint author), Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. EM sharans@mail.nih.gov RI Mun, Kein Seong/E-4155-2010; Looi, Lai Meng/A-3382-2009; Teo, Soo-hwang/H-2353-2014; deng, chuxia/N-6713-2016 OI Looi, Lai Meng/0000-0001-8325-0117; FU Center for Cancer Research, US National Cancer Institute; US National Institutes of Health FX We thank J. Acharya, K. Biswas, R. Chittela, I. Daar, K. Reilly and A. Spurdle for helpful discussions and critical review of the manuscript. We also thank D. M. Livingston (Dana-Farber Cancer Institute) and D. L. Turner (University of Michigan) for providing DNA constructs; D. Swing for help with BAC transgenic mice and allograft experiment; W. D. Foulkes, A. Spurdle, H. Thorne, Y.C. Har, P.S. Yee, A. Saleh, the Georgetown-Lombardi Comprehensive Cancer Center, Familial Cancer and Histopathology and Tissue Share Resources, who helped with the human tumor samples; S. Burkett for cytogenetic analysis; C. H. Kim for microarray analysis, and A. Kane and R. Frederickson for illustrations. The research was sponsored by the Center for Cancer Research, US National Cancer Institute and US National Institutes of Health. NR 46 TC 95 Z9 102 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2011 VL 17 IS 10 BP 1275 EP U308 DI 10.1038/nm.2459 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 835FW UT WOS:000296022100046 PM 21946536 ER PT J AU Gattinoni, L Lugli, E Ji, Y Pos, Z Paulos, CM Quigley, MF Almeida, JR Gostick, E Yu, ZY Carpenito, C Wang, E Douek, DC Price, DA June, CH Marincola, FM Roederer, M Restifo, NP AF Gattinoni, Luca Lugli, Enrico Ji, Yun Pos, Zoltan Paulos, Chrystal M. Quigley, Maire F. Almeida, Jorge R. Gostick, Emma Yu, Zhiya Carpenito, Carmine Wang, Ena Douek, Daniel C. Price, David A. June, Carl H. Marincola, Francesco M. Roederer, Mario Restifo, Nicholas P. TI A human memory T cell subset with stem cell-like properties SO NATURE MEDICINE LA English DT Article ID SUPERIOR ANTITUMOR IMMUNITY; TRANSCRIPTION FACTOR; ADOPTIVE IMMUNOTHERAPY; BETA-CATENIN; NAIVE RATHER; CANCER; DIFFERENTIATION; LYMPHOCYTE; EXPRESSION; PHENOTYPE AB Immunological memory is thought to depend on a stem cell-like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T cell population that has an enhanced capacity for self-renewal and a multipotent ability to derive central memory, effector memory and effector T cells. These cells, specific to multiple viral and self-tumor antigens, were found within a CD45RO(-), CCR7(+), CD45RA(+), CD62L(+), CD27(+), CD28(+) and IL-7R alpha(+) T cell compartment characteristic of naive T cells. However, they expressed large amounts of CD95, IL-2R beta, CXCR3, and LFA-1, and showed numerous functional attributes distinctive of memory cells. Compared with known memory populations, these lymphocytes had increased proliferative capacity and more efficiently reconstituted immunodeficient hosts, and they mediated superior antitumor responses in a humanized mouse model. The identification of a human stem cell-like memory T cell population is of direct relevance to the design of vaccines and T cell therapies. C1 [Gattinoni, Luca; Ji, Yun; Yu, Zhiya; Restifo, Nicholas P.] NCI, Ctr Canc Res, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Lugli, Enrico; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Pos, Zoltan; Wang, Ena; Marincola, Francesco M.] US Natl Inst Hlth, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. [Pos, Zoltan; Wang, Ena; Marincola, Francesco M.] US Natl Inst Hlth, Ctr Human Immunol, Bethesda, MD USA. [Paulos, Chrystal M.; Carpenito, Carmine; June, Carl H.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Paulos, Chrystal M.; Carpenito, Carmine; June, Carl H.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Quigley, Maire F.; Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales. [Quigley, Maire F.; Almeida, Jorge R.; Douek, Daniel C.; Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gattinoni, L (reprint author), NCI, Ctr Canc Res, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. EM gattinol@mail.nih.gov; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Restifo, Nicholas/A-5713-2008; Pos, Zoltan/C-3623-2014; Price, David/C-7876-2013; OI Gattinoni, Luca/0000-0003-2239-3282; Restifo, Nicholas P./0000-0003-4229-4580; Ji, Yun/0000-0001-6340-7009; Pos, Zoltan/0000-0002-2574-7616; Price, David/0000-0001-9416-2737; Ramos de Almeida, Jorge/0000-0002-5009-8478 FU US National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Programs of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research and National Institute of Allergy and Infectious Diseases. We thank S.A. Rosenberg and J.R. Wunderlich for providing samples from HLA-A*0201 patients with melanoma; P. Scheinberg for providing HLA-A*0201 samples; M. Sabatino for coordinating phereses; B.J. Hill for assistance with the TREC assay; S. P. Perfetto, R. Nguyen, D. A. Ambrozak, A. Mixon and S. Farid for help with cell sorting; P. K. Chattopadhyay and J. Yu for antibody conjugation; and R. A. Seder and C. A. Klebanoff for critical review of the manuscript. NR 56 TC 444 Z9 460 U1 3 U2 47 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2011 VL 17 IS 10 BP 1290 EP U325 DI 10.1038/nm.2446 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 835FW UT WOS:000296022100048 PM 21926977 ER PT J AU Diouf, B Cheng, Q Krynetskaia, NF Yang, WJ Cheok, M Pei, DQ Fan, YP Cheng, C Krynetskiy, EY Geng, H Chen, SY Thierfelder, WE Mullighan, CG Downing, JR Hsieh, P Pui, CH Relling, MV Evans, WE AF Diouf, Barthelemy Cheng, Qing Krynetskaia, Natalia F. Yang, Wenjian Cheok, Meyling Pei, Deqing Fan, Yiping Cheng, Cheng Krynetskiy, Evgeny Y. Geng, Hui Chen, Siying Thierfelder, William E. Mullighan, Charles G. Downing, James R. Hsieh, Peggy Pui, Ching-Hon Relling, Mary V. Evans, William E. TI Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells SO NATURE MEDICINE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COLORECTAL-CANCER; HMUTS-ALPHA; EXPRESSION; MECHANISMS; DISEASE; BINDING; GROWTH; ADULT; TSC1 AB DNA mismatch repair enzymes (for example, MSH2) maintain genomic integrity, and their deficiency predisposes to several human cancers and to drug resistance. We found that leukemia cells from a substantial proportion of children (similar to 11%) with newly diagnosed acute lymphoblastic leukemia have low or undetectable MSH2 protein levels, despite abundant wild-type MSH2 mRNA. Leukemia cells with low levels of MSH2 contained partial or complete somatic deletions of one to four genes that regulate MSH2 degradation (FRAP1 (also known as MTOR), HERC1, PRKCZ and PIK3C2B); we also found these deletions in individuals with adult acute lymphoblastic leukemia (16%) and sporadic colorectal cancer (13.5%). Knockdown of these genes in human leukemia cells recapitulated the MSH2 protein deficiency by enhancing MSH2 degradation, leading to substantial reduction in DNA mismatch repair and increased resistance to thiopurines. These findings reveal a previously unrecognized mechanism whereby somatic deletions of genes regulating MSH2 degradation result in undetectable levels of MSH2 protein in leukemia cells, DNA mismatch repair deficiency and drug resistance. C1 [Diouf, Barthelemy; Cheng, Qing; Krynetskaia, Natalia F.; Yang, Wenjian; Cheok, Meyling; Pei, Deqing; Cheng, Cheng; Krynetskiy, Evgeny Y.; Thierfelder, William E.; Mullighan, Charles G.; Downing, James R.; Pui, Ching-Hon; Relling, Mary V.; Evans, William E.] St Jude Childrens Hosp, Hematol Malignancies Program, Memphis, TN 38105 USA. [Diouf, Barthelemy; Cheng, Qing; Krynetskaia, Natalia F.; Yang, Wenjian; Cheok, Meyling; Krynetskiy, Evgeny Y.; Thierfelder, William E.; Relling, Mary V.; Evans, William E.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Pei, Deqing; Cheng, Cheng] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA. [Fan, Yiping] St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. [Geng, Hui; Chen, Siying; Hsieh, Peggy] NIDDK, Genet & Biochem Branch, US Natl Inst Hlth NIH, Bethesda, MD USA. [Mullighan, Charles G.; Downing, James R.; Pui, Ching-Hon] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Pui, Ching-Hon] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. RP Evans, WE (reprint author), St Jude Childrens Hosp, Hematol Malignancies Program, 332 N Lauderdale St, Memphis, TN 38105 USA. EM william.evans@stjude.org RI Cheok, Meyling/C-3822-2014; OI Cheok, Meyling/0000-0002-7820-8026; Mullighan, Charles/0000-0002-1871-1850 FU NIH National Institute of General Medical Sciences [U01 GM92666]; National Cancer Institute [CA 21765]; American Lebanese Syrian Associated Charities (ALSAC); National Institute of Diabetes and Digestive and Kidney Diseases of the NIH; [R37 CA36401] FX We gratefully acknowledge the subjects and parents who participated in this study and the outstanding technical support of the Hartwell Center for Bioinformatics and Biotechnology at St. Jude Children's Research Hospital. We also thank Y. Wang, T. Brooks, J. Smith, W. Du, S. Mukatira, Y. Chu, M. Needham, P. Hargrove, G. Stocco and S. Paugh for their advice and technical support; J. Groff for preparation of the figures; K. Crews, N. Kornegay and M. Wilkinson for their research database expertise; J. C. Panetta for his modeling expertise; J. Jenkins for his immunohistochemistry expertise; T. Kunkel and A. B. Clark (National Institute of Environmental Health Sciences) for providing the E. coli strains, the wild-type and mutant M13mp2 phage and for their contributions to our MMR experiments; and J. Luis Rosa (Universitat de Barcelona) for providing us with antibodies to HERC1. We thank M. Kastan and D. Green for their critical review and advice. This work was supported in part by grant R37 CA36401 (W. E. E. and M. V. R.), NIH National Institute of General Medical Sciences Pharmacogenomics Research Network grant U01 GM92666 (M. V. R. and W. E. E.), CGM is a Pew Scholar and a St. Baldrick's scholar, and St. Jude is supported by a Cancer Center Support Grant CA 21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities (ALSAC). H. G., S. C. and P. H. were funded by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH. NR 36 TC 43 Z9 43 U1 4 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2011 VL 17 IS 10 BP 1298 EP U332 DI 10.1038/nm.2430 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 835FW UT WOS:000296022100049 PM 21946537 ER PT J AU Grunwald, L Newcomb, CW Daniel, E Kacmaz, RO Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Kempen, JH AF Grunwald, Lili Newcomb, Craig W. Daniel, Ebenezer Kacmaz, R. Oktay Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Kempen, John H. CA Syst Immunosuppressive Therapy Eye TI Risk of Relapse in Primary Acute Anterior Uveitis SO OPHTHALMOLOGY LA English DT Article ID OCULAR INFLAMMATION; CLINICAL-FEATURES; HLA-B27 UVEITIS; DISEASES; OUTCOMES AB Purpose: To evaluate the risk of and risk factors for a second episode (relapse) among patients with remitted primary anterior uveitis. Design: Retrospective cohort study. Participants: Patients with primary anterior uveitis presenting to 1 of 4 academic ocular inflammation subspecialty practices achieving remission of the primary episode within 90 days of initial uveitis diagnosis. Methods: Data were obtained by standardized chart review. Main Outcome Measures: Time to relapse of anterior uveitis and risk factors for relapse. Results: We included 102 patients with a first episode of anterior uveitis who were seen within 90 days of first-ever uveitis onset and followed for 165 person-years after achieving remission of the initial episode. Most patients were female (60%) and white (78%). Forty patients had a recurrence of anterior uveitis. The incidence of relapse was 24% per person-year (95% confidence interval [CI], 17%-33%). At 1.5 years after remission, 61% (95% CI, 48%-71%) were still in remission. Younger adults had significantly higher relapse risk than middle-aged adults (hazard ratio [18-to 35-year-old persons vs. 35-to 55-year-old persons], 2.7; 95% CI, 1.3-6.0). Conclusions: Our results suggest that many patients with remitted primary anterior uveitis presenting for tertiary uveitis care will relapse. Age in the young adult range was associated with higher risk of relapse. Given the high relapse risk, management of patients with primary anterior uveitis should include an explicit plan for detecting and managing relapses. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118: 1911-1915 (C) 2011 by the American Academy of Ophthalmology. C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Univ Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol & Ophthalmol, Philadelphia, PA 19104 USA. [Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Kacmaz, R. Oktay; Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept & Epidemiol, Baltimore, MD USA. [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Eye Institute [EY014943]; National Eye Institute; Department of Veterans' Affairs FX Supported primarily by National Eye Institute Grant EY014943 (Dr. Kempen). Additional support was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. During part of the conduct of this project, Dr Kempen was an RPB James S. Adams Special Scholar Award recipient, Dr. Thorne was an RPB Harrington Special Scholar Award recipient, and Drs. Jabs and Rosenbaum were Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr. Levy-Clarke was previously supported by and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. Dr. Suhler receives support from the Department of Veterans' Affairs. NR 23 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2011 VL 118 IS 10 BP 1911 EP 1915 DI 10.1016/j.ophtha.2011.02.044 PG 5 WC Ophthalmology SC Ophthalmology GA 835WG UT WOS:000296066900004 PM 21680024 ER PT J AU Whiteman, DC Pavan, WJ Bastian, BC AF Whiteman, David C. Pavan, William J. Bastian, Boris C. TI The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Review DE Melanoma; melanocytes; risk factors; gene mutation; pathology ID CUTANEOUS MALIGNANT-MELANOMA; SITE-SPECIFIC RISK; GENOME-WIDE ASSOCIATION; MELANOCYTIC NEVI; SUN EXPOSURE; NEURAL CREST; BRAF MUTATIONS; HUMAN-SKIN; UVEAL MELANOMA; EPIDERMAL MELANOCYTES AB Converging lines of evidence from varied scientific disciplines suggest that cutaneous melanomas comprise biologically distinct subtypes that arise through multiple causal pathways. Understanding the respective relationships of each subtype with etiologic factors such as UV radiation and constitutional factors is the first necessary step toward developing refined prevention strategies for the specific forms of melanoma. Furthermore, classifying this disease precisely into biologically distinct subtypes is the key to developing mechanism-based treatments, as highlighted by recent discoveries. In this review, we outline the historical developments that underpin our understanding of melanoma heterogeneity, and we do this from the perspectives of clinical presentation, histopathology, epidemiology, molecular genetics, and developmental biology. We integrate the evidence from these separate trajectories to catalog the emerging major categories of melanomas and conclude with important unanswered questions relating to the development of melanoma and its cells of origin. C1 [Whiteman, David C.] Queensland Inst Med Res, Canc Control Grp, Brisbane, Qld 4006, Australia. [Pavan, William J.] NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Bastian, Boris C.] Mem Sloan Kettering Canc Ctr, Dept Pathol & Member, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. RP Whiteman, DC (reprint author), Queensland Inst Med Res, Canc Control Grp, Brisbane, Qld 4006, Australia. EM david.whiteman@qimr.edu.au; BastianB@mskcc.org RI Whiteman, David/P-2728-2014 OI Whiteman, David/0000-0003-2563-9559 FU Australian Research Council; National Human Genome Research Institute; National Cancer Institute [CA025874, CA142873, CA131524] FX David C. Whiteman is supported by a Future Fellowship from the Australian Research Council. William J. Pavan is supported by the National Human Genome Research Institute's Intramural Research Program. Boris C. Bastian is supported by grants from the National Cancer Institute (CA025874, CA142873, CA131524). NR 154 TC 92 Z9 94 U1 2 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD OCT PY 2011 VL 24 IS 5 BP 879 EP 897 DI 10.1111/j.1755-148X.2011.00880.x PG 19 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 835SZ UT WOS:000296057600005 PM 21707960 ER PT J AU Tock, CL Turner, LR Altiner, A Batra, P Booher, SL Coelho, SG Warner, JA Therrien, JP Turner, ML Miller, SA Beer, JZ Kraemer, KH Udey, MC Vogel, JC Terunuma, A AF Tock, Christine L. Turner, Lexa R. Altiner, Ahmet Batra, Priya Booher, Susan L. Coelho, Sergio G. Warner, Jennifer A. Therrien, Jean-Philippe Turner, Maria L. Miller, Sharon A. Beer, Janusz Z. Kraemer, Kenneth H. Udey, Mark C. Vogel, Jonathan C. Terunuma, Atsushi TI Transcriptional signatures of full-spectrum and non-UVB-spectrum solar irradiation in human skin SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Letter ID SUNSCREENS; PROTECTION C1 [Tock, Christine L.; Turner, Lexa R.; Altiner, Ahmet; Batra, Priya; Booher, Susan L.; Warner, Jennifer A.; Therrien, Jean-Philippe; Turner, Maria L.; Kraemer, Kenneth H.; Udey, Mark C.; Vogel, Jonathan C.; Terunuma, Atsushi] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Coelho, Sergio G.; Miller, Sharon A.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Terunuma, A (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM atsushi@mail.nih.gov FU Intramural NIH HHS [ZIA BC004517-35] NR 5 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD OCT PY 2011 VL 24 IS 5 BP 972 EP 974 DI 10.1111/j.1755-148X.2011.00899.x PG 3 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 835SZ UT WOS:000296057600013 PM 21848663 ER PT J AU Terracciano, A Lobina, M Piras, MG Mulas, A Cannas, A Meirelles, O Sutin, AR Zonderman, AB Uda, M Crisponi, L Schlessinger, D AF Terracciano, Antonio Lobina, Monia Piras, Maria Grazia Mulas, Antonella Cannas, Alessandra Meirelles, Osorio Sutin, Angelina R. Zonderman, Alan B. Uda, Manuela Crisponi, Laura Schlessinger, David TI Neuroticism, Depressive Symptoms, and Serum BDNF SO PSYCHOSOMATIC MEDICINE LA English DT Article DE neuroticism; depression; brain-derived neurotrophic factor; serum; plasma ID NEUROTROPHIC FACTOR BDNF; POPULATION-BASED TWIN; PERSONALITY-TRAITS; MAJOR DEPRESSION; BEHAVIORAL-MODELS; HUMAN PLATELETS; BRAIN; PLASMA; AGE; STRESS AB Objective: Animal models and clinical studies suggest that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of depression. We test whether serum and plasma levels of BDNF are associated with trait neuroticism and its facets and with state measures of depressive symptoms. Methods: In a community-based cohort (N = 2099), we measured serum and plasma BDNF concentrations and administered the Revised NEO Personality Inventory and the Center for Epidemiological Studies Depression Scale. Covariates included age, sex, cigarette smoking, obesity, and antidepressant use. Results: Serum BDNF concentrations were inversely related to neuroticism (r = -0.074, p < .001), in particular the depression facet (r = -0.08, p < .001). Lower BDNF concentrations were also associated with severe depressive symptoms (Center for Epidemiological Studies Depression Scale >= 28; odds ratio - 0.906; 95% confidence interval - 0.851-0.965). The association of serum BDNF with neuroticism was independent of depressive symptoms, indicating that serum BDNF might represent a biological correlate of neuroticism and not just of transient depressive states. Plasma BDNF was not associated with measures of depression. Conclusions: Our study suggests that lower serum BDNF is associated with both a dispositional vulnerability to depression and acute depressive states in the general population. C1 [Terracciano, Antonio; Meirelles, Osorio; Sutin, Angelina R.; Zonderman, Alan B.; Schlessinger, David] NIA, NIH, US Dept HHS, Baltimore, MD 21224 USA. [Lobina, Monia; Piras, Maria Grazia; Mulas, Antonella; Cannas, Alessandra; Uda, Manuela; Crisponi, Laura] CNR, Ist Ric Genet & Biomed, Cagliari, Italy. RP Terracciano, A (reprint author), NIA, NIH, US Dept HHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM Terraccianoa@mail.nih.gov RI terracciano, antonio/B-1884-2008; OI Mulas, Antonella/0000-0002-6856-1483; Lobina, Monia/0000-0003-3620-3160; piras, maria grazia/0000-0001-9004-0900; Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 41 TC 24 Z9 24 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2011 VL 73 IS 8 BP 638 EP 642 DI 10.1097/PSY.0b013e3182306a4f PG 5 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 835QP UT WOS:000296051200001 PM 21949427 ER PT J AU Pietrzak, RH Goldstein, RB Southwick, SM Grant, BF AF Pietrzak, Robert H. Goldstein, Rise B. Southwick, Steven M. Grant, Bridget F. TI Medical Comorbidity of Full and Partial Posttraumatic Stress Disorder in US Adults: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions SO PSYCHOSOMATIC MEDICINE LA English DT Article DE comorbidity; epidemiology; posttraumatic stress disorder; medical illness; cardiovascular ID BORDERLINE PERSONALITY-DISORDER; PSYCHIATRIC DIAGNOSTIC MODULES; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; CORONARY-HEART-DISEASE; DSM-IV ALCOHOL; UNITED-STATES; PRIMARY-CARE; CARDIOVASCULAR-DISEASE; REENGINEERING SYSTEMS AB Objective: This study examined associations between lifetime trauma exposures, PTSD and partial PTSD, and past-year medical conditions in a nationally representative sample of US adults. Methods: Face-to-face interviews were conducted with 34,653 participants in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Logistic regression analyses evaluated associations of trauma exposure, PTSD, and partial PTSD with respondent-reported medical diagnoses. Results: After adjustment for sociodemographic characteristics and comorbid Axis I and II disorders, respondents with full PTSD were more likely than traumatized respondents without full or partial PTSD (comparison group) to report diagnoses of diabetes mellitus, noncirrhotic liver disease, angina pectoris, tachycardia, hypercholesterolemia, other heart disease, stomach ulcer, human immunodeficiency virus seropositivity, gastritis, and arthritis (odds ratios [ORs] = 1.2-2.5). Respondents with partial PTSD were more likely than the comparison group to report past-year diagnoses of stomach ulcer, angina pectoris, tachycardia, and arthritis (ORs = 1.3-1.6). Men with full and partial PTSD were more likely than controls to report diagnoses of hypertension (both ORs = 1.6), and both men and women with PTSD (OR = 1.8 and OR = 1.6, respectively) and men with partial PTSD (OR = 2.0) were more likely to report gastritis. The total number of lifetime traumatic event types was associated with many assessed medical conditions (ORs = 1.04-1.16), reducing the magnitudes and rendering some of the associations between PTSD status and medical conditions nonsignificant. Conclusions: Greater lifetime trauma exposure and PTSD are associated with numerous medical conditions, many of which are stress-related and chronic, in US adults. Partial PTSD is associated with intermediate odds of some of these conditions. C1 [Pietrzak, Robert H.; Southwick, Steven M.] VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, West Haven, CT 06516 USA. [Pietrzak, Robert H.; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Pietrzak, RH (reprint author), VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 950 Campbell Ave 151-E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu OI Goldstein, Rise/0000-0002-9603-9473 FU National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism; National Center for Posttraumatic Stress Disorder; CogState, Inc FX The National Epidemiologic Survey on Alcohol and Related Conditions is funded by the National Institute on Alcohol Abuse and Alcoholism with supplemental support from the National Institute on Drug Abuse. This research was supported in part by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. Preparation of this article was also supported in part by the National Center for Posttraumatic Stress Disorder and a private donation. The funding agencies had no role in the design and conduct of the study; analysis or interpretation of the data; or preparation, review, or approval of the article.; Dr Pietrzak receives partial salary support from CogState, Inc, for work that bears no relationship to the present study. None of the authors have any financial conflict of interest to report. NR 86 TC 46 Z9 46 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2011 VL 73 IS 8 BP 697 EP 707 DI 10.1097/PSY.0b013e3182303775 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 835QP UT WOS:000296051200010 PM 21949429 ER PT J AU Laditka, JN Laditka, SB Liu, R Price, AE Wu, B Friedman, DB Corwin, SJ Sharkey, JR Tseng, W Hunter, R Logsdon, RG AF Laditka, James N. Laditka, Sarah B. Liu, Rui Price, Anna E. Wu, Bei Friedman, Daniela B. Corwin, Sara J. Sharkey, Joseph R. Tseng, Winston Hunter, Rebecca Logsdon, Rebecca G. TI Older adults' concerns about cognitive health: commonalities and differences among six United States ethnic groups SO AGEING & SOCIETY LA English DT Article DE cognition; ageing; Alzheimer's disease; dementia; memory; qualitative research; focus groups; brain health ID ALZHEIMERS-DISEASE; PHYSICAL-ACTIVITY; DEMENTIA; MEMORY; BRAIN; PERCEPTIONS; AMERICANS; PERFORMANCE; POPULATION; IMPAIRMENT AB We studied concerns about cognitive health among ethnically diverse groups of older adults. The study was grounded in theories of health behaviour and the representation of health and illness. We conducted 42 focus groups (N = 396, ages 50+) in four languages, with African Americans, American Indians, Chinese Americans, Latinos, Whites other than Latinos (hereafter, Whites) and Vietnamese Americans, in nine United States locations. Participants discussed concerns about keeping their memory or ability to think as they age. Audio recordings were transcribed verbatim. Constant comparison methods identified themes. In findings, all ethnic groups expressed concern and fear about memory loss, losing independence, and becoming 'a burden'. Knowing someone with Alzheimer's disease increased concern. American Indians, Chinese Americans, Latinos and Vietnamese Americans expected memory loss. American Indians, Chinese Americans and Vietnamese Americans were concerned about stigma associated with Alzheimer's disease. Only African Americans, Chinese and Whites expressed concern about genetic risks. Only African Americans and Whites expressed concern about behaviour changes. Although we asked participants for their thoughts about their ability to think as they age, they focused almost exclusively on memory. This suggests that health education promoting cognitive health should focus on memory, but should also educate the public about the importance of maintaining all aspects of cognitive health. C1 [Laditka, James N.; Laditka, Sarah B.] Univ N Carolina, Dept Publ Hlth Sci, Charlotte, NC 28223 USA. [Liu, Rui] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Price, Anna E.] Furman Univ, Dept Hlth & Exercise Sci, Greenville, SC 29613 USA. [Wu, Bei] Univ N Carolina, Gerontol Program, Greensboro, NC 27412 USA. [Friedman, Daniela B.; Corwin, Sara J.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Sharkey, Joseph R.] Texas A&M Hlth Sci Ctr, Sch Rural Publ Hlth, Texas Hlth Aging Res Network Collaborating Ctr Tx, College Stn, TX USA. [Tseng, Winston] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Hunter, Rebecca] Univ N Carolina, Carolina Geriatr Educ Ctr, Chapel Hill, NC USA. [Hunter, Rebecca] Univ N Carolina, Ctr Ageing & Hlth, Chapel Hill, NC USA. [Logsdon, Rebecca G.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Laditka, JN (reprint author), Univ N Carolina, Dept Publ Hlth Sci, 9201 Univ City Blvd, Charlotte, NC 28223 USA. EM jladitka@uncc.edu NR 51 TC 13 Z9 13 U1 4 U2 18 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0144-686X J9 AGEING SOC JI Ageing Soc. PD OCT PY 2011 VL 31 BP 1202 EP 1228 DI 10.1017/S0144686X10001273 PN 7 PG 27 WC Gerontology SC Geriatrics & Gerontology GA 829QE UT WOS:000295598300008 ER PT J AU Alpert, MD Harvey, JD Lauer, WA Reeves, RK Piatak, M Carville, A Mansfield, KG Lifson, JD Li, W Desrosiers, RC Johnson, RP Evans, DT AF Alpert, M. D. Harvey, J. D. Lauer, W. A. Reeves, R. K. Piatak, M. Carville, A. Mansfield, K. G. Lifson, J. D. Li, W. Desrosiers, R. C. Johnson, R. P. Evans, D. T. TI Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Is a Correlate of Protection by Live-Attenuated SIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Alpert, M. D.; Harvey, J. D.; Lauer, W. A.; Desrosiers, R. C.; Evans, D. T.] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. [Reeves, R. K.; Johnson, R. P.] Harvard Univ, Sch Med, Div Immunol, NEPRC, Southborough, MA 01772 USA. [Piatak, M.; Lifson, J. D.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Carville, A.; Mansfield, K. G.] Harvard Univ, Sch Med, Dept Pathol, NEPRC, Southborough, MA 01772 USA. [Li, W.] Univ Massachusetts, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A112 EP A112 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500289 ER PT J AU Amara, R Kannanganat, S Lai, L Gangadhara, S Kwa, S Kozlowski, P Hirsch, V Wyatt, LS Earl, PL Moss, B Robinson, HL AF Amara, R. Kannanganat, S. Lai, L. Gangadhara, S. Kwa, S. Kozlowski, P. Hirsch, V. Wyatt, L. S. Earl, P. L. Moss, B. Robinson, H. L. TI GM-CSF as an Adjuvant for MVA Vaccine: High Dose but Not Low Dose Inhibits T Cell Responses and Rectal IgA by Modulating DC Activation and Phenotype SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Amara, R.; Kannanganat, S.; Lai, L.; Gangadhara, S.; Kwa, S.] Emory Univ, Atlanta, GA 30322 USA. [Kozlowski, P.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Hirsch, V.; Wyatt, L. S.; Earl, P. L.; Moss, B.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A38 EP A38 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500088 ER PT J AU Baden, LR Liu, J Li, H Walsh, S Johnson, J Milner, D Seaman, M Krause, K Swan, E Tucker, R Weijtens, M Pau, M Dolin, R Barouch, DH AF Baden, L. R. Liu, J. Li, H. Walsh, S. Johnson, J. Milner, D. Seaman, M. Krause, K. Swan, E. Tucker, R. Weijtens, M. Pau, M. Dolin, R. Barouch, D. H. TI A Phase1 Clinical Trial to Evaluate the Safety, Mucosal and Innate Immunity of Adenovirus Type 26 HIV-1 Vaccine in Healthy, HIV-1 Uninfected Adults SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Baden, L. R.; Walsh, S.; Johnson, J.; Milner, D.; Krause, K.; Tucker, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Liu, J.; Li, H.; Seaman, M.; Dolin, R.; Barouch, D. H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Swan, E.] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A124 EP A124 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500322 ER PT J AU Bonsignori, M Wu, X Moody, MA Liao, H Hwang, K Crump, JA Capiga, SH Sam, NE Tomaras, GD Chen, X Tsao, C Alam, SM Nabel, GJ Kwong, PD Morris, L Montefiori, D Mascola, JR Haynes, BF AF Bonsignori, M. Wu, X. Moody, M. A. Liao, H. Hwang, K. Crump, J. A. Capiga, S. H. Sam, N. E. Tomaras, G. D. Chen, X. Tsao, C. Alam, S. M. Nabel, G. J. Kwong, P. D. Morris, L. Montefiori, D. Mascola, J. R. Haynes, B. F. TI Isolation of CD4-Binding Site and V2/V3 Conformational (Quaternary) Broadly Neutralizing Antibodies from the Same HIV-1 Infected African Subject SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Bonsignori, M.; Moody, M. A.; Liao, H.; Hwang, K.; Tomaras, G. D.; Chen, X.; Tsao, C.; Alam, S. M.; Haynes, B. F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Wu, X.; Nabel, G. J.; Kwong, P. D.; Mascola, J. R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Crump, J. A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Capiga, S. H.] London Sch Hyg & Trop Med, London WC1, England. [Sam, N. E.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania. [Morris, L.] Natl Inst Communicable Dis, Johannesburg, South Africa. [Montefiori, D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RI Tomaras, Georgia/J-5041-2016 NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A120 EP A120 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500310 ER PT J AU Chen, W Xiao, X Zhang, C Zhu, Z Wang, Y Goldstein, H Dimitrov, DS AF Chen, W. Xiao, X. Zhang, C. Zhu, Z. Wang, Y. Goldstein, H. Dimitrov, D. S. TI Multifunctional Fusion Proteins of the Human Engineered Antibody Domain m36.4 with Human Soluble CD4 and Fc as Potential Prophylactics SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Zhang, C.; Goldstein, H.] Albert Einstein Coll Med, New York, NY USA. [Chen, W.; Xiao, X.; Zhu, Z.; Wang, Y.; Dimitrov, D. S.] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A73 EP A74 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500185 ER PT J AU Cheng, H Moscoso, CG Xing, L Martin, L Barnett, S Srivastava, I AF Cheng, H. Moscoso, C. G. Xing, L. Martin, L. Barnett, S. Srivastava, I. TI Role of Hypervariable Loops in Intersubunit Associations of Env: Trimeric Gp140 Immunogen as a Platform for Novel Epitope Display SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Cheng, H.; Moscoso, C. G.; Xing, L.] Univ Calif Davis, Davis, CA 95616 USA. [Martin, L.] CEA, Gif Sur Yvette, France. [Barnett, S.] Novartis Inc, Cambridge, MA USA. [Srivastava, I.] NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A28 EP A29 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500068 ER PT J AU Cicala, C Van Ryk, D Nawaz, F Pascuccio, M Jelicic, K Wei, D Patel, N Block, K Arthos, J Fauci, AS AF Cicala, C. Van Ryk, D. Nawaz, F. Pascuccio, M. Jelicic, K. Wei, D. Patel, N. Block, K. Arthos, J. Fauci, A. S. TI The Removal of Transmission-linked Glycosylation Sites in HIV gp120 Promotes High a4b7-Reactivity SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Cicala, C.; Van Ryk, D.; Nawaz, F.; Pascuccio, M.; Jelicic, K.; Wei, D.; Patel, N.; Block, K.; Arthos, J.; Fauci, A. S.] Natl Inst Allergy & Infect Dis USA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A117 EP A117 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500304 ER PT J AU Currier, JR Ratto-Kim, S Ngauy, V Ake, J Lau, C Doris, T Herrera, E David, WB Sardesai, NY Boyer, J Khan, AS Lee, J Bagarazzi, M Yan, J Adams, E Earl, P Moss, B Kim, J Michael, N Robb, M Marovich, MA AF Currier, J. R. Ratto-Kim, S. Ngauy, V. Ake, J. Lau, C. Doris, T. Herrera, E. David, W. B. Sardesai, N. Y. Boyer, J. Khan, A. S. Lee, J. Bagarazzi, M. Yan, J. Adams, E. Earl, P. Moss, B. Kim, J. Michael, N. Robb, M. Marovich, M. A. TI Cell-Mediated Immune Responses After DNA Delivered by Either Biojector or Electroporation and Boosted with a Heterologous Insert Recombinant Poxvirus SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Currier, J. R.; Ratto-Kim, S.; Ake, J.; Lau, C.; Doris, T.; Herrera, E.; Kim, J.; Michael, N.; Robb, M.; Marovich, M. A.] Mil HIV Res Program, Rockville, MD USA. [Ngauy, V.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. [David, W. B.; Boyer, J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Adams, E.] NIAID, Div Aids, Bethesda, MD 20892 USA. [Earl, P.; Moss, B.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A3 EP A4 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500003 ER PT J AU Doria-Rose, NA Wu, X Yang, Z Louder, MK Mckee, K O'Dell, S Schmidt, S Koff, WC Seaman, MS Bailer, R Burton, DR Mascola, JR AF Doria-Rose, N. A. Wu, X. Yang, Z. Louder, M. K. McKee, K. O'Dell, S. Schmidt, S. Koff, W. C. Seaman, M. S. Bailer, R. Burton, D. R. Mascola, J. R. TI Combined HIV-1 Neutralization Coverage by VRC01, PG9, and PG16 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Doria-Rose, N. A.; Wu, X.; Yang, Z.; Louder, M. K.; McKee, K.; O'Dell, S.; Schmidt, S.; Bailer, R.; Mascola, J. R.] NIH, Bethesda, MD 20892 USA. [Koff, W. C.] Int AIDS Vaccine Initiat, New York, NY USA. [Seaman, M. S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Burton, D. R.] Scripps Res Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A48 EP A48 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500118 ER PT J AU Eller, L Currier, J Ratto-Kim, S Robb, M Kim, J Eller, M Barouch, D Moss, B Michael, N Marovich, M Earl, P AF Eller, L. Currier, J. Ratto-Kim, S. Robb, M. Kim, J. Eller, M. Barouch, D. Moss, B. Michael, N. Marovich, M. Earl, P. TI Construction and Characterization of HIV-1 Mosaic Modified Vaccinia Ankara (MVA) Vaccines SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Eller, L.; Currier, J.; Ratto-Kim, S.; Robb, M.; Kim, J.; Eller, M.; Michael, N.; Marovich, M.] US Mil, HIV Res Program, Rockville, MD USA. [Barouch, D.] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA. [Moss, B.] Natl Inst Allergy & I, Viral Dis Lab, NIH, Bethesda, MD USA. [Earl, P.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A75 EP A75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500188 ER PT J AU Falkowska, E Burton, DR Poignard, P Mascola, J Kwong, PD Wu, X AF Falkowska, E. Burton, D. R. Poignard, P. Mascola, J. Kwong, P. D. Wu, X. TI Potent and Broad Neutralization by a CD4 Binding Site Monoclonal Antibody from an HIV-1 Infected Donor SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Falkowska, E.; Poignard, P.] Scripps Res Inst, La Jolla, CA 92037 USA. [Falkowska, E.; Poignard, P.] IAVI Neutralizing Antibody Ctr, La Jolla, CA USA. [Burton, D. R.] IAVI Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Mascola, J.; Kwong, P. D.; Wu, X.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RI poignard, pascal/N-6678-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A8 EP A9 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500017 ER PT J AU Ferrari, G Cox, J Garcia, A Rountree, W DeCastro, C Louzao, R Liebl, B Sambor, A Sanchez, A Sarzotti-Kelsoe, M Lane, J D'Souza, P Koup, R Denny, T AF Ferrari, G. Cox, J. Garcia, A. Rountree, W. DeCastro, C. Louzao, R. Liebl, B. Sambor, A. Sanchez, A. Sarzotti-Kelsoe, M. Lane, J. D'Souza, P. Koup, R. Denny, T. TI Development of CAVD/EQAPOL Long-Term PBMC Repository ('07-'10) @ DUMC; T-Cell Functionality as Measured by ELISpot and Flow Cytometry Is Maintained Ov SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Garcia, A.; Rountree, W.; Louzao, R.; Liebl, B.; Sanchez, A.] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27706 USA. [Cox, J.] Int AIDS Vaccine Initiat, Rockville, MD USA. [DeCastro, C.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC 27706 USA. [Sambor, A.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Sarzotti-Kelsoe, M.] Duke Univ, Ctr AIDS Res, Cent QA Unit, Durham, NC 27706 USA. [Lane, J.; D'Souza, P.] Natl Inst All, Div AIDS, Bethesda, MD USA. [Koup, R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Denny, T.] Ctr HIV AIDS Vaccine Immunol, Duke Human Vaccine Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A55 EP A55 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500136 ER PT J AU Fletcher, J Ridtitid, W Marovich, M Sereti, I Rerknimitr, R Schuetz, A Pinyakorn, S Suttichom, D Rattanamanee, S Trichavaroj, R Nguay, V Kim, JH Ananworanich, J AF Fletcher, J. Ridtitid, W. Marovich, M. Sereti, I. Rerknimitr, R. Schuetz, A. Pinyakorn, S. Suttichom, D. Rattanamanee, S. Trichavaroj, R. Nguay, V. Kim, J. H. Ananworanich, J. TI Abnormal Liver Function During Acute HIV Infection Correlates with Fiebig Stage and Systemic Inflammation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Fletcher, J.; Pinyakorn, S.; Suttichom, D.; Rattanamanee, S.; Ananworanich, J.] Thai Red Cross AIDS Res Ctr, SEARCH, Bangkok, Thailand. [Ridtitid, W.; Rerknimitr, R.] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand. [Marovich, M.] US Mil HIV Res Program, Rockville, MD USA. [Sereti, I.] NIAID, Bethesda, MD 20892 USA. [Schuetz, A.] Armed Forces Res Inst Med, Div Retrovirol, Bangkok, Thailand. [Trichavaroj, R.; Nguay, V.; Kim, J. H.] AFRIMS, Div Retrovirol, Bangkok, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A33 EP A33 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500075 ER PT J AU Franchini, G Vaccari, M Keele, B Doster, M Ma, Z Hryniewicz, A Morgan, T Guan, Y Ferrari, G Montefiori, D Venzon, D Fenizia, C Lifson, JD Miller, C Tartaglia, J AF Franchini, G. Vaccari, M. Keele, B. Doster, M. Ma, Z. Hryniewicz, A. Morgan, T. Guan, Y. Ferrari, G. Montefiori, D. Venzon, D. Fenizia, C. Lifson, J. D. Miller, C. Tartaglia, J. TI Efficacy of HIV Vaccine Candidate in Macaques Dependent on the Dose of SIVmac251 Challenge Exposure: Immune Correlates of Vaccine Efficacy SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Franchini, G.; Vaccari, M.; Doster, M.; Hryniewicz, A.; Morgan, T.; Fenizia, C.] NCI, NIH, Bethesda, MD 20892 USA. [Keele, B.] NCI, AIDS & Canc Virus Program, Frederick, MD 21701 USA. [Guan, Y.] Univ Maryland, Human Monoclonal Antibody Core Lab, College Pk, MD 20742 USA. [Ferrari, G.; Montefiori, D.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Venzon, D.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Lifson, J. D.] NCI Frederick, Human Retrovirus Sect, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A111 EP A111 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500287 ER PT J AU Franchini, G Fenizia, C Nichols, D Cornara, S Binello, N Vaccari, M Pegu, P Robert-Guroff, M Ma, Z Miller, C Keele, B Venzon, D Hirsch, V AF Franchini, G. Fenizia, C. Nichols, D. Cornara, S. Binello, N. Vaccari, M. Pegu, P. Robert-Guroff, M. Ma, Z. Miller, C. Keele, B. Venzon, D. Hirsch, V. TI TRIM5 alpha Does Not Affect SIVmac251 Replication in Vaccinated or Unvaccinated Indian Rhesus Macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Robert-Guroff, M.] NCI, Lab Immune Biol, Retroviral Infect Sect, NIH, Bethesda, MD 20892 USA. [Keele, B.] NCI Frederick, Canc Virus Program, Frederick, MD USA. [Venzon, D.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Hirsch, V.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A59 EP A59 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500147 ER PT J AU Franchini, G Pegu, P Vaccari, M Gordon, S Keele, B Doster, M Guan, Y Ferrari, G Montefiori, D Venzon, D Fenizia, C Lifson, J Michael, N Kim, J Tartaglia, J AF Franchini, G. Pegu, P. Vaccari, M. Gordon, S. Keele, B. Doster, M. Guan, Y. Ferrari, G. Montefiori, D. Venzon, D. Fenizia, C. Lifson, J. Michael, N. Kim, J. Tartaglia, J. TI Titered Mucosal Challenge of Rhesus Macaques with SIVmac251 Recapitulates HIV Vaccine Efficacy in Humans SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Venzon, D.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Keele, B.] NCI Frederick, AIDS & Canc Virus Program, Frederick, MD USA. [Guan, Y.] Univ Maryland, Human Monoclonal Antibody Core Lab, College Pk, MD 20742 USA. [Ferrari, G.; Montefiori, D.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Lifson, J.] NCI, Human Retrovirus Sect, NIH, Bethesda, MD 20892 USA. [Michael, N.; Kim, J.] Walter Reed Army Inst Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A4 EP A4 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500004 ER PT J AU Gordon, SN Kines, RC Kutsyna, G Ma Hryniewicz, A Keele, BF Roberts, JN Fenizia, C Hidajat Cuburu, N Buck, B Bernardo, ML Robert-Guroff, M Miller, J Graham, BS Lowy, DR Schiller, T Franchini, G AF Gordon, S. N. Kines, R. C. Kutsyna, G. Ma Hryniewicz, A. Keele, B. F. Roberts, J. N. Fenizia, C. Hidajat Cuburu, N. Buck, B. Bernardo, M. L. Robert-Guroff, M. Miller, J. Graham, B. S. Lowy, D. R. Schiller, T. Franchini, G. TI Targeting the Vaginal Mucosa with Human Papillomavirus Pseudovirion Vaccines Delivering SIV DNA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Gordon, S. N.; Kutsyna, G.; Hryniewicz, A.; Fenizia, C.; Franchini, G.] NCI, NIH, Bethesda, MD 20892 USA. [Kines, R. C.; Roberts, J. N.; Cuburu, N.; Buck, B.; Bernardo, M. L.; Lowy, D. R.; Schiller, T.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. [Ma; Miller, J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Keele, B. F.] SAIC NCI Frederick, AIDS & Canc Virus Program, Frederick, MD USA. [Hidajat; Robert-Guroff, M.] NCI, Immune Biol Retroviral Infect Sect, Bethesda, MD 20892 USA. [Graham, B. S.] Natl Inst Allergy & Infect, Vaccine Res Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A26 EP A26 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500063 ER PT J AU Jalah, R Patel, V Kulkarni, V Valentin, A Alicea, C Rosati, M von Gegerfelt, A Sardesai, NY Bess, J Lifson, JD Keele, B Amara, RR Robinson, HL Hirsch, VM Guan, Y Venzon, D Montefiori, DC Felber, BK Pavlakis, GN AF Jalah, R. Patel, V. Kulkarni, V. Valentin, A. Alicea, C. Rosati, M. von Gegerfelt, A. Sardesai, N. Y. Bess, J., Jr. Lifson, J. D. Keele, B. Amara, R. R. Robinson, H. L. Hirsch, V. M. Guan, Y. Venzon, D. Montefiori, D. C. Felber, B. K. Pavlakis, G. N. TI DNA and Protein Vaccination Confers Protection Upon Mucosal Challenge with Heterologous SIVsmE660 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Bess, J., Jr.; Lifson, J. D.; Keele, B.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Amara, R. R.] Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Hirsch, V. M.] NIAID, Bethesda, MD 20892 USA. [Guan, Y.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Venzon, D.] NCI, Bethesda, MD 20892 USA. [Montefiori, D. C.] Duke Univ, Med Ctr, Durham, NC 27706 USA. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A24 EP A24 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500058 ER PT J AU Joyce, M Zhou, T Pancera, M Moquin, S Wu, X Zhang, B Lu, NJ Zhu, J Chen, X Georgiev, I Shapiro, L Mascola, JR Nabel, GJ Kwong, PD AF Joyce, M. Zhou, T. Pancera, M. Moquin, S. Wu, X. Zhang, B. Lu, N. J. Zhu, J. Chen, X. Georgiev, I. Shapiro, L. Mascola, J. R. Nabel, G. J. Kwong, P. D. TI Structures of Reverted and Mature VRC01-Like Antibodies Illustrate the Evolution Required to Generate Effective HIV-1 Neutralizing Antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Joyce, M.; Zhou, T.; Pancera, M.; Moquin, S.; Wu, X.; Zhang, B.; Lu, N. J.; Zhu, J.; Chen, X.; Georgiev, I.; Shapiro, L.; Mascola, J. R.; Nabel, G. J.; Kwong, P. D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A119 EP A119 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500308 ER PT J AU Kalams, SA Edupuganti, S Elizaga, M Metch, B Eldridge, J Sherwat, A De Rosa, S Khan, AS Sardesai, N Weiner, DB AF Kalams, S. A. Edupuganti, S. Elizaga, M. Metch, B. Eldridge, J. Sherwat, A. De Rosa, S. Khan, A. S. Sardesai, N. Weiner, D. B. TI Robust Immunogenicity after HIV DNA Vaccination with IL-12 Plasmid Cytokine Adjuvant Delivered via Electroporation in HIV Uninfected Adults SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Kalams, S. A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Elizaga, M.; Metch, B.; De Rosa, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Edupuganti, S.] Emory Univ, Sch Med, Atlanta, GA USA. [Eldridge, J.] Profectus BioSci Inc, Tarrytown, NY USA. [Sherwat, A.] NIAID, Bethesda, MD 20892 USA. [Khan, A. S.; Sardesai, N.] Inovio Pharmaceut, Blue Bell, PA USA. [Weiner, D. B.] Univ Penn, Philadelphia, PA 19104 USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A131 EP A131 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500340 ER PT J AU Klatt, NR Vinton, CL Ho, J Darrah, PA Lifson, JD Moir, SL Seder, RA Brenchley, JM AF Klatt, N. R. Vinton, C. L. Ho, J. Darrah, P. A. Lifson, J. D. Moir, S. L. Seder, R. A. Brenchley, J. M. TI SIV Infection of Rhesus Macaques Results in Dysfunctional T and B Cell Responses to Neo and Recall Leishmania Major Vaccination SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Klatt, N. R.; Vinton, C. L.; Brenchley, J. M.] Natl Inst Allergy & Infect, NIH, Bethesda, MD USA. [Ho, J.; Moir, S. L.] NIAID, NIH, LIR, Bethesda, MD 20892 USA. [Darrah, P. A.; Seder, R. A.] NIAID, NIH, VRC, Bethesda, MD 20892 USA. [Lifson, J. D.] NCI, ACVP, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A93 EP A93 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500237 ER PT J AU Li, Y O'Dell, S Wu, X Schmidt, S Hogerkorp, C Feng, Y Chakrabarti, B Wilson, R Longo, N Doria-Rose, N Roederer, M Connors, M Wyatt, R Mascola, J AF Li, Y. O'Dell, S. Wu, X. Schmidt, S. Hogerkorp, C. Feng, Y. Chakrabarti, B. Wilson, R. Longo, N. Doria-Rose, N. Roederer, M. Connors, M. Wyatt, R. Mascola, J. TI Isolation of a Subset of Novel HIV-1 Broadly Neutralizing Antibodies with Dual Specificity Overlapping the Env Receptor and Coreceptor Binding Sites SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Li, Y.; Feng, Y.; Chakrabarti, B.; Wilson, R.; Wyatt, R.] Scripps Res Inst, IAVI, La Jolla, CA 92037 USA. [O'Dell, S.; Wu, X.; Schmidt, S.; Hogerkorp, C.; Longo, N.; Roederer, M.; Mascola, J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Doria-Rose, N.; Connors, M.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RI Feng, Yu/A-3396-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A16 EP A16 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500037 ER PT J AU Louder, RK McLellan, J Pancera, M Schmidt, SD Yang, Y Zhang, B Phogat, S Bonsignori, M Hwang, K Liao, H Chen, X Moody, MA Haynes, BF Mascola, JR Kwong, PD AF Louder, R. K. McLellan, J. Pancera, M. Schmidt, S. D. Yang, Y. Zhang, B. Phogat, S. Bonsignori, M. Hwang, K. Liao, H. Chen, X. Moody, M. A. Haynes, B. F. Mascola, J. R. Kwong, P. D. TI Structures of HIV-1 Quaternary-Structure-Preferring Antibodies, CH04 And PG9, Show Conserved Structural Elements Within a Generallly Flexible CDR H3 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Louder, R. K.; McLellan, J.; Pancera, M.; Schmidt, S. D.; Yang, Y.; Zhang, B.; Mascola, J. R.; Kwong, P. D.] NIH, Bethesda, MD 20892 USA. [Phogat, S.] Int AIDS Vaccine Initiat, Brooklyn, NY USA. [Bonsignori, M.; Hwang, K.; Liao, H.; Chen, X.; Moody, M. A.; Haynes, B. F.] Duke Univ, Sch Med, Durham, NC USA. RI McLellan, Jason/A-6874-2010; Louder, Robert/F-4713-2014 OI Louder, Robert/0000-0002-6944-9346 NR 0 TC 0 Z9 0 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A118 EP A119 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500307 ER PT J AU Lynch, RM Louder, MK Tran, L Yang, Z Tomaras, G Cohen, M Gray, ES Sibeko, S Karim, SA Euler, Z Nabel, GJ Schuitemaker, H Montefiori, DC Morris, L Haynes, BF Mascola, J AF Lynch, R. M. Louder, M. K. Tran, L. Yang, Z. Tomaras, G. Cohen, M. Gray, E. S. Sibeko, S. Karim, S. A. Euler, Z. Nabel, G. J. Schuitemaker, H. Montefiori, D. C. Morris, L. Haynes, B. F. Mascola, J. TI Detection of CD4-Binding Site Antibodies in Three HIV-1 Seroconverter Cohorts SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Lynch, R. M.; Louder, M. K.; Tran, L.; Yang, Z.; Nabel, G. J.; Mascola, J.] NIH, Bethesda, MD 20892 USA. [Tomaras, G.; Montefiori, D. C.; Haynes, B. F.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Cohen, M.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Gray, E. S.; Morris, L.] Natl Inst Communicable Dis, Johannesburg, South Africa. [Sibeko, S.; Karim, S. A.] Univ KwaZulu Natal, Durban, South Africa. [Euler, Z.; Schuitemaker, H.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RI Tomaras, Georgia/J-5041-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A47 EP A47 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500115 ER PT J AU Madenwald, T Fuchs, J Sobieszczyk, M Karuna, S Sherwat, A Koblin, B Broder, G Eaton, N Andrasik, M Hammer, S AF Madenwald, T. Fuchs, J. Sobieszczyk, M. Karuna, S. Sherwat, A. Koblin, B. Broder, G. Eaton, N. Andrasik, M. Hammer, S. CA Div AIDS DAIDS HIV Vaccine Trials TI Attitudes and Intent to Use PrEP Among Current Phase II Preventive HIV-1 Vaccine Trial Participants SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Madenwald, T.; Karuna, S.; Broder, G.; Eaton, N.; Andrasik, M.] Fred Hutchinson Canc Res, HIV Vaccine Trials Network, Seattle, WA USA. [Fuchs, J.] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Sobieszczyk, M.; Hammer, S.] Columbia Univ, New York, NY USA. [Sherwat, A.] NIAID, Div AID, Washington, DC USA. [Koblin, B.] New York Blood Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A81 EP A81 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500205 ER PT J AU Mccoy, L Forsman, A Bulmer-Thomas, B Strokappe, N Verrips, T Chen, L Kwong, PD Weiss, RA AF McCoy, L. Forsman, A. Bulmer-Thomas, B. Strokappe, N. Verrips, T. Chen, L. Kwong, P. D. Weiss, R. A. TI Llama Antibody Fragments that Potently Neutralize HIV-1 at the CD4 Binding Site of HIV-1 Gp120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [McCoy, L.; Forsman, A.; Bulmer-Thomas, B.; Weiss, R. A.] UCL, London, England. [Strokappe, N.; Verrips, T.] Univ Utrecht, Utrecht, Netherlands. [Chen, L.; Kwong, P. D.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A44 EP A44 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500105 ER PT J AU McLellan, J Pancera, M Dai, K Boyington, J Yang, Z Carrico, C Shahzad-ul-Hussan, S Sastry, M Schmidt, S Yang, Y Bonsignori, M Haynes, B Phogat, S Bewley, C Mascola, J Schief, W Nabel, G Kwong, P AF McLellan, J. Pancera, M. Dai, K. Boyington, J. Yang, Z. Carrico, C. Shahzad-ul-Hussan, S. Sastry, M. Schmidt, S. Yang, Y. Bonsignori, M. Haynes, B. Phogat, S. Bewley, C. Mascola, J. Schief, W. Nabel, G. Kwong, P. TI HIV-1 gp120 V1V2-Scaffolds for Structural Analysis and Immunogen Design SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [McLellan, J.; Pancera, M.; Dai, K.; Boyington, J.; Yang, Z.; Shahzad-ul-Hussan, S.; Sastry, M.; Schmidt, S.; Yang, Y.; Mascola, J.; Nabel, G.; Kwong, P.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Carrico, C.; Schief, W.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Bonsignori, M.; Haynes, B.] Duke Human Vaccine Inst, Durham, NC USA. [Bonsignori, M.; Haynes, B.] Duke Ctr AIDS Res, Durham, NC USA. [Phogat, S.] Int AIDS Vaccine Initiat, Brooklyn, NY USA. [Bewley, C.] NIDDK, NIH, Bethesda, MD USA. RI McLellan, Jason/A-6874-2010 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A7 EP A8 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500014 ER PT J AU Mendoza, D Johnson, S Peterson, B Doria-Rose, N Franchini, G Schneider, D Trivett, MT Trubey, CM Coalter, V Watkins, DI Lifson, JD Migueles, SA Connors, M AF Mendoza, D. Johnson, S. Peterson, B. Doria-Rose, N. Franchini, G. Schneider, D. Trivett, M. T. Trubey, C. M. Coalter, V. Watkins, D. I. Lifson, J. D. Migueles, S. A. Connors, M. TI Cytotoxicity Capacity of SIV-Specific CD8+T Cells Against Primary Autologous Targets Correlates with Immune Control in SIV-Infected Rhesus Macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Mendoza, D.; Johnson, S.; Peterson, B.; Doria-Rose, N.; Migueles, S. A.; Connors, M.] NIAID, NIH, Chevy Chase, MD USA. [Franchini, G.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Schneider, D.; Trivett, M. T.; Trubey, C. M.; Coalter, V.; Lifson, J. D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA. [Watkins, D. I.] Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A19 EP A20 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500047 ER PT J AU Munier, S Mercier, P Calamel, A Bosquet, N Delair, T Paul, S Earl, P Le Grand, R Verrier, B AF Munier, S. Mercier, P. Calamel, A. Bosquet, N. Delair, T. Paul, S. Earl, P. Le Grand, R. Verrier, B. TI Priming with Synthetic Nanovaccine Followed by rMVA Boost Is the Best Combination to Elicit Strong and Long-Lasting Gag or Env Immune Responses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Bosquet, N.; Le Grand, R.] CEA, Fontenay Aux Roses, France. [Delair, T.] Univ Lyon, Lyon, France. [Paul, S.] Univ St Etienne, St Etienne, France. [Earl, P.] NIH, Bethesda, MD 20892 USA. [Munier, S.; Mercier, P.; Calamel, A.; Verrier, B.] Ctr Natl Rech Sci, Lyon, France. NR 0 TC 0 Z9 0 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A108 EP A108 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500278 ER PT J AU Ortiz, A Li, B Klatt, NR Lawson, B Ryzhova, E Carnathan, P Paiardini, M Else, J Gonzalez-Scarano, F Ratcliffe, SJ Brenchley, J Estes, J Derdeyn, C Silvestri, G AF Ortiz, A. Li, B. Klatt, N. R. Lawson, B. Ryzhova, E. Carnathan, P. Paiardini, M. Else, J. Gonzalez-Scarano, F. Ratcliffe, S. J. Brenchley, J. Estes, J. Derdeyn, C. Silvestri, G. TI Evidence for CD4 T-Cell Mediated Immune Control of Macrophage Infection in Rhesus Macaques Undergoing CD4+Lymphocyte Depletion Prior to SIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Ortiz, A.; Li, B.; Lawson, B.; Carnathan, P.; Paiardini, M.; Else, J.; Derdeyn, C.; Silvestri, G.] Emory Univ, Atlanta, GA 30322 USA. [Klatt, N. R.; Brenchley, J.] NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. [Ryzhova, E.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Gonzalez-Scarano, F.] UT Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX USA. [Ratcliffe, S. J.] Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA. [Estes, J.] NCI, AIDS & Canc Virus Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A17 EP A18 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500042 ER PT J AU Pancera, M Zhu, J O'Dell, S Wu, X Yang, Y Zhang, B Doria-Rose, N Connors, M Moore, P Karim, S Morris, L Simek, M Poignard, P Burton, DR Koff, W Mascola, JR Kwong, PD AF Pancera, M. Zhu, J. O'Dell, S. Wu, X. Yang, Y. Zhang, B. Doria-Rose, N. Connors, M. Moore, P. Karim, S. Morris, L. Simek, M. Poignard, P. Burton, D. R. Koff, W. Mascola, J. R. Kwong, P. D. TI 454 Pryosequencing of B Cells From HIV-1 Infected Donors With Quaternary-Structure-Preferring Antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Pancera, M.; Zhu, J.; O'Dell, S.; Wu, X.; Yang, Y.; Zhang, B.; Mascola, J. R.; Kwong, P. D.] NIAID, VRC, NIH, Bethesda, MD 20892 USA. [Moore, P.; Morris, L.] Natl Inst Communicable Dis, AIDS Virus Res Unit, Johannesburg, South Africa. [Karim, S.] Univ KwaZulu Natal, CAPRISA, Durban, South Africa. [Simek, M.; Koff, W.] Int AIDS Vaccine Initiat, New York, NY USA. [Poignard, P.; Burton, D. R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. RI poignard, pascal/N-6678-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A121 EP A121 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500313 ER PT J AU Pavlakis, GN Rolland, M Felber, BK Kulkarni, V Mothe, B Brander, C Termini, J Stone, GW Le Gall, S Yan, J Weiner, DB Manocheewa, S Swain, JV Lanxon-Cookson, E Mullins, JI AF Pavlakis, G. N. Rolland, M. Felber, B. K. Kulkarni, V. Mothe, B. Brander, C. Termini, J. Stone, G. W. Le Gall, S. Yan, J. Weiner, D. B. Manocheewa, S. Swain, J. V. Lanxon-Cookson, E. Mullins, J. I. TI Conserved Elements (CE) Vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Pavlakis, G. N.; Felber, B. K.; Kulkarni, V.] NCI, NIH, Frederick, MD 21701 USA. [Mothe, B.; Brander, C.] Irsi Caixa HIVACAT, Barcelona, Spain. [Termini, J.; Stone, G. W.] Univ Miami, Miami, FL USA. [Le Gall, S.] Ragon Inst, Boston, MA USA. [Yan, J.; Weiner, D. B.] Univ Penn, Philadelphia, PA 19104 USA. [Rolland, M.; Manocheewa, S.; Swain, J. V.; Lanxon-Cookson, E.; Mullins, J. I.] Univ Washington, Seattle, WA 98195 USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A110 EP A110 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500284 ER PT J AU Qureshi, H Ma, Z Huang, Y Hodge, G Thomas, M DiPasquale, J DeSilva, V Fritts, L Bett, AJ Shiver, J Robert-Guroff, M Robertson, M Casimiro, D McChesney, M Gilbert, P Miller, C AF Qureshi, H. Ma, Z. Huang, Y. Hodge, G. Thomas, M. DiPasquale, J. DeSilva, V. Fritts, L. Bett, A. J. Shiver, J. Robert-Guroff, M. Robertson, M. Casimiro, D. McChesney, M. Gilbert, P. Miller, C. TI Penile SIV Challenge of Ad5-Infected Macaques Immunized With an Ad5-Based Vaccine Recapitulates the Enhanced Infection Rate Among STEP Trial Vaccines SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Huang, Y.; Gilbert, P.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. [Thomas, M.; DiPasquale, J.; Robert-Guroff, M.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Bett, A. J.; Shiver, J.; Robertson, M.; Casimiro, D.] Merck Res Labs, West Point, PA USA. [Qureshi, H.; Ma, Z.; Hodge, G.; DeSilva, V.; Fritts, L.; McChesney, M.; Miller, C.] UC Davis, Davis, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A126 EP A126 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500327 ER PT J AU Rerks-Ngarm, S Paris, RM Chunsutthiwat, S Premsri, N Namwat, C Bowornwatanuwong, J Li, S Kaewkungkal, J Trichavaroj, R de Souza, M Francis, D Adams, E Gurunathan, S Tartaglia, J O'Connell, R Eamsila, C Nitayaphan, S Ngauy, V Thongcharoen, P Kunasol, P Michael, N Robb, M Gilbert, P Kim, J AF Rerks-Ngarm, S. Paris, R. M. Chunsutthiwat, S. Premsri, N. Namwat, C. Bowornwatanuwong, J. Li, S. Kaewkungkal, J. Trichavaroj, R. de Souza, M. Francis, D. Adams, E. Gurunathan, S. Tartaglia, J. O'Connell, R. Eamsila, C. Nitayaphan, S. Ngauy, V. Thongcharoen, P. Kunasol, P. Michael, N. Robb, M. Gilbert, P. Kim, J. TI Extended Evaluation of Volunteers Who Become HIV-1 Infected During Participation in a Phase III Vaccine Trial of ALVAC-HIV and AIDSVAX (R) B/E SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Rerks-Ngarm, S.; Chunsutthiwat, S.; Premsri, N.; Namwat, C.; Kunasol, P.] Prime Boost HIV Vaccine Phase III Trial, Nonthaburi, Thailand. [Paris, R. M.; O'Connell, R.; Robb, M.; Kim, J.] US Mil HIV Res Program, Rockville, MD USA. [Bowornwatanuwong, J.] Chonburi Reg Hosp, Chon Buri, Thailand. [Li, S.; Gilbert, P.] SCHARP, Seattle, WA USA. [Kaewkungkal, J.] Mahidol Univ, Fac Trop Med, Bangkok, Thailand. [Trichavaroj, R.] USAMC AFRIMS, Dept Retrovirol, Bangkok, Thailand. [de Souza, M.; Ngauy, V.] MHRP AFRIMS, Bangkok, Thailand. [Francis, D.] GSID, San Francisco, CA USA. [Adams, E.] NIAID, NIH, Bethesda, MD 20892 USA. [Gurunathan, S.; Tartaglia, J.] Sanofi Pasteur, Swiftwater, PA USA. [Eamsila, C.; Nitayaphan, S.] Royal Thai Army, AFRIMS, Bangkok, Thailand. [Thongcharoen, P.] Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand. [Michael, N.] US Mil HIV Res Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A28 EP A28 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500066 ER PT J AU Robinson, HL Lai, L Kwa, S Kozlowski, PA Hirsch, V Felber, BK Pavlakis, GN Earl, PL Moss, B Amara, RR AF Robinson, H. L. Lai, L. Kwa, S. Kozlowski, P. A. Hirsch, V. Felber, B. K. Pavlakis, G. N. Earl, P. L. Moss, B. Amara, R. R. TI Homologous Priming and Boosting with Recombinant MVA, Prevention of Infection as Good as With the Heterologous Regimen of DNA Priming and MVA Boosting SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Lai, L.; Kwa, S.] Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Kozlowski, P. A.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Hirsch, V.; Earl, P. L.; Moss, B.] NIAID, NIH, Bethesda, MD 20892 USA. [Felber, B. K.; Pavlakis, G. N.] NCI, Frederick, MD 21701 USA. [Amara, R. R.] Emory Univ, Vaccine Res Ctr, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A4 EP A5 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500006 ER PT J AU Simmons, RP Groden, E Chang, JJ Lindsay, R Fadda, L Lifson, JD Lane, K Axten, K Rosenberg, E Allen, T Altfeld, M AF Simmons, R. P. Groden, E. Chang, J. J. Lindsay, R. Fadda, L. Lifson, J. D. Lane, K. Axten, K. Rosenberg, E. Allen, T. Altfeld, M. TI Different Cytokine Profiles Induced by HIV-1 and HIV-1-Derived TLR Ligands in Monocytes and mDCs SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Simmons, R. P.; Groden, E.; Chang, J. J.; Lindsay, R.; Fadda, L.; Lane, K.; Axten, K.; Allen, T.; Altfeld, M.] MIT & Harvard, Ragon Inst MGH, Charlestown, MA USA. [Lifson, J. D.] NCI, AIDS & Canc Virus Program, Frederick, MD 21701 USA. [Rosenberg, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A63 EP A63 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500158 ER PT J AU Smith, LM Parodi, LM Hodara, VL Pavlakis, G Felber, B Giavedoni, LD AF Smith, L. M. Parodi, L. M. Hodara, V. L. Pavlakis, G. Felber, B. Giavedoni, L. D. TI Biologically Active Fusion Proteins of CD154 and SIVgp41 as Novel Vaccine Components SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Pavlakis, G.; Felber, B.] NCI, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Smith, L. M.; Parodi, L. M.; Hodara, V. L.; Giavedoni, L. D.] Texas Biomed Res Inst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A111 EP A112 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500288 ER PT J AU Sundling, C Li, Y Huynh, N Wilson, R O'Dell, S Mascola, JR Wyatt, RT Hedestam, GBK AF Sundling, C. Li, Y. Huynh, N. Wilson, R. O'Dell, S. Mascola, J. R. Wyatt, R. T. Hedestam, G. B. Karlsson TI Characterization of CD4-Binding Site Directed Monoclonal Antibodies Isolated from HIV-1 gp140 Env Immunized Rhesus Macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Sundling, C.; Huynh, N.; Hedestam, G. B. Karlsson] Karolinska Inst, Stockholm, Sweden. [Li, Y.; Wilson, R.; Wyatt, R. T.] Dept Immunol & Microbial Sci, La Jolla, CA USA. [O'Dell, S.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A9 EP A10 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500020 ER PT J AU van Gils, MJ Crooks, ET Decker, JM Gray, ES Tumba, NL Lynch, R Mascola, JR Morris, L Binley, J Schuitemaker, H AF van Gils, M. J. Crooks, E. T. Decker, J. M. Gray, E. S. Tumba, N. L. Lynch, R. Mascola, J. R. Morris, L. Binley, J. Schuitemaker, H. TI Neutralizing Activity Against Both Gp120 and Gp41 in Patients with HIV-Specific Cross-Reactive Neutralizing Humoral Immunity SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [van Gils, M. J.; Schuitemaker, H.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Crooks, E. T.; Binley, J.] Torrey Pines Inst Mol Studies, San Diego, CA USA. [Decker, J. M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Gray, E. S.; Tumba, N. L.; Morris, L.] Natl Inst Communicable Dis, Johannesburg, South Africa. [Lynch, R.] Natl Inst Allergy & Infect, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A41 EP A41 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500098 ER PT J AU Wagner, D Gaekwad, J Narpala, S Carpov, A Pancera, M Walker, LM Hoffenberg, S Kwong, PD Mascola, JR Burton, DR Koff, WC King, R Wyatt, RT Phogat, SK AF Wagner, D. Gaekwad, J. Narpala, S. Carpov, A. Pancera, M. Walker, L. M. Hoffenberg, S. Kwong, P. D. Mascola, J. R. Burton, D. R. Koff, W. C. King, R. Wyatt, R. T. Phogat, S. K. TI PG16 Binding Early Transmitted HIV-1 Clade C Virus 16055 Soluble Envelope Glycoprotein as Candidate Vaccine Immunogen SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Gaekwad, J.; Wyatt, R. T.] Scripps Res Inst, IAVI NAC Ctr, La Jolla, CA 92037 USA. [Pancera, M.] NIAID, Vaccine Reserach Ctr, NIH, Bethesda, MD 20892 USA. [Kwong, P. D.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Koff, W. C.; King, R.; Phogat, S. K.] Int AIDS Vaccine Initiat, Brooklyn, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A53 EP A53 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500131 ER PT J AU Wang, YE Oniangue-Nzda, C Schneidewind, A Kemper, M Mellors, E Qi, Y Gladden, AD Power, KA Pereyra, F Walker, BD Carrington, M Allen, TM AF Wang, Y. E. Oniangue-Nzda, C. Schneidewind, A. Kemper, M. Mellors, E. Qi, Y. Gladden, A. D. Power, K. A. Pereyra, F. Walker, B. D. Carrington, M. Allen, T. M. TI Control of HIV Viral Replication Mediated by the Synergistic Effects of Unique Combinations of HLA Class I Alleles SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Wang, Y. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oniangue-Nzda, C.; Kemper, M.; Mellors, E.; Gladden, A. D.; Power, K. A.; Pereyra, F.; Walker, B. D.; Allen, T. M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Schneidewind, A.] Univ Regensburg, Regensburg, Germany. [Carrington, M.] NCI Frederick, SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A60 EP A60 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500150 ER PT J AU Whitney, JB Rolland, M Lacerda, M Hraber, PT DeCamp, A Luedemann, C Rao, SS Mascola, JR Korber, B Nabel, GJ Gilbert, P Seoighe, C Letvin, NL AF Whitney, J. B. Rolland, M. Lacerda, M. Hraber, P. T. DeCamp, A. Luedemann, C. Rao, S. S. Mascola, J. R. Korber, B. Nabel, G. J. Gilbert, P. Seoighe, C. Letvin, N. L. TI Reduction of Founder Virus in Vaccinated Monkeys After Mucosal SIV Challenge SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Whitney, J. B.; Luedemann, C.; Letvin, N. L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Whitney, J. B.; Luedemann, C.; Letvin, N. L.] Harvard Univ, Boston, MA 02115 USA. [Rolland, M.] US Mil HIV Res Program MHRP, Rockville, MD USA. [Lacerda, M.] NUI, Sch Math Stat & Appl Math, Galway, Ireland. [Hraber, P. T.; Korber, B.] Los Alamos Natl Lab, Los Alamos, NM USA. [DeCamp, A.; Gilbert, P.] Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA. [Rao, S. S.] NIAID, Vaccine Res Ctr, Bethesda, MD USA. [Mascola, J. R.; Nabel, G. J.] Vaccine Res Ctr NIAID, Bethesda, MD USA. [Seoighe, C.] Sch Math Stat & Appl Math, Galway, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A30 EP A30 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500071 ER PT J AU Wyatt, L Xiao, W Earl, P Moss, B AF Wyatt, L. Xiao, W. Earl, P. Moss, B. TI Optimizing the Immune Response to MVA/HIV Vaccine Candidates in Mice SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Wyatt, L.; Xiao, W.; Earl, P.; Moss, B.] NIAID, LVD, Natl In, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A105 EP A105 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500271 ER PT J AU Zeng, M Duan, L Li, Q Smith, A Wietgrefe, S Southern, PJ Reilly, CS Pambuccian, S Shang, L Skinner, PJ Zupancic, M Piatak, M Waterman, D Reeves, K Lifson, JD Johnson, P Haase, AT AF Zeng, M. Duan, L. Li, Q. Smith, A. Wietgrefe, S. Southern, P. J. Reilly, C. S. Pambuccian, S. Shang, L. Skinner, P. J. Zupancic, M. Piatak, M., Jr. Waterman, D. Reeves, K. Lifson, J. D. Johnson, P. Haase, A. T. TI SIV Attenuated Vaccine-Induced Plasma Cells and Antibodies Limit Infection at the Portal of Entry and Systemically Following Vaginal Challenge SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Zeng, M.; Duan, L.; Smith, A.; Wietgrefe, S.; Southern, P. J.; Reilly, C. S.; Pambuccian, S.; Shang, L.; Skinner, P. J.; Zupancic, M.; Haase, A. T.] Univ Minnesota, Minneapolis, MN USA. [Li, Q.] Univ Nebraska, Lincoln, NE USA. [Piatak, M., Jr.; Lifson, J. D.] NCI, Frederick, MD 21701 USA. [Waterman, D.] ZeptoMetrix Corp, Buffalo, NY USA. [Reeves, K.; Johnson, P.] Harvard Univ, Sch Med, Southborough, MA 01772 USA. [Johnson, P.] Ragon Inst, Southborough, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A30 EP A30 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500072 ER PT J AU Zhang, M Yuan, T Li, J Zhang, Y Wang, Y Streaker, E Dimitrov, DS AF Zhang, M. Yuan, T. Li, J. Zhang, Y. Wang, Y. Streaker, E. Dimitrov, D. S. TI Putative Rhesus Macaque Germline Antibodies of Broadly HIV-Neutralizing Antibodies: Similarities and Differences Compared with the Human Counterparts SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Zhang, M.; Yuan, T.; Li, J.; Zhang, Y.] Univ Hong Kong, Pokfulam, Hong Kong, Peoples R China. [Wang, Y.; Streaker, E.; Dimitrov, D. S.] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A39 EP A39 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500092 ER PT J AU Zhou, T Wu, X Zhang, B Moquin, S Zhu, J Georgiev, I Bonsignori, M Crump, JA Kapiga, SH Noel, SE Haynes, BF Simek, M Burton, DR Koff, WC Shapiro, L Mascola, JR Kwong, PD AF Zhou, T. Wu, X. Zhang, B. Moquin, S. Zhu, J. Georgiev, I. Bonsignori, M. Crump, J. A. Kapiga, S. H. Noel, S. E. Haynes, B. F. Simek, M. Burton, D. R. Koff, W. C. Shapiro, L. Mascola, J. R. Kwong, P. D. TI Structural Basis for VRC01-Like-Antibody Recognition of Variable Loops that Surround the Site of CD4 Attachment on HIV-1 Gp120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Zhou, T.; Wu, X.; Zhang, B.; Moquin, S.; Zhu, J.; Georgiev, I.; Mascola, J. R.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA. [Bonsignori, M.; Haynes, B. F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC USA. [Crump, J. A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Crump, J. A.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Kapiga, S. H.] Kilimanjaro Reprod Hlth Programme, Moshi, Tanzania. [Noel, S. E.] Tumaini Univ, Moshi, Tanzania. [Simek, M.; Koff, W. C.] Int AIDS Vaccine Initiat IAVI, New York, NY USA. [Burton, D. R.] Scripps Res Inst, La Jolla, CA 92037 USA. [Shapiro, L.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA. RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A120 EP A120 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500311 ER PT J AU Zhu, Z Qin, HR Chen, W Zhao, Q Shen, X Schutte, R Wang, Y Ofek, G Streaker, E Prabakaran, P Fouda, GG Liao, H Owens, J Louder, M Yang, Y Klaric, K Moody, MA Mascola, JR Scott, JK Kwong, PD Montefiori, D Haynes, BF Tomaras, GD Dimitrov, DS AF Zhu, Z. Qin, H. R. Chen, W. Zhao, Q. Shen, X. Schutte, R. Wang, Y. Ofek, G. Streaker, E. Prabakaran, P. Fouda, G. G. Liao, H. Owens, J. Louder, M. Yang, Y. Klaric, K. Moody, M. A. Mascola, J. R. Scott, J. K. Kwong, P. D. Montefiori, D. Haynes, B. F. Tomaras, G. D. Dimitrov, D. S. TI 2F5-like Cross-Reactive HIV-1-Neutralizing Monoclonal Antibodies with Low Number of Somatic Mutations SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Shen, X.] Vaccine Inst, Durham, NC USA. [Schutte, R.; Fouda, G. G.; Liao, H.; Moody, M. A.; Montefiori, D.; Haynes, B. F.; Tomaras, G. D.] Human Vaccine Inst, Durham, NC USA. [Ofek, G.; Louder, M.; Yang, Y.; Mascola, J. R.; Kwong, P. D.] Vaccine Res Ctr, Bethesda, MD USA. [Klaric, K.; Scott, J. K.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Zhu, Z.; Qin, H. R.; Chen, W.; Zhao, Q.; Wang, Y.; Streaker, E.; Prabakaran, P.; Owens, J.; Dimitrov, D. S.] NCI, NIH, Frederick, MD 21701 USA. RI Tomaras, Georgia/J-5041-2016 NR 0 TC 0 Z9 0 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A9 EP A9 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500019 ER PT J AU Chen, G Carlson, VCC Wang, J Beck, A Heinz, A Ron, D Lovinger, DM Buck, KJ AF Chen, Gang Carlson, Verginia C. Cuzon Wang, Jun Beck, Anne Heinz, Andreas Ron, Dorit Lovinger, David M. Buck, Kari J. TI Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE c-Fos; Electrophysiology; fMRI; Fyn Kinase; PET; Self-Administration ID NR2B-CONTAINING NMDA RECEPTORS; ETHANOL WITHDRAWAL; PREFRONTAL CORTEX; DORSAL STRIATUM; STRIATOPALLIDAL NEURONS; MACACA-FASCICULARIS; CHROMOSOME-4 LOCUS; VENTRAL STRIATUM; BASAL GANGLIA; C57BL/6J MICE AB Background: Different regions of the striatum may have distinct roles in acute intoxication, alcohol seeking, dependence, and withdrawal. Methods: The recent advances are reviewed and discussed in our understanding of the role of the dorsolateral striatum (DLS), dorsomedial striatum (DMS), and ventral striatum in behavioral responses to alcohol, including alcohol craving in abstinent alcoholics, and alcohol consumption and withdrawal in rat, mouse, and nonhuman primate models. Results: Reduced neuronal activity as well as dysfunctional connectivity between the ventral striatum and the dorsolateral prefrontal cortex is associated with alcohol craving and impairment of new learning processes in abstinent alcoholics. Within the DLS of mice and nonhuman primates withdrawn from alcohol after chronic exposure, glutamatergic transmission in striatal projection neurons is increased, while GABAergic transmission is decreased. Glutamatergic transmission in DMS projection neurons is also increased in ethanol withdrawn rats. Ex vivo or in vivo ethanol exposure and withdrawal causes a long-lasting increase in NR2B subunit-containing NMDA receptor activity in the DMS, contributing to ethanol drinking. Analyses of neuronal activation associated with alcohol withdrawal and site-directed lesions in mice implicate the rostroventral caudate putamen, a ventrolateral segment of the DMS, in genetically determined differences in risk for alcohol withdrawal involved in physical association of the multi-PDZ domain protein, MPDZ, with 5-HT(2C) receptors and/or NR2B. Conclusions: Alterations of dopaminergic, glutamatergic, and GABAergic signaling within different regions of the striatum by alcohol is critical for alcohol craving, consumption, dependence, and withdrawal in humans and animal models. C1 [Chen, Gang; Buck, Kari J.] Portland VA Med Ctr, Dept Behav Neurosci, Portland, OR USA. [Chen, Gang; Buck, Kari J.] Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR USA. [Chen, Gang; Buck, Kari J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Carlson, Verginia C. Cuzon; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Wang, Jun; Ron, Dorit] Univ Calif San Francisco, Dept Neurol, Ernest Gallo Res Ctr, San Francisco, CA USA. [Beck, Anne; Heinz, Andreas] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. RP Chen, G (reprint author), Univ Minnesota, Inst Translat Neurosci, RM 4-140,MBB 2101 6th SE,East Campus, Minneapolis, MN 55455 USA. EM hdn_2001@yahoo.com RI Wang, Jun/N-8472-2015; Wang, Jun/M-2337-2016 OI Wang, Jun/0000-0002-0085-4722; Wang, Jun/0000-0002-0085-4722 FU division of Intramural Clinical and Basic Research NIAAA [AA13510, AA13641]; State of California for medical research on alcohol and substance abuse through the University of California, San Francisco; Department of Veterans Affairs; German Research Foundation (Deutsche Forschungsgemeinschaft) [HE2597/4-3, 7-3]; Bernstein Center for Computational Neuroscience Berlin [01GQ0411, 01GS08159]; [R01AA014366]; [MH13438]; [AA011114]; [AA10760]; [DA05228] FX The work described in this review was supported by the division of Intramural Clinical and Basic Research NIAAA, AA13510, AA13641 (VCCC, DML); R01AA014366, MH13438, and funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (DR); AA011114, AA10760, DA05228, and the Department of Veterans Affairs (KJB); the German Research Foundation (Deutsche Forschungsgemeinschaft, HE2597/4-3 and 7-3) and the Bernstein Center for Computational Neuroscience Berlin (Bundesministerium fur Bildung und Forschung Grants 01GQ0411 and 01GS08159) (AH). NR 80 TC 34 Z9 36 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2011 VL 35 IS 10 BP 1739 EP 1748 DI 10.1111/j.1530-0277.2011.01520.x PG 10 WC Substance Abuse SC Substance Abuse GA 824QX UT WOS:000295218200006 PM 21615425 ER PT J AU Schuckit, MA Smith, TL Heron, J Hickman, M Macleod, J Lewis, G Davis, JM Hibbeln, JR Brown, S Zuccolo, L Miller, LL Davey-Smith, G AF Schuckit, Marc A. Smith, Tom L. Heron, Jon Hickman, Matthew Macleod, John Lewis, Glyn Davis, John M. Hibbeln, Joseph R. Brown, Sandra Zuccolo, Luisa Miller, Laura L. Davey-Smith, George TI Testing a Level of Response to Alcohol-Based Model of Heavy Drinking and Alcohol Problems in 1,905 17-year-olds SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Avon Longitudinal Study of Parents and Children; Alcohol; Level of Response; Structural Equation Models; Adolescents ID STRUCTURAL EQUATION MODELS; FAMILY-HISTORY; GENETIC RISK; FIT INDEXES; QUESTIONNAIRE; PERFORMANCE; MEN; EXPECTANCIES; ADOLESCENTS; SENSITIVITY AB Background: The low level of response (LR) to alcohol is one of several genetically influenced characteristics that increase the risk for heavy drinking and alcohol problems. Efforts to understand how LR operates through additional life influences have been carried out primarily in modest-sized U.S.-based samples with limited statistical power, raising questions about generalizability and about the importance of components with smaller effects. This study evaluates a full LR-based model of risk in a large sample of adolescents from the United Kingdom. Methods: Cross-sectional structural equation models were used for the approximate first half of the age 17 subjects assessed by the Avon Longitudinal Study of Parents and Children, generating data on 1,905 adolescents (mean age 17.8 years, 44.2% boys). LR was measured with the Self-Rating of the Effects of Alcohol Questionnaire, outcomes were based on drinking quantities and problems, and standardized questionnaires were used to evaluate peer substance use, alcohol expectancies, and using alcohol to cope with stress. Results: In this young and large U.K. sample, a low LR related to more adverse alcohol outcomes both directly and through partial mediation by all 3 additional key variables (peer substance use, expectancies, and coping). The models were similar in boys and girls. Conclusions: These results confirm key elements of the hypothesized LR-based model in a large U.K. sample, supporting some generalizability beyond U.S. groups. They also indicate that with enough statistical power, multiple elements contribute to how LR relates to alcohol outcomes and reinforce the applicability of the model to both genders. C1 [Schuckit, Marc A.; Smith, Tom L.; Brown, Sandra] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. [Heron, Jon; Hickman, Matthew; Macleod, John; Lewis, Glyn; Zuccolo, Luisa; Miller, Laura L.; Davey-Smith, George] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England. [Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Hibbeln, Joseph R.] NIAAA, LMBB, Bethesda, MD USA. RP Schuckit, MA (reprint author), Univ Calif San Diego, Dept Psychiat, 8950 Villa La Jolla Dr,Suite B-218, La Jolla, CA 92037 USA. EM mschuckit@ucsd.edu RI Lewis, Glyn/E-9944-2012; Price, Katie/H-1931-2012; Heron, Jon/D-5884-2011; Davey Smith, George/A-7407-2013; OI Macleod, John/0000-0001-8202-1144; Lewis, Glyn/0000-0001-5205-8245; Heron, Jon/0000-0001-6199-5644; Davey Smith, George/0000-0002-1407-8314; Zuccolo, Luisa/0000-0002-7049-3037; Hickman, Matthew/0000-0001-9864-459X FU U.K. Medical Research Council [74882, G0902144]; Wellcome Trust [076467]; University of Bristol; NIAAA [AA00526] FX We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The U.K. Medical Research Council (Grant ref: 74882), the Wellcome Trust (Grant ref: 076467), and the University of Bristol provided core support for ALSPAC and for general office, and statistical support was from NIAAA grant AA00526. LZ is funded by a Population Health Scientist fellowship from the U.K. Medical Research Council (Grant ref: G0902144). This publication is the work of the authors and Dr. Marc A. Schuckit will serve as guarantor for the contents of this paper. NR 56 TC 14 Z9 14 U1 9 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2011 VL 35 IS 10 BP 1897 EP 1904 DI 10.1111/j.1530-0277.2011.01536.x PG 8 WC Substance Abuse SC Substance Abuse GA 824QX UT WOS:000295218200022 PM 21762180 ER PT J AU Kroner, BL Tolunay, HE Basson, CT Pyeritz, RE Holmes, KW Maslen, CL Milewicz, DM LeMaire, SA Hendershot, T Desvigne-Nickens, P Devereux, RB Dietz, HC Song, HK Ringer, D Mitchell, M Weinsaft, JW Ravekes, W Menashe, V Eagle, KA AF Kroner, Barbara L. Tolunay, H. Eser Basson, Craig T. Pyeritz, Reed E. Holmes, Kathryn W. Maslen, Cheryl L. Milewicz, Dianna M. LeMaire, Scott A. Hendershot, Tabitha Desvigne-Nickens, Patrice Devereux, Richard B. Dietz, Harry C. Song, Howard K. Ringer, Danny Mitchell, Megan Weinsaft, Jonathan W. Ravekes, William Menashe, Victor Eagle, Kim A. CA GenTAC Registry Consortium TI The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC): Results from phase I and scientific opportunities in phase II SO AMERICAN HEART JOURNAL LA English DT Article ID MARFAN-SYNDROME AB Background Genetically triggered thoracic aortic conditions (GenTACs) represent an important problem for patients and their families. Accordingly, the National Heart, Lung, and Blood Institute established the first phase of its national GenTAC Registry in 2006. Enrollment and Diagnoses Between 2007 and 2010, 6 enrolling centers established the GenTAC I Registry consisting of 2,046 patients (Marfan syndrome 576 [28.2%], bicuspid aortic valve disease 504 [24.6%], aneurysm or dissection age <50 years 369 [18%], and others). Biologic samples for DNA analyses (white blood cells or saliva) are available in 97%, and stored plasma is available in 60% of enrollees. Results Initial scientific inquiry using the GenTAC Registry has included validation studies of genetic causes for aortic syndromes, potential usefulness of transforming growth factor beta (TGFB) blood levels in Marfan subjects, and current surgical approaches to ascending aortic conditions. Future Opportunity The second phase of GenTAC will allow biannual follow-up of GenTAC I enrollees for up to 9 years, enrollment of an additional 1,500 subjects, further integration of imaging findings with clinical and genetic data through utilization of an imaging core laboratory, important validation of phenotype-genotype correlations through a phenotyping core laboratory, and integration of a scientific advisory committee to help define the full range and depth of the Registry's scientific capabilities. The registry resources are available to the external scientific community through an application process accessible at https://gentac.rti.org. (Am Heart J 2011;162:627-632.e1.) C1 [Kroner, Barbara L.; Hendershot, Tabitha; Ringer, Danny] RTI Int, Rockville, MD 20852 USA. [Tolunay, H. Eser; Desvigne-Nickens, Patrice; Mitchell, Megan] NIH, Bethesda, MD 20892 USA. [Basson, Craig T.; Devereux, Richard B.; Weinsaft, Jonathan W.; Ravekes, William] Weill Cornell Med Coll, New York, NY USA. [Pyeritz, Reed E.] Univ Penn, Philadelphia, PA 19104 USA. [Holmes, Kathryn W.; Dietz, Harry C.] Johns Hopkins Univ, Baltimore, MD USA. [Maslen, Cheryl L.; Song, Howard K.; Menashe, Victor] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Milewicz, Dianna M.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [LeMaire, Scott A.] Baylor Coll Med, Houston, TX 77030 USA. [Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Kroner, BL (reprint author), RTI Int, 6110 Execut Blvd,Suite 901, Rockville, MD 20852 USA. EM byk@rti.org FU NHLBI NIH HHS [N01 HV68199-3-0-0] NR 9 TC 16 Z9 17 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2011 VL 162 IS 4 BP 627 EP U77 DI 10.1016/j.ahj.2011.07.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833ZO UT WOS:000295925100010 PM 21982653 ER PT J AU Pauly, DF Johnson, BD Anderson, RD Handberg, EM Smith, KM Cooper-DeHoff, RM Sopko, G Sharaf, BM Kelsey, SF Merz, CNB Pepine, CJ AF Pauly, Daniel F. Johnson, B. Delia Anderson, R. David Handberg, Eileen M. Smith, Karen M. Cooper-DeHoff, Rhonda M. Sopko, George Sharaf, Barry M. Kelsey, Sheryl F. Merz, C. Noel Bairey Pepine, Carl J. TI In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE) SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; LONG-TERM OUTCOMES; HYPERTENSIVE PATIENTS; CHEST-PAIN; SYNDROME-X; GENDER-DIFFERENCES; VASCULAR-DISEASE; FLOW VELOCITY; RESERVE; ANGINA AB Background We investigated the role of the renin-angiotensin system in women with signs and symptoms of ischemia without obstructive coronary artery disease (CAD). Although microvascular dysfunction has been suggested to explain this syndrome and recently was found to predict adverse outcomes, the mechanisms and treatments remain unclear. Methods In a substudy within the WISE, 78 women with microvascular dysfunction (coronary flow reserve [CFR] <3.0 following adenosine) and no obstructive CAD were randomly assigned to either an angiotensin-converting enzyme inhibition (ACE-I) with quinapril or a placebo treatment group. The primary efficacy parameter was CFR at 16 weeks adjusted for baseline characteristics and clinical site. The secondary response variable was freedom from angina symptoms assessed using the Seattle Angina Questionnaire. Results A total of 61 women completed the 16-week treatment period with repeat CFR measurements, and treatment was well tolerated. For the primary outcome, at 16 weeks, CFR improved more with ACE-I than placebo (P < .02). For the secondary outcome of symptom improvement, ACE-I treatment (P = .037) and CFR increase (P = .008) both contributed. Conclusions Microvascular function improves with ACE-I therapy in women with signs and symptoms of ischemia without obstructive CAD. This improvement is associated with reduction in angina. The beneficial response of the coronary microvasculature was limited to women with lower baseline CFR values, suggesting that the renin-angiotensin system may be more involved among women with more severe microvascular defects. (Am Heart J 2011;162:678-84.) C1 [Pepine, Carl J.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32610 USA. [Johnson, B. Delia; Kelsey, Sheryl F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Cooper-DeHoff, Rhonda M.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA. [Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA. [Sharaf, Barry M.] Rhode Isl Hosp, Div Cardiol, Providence, RI USA. [Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. RP Pepine, CJ (reprint author), Univ Florida, Coll Med, Div Cardiovasc Med, POB 100277, Gainesville, FL 32610 USA. EM pepincj@medicine.ufl.edu FU National Heart, Lung and Blood Institute [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164]; National Center for Research Resources [MO1-RR00425]; Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey; Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California; Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania; Pfizer Labs; Edythe L. Broad Endowment for Women's Heart Research, Los Angeles, California; Eminent Scholar Research Chair, AHA Suncoast Chapter; NIH/NHLBI [5 U01 HL087366-04, 5 R01 HL091005-03, 5 R01 HL090957-03, 2 U01 GM074492-06]; NIH/AG [3 U01 AG022376-05A2S1]; NIH/NCRR [5 UL1 RR029890-02]; [U0164829]; [U01 HL649141]; [U01 HL649241] FX This work was supported by contracts from the National Heart, Lung and Blood Institute, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164; grants U0164829, U01 HL649141, U01 HL649241; a GCRC grant MO1-RR00425 from the National Center for Research Resources; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey; Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California; Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania; Pfizer Labs; and The Edythe L. Broad Endowment for Women's Heart Research, Los Angeles, California. Dr Pepine was funded, in part, by the Eminent Scholar Research Chair, AHA Suncoast Chapter; by NIH/NHLBI grants 5 U01 HL087366-04, 5 R01 HL091005-03, 5 R01 HL090957-03, 2 U01 GM074492-06; NIH/AG grant 3 U01 AG022376-05A2S1; NIH/NCRR grant 5 UL1 RR029890-02; and a research grant from Pfizer Labs. NR 38 TC 38 Z9 40 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2011 VL 162 IS 4 BP 678 EP 684 DI 10.1016/j.ahj.2011.07.011 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833ZO UT WOS:000295925100017 PM 21982660 ER PT J AU Cheng, S Fox, CS Larson, MG Massaro, JM McCabe, EL Khan, AM Levy, D Hoffmann, U O'Donnell, CJ Miller, KK Newton-Cheh, C Coviello, AD Bhasin, S Vasan, RS Wang, TJ AF Cheng, Susan Fox, Caroline S. Larson, Martin G. Massaro, Joseph M. McCabe, Elizabeth L. Khan, Abigail May Levy, Daniel Hoffmann, Udo O'Donnell, Christopher J. Miller, Karen K. Newton-Cheh, Christopher Coviello, Andrea D. Bhasin, Shalender Vasan, Ramachandran S. Wang, Thomas J. TI Relation of Visceral Adiposity to Circulating Natriuretic Peptides in Ambulatory Individuals SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; METABOLIC RISK-FACTORS; INSULIN-RESISTANCE; BODY-MASS; ASSOCIATION; ATRIAL; SENSITIVITY; DIAGNOSIS; IMPACT; AGE AB Natriuretic peptides have important roles in the regulation of vasomotor tone, salt homeostasis, and ventricular remodeling. Lower natriuretic peptide levels observed in obese individuals may underlie the greater cardiovascular risk associated with obesity. Thus the aim of this study was to determine whether lower natriuretic peptide levels in obesity are attributable to differences in regional fat distribution. We investigated the relation of plasma N-terminal pro B-type natriuretic peptide (NT pro-BNP) to regional adiposity in 1,873 community-based individuals (46% women, mean age 45 years). Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured by multidetector computed tomography. In gender-specific multivariable analyses adjusting for age and blood pressure, log NT pro-BNP was inversely associated with VAT in men (beta -0.11 per standard deviation increment, p < 0.001) and women (beta -0.19, p < 0.001). Log NT pro-BNP was inversely associated with SAT in women only (beta -0.14, p < 0.001). In models containing VAT and SAT, only VAT was significantly associated with log NT pro-BNP (men, beta -0.137, p < 0.001; women, beta -0.184, p < 0.001). VAT remained associated with log NT pro-BNP even after adjustment for body mass index and waist circumference (beta -0.119, p < 0.001) and in analyses restricted to nonobese patients (beta -0.165, p < 0.001). Adjustment for insulin resistance attenuated the associations of NT pro-BNP with VAT and SAT. In conclusion, this study demonstrates that circulating NT pro-BNP is related to variations in regional and particularly visceral adiposity. These findings suggest that excess visceral adiposity and concomitant hyperinsulinemia may contribute to the natriuretic peptide "deficiency" observed in obesity. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:979-984) C1 [Cheng, Susan; Fox, Caroline S.; Larson, Martin G.; Massaro, Joseph M.; McCabe, Elizabeth L.; Levy, Daniel; O'Donnell, Christopher J.; Newton-Cheh, Christopher; Coviello, Andrea D.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Cheng, Susan; McCabe, Elizabeth L.; Khan, Abigail May; O'Donnell, Christopher J.; Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Miller, Karen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02115 USA. [Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02115 USA. [Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Larson, Martin G.; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Levy, Daniel; Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Levy, Daniel; Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Coviello, Andrea D.; Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Newton-Cheh, Christopher] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. RP Wang, TJ (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. EM tjwang@partners.org OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland [N01-HC-25195, R01-HL-086875]; Ellison Foundation, Bethesda, Maryland FX This work was supported in part by Contracts N01-HC-25195 and R01-HL-086875 from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland (Dr. Wang and Dr. Newton-Cheh) and the Ellison Foundation, Bethesda, Maryland (Dr. Cheng). NR 30 TC 23 Z9 23 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2011 VL 108 IS 7 BP 979 EP 984 DI 10.1016/j.amjcard.2011.05.033 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833DY UT WOS:000295863200014 PM 21813106 ER PT J AU Yasuda, M Wilson, DR Fugmann, SD Moaddel, R AF Yasuda, M. Wilson, D. R. Fugmann, S. D. Moaddel, R. TI Synthesis and Characterization of SIRT6 Protein Coated Magnetic Beads: Identification of a Novel Inhibitor of SIRT6 Deacetylase from Medicinal Plant Extracts SO ANALYTICAL CHEMISTRY LA English DT Article ID HISTONE-DEACETYLASE; ADP-RIBOSYLTRANSFERASE; GENE-EXPRESSION; CHROMATIN; REGULATORS; GLUCOSE; LIGAND; CANCER; DRUGS AB SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. Thus, the identification of compounds that modulate SIRT6 activity could be of great therapeutic importance. The aim of this study was to develop a screening method for the identification of novel modulators of SIRT6 from a natural plant extract. We immobilized SIRT6 onto the surface of magnetic beads, and assessed SIRT6 enzymatic activity on synthetic acetylated histone tails (H3K9Ac) by measuring products of the deacetylation process. The SIRT6 coated magnetic beads were then suspended in fenugreek seed extract (Trigonella foenum-graecum) as a bait to identify active ligands that suppress SIRT6 activity. While the entire extract also inhibited SIRT6 activity in a cell-based assay, the inhibitory effect of two flavonoids from this extract, quercetin and vitexin, was only detected in vitro. This is the first report on the use of protein-coated magnetic beads for the identification of an active ligand from a botanical matrix, and it sets the basis for the de novo identification of SIRT6 modulators from complex biological mixtures. C1 [Moaddel, R.] NIA, Biomed Res Ctr, Bioanalyt & Drug Discovery Unit, Clin Invest Lab,NIH, Baltimore, MD 21224 USA. RP Moaddel, R (reprint author), NIA, Biomed Res Ctr, Bioanalyt & Drug Discovery Unit, Clin Invest Lab,NIH, Suite 100,8B131 Biomed Res Ctr,251 Bayview Blvd, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov FU NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. There are no financial conflicts. We would like to thank Dr. Michel Bernier for critical review of the manuscript and Dr. Irving W. Wainer for his continued support. NR 26 TC 30 Z9 31 U1 0 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD OCT 1 PY 2011 VL 83 IS 19 BP 7400 EP 7407 DI 10.1021/ac201403y PG 8 WC Chemistry, Analytical SC Chemistry GA 825SY UT WOS:000295303600024 PM 21854049 ER PT J AU Cella, D Nowinski, C Peterman, A Victorson, D Miller, D Lai, JS Moy, C AF Cella, David Nowinski, Cindy Peterman, Amy Victorson, David Miller, Deborah Lai, Jin-Shei Moy, Claudia TI The Neurology Quality-of-Life Measurement Initiative SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Clinical research; Health-related quality of life; Neurology; Patient-reported outcomes; Quality of life; Rehabilitation AB Cella D, Nowinski C, Peterman A, Victorson D, Miller D, Lai J-S, Moy C. The neurology quality-of-life measurement initiative. Arch Phys Med Rehabil 2011;92 (10 Suppl 1):S28-S36. Objective: To describe the development and calibration of the banks and scales of the Quality of Life in Neurological Disorders (Neuro-QOL) project, commissioned by the National Institute of Neurological Disorders and Stroke to develop a bilingual (English/Spanish), clinically relevant, and psychometrically robust health-related quality-of-life (HRQOL) assessment tool. Design: Classic and modern test construction methods were used, including input from essential stakeholder groups. Setting: An online patient panel testing service and 11 academic medical centers and clinics from across the United States and Puerto Rico that treat major neurologic disorders. Participants: Adult and pediatric patients representing different neurologic disorders specified in this study, proxy respondents for select conditions (stroke, pediatric conditions), and English- and Spanish-speaking participants from the general population. Interventions: Not applicable. Main Outcome Measures: Multiple generic and condition-specific measures used to provide construct validity evidence for the new Neuro-QOL tool. Results: Neuro-QOL has developed 14 generic item banks and 8 targeted scales to assess HRQOL in 5 adult (stroke, multiple sclerosis, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis) and 2 pediatric conditions (epilepsy, muscular dystrophies). Conclusions: The Neuro-QOL system will continue to evolve, with validation efforts in clinical populations and new bank development in health domains not presently included. The potential for Neuro-QOL measures in rehabilitation research and clinical settings is discussed. C1 [Cella, David; Nowinski, Cindy; Victorson, David; Lai, Jin-Shei] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Peterman, Amy] Univ N Carolina, Dept Psychol, Charlotte, NC 28223 USA. [Miller, Deborah] Cleveland Clin Fdn, Mellen Ctr Multiple Sclerosis Treatment & Res, Cleveland, OH 44195 USA. [Moy, Claudia] NINDS, NIH, Bethesda, MD 20892 USA. RP Cella, D (reprint author), Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, 710 N Lake Shore Dr,Ste 729, Chicago, IL 60611 USA. EM d-cella@northwestern.edu FU National Institute of Neurological Disorders and Stroke [HHSN265200423601C] FX Supported by the National Institute of Neurological Disorders and Stroke (contract no. HHSN265200423601C). NR 11 TC 59 Z9 59 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2011 VL 92 IS 10 SU 1 BP S28 EP S36 DI 10.1016/j.apmr.2011.01.025 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 833DG UT WOS:000295861400005 PM 21958920 ER PT J AU Quatrano, LA Cruz, TH AF Quatrano, Louis A. Cruz, Theresa H. TI Future of Outcomes Measurement: Impact on Research in Medical Rehabilitation and Neurologic Populations SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Outcome measures; Rehabilitation ID QUALITY-OF-LIFE; HEALTH OUTCOMES; PARTICIPATION; INJURY AB Quatrano LA, Cruz TH. Future of outcomes measurement: impact on research in medical rehabilitation and neurologic populations. Arch Phys Med Rehabil 2011;92 (10 Suppl 1):S7-11. The National Institutes of Health (NIH) has embraced the investigation and development of health-related patient-reported outcomes (PROs) for their potential use in clinical trials, as well as in examining health care reimbursements and regulatory affairs. The NIH has 3 major programs to address this topic: the Patient-Reported Outcomes Measurement Information System (PROMIS), NIH Toolbox for Assessment of Neurological and Behavioral Function, and Quality of Life in Neurological Disorders (Neuro-QOL), a health-related quality-of-life assessment tool for adults and children with neurologic disorders. These initiatives are focused on developing, validating, and measuring aspects of health by using assessment tools that bridge disease type. Given that rehabilitation takes place across a variety of environments with differing levels of specialized equipment and skilled personnel, PROs may provide consistent measures over time and therefore are anticipated to have substantial impacts on the medical rehabilitation community. Despite their advantages, the widespread use of PROs in rehabilitation faces significant and diverse challenges. This article describes the background behind the NIH PRO initiatives and illustrates both potential benefits and challenges to PRO use in the medical rehabilitation setting. C1 [Quatrano, Louis A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, BSRE, NCMRR, NIH, Bethesda, MD 20892 USA. RP Quatrano, LA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, BSRE, NCMRR, NIH, 6100 Execut Blvd,Rm 2A03,MSC 7510, Bethesda, MD 20892 USA. EM quatranol@mail.nih.gov FU Northwestern University; technology center (Northwestern University); network center (American Institutes for Research); State University of New York FX PROMIS II was funded by cooperative agreements with a statistical center (Northwestern University, Principal Investigator [PI]: David Cella, PhD), a technology center (Northwestern University, PI: Richard C. Gershon, PhD), a network center (American Institutes for Research, PI: Susan [San] D. Keller, PhD), and 13 primary research sites (State University of New York, Stonybrook, PIs: Joan E. Broderick, PhD, and Arthur A. Stone, PhD; University of Washington, Seattle, Pis: Heidi M. Crane, MD, MPH, Paul K. Crane, MD, MPH, and Donald L. Patrick, PhD; University of Washington, PI: Dagmar Amtmann, PhD; University of North Carolina, Chapel Hill, PI: Darren A. DeWalt, MD; Children's Hospital of Philadelphia, PI: Christopher Forrest, MD; Stanford University, PI: James M. Fries, MD; Boston University, PI: Stephen M. Haley, PhD; University of Michigan, Ann Arbor, PI: David Scott Tulsky, PhD; University of California, Los Angeles, Pis: Dinesh Khanna, MD, and Brennan Spiegel, MD, MSHS; University of Pittsburgh, PI: Paul A. Pilkonis, PhD; Georgetown University, Washington, DC, Pis: Carol M. Moinpour, PhD, and Arnold L. Pitosky, PhD; Children's Hospital Medical Center, Cincinnati, PI: Esi M. Morgan Dewitt, MD; University of Maryland, Baltimore, PI: Lisa M. Shulman, MD; and Duke University, PI: Kevin P. Weinfurt, PhD). NIH Science Officers on this project have included Vanessa Ameen, MD, Susan Czajkowski, PhD, Basil Eldadah, MD, PhD, Lawrence Fox, MD, PhD, Lynne Haverkos, MD, MPH, Thomas Hilton, PhD, Laura Lee Johnson, PhD, Michael Kozak, PhD, Peter Lyster, PhD, Donald Mattison, MD, Claudia Moy, PhD, Louis Quatrano, PhD, Bryce Reeve, PhD, Ellen Werner, PhD, and James Witter, MD, PhD. NR 23 TC 13 Z9 13 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2011 VL 92 IS 10 SU 1 BP S7 EP S11 DI 10.1016/j.apmr.2010.08.032 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 833DG UT WOS:000295861400002 PM 21958925 ER PT J AU Young, K Drevets, WC Schulkin, J Erickson, K AF Young, Kymberly Drevets, Wayne C. Schulkin, Jay Erickson, Kristine TI Dose-Dependent Effects of Hydrocortisone Infusion on Autobiographical Memory Recall SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE cortisol; autobiographical memory; human; declarative memory; depression ID GLUCOCORTICOID-INDUCED IMPAIRMENT; HEALTHY-YOUNG MEN; DECLARATIVE MEMORY; EPISODIC MEMORY; CORTISOL-LEVELS; SEX-DIFFERENCES; HORMONAL RESPONSES; MAJOR DEPRESSION; PLASMA-CORTISOL; ACUTE STRESS AB The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n = 66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n = 33) or high-dose (0.45 mg/kg IV; n = 33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p =.04), increased the percent of categorical (nonspecific) memories recalled (p <.001), and slowed response times for categorical memories (p <.001), compared with placebo performance. Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories. C1 [Young, Kymberly; Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA. [Young, Kymberly; Drevets, Wayne C.; Erickson, Kristine] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Young, Kymberly; Erickson, Kristine] American Univ, Dept Psychol, Washington, DC 20016 USA. [Drevets, Wayne C.] Univ Oklahoma, Coll Med, Dept Psychiat, Norman, OK 73019 USA. [Schulkin, Jay] Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. RP Young, K (reprint author), Laureate Inst Brain Res, 6655 S Yale Ave, Tulsa, OK 74136 USA. EM kyoung@laureateinstitute.org OI Young, Kymberly/0000-0001-5133-2142 FU NIMH [Z01-MH002814] FX We acknowledge the support of the NIMH Intramural Research Program, and Joan Williams and Michele Drevets for assistance with recruitment and clinical assessment of the participants. Funding for this study was provided by NIMH Z01-MH002814. The DIRP within NIMH provided critical peer review for the study design and approval of manuscript submission. NIMH had no further role in the collection, analysis, and interpretation of data, or in the writing of the report. NR 49 TC 11 Z9 11 U1 2 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2011 VL 125 IS 5 BP 735 EP 741 DI 10.1037/a0024764 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 826GA UT WOS:000295339400006 PM 21942435 ER PT J AU Stangl, B Hirshman, E Verbalis, J AF Stangl, Bethany Hirshman, Elliot Verbalis, Joseph TI Administration of Dehydroepiandrosterone (DHEA) Enhances Visual-Spatial Performance in Postmenopausal Women SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE dehydroepiadrosterone (DHEA); postmenopausal women; cognition; visual-spatial tasks; androgens ID TANDEM MASS-SPECTROMETRY; HEALTHY OLDER MEN; WORKING-MEMORY; LIQUID-CHROMATOGRAPHY; REPLACEMENT THERAPY; HORMONE REPLACEMENT; EXPLICIT MEMORY; ELDERLY-WOMEN; SEX STEROIDS; TESTOSTERONE AB The current article examines the effect of administering dehydroepiandrosterone (DHEA) on visualspatial performance in postmenopausal women (N = 24, ages 55-80). The concurrent reduction of serum DHEA levels and visual-spatial performance in this population, coupled with the documented effects of DHEA's androgenic metabolites on visual-spatial performance, suggests that DHEA administration may enhance visual-spatial performance. The current experiment used a double-blind, placebo-controlled crossover design in which 50 mg of oral DHEA was administered daily in the drug condition to explore this hypothesis. Performance on the Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, Same-Different Judgment, and Visual Search tasks and serum levels of DHEA, DHEAS, testosterone, estrone, and cortisol were measured in the DHEA and placebo conditions. In contrast to prior experiments using the current methodology that did not demonstrate effects of DHEA administration on episodic and short-term memory tasks, the current experiment demonstrated large beneficial effects of DHEA administration on Mental Rotation, Subject-Ordered Pointing, Fragmented Picture Identification, Perceptual Identification, and Same-Different Judgment. Moreover, DHEA administration enhanced serum levels of DHEA, DHEAS, testosterone, and estrone, and regression analyses demonstrated that levels of DHEA and its metabolites were positively related to cognitive performance on the visual-spatial tasks in the DHEA condition. C1 [Hirshman, Elliot] San Diego State Univ, Off President, Dept Psychol, San Diego, CA 92182 USA. [Stangl, Bethany] NIAAA, NIH, Bethesda, MD 20892 USA. [Verbalis, Joseph] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20057 USA. RP Hirshman, E (reprint author), San Diego State Univ, Off President, Dept Psychol, 5500 Campanile Dr, San Diego, CA 92182 USA. EM ellioth@sdsu.edu FU National Institute on Aging of the National Institutes of Health [27675-1-CCLS-2035F, 5RO1AG020543] FX The work presented here was supported by the National Institute on Aging of the National Institutes of Health grant (27675-1-CCLS-2035F, 5RO1AG020543). Correspondence should be directed to the second author at ellioth@sdsu.edu NR 52 TC 8 Z9 9 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2011 VL 125 IS 5 BP 742 EP 752 DI 10.1037/a0025151 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 826GA UT WOS:000295339400007 PM 21942436 ER PT J AU Bond, LM Brandstaetter, H Sellers, JR Kendrick-Jones, J Buss, F AF Bond, Lisa M. Brandstaetter, Hemma Sellers, James R. Kendrick-Jones, John Buss, Folma TI Myosin motor proteins are involved in the final stages of the secretory pathways SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE actin; exocytosis; fusion; myosin; secretion; vesicle ID CELL RIBBON SYNAPSES; F-ACTIN; PLASMA-MEMBRANE; FUSION PORE; CHROMAFFIN CELLS; VESICLE DOCKING; GOLGI-COMPLEX; EXOCYTOSIS; VI; VA AB In eukaryotes, the final steps in both the regulated and constitutive secretory pathways can be divided into four distinct stages: (i) the 'approach' of secretory vesicles/granules to the PM (plasma membrane), (ii) the 'docking' of these vesicles/granules at the membrane itself, (iii) the 'priming' of the secretory vesicles/granules for the fusion process, and, finally, (iv) the 'fusion' of vesicular/granular membranes with the PM to permit content release from the cell. Recent work indicates that non-muscle myosin II and the unconventional myosin motor proteins in classes 1c/1e, Va and VI are specifically involved in these final stages of secretion. In the present review, we examine the roles of these myosins in these stages of the secretory pathway and the implications of their roles for an enhanced understanding of secretion in general. C1 [Bond, Lisa M.; Brandstaetter, Hemma; Buss, Folma] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England. [Bond, Lisa M.; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Kendrick-Jones, John] MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Buss, F (reprint author), Univ Cambridge, Cambridge Inst Med Res, Wellcome Trust MRC Bldg,Hills Rd, Cambridge CB2 0XY, England. EM fb1@mole.bio.cam.ac.uk FU Wellcome Trust; Winston Churchill Foundation of the United States; NIH-Oxford-Cambridge; Medical Research Council FX This work was funded by the Wellcome Trust (to F.B. and H.B.), a scholarship from the Winston Churchill Foundation of the United States (to LB.) and an NIH-Oxford-Cambridge Ph.D. studentship (to LB.), and was supported by the Medical Research Council (to J.K.J.). The Cambridge Institute for Medical Research is in receipt of a strategic award from the Wellcome Trust. NR 50 TC 18 Z9 18 U1 3 U2 15 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD OCT PY 2011 VL 39 BP 1115 EP 1119 DI 10.1042/BST0391115 PN 5 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831QC UT WOS:000295745200001 PM 21936774 ER PT J AU Wang, AB Ma, XF Conti, MA Adelstein, RS AF Wang, Aibing Ma, Xuefei Conti, Mary Anne Adelstein, Robert S. TI Distinct and redundant roles of the non-muscle myosin II isoforms and functional domains SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE cell-cell adhesion; cell migration; hydrocephalus; myosin; non-muscle myosin II ID HEAVY-CHAIN; MYH9-RELATED DISEASE; CELL-ADHESION; ABLATION; MUTATION; MICE; DEFECTS; BRAIN AB We propose that the in vivo functions of NM II (non-muscle myosin II) can be divided between those that depend on the N-terminal globular motor domain and those less dependent on motor activity but more dependent on the C-terminal domain. The former, being more dependent on the kinetic properties of NM II to translocate actin filaments, are less amenable to substitution by different NM II isoforms, whereas the in vivo functions of the latter, which involve the structural properties of NM II to cross-link actin filaments, are more amenable to substitution. In light of this hypothesis, we examine the ability of NM II-A, as well as a motor-compromised form of NM II-B, to replace NM II-B and rescue neuroepithelial cell-cell adhesion defects and hydrocephalus in the brain of NM II-B-depleted mice. We also examine the ability of NM II-B as well as chimaeric forms of NM II(II-A head and II-B tail and vice versa) to substitute for NM II-A in cell-cell adhesions in II-A-ablated mice. However, we also show that certain functions, such as neuronal cell migration in the developing brain and vascularization of the mouse embryo and placenta, specifically require NM II-B and II-A respectively. C1 [Wang, Aibing; Ma, Xuefei; Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. EM adelster@mail.nih.gov OI Adelstein, Robert/0000-0002-8683-2144 FU National Heart, Lung, and Blood Institute/National Institutes of Health, Division of Intramural Research FX This work was funded by the National Heart, Lung, and Blood Institute/National Institutes of Health, Division of Intramural Research. NR 19 TC 29 Z9 31 U1 2 U2 15 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD OCT PY 2011 VL 39 BP 1131 EP 1135 DI 10.1042/BST0391131 PN 5 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831QC UT WOS:000295745200004 PM 21936777 ER PT J AU Siththanandan, VB Sellers, JR AF Siththanandan, Verl B. Sellers, James R. TI Regulation of myosin 5a and myosin 7a SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE actin; ATPase activity; calcium; myosin ID GLOBULAR TAIL DOMAIN; DUTY RATIO MOTOR; MELANOSOME TRANSPORT; PROCESSIVE MOVEMENT; KINETIC MECHANISM; ATPASE ACTIVITY; V PROCESSIVITY; DROSOPHILA; VIIA; CALMODULIN AB The myosin superfamily is diverse in its structure, kinetic mechanisms and cellular function. The enzymatic activities of most myosins are regulated by some means such as Ca(2+) ion binding, phosphorylation or binding of other proteins. In the present review, we discuss the structural basis for the regulation of mammalian myosin Sa and Drosophila myosin 7a. We show that, although both myosins have a folded inactive state in which domains in the myosin tail interact with the motor domain, the details of the regulation of these two myosins differ greatly. C1 [Siththanandan, Verl B.; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov FU Intramural Research Division of the National Heart, Lung and Blood Institute FX This work was funded by the Intramural Research Division of the National Heart, Lung and Blood Institute. NR 48 TC 2 Z9 2 U1 1 U2 11 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD OCT PY 2011 VL 39 BP 1136 EP 1141 DI 10.1042/BST0391136 PN 5 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831QC UT WOS:000295745200005 PM 21936778 ER PT J AU Lam, TK Cross, AJ Freedman, N Park, Y Hollenbeck, AR Schatzkin, A Abnet, C AF Lam, Tram Kim Cross, Amanda J. Freedman, Neal Park, Yikyung Hollenbeck, Albert R. Schatzkin, Arthur Abnet, Christian TI Dietary fiber and grain consumption in relation to head and neck cancer in the NIH-AARP Diet and Health Study SO CANCER CAUSES & CONTROL LA English DT Article DE Diet; Fiber; Grains; Head and neck cancer; Prospective study ID UPPER AERODIGESTIVE TRACT; RETIRED-PERSONS DIET; LARYNGEAL-CANCER; RISK-FACTORS; AMERICAN-ASSOCIATION; NATIONAL-INSTITUTES; ESOPHAGEAL CANCER; PHARYNGEAL CANCER; NUTRITION; ALCOHOL AB Background Dietary fiber and grain consumption may reduce the risk of head and neck cancer; however, the epidemiological evidence is limited. We investigated this relationship in the National Institutes of Health (NIH)-AARP Diet and Health Study. Methods Cox proportional hazards models were used to calculate multivariable hazard ratios (HR) and 95% confidence intervals (CI) to investigate dietary fiber and grain intake in relation to head and neck cancer. Results During approximately 11 years of follow-up, 1,867 (401 women/1,466 men) cases of head and neck cancer were diagnosed. Our data indicated that the relationship between fiber and grain intake and head and neck cancer is modified by sex (p-interactions < 0.001 and 0.001, respectively). Women with higher intake of total fiber and total grains had a lower risk of head and neck cancer (HR(10g/day) = 0.77, 95% CI = 0.64-0.93; HR(serving/1,000kcal) = 0.89, 95% CI = 0.80-0.99, respectively); this inverse relation was consistent across subtypes of fiber and grains. Conversely in men, the inverse associations were weaker and nonsignificant. Conclusions In the largest prospective cohort study to investigate this relation to date, intake of total fiber and grain foods was inversely associated with head and neck cancer incidence among women, but not among men. C1 [Lam, Tram Kim] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet DCEG, NIH, Rockville, MD 20852 USA. [Lam, Tram Kim] NCI, Canc Prevent Fellowship Program, Off Directors, NIH, Rockville, MD 20852 USA. [Cross, Amanda J.; Freedman, Neal; Park, Yikyung; Schatzkin, Arthur; Abnet, Christian] NCI, Nutr Epidemiol Branch, DCEG, NIH, Rockville, MD 20852 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Lam, TK (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet DCEG, NIH, Rockville, MD 20852 USA. EM lamt@mail.nih.gov RI Abnet, Christian/C-4111-2015; OI Abnet, Christian/0000-0002-3008-7843; Park, Yikyung/0000-0002-6281-489X FU NIH, National Cancer Institute; Florida Department of Health (FDOH) FX This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDC) under contract with the Florida Department of Health (FDOH). The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services. We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcomes ascertainment and management and Leslie Carroll at Information Management Services for data support and analysis. NR 50 TC 5 Z9 5 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2011 VL 22 IS 10 BP 1405 EP 1414 DI 10.1007/s10552-011-9813-9 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 834VJ UT WOS:000295992000006 PM 21785948 ER PT J AU Ben-Sasson, SZ Caucheteux, S Crank, M Hu-Li, J Paul, WE AF Ben-Sasson, S. Z. Caucheteux, Stephane Crank, Michelle Hu-Li, Jane Paul, William E. TI IL-1 acts on T cells to enhance the magnitude of in vivo immune responses SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Ben-Sasson, S. Z.; Caucheteux, Stephane; Crank, Michelle; Hu-Li, Jane; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20891 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 3 EP 3 DI 10.1016/j.cyto.2011.07.292 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800004 ER PT J AU Le Saout, C Hasley, R Tcheung, L Imamichi, H Park, JH Sneller, M Roby, G Rehm, C Lane, C Catalfamo, M AF Le Saout, Cecile Hasley, Rebecca Tcheung, Lueng Imamichi, Hiromi Park, Jung-Hyun Sneller, Michael Roby, Gregg Rehm, Catherine Lane, Clifford Catalfamo, Marta TI In vivo IL-7 exposure of CD4 T cells during HIV induced lymphopenia leads to an enhanced Type-I IFN response SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 NIAID, CMRS, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 6 EP 6 DI 10.1016/j.cyto.2011.07.309 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800014 ER PT J AU Liao, W Lin, JX Wang, L Li, P Leonard, WJ AF Liao, Wei Lin, Jian-Xin Wang, Lu Li, Peng Leonard, Warren J. TI Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Liao, Wei; Lin, Jian-Xin; Wang, Lu; Li, Peng; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 6 EP 6 DI 10.1016/j.cyto.2011.07.310 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800015 ER PT J AU Verthelyi, D Pedras-Vasconcelos, J Butts, C Jones, Y Puig, M Wang, V Trinchieri, G Tami, C AF Verthelyi, Daniela Pedras-Vasconcelos, Joao Butts, Cherie Jones, Yava Puig, Montserrat Wang, Vivian Trinchieri, Giorgio Tami, Cecilia TI Innate immune response modulators control inflammation and improve survival in viral encephalitis SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Verthelyi, Daniela; Pedras-Vasconcelos, Joao; Butts, Cherie; Puig, Montserrat; Wang, Vivian; Tami, Cecilia] FDA, Div Therapeut Prot, Off Biotechnol, CDER, Jefferson, AR USA. [Verthelyi, Daniela; Jones, Yava; Trinchieri, Giorgio] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 11 EP 11 DI 10.1016/j.cyto.2011.07.329 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800030 ER PT J AU Schmeisser, H Fey, SB Horowitz, J Fischer, ER Miyake, K Balinsky, CA Bekisz, J Zoon, KC AF Schmeisser, Hana Fey, Samuel B. Horowitz, Julie Fischer, Elizabeth R. Miyake, Kotaro Balinsky, Corey A. Bekisz, Joseph Zoon, Kathryn C. TI Human interferon-alpha2c induces autophagy in Daudi Burkitt's lymphoma cells SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Schmeisser, Hana; Fey, Samuel B.; Horowitz, Julie; Miyake, Kotaro; Balinsky, Corey A.; Bekisz, Joseph; Zoon, Kathryn C.] NIAID, NIH, Cytokine Biol Sect, Bethesda, MD 20892 USA. [Fischer, Elizabeth R.] NIAID, NIH, Rocky Mt Labs, Res Technol Sect, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 22 EP 22 DI 10.1016/j.cyto.2011.07.042 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800067 ER PT J AU Bekisz, J Zhao, TM Zoon, KC AF Bekisz, Joseph Zhao, Tongmao Zoon, Kathryn C. TI Pro-Inflammatory Cytokine Expression in Three Cell Types after Treatment with IFN-alpha subtypes as Assessed by Multiplex Assays SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Bekisz, Joseph; Zhao, Tongmao; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 29 EP 30 DI 10.1016/j.cyto.2011.07.080 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800094 ER PT J AU Thomas, E Gonzalez, VD Li, QS Modi, AA Uccellini, L Thomas, JM Chen, WP Noureddin, M Rotman, Y Liang, TJ AF Thomas, Emmanuel Gonzalez, Veronica D. Li, Qisheng Modi, Ankit A. Uccellini, Lorenzo Thomas, Jaime M. Chen, Weiping Noureddin, Mazen Rotman, Yaron Liang, T. Jake TI A robust induction of type III interferons and chemokines defines a unique pattern of hepatic innate immunity in response to hepatitis C virus infection SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Thomas, Emmanuel; Gonzalez, Veronica D.; Li, Qisheng; Modi, Ankit A.; Uccellini, Lorenzo; Thomas, Jaime M.; Chen, Weiping; Noureddin, Mazen; Rotman, Yaron; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RI Li, Qisheng/K-1909-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 49 EP 49 DI 10.1016/j.cyto.2011.07.158 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800169 ER PT J AU Germain, RN Meier-Schellersheim, M Angermann, B Klauschen, F Zhang, FH Brandes-Kuchen, M Garcia, A Prustel, T Fraser, I Li, N Deng, L Sun, J Benet, Z Nita-Lazar, A Tsang, J AF Germain, Ronald N. Meier-Schellersheim, Martin Angermann, Bastian Klauschen, Frederick Zhang, Fenghai Brandes-Kuchen, Marlene Garcia, Alex Prustel, Thorsten Fraser, Iain Li, Ning Deng, Li Sun, Jing Benet, Zachary Nita-Lazar, Aleksandra Tsang, John TI Bottom-up and Top-Down Systems Biology Approaches to Understanding Immunity SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Germain, Ronald N.; Meier-Schellersheim, Martin; Angermann, Bastian; Klauschen, Frederick; Zhang, Fenghai; Brandes-Kuchen, Marlene; Garcia, Alex; Prustel, Thorsten; Fraser, Iain; Li, Ning; Deng, Li; Sun, Jing; Benet, Zachary; Nita-Lazar, Aleksandra; Tsang, John] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Germain, Ronald N.; Tsang, John] NIH, Ctr Human Immunol Autoimmun & Inflammat CHI, Bethesda, MD 20892 USA. [Klauschen, Frederick] Charite, Inst Pathol, D-10117 Berlin, Germany. RI Klauschen, Frederick/C-5637-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 50 EP 50 DI 10.1016/j.cyto.2011.07.295 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800171 ER PT J AU Durum, SK Li, WQ Zenatti, P Ribeiro, D Zuurbier, L Silva, MC Paganin, M Tritapoe, J Hixon, JA Silveira, AB Cardoso, BA Sarmento, LM Correia, N Toribio, ML Kobarg, J Horstmann, M Pieters, R Brandalise, SR AF Durum, Soctt K. Li, W. Q. Zenatti, P. Ribeiro, D. Zuurbier, L. Silva, M. C. Paganin, M. Tritapoe, J. Hixon, J. A. Silveira, A. B. Cardoso, B. A. Sarmento, L. M. Correia, N. Toribio, M. L. Kobarg, J. Horstmann, M. Pieters, R. Brandalise, S. R. TI Oncogenic IL-7R gain-of-function mutations in childhood T-ALL SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Durum, Soctt K.; Li, W. Q.; Tritapoe, J.; Hixon, J. A.; Brandalise, S. R.] NCI, Bethesda, MD 20892 USA. [Zenatti, P.; Silveira, A. B.; Brandalise, S. R.] Ctr Infantil Boldrini, Boldrini, Brazil. [Ribeiro, D.; Silva, M. C.; Cardoso, B. A.; Sarmento, L. M.; Correia, N.] Univ Lisbon, P-1699 Lisbon, Portugal. [Zuurbier, L.; Pieters, R.] Erasmus MC, Rotterdam, Netherlands. [Durum, Soctt K.; Paganin, M.] Columbia Univ, New York, NY 10027 USA. [Toribio, M. L.] Univ Autonoma Madrid, E-28049 Madrid, Spain. [Horstmann, M.] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Durum, Soctt K.] Univ Estadual Campinas, BR-13081970 Campinas, SP, Brazil. [Durum, Soctt K.] 12 Univ Estadual Campinas, Campinas, SP, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 52 EP 53 DI 10.1016/j.cyto.2011.07.344 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800179 ER PT J AU Smith, M Hurley, A Karpova, T Belkina, N Shaw, S Nickel, E Packard, B Imamichi, H MacNally, J Sneller, M Lane, C Catalfamo, M AF Smith, Mindy Hurley, Amanda Karpova, Tatiana Belkina, Natalya Shaw, Steve Nickel, Erin Packard, Beverly Imamichi, Hiromi MacNally, James Sneller, Michael Lane, Clifford Catalfamo, Marta TI Thrombin mediates chemokinesis in human resting CD8 T cells through specific interaction with thrombin receptor (PAR-1) SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Smith, Mindy; Hurley, Amanda; Nickel, Erin; Imamichi, Hiromi; Sneller, Michael; Lane, Clifford; Catalfamo, Marta] NIAID, CMRS Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. [Belkina, Natalya; Shaw, Steve] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Packard, Beverly] Oncolmmunin Inc, Gaithersburg, MD 20877 USA. [Karpova, Tatiana; MacNally, James] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 58 EP 58 DI 10.1016/j.cyto.2011.07.362 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800194 ER PT J AU Tewary, P De, GD Sharma, N Rodriguez, L Shirota, H Steinhagen, F Klinman, DM Yang, D Oppenheim, JJ AF Tewary, Poonam de la Rosa, Gonzalo Sharma, Neeraj Rodriguez, Luis Shirota, Hidekatzu Steinhagen, Folkert Klinman, Dennis M. Yang, De Oppenheim, Joost J. TI Effect of antimicrobial proteins/alarmins on DNA mediated activation of pDC and inflammation SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Tewary, Poonam; de la Rosa, Gonzalo; Yang, De; Oppenheim, Joost J.] NCI, Lab Mol lmmunoregulat, Anal Lab, NCI SAIC Frederick,Ctr Canc Res, Frederick, MD 21702 USA. [Sharma, Neeraj] NCI, Lab Expt Immunol, Anal Lab, NCI SAIC Frederick,Ctr Canc Res, Frederick, MD 21702 USA. [Rodriguez, Luis] NCI, Opt Microscopy & Anal Lab, NCI SAIC Frederick, Ctr Canc Res, Frederick, MD 21702 USA. [Shirota, Hidekatzu; Steinhagen, Folkert; Klinman, Dennis M.] NCI, Canc & Inflammat Programm, NCI SAIC Frederick, Ctr Canc Res,Anal Lab, Frederick, MD 21702 USA. [Yang, De] NCI, Basic Sci Program, NCI SAIC Frederick, Ctr Canc Res,Anal Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 59 EP 59 DI 10.1016/j.cyto.2011.07.367 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800199 ER PT J AU Palmer, DC Reger, RN Garvin, LM Frasheri, D Ji, Y Franco, ZJ Gattinoni, CAKL Restifo, L AF Palmer, Douglas C. Reger, Robert N. Garvin, Lindsay M. Frasheri, Donna Ji, Yun Franco, Zulmarie J. Gattinoni, Christopher A. Klebanoff Luca Restifo, Nicholas P. TI Cish degradation of Htra1 regulates TGF-b signaling SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Palmer, Douglas C.; Reger, Robert N.; Garvin, Lindsay M.; Frasheri, Donna; Ji, Yun; Franco, Zulmarie J.; Gattinoni, Christopher A. Klebanoff Luca; Restifo, Nicholas P.] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 60 EP 60 DI 10.1016/j.cyto.2011.07.372 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800203 ER PT J AU Murphy, PM AF Murphy, Philip M. TI Targeting CXCR4 in WHIM Syndrome SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 62 EP 62 DI 10.1016/j.cyto.2011.07.377 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800207 ER PT J AU Miyake, K Bekisz, J Zhao, T Clark, C Zoon, KC AF Miyake, Kotaro Bekisz, Joseph Zhao, Tongmao Clark, Christopher Zoon, Kathryn C. TI Apoptosis-inducing factor (AIF) is targeted in IFN-alpha 2a-induced Bid mediated apoptosis through Bak activation in ovarian cancer cells SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Miyake, Kotaro; Bekisz, Joseph; Zhao, Tongmao; Clark, Christopher; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 97 EP 97 DI 10.1016/j.cyto.2011.07.286 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800330 ER PT J AU Ozato, K Chang, TH Xu, SX Kubota, T Matsuoka, M AF Ozato, Keiko Chang, Tsung-Hsien Xu, Song Xiao Kubota, Toru Matsuoka, Mayumi TI SUMO Modification of IRF Family Proteins and Regulation of Anti-Viral Innate Immunity SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Ozato, Keiko; Chang, Tsung-Hsien; Xu, Song Xiao] NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA. [Kubota, Toru; Matsuoka, Mayumi] Natl Inst Infect Dis, Tokyo, Japan. NR 3 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 99 EP 99 DI 10.1016/j.cyto.2011.07.383 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800334 ER PT J AU Hodge, DL Berthet, C Coppola, V Shirota, H Reynolds, D Klinman, DM Young, HA AF Hodge, Deborah L. Berthet, Cyril Coppola, Vincenzo Shirota, Hidekazu Reynolds, Della Klinman, Dennis M. Young, Howard A. TI Loss of Ifn-g 3 ' Untranslated Region Au-rich Element Affects b220+b Cell and Plasmacytoid Dendritic cell Populations in a Novel Murine Lupus Model SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Hodge, Deborah L.; Shirota, Hidekazu; Reynolds, Della; Klinman, Dennis M.; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Coppola, Vincenzo] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Berthet, Cyril] Oncodesign, Dijon, France. RI Coppola, Vincenzo/E-2917-2011 OI Coppola, Vincenzo/0000-0001-6163-1779 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 100 EP 100 DI 10.1016/j.cyto.2011.07.389 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800340 ER PT J AU Zoon, KC Nakashima, H Miyake, K Clark, C Bekisz, J Baron, S Husain, SR Puri, RK AF Zoon, Kathryn C. Nakashima, Hideyuki Miyake, Kotaro Clark, Christopher Bekisz, Joseph Baron, Samuel Husain, Syed R. Puri, Raj K. TI Combination therapy with IFN-alpha plus IFN-gamma and monocytes mediates synergistic antitumor effects against established human ovarian and melanoma tumors in mouse models SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Zoon, Kathryn C.; Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Zoon, Kathryn C.; Miyake, Kotaro; Clark, Christopher; Bekisz, Joseph; Baron, Samuel] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 102 EP 102 DI 10.1016/j.cyto.2011.07.397 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800347 ER PT J AU Sher, A Mayer-Barber, K Novikov, A Andrade, B Barber, D Shenderov, K Feng, C AF Sher, A. Mayer-Barber, K. Novikov, A. Andrade, B. Barber, D. Shenderov, K. Feng, C. TI Cytokine pathways regulating the innate immune response to mycobacteria SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Sher, A.; Mayer-Barber, K.; Novikov, A.; Andrade, B.; Barber, D.; Shenderov, K.; Feng, C.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RI Andrade, Bruno/J-9111-2012 OI Andrade, Bruno/0000-0001-6833-3811 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 107 EP 107 DI 10.1016/j.cyto.2011.07.415 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800362 ER PT J AU Ben-Sasson, SZ Caucheteux, S Crank, M Hu-Li, J Paul, WE AF Ben-Sasson, S. Z. Caucheteux, Stephane Crank, Michelle Hu-Li, Jane Paul, William E. TI IL-1 acts on T cells to enhance the magnitude of in vivo immune responses SO CYTOKINE LA English DT Review DE CD4; CD8; IL-1 receptor; Lipopolysaccharide; IL-1RA ID EXPANSION; TH17 AB IL-1 strikingly enhances antigen-driven responses of CD4 and CD8 T cells. It is substantially more effective than LPS and when added to a priming regime of antigen plus LPS, it strikingly enhances cell expansion. The effect is mediated by direct action on CD4 and CD8 T cells; the response occurs when OT-I or OT-II cells are transferred to B6 IL-1R1-/- recipients and only cells that express IL-1 receptors can respond. The major mechanism through which IL-1 enhances responses is by increasing survival of responding cells. IL-1 enhances the proportion of responding CD4 T cells that differentiate into Th17 cells and increases the proportion of responding CD8 cells that express granzyme B. Of a wide range of cytokines tested, only IL-1 alpha and IL-1 beta mediate this function. The potency of IL-1 as an enhancer of T cell responses suggests that it could act to enhance responses to weak vaccines and that the pathway utilized by IL-1 might be considered in the design of new generations of adjuvants. Published by Elsevier Ltd. C1 [Ben-Sasson, S. Z.; Caucheteux, Stephane; Crank, Michelle; Hu-Li, Jane; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU NIAID Division of Intramural Research [1-Z01-AI000926-09-LI] FX This work was supported by the NIAID Division of Intramural Research through Project 1-Z01-AI000926-09-LI. The care and handling of the animals used in our studies were in accordance with the guidelines of the National Institutes of Health Animal Care and Use Committee. We thank Shirley Starnes for excellent editorial assistance. NR 11 TC 24 Z9 25 U1 0 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 122 EP 125 DI 10.1016/j.cyto.2011.07.006 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800378 PM 21843950 ER PT J AU Harris, PJ Bible, KC AF Harris, Pamela Jo Bible, Keith C. TI Emerging therapeutics for advanced thyroid malignancies: rationale and targeted approaches SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE anaplastic thyroid cancer; differentiated thyroid cancer; medullary thyroid cancer; taxanes; tyrosine kinase inhibitors ID PHASE-II TRIAL; ADVANCED SOLID TUMORS; CANCER CELL-LINES; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; GENETIC ALTERATIONS; SIGNALING PATHWAYS; RADIOIODINE UPTAKE; NA+/I-SYMPORTER; RETINOIC ACID; UNITED-STATES AB Introduction: Thyroid cancer is an emerging public health concern. In the USA, its incidence has doubled in the past decade, making it the eighth most commonly diagnosed neoplasmin 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options. Areas covered: Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers. Expert opinion: Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity-modulated radiation therapy appears to extend survival for patients with locoregionally confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes. C1 [Harris, Pamela Jo] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Bible, Keith C.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. RP Harris, PJ (reprint author), NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. EM harrispj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 97 TC 14 Z9 16 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD OCT PY 2011 VL 20 IS 10 BP 1357 EP 1375 DI 10.1517/13543784.2011.614230 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 831GZ UT WOS:000295718800005 PM 21910667 ER PT J AU Khoury, MJ Gwinn, M Dotson, D Bowen, MS AF Khoury, Muin J. Gwinn, Marta Dotson, David Bowen, M. Scott TI Is there a need for PGxceptionalism? SO GENETICS IN MEDICINE LA English DT Editorial Material C1 [Khoury, Muin J.; Gwinn, Marta; Dotson, David; Bowen, M. Scott] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Khoury, MJ (reprint author), CDC, Off Publ Hlth Genom, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM muk1@cdc.gov OI Dotson, William David/0000-0002-9606-6594 NR 12 TC 5 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2011 VL 13 IS 10 BP 866 EP 867 DI 10.1097/GIM.0b013e3182265bed PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 833KN UT WOS:000295884200003 PM 21799428 ER PT J AU Melis, M Diaz, G Mogavero, G Tice, AB Lam, JH Brown, CR Becker, S Kabat, J Hanson, J Rodriguez-Canales, J Emmert-Buck, MR Kleiner, DE Govindarajan, S Zamboni, F Farci, P AF Melis, Marta Diaz, Giacomo Mogavero, Giulia Tice, Ashley B. Lam, Joyce H. Brown, Charles R. Becker, Steven Kabat, Juraj Hanson, Jeffrey Rodriguez-Canales, Jaime Emmert-Buck, Michael R. Kleiner, David E. Govindarajan, Sugantha Zamboni, Fausto Farci, Patrizia TI GENE EXPRESSION PROFILING OF HEPATITIS B VIRUS (HBV)-ASSOCIATED HEPATOCELLULAR CARCINOMA (HCC) SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Melis, Marta; Tice, Ashley B.; Lam, Joyce H.; Farci, Patrizia] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci & Technol, Cagliari, Italy. [Mogavero, Giulia; Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. [Brown, Charles R.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Becker, Steven; Kabat, Juraj] NIAID, Biol Imaging Facil, NIH, Bethesda, MD 20892 USA. [Hanson, Jeffrey; Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.; Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Govindarajan, Sugantha] Univ So Calif, Rancho Los Amigos Hosp, Dept Pathol, Downey, CA 90242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 371A EP 372A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002025 ER PT J AU Shin, EC Park, SH Nascimbeni, M Major, ME Rice, CM Rehermann, B AF Shin, Eui-Cheol Park, Su-Hyung Nascimbeni, Michelina Major, Marian E. Rice, Charles M. Rehermann, Barbara TI THE PERCENTAGE OF HEPATITIS C VIRUS-SPECIFIC CD127+MEMORY T CELLS IN THE ACUTE PHASE T CELL RESPONSE PREDICTS THE OUTCOME OF HCV INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shin, Eui-Cheol; Park, Su-Hyung; Nascimbeni, Michelina; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD USA. [Shin, Eui-Cheol] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Major, Marian E.] US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 380A EP 380A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002040 ER PT J AU Wu, R Lin, M Lehil, M Shen, H Cozen, M Gao, X Martin, M Lanier, LL Yee, R Duh, FM Monto, A Carrington, M Ryan, JC AF Wu, Richard Lin, Monika Lehil, Mandeep Shen, Hui Cozen, Myrna Gao, Xiang Martin, Maureen Lanier, Lewis L. Yee, Russell Duh, Fuh-Mei Monto, Alexander Carrington, Mary Ryan, James C. TI INDEPENDENT INFLUENCES OF KILLER IMMUNOGLOBULIN RECEPTORS (KIR) AND THE RS12979860 IL28B POLYMORPHISM ON SPONTANEOUS HCV RESOLUTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Wu, Richard; Lin, Monika; Lehil, Mandeep; Shen, Hui; Cozen, Myrna; Lanier, Lewis L.; Yee, Russell; Monto, Alexander; Ryan, James C.] UCSF, San Francisco, CA USA. [Gao, Xiang; Martin, Maureen; Duh, Fuh-Mei; Carrington, Mary] NCI, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 381A EP 381A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002042 ER PT J AU Noureddin, M Rotman, Y Feld, JJ Han, H Park, YJ Thomas, E Koh, C Abdalla, AA Gara, N Sarkar, S Doo, E Ghany, MG Heller, T Hoofnagle, JH Liang, TJ AF Noureddin, Mazen Rotman, Yaron Feld, Jordan J. Han, Hwalih Park, Yoon J. Thomas, Emmanuel Koh, Christopher Abdalla, Adil A. Gara, Naveen Sarkar, Souvik Doo, Edward Ghany, Marc G. Heller, Theo Hoofnagle, Jay H. Liang, T. Jake TI DIFFERENTIAL HEPATIC EXPRESSION OF INTERFERON STIMULATED GENES BETWEEN HCV GENOTYPES 1 AND 2/3 CORRELATES WITH RESPONSIVENESS TO PEGINTERFERON SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Rotman, Yaron; Han, Hwalih; Park, Yoon J.; Thomas, Emmanuel; Koh, Christopher; Abdalla, Adil A.; Gara, Naveen; Sarkar, Souvik; Doo, Edward; Ghany, Marc G.; Heller, Theo; Hoofnagle, Jay H.; Liang, T. Jake] NIDDK, Bethesda, MD USA. [Feld, Jordan J.] Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 401A EP 402A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002085 ER PT J AU Park, SH Veerapu, NS Rehermann, B AF Park, Su-Hyung Veerapu, Naga Suresh Rehermann, Barbara TI REPEATED EXPOSURE TO TRACE AMOUNTS OF HEPATITIS C VIRUS SUPPRESSES T CELL RESPONSES TO SUBSEQUENT HIGH DOSE HCV CHALLENGE VIA INDUCTION OF REGULATORY T CELLS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Park, Su-Hyung; Veerapu, Naga Suresh; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 403A EP 403A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002087 ER PT J AU Hara, K Koh, C Sakiani, S Rivera, M Liang, TJ Hoofnagle, JH Heller, T AF Hara, Koji Koh, Christopher Sakiani, Sasan Rivera, Maria Liang, T. Jake Hoofnagle, Jay H. Heller, Theo TI IMPORTANT DETERMINANTS OF 5 ' UNTRANSLATED REGION (UTR) IN HEPATITIS C VIRUS (HCV) GENOTYPING: CLINICAL IMPLICATIONS FOR TODAY AND THE FUTURE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Hara, Koji; Koh, Christopher; Sakiani, Sasan; Rivera, Maria; Liang, T. Jake; Hoofnagle, Jay H.; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 404A EP 405A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002090 ER PT J AU Li, QS Krishnamurthy, S El-Diwany, R Liang, TJ AF Li, Qisheng Krishnamurthy, Siddharth El-Diwany, Ramy Liang, T. Jake TI GENOME-WIDE FUNCTIONAL SCREEN DISCOVERS NOVEL HOST MICRORNAS THAT MODULATE HEPATITIS C VIRUS INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Li, Qisheng; Krishnamurthy, Siddharth; El-Diwany, Ramy; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RI Li, Qisheng/K-1909-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 406A EP 406A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002094 ER PT J AU Baghdasaryan, A Claudel, T Gumhold, J Silbert, D Adorini, L Gonzalez, F Schoonjans, K Fickert, P Trauner, M AF Baghdasaryan, Anna Claudel, Thierry Gumhold, Judith Silbert, Dagmar Adorini, Luciano Gonzalez, Frank Schoonjans, Kristina Fickert, Peter Trauner, Michael TI FXR BUT NOT TGR5 ACTIVATION STIMULATES HCO3-RICH BILE SECRETION AND AMELIORATES LIVER DAMAGE IN MDR2-/- (ABCB4-/-) MOUSE MODEL OF CHRONIC LIVER INJURY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Baghdasaryan, Anna; Claudel, Thierry; Gumhold, Judith; Silbert, Dagmar; Fickert, Peter; Trauner, Michael] Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Lab Expt & Mol Hepatol, Graz, Austria. [Claudel, Thierry; Trauner, Michael] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Vienna, Austria. [Adorini, Luciano] Intercept Pharmaceut, New York, NY USA. [Gonzalez, Frank] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Schoonjans, Kristina] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 425A EP 425A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002133 ER PT J AU Kitade, M Factor, VM Akita, H Holczbauer, A Conner, EA Lee, YH Lee, SB Thorgeirsson, SS AF Kitade, Mitsuteru Factor, Valentina M. Akita, Hirofumi Holczbauer, Agnes Conner, Elizabeth A. Lee, Yun-Han Lee, Seung Bum Thorgeirsson, Snorri S. TI THE FUNCTIONS OF EGFR AND MET IN HEPATIC PROGENITOR CELL DIFFERENTIATION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kitade, Mitsuteru; Factor, Valentina M.; Akita, Hirofumi; Holczbauer, Agnes; Conner, Elizabeth A.; Lee, Yun-Han; Lee, Seung Bum; Thorgeirsson, Snorri S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 449A EP 449A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002180 ER PT J AU Yamashita, T Honda, M Nakamoto, Y Mizukoshi, E Yamashita, T Arai, K Nio, K Hara, Y Wang, XW Kaneko, S AF Yamashita, Taro Honda, Masao Nakamoto, Yasunari Mizukoshi, Eishiro Yamashita, Tatsuya Arai, Kuniaki Nio, Kouki Hara, Yasumasa Wang, Xin W. Kaneko, Shuichi TI DISTINCT LIVER CANCER STEM CELLS DEFINED BY EPCAM AND CD90 IN HUMAN HEPATOCELLULAR CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Yamashita, Taro; Honda, Masao; Nakamoto, Yasunari; Mizukoshi, Eishiro; Yamashita, Tatsuya; Arai, Kuniaki; Nio, Kouki; Hara, Yasumasa; Kaneko, Shuichi] Kanazawa Univ, Grad Sch Med Sci, Dept Gastroenterol, Kanazawa, Ishikawa, Japan. [Wang, Xin W.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 449A EP 449A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002179 ER PT J AU Maldonado, EN Sheldon, KL Patnaik, JR Rostovtseva, TK Lemasters, JJ AF Maldonado, Eduardo N. Sheldon, Kely L. Patnaik, Jyoti R. Rostovtseva, Tatiana K. Lemasters, John J. TI ERASTIN ANTAGONIZES THE INHIBITORY EFFECT OF FREE TUBULIN ON VDAC AND INCREASES MITOCHONDRIAL MEMBRANE POTENTIAL IN HEPG2 CELLS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Maldonado, Eduardo N.; Patnaik, Jyoti R.; Lemasters, John J.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Maldonado, Eduardo N.; Patnaik, Jyoti R.; Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Sheldon, Kely L.; Rostovtseva, Tatiana K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Struct Biol, NIH, Bethesda, MD USA. [Sheldon, Kely L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstein Dept Mol Microbiol & Immunol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 455A EP 455A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002191 ER PT J AU Shneider, BL Magee, JC Karpen, SJ Rand, E Narkewicz, MR Schwarz, KB Whitington, PF Bezerra, JA Kerkar, N Haber, B Rosenthal, P Turmelle, YP Molleston, JP Murray, KF Ng, VL Wang, KS Romero, R Moore, J Robuck, PR Sokol, RJ AF Shneider, Benjamin L. Magee, John C. Karpen, Saul J. Rand, Elizabeth Narkewicz, Michael R. Schwarz, Kathleen B. Whitington, Peter F. Bezerra, Jorge A. Kerkar, Nanda Haber, Barbara Rosenthal, Philip Turmelle, Yumirle P. Molleston, Jean P. Murray, Karen F. Ng, Vicky L. Wang, Kasper S. Romero, Rene Moore, Jeffrey Robuck, Patricia R. Sokol, Ronald J. TI PROSPECTIVE MULTICENTER ANALYSIS OF POST-OPERATIVE TOTAL BILIRUBIN AS A BIOMARKER FOR SHORT-TERM OUTCOME AFTER HEPATOPORTOENTEROSTOMY FOR BILIARY ATRESIA SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shneider, Benjamin L.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Magee, John C.; Moore, Jeffrey] Univ Michigan, Ann Arbor, MI 48109 USA. [Karpen, Saul J.] Texas Childrens Hosp, Houston, TX 77030 USA. [Rand, Elizabeth; Haber, Barbara] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Narkewicz, Michael R.; Sokol, Ronald J.] Univ Colorado, Denver, CO 80202 USA. [Schwarz, Kathleen B.] Johns Hopkins Univ, Baltimore, MD USA. [Whitington, Peter F.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Bezerra, Jorge A.] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Kerkar, Nanda] Mt Sinai Sch Med, New York, NY USA. [Rosenthal, Philip] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Turmelle, Yumirle P.] Washington Univ, St Louis, MO USA. [Molleston, Jean P.] Indiana Univ, Indianapolis, IN 46204 USA. [Murray, Karen F.] Univ Washington, Seattle, WA 98195 USA. [Ng, Vicky L.] Univ Toronto, Toronto, ON, Canada. [Wang, Kasper S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Romero, Rene] Childrens Hosp Atlanta, Atlanta, GA USA. [Robuck, Patricia R.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 468A EP 468A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002217 ER PT J AU Fried, MW Navarro, VJ Afdhal, NH Wahed, AS Hawke, RL Belle, SH Doo, E Meyers, CM Reddy, KR AF Fried, Michael W. Navarro, Victor J. Afdhal, Nezam H. Wahed, Abdus S. Hawke, Roy L. Belle, Steven H. Doo, Edward Meyers, Catherine M. Reddy, K. Rajender TI A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF ORAL SILYMARIN (MILK THISTLE) FOR CHRONIC HEPATITIS C: FINAL RESULTS OF THE SYNCH MULTICENTER STUDY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Fried, Michael W.] Univ N Carolina, UNC Liver Ctr, Chapel Hill, NC USA. [Navarro, Victor J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Afdhal, Nezam H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wahed, Abdus S.; Belle, Steven H.] Univ Pittsburgh, Pittsburgh, PA USA. [Hawke, Roy L.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA. [Doo, Edward] NIDDK, NIH, Bethesda, MD USA. [Meyers, Catherine M.] NIH, NCCAM, Bethesda, MD 20892 USA. [Reddy, K. Rajender] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 475A EP 475A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002228 ER PT J AU Gara, N Ghany, MG Zhao, XC Collins, MT Hoofnagle, JH AF Gara, Naveen Ghany, Marc G. Zhao, Xiongce Collins, Michael T. Hoofnagle, Jay H. TI PHOSPHATE WASTING NEPHROPATHY IN PATIENTS WITH CHRONIC HEPATITIS B TREATED WITH LONG-TERM ADEFOVIR OR TENOFOVIR SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Gara, Naveen; Ghany, Marc G.; Hoofnagle, Jay H.] NIH, LDB, Bethesda, MD 20892 USA. [Collins, Michael T.] NIDCR, Skeletal Clin Studies Unit, Bethesda, MD USA. [Zhao, Xiongce] NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 479A EP 480A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002237 ER PT J AU Sarkar, M French, A Tien, P Bacchetti, P Glesby, M Gange, SJ Plankey, M Sharp, G Nowicki, MJ Minkoff, H Peters, MG AF Sarkar, Monika French, Audrey Tien, Phyllis Bacchetti, Peter Glesby, Marshall Gange, Stephen J. Plankey, Michael Sharp, Gerald Nowicki, Marek J. Minkoff, Howard Peters, Marion G. TI RACIAL/ETHNIC DIFFERENCES IN OVERALL AND LIVER-RELATED MORTALITY IN HIV INFECTED WOMEN WITH CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Sarkar, Monika; Tien, Phyllis; Bacchetti, Peter; Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [French, Audrey] Rush Univ, Chicago, IL 60612 USA. [Gange, Stephen J.] Johns Hopkins Univ, Baltimore, MD USA. [Glesby, Marshall] Cornell Univ, New York, NY 10021 USA. [Minkoff, Howard] SUNY Downstate, Brooklyn, NY USA. [Nowicki, Marek J.] Univ So Calif, Los Angeles, CA USA. [Plankey, Michael] Georgetown Univ, Washington, DC USA. [Sharp, Gerald] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 483A EP 484A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002244 ER PT J AU Odigie, M Zhang, XZ Masur, H Polis, MA Kottilil, S Osinusi, A AF Odigie, Madeline Zhang, Xiaozhen Masur, Henry Polis, Michael A. Kottilil, Shyam Osinusi, Anu TI IL23 PROMOTES INTERFERON RESPONSIVENESS IN HIV/HCV COINFECTED PATIENTS TREATED WITH PEGYLATED INTERFERON AND RIBAVIRIN SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Odigie, Madeline; Zhang, Xiaozhen; Polis, Michael A.; Kottilil, Shyam; Osinusi, Anu] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Osinusi, Anu] NCI Frederick Inc, Clin Res Directorate, CMRP, SAIC Frederick, Frederick, MD USA. [Masur, Henry] CC, CCMD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 488A EP 488A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002252 ER PT J AU Thomas, E Gonzalez, VD Li, QS Noureddin, M Rotman, Y Liang, TJ AF Thomas, Emmanuel Gonzalez, Veronica D. Li, Qisheng Noureddin, Mazen Rotman, Yaron Liang, T. Jake TI ROBUST INDUCTION OF TYPE III INTERFERONS AND OTHER CYTOKINES DEFINES A UNIQUE PATTERN OF INNATE IMMUNITY IN RESPONSE TO HEPATITIS C VIRUS INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Thomas, Emmanuel; Gonzalez, Veronica D.; Li, Qisheng; Noureddin, Mazen; Rotman, Yaron; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RI Li, Qisheng/K-1909-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 493A EP 493A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002262 ER PT J AU Nagata, T Huang, YG AF Nagata, Takako Huang, Yuning G. TI ROLE OF ADENOSINE A1 RECEPTORS IN EXACERBATION OF INFLAMMATION AND LIVER DAMAGE UNDER EXCESSIVE ALCOHOL CONSUMPTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Nagata, Takako] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Huang, Yuning G.] NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 512A EP 512A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002305 ER PT J AU Alqahtani, S Hoofnagle, JH Ghabril, M Chalasani, NP Rockey, DC AF Alqahtani, Saleh Hoofnagle, Jay H. Ghabril, Marwan Chalasani, Naga P. Rockey, Don C. TI CEPHALOSPORIN INDUCED LIVER INJURY: CLINICAL AND BIOCHEMICAL FEATURES SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Alqahtani, Saleh; Rockey, Don C.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Hoofnagle, Jay H.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. [Ghabril, Marwan; Chalasani, Naga P.] Indiana Univ, Div Gastroenterol & Hepatol, Indianapolis, IN 46204 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 516A EP 516A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002314 ER PT J AU Kleiner, DE Fontana, RJ Rockey, DC Chalasani, NP Watkins, PB Bonkovsky, HL Davern, TJ Navarro, VJ Reddy, KR Talwalkar, JA Lee, WM Stolz, A Hoofnagle, JH Gu, JZ AF Kleiner, David E. Fontana, Robert J. Rockey, Don C. Chalasani, Naga P. Watkins, Paul B. Bonkovsky, Herbert L. Davern, Timothy J. Navarro, Victor J. Reddy, K. Rajender Talwalkar, Jayant A. Lee, William M. Stolz, Andrew Hoofnagle, Jay H. Gu, Jiezhun TI HISTOLOGIC ANALYSIS AND CORRELATION WITH CLINICAL OUTCOMES IN THE DRUG-INDUCED LIVER INJURY NETWORK (DILIN) SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Rockey, Don C.; Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Watkins, Paul B.] Univ N Carolina, Chapel Hill, NC USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Davern, Timothy J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Navarro, Victor J.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Reddy, K. Rajender] Univ Penn, Philadelphia, PA 19104 USA. [Talwalkar, Jayant A.] Mayo Clin, Coll Med, Rochester, MN USA. [Hoofnagle, Jay H.] NIDDK, Bethesda, MD USA. [Gu, Jiezhun] Duke Clin Res Inst, Durham, NC USA. [Stolz, Andrew] Univ So Calif, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 518A EP 519A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002320 ER PT J AU Bell, LN Vuppalanchi, R Watkins, PB Bonkovsky, HL Serrano, J Fontana, RJ Wang, M Rochon, J Chalasani, NP AF Bell, Lauren N. Vuppalanchi, Raj Watkins, Paul B. Bonkovsky, Herbert L. Serrano, Jose Fontana, Robert J. Wang, Mu Rochon, James Chalasani, Naga P. TI SERUM PROTEOMIC PROFILING IN PATIENTS WITH DRUG-INDUCED LIVER INJURY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Wang, Mu] Indiana Univ, Prot Anal Res Ctr, Indianapolis, IN 46204 USA. [Watkins, Paul B.] Univ N Carolina, Chapel Hill, NC USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Cannon Res Ctr, Charlotte, NC 28203 USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Ctr Liver & Digest Dis, Charlotte, NC 28203 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Farmington, CT USA. [Serrano, Jose] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Rochon, James] Duke Univ, Duke Clin Res Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 521A EP 522A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002326 ER PT J AU Vega, M Vuppalanchi, R Bonkovsky, HL Reddy, KR Talwalkar, JA Seeff, LB Serrano, J Navarro, VJ AF Vega, Maricruz Vuppalanchi, Raj Bonkovsky, Herbert L. Reddy, K. Rajender Talwalkar, Jayant A. Seeff, Leonard B. Serrano, Jose Navarro, Victor J. TI THE US DRUG INDUCED LIVER INJURY NETWORK: ESTABLISHMENT OF AN HERBAL AND DIETARY SUPPLEMENT (HDS) REPOSITORY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Vega, Maricruz; Navarro, Victor J.] Thomas Jefferson Univ, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. [Vuppalanchi, Raj] Indiana Univ, Indianapolis, IN 46204 USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Reddy, K. Rajender] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Talwalkar, Jayant A.] Mayo Clin, Rochester, MN USA. [Seeff, Leonard B.] US FDA, Bethesda, MD 20014 USA. [Serrano, Jose] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 528A EP 529A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002341 ER PT J AU Steuerwald, N Parsons, J Norton, HJ Saha, D Chalasani, NP Bell, LN Fontana, RJ Watkins, PB Serrano, J Bonkovsky, HL AF Steuerwald, Nury Parsons, Judith Norton, Harry J. Saha, Dhanonjoy Chalasani, Naga P. Bell, Lauren N. Fontana, Robert J. Watkins, Paul B. Serrano, Jose Bonkovsky, Herbert L. TI CHEMOKINE/CYTOKINE PROFILES IN PATIENTS WITH ACUTE DILI: RESULTS FROM THE US DRUG-INDUCED LIVER INJURY NETWORK SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Steuerwald, Nury; Parsons, Judith; Norton, Harry J.; Saha, Dhanonjoy; Bonkovsky, Herbert L.] Carolinas Med Ctr, Cannon Res Ctr, Charlotte, NC 28203 USA. [Chalasani, Naga P.; Bell, Lauren N.] Indiana Univ, Indianapolis, IN 46204 USA. [Fontana, Robert J.] Univ Michigan Hosp, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Watkins, Paul B.] Hamner Univ N Carolina, Inst Drug Safety Sci, Res Triangle Pk, NC USA. [Serrano, Jose] NIDDK, Digest Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 529A EP 529A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002342 ER PT J AU Werner, JM Heller, T Rehermann, B AF Werner, Jens M. Heller, Theo Rehermann, Barbara TI NATURAL KILLER CELL RESPONSES IN HEPATITIS C VIRUS EXPOSED HEALTHCARE WORKERS WHO DO NOT DEVELOP ACUTE INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Werner, Jens M.; Heller, Theo; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 557A EP 557A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002399 ER PT J AU Noureddin, M Wright, EC Zhao, XC Clark, S Thomas, E Alter, HJ Kleiner, DE Liang, TJ Ghany, MG AF Noureddin, Mazen Wright, Elizabeth C. Zhao, Xiongce Clark, Shauna Thomas, Emmanuel Alter, Harvey J. Kleiner, David E. Liang, T. Jake Ghany, Marc G. TI RELATIONSHIP BETWEEN IL28B GENOTYPE AND HISTOLOGICAL PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Wright, Elizabeth C.; Zhao, Xiongce; Clark, Shauna; Thomas, Emmanuel; Liang, T. Jake; Ghany, Marc G.] NIDDK, Bethesda, MD USA. [Alter, Harvey J.] NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 562A EP 562A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002409 ER PT J AU Gara, N Kleiner, DE Zhao, XC Koh, C Rotman, Y Heller, T Abdalla, AA Sarkar, S Noureddin, M Wright, EC Hoofnagle, JH Liang, TJ Ghany, MG AF Gara, Naveen Kleiner, David E. Zhao, Xiongce Koh, Christopher Rotman, Yaron Heller, Theo Abdalla, Adil A. Sarkar, Souvik Noureddin, Mazen Wright, Elizabeth C. Hoofnagle, Jay H. Liang, T. Jake Ghany, Marc G. TI PERFORMANCE OF TRANSIENT ELASTOGRAPHY AND APRI FOR PREDICTION OF ADVANCED LIVER DISEASE IN A NORTH AMERICAN POPULATION WITH CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Gara, Naveen; Koh, Christopher; Rotman, Yaron; Heller, Theo; Abdalla, Adil A.; Sarkar, Souvik; Noureddin, Mazen; Hoofnagle, Jay H.; Liang, T. Jake; Ghany, Marc G.] NIH, LDB, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA. [Zhao, Xiongce; Wright, Elizabeth C.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 570A EP 570A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002423 ER PT J AU Noureddin, M Rotman, Y Feld, JJ Han, H Park, YJ Koh, C Abdalla, AA Sarkar, S Gara, N Thomas, E Holz, L Park, SH Clark, S Ghany, MG Doo, E Heller, T Rehermann, B Hoofnagle, JH Liang, TJ AF Noureddin, Mazen Rotman, Yaron Feld, Jordan J. Han, Hwalih Park, Yoon J. Koh, Christopher Abdalla, Adil A. Sarkar, Souvik Gara, Naveen Thomas, Emmanuel Holz, Lauren Park, Su-Hyung Clark, Shauna Ghany, Marc G. Doo, Edward Heller, Theo Rehermann, Barbara Hoofnagle, Jay H. Liang, T. Jake TI THE IL28B POLYMORPHISM RS12979860 DOES NOT PREDICT RESPONSE TO RIBAVIRIN MONOTHERAPY IN PATIENTS WITH CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Rotman, Yaron; Han, Hwalih; Park, Yoon J.; Koh, Christopher; Abdalla, Adil A.; Sarkar, Souvik; Gara, Naveen; Thomas, Emmanuel; Holz, Lauren; Park, Su-Hyung; Clark, Shauna; Ghany, Marc G.; Doo, Edward; Heller, Theo; Rehermann, Barbara; Hoofnagle, Jay H.; Liang, T. Jake] NIDDK, Bethesda, MD USA. [Feld, Jordan J.] Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 576A EP 577A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002437 ER PT J AU Han, H Noureddin, M Park, YJ Hoofnagle, JH Liang, TJ Rotman, Y AF Han, Hwalih Noureddin, Mazen Park, Yoon J. Hoofnagle, Jay H. Liang, T. Jake Rotman, Yaron TI CHANGES IN ORAL TEMPERATURE AFTER THE INITIAL INJECTION OF PEGINTERFERON ALFA-2A IN PATIENTS WITH CHRONIC HEPATITIS C REFLECT HOST-INTERFERON RESPONSIVENESS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Han, Hwalih; Noureddin, Mazen; Park, Yoon J.; Hoofnagle, Jay H.; Liang, T. Jake; Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 600A EP 601A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002486 ER PT J AU Mi, LJ Rincon-Bejarano, LA Babbar, R Chiu, EK Martell, M Karsdon, J Ghany, MG AF Mi, Li-Jun Rincon-Bejarano, Luz A. Babbar, Rajeev Chiu, Edward K. Martell, Marialina Karsdon, Jeffrey Ghany, Marc G. TI VITAMIN D DEFICIENCY IN ASIAN-AMERICAN PATIENTS WITH CHRONIC HEPATITIS B IN NEW YORK DOWNTOWN HOSPITAL SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Mi, Li-Jun; Rincon-Bejarano, Luz A.; Babbar, Rajeev; Chiu, Edward K.; Martell, Marialina; Karsdon, Jeffrey] New York Downtown Hosp, New York, NY USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 614A EP 614A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002514 ER PT J AU Bell, LN Molleston, JP Lavine, JE Schwimmer, JB Murray, KF Rosenthal, P Abrams, SH Sanyal, AJ Brunt, EM Kleiner, DE Unalp, A Wang, JX Wilson, L Chalasani, NP AF Bell, Lauren N. Molleston, Jean P. Lavine, Joel E. Schwimmer, Jeffrey B. Murray, Karen F. Rosenthal, Philip Abrams, Stephanie H. Sanyal, Arun J. Brunt, Elizabeth M. Kleiner, David E. Unalp, Aynur Wang, Jiangxia Wilson, Laura Chalasani, Naga P. TI CHANGES IN ADIPOSE TISSUE INSULIN RESISTANCE CORRELATE WITH CHANGES IN ALT AND LOBULAR INFLAMMATION IN CHILDREN ENROLLED IN THE TONIC TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Bell, Lauren N.; Molleston, Jean P.; Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Lavine, Joel E.] Columbia Univ, New York, NY USA. [Schwimmer, Jeffrey B.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Murray, Karen F.] Seattle Childrens Hosp, Seattle, WA USA. [Rosenthal, Philip] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA. [Abrams, Stephanie H.] Baylor Coll Med, Houston, TX 77030 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Brunt, Elizabeth M.] Washington Univ, Sch Med, St Louis, MO USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Unalp, Aynur; Wang, Jiangxia; Wilson, Laura] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 711A EP 711A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002724 ER PT J AU Liu, HX Zhan, Q Gonzalez, FJ Wan, YJY AF Liu, Hui-Xin Zhan, Qi Gonzalez, Frank J. Wan, Yu-Jui Yvonne TI PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) beta IS ESSENTIAL FOR NORMAL PROGRESSION OF LIVER REGENERATION BY MODULATING LIPID HOMEOSTASIS AND PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1 (PDK1)/AKT-MEDIATED SIGNALING SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liu, Hui-Xin; Zhan, Qi; Wan, Yu-Jui Yvonne] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Gonzalez, Frank J.] NCI, Natl Ilnstitutes Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 714A EP 715A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002732 ER PT J AU Enriquez-Cortina, GC Cornejo, MDDC Lombarri, NN Dominguez, M Bucio, L Souza, V Thorgeirsson, SS Factor, VM Conner, EA Dominguez, M Gomez-Quiroz, LE Gutierrez-Ruiz, MC AF Enriquez-Cortina, Gloria C. Clavijo Cornejo, Maria del Refugio Denise Lombarri, Natalia Nuno Dominguez, Mayra Bucio, Leticia Souza, Veronica Thorgeirsson, Snorri S. Factor, Valentina M. Conner, Elizabeth A. Dominguez, Marcela Gomez-Quiroz, Luis E. Gutierrez-Ruiz, Maria C. TI HGF INDUCES THE ACTIVATION OF NRF2 IN MOUSE HEPATOCYTES BY A NADPH OXIDASE AND PKC DEPENDENT MECHANISM SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Enriquez-Cortina, Gloria C.; Clavijo Cornejo, Maria del Refugio Denise; Lombarri, Natalia Nuno; Dominguez, Mayra; Bucio, Leticia; Souza, Veronica; Dominguez, Marcela; Gomez-Quiroz, Luis E.; Gutierrez-Ruiz, Maria C.] Univ Autonoma Metropolitana, Mexico City, DF, Mexico. [Thorgeirsson, Snorri S.; Factor, Valentina M.; Conner, Elizabeth A.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RI Gomez-Quiroz, Luis/L-8415-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 717A EP 718A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002740 ER PT J AU Kong, XN Feng, DC Bertola, A Park, O Wang, H Yin, S Gao, B AF Kong, Xiaoni Feng, Dechun Bertola, Adeline Park, Ogyi Wang, Hua Yin, Shi Gao, Bin TI INTERLUKIN-22 INDUCES HEPATIC STELLATE CELL SENESCENCE AND RESTRICTS LIVER FIBROSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kong, Xiaoni; Feng, Dechun; Bertola, Adeline; Park, Ogyi; Wang, Hua; Yin, Shi; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 733A EP 733A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003013 ER PT J AU Marquardt, JU Maass, T Krupp, M Staib, F Andersen, JB Galle, PR Thorgeirsson, SS Teufel, A AF Marquardt, Jens U. Maass, Thorsten Krupp, Markus Staib, Frank Andersen, Jesper B. Galle, Peter R. Thorgeirsson, Snorri S. Teufel, Andreas TI DISSECTING THE ROLE OF PDGF-B DURING LIVER FIBROGENESIS: MECHANISTIC AND THERAPEUTIC IMPLICATIONS FROM A TRANSGENIC MOUSE MODEL SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Marquardt, Jens U.; Maass, Thorsten; Krupp, Markus; Staib, Frank; Galle, Peter R.; Teufel, Andreas] Johannes Gutenberg Univ Mainz, Dept Internal Med 1, D-6500 Mainz, Germany. [Marquardt, Jens U.; Andersen, Jesper B.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 738A EP 738A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003024 ER PT J AU Zhang, YX Bonzo, JA Gonzalez, FJ Wang, L AF Zhang, Yuxia Bonzo, Jessica A. Gonzalez, Frank J. Wang, Li TI DIURNAL REGULATION OF EGR-1 EXPRESSION BY HNF4 alpha AND SHP CROSSTALK IN LIVER FIBROSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Zhang, Yuxia; Wang, Li] Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA. [Zhang, Yuxia; Wang, Li] Univ Utah, Sch Med, Dept Oncol Sci, Salt Lake City, UT USA. [Bonzo, Jessica A.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 744A EP 745A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003039 ER PT J AU Fu, D Mitra, K Lippincott-Schwartz, J Arias, IM AF Fu, Dong Mitra, Kasturi Lippincott-Schwartz, Jennifer Arias, Irwin M. TI HEPATOCYTE POLARIZATION REQUIRES MITOCHONDRIAL FUSION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Fu, Dong; Lippincott-Schwartz, Jennifer; Arias, Irwin M.] NICHD, NIH, Bethesda, MD USA. [Mitra, Kasturi] NHLBI, NIH, Bethesda, MD 20892 USA. RI Fu, Dong /J-1426-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 772A EP 773A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003104 ER PT J AU Andersen, JB Spee, B Blechacz, B Avital, I Komuta, M Barbour, A Roskams, T Roberts, LR Factor, VM Thorgeirsson, SS AF Andersen, Jesper B. Spee, Bart Blechacz, Boris Avital, Itzhak Komuta, Mina Barbour, Andrew Roskams, Tania Roberts, Lewis R. Factor, Valentina M. Thorgeirsson, Snorri S. TI GENOMIC AND GENETIC CHARACTERIZATION OF HUMAN CHOLANGIOCARCINOMA IDENTIFIES TREATMENT OPTIONS FOR TYROSINE KINASE INHIBITORS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Andersen, Jesper B.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, LEC, Bethesda, MD 20892 USA. [Spee, Bart; Komuta, Mina; Roskams, Tania] Katholieke Univ Leuven, Louvain, Belgium. [Blechacz, Boris; Roberts, Lewis R.] Mayo Clin, Rochester, MN USA. [Avital, Itzhak] NCI, Surg Branch, Bethesda, MD 20892 USA. [Barbour, Andrew] Univ Queensland, Brisbane, Qld, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 777A EP 778A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003115 ER PT J AU Ahlenstiel, G Edlich, B Zabaleta, A Rehermann, B Noureddin, M Feld, JJ Liang, TJ Rotman, Y AF Ahlenstiel, Golo Edlich, Birgit Zabaleta, Aintzane Rehermann, Barbara Noureddin, Mazen Feld, Jordan J. Liang, T. Jake Rotman, Yaron TI EARLY CHANGES IN INTERFERON SIGNALING DEFINE NATURAL KILLER CELL RESPONSE AND REFRACTORINESS DURING INTERFERON-BASED THERAPY OF HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Ahlenstiel, Golo; Edlich, Birgit; Zabaleta, Aintzane; Rehermann, Barbara; Noureddin, Mazen; Feld, Jordan J.; Liang, T. Jake; Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 796A EP 796A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003157 ER PT J AU Thompson, AJ Clark, PJ Vock, DM Pfeiffer, R Tillmann, HL Patel, K Naggie, S Poordad, FF Nyberg, LM Noviello, S Pedicone, L Brass, CA Albrecht, JK Goldstein, DB McHutchison, JG O'Brien, TR Sulkowski, MS Muir, AJ AF Thompson, Alexander J. Clark, Paul J. Vock, David M. Pfeiffer, Ruth Tillmann, Hans L. Patel, Keyur Naggie, Susanna Poordad, F. Fred Nyberg, Lisa M. Noviello, Stephanie Pedicone, Lisa Brass, Clifford A. Albrecht, Janice K. Goldstein, David B. McHutchison, John G. O'Brien, Thomas R. Sulkowski, Mark S. Muir, Andrew J. TI PREDICTING PEGINTERFERON-alpha AND RIBAVIRIN TREATMENT RESPONSE IN GENOTYPE 1 HCV PATIENTS - SIMPLE NOMOGRAMS TO SUPPORT CLINICIANS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Thompson, Alexander J.; Clark, Paul J.; Vock, David M.; Tillmann, Hans L.; Patel, Keyur; Naggie, Susanna; Muir, Andrew J.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Thompson, Alexander J.] St Vincents Hosp, Fitzroy, Vic 3065, Australia. [Goldstein, David B.] Duke Univ, Ctr Human Genome Variat, Durham, NC USA. [Pfeiffer, Ruth; O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Poordad, F. Fred] Cedars Sinai Med Ctr, Dept Gastroenterol, Los Angeles, CA 90048 USA. [Nyberg, Lisa M.] Kaiser Permanente, San Diego, CA USA. [Noviello, Stephanie; Pedicone, Lisa; Brass, Clifford A.; Albrecht, Janice K.] Merck & Co Inc, Whitehouse Stn, NJ USA. [McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Sulkowski, Mark S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RI Clark, Paul/A-1480-2012 OI Clark, Paul/0000-0002-1821-4969 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 803A EP 804A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003171 ER PT J AU Osinusi, A Chary, A Kottilil, S Winters, MA Naggie, S Masur, H Polis, MA Holodniy, M AF Osinusi, Anu Chary, Aarthi Kottilil, Shyam Winters, Mark A. Naggie, Susanna Masur, Henry Polis, Michael A. Holodniy, Mark TI IL28B POLYMORPHISM IS NOT ASSOCIATED WITH HCV PROTEASE DIVERSITY IN HIV/HCV-COINFECTED PATIENTS TREATED WITH AN INTERFERON-BASED REGIMEN SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Osinusi, Anu; Kottilil, Shyam; Polis, Michael A.] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Osinusi, Anu] NCI Frederick Inc, SAIC Frederick, CMRP, Clin Res Directorate, Frederick, MD USA. [Chary, Aarthi; Winters, Mark A.; Holodniy, Mark] Veterans Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Chary, Aarthi; Winters, Mark A.; Holodniy, Mark] Stanford Univ, Stanford, CA 94305 USA. [Naggie, Susanna] Duke Clin Res Inst, Durham, NC USA. [Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 815A EP 815A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003193 ER PT J AU Kohli, A Naggie, S Polis, MA Masur, H Kottilil, S AF Kohli, Anita Naggie, Susanna Polis, Michael A. Masur, Henry Kottilil, Shyam TI HIV/HCV-COINFECTED NATURAL VIRAL SUPPRESSORS HAVE BETTER VIROLOGIC RESPONSES TO PEG-IFN AND RIBAVIRIN THAN ARV-TREATED HIV/HCV PATIENTS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kohli, Anita; Polis, Michael A.; Masur, Henry; Kottilil, Shyam] NIH, Bethesda, MD 20892 USA. [Naggie, Susanna] Duke, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 847A EP 847A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003254 ER PT J AU Buckett, D Shebl, FM Pfeiffer, R O'Brien, TR AF Buckett, Dianna Shebl, Fatma M. Pfeiffer, Ruth O'Brien, Thomas R. TI IS ONE ALLELE BETTER THAN NONE? A META-ANALYSIS OF IL28B RS12979860 GENOTYPES AND CLEARANCE OF HEPATITIS C VIRUS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Buckett, Dianna; Shebl, Fatma M.; Pfeiffer, Ruth; O'Brien, Thomas R.] NIH, Dept Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 854A EP 855A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003269 ER PT J AU Osinusi, A Naggie, S Poonia, S Trippler, M Hu, ZH Funk, E Schlaak, JF Fishbein, D Masur, H Polis, MA Kottilil, S AF Osinusi, Anu Naggie, Susanna Poonia, Seerat Trippler, Martin Hu, Zonghui Funk, Emily Schlaak, Joerg F. Fishbein, Dawn Masur, Henry Polis, Michael A. Kottilil, Shyam TI ITPA GENE POLYMORPHISMS SIGNIFICANTLY AFFECT HEMOGLOBIN DECLINE AND TREATMENT OUTCOMES IN HIV/HCV CO-INFECTED PATIENTS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Osinusi, Anu; Poonia, Seerat; Funk, Emily; Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Osinusi, Anu; Fishbein, Dawn] NCI Frederick Inc, Clin Res Directorate, CMRP, SAIC Frederick, Frederick, MD USA. [Naggie, Susanna] Duke Clin Res Inst, Durham, NC USA. [Trippler, Martin; Schlaak, Joerg F.] Univ Hosp Essen, Essen, Germany. [Hu, Zonghui] NIAID, BRB, NIH, Bethesda, MD 20892 USA. [Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 854A EP 854A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003268 ER PT J AU Feld, JJ Kleiner, DE Haynes-Williams, V Nichols, J Hoofnagle, JH Liang, TJ Gladwin, M Kato, GJ Heller, T AF Feld, Jordan J. Kleiner, David E. Haynes-Williams, Vanessa Nichols, James Hoofnagle, Jay H. Liang, T. Jake Gladwin, Mark Kato, Gregory J. Heller, Theo TI DIRECT HYPERBILIRUBINEMIA IN SICKLE CELL DISEASE IS A MARKER OF INTRINSIC LIVER PATHOLOGY AND A PREDICTOR OF MORTALITY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Feld, Jordan J.; Haynes-Williams, Vanessa; Hoofnagle, Jay H.; Liang, T. Jake; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Gladwin, Mark] Univ Pittsburgh, Pittsburgh, PA USA. [Nichols, James; Kato, Gregory J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 923A EP 923A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003410 ER PT J AU Feld, JJ Kleiner, DE Haynes-Williams, V Nichols, J Hoofnagle, JH Liang, TJ Gladwin, M Kato, GJ Heller, T AF Feld, Jordan J. Kleiner, David E. Haynes-Williams, Vanessa Nichols, James Hoofnagle, Jay H. Liang, T. Jake Gladwin, Mark Kato, Gregory J. Heller, Theo TI FERRITIN ELEVATION IS A MARKER OF TOTAL BODY IRON AND PREDICTOR OF MORTALITY IN SICKLE CELL DISEASE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Feld, Jordan J.; Haynes-Williams, Vanessa; Hoofnagle, Jay H.; Liang, T. Jake; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Gladwin, Mark] Univ Pittsburgh, Pittsburgh, PA USA. [Nichols, James; Kato, Gregory J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 929A EP 930A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003424 ER PT J AU Yamazaki, Y Kakizaki, S Moore, R Mori, M Negishi, M AF Yamazaki, Yuichi Kakizaki, Satoru Moore, Rick Mori, Masatomo Negishi, Masahiko TI NUCLEAR RECEPTOR CAR (NR1I3) IS ESSENTIAL FOR DDC-INDUCED LIVER INJURY AND OVAL CELL PROLIFERATION IN MOUSE LIVER SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Yamazaki, Yuichi; Moore, Rick; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, LRDT, NIH, Res Triangle Pk, NC 27709 USA. [Yamazaki, Yuichi; Kakizaki, Satoru; Mori, Masatomo] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Gunma, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 956A EP 956A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003485 ER PT J AU Li, Y Wang, H Wong, KA Gao, B Zang, MW AF Li, Yu Wang, Hua Wong, Kimberly A. Gao, Bin Zang, Mengwei TI MTORC1 IS AN IMPORTANT REGULATOR FOR INDUCTION OF ER STRESS AND INFLAMMATORY RESPONSE DURING ALCOHOLIC LIVER INJURY IN MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Li, Yu; Wong, Kimberly A.; Zang, Mengwei] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 971A EP 971A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003522 ER PT J AU Feng, DC Kong, XN Weng, HL Park, O Wang, H Zheng, MQ Dooley, S Kolls, J Young, HA Gao, B AF Feng, Dechun Kong, Xiaoni Weng, Honglei Park, Ogyi Wang, Hua Zheng, Mingquan Dooley, Steven Kolls, Jay Young, Howard A. Gao, Bin TI IL-22 PROMOTES LIVER PROGENITOR CELL PROLIFERATION IN MICE: A KEY LINKER BETWEEN LIVER INFLAMMATION AND DUCTULAR REACTION IN PATIENTS WITH VIRAL HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Feng, Dechun; Kong, Xiaoni; Park, Ogyi; Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, D-6800 Bethesda, MD USA. [Weng, Honglei; Dooley, Steven] Univ Heidelberg, Med Clin Fac Med Mannheim, Mannheim, Germany. [Zheng, Mingquan; Kolls, Jay] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 21701 USA. [Young, Howard A.] NCI, Lab Expt Immunol, Canc & Inflammat Program, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 979A EP 979A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003539 ER PT J AU Trehanpati, N Shrivastava, S Kumar, B Sukriti, S Tripathi, DM Singh, S Gupta, S Kottilil, S Sarin, SK AF Trehanpati, Nirupma Shrivastava, Shikha Kumar, Binayak Sukriti, Sukriti Tripathi, Dinesh M. Singh, Shivender Gupta, Subhash Kottilil, Shyam Sarin, Shiv K. TI NOTCH 1 HELPS DIFFERENTIATE IMMUNE CELLS IN ACUTE HEPATITIS B AND WITH TGF beta REGULATES FOXP3 EXPRESSION ON LIVER INFILTRATING LYMPHOCYTES IN HBV RELATED CIRRHOSIS AND HCC SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Trehanpati, Nirupma; Shrivastava, Shikha; Kumar, Binayak; Sukriti, Sukriti; Tripathi, Dinesh M.; Singh, Shivender; Sarin, Shiv K.] Inst Liver & Biliary Sci, New Delhi, India. [Kottilil, Shyam] NIAID, NIH, Bethesda, WA USA. [Gupta, Subhash] Indraprastha Apollo Hosp, New Delhi, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1093A EP 1094A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004007 ER PT J AU Noureddin, M Vaughn, IA Neuschwander-Tetri, BA Sanyal, AJ McCullough, AJ Merriman, RB Yates, KP Tonascia, J Unalp-Arida, A Doo, E Kleiner, DE Behling, CA Loomba, R AF Noureddin, Mazen Vaughn, Ivana A. Neuschwander-Tetri, Brent A. Sanyal, Arun J. McCullough, Arthur J. Merriman, Raphael B. Yates, Katherine P. Tonascia, James Unalp-Arida, Aynur Doo, Edward Kleiner, David E. Behling, Cynthia A. Loomba, Rohit TI CLINICAL AND HISTOLOGICAL DETERMINANTS OF NONALCOHOLIC STEATOHEPATITIS (NASH) AND ADVANCED FIBROSIS IN THE ELDERLY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Loomba, Rohit] UCSD, La Jolla, CA USA. [Vaughn, Ivana A.; Yates, Katherine P.; Tonascia, James] Johns Hopkins Univ, Baltimore, MD USA. [Neuschwander-Tetri, Brent A.; Unalp-Arida, Aynur] St Louis Univ, St Louis, MO 63103 USA. [Sanyal, Arun J.] VCU, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. [McCullough, Arthur J.] Cleveland Clin, Cleveland, OH 44106 USA. [Merriman, Raphael B.] Calif Pacific Med Ctr & Res Inst, San Francisco, CA USA. [Doo, Edward] NIDDK, Bethesda, MD USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Behling, Cynthia A.] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. RI Vaughn, Ivana/B-6138-2016 OI Vaughn, Ivana/0000-0002-7201-0289 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1118A EP 1118A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004062 ER PT J AU Rotman, Y Gara, N Koh, C Han, H Kleiner, DE Liang, TJ AF Rotman, Yaron Gara, Naveen Koh, Christopher Han, Hwalih Kleiner, David E. Liang, T. Jake TI SUCCESSFUL TREATMENT OF NON-ALCOHOLIC STEATOHEPATITIS DOES NOT IMPROVE SERUM FGF-21 LEVELS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Rotman, Yaron; Gara, Naveen; Koh, Christopher; Han, Hwalih; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1122A EP 1123A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004072 ER PT J AU Ruh, CE Matthews, CE Freedman, ND Everhart, JE AF Ruh, Constance E. Matthews, Charles E. Freedman, Neal D. Everhart, James E. TI RELATIONSHIP OF LIVER INJURY WITH PHYSICAL ACTIVITY MEASURED BY ACCELEROMETER IN THE UNITED STATES POPULATION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Ruh, Constance E.] Social & Sci Syst Inc, Silver Spring, MD USA. [Matthews, Charles E.; Freedman, Neal D.] NCI, Rockville, MD USA. [Everhart, James E.] NIDDK, Bethesda, MD USA. RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1133A EP 1134A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004095 ER PT J AU Buetow, KH Braun, R Hu, Y Sanyal, AJ AF Buetow, Kenneth H. Braun, Rosemary Hu, Ying Sanyal, Arun J. TI ANALYSIS OF GENOME-WIDE VARIATION WITHIN NAFLD POPULATION IDENTIFIES BIOLOGIC NETWORKS THAT ARE ASSOCIATED WITH DIFFERENT DISEASE PHENOTYPES SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Buetow, Kenneth H.; Braun, Rosemary; Hu, Ying] NCI, Lab Populat Genet, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1151A EP 1151A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004133 ER PT J AU Holz, L Yoon, JC Raghuraman, S Moir, S Sneller, M Rehermann, B AF Holz, Lauren Yoon, Joo Chun Raghuraman, Sukanya Moir, Susan Sneller, Michael Rehermann, Barbara TI B CELL HOMEOSTASIS IN CHRONIC HEPATITIS C VIRUS-RELATED MIXED CRYOGLOBULINEMIA SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Holz, Lauren; Yoon, Joo Chun; Raghuraman, Sukanya; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD USA. [Moir, Susan; Sneller, Michael] NIAID, Immunoregulat Lab, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1179A EP 1179A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004197 ER PT J AU Silver, D Karnik, G Osinusi, A Silk, R Stabinski, L Doonquah, L Henn, S Teferi, G Masur, H Kottilil, S Fishbein, D AF Silver, Dana Karnik, Geeta Osinusi, Anu Silk, Rachel Stabinski, Larissa Doonquah, Leleka Henn, Sarah Teferi, Gebeyehu Masur, Henry Kottilil, Shyam Fishbein, Dawn TI LIVER FIBROSIS IN AFRICAN AMERICANS, COMPARING HCV MONO-INFECTION WITH HIV-HCV COINFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Silver, Dana; Masur, Henry] NIH CCMD, NIH, Bethesda, MD USA. [Karnik, Geeta; Osinusi, Anu; Silk, Rachel; Fishbein, Dawn] NCI Frederic Inc, Support NIH CCMD, Clin Res Directorate CMRP, SAIC Frederick, Frederick, MD USA. [Osinusi, Anu; Stabinski, Larissa; Kottilil, Shyam] NIH NIAID, NIH, Bethesda, MD USA. [Doonquah, Leleka] Family & Med Counselling Serv Inc, Washington, DC USA. [Teferi, Gebeyehu] Unity Healthcare Inc, Washington, DC USA. [Henn, Sarah] Whitman Walker Hlth, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1186A EP 1187A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004213 ER PT J AU Shebl, FM Pfeiffer, R Buckett, D Muchmore, B Chen, S Dotrang, M Prokunina-Olsson, L Edlin, BR O'Brien, TR AF Shebl, Fatma M. Pfeiffer, Ruth Buckett, Dianna Muchmore, Brian Chen, Sabrina Dotrang, Myhanh Prokunina-Olsson, Ludmila Edlin, Brian R. O'Brien, Thomas R. TI IL28B GENOTYPE AND SPONTANEOUS HCV CLEARANCE: IS A RECESSIVE GENETIC MODEL BEST? SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shebl, Fatma M.; Pfeiffer, Ruth; Buckett, Dianna; Muchmore, Brian; Prokunina-Olsson, Ludmila; O'Brien, Thomas R.] NCI, Rockville, MD USA. [Chen, Sabrina] Informat Management Serv Inc, Silver Spring, MD USA. [Edlin, Brian R.] SUNY Downstate Coll Med, Brooklyn, NY USA. [Edlin, Brian R.] Urban Hlth Study, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1190A EP 1190A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004221 ER PT J AU Sarkar, S Jiang, Z Evon, DM Wahed, AS Hoofnagle, JH AF Sarkar, Souvik Jiang, Zhen Evon, Donna M. Wahed, Abdus S. Hoofnagle, Jay H. TI FATIGUE BEFORE, DURING AND AFTER ANTIVIRAL THERAPY OF CHRONIC HEPATITIS C: ANALYSIS OF THE VIRAHEP-C TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Sarkar, Souvik; Hoofnagle, Jay H.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Jiang, Zhen; Wahed, Abdus S.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Evon, Donna M.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1195A EP 1195A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004231 ER PT J AU Noureddin, M Woolridge, D Zhao, XC Noureddin, N DeMino, M Liang, TJ Kleiner, DE Heller, T Hoofnagle, JH AF Noureddin, Mazen Woolridge, Daniel Zhao, Xiongce Noureddin, Nabil DeMino, Mary Liang, T. Jake Kleiner, David E. Heller, Theo Hoofnagle, Jay H. TI NON-INVASIVE PREDICTORS OF ADVANCED DISEASE IN PRIMARY BILIARY CIRRHOSIS (PBC) SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Woolridge, Daniel; Zhao, Xiongce; Noureddin, Nabil; DeMino, Mary; Liang, T. Jake; Heller, Theo; Hoofnagle, Jay H.] NIDDK, Bethesda, MD USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1213A EP 1213A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004269 ER PT J AU Noureddin, M Matta, JR Noureddin, N Muldoon, N Woolridge, D Rotman, Y Pettigrew, RI Liang, TJ Hoofnagle, JH Heller, T Gharib, AM AF Noureddin, Mazen Matta, Jatin R. Noureddin, Nabil Muldoon, Nancy Woolridge, Daniel Rotman, Yaron Pettigrew, Roderic I. Liang, T. Jake Hoofnagle, Jay H. Heller, Theo Gharib, Ahmed M. TI CORONARY ARTERY DISEASE IN PRIMARY BILIARY CIRRHOSIS (PBC) AS SHOWN BY MULTI-DETECTOR CARDIAC COMPUTER TOMOGRAPHY (CT) SCAN SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Matta, Jatin R.; Noureddin, Nabil; Woolridge, Daniel; Rotman, Yaron; Liang, T. Jake; Hoofnagle, Jay H.; Heller, Theo; Gharib, Ahmed M.] NIDDK, Bethesda, MD USA. [Muldoon, Nancy] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RI Gharib, Ahmed/O-2629-2016 OI Gharib, Ahmed/0000-0002-2476-481X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1213A EP 1213A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004270 ER PT J AU Feld, JJ Kleiner, DE Sandler, NG Haynes-Williams, V Nichols, J Hoofnagle, JH Liang, TJ Dovek, D Gladwin, M Kato, GJ Heller, T AF Feld, Jordan J. Kleiner, David E. Sandler, Netanya G. Haynes-Williams, Vanessa Nichols, James Hoofnagle, Jay H. Liang, T. Jake Dovek, Daniel Gladwin, Mark Kato, Gregory J. Heller, Theo TI NON-CIRRHOTIC PORTAL HYPERTENSION IN SICKLE CELL DISEASE: AN UNDERAPPRECIATED ENTITY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Feld, Jordan J.; Haynes-Williams, Vanessa; Hoofnagle, Jay H.; Liang, T. Jake; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Gladwin, Mark] Univ Pittsburgh, Pittsburgh, PA USA. [Nichols, James; Kato, Gregory J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA. [Sandler, Netanya G.; Dovek, Daniel] NIAID, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1236A EP 1236A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004319 ER PT J AU Marquardt, JU Fischer, K Teufel, A Thorgeirsson, SS Galle, PR Strand, S AF Marquardt, Jens U. Fischer, Kerstin Teufel, Andreas Thorgeirsson, Snorri S. Galle, Peter R. Strand, Susanne TI PROGNOSTIC IMPLICATIONS OF SIRT6 IN HEPATOCELLULAR CARCINOMAS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Marquardt, Jens U.; Fischer, Kerstin; Teufel, Andreas; Galle, Peter R.; Strand, Susanne] Johannes Gutenberg Univ Mainz, Dept Internal Med, D-6500 Mainz, Germany. [Marquardt, Jens U.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1285A EP 1285A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004424 ER PT J AU Maass, T Westphal, H Galle, PR Teufel, A AF Maass, Thorsten Westphal, Heiner Galle, Peter R. Teufel, Andreas TI DICKKOPF 2 (DKK2) DELETION RESULTS IN ENHANCED LIVER CANCER DEVELOPMENT SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Maass, Thorsten; Galle, Peter R.; Teufel, Andreas] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Westphal, Heiner] NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1292A EP 1292A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004438 ER PT J AU Zheng, X Gai, XH Hu, CL Shire, AM Elsawa, SF Thorgeirsson, SS Fernandez-Zapico, ME Roberts, LR AF Zheng, Xin Gai, Xiaohong Hu, Chunling Shire, Abdirashid M. Elsawa, Sherine F. Thorgeirsson, Snorri S. Fernandez-Zapico, Martin E. Roberts, Lewis R. TI GLI1 PROMOTES HCC RECURRENCE PARTLY VIA INDUCTION OF THE EPITHELIAL-TO-MESENCHYMAL TRANSITION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Zheng, Xin; Gai, Xiaohong; Hu, Chunling; Shire, Abdirashid M.; Roberts, Lewis R.] Mayo Clin, Coll Med, Rochester, MN USA. [Zheng, Xin; Gai, Xiaohong; Hu, Chunling; Shire, Abdirashid M.; Elsawa, Sherine F.; Fernandez-Zapico, Martin E.; Roberts, Lewis R.] Mayo Clin, Schulze Ctr Novel Therapeut, Div Oncol Res, Rochester, MN USA. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1298A EP 1298A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004454 ER PT J AU Rotman, Y Noureddin, M Feld, JJ Han, H Park, YJ Thomas, E Abdalla, AA Gara, N Sarkar, S Koh, C Doo, E Heller, T Ghany, MG Rehermann, B Hoofnagle, JH Liang, TJ AF Rotman, Yaron Noureddin, Mazen Feld, Jordan J. Han, Hwalih Park, Yoon J. Thomas, Emmanuel Abdalla, Adil A. Gara, Naveen Sarkar, Souvik Koh, Christopher Doo, Edward Heller, Theo Ghany, Marc G. Rehermann, Barbara Hoofnagle, Jay H. Liang, T. Jake TI RIBAVIRIN EXERTS A WEAK INTERFERON-LIKE EFFECT ON GENE EXPRESSION IN THE LIVER OF PATIENTS WITH CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Rotman, Yaron; Noureddin, Mazen; Feld, Jordan J.; Han, Hwalih; Park, Yoon J.; Thomas, Emmanuel; Abdalla, Adil A.; Gara, Naveen; Sarkar, Souvik; Koh, Christopher; Doo, Edward; Heller, Theo; Ghany, Marc G.; Rehermann, Barbara; Hoofnagle, Jay H.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1327A EP 1328A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004521 ER PT J AU Kohli, A Zhang, XZ Funk, E Polis, MA Masur, H Kottilil, S AF Kohli, Anita Zhang, Xiaozhen Funk, Emily Polis, Michael A. Masur, Henry Kottilil, Shyam TI HCV INFECTION SELECTIVELY UPREGULATES IFN-lambda RA, ENHANCING SUSCEPTIBILITY OF INFECTED HEPATOCYTES TO IFN-lambda OVER TIME SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kohli, Anita; Zhang, Xiaozhen; Funk, Emily; Polis, Michael A.; Masur, Henry; Kottilil, Shyam] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1330A EP 1330A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004527 ER PT J AU Aggarwal, R Naik, A Goel, A Yu, CR Goel, D AF Aggarwal, Rakesh Naik, Anshu Goel, Amit Yu, Claro Goel, Divya TI GENE EXPRESSION ANALYSIS IN PERIPHERAL BLOOD MONONUCLEAR CELLS IN PATIENTS WITH ACUTE HEPATITIS E SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Aggarwal, Rakesh; Naik, Anshu; Goel, Amit; Goel, Divya] Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India. [Yu, Claro] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1335A EP 1335A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004539 ER PT J AU Dou, DR Zhang, XZ Kohli, A Kottilil, S AF Dou, Diana R. Zhang, Xiaozhen Kohli, Anita Kottilil, Shyam TI A NOVEL ANTIVIRAL MECHANISM OF INTERFERON-ALPHA: INTERFERON-ALPHA INDUCED IFIT3 MEDIATES ANTI-HCV EFFECT SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Dou, Diana R.; Zhang, Xiaozhen; Kohli, Anita; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1336A EP 1337A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004542 ER PT J AU Kuntzen, T Neumann-Haefelin, C Lennon, N Carlson, J Berical, AC Berlin, AM Timm, J Oniangue-Ndza, C Young, S Adams, S Kleyman, M Birch, CE Ledlie, T Roberts, AD Rosen, HR Bihl, FK Cerny, A Brander, C Spengler, U Galagan, J Marincola, FM Nusbaum, C Walker, BD Lake-Bakaar, G Daari, ES Jacobson, IM Gomperts, ED Edlin, BR Thimme, R Birren, BW Donfield, SM Chung, RT Kim, AY Lauer, GM Talal, A Marion, T Carrington, M Heckerman, D Henn, MR Allen, TM AF Kuntzen, Thomas Neumann-Haefelin, Christoph Lennon, Niall Carlson, Jonathan Berical, Andrew C. Berlin, Aaron M. Timm, Joerg Oniangue-Ndza, Cesar Young, Sarah Adams, Sharon Kleyman, Marianna Birch, Christopher E. Ledlie, Timothy Roberts, Andrew D. Rosen, Hugo R. Bihl, Florian K. Cerny, Andreas Brander, Christian Spengler, Ulrich Galagan, James Marincola, Francesco M. Nusbaum, Chad Walker, Bruce D. Lake-Bakaar, Gerond Daari, Eric S. Jacobson, Ira M. Gomperts, Edward D. Edlin, Brian R. Thimme, Robert Birren, Bruce W. Donfield, Sharyne M. Chung, Raymond T. Kim, Arthur Y. Lauer, Georg M. Talal, Andrew Marion, Tony Carrington, Mary Heckerman, David Henn, Matthew R. Allen, Todd M. TI PROTECTIVE HLA CLASS I ALLELES IN HCV INFECTION: IMMUNE CONTROL LINKED TO CLUSTERED CD8 ESCAPE MUTATIONS IN NS5B BY LARGE SCALE SEQUENCE ANALYSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kuntzen, Thomas] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland. [Kuntzen, Thomas; Neumann-Haefelin, Christoph; Berical, Andrew C.; Oniangue-Ndza, Cesar; Kleyman, Marianna; Birch, Christopher E.; Walker, Bruce D.; Kim, Arthur Y.; Lauer, Georg M.; Carrington, Mary; Allen, Todd M.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Neumann-Haefelin, Christoph; Thimme, Robert] Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. [Lennon, Niall; Berlin, Aaron M.; Young, Sarah; Ledlie, Timothy; Roberts, Andrew D.; Galagan, James; Nusbaum, Chad; Birren, Bruce W.; Henn, Matthew R.] Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA USA. [Carlson, Jonathan; Heckerman, David] Microsoft Res, Redmond, WA USA. [Timm, Joerg] Essen Univ Hosp, Dept Virol, Essen, Germany. [Adams, Sharon; Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Adams, Sharon; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA. [Rosen, Hugo R.] Univ Colorado, Div Gastroenterol & Hepatol, Hlth Sci Ctr, Denver, CO USA. [Bihl, Florian K.] Osped San Giovanni Bellinzona, Serv Gastroenterol, Bellinzona, Switzerland. [Cerny, Andreas] Clin Moncucco, Lugano, Switzerland. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, AIDS Res Inst IrsiCaixa HIVACAT, Barcelona, Spain. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain. [Spengler, Ulrich] Bonn Univ Hosp, Dept Internal Med 1, Bonn, Germany. [Marion, Tony] Univ Tennessee, Ctr Hlth Sci, Hepatitis Cooperat C, Memphis, TN 38163 USA. [Lake-Bakaar, Gerond; Jacobson, Ira M.; Edlin, Brian R.; Talal, Andrew] Weill Cornell Med Coll, Ctr Study Hepatitis C, New York, NY USA. [Daari, Eric S.] Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA 90095 USA. [Gomperts, Edward D.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Donfield, Sharyne M.] Rho Inc, Dept Biostat, Chapel Hill, NC USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Carrington, Mary] NCI, Expt Immunol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RI Neumann-Haefelin, Christoph/E-5550-2011 NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1341A EP 1342A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004552 ER PT J AU Nara, K Rivera, M Raghuraman, S Tsai, EH Ko, MS Saito, S DeMino, M Kirkland, H Salehizadeh, Y Auerbach, JS Hoofnagle, JH Liang, TJ Rehermann, B Heller, T AF Nara, Koji Rivera, Maria Raghuraman, Sukanya Tsai, Edward H. Ko, Myung S. Saito, Satoru DeMino, Mary Kirkland, Heather Salehizadeh, Yasmin Auerbach, Jonathan S. Hoofnagle, Jay H. Liang, T. Jake Rehermann, Barbara Heller, Theo TI BREAKTHROUGH OF ACUTE HEPATITIS C WHILE ON INTERFERON IS ASSOCIATED WITH CHANGES IN DIVERSITY IN HEPATITIS C VIRUS NONSTRUCTURAL PROTEINS BUT NOT CHANGES IN T CELL RESPONSIVENESS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Nara, Koji; Rivera, Maria; Raghuraman, Sukanya; Tsai, Edward H.; Ko, Myung S.; Saito, Satoru; DeMino, Mary; Kirkland, Heather; Salehizadeh, Yasmin; Auerbach, Jonathan S.; Hoofnagle, Jay H.; Liang, T. Jake; Rehermann, Barbara; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1342A EP 1342A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004553 ER PT J AU Kawaguchi, K Honda, M Shirasaki, T Emerson, SU Purcell, RH Kaneko, S AF Kawaguchi, Kazunori Honda, Masao Shirasaki, Takayoshi Emerson, Suzanne U. Purcell, Robert H. Kaneko, Shuichi TI HCV INFECTIVITY VARIATION AND HVR1 QUASISPECIES SELECTION ARE ASSOCIATED WITH THE DISTRIBUTION OF HCV E1/E2 SYNONYMOUS MUTATIONS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kawaguchi, Kazunori; Honda, Masao; Shirasaki, Takayoshi; Kaneko, Shuichi] Kanazawa Univ, Kanazawa, Ishikawa, Japan. [Kawaguchi, Kazunori; Emerson, Suzanne U.; Purcell, Robert H.] NIAID, MHS, Bethesda, MD 20892 USA. [Kawaguchi, Kazunori; Emerson, Suzanne U.; Purcell, Robert H.] NIAID, HVS, LID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1352A EP 1353A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004575 ER PT J AU Iribarren, P Wang, JM AF Iribarren, Pablo Wang, Ji Ming TI Toll-like receptors and diseases SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Editorial Material C1 [Iribarren, Pablo] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, Ctr Invest Bioquim Clin & Inmunol CIBICI CONICET, RA-5000 Cordoba, Argentina. [Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Iribarren, P (reprint author), Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, CIBICI CONICET, Ciudad Univ,X5000HUA, RA-5000 Cordoba, Argentina. EM piribarr@fcq.unc.edu.ar FU FIC NIH HHS [1R01TW007621-01A2] NR 9 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD OCT PY 2011 VL 11 IS 10 BP 1389 EP 1390 DI 10.1016/j.intimp.2011.08.010 PG 2 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 834YI UT WOS:000296000000001 PM 21884825 ER PT J AU Chen, KQ Xiang, Y Yao, XH Liu, Y Gong, WH Yoshimura, T Wang, JM AF Chen, Keqiang Xiang, Yi Yao, Xiaohong Liu, Ying Gong, Wanghua Yoshimura, Teizo Wang, Ji Ming TI The active contribution of Toll-like receptors to allergic airway inflammation SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Allergic airway inflammation; Host response; TLRs ID THYMIC STROMAL LYMPHOPOIETIN; DENDRITIC CELLS; MAST-CELLS; T-CELLS; MEDIATED ACTIVATION; EPITHELIAL-CELLS; INNATE IMMUNITY; LUNG INJURY; ASTHMA; DIFFERENTIATION AB Epithelia lining the respiratory tract represent a major portal of entry for microorganisms and allergens and are equipped with innate and adaptive immune signaling receptors for host protection. These include Toll-like receptors (TLRs) that recognize microbial components and evoke diverse responses in cells of the respiratory system. TLR stimulation by microorganism-derived molecules activates antigen presenting cells, control T helper (Th) 1, Th2, and Th17 immune cell differentiation, cytokine production by mast cells, and activation of eosinophils. It is clear that TLR are involved in the pathophysiology of allergic airway diseases such as asthma. Dendritic cells (DCs), a kind of antigen presenting cells, which play a key role in the induction of allergic airway inflammation, are privileged targets for pathogen associated molecular patterns (PAMPs). During the allergic responses, engagement of TLRs on DCs determines the Th2 polarization of the T cells. TLR signaling in mast cells increases the release of IL-5, and TLR activation of airway epithelial cells forces the generation of proallergic Th2 type of cytokines. Although these responses aim to protect the host, they may also result in inflammatory tissue damage in the airway. Under certain conditions, stimulation of TLRs, in particular. TLR9, may reduce Th2-dependent allergic inflammation by induction of Th1 responses. Therefore, understanding the complex regulatory roles of TLRs in the pathogenesis of allergic airway inflammation should facilitate the development of preventive and therapeutic measures for asthmatic patients. (C) 2011 Elsevier B.V. All rights reserved. C1 [Chen, Keqiang; Liu, Ying; Yoshimura, Teizo; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Xiang, Yi] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Respirat, Shanghai 200025, Peoples R China. [Yao, Xiaohong] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing 400038, Peoples R China. [Yao, Xiaohong] Third Mil Med Univ, Southwest Hosp, SW Canc Ctr, Chongqing 400038, Peoples R China. [Gong, Wanghua] SAIC Frederick, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Bldg 560,Room 31-76, Frederick, MD 21702 USA. EM wangji@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The research was also supported in part by the Intramural Research Program of the NCI, NIH. NR 60 TC 29 Z9 33 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD OCT PY 2011 VL 11 IS 10 BP 1391 EP 1398 DI 10.1016/j.intimp.2011.05.003 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 834YI UT WOS:000296000000002 PM 21624504 ER PT J AU Chen, X Oppenheim, JJ AF Chen, Xin Oppenheim, Joost J. TI Resolving the identity myth: Key markers of functional CD4(+)FoxP3(+) regulatory T cells SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE Regulatory T cells; Cellular markers; Immunosuppressive function ID HUMAN PERIPHERAL-BLOOD; REMITTING MULTIPLE-SCLEROSIS; LATENT TGF-BETA; FOXP3 EXPRESSION; RHEUMATOID-ARTHRITIS; SUPPRESSIVE FUNCTION; RECEPTOR EXPRESSION; NEGATIVE REGULATION; CD127 EXPRESSION; WASTING DISEASE AB Authenticating markers for the functional suppressive CD4(+)FoxP3(+) regulatory T cells (Tregs) are important for the quantitative identification and enrichment of viable Tregs for possible therapeutic use. CD25 as a surrogate marker of Tregs has some limitations, which prompted investigators to identify more specific marker(s) of Tregs. The search for a firm molecular definition of Tregs resulted in the identification of FoxP3 as a better marker of this subset of CD4 cells. Nevertheless, FoxP3(+) Tregs are phenotypically and functionally heterogeneous. Even in normal mice, only a minority of FoxP3(+) T cells are potent suppressor cells. Therefore, additional marker(s) are required for delineation of truly functional Tregs. In this review, the studies identifying markers of functional Tregs, both in mouse and in human, and their functional implications are discussed. Our finding that TNFR2, which mediates the effect of TNF on the activation of Tregs, is a superb marker of the most suppressive subset of mouse Tregs and its application in the identification of functional human Tregs will also be reviewed. (C) 2011 Elsevier B.V. All rights reserved. C1 [Chen, Xin] NCI Frederick, BSP, SAIC Frederick Inc, Mol Immunoregulat Lab,CIP, Frederick, MD 21702 USA. [Oppenheim, Joost J.] NCI Frederick, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Chen, X (reprint author), NCI Frederick, BSP, SAIC Frederick Inc, Mol Immunoregulat Lab,CIP, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov RI Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. This Research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 109 TC 25 Z9 30 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD OCT PY 2011 VL 11 IS 10 BP 1489 EP 1496 DI 10.1016/j.intimp.2011.05.018 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 834YI UT WOS:000296000000012 PM 21635972 ER PT J AU Yilmaz, P Gilbert, JA Knight, R Amaral-Zettler, L Karsch-Mizrachi, I Cochrane, G Nakamura, Y Sansone, SA Glockner, FO Field, D AF Yilmaz, Pelin Gilbert, Jack A. Knight, Rob Amaral-Zettler, Linda Karsch-Mizrachi, Ilene Cochrane, Guy Nakamura, Yasukazu Sansone, Susanna-Assunta Gloeckner, Frank Oliver Field, Dawn TI The genomic standards consortium: bringing standards to life for microbial ecology SO ISME JOURNAL LA English DT Editorial Material ID METAGENOMICS C1 [Yilmaz, Pelin; Gloeckner, Frank Oliver] Max Planck Inst Marine Microbiol, Microbial Genom & Bioinformat Grp, Bremen, Germany. [Yilmaz, Pelin; Gloeckner, Frank Oliver] Jacobs Univ Bremen gGmbH, Bremen, Germany. [Gilbert, Jack A.] Argonne Natl Lab, Div Math & Comp Sci, Argonne, IL 60439 USA. [Gilbert, Jack A.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Amaral-Zettler, Linda] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Karsch-Mizrachi, Ilene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Cochrane, Guy] European Bioinformat Inst, EMBL Outstn, Cambridge, England. [Nakamura, Yasukazu] Res Org Informat & Syst, Ctr Informat Biol, Mishima, Shizuoka 4118540, Japan. [Nakamura, Yasukazu] Res Org Informat & Syst, DNA Data Bank Japan, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. [Sansone, Susanna-Assunta] Univ Oxford, Oxford E Res Ctr, Oxford, England. [Field, Dawn] NERC Ctr Ecol & Hydrol, Oxford, England. RP Yilmaz, P (reprint author), Max Planck Inst Marine Microbiol, Microbial Genom & Bioinformat Grp, Bremen, Germany. EM fog@mpi-bremen.de RI Knight, Rob/D-1299-2010; OI Yilmaz, Pelin/0000-0003-4724-323X; Cochrane, Guy/0000-0001-7954-7057; Sansone, Susanna-Assunta/0000-0001-5306-5690; Nakamura, Yasukazu/0000-0002-6782-5715 FU Biotechnology and Biological Sciences Research Council [BB/E025080/1, BB/I000771/1] NR 13 TC 18 Z9 18 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1751-7362 EI 1751-7370 J9 ISME J JI ISME J. PD OCT PY 2011 VL 5 IS 10 BP 1565 EP 1567 DI 10.1038/ismej.2011.39 PG 3 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA 832DX UT WOS:000295783200001 PM 21472015 ER PT J AU Shohreh, R Sherafat-Kazemzadeh, R Jee, YH Blitz, A Salvatori, R AF Shohreh, Rugia Sherafat-Kazemzadeh, Rosa Jee, Youn Hee Blitz, Ari Salvatori, Roberto TI A Novel Frame Shift Mutation in the GHRH Receptor Gene in Familial Isolated GHD eficiency: Early Occurrence of Anterior Pituitary Hypoplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE DEFICIENCY; MAGNETIC-RESONANCE; ENDOCRINE FUNCTION; SHORT STATURE; GH-1 GENE; CHILDREN; GLAND; PREVALENCE; DWARFISM; MOUSE AB Background: Mutations in the genes encoding for GHRH receptor (GHRHR) and GH (GH1) are the most common cause of familial isolated GH deficiency (IGHD). GHRHR mutations are often associated with anterior pituitary hypoplasia (APH), but this has been reported almost exclusively in children older than 8 yr. We analyzed the GHRHR and measured pituitary size in a consanguineous family with the father and three of the five siblings with IGHD. Objective: The aim of the study was to find the mutated gene in a family with severe IGHD. Methods: We sequenced the whole GHRHR coding regions and the intron-exon boundaries from peripheral DNA of the index patient. After identifying the novel mutation, we sequenced the region of interest in the other members of the family. We measured the anterior pituitary volume from magnetic resonance imaging (MRI). Results: The father and the three affected children were homozygous for a new frame-shift mutation in the coding sequence of exon 4 (corresponding to the extracellular domain of the receptor) (c.391delG) that places the downstream sequence out of frame. The mother and two unaffected siblings were heterozygous for the mutation. Two of the affected children had MRI evidence of APH before reaching 6 yr of age. Conclusions: We describe a new mutation in the GHRHR in a family with IGHD. The presence of frank APH before age 6 yr shows that MRI-evident reduced pituitary size can be present in GHRHR mutations even in children younger than 8 yr of age. (J Clin Endocrinol Metab 96: 2982-2986, 2011) C1 [Shohreh, Rugia; Salvatori, Roberto] Johns Hopkins Univ, Dept Med, Div Endocrinol, Baltimore, MD 21287 USA. [Blitz, Ari] Johns Hopkins Univ, Dept Radiol, Div Neuroradiol, Baltimore, MD 21287 USA. [Sherafat-Kazemzadeh, Rosa] Georgetown Univ Hosp, Dept Pediat, Div Endocrinol, Washington, DC USA. [Jee, Youn Hee] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Salvatori, R (reprint author), Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, 1830 E Monument St,Suite 333, Baltimore, MD 21287 USA. EM salvator@jhmi.edu NR 30 TC 10 Z9 10 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP 2982 EP 2986 DI 10.1210/jc.2011-1031 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600030 PM 21816782 ER PT J AU Zemel, BS Kalkwarf, HJ Gilsanz, V Lappe, JM Oberfield, S Shepherd, JA Frederick, MM Huang, XK Lu, M Mahboubi, S Hangartner, T Winer, KK AF Zemel, Babette S. Kalkwarf, Heidi J. Gilsanz, Vicente Lappe, Joan M. Oberfield, Sharon Shepherd, John A. Frederick, Margaret M. Huang, Xiangke Lu, Ming Mahboubi, Soroosh Hangartner, Thomas Winer, Karen K. TI Revised Reference Curves for Bone Mineral Content and Areal Bone Mineral Density According to Age and Sex for Black and Non-Black Children: Results of the Bone Mineral Density in Childhood Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PEDIATRIC OFFICIAL POSITIONS; BODY-COMPOSITION; FRACTURE RISK; US ADULTS; ADOLESCENTS; GIRLS; PUBERTY; YOUNG; RACE; ASSOCIATION AB Context: Deficits in bone acquisition during growth may increase fracture risk. Assessment of bone health during childhood requires appropriate reference values relative to age, sex, and population ancestry to identify bone deficits. Objective: The objective of this study was to provide revised and extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) in children. Design: The Bone Mineral Density in Childhood Study was a multicenter longitudinal study with annual assessments for up to 7 yr. Setting: The study was conducted at five clinical centers in the United States. Participants: Two thousand fourteen healthy children (992 males, 22% African-Americans) aged 5-23 yr participated in the study. Intervention: There were no interventions. Main Outcome Measures: Reference percentiles for BMC and aBMD of the total body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry for Black and non-Black children. Adjustment factors for height status were also calculated. Results: Extended reference curves for BMC and aBMD of the total body, total body less head, lumbar spine, total hip, femoral neck, and forearm for ages 5-20 yr were constructed relative to sex and age for Black and non-Black children. Curves are similar to those previously published for 7-17 year olds. BMC and aBMD values were greater for Black vs. non-Black children at all measurement sites. Conclusions: We provide here dual-energy x-ray absorptiometry reference data on a well-characterized cohort of 2012 children and adolescents. These reference curves provide the most robust reference values for the assessment and monitoring of bone health in children and adolescents in the literature to date. (J Clin Endocrinol Metab 96: 3160-3169, 2011) C1 [Zemel, Babette S.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Gastroenterol Hepatol & Nutr,Dept Pediat, Philadelphia, PA 19104 USA. [Mahboubi, Soroosh] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Kalkwarf, Heidi J.] Cincinnati Childrens Hosp, Med Ctr, Dept Gen & Community Pediat, Cincinnati, OH 45229 USA. [Gilsanz, Vicente] Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA. [Gilsanz, Vicente] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. [Lappe, Joan M.] Creighton Univ, Dept Med, Omaha, NE 68178 USA. [Oberfield, Sharon] Columbia Univ, Dept Pediat, New York, NY 10032 USA. [Shepherd, John A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Frederick, Margaret M.; Huang, Xiangke; Lu, Ming] Clin Trials & Surveys Corp, Owings Mills, MD 21117 USA. [Hangartner, Thomas] Wright State Univ, Biomed Imaging Lab, Dayton, OH 45435 USA. [Winer, Karen K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Endocrinol Nutr & Growth Branch, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. RP Zemel, BS (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Gastroenterol Hepatol & Nutr,Dept Pediat, 3535 Market St,Room 1560, Philadelphia, PA 19104 USA. EM zemel@email.chop.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331, NO1-HD-1-3332, NO1-HD-1-3333]; Clinical and Translational Research Center [5-MO1-RR-000240, UL1 RR-026314] FX This work was supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development Contracts NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331, NO1-HD-1-3332 and NO1-HD-1-3333 and the Clinical and Translational Research Center Grant 5-MO1-RR-000240 and UL1 RR-026314. NR 32 TC 105 Z9 106 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP 3160 EP 3169 DI 10.1210/jc.2011-1111 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600052 PM 21917867 ER PT J AU Khan, AM Cheng, S Magnusson, M Larson, MG Newton-Cheh, C McCabe, EL Coviello, AD Florez, JC Fox, CS Levy, D Robins, SJ Arora, P Bhasin, S Lam, CSP Vasan, RS Melander, O Wang, TJ AF Khan, Abigail May Cheng, Susan Magnusson, Martin Larson, Martin G. Newton-Cheh, Christopher McCabe, Elizabeth L. Coviello, Andrea D. Florez, Jose C. Fox, Caroline S. Levy, Daniel Robins, Sander J. Arora, Pankaj Bhasin, Shalender Lam, Carolyn S. P. Vasan, Ramachandran S. Melander, Olle Wang, Thomas J. TI Cardiac Natriuretic Peptides, Obesity, and Insulin Resistance: Evidence from Two Community-Based Studies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; INCIDENT CARDIOVASCULAR EVENTS; EMERGENCY-DEPARTMENT PRIDE; TERMINAL PRO-BNP; HEART-FAILURE; METABOLIC SYNDROME; NORMAL-WEIGHT; MICE LACKING; ANGIOTENSIN-II; ADIPOSE-TISSUE AB Background: The natriuretic peptides play an important role in salt homeostasis and blood pressure regulation. It has been suggested that obesity promotes a relative natriuretic peptide deficiency, but this has been a variable finding in prior studies and the cause is unknown. Aim: The aim of this study was to examine the association between obesity and natriuretic peptide levels and evaluate the role of hyperinsulinemia and testosterone as mediators of this interaction. Methods: We studied 7770 individuals from the Framingham Heart Study (n = 3833, 54% women) and the Malmo Diet and Cancer study (n = 3918, 60% women). We examined the relation of plasma N-terminal pro-B-type natriuretic peptide levels (N-BNP) with obesity, insulin resistance, and various metabolic subtypes. Results: Obesity was associated with 6-20% lower levels of N-BNP (P < 0.001 in Framingham, P = 0.001 in Malmo), whereas insulin resistance was associated with 10-30% lower levels of N-BNP (P < 0.001 in both cohorts). Individuals with obesity who were insulin sensitive had only modest reductions in N-BNP compared with nonobese, insulin-sensitive individuals. On the other hand, individuals who were nonobese but insulin resistant had 26% lower N-BNP in Framingham (P < 0.001) and 10% lower N-BNP in Malmo (P < 0.001), compared with nonobese and insulin-sensitive individuals. Adjustment for serum-free testosterone did not alter these associations. Conclusions: In both nonobese and obese individuals, insulin resistance is associated with lower natriuretic peptide levels. The relative natriuretic peptide deficiency seen in obesity could be partly attributable to insulin resistance, and could be one mechanism by which insulin resistance promotes hypertension. (J Clin Endocrinol Metab 96: 3242-3249, 2011) C1 [Khan, Abigail May; Cheng, Susan; Newton-Cheh, Christopher; McCabe, Elizabeth L.; Arora, Pankaj; Wang, Thomas J.] Harvard Univ, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Florez, Jose C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Khan, Abigail May] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Cheng, Susan; Larson, Martin G.; Newton-Cheh, Christopher; McCabe, Elizabeth L.; Fox, Caroline S.; Levy, Daniel; Robins, Sander J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02115 USA. [Magnusson, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, SE-20041 Malmo, Sweden. Lund Univ, Dept Cardiol, Skanes Univ Hosp, SE-20502 Malmo, Sweden. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Newton-Cheh, Christopher; Florez, Jose C.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Fox, Caroline S.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20824 USA. [Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Prevent Med, Dept Med, Boston, MA 02118 USA. [Bhasin, Shalender] Boston Univ, Sch Med, Div Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Lam, Carolyn S. P.] Natl Univ Hlth Syst, Singapore 119228, Singapore. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org RI Arora, Pankaj/F-3437-2011; OI Arora, Pankaj/0000-0003-2420-3550; Larson, Martin/0000-0002-9631-1254; Magnusson, Martin/0000-0003-1710-5936; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195, R01-HL-086875, R01-HL-094755]; Ellison Foundation FX This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Contract N01-HC-25195 and Grants R01-HL-086875 and R01-HL-094755. S.C. is supported by a grant from the Ellison Foundation. NR 62 TC 60 Z9 64 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP 3242 EP 3249 DI 10.1210/jc.2011-1182 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600062 PM 21849523 ER PT J AU Abrams, JY Schonberger, LB Belay, ED Maddox, RA Leschek, EW Mills, JL Wysowski, DK Fradkin, JE AF Abrams, Joseph Y. Schonberger, Lawrence B. Belay, Ermias D. Maddox, Ryan A. Leschek, Ellen W. Mills, James L. Wysowski, Diane K. Fradkin, Judith E. TI Lower Risk of Creutzfeldt-Jakob Disease in Pituitary Growth Hormone Recipients Initiating Treatment after 1977 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID UNITED-STATES; CONTAMINATION; THERAPY; TIME AB Context: Creutzfeldt-Jakob disease (CJD) caused by contaminated cadaveric pituitary-derived human GH (hGH) has been responsible for hundreds of deaths worldwide. Studies of U. S. National Hormone and Pituitary Program (NHPP) hGH recipients have found CJD only in patients treated before 1977, when a new purification procedure with column chromatography was implemented for hGH extraction. Objective: Our objective was to provide updated information on transmission of CJD to NHPP hGH recipients and determine whether recipients of hGH produced after 1977 had a significantly lower CJD risk than pre-1977 recipients. Patients: A total of 5570 NHPP hGH recipients were included in the study: 2099 in the pre-1977 cohort and 3471 in the post-1977 cohort. Main Outcome Measure: We used probability distribution functions to determine whether the observed number of CJD cases in the post-1977 cohort was significantly fewer than expected if the CJD risk was equal to that of the pre-1977 cohort, controlling for treatment duration and follow-up time. Results: All 22 CJD cases (diagnosed from 1984-2009) occurred in the pre-1977 hGH recipients. Almost half (47.9%) of pre-1977 recipients had a treatment duration of at least 5 yr compared with only 13.8% for post-1977 recipients. Based on the rates present in the pre-1977 cohort, the probability of observing no cases in the post-1977 cohort by chance alone was low (P = 0.0019). Conclusions: Risk of acquiring CJD was significantly lower for post-1977 NHPP hGH recipients than for pre-1977 recipients, suggesting that the new purification procedure in 1977 may have greatly reduced or eliminated CJD agent in hGH. (J Clin Endocrinol Metab 96: E1666-E1669, 2011) C1 [Abrams, Joseph Y.; Schonberger, Lawrence B.; Belay, Ermias D.; Maddox, Ryan A.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Leschek, Ellen W.; Fradkin, Judith E.] NIDDK, Bethesda, MD 20817 USA. [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Wysowski, Diane K.] US FDA, Silver Spring, MD 20993 USA. RP Abrams, JY (reprint author), Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, 1600 Clifton Rd NE,CDC Mailstop A30, Atlanta, GA 30333 USA. EM JAbrams@cdc.gov RI Belay, Ermias/A-8829-2013 NR 12 TC 5 Z9 5 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP E1666 EP E1669 DI 10.1210/jc.2011-1357 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600016 PM 21816775 ER PT J AU Cizza, G Bernardi, L Smirne, N Maletta, R Tomaino, C Costanzo, A Gallo, M Lewis, JG Geracitano, S Grasso, MB Potenza, G Monteleone, C Brancati, G Ho, JT Torpy, DJ Bruni, AC AF Cizza, Giovanni Bernardi, Livia Smirne, Nicoletta Maletta, Raffaele Tomaino, Carmine Costanzo, Angela Gallo, Maura Lewis, John G. Geracitano, Silvana Grasso, Maria Beatrice Potenza, Giuseppe Monteleone, Cosimo Brancati, Giacomino Ho, Jui T. Torpy, David J. Bruni, Amalia C. TI Clinical Manifestations of Highly Prevalent Corticosteroid-Binding Globulin Mutations in a Village in Southern Italy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GENETIC-VARIATION; FREE CORTISOL; DEFICIENCY; FATIGUE; AFFINITY; GLUCOCORTICOIDS; SUBSTITUTION; ASSOCIATION; POPULATION; EPIFUND AB Context: Corticosteroid-binding globulin (CBG) is the binding protein for cortisol. Rare kindreds with CBG mutations reducing CBG levels or altering binding affinity have been described, along with clinical manifestations encompassing fatigue, chronic pain, and hypotension. The largest kindred, exhibiting two mutations (null and Lyon) were Australian immigrants from Italy. Objective: Our objective was to determine the prevalence of the null/Lyon mutations in the village where the original null/Lyon family emigrated and compare subjects with and without CBG mutations, without previous knowledge of their mutation status. Design, Setting, and Participants: We conducted a survey field study that included 495 adult residents. Main Outcomes: We assessed clinical history, CBG mutation analysis, plasma CBG, salivary cortisol, body mass index, waist circumference, blood pressure, and the Krupp fatigue scale. Results: Eighteen of 495 participants (3.6%, seven males and 11 females) had one of two functionaltering CBG mutations. All were heterozygous for the null (n = 6) or Lyon mutations (n = 12). Of 12 Lyon participants (four males and eight females), eight (two males and six females) had chronic widespread pain and five osteoarthritis with associated pain (one male and four females). Of six null participants (three males and three females), three (one male and two females) had chronic pain and four osteoarthritis with associated pain (two males and two females). Conclusions: A high combined prevalence (3.6%) of these two CBG mutations was detected. The presence of either mutation conferred a propensity to chronic pain. In other communities, individuals with the same genetic background complain more of fatigue than pain, suggesting an environmental effect on the phenotype. These findings, combined with animal CBG gene knockout and human CBG single-nucleotide polymorphism haplotype studies, suggest that CBG influences the endocrine and neurobehavioral response to stress, including the development of pain/fatigue syndromes. (J Clin Endocrinol Metab 96: E1684-E1693, 2011) C1 [Cizza, Giovanni] NIDDK, Diabet Endocrine & Obes Branch, CRC, Bethesda, MD 20892 USA. [Bernardi, Livia; Smirne, Nicoletta; Maletta, Raffaele; Tomaino, Carmine; Costanzo, Angela; Gallo, Maura; Geracitano, Silvana; Monteleone, Cosimo; Bruni, Amalia C.] Reg Neurogenet Ctr, I-88046 Catanzaro, Italy. [Lewis, John G.] Canterbury Hlth Labs, Christchurch, New Zealand. [Brancati, Giacomino] Dept Hlth, Epidemiol & Res Serv, I-88100 Catanzaro, Italy. [Ho, Jui T.; Torpy, David J.] Royal Adelaide Hosp, Endocrine & Metab Unit, Adelaide, SA 5005, Australia. RP Cizza, G (reprint author), NIDDK, Diabet Endocrine & Obes Branch, CRC, Bldg 10,Room 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov RI , raffaele/K-4421-2016 OI Lewis, John/0000-0003-2757-4111; , raffaele/0000-0002-0758-1835 FU Assessorato alla Salute-Regione Calabria [772]; Italian Minister of Health [42]; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by a Project Grant (G. R. no. 772, August 6, 2002) of the Assessorato alla Salute-Regione Calabria; the Italian Minister of Health (convention no. 42 of November 26, 2003, approved on October 11, 2004), and by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Intramural Program. NR 35 TC 13 Z9 13 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP E1684 EP E1693 DI 10.1210/jc.2011-1321 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600020 PM 21795453 ER PT J AU Davidson, MH Ballantyne, CM Jacobson, TA Bittner, VA Braun, LT Brown, AS Brown, WV Cromwell, WC Goldberg, RB McKenney, JM Remaley, AT Sniderman, AD Toth, PP Tsimikas, S Ziajka, PE Maki, KC Dicklin, MR AF Davidson, Michael H. Ballantyne, Christie M. Jacobson, Terry A. Bittner, Vera A. Braun, Lynne T. Brown, Alan S. Brown, W. Virgil Cromwell, William C. Goldberg, Ronald B. McKenney, James M. Remaley, Alan T. Sniderman, Allan D. Toth, Peter P. Tsimikas, Sotirios Ziajka, Paul E. Maki, Kevin C. Dicklin, Mary R. TI Clinical utility of inflammatory markers and advanced lipoprotein testing: Advice from an expert panel of lipid specialists SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Article DE C-reactive protein; Lipoprotein-associated phospholipase A2; Apolipoprotein B; Low-density lipoprotein particle concentration; Lipoprotein(a); Lipoprotein subfractions ID C-REACTIVE-PROTEIN; CORONARY-HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; NUCLEAR-MAGNETIC-RESONANCE; NON-HDL CHOLESTEROL; FAMILIAL-COMBINED HYPERLIPIDEMIA; MIDDLE-AGED MEN; ACTIVATING-FACTOR ACETYLHYDROLASE; TRIAL EVALUATING ROSUVASTATIN; FUTURE CARDIOVASCULAR EVENTS AB The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density lipoprotein (HDL)-C treatment goals for persons with hypertriglyceridemia. The use of lipid-lowering therapies, particularly statins, to achieve these goals has reduced cardiovascular disease (CVD) morbidity and mortality; however, significant residual risk for events remains. This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments. Furthermore, the cost effectiveness of pharmacological intervention for both the initiation of therapy and the intensification of therapy has been enhanced by the availability of a variety of generic statins. This report describes the consensus view of an expert panel convened by the National Lipid Association to evaluate the use of selected biomarkers [C-reactive protein, lipoprotein-associated phospholipase A(2), apolipoprotein B, LDL particle concentration, lipoprotein(a), and LDL and HDL subfractions] to improve risk assessment, or to adjust therapy. These panel recommendations are intended to provide practical advice to clinicians who wrestle with the challenges of identifying the patients who are most likely to benefit from therapy, or intensification of therapy, to provide the optimum protection from CV risk. (C) 2011 National Lipid Association. All rights reserved. C1 [Davidson, Michael H.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60610 USA. [Maki, Kevin C.; Dicklin, Mary R.] Provident Clin Res, Glen Ellyn, IL USA. [Goldberg, Ronald B.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Jacobson, Terry A.] Emory Univ, Lipoprot Biomarkers Sub Grp, Atlanta, GA 30322 USA. [McKenney, James M.] Natl Clin Res Inc, Manakin Sabot, VA USA. [McKenney, James M.] Virginia Commonwealth Univ, Manakin Sabot, VA USA. [Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Sniderman, Allan D.] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Toth, Peter P.] Univ Illinois, Coll Med, Sterling Rock Falls Clin Ltd, Peoria, IL 61656 USA. [Tsimikas, Sotirios] Univ Calif San Diego, La Jolla, CA 92093 USA. [Ziajka, Paul E.] Florida Lipid Inst, Winter Pk, FL USA. [Ballantyne, Christie M.] Baylor Coll Med, Inflammatory Biomarkers Sub Grp, Houston, TX 77030 USA. [Bittner, Vera A.] Univ Alabama, Birmingham, AL USA. [Braun, Lynne T.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Brown, Alan S.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Brown, W. Virgil] Emory Univ, Sch Med, Atlanta, GA USA. [Cromwell, William C.] Lipoprot & Metab Disorders Inst, Raleigh, NC USA. [Cromwell, William C.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Davidson, MH (reprint author), Univ Chicago, Pritzker Sch Med, 515 N State St,Suite 2700, Chicago, IL 60610 USA. EM MDavidso@medicine.bsd.uchicago.edu OI Cromwell, William/0000-0001-7610-4920; Jacobson, Terry/0000-0002-9926-2179; Bittner, Vera/0000-0001-9456-850X FU Abbott Laboratories; Atherotech Diagnostics Laboratory; Berkley Heart Lab, Inc.; Boston Heart Diagnostics; diaDexus, Inc.; LipoScience; Merck Co., Inc.; Spectracell Laboratories; Daiichi Sankyo; GlaxoSmithKline; Merck Co.; Roche; Aegerion Pharmaceuticals; Amgen; AstraZeneca; Atherotech Inc.; DTC MD; Esperion; Intelligent Medical Decisions; Kinemed; Novo Nordisk; Sanofi-Aventis; Synarc; Takeda Pharmaceuticals; Vindico Medical Education; Bristol-Myers Squibb; Kowa Pharmaceuticals; Novartis Pharmaceuticals; Sanofi-Synthelabo; Adnexus; Amylin Pharmaceuticals; Bristol Myers-Squibb; Genentech; Idera Pharmaceuticals; Omthera; Resverlogix; Amarin Pharmaceuticals; National Institutes of Health; Spirocor; Gilead; Pfizer Inc.; Anthera; Genzyme; Isis Pharmaceuticals; LabCorp; Health Diagnostics Laboratory; Alpha-Core Pharmaceuticals; VirxSys Inc.; ISIS; Genzyme/Sanofi; Quest; Atherotech; Bio-Sante Pharmaceuticals; Cargill; Coca-Cola; Dairy Research Institute; Fermenich; Kao Corporation; Kellogg Co.; Monsanto; National Starch/Corn Products; Ocean Spray; PepsiCo; Pharmavite; Shaklee; Solae; Trygg Pharmaceuticals; Welch's; General Mills; Biofortis FX The January 2011 National Lipid Association (NLA) consensus conference on inflammatory markers and advanced lipoprotein testing was supported by unrestricted grant funding from the following companies: Abbott Laboratories, Atherotech Diagnostics Laboratory, Berkley Heart Lab, Inc., Boston Heart Diagnostics, diaDexus, Inc., LipoScience, Merck & Co., Inc., and Spectracell Laboratories.; The NLA would like to thank each company for its support of this endeavor. In accordance with the National Lipid Association Code for Interactions with Companies, the NLA maintained full control over the planning, content, quality, scientific integrity, implementation, and evaluation of the consensus conference and this inflammatory markers and advanced lipoprotein testing consensus document. All related activities are free from commercial influence and bias.; Dr. Davidson has received research grants from Abbott Laboratories, Daiichi Sankyo, GlaxoSmithKline, Merck & Co. and Roche. Dr. Davidson has received consulting fees from Abbott Laboratories, Aegerion Pharmaceuticals, Amgen, AstraZeneca, Atherotech Inc., Daiichi Sankyo, DTC MD, Esperion, GlaxoSmithKline, Intelligent Medical Decisions, Kinemed, LipoScience, Merck & Co, Novo Nordisk, Roche, Sanofi-Aventis, Synarc, Takeda Pharmaceuticals, and Vindico Medical Education. Dr. Davidson has received honoraria related to speaking from Abbott Laboratories, GlaxoSmithKline and Merck & Co. Dr. Davidson has served on the Board of Directors of DTC MD, Omthera, Professional Evaluation Inc., and Sonogene.; Dr. Ballantyne has received research grants from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, diaDexus Inc., GlaxoSmithKline, Kowa Pharmaceuticals, Merck & Co., Novartis Pharmaceuticals, Roche, Sanofi-Synthelabo, and Takeda Pharmaceuticals. Dr. Ballantyne has received consulting fees from Abbott Laboratories, Adnexus, Amylin Pharmaceuticals, AstraZeneca, Bristol Myers-Squibb, Esperion, Genentech, GlaxoSmithKline, Idera Pharmaceuticals, Kowa Pharmaceuticals, Merck & Co., Novartis Pharmaceuticals, Omthera, Resverlogix, Roche, Sanofi-Synthelabo, and Takeda Pharmaceuticals. Dr. Ballantyne has received honoraria related to speaking from Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Merck & Co., Sanofi-Synthelabo, and Takeda Pharmaceuticals.; Dr. Jacobson has received consulting fees from Abbott Laboratories, Amarin Pharmaceuticals, AstraZeneca, GlaxoSmithKline and Merck & Co.; Dr. Bittner has received research grants from Abbott Laboratories, National Institutes of Health, Spirocor, Roche, GlaxoSmithKline, Gilead, and Pfizer Inc.; Dr. Braun has received honoraria related to speaking from the American Heart Association and the Preventive Cardiovascular Nurses Association. Dr. Braun has received salary support from the National Institutes of Health.; Dr. Alan S. Brown has received honoraria related to speaking from Abbott Laboratories, Forest Laboratories and Daiichi Sankyo.; Dr. W. Virgil Brown has received consulting fees from Abbott Laboratories, Amgen, Anthera, Genzyme, Pfizer Inc., LipoScience, and Merck & Co. Dr. W. Virgil Brown has received honoraria related to speaking from Abbott Laboratories, LipoScience, and Merck & Co.; Dr. Cromwell has received consulting fees from Isis Pharmaceuticals, LabCorp, and Health Diagnostics Laboratory. Dr. Cromwell has received research grants from Isis Pharmaceuticals. Dr. Cromwell has received honoraria related to speaking from Abbott Laboratories, LipoScience, Merck & Co., and Merck Schering Plough.; Dr. Goldberg has received research grants from Abbott Laboratories, GlaxoSmithKline and Roche. Dr. Goldberg has received consulting fees from GlaxoSmithKline, Daiichi Sankyo, and Pfizer Inc. Dr. Goldberg has received honoraria related to speaking from Daiichi Sankyo, GlaxoSmithKline, and Merck & Co.; Dr. McKenney has no relevant disclosures.; Dr. Remaley has received research grants from Alpha-Core Pharmaceuticals, Kinemed, and VirxSys Inc.; Dr. Sniderman has received research grants from AstraZeneca. A. D. S. has received honoraria related to speaking from Merck & Co.; Dr. Toth has received consulting fees from Abbott Laboratories, AstraZeneca, GlaxoSmithKline, Kowa Pharmaceuticals, Pfizer Inc., and Merck & Co. Dr. Toth has received honoraria related to speaking from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer Inc., Merck & Co., and Takeda Pharmaceuticals.; Dr. Tsimikas has received consulting fees from ISIS, Merck & Co., Genzyme/Sanofi and Quest. Dr. Tsimikas has received honoraria related to speaking from Merck & Co. Dr. Tsimikas has received research grants from Merck & Co. and Pfizer Inc. Dr. Tsimikas has received equity interest from Atherotope.; Dr. Ziajka has received honoraria related to speaking from Abbott Laboratories, AstraZeneca and Merck & Co. Dr. Ziajka has received research grants from Genzyme.; Dr. Maki has received research grants from Abbott Laboratories, Amarin Pharmaceuticals, Atherotech, Bio-Sante Pharmaceuticals, Cargill, Coca-Cola, Dairy Research Institute, Fermenich, GlaxoSmithKline, Kao Corporation, Kellogg Co., Monsanto, National Starch/Corn Products, Ocean Spray, Omthera, PepsiCo, Pharmavite, Shaklee, Solae, Trygg Pharmaceuticals and Welch's. Dr. Maki has received consulting fees from Abbott Laboratories, Cargill, Dairy Research Institute, General Mills, GlaxoSmithKline, Omthera, PepsiCo, Pharmavite and Trygg Pharmaceuticals. Dr. Maki has received salary support from Biofortis.; Dr. Dicklin has received research grants from Abbott Laboratories, Amarin Pharmaceuticals, Atherotech, Bio-Sante Pharmaceuticals, Cargill, Coca-Cola, Dairy Research Institute, Fermenich, GlaxoSmithKline, Kao Corporation, Kellogg Co., Monsanto, National Starch/Corn Products, Ocean Spray, Omthera, PepsiCo, Pharmavite, Shaklee, Solae, Trygg Pharmaceuticals and Welch's. Dr. Dicklin has received consulting fees from Abbott Laboratories, Dairy Research Institute, General Mills, GlaxoSmithKline, Omthera, PepsiCo, Pharmavite, and Trygg Pharmaceuticals. Dr. Dicklin has received salary support from Biofortis. NR 219 TC 131 Z9 133 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-2874 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD OCT PY 2011 VL 5 IS 5 BP 338 EP 367 DI 10.1016/j.jacl.2011.07.005 PG 30 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 833QR UT WOS:000295900500002 PM 21981835 ER PT J AU Horai, R Caspi, RR AF Horai, Reiko Caspi, Rachel R. TI Cytokines in Autoimmune Uveitis SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; KOYANAGI-HARADA-DISEASE; NECROSIS-FACTOR-ALPHA; ROR-GAMMA-T; BEHCETS-DISEASE; IFN-GAMMA; TH17 CELLS; TGF-BETA; NONINFECTIOUS UVEITIS AB Autoimmune uveitis is a complex group of sight-threatening diseases that arise without a known infectious trigger. The disorder is often associated with immunological responses to retinal proteins. Experimental models of autoimmune uveitis targeting retinal proteins have led to a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and have provided a template for the development of novel therapies. The disease in humans is believed to be T cell-dependent, as clinical uveitis is ameliorated by T cell-targeting therapies. The roles of T helper 1 (Th1) and Th17 cells have been major topics of interest in the past decade. Studies in uveitis patients and experiments in animal models have revealed that Th1 and Th17 cells can both be pathogenic effectors, although, paradoxically, some cytokines produced by these subsets can also be protective, depending on when and where they are produced. The major proinflammatory as well as regulatory cytokines in uveitis, the therapeutic approaches, and benefits of targeting these cytokines will be discussed in this review. C1 [Horai, Reiko; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU NIH/NEI FX This work has been supported by NIH/NEI Intramural Funding. NR 105 TC 54 Z9 60 U1 1 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD OCT PY 2011 VL 31 IS 10 BP 733 EP 744 DI 10.1089/jir.2011.0042 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 834UJ UT WOS:000295989300006 PM 21787221 ER PT J AU Buckley, PF AF Buckley, Peter F. TI Bromization The Truths We Know About the Psychopharmacology of Schizophrenia SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Editorial Material ID ANTIPSYCHOTIC POLYPHARMACY; OLANZAPINE C1 [Buckley, Peter F.] Georgia Hlth Sci Univ, Sch Med, Augusta, GA 30912 USA. [Buckley, Peter F.] NIMH, Bethesda, MD USA. RP Buckley, PF (reprint author), Georgia Hlth Sci Univ, Sch Med, 1120 15th St, Augusta, GA 30912 USA. EM pbuckley@georgiahealth.edu NR 17 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2011 VL 199 IS 10 BP 736 EP 737 DI 10.1097/NMD.0b013e31822fc639 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 827BD UT WOS:000295399300002 PM 21964265 ER PT J AU Rovsing, L Clokie, S Bustos, DM Rohde, K Coon, SL Litman, T Rath, MF Moller, M Klein, DC AF Rovsing, Louise Clokie, Samuel Bustos, Diego M. Rohde, Kristian Coon, Steven L. Litman, Thomas Rath, Martin F. Moller, Morten Klein, David C. TI Crx broadly modulates the pineal transcriptome SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Crx; gene expression; Hoxc4; microarray; pineal gland; transcriptome profiling ID ARYLALKYLAMINE N-ACETYLTRANSFERASE; OTX2 HOMEOBOX GENE; REV-ERB-ALPHA; HOMEODOMAIN PROTEIN; CIRCADIAN CLOCK; MESSENGER-RNA; MOUSE PINEAL; EXPRESSION; GLAND; MELATONIN AB Cone-rod homeobox (Crx) encodes Crx, a transcription factor expressed selectively in retinal photoreceptors and pinealocytes, the major cell type of the pineal gland. In this study, the influence of Crx on the mammalian pineal gland was studied by light and electron microscopy and by use of microarray and qRTPCR technology, thereby extending previous studies on selected genes (Furukawa et al. 1999). Deletion of Crx was not found to alter pineal morphology, but was found to broadly modulate the mouse pineal transcriptome, characterized by a > 2-fold down-regulation of 543 genes and a > 2-fold up-regulation of 745 genes (p < 0.05). Of these, one of the most highly up-regulated (18-fold) was Hoxc4, a member of the Hox gene family, members of which are known to control gene expression cascades. During a 24-h period, a set of 51 genes exhibited differential day/night expression in pineal glands of wild-type animals; only eight of these were also day/night expressed in the Crx(-/-) pineal gland. However, in the Crx(-/-) pineal gland 41 genes exhibited differential night/day expression that was not seen in wild-type animals. These findings indicate that Crx broadly modulates the pineal transcriptome and also influences differential night/day gene expression in this tissue. Some effects of Crx deletion on the pineal transcriptome might be mediated by Hoxc4 up-regulation. C1 [Rovsing, Louise; Clokie, Samuel; Bustos, Diego M.; Coon, Steven L.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Rovsing, Louise; Rohde, Kristian; Rath, Martin F.; Moller, Morten] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark. [Litman, Thomas] Univ Copenhagen, Panum Inst, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen, Denmark. [Bustos, Diego M.] INTECH, Chascomus, Argentina. RP Klein, DC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, 49 Convent Dr,Room 6A82, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov RI Rovsing, Louise/E-3225-2014; OI Clokie, Samuel/0000-0002-0025-3652; Rath, Martin/0000-0002-4047-6324 FU Lundbeck Foundation; Danish Medical Research Council [271-07-0412]; Novo Nordisk Foundation; Carlsberg Foundation; Fonden til Laegevidenskabens Fremme; Simon Fougner Hartmanns Familiefond; Danish Eye Health Society; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This study was supported by the Lundbeck Foundation, the Danish Medical Research Council (grant no. 271-07-0412), the Novo Nordisk Foundation, the Carlsberg Foundation, Fonden til Laegevidenskabens Fremme, Simon Fougner Hartmanns Familiefond, the Danish Eye Health Society (Vaern om Synet) and the Intramural Research Program of the The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors wish to express their appreciation to Dr. Connie Cepko for the generous gift of the Crx-/- mice. The authors have no conflicts of interest. NR 45 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2011 VL 119 IS 2 BP 262 EP 274 DI 10.1111/j.1471-4159.2011.07405.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 834PE UT WOS:000295973900002 PM 21797868 ER PT J AU Torres-Altoro, MI Mathur, BN Drerup, JM Thomas, R Lovinger, DM O'Callaghan, JP Bibb, JA AF Torres-Altoro, Melissa I. Mathur, Brian N. Drerup, Justin M. Thomas, Rachel Lovinger, David M. O'Callaghan, James P. Bibb, James A. TI Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE chlorpyrifos; dopamine; Gulf War illness; insecticide; neurotoxicity; organophosphate ID CYCLIN-DEPENDENT KINASE-5; NEONATAL CHLORPYRIFOS EXPOSURE; ALPHA-7 NICOTINIC RECEPTORS; CENTRAL-NERVOUS-SYSTEM; GULF-WAR SYNDROME; SYNAPTIC PLASTICITY; NEOSTRIATAL NEURONS; ALZHEIMERS-DISEASE; PESTICIDE EXPOSURE; PRENATAL EXPOSURE AB The neurological effects of organophosphate (OP) pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here, we characterized the effects of the broadly used insecticide chlorpyrifos (CPF) on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry. CPF potentiated protein kinase A (PKA)-dependent phosphorylation of the striatal protein dopamine-and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) and the glutamate receptor 1 (GluR1) subunit of alpha-amino-3-hydroxy-5methyl- 4-isoxazolepropionic acid (AMPA) receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA when administered systemically. This correlated with enhanced glutamate release from cortical projections in rat striatum. Similar effects were induced by the sarin congener, diisopropyl fluorophosphate, alone or in combination with the putative neuroprotectant, pyridostigmine bromide and the pesticide N,N-diethyl-meta-toluamide (DEET). This combination, meant to mimic the neurotoxicant exposure encountered by veterans of the 1991 Persian Gulf War, also induced hyperphosphorylation of the neurofibrillary tangle-associated protein tau. Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. Thus, consistent with recent findings in humans and animals, organophosphate exposure causes dysregulation in the motor/reward circuitry and invokes mechanisms associated with neurological disorders and neurodegeneration. C1 [Torres-Altoro, Melissa I.; Drerup, Justin M.; Thomas, Rachel; Bibb, James A.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Mathur, Brian N.; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [O'Callaghan, James P.] NIOSH, Ctr Dis Control & Prevent, Morgantown, WV USA. [Bibb, James A.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. RP Bibb, JA (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd,NC5-410, Dallas, TX 75390 USA. EM james.bibb@utsouthwestern.edu RI O'Callaghan, James/O-2958-2013 FU US National Institutes of Health [MH79710, MH083711, DA016672]; Centers for Disease Control and Prevention-NIOSH; Division of Intramural Clinical and Biological Research of NIAAA; IDIQ [VA549-P-0027]; Department of Veterans Affairs Medical Center, Dallas, TX FX We thank Suzanne Saldanha, Brenda Billig, and Christopher Felton for technical assistance. This work was supported by US National Institutes of Health Grants to J.A.B (MH79710, MH083711, and DA016672), Intramural funds from Centers for Disease Control and Prevention-NIOSH, and the Division of Intramural Clinical and Biological Research of NIAAA. Portions of this research were supported by IDIQ contract VA549-P-0027 (Robert W. Haley, M.D., PI), awarded and administered by the Department of Veterans Affairs Medical Center, Dallas, TX. The content does not necessarily reflect the position or the policy of the Federal government or the sponsoring agency, and no official endorsement should be inferred. NR 54 TC 29 Z9 30 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2011 VL 119 IS 2 BP 303 EP 313 DI 10.1111/j.1471-4159.2011.07428.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 834PE UT WOS:000295973900006 PM 21848865 ER PT J AU Cheon, Y Park, JY Modi, HR Kim, HW Lee, HJ Chang, L Rao, JS Rapoport, SI AF Cheon, Yewon Park, Jee-Young Modi, Hiren R. Kim, Hyung-Wook Lee, Ho-Joo Chang, Lisa Rao, Jagadeesh S. Rapoport, Stanley I. TI Chronic olanzapine treatment decreases arachidonic acid turnover and prostaglandin E-2 concentration in rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE anti-psychotic; bipolar disorder; cyclooxygenase; phospholipid; prostaglandin E-2; washout ID CYTOSOLIC PHOSPHOLIPASE A(2); POLYUNSATURATED FATTY-ACIDS; THIN-LAYER CHROMATOGRAPHY; GROUP-SPECIFIC ASSAYS; DOCOSAHEXAENOIC ACID; BIPOLAR DISORDER; UNANESTHETIZED RAT; IN-VIVO; ANTIPSYCHOTIC MEDICATIONS; ATYPICAL ANTIPSYCHOTICS AB The atypical antipsychotic, olanzapine (OLZ), is used to treat bipolar disorder, but its therapeutic mechanism of action is not clear. Arachidonic acid (AA, 20:4n-6) plays a critical role in brain signaling and an up-regulated AA metabolic cascade was reported in postmortem brains from bipolar disorder patients. In this study, we tested whether, similar to the action of the mood stabilizers lithium, carbamazepine and valproate, chronic OLZ treatment would reduce AA turnover in rat brain. We administered OLZ (6 mg/kg/day) or vehicle i.p. to male rats once daily for 21 days. A washout group received 21 days of OLZ followed by vehicle on day 22. Two hours after the last injection, [1-C-14] AA was infused intravenously for 5 min, and timed arterial blood samples were taken. After the rat was killed at 5 min, its brain was microwaved, removed and analyzed. Chronic OLZ decreased plasma unesterified AA concentration, AA incorporation rates and AA turnover in brain phospholipids. These effects were absent after washout. Consistent with reduced AA turnover, OLZ decreased brain cyclooxygenase activity and the brain concentration of the proinflammatory AA-derived metabolite, prostaglandin E-2, In view of up-regulated brain AA metabolic markers in bipolar disorder, the abilities of OLZ and the mood stabilizers to commonly decrease prostaglandin E-2, and AA turnover in rat brain phospholipids, albeit by different mechanisms, may be related to their efficacy against the disease. C1 [Cheon, Yewon; Park, Jee-Young; Modi, Hiren R.; Kim, Hyung-Wook; Lee, Ho-Joo; Chang, Lisa; Rao, Jagadeesh S.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Cheon, Y (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA. EM cheony@mail.nih.gov FU National Institute on Aging, NIH FX This work was supported entirely by the Intramural Research Program of the National Institute on Aging, NIH. Olanzapine was kindly provided by Eli Lilly (Indianapolis, IN, USA). The authors thank, for their editorial assistance, the NIH Fellows' Editorial Board. NR 86 TC 28 Z9 28 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2011 VL 119 IS 2 BP 364 EP 376 DI 10.1111/j.1471-4159.2011.07410.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 834PE UT WOS:000295973900012 PM 21812779 ER PT J AU Rich, BA Carver, FW Holroyd, T Rosen, HR Mendoza, JK Cornwell, BR Fox, NA Pine, DS Coppola, R Leibenluft, E AF Rich, Brendan A. Carver, Frederick W. Holroyd, Tom Rosen, Heather R. Mendoza, Jennifer K. Cornwell, Brian R. Fox, Nathan A. Pine, Daniel S. Coppola, Richard Leibenluft, Ellen TI Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Bipolar disorder; Pediatric; Mood dysregulation; Irritability; Frustration; Magnetoencephalography ID MAJOR DEPRESSIVE DISORDER; ANTERIOR CINGULATE CORTEX; SUBCORTICAL BRAIN-REGIONS; MEDIAL PREFRONTAL CORTEX; FRONTAL MIDLINE THETA; INDIVIDUAL-DIFFERENCES; BEHAVIORAL-RESPONSES; SOURCE LOCALIZATION; AFFECTIVE PICTURES; BRODMANN AREA-6 AB Questions persist regarding the presentation of bipolar disorder (BD) in youth and the nosological significance of irritability. Of particular interest is whether severe mood dysregulation (SMD), characterized by severe non-episodic irritability, hyper-arousal, and hyper-reactivity to negative emotional stimuli, is a developmental presentation of pediatric BD and, therefore, whether the two conditions are pathophysiologically similar. We administered the affective Posner paradigm, an attentional task with a condition involving blocked goal attainment via rigged feedback. The sample included 60 youth (20 BD, 20 SMD, and 20 controls) ages 8-17. Magnetoencephalography (MEG) examined neuronal activity (4-50 Hz) following negative versus positive feedback. We also examined reaction time (RI), response accuracy, and self-reported affect. Both BD and SMD youth reported being less happy than controls during the rigged condition. Also, SMD youth reported greater arousal following negative feedback than both BD and controls, and they responded to negative feedback with significantly greater activation of the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG) than controls. Compared to SMD and controls, BD youth displayed greater superior frontal gyrus (SFG) activation and decreased insula activation following negative feedback. Data suggest a greater negative affective response to blocked goal attainment in SMD versus BD and control youth. This occurs in tandem with hyperactivation of medial frontal regions in SMD youth, while BD youth show dysfunction in the SFG and insula. Data add to a growing empirical base that differentiates pediatric BD and SMD and begin to elucidate potential neural mechanisms of irritability. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Rich, Brendan A.; Rosen, Heather R.] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. [Carver, Frederick W.; Holroyd, Tom; Coppola, Richard] MEG Core Facil, Bethesda, MD USA. [Mendoza, Jennifer K.; Cornwell, Brian R.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Fox, Nathan A.] Univ Maryland, Child Dev Lab, College Pk, MD 20742 USA. RP Rich, BA (reprint author), Catholic Univ Amer, Dept Psychol, 620 Michigan Ave NE, Washington, DC 20064 USA. EM richb@cua.edu FU NIH, NIMH; NIMH [K22-MH078044] FX This research was supported by the Intramural Research Program of the NIH, NIMH. This funding organization was not involved in research aspects such as study design and conduct; data collection, analysis, nor interpretation. Dr. Rich is supported by NIMH grant K22-MH078044. NR 108 TC 25 Z9 25 U1 5 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2011 VL 45 IS 10 BP 1283 EP 1294 DI 10.1016/j.jpsychires.2011.04.006 PG 12 WC Psychiatry SC Psychiatry GA 834XT UT WOS:000295998500002 PM 21561628 ER PT J AU Leibenluft, E AF Leibenluft, Ellen TI DSM-10: Coming Soon to a Psychiatric Practice Near You SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID ADOLESCENTS; CHILDREN C1 [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), Bldg 15K,MSC-2670, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2011 VL 50 IS 10 BP 972 EP 974 DI 10.1016/j.jaac.2011.07.008 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 829EZ UT WOS:000295562700004 PM 21961771 ER PT J AU Axelson, DA Birmaher, B Strober, MA Goldstein, BI Ha, W Gill, MK Goldstein, TR Yen, SR Hower, H Hunt, JI Liao, FZ Iyengar, S Dickstein, D Kim, E Ryan, ND Frankel, E Keller, MB AF Axelson, David A. Birmaher, Boris Strober, Michael A. Goldstein, Benjamin I. Ha, Wonho Gill, Mary Kay Goldstein, Tina R. Yen, Shirley Hower, Heather Hunt, Jeffrey I. Liao, Fangzi Iyengar, Satish Dickstein, Daniel Kim, Eunice Ryan, Neal D. Frankel, Erica Keller, Martin B. TI Course of Subthreshold Bipolar Disorder in Youth: Diagnostic Progression From Bipolar Disorder Not Otherwise Specified SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar mood disorders; child psychiatry; diagnosis and classification ID COMORBIDITY SURVEY REPLICATION; SCHOOL-AGE-CHILDREN; SPECTRUM DISORDERS; MANIC SYMPTOMS; COMMUNITY SAMPLE; CLINICAL-COURSE; II DISORDER; ADOLESCENTS; PREVALENCE; LIFETIME AB Objective: To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-H) in youth over prospective follow-up and to identify factors associated with conversion. Method: Subjects were 140 children and adolescents recruited from clinical referrals or advertisement who met operationalized criteria for BP-NOS at intake and participated in at least one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The mean duration of follow-up was 5 years and the mean interval between assessments was 8.2 months. Results: Diagnostic conversion to BP-I or BP-II occurred in 63 subjects (45%): 32 (23%) to BP-I (nine of whom had initially converted to BP-II) and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks. First- or second-degree family history of mania or hypomania was the strongest baseline predictor of diagnostic conversion (p = .006). Over follow-up, conversion was associated with greater intensity of hypomanic symptoms and with greater exposure to specialized, intensive outpatient psychosocial treatments. There was no association between conversion and exposure to treatment with particular medication classes. Conclusions: Children and adolescents referred with mood symptoms that meet operationalized criteria for BP-NOS, particularly those with a family history of BP, frequently progress to BP-I or BP-H. Efforts to identify these youth and effectively intervene may have the potential to curtail the progression of mood disorders in this high-risk population. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(10):1001-1016. C1 [Axelson, David A.; Birmaher, Boris; Ha, Wonho; Gill, Mary Kay; Goldstein, Tina R.; Liao, Fangzi; Iyengar, Satish; Ryan, Neal D.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Goldstein, Benjamin I.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Strober, Michael A.; Kim, Eunice] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hunt, Jeffrey I.; Dickstein, Daniel] Brown Univ, Alpert Med Sch, Bradley Hosp, Providence, RI 02912 USA. [Frankel, Erica] NIMH, Expt Therapeut Pathophysiol Branch, Bethesda, MD USA. RP Axelson, DA (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM axelsonda@upmc.edu RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 FU National Institute of Mental Health [MH59929, MH59977, MH59691, MH74945, MH69904, MH074581]; Sunnybrook Foundation; Pfizer FX This research was supported by National Institute of Mental Health Grants MH59929 (B.B.), MH59977 (M.A.S.), and MH59691 (M.B.K.), MH74945 (D.D.), MH69904 (S.Y.), MH074581 (T.R.G.), and the Sunnybrook Foundation (B.I.G.).; Dr. Birmaher has served as a consultant for Schering Plough, and receives royalties Random House, Inc. and Lippincott Williams and Wilkins. Dr. Hunt is a Senior Editor for the Brown Psychopharm Newsletter published by Wiley Publishers. Dr. B. Goldstein has received research grant support from Pfizer, and has received honoraria from Purdue Pharma. Dr. Keller has received research grant support from Pfizer. He has received honoraria from and/or served as a consultant for Abbot, CENEREX, Cephalon, Cypress Bioscience, Cyberonics, Forest, Janssen, JDS, Medtronic, Organon, Novartis, Pfizer, Roche, Solvay, Wyeth, and Sierra Neuropharmaceuticals. He has served on the advisory board for Abbott, Bristol-Myers Squibb, CENEREX, Cyberonics, Cypress Bioscience, Forest, Janssen, Neuronetics, Novartis, Orgonon, and Pfizer. Drs. Axelson, Strober, Ha, T. Goldstein, Dickstein, Yen, Kim, Iyengar, and Ryan, and Ms. Frankel, Ms. Gill, Ms. Hower, and Ms. Liao report no biomedical financial interests or potential conflicts of interest. NR 47 TC 75 Z9 77 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2011 VL 50 IS 10 BP 1001 EP 1016 DI 10.1016/j.jaac.2011.07.005 PG 16 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 829EZ UT WOS:000295562700008 PM 21961775 ER PT J AU Choi, YY Kim, J Seo, D Choi, D Kim, MJ Kim, JH Lee, KJ Hur, KY AF Choi, Yoon Young Kim, Jungman Seo, Daekwan Choi, Dongho Kim, Min Joo Kim, Jung Hoon Lee, Kyung-Jae Hur, Kyung Yul TI Is routine nasogastric tube insertion necessary in pancreaticoduodenectomy? SO JOURNAL OF THE KOREAN SURGICAL SOCIETY LA English DT Article DE Pancreaticoduodenectomy; Gastrointestinal intubation ID PROSPECTIVE RANDOMIZED-TRIAL; ELECTIVE LAPAROTOMY; GASTRIC-CANCER; DECOMPRESSION; SURGERY; GASTRECTOMY; INTUBATION; OPERATIONS; NEED AB Purpose: The necessity of nasogastric decompression after abdominal surgical procedures has been increasingly questioned for several years. Traditionally,. nasogastric decompression is a mandatory procedure after classical pancreaticoduodenectomy (PD); however, we still do not know whether or not it is necessary for PD. The present study was designed to assess the clinical benefit of nasogastric decompression after PD. Methods: Between July 2004 and May 2007, 41 consecutive patients who underwent PD were enrolled in this study. Eighteen patients were enrolled in the nasogastric tube (NGT) group and 23 patients were enrolled in the no NGT group. Results: There were no differences in the demographics, pathology, co-morbid medical conditions, and pre-operative laboratory values between the two groups. In addition, the passage of flatus (P = 0.963) and starting time of oral intake (P = 0.951) were similar in both groups. In the NGT group, 61% of the patients complained of discomfort related to the NGT. Pleural effusions were frequent in the NGT group (P = 0.037); however, other post-operative complications, such as wound dehiscence and anastomotic leakage, occurred similarly in both groups. There was one case of NGT re-insertion in the NGT group. Conclusion: Routine nasogastric decompression in patients undergoing PD is not mandatory because it has no clinical advantages and increases patient discomfort. C1 [Choi, Yoon Young; Kim, Jungman; Choi, Dongho; Kim, Min Joo; Hur, Kyung Yul] Soonchunhyang Univ, Coll Med, Dept Surg, Seoul 140743, South Korea. [Seo, Daekwan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kim, Jung Hoon] Seoul Natl Univ, Coll Med, Dept Radiol, Seoul, South Korea. [Lee, Kyung-Jae] Soonchunhyang Univ, Coll Med, Dept Occupat Med, Seoul 140743, South Korea. RP Choi, D (reprint author), Soonchunhyang Univ, Coll Med, Soonchunhyang Univ Hosp, Dept Surg, 657 Hannam Dong, Seoul 140743, South Korea. EM dhchoi@schmc.ac.kr NR 17 TC 5 Z9 5 U1 0 U2 2 PU KOREAN SURGICAL SOCIETY PI SEOUL PA 3304HO, 101 DONG, BROWNSTONE SEOUL, 335, JUNGMIN-DONG, JUNG-GU, SEOUL, 100-859, SOUTH KOREA SN 2233-7903 J9 J KOREAN SURG SOC JI J. Korean Surg. Soc. PD OCT PY 2011 VL 81 IS 4 BP 257 EP 262 DI 10.4174/jkss.2011.81.4.257 PG 6 WC Surgery SC Surgery GA 827JE UT WOS:000295424000005 PM 22111081 ER PT J AU Barbash, IM Schenke, WH Halabi, M Ratnayaka, K Faranesh, AZ Kocaturk, O Lederman, RJ AF Barbash, Israel M. Schenke, William H. Halabi, Majdi Ratnayaka, Kanishka Faranesh, Anthony Z. Kocaturk, Ozgur Lederman, Robert J. TI Experimental Model of Large Pulmonary Embolism Employing Controlled Release of Subacute Caval Thrombus in Swine SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID DEEP-VEIN THROMBOSIS; IN-VITRO; RHEOLYTIC THROMBECTOMY; PORCINE MODEL; CATHETER; MANAGEMENT; HYPERTENSION; OUTCOMES; REGISTRY; ANGIOJET AB Purpose: To develop a catheter-based model of large pulmonary embolism (PE) in swine based on in situ venous thrombus formation. Materials and Methods: Ten Yorkshire swine underwent transjugular implantation of a retrievable inferior vena cava (IVC) filter. A thrombin and collagen mixture was injected into a confined space created by two balloons inflated proximal and distal to the IVC filter. Animals were left to survive for 7 days +/- 3 to allow thrombus to organize in situ. The caval thrombus was released on transcatheter retrieval of the IVC filter and embolized into the main and branch pulmonary arteries. The severity of PE was scored based on digital subtraction angiography with the Miller index. At necropsy, thrombi were recovered and analyzed histopathologically. Results: Large PE was induced in all animals (Miller index score of 15 +/- 5). Two animals developed saddle embolus with bilateral pulmonary artery occlusion, and five developed proximal occlusion of the left or right pulmonary artery. Nevertheless, no animal exhibited significant hemodynamic compromise. Large tubular thrombi were explanted in the size range of 5-10 cm long and 0.5-1 cm wide. Histologic analysis indicated an organized thrombus with infiltration of white blood cells and fibrin deposition. Conclusions: Large caval thrombi can be formed in vivo and released at a predetermined time to induce large PE in a large animal model. This may help in the development and testing of new therapeutic approaches for PE. C1 [Barbash, Israel M.; Schenke, William H.; Halabi, Majdi; Ratnayaka, Kanishka; Faranesh, Anthony Z.; Kocaturk, Ozgur; Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2C713,MSC 1538, Bethesda, MD 20892 USA. EM lederman@nih.gov OI lederman, robert/0000-0003-1202-6673 FU Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health [1ZIAHL005062-08, Z01-HL006041-01] FX This work was supported by Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health Grants 1ZIAHL005062-08 and Z01-HL006041-01. None of the authors have identified a conflict of interest. NR 27 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2011 VL 22 IS 10 BP 1471 EP 1477 DI 10.1016/j.jvir.2011.06.011 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 831DH UT WOS:000295708400020 PM 21802315 ER PT J AU Singleton, AB AF Singleton, Andrew B. TI Exome sequencing: a transformative technology SO LANCET NEUROLOGY LA English DT Review ID DE-NOVO MUTATIONS; PARKINSONS-DISEASE; MENTAL-RETARDATION; ALZHEIMERS-DISEASE; HEARING-LOSS; GENE; REVEALS; RISK; IDENTIFICATION; DEFICIENCY AB Background Much basic research into disease mechanisms has made use of genetic findings to model and understand aetiology. Broad success has been achieved in finding disease-linked mutations with traditional positional cloning approaches; however, because of the requirements of this method, these successes have been limited by the availability of large, well characterised families. Because of these and other restrictions the genetic basis of many diseases, and diseases in many families, remains unknown. Recent developments Exome sequencing uses DNA-enrichment methods and massively parallel nucleotide sequencing to comprehensively identify and type protein-coding variants throughout the genome. Coupled with growing databases that contain known variants, exome sequencing makes identification of genetic mutations and risk factors possible in families and samples that were deemed insufficiently informative for previous genetic studies. Not only does exome sequencing enable identification of mutations in families that were undetectable with linkage and positional cloning methods, but compared with these methods, it is also much quicker and cheaper. Use of exome sequencing has so far been successful in many rare diseases. Where next? Exome sequencing is being adopted widely and we can expect an abundance of mutation discovery, similar to the deluge of genome-wide-association findings reported over the past 5 years; it is expected to enable the discovery of not only rare causal variants, but also protein-coding risk variants. This method will have application in both the research and clinical arenas and sets the scene for the use of whole-genome sequencing. C1 NIA, Neurogenet Lab, NIH, Poolesville, MD 20837 USA. RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, Poolesville, MD 20837 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009 FU National Institute on Aging, US National Institutes of Health, Department of Health and Human Services [Z01 AG000958-08] FX This work was supported by the Intramural Research Program of the National Institute on Aging, US National Institutes of Health, Department of Health and Human Services; project Z01 AG000958-08. NR 43 TC 59 Z9 66 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2011 VL 10 IS 10 BP 942 EP 946 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 832OP UT WOS:000295814600015 PM 21939903 ER PT J AU Katki, HA Kinney, WK Fetterman, B Lorey, T Poitras, NE Cheung, L Demuth, F Schiffman, M Wacholder, S Castle, PE AF Katki, Hormuzd A. Kinney, Walter K. Fetterman, Barbara Lorey, Thomas Poitras, Nancy E. Cheung, Li Demuth, Franklin Schiffman, Mark Wacholder, Sholom Castle, Philip E. TI Premature conclusions on HPV-only testing Reply SO LANCET ONCOLOGY LA English DT Letter C1 [Katki, Hormuzd A.; Schiffman, Mark; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Kinney, Walter K.] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. [Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy E.] Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA. [Cheung, Li; Demuth, Franklin] Informat Management Serv Inc, Silver Spring, MD USA. [Castle, Philip E.] Amer Soc Clin Pathologists, Washington, DC USA. RP Katki, HA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM katkih@mail.nih.gov RI Katki, Hormuzd/B-4003-2015 NR 2 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2011 VL 12 IS 11 BP 993 EP 993 PG 1 WC Oncology SC Oncology GA 833KW UT WOS:000295885200014 ER PT J AU Shen, J AF Shen, Jun TI Derivative encoding for parallel magnetic resonance imaging SO MEDICAL PHYSICS LA English DT Article DE parallel imaging; magnetic resonance imaging (MRI); derivative encoding; image reconstruction; noise reduction ID GRAPPA RECONSTRUCTION; MRI; REGULARIZATION; SENSE; COIL; MOTION AB Purpose: To introduce a linear shift-invariant relationship between the partial derivatives of k space signals acquired using multichannel receive coils and to demonstrate that k space derivatives can be used for image unwrapping. Methods: Fourier transform of k space derivatives contains information on the spatial origins of aliased pixels; therefore, images can be reconstructed by k space derivatives. Fully sampled phantom and brain images acquired at 3 T using a standard eight channel receive coil were used to validate the k space derivatives theorem by unwrapping aliased images. Results: Derivative encoding leads to new methods for parallel imaging reconstruction in both k space and image domains. Noise amplification in sensitivity encoding image reconstruction, which is considered to produce the optimal SNR, can be further reduced using k space derivative encoding without making any assumptions on the characteristics of the images to be reconstructed. Conclusions: This work demonstrated that the partial derivative of the k space signal acquired from one coil with respect to one direction can be expressed as a sum of partial derivatives of signals from multiple coils with respect to the perpendicular k space direction(s). This relationship between the partial derivatives of k space signals is linear and shift-invariant in the Cartesian coordinate system. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3633908] C1 NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX The author gratefully acknowledges the support by the Intramural Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS). The author also thanks Dr. Fa-Hsuan Lin, MGH, and Dr. Yan Zhang, NIMH, for valuable help. NR 32 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2011 VL 38 IS 10 BP 5582 EP 5589 DI 10.1118/1.3633908 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 829WU UT WOS:000295617400033 PM 21992376 ER PT J AU Freed, M de Zwart, JA Hariharan, P Myers, MR Badano, A AF Freed, Melanie de Zwart, Jacco A. Hariharan, Prasanna Myers, Matthew R. Badano, Aldo TI Development and characterization of a dynamic lesion phantom for the quantitative evaluation of dynamic contrast-enhanced MRI SO MEDICAL PHYSICS LA English DT Article DE dynamic phantom; DCE-MRI; breast imaging ID SPOILED GRADIENT-ECHO; MYOCARDIAL-PERFUSION; DIAGNOSTIC-ACCURACY; BREAST MRI; PARAMETERS; SEQUENCES; RESONANCE; DTPA; STANDARDIZATION; QUANTIFICATION AB Purpose: To develop a dynamic lesion phantom that is capable of producing physiological kinetic curves representative of those seen in human dynamic contrast-enhanced MRI (DCE-MRI) data. The objective of this phantom is to provide a platform for the quantitative comparison of DCE-MRI protocols to aid in the standardization and optimization of breast DCE-MRI. Methods: The dynamic lesion consists of a hollow, plastic mold with inlet and outlet tubes to allow flow of a contrast agent solution through the lesion over time. Border shape of the lesion can be controlled using the lesion mold production method. The configuration of the inlet and outlet tubes was determined using fluid transfer simulations. The total fluid flow rate was determined using x-ray images of the lesion for four different flow rates (0.25, 0.5, 1.0, and 1.5 ml/s) to evaluate the resultant kinetic curve shape and homogeneity of the contrast agent distribution in the dynamic lesion. High spatial and temporal resolution x-ray measurements were used to estimate the true kinetic curve behavior in the dynamic lesion for benign and malignant example curves. DCE-MRI example data were acquired of the dynamic phantom using a clinical protocol. Results: The optimal inlet and outlet tube configuration for the lesion molds was two inlet molds separated by 30 degrees and a single outlet tube directly between the two inlet tubes. X-ray measurements indicated that 1.0 ml/s was an appropriate total fluid flow rate and provided truth for comparison with MRI data of kinetic curves representative of benign and malignant lesions. DCE-MRI data demonstrated the ability of the phantom to produce realistic kinetic curves. Conclusions: The authors have constructed a dynamic lesion phantom, demonstrated its ability to produce physiological kinetic curves, and provided estimations of its true kinetic curve behavior. This lesion phantom provides a tool for the quantitative evaluation of DCE-MRI protocols, which may lead to improved discrimination of breast cancer lesions. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3633911] C1 [Freed, Melanie; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [de Zwart, Jacco A.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, Adv MRI Sect, NIH, Bethesda, MD 20892 USA. [Hariharan, Prasanna; Myers, Matthew R.] US FDA, Div Solid & Fluid Mech, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Freed, M (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU FDA's Office of Women Health; Center for Devices and Radiological Health; NINDS/NIH FX The authors wish to thank Han Wen (NIH/NHLBI) for providing MRI scan time, Hellmut Merkle (NIH/NINDS) for providing noise reduction filters for the fluid pump, Eugene O'Bryan (FDA) for help with setting up the timing circuit and his tireless material acquisition efforts, and Randy Bidinger (FDA) and Bruce Fleharty (FDA) for machining of a variety of experimental components. The authors also acknowledge funding from the FDA's Office of Women Health. This project was supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. This research was sponsored, in part, by the Intramural Research Program of NINDS/NIH. NR 33 TC 8 Z9 8 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2011 VL 38 IS 10 BP 5601 EP 5611 DI 10.1118/1.3633911 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 829WU UT WOS:000295617400035 PM 21992378 ER PT J AU Linguraru, MG Wang, SJ Shah, F Gautam, R Peterson, J Linehan, WM Summers, RM AF Linguraru, Marius George Wang, Shijun Shah, Furhawn Gautam, Rabindra Peterson, James Linehan, W. Marston Summers, Ronald M. TI Automated noninvasive classification of renal cancer on multiphase CT SO MEDICAL PHYSICS LA English DT Article DE kidney; cancer; segmentation; classification; computer-aided diagnosis ID COMPUTER-AIDED DIAGNOSIS; BRAIN-TUMOR SEGMENTATION; SUPPORT VECTOR MACHINES; ENHANCED ABDOMINAL CT; KIDNEY CANCER; PULMONARY NODULES; COLONIC POLYPS; IMAGES; SHAPE; TOMOGRAPHY AB Purpose: To explore the added value of the shape of renal lesions for classifying renal neoplasms. To investigate the potential of computer-aided analysis of contrast-enhanced computed-tomography (CT) to quantify and classify renal lesions. Methods: A computer-aided clinical tool based on adaptive level sets was employed to analyze 125 renal lesions from contrast-enhanced abdominal CT studies of 43 patients. There were 47 cysts and 78 neoplasms: 22 Von Hippel-Lindau (VHL), 16 Birt-Hogg-Dube (BHD), 19 hereditary papillary renal carcinomas (HPRC), and 21 hereditary leiomyomatosis and renal cell cancers (HLRCC). The technique quantified the three-dimensional size and enhancement of lesions. Intrapatient and interphase registration facilitated the study of lesion serial enhancement. The histograms of curvature-related features were used to classify the lesion types. The areas under the curve (AUC) were calculated for receiver operating characteristic curves. Results: Tumors were robustly segmented with 0.80 overlap (0.98 correlation) between manual and semi-automated quantifications. The method further identified morphological discrepancies between the types of lesions. The classification based on lesion appearance, enhancement and morphology between cysts and cancers showed AUC = 0.98; for BHD + VHL (solid cancers) vs. HPRC + HLRCC AUC = 0.99; for VHL vs. BHD AUC = 0.82; and for HPRC vs. HLRCC AUC = 0.84. All semi-automated classifications were statistically significant (p < 0.05) and superior to the analyses based solely on serial enhancement. Conclusions: The computer-aided clinical tool allowed the accurate quantification of cystic, solid, and mixed renal tumors. Cancer types were classified into four categories using their shape and enhancement. Comprehensive imaging biomarkers of renal neoplasms on abdominal CT may facilitate their noninvasive classification, guide clinical management, and monitor responses to drugs or interventions. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3633898] C1 [Linguraru, Marius George; Wang, Shijun; Shah, Furhawn; Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Gautam, Rabindra; Peterson, James; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), NIH, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. FU National Institutes of Health, Clinical Center; National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center and National Cancer Institute, Center for Cancer Research. The authors would like to thank John A. Pura for helping with the data analysis. NR 55 TC 6 Z9 6 U1 2 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2011 VL 38 IS 10 BP 5738 EP 5746 DI 10.1118/1.3633898 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 829WU UT WOS:000295617400045 PM 21992388 ER PT J AU Nash, TE Garcia, HH AF Nash, Theodore E. Garcia, Hector H. TI Diagnosis and treatment of neurocysticercosis SO NATURE REVIEWS NEUROLOGY LA English DT Review ID SOLITARY CYSTICERCUS GRANULOMA; HIGH-DOSE PRAZIQUANTEL; LINKED IMMUNOELECTROTRANSFER BLOT; TAENIA-SOLIUM CYSTICERCOSIS; DOUBLE-BLIND-TRIAL; CEREBRAL CYSTICERCOSIS; ALBENDAZOLE THERAPY; FOLLOW-UP; EXTRAPARENCHYMAL NEUROCYSTICERCOSIS; CALCIFIED NEUROCYSTICERCOSIS AB Neurocysticercosis is a parasitic disease caused by the larval (cystic) form of the pork cestode tapeworm, Taenia solium, and is a major cause of acquired seizures and epilepsy worldwide. Development of sensitive and specific diagnostic methods, particularly CT and MRI, has revolutionized our knowledge of the burden of cysticercosis infection and disease, and has led to the development of effective antihelminthic treatments for neurocysticercosis. The importance of calcified granulomas with perilesional edema as foci of seizures and epilepsy in populations where neurocysticercosis is endemic is newly recognized, and indicates that treatment with anti-inflammatory agents could have a role in controlling or preventing epilepsy in these patients. Importantly, neurocysticercosis is one of the few diseases that could potentially be controlled or eliminated-an accomplishment that would prevent millions of cases of epilepsy. This Review examines the rationale for treatment of neurocysticercosis and highlights the essential role of inflammation in the pathogenesis of disease, the exacerbation of symptoms that occurs as a result of antihelminthic treatment, and the limitations of current antihelminthic and anti-inflammatory treatments. Nash, T. E. & Garcia, H. H. Nat. Rev. Neurol. 7, 584-594 (2011); published online 13 September 2011; doi:10.1038/nrneurol.2011.135 C1 [Garcia, Hector H.] Inst Nacl Ciencias Neurol, Cysticercosis Unit, Lima, Peru. [Nash, Theodore E.] NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Garcia, HH (reprint author), Inst Nacl Ciencias Neurol, Cysticercosis Unit, Jr Ancash 1271, Lima, Peru. EM hgarcia@jhsph.edu FU National Institutes of Health, National Institutes of Allergy and Infection Diseases FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institutes of Allergy and Infection Diseases. H. H. Garcia is a Wellcome Trust International Senior Research Fellow. NR 116 TC 68 Z9 71 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD OCT PY 2011 VL 7 IS 10 BP 584 EP 594 DI 10.1038/nrneurol.2011.135 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 834BU UT WOS:000295933500008 PM 21912406 ER PT J AU Reyes-Turcu, FE Zhang, K Zofall, M Chen, E Grewal, SIS AF Reyes-Turcu, Francisca E. Zhang, Ke Zofall, Martin Chen, Eesin Grewal, Shiv I. S. TI Defects in RNA quality control factors reveal RNAi-independent nucleation of heterochromatin SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID FISSION YEAST; POLYMERASE-II; EPIGENETIC CONTROL; TRIGGER RNAI; HP1 PROTEINS; TRANSCRIPTION; INTERFERENCE; ELONGATION; MECHANISMS; CHROMATIN AB Heterochromatin assembly at Schizosaccharomyces pombe centromeres involves a self-reinforcing loop mechanism wherein chromatin-bound RNAi factors facilitate targeting of Clr4-Rik1 methyltransferase. However, the initial nucleation of heterochromatin has remained elusive. We show that cells lacking Mlo3, a protein involved in mRNP biogenesis and RNA quality control, assemble functional heterochromatin in RNAi-deficient cells. Heterochromatin restoration is linked to RNA surveillance because loss of Mlo3-associated TRAMP also rescues heterochromatin defects of RNAi mutants. mlo3 Delta, which causes accumulation of bidirectional repeat-transcripts, restores Rik1 enrichment at repeats and triggers de novo heterochromatin formation in the absence of RNAi. RNAi-independent heterochromatin nucleation occurs at selected euchromatic loci that show upregulation of antisense RNAs in mlo3 Delta cells. We find that the exosome RNA degradation machinery acts parallel to RNAi to promote heterochromatin formation at centromeres. These results suggest that RNAi-independent mechanisms exploit transcription and non-coding RNAs to nucleate heterochromatin. C1 [Reyes-Turcu, Francisca E.; Zhang, Ke; Zofall, Martin; Chen, Eesin; Grewal, Shiv I. S.] NCI, Lab Biochem & Mol Biol, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Lab Biochem & Mol Biol, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov FU US National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We are thankful to D. Eick (Helmholtz Center Munich) for the gift of phospho (Ser2) RNAPII antibody, R. Dhar and N. Krogan (University of California, San Francisco) for strains, J. Dhakshnamoorthy, N. Komissarova and S. Mehta for helpful contributions, and members of the Grewal laboratory for discussions. This research was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 60 TC 45 Z9 45 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD OCT PY 2011 VL 18 IS 10 BP 1132 EP U114 DI 10.1038/nsmb.2122 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 834BF UT WOS:000295931400007 PM 21892171 ER PT J AU Collins, J Hu, S Devarajan, P Bonnemann, CG Bennett, M AF Collins, J. Hu, S. Devarajan, P. Bonnemann, C. G. Bennett, M. TI Candidate biomarkers in merosin-deficient congenital muscular dystrophy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 16th International Congress of the World-Muscle-Society CY OCT 18-22, 2011 CL Algarve, PORTUGAL SP World Muscle Soc C1 [Collins, J.; Hu, S.; Devarajan, P.; Bennett, M.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Bonnemann, C. G.] NINCDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2011 VL 21 IS 9-10 BP 660 EP 661 DI 10.1016/j.nmd.2011.06.824 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834JP UT WOS:000295955900073 ER PT J AU Foley, AR Quijano-Roy, S Collins, J Straub, V Deconinck, N Mercuri, E D'Amico, A Bertini, E North, K Ryan, M Rummey, C Meier, T Cole, T Muntoni, F Bonnemann, C AF Foley, A. R. Quijano-Roy, S. Collins, J. Straub, V. Deconinck, N. Mercuri, E. D'Amico, A. Bertini, E. North, K. Ryan, M. Rummey, C. Meier, T. Cole, T. Muntoni, F. Boennemann, C. TI The identification of a viable outcome measure in the collagen VI myopathies promotes progress toward clinical trials SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 16th International Congress of the World-Muscle-Society CY OCT 18-22, 2011 CL Algarve, PORTUGAL SP World Muscle Soc C1 [Foley, A. R.; Muntoni, F.] Dubowitz Neuromuscular Ctr, UCL Inst Child Hlth, London, England. [Foley, A. R.; Muntoni, F.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Quijano-Roy, S.] Hop Raymond Poincare, Neuromuscular Ctr, Garches, France. [Collins, J.] Cincinnati Childrens Hosp, Med Ctr, Div Neurol, Cincinnati, OH USA. [Straub, V.] Univ Newcastle, Int Ctr Life, Inst Human Genet, Newcastle, England. [Deconinck, N.] Hop Univ Enfants Reine Fabiola, Dept Neurol, Brussels, Belgium. [Mercuri, E.] Catholic Univ, Dept Paediat Neurol, Rome, Italy. [D'Amico, A.; Bertini, E.] Bambino Gesu Pediat Hosp, Mol Med Unit, Rome, Italy. [North, K.] Univ Sydney, Childrens Hosp Westmead, Inst Neuromuscular Res, Sydney, NSW 2006, Australia. [Ryan, M.] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia. [Rummey, C.; Meier, T.] Santhera Pharmaceut, Liestal, Switzerland. [Boennemann, C.] Natl Inst Neurol Disorders & Stroke NIH, Neuromuscular & Neurogenet Disorders Childhood Se, Bethesda, MD USA. RI d'amico, adele/J-9203-2016 OI d'amico, adele/0000-0003-2438-2624 NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2011 VL 21 IS 9-10 BP 662 EP 662 DI 10.1016/j.nmd.2011.06.828 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834JP UT WOS:000295955900077 ER PT J AU Meilleur, KG Medne, L Hu, Y Perkins, K Powell-Hamilton, N Finkel, R Scavina, M Bonnemann, C AF Meilleur, K. G. Medne, L. Hu, Y. Perkins, K. Powell-Hamilton, N. Finkel, R. Scavina, M. Bonnemann, C. TI Further characterization of the clinical and mutational spectrum of alpha-dystroglycanopathy caused by mutations in the LARGE gene SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 16th International Congress of the World-Muscle-Society CY OCT 18-22, 2011 CL Algarve, PORTUGAL SP World Muscle Soc C1 [Meilleur, K. G.; Hu, Y.; Perkins, K.; Bonnemann, C.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, Bethesda, MD USA. [Medne, L.; Finkel, R.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Perkins, K.; Scavina, M.] AI Dupont Childrens Hosp, Wilmington, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2011 VL 21 IS 9-10 BP 664 EP 665 DI 10.1016/j.nmd.2011.06.836 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834JP UT WOS:000295955900085 ER PT J AU Perkins, KZ Meilleur, K Medne, L Devoto, M Tennekoon, G Yum, S Yang, M Finkel, R Johnson, J Gibbs, JR Ferguson, T Zou, Y Traynor, B Bonnemann, C AF Perkins, K. Z. Meilleur, K. Medne, L. Devoto, M. Tennekoon, G. Yum, S. Yang, M. Finkel, R. Johnson, J. Gibbs, J. R. Ferguson, T. Zou, Y. Traynor, B. Bonnemann, C. TI Exome sequencing with linkage analysis identifies a novel ACTA1 variant in a large family with progressive muscle weakness SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 16th International Congress of the World-Muscle-Society CY OCT 18-22, 2011 CL Algarve, PORTUGAL SP World Muscle Soc C1 [Perkins, K. Z.; Meilleur, K.; Zou, Y.; Bonnemann, C.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Medne, L.; Devoto, M.; Tennekoon, G.; Yum, S.; Yang, M.; Finkel, R.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Johnson, J.; Gibbs, J. R.; Traynor, B.] NIA, Bethesda, MD 20892 USA. [Ferguson, T.] Temple Univ, Philadelphia, PA 19122 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2011 VL 21 IS 9-10 BP 696 EP 697 DI 10.1016/j.nmd.2011.06.942 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834JP UT WOS:000295955900191 ER PT J AU Dowling, JJ Arbogast, S McEvoy, A Nelson, DD Brooks, SV Kuwada, JY Bonnemann, CG Ferreiro, A AF Dowling, J. J. Arbogast, S. McEvoy, A. Nelson, D. D. Brooks, S. V. Kuwada, J. Y. Bonnemann, C. G. Ferreiro, A. TI Increased oxidative stress and successful antioxidant treatment in a vertebrate model of RYR1 related myopathy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 16th International Congress of the World-Muscle-Society CY OCT 18-22, 2011 CL Algarve, PORTUGAL SP World Muscle Soc C1 [Dowling, J. J.; McEvoy, A.; Nelson, D. D.; Brooks, S. V.; Kuwada, J. Y.] Univ Michigan, Ann Arbor, MI 48109 USA. [Arbogast, S.; Ferreiro, A.] INSERM, Inst Myol, Paris, France. [Bonnemann, C. G.] NIH, Bethesda, MD 20892 USA. RI Ferreiro, Ana/F-5371-2011 NR 0 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2011 VL 21 IS 9-10 BP 720 EP 721 DI 10.1016/j.nmd.2011.06.1019 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834JP UT WOS:000295955900268 ER PT J AU Vorgerd, M Kley, RA Serdaroglu-Oflazer, P Odgerel, Z Olive, M Lee, HS Hahn, Y van der Ven, PFM Hohfeld, J Kirschner, J Bilbao, JM Goldfarb, LG Furst, DO AF Vorgerd, M. Kley, R. A. Serdaroglu-Oflazer, P. Odgerel, Z. Olive, M. Lee, H. S. Hahn, Y. van der Ven, P. F. M. Hoehfeld, J. Kirschner, J. Bilbao, J. M. Goldfarb, L. G. Fuerst, D. O. TI Myofibrillar myopathy associated with filamin C mutations: Refining the phenotype and new insights in pathogenesis SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 16th International Congress of the World-Muscle-Society CY OCT 18-22, 2011 CL Algarve, PORTUGAL SP World Muscle Soc C1 [Vorgerd, M.; Kley, R. A.] Ruhr Univ Bochum, Univ Hosp Bergmannsheil, Dept Neurol, Bochum, Germany. [Serdaroglu-Oflazer, P.] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Istanbul, Turkey. [Odgerel, Z.; Lee, H. S.; Goldfarb, L. G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Olive, M.] IDIBELL Hosp Univ Bellvitge, Inst Neuropatol, Barcelona, Spain. [Hahn, Y.; van der Ven, P. F. M.; Hoehfeld, J.; Fuerst, D. O.] Univ Bonn, Inst Cell Biol, D-5300 Bonn, Germany. [Kirschner, J.] Univ Childrens Hosp Freiburg, Div Neuropediat & Muscle Disorders, Freiburg, Germany. RI Kirschner, Janbernd/H-7418-2016 OI Kirschner, Janbernd/0000-0003-1618-7386 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2011 VL 21 IS 9-10 BP 741 EP 741 DI 10.1016/j.nmd.2011.06.1085 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 834JP UT WOS:000295955900334 ER PT J AU Munafo, MR Johnstone, EC Walther, D Uhl, GR Murphy, MFG Aveyard, P AF Munafo, Marcus R. Johnstone, Elaine C. Walther, Donna Uhl, George R. Murphy, Michael F. G. Aveyard, Paul TI CHRNA3 rs1051730 Genotype and Short-Term Smoking Cessation SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID NICOTINE REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; TOBACCO DEPENDENCE; GENETIC-VARIATION; TRANSDERMAL NICOTINE; CLINICAL-TRIALS; RECEPTOR DRD2; STOP SMOKING; FOLLOW-UP; ASSOCIATION AB Introduction: The rs1051730 genetic variant within the CHRNA5-A3-B4 gene cluster is associated with heaviness of smoking and has recently been reported to be associated with likelihood of stopping smoking. We investigated the potential association of rs1051730 genotype with reduced likelihood of smoking cessation in 2 cohorts of treatment-seeking smokers in primary care in the United Kingdom. Methods: Data were drawn from 2 clinical trials on which DNA was available. One sample was a randomized placebo-controlled trial of nicotine transdermal patch and the other sample an open-label trial where all participants received nicotine transdermal patch. Smoking status was biochemically verified. Logistic regression was used to assess evidence for association in each sample, and data were combined within a meta-analysis. Results: There was evidence of association of rs1051730 genotype with short-term (4-week) cessation in our open-label trial sample but not our placebo-controlled trial sample. When combined in a meta-analysis, this effect remained. There was no evidence of association at later follow-up intervals. Adjustment for cigarette consumption and tobacco dependence did not alter these results substantially. Conclusions: Our data, taken together with previous recent studies, provide some support for a weak association between this variant and short-term smoking cessation in treatment-seeking smokers, which does not seem to operate only among those receiving nicotine replacement therapy. Moreover, the rs1051730 variant may not merely operate as a marker for dependence or heaviness of smoking. C1 [Munafo, Marcus R.] Univ Bristol, Sch Expt Psychol, Bristol BS8 1TU, Avon, England. [Johnstone, Elaine C.] Univ Oxford, Dept Clin Pharmacol, Oxford, England. [Walther, Donna; Uhl, George R.] Natl Inst Drug Abuse, Mol Neurobiol Branch, Natl Inst Hlth, Intramural Res Program, Baltimore, MD USA. [Murphy, Michael F. G.] Univ Oxford, Childhood Canc Res Grp, Oxford, England. [Aveyard, Paul] Univ Birmingham, Birmingham, W Midlands, England. RP Munafo, MR (reprint author), Univ Bristol, Sch Expt Psychol, 12A Priory Rd, Bristol BS8 1TU, Avon, England. EM marcus.munafo@bristol.ac.uk OI Aveyard, Paul/0000-0002-1802-4217; Munafo, Marcus/0000-0002-4049-993X FU Cancer Research UK [C53/A6281]; National Institutes of Health (National Institute on Drug Abuse) Department of Health and Human Services, USA; National Institute of Health Research; Economic and Social Research Council; British Heart Foundation; Cancer Research UK; Department of Health; Medical Research Council of the UK Clinical Research FX This research was supported in part by a Cancer Research UK programme grant (C53/A6281) and by the National Institutes of Health intramural research program (National Institute on Drug Abuse) Department of Health and Human Services, USA. PA is supported by the National Institute of Health Research.; MRM and PA are members of the UK Centre for Tobacco Control Studies, a U.K. Clinical Research Collaboration Public Health Research Centre of Excellence. Funding from the Economic and Social Research Council, the British Heart Foundation, Cancer Research UK, the Department of Health, and the Medical Research Council, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The authors are grateful for the support of the Patch Study Team and the general practices which participated in the trial. NR 35 TC 43 Z9 44 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD OCT PY 2011 VL 13 IS 10 BP 982 EP 988 DI 10.1093/ntr/ntr106 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 828NL UT WOS:000295508500012 PM 21690317 ER PT J AU Lee, YH Judge, AD Seo, D Kitade, M Gomez-Quiroz, LE Ishikawa, T Andersen, JB Kim, BK Marquardt, JU Raggi, C Avital, I Conner, EA MacLachlan, I Factor, VM Thorgeirsson, SS AF Lee, Y-H Judge, A. D. Seo, D. Kitade, M. Gomez-Quiroz, L. E. Ishikawa, T. Andersen, J. B. Kim, B-K Marquardt, J. U. Raggi, C. Avital, I. Conner, E. A. MacLachlan, I. Factor, V. M. Thorgeirsson, S. S. TI Molecular targeting of CSN5 in human hepatocellular carcinoma: a mechanism of therapeutic response SO ONCOGENE LA English DT Article DE hepatocellular carcinoma; CSN5; targeted siRNA therapeutics; SNALP ID BINDING PROTEIN-1 EXPRESSION; CYCLE INHIBITOR P27(KIP1); COP9 SIGNALOSOME; RNA INTERFERENCE; BREAST-CANCER; IN-VIVO; PANCREATIC-CANCER; SYNTHETIC SIRNA; GENE-EXPRESSION; C-MYC AB Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. We have recently identified an elevated expression of the fifth subunit of COP9 signalosome (CSN5) in early HCC as compared with dysplastic stage. In the present study, we explored the possibility of CSN5 being a potential therapeutic target for HCC. Our results show that CSN5 knockdown by small-interfering (si) RNA caused a strong induction of apoptosis and inhibition of cell-cycle progression in HCC cells in vitro. The down-regulation of CSN5 was sufficient to interfere with CSN function as evidenced by the accumulation of neddylated Cullin 1 and changes in the protein levels of CSN-controlled substrates SKP2, p53, p27 and nuclear factor-kappa B, albeit to a different degree depending on the HCC cell line, which could account for the CSN5 knockdown phenotype. The transcriptomic analysis of CSN5 knockdown signature showed that the anti-proliferative effect was driven by a common subset of molecular alterations including down-regulation of cyclin-dependent kinase 6 (CDK6) and integrin beta 1 (ITGB1), which were functionally interconnected with key oncogenic regulators MYC and TGF beta 1 involved in the control of proliferation, apoptotic cell death and HCC progression. Consistent with microarray analysis, western blotting revealed that CSN5 depletion increased phosphorylation of Smad 2/3, key mediators of TGF beta 1 signaling, decreased the protein levels of ITGB1, CDK6 and cyclin D1 and caused reduced expression of anti-apoptotic Bcl-2, while elevating the levels of proapoptotic Bak. A chemically modified variant of CSN5 siRNA was then selected for in vivo application based on the growth inhibitory effect and minimal induction of unwanted immune response. Systemic delivery of the CSN5 3/8 variant by stable-nucleic-acid-lipid particles significantly suppressed the tumor growth in Huh7-luc(+) orthotopic xenograft model. Taken together, these results indicate that CSN5 has a pivotal role in HCC pathogenesis and maybe an attractive molecular target for systemic HCC therapy. Oncogene (2011) 30, 4175-4184; doi:10.1038/onc.2011.126; published online 18 April 2011 C1 [Lee, Y-H; Seo, D.; Kitade, M.; Gomez-Quiroz, L. E.; Ishikawa, T.; Andersen, J. B.; Kim, B-K; Marquardt, J. U.; Raggi, C.; Conner, E. A.; Factor, V. M.; Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Judge, A. D.; MacLachlan, I.] Tekmira Pharmaceut Corp, Burnaby, BC, Canada. [Avital, I.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr Dr MSC,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov RI Gomez-Quiroz, Luis/L-8415-2013; OI Andersen , Jesper B/0000-0003-1760-5244; RAGGI, Chiara/0000-0003-2473-3535; Gomez-Quiroz, Luis Enrique/0000-0002-5704-5985 FU Center for Cancer Research, NCI FX This project was supported by the Intramural Research Program of the Center for Cancer Research, NCI. NR 53 TC 31 Z9 33 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2011 VL 30 IS 40 BP 4175 EP 4184 DI 10.1038/onc.2011.126 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 833ZK UT WOS:000295924600004 PM 21499307 ER PT J AU Baladi, MG Newman, AH France, CP AF Baladi, Michelle G. Newman, Amy H. France, Charles P. TI Influence of body weight and type of chow on the sensitivity of rats to the behavioral effects of the direct-acting dopamine-receptor agonist quinpirole SO PSYCHOPHARMACOLOGY LA English DT Article DE Direct-acting dopamine-receptor agonist; Quinpirole; Yawning; High-fat chow; Body weight; Insulin; Dopamine; Rat; High fat ID CHRONIC FOOD RESTRICTION; HIGH-FAT DIET; LOCOMOTOR SENSITIZATION; DIFFERENTIALLY MODIFY; PARKINSONS-DISEASE; RHESUS-MONKEYS; MESSENGER-RNA; D3 RECEPTOR; D-3; COCAINE AB Rationale Amount and type of food can alter dopamine systems and sensitivity to drugs acting on those systems. Objectives This study examined whether changes in body weight, food type, or both body weight and food type contribute to these effects. Methods Rats had free or restricted access (increasing, decreasing, or maintaining body weight) to standard (5.7% fat) or high-fat (34.3%) chow. Results In rats gaining weight with restricted or free access to high-fat chow, both limbs of the quinpirole yawning dose-response curve (0.0032-0.32 mg/kg) shifted leftward compared with rats eating standard chow. Restricting access to standard or high-fat chow (maintaining or decreasing body weight) decreased or eliminated quinpirole-induced yawning; within 1 week of resuming free feeding, sensitivity to quinpirole was restored, although the descending limb of the dose-response curve was shifted leftward in rats eating high-fat chow. These are not likely pharmacokinetic differences because quinpirole-induced hypothermia was not different among groups. PG01037 and L-741,626 antagonized the ascending and descending limbs of the quinpirole dose-response curve in rats eating high-fat chow, indicating D3 and D2 receptor mediation, respectively. Rats eating high-fat chow also developed insulin resistance. Conclusions These results show that amount and type of chow alter sensitivity to a direct-acting dopamine-receptor agonist with the impact of each factor depending on whether body weight increases, decreases, or is maintained. These data demonstrate that feeding conditions, perhaps related to insulin and insulin sensitivity, profoundly impact the actions of drugs acting on dopamine systems. C1 [Baladi, Michelle G.; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Newman, Amy H.] NIDA, Med Chem Sect AHN, Intramural Res Program, NIH, Baltimore, MD USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu FU National Institute on Drug Abuse; Senior Scientist Award [KO5 DA17918] FX AHN is supported by the National Institute on Drug Abuse, Intramural Research Program. CPF is supported by a Senior Scientist Award (KO5 DA17918) NR 50 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2011 VL 217 IS 4 BP 573 EP 585 DI 10.1007/s00213-011-2320-6 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 833GI UT WOS:000295870200011 PM 21544521 ER PT J AU Malayeri, AA El Khouli, RH Zaheer, A Jacobs, MA Corona-Villalobos, CP Kamel, IR Macura, KJ AF Malayeri, Ashkan A. El Khouli, Riham H. Zaheer, Atif Jacobs, Michael A. Corona-Villalobos, Celia P. Kamel, Ihab R. Macura, Katarzyna J. TI Principles and Applications of Diffusion-weighted Imaging in Cancer Detection, Staging, and Treatment Follow-up SO RADIOGRAPHICS LA English DT Article ID PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; NEOADJUVANT CHEMOTHERAPY; DIAGNOSTIC-ACCURACY; COEFFICIENT VALUES; TREATMENT RESPONSE; PERIPHERAL ZONES; TUMOR RESPONSE; LIVER FIBROSIS AB Diffusion-weighted imaging relies on the detection of the random microscopic motion of free water molecules known as Brownian movement. With the development of new magnetic resonance (MR) imaging technologies and stronger diffusion gradients, recent applications of diffusion-weighted imaging in whole-body imaging have attracted considerable attention, especially in the field of oncology. Diffusion-weighted imaging is being established as a pivotal aspect of MR imaging in the evaluation of specific organs, including the breast, liver, kidney, and those in the pelvis. When used in conjunction with apparent diffusion coefficient mapping, diffusion-weighted imaging provides information about the functional environment of water in tissues, thereby augmenting the morphologic information provided by conventional MR imaging. Detected changes include shifts of water from extracellular to intracellular spaces, restriction of cellular membrane permeability, increased cellular density, and disruption of cellular membrane depolarization. These findings are commonly associated with malignancies; therefore, diffusion-weighted imaging has many applications in oncologic imaging and can aid in tumor detection and characterization and in the prediction and assessment of response to therapy. (C) RSNA, 2011 . radiographics.rsna.org C1 [Malayeri, Ashkan A.; Zaheer, Atif; Jacobs, Michael A.; Corona-Villalobos, Celia P.; Kamel, Ihab R.; Macura, Katarzyna J.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [El Khouli, Riham H.] NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Malayeri, AA (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St, Baltimore, MD 21287 USA. EM amalayeri@jhmi.edu RI Jacobs, Michael/G-2901-2010 FU Siemens Medical FX I.R.K.: Related financial activities: patent with Siemens Medical. Other financial activities: none. K.J.M.: Related financial activities: grant from Siemens Medical. Other financial activities: consultant for ACR ImageMetrix. NR 51 TC 79 Z9 82 U1 3 U2 14 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2011 VL 31 IS 6 SI SI BP 1773 EP 1791 DI 10.1148/rg.316115515 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 834SU UT WOS:000295985200020 PM 21997994 ER PT J AU Calado, RT AF Calado, Rodrigo T. TI Immunologic Aspects of Hypoplastic Myelodysplastic Syndrome SO SEMINARS IN ONCOLOGY LA English DT Review ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; BONE-MARROW FAILURE; SEVERE APLASTIC-ANEMIA; NITRIC-OXIDE SYNTHASE; ANTITHYMOCYTE GLOBULIN; CYCLOSPORINE-A; IMMUNOSUPPRESSIVE THERAPY; DYSKERATOSIS-CONGENITA; REFRACTORY-ANEMIA; MUTATIONS AB The pathophysiology of myelodysplastic syndromes (MDS) is multiple, complex, and poorly understood. In some cases of MDS, especially those in which the bone marrow is hypocellular, there is increasing experimental and clinical indication that an immune-mediated damage to hematopoietic precursors and changes in the hematopoiesis-supporting microenvironment contribute to disease development. Increased serum levels of type-1 cytokines, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (INF-gamma), and oligoclonal expansion of cytotoxic T cells are observed in human MDS. In some cases, the immunologic attack to the marrow appears to be triggered by MDS-specific antigens, damaging the microenvironment and inducing cell apoptosis especially of normal progenitors. In murine models, dysregulation of osteoprogenitors leads to disrupted hematopoiesis of healthy hematopoietic progenitor and stem cells, eventually resulting in MDS and leukemia. In hypocellular MDS, marrow failure appears to be not only the result of ineffective erythropoiesis of abnormal clones, but also due to inhibition of normal progenitors. Immunosuppressive therapy with cyclosporine, anti-thymocyte globulin, or alemtuzumab may alleviate cytopenias and in some instances induce cytogenetic remission. However, not all patients respond to immunosuppression, and the identification of relevant biomarkers for an immune mechanism is necessary to identify those patients who may benefit from this treatment modality. Semin Oncol 38:667-672. Published by Elsevier Inc. C1 [Calado, Rodrigo T.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Calado, RT (reprint author), 10 Ctr Dr,Bldg 10 CRC,Room 3E5140, Bethesda, MD 20892 USA. EM calador@nhlbi.nih.gov RI Calado, Rodrigo/G-2619-2011; OI Calado, Rodrigo/0000-0002-7966-6029 FU NIH FX This work was supported by the NIH Intramural Research Program. NR 51 TC 20 Z9 23 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2011 VL 38 IS 5 BP 667 EP 672 DI 10.1053/j.seminoncol.2011.04.006 PG 6 WC Oncology SC Oncology GA 833BT UT WOS:000295857500009 PM 21943673 ER PT J AU Chason, RJ Csokmay, J Segars, JH DeCherney, AH Armant, DR AF Chason, Rebecca J. Csokmay, John Segars, James H. DeCherney, Alan H. Armant, D. Randall TI Environmental and epigenetic effects upon preimplantation embryo metabolism and development SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID ASSISTED REPRODUCTIVE TECHNOLOGY; X-CHROMOSOME INACTIVATION; EARLY MOUSE EMBRYO; IN-VITRO; DNA METHYLATION; GENE-EXPRESSION; HISTONE MODIFICATIONS; OXIDATIVE STRESS; IMPRINTED GENES; OXYGEN-TENSION AB In vitro fertilization has provided a unique window into the metabolic processes that drive embryonic growth and development from a fertilized ovum to a competent blastocyst. Post-fertilization development is dependent upon a dramatic reshuffling of the parental genomes during meiosis, as well as epigenetic changes that provide a new and autonomous set of instructions to guide cellular differentiation both in the embryo and beyond. Although early literature focused simply on the substrates and culture conditions required for progress through embryonic development, more recent insights lead us to suggest that the surrounding environment can alter the epigenome, which can, in turn, impact upon embryonic metabolism and developmental competence. C1 [Chason, Rebecca J.; Segars, James H.; DeCherney, Alan H.; Armant, D. Randall] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Csokmay, John] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Armant, D. Randall] Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. [Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Armant, D. Randall] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. RP Armant, DR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. EM D.Armant@Wayne.edu OI Armant, D. Randall/0000-0001-5904-9325 FU NIH [HD045966]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported in part by the Intramural Research Program of the NIH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and NIH grant HD045966 (to D.R.A.). NR 108 TC 35 Z9 36 U1 2 U2 17 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD OCT PY 2011 VL 22 IS 10 BP 412 EP 420 DI 10.1016/j.tem.2011.05.005 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 835LI UT WOS:000296037500004 PM 21741268 ER PT J AU Compton, P AF Compton, P. TI Acquisition of immunity against malaria: are we anywhere near understanding it? SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Compton, P.] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2011 VL 16 SU 1 SI SI BP 10 EP 10 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 828RC UT WOS:000295519100010 ER PT J AU Doumbia, S Lopera-Mesa, TM Diakite, SAS Konate, D Traore, K Doumbia, M Tullo, G Miura, K Anderson, JM Fay, MP AF Doumbia, S. Lopera-Mesa, T. M. Diakite, S. A. S. Konate, D. Traore, K. Doumbia, M. Tullo, G. Miura, K. Anderson, J. M. Fay, M. P. TI The importance of hemoglobin level at enrollment on subsequent malaria risk: results from a pediatric cohort in Mali, West Africa SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Doumbia, S.; Diakite, S. A. S.; Konate, D.; Traore, K.; Doumbia, M.] MRTC, Bamako, Mali. [Lopera-Mesa, T. M.; Tullo, G.; Miura, K.; Anderson, J. M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Fay, M. P.] NIAID, Biostat Res Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2011 VL 16 SU 1 SI SI BP 99 EP 99 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 828RC UT WOS:000295519100279 ER PT J AU Pindolia, D Wesolowski, A Garcia, A Eagle, N Buckee, C Smith, D Tatem, A AF Pindolia, D. Wesolowski, A. Garcia, A. Eagle, N. Buckee, C. Smith, D. Tatem, A. TI Mapping communities in networks for malaria transmission and control in Kenya SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Pindolia, D.; Garcia, A.; Tatem, A.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA. [Pindolia, D.; Garcia, A.; Smith, D.; Tatem, A.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA. [Pindolia, D.] Univ Oxford, Collaborat Programme, Malaria Publ Hlth & Epidemiol Grp, Ctr Geog Med,KEMRI Wellcome Trust, Nairobi, Kenya. [Eagle, N.; Buckee, C.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Cambridge, MA 02138 USA. [Smith, D.] Ctr Dis Dynam Econ & policy, Washington, DC USA. [Tatem, A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2011 VL 16 SU 1 SI SI BP 130 EP 130 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 828RC UT WOS:000295519100371 ER PT J AU Kumar, R Ansari, NA Gautam, S Nylen, S Singh, OP Sundar, S Sacks, D AF Kumar, R. Ansari, N. A. Gautam, S. Nylen, S. Singh, O. P. Sundar, S. Sacks, D. TI IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Kumar, R.; Ansari, N. A.; Gautam, S.; Singh, O. P.; Sundar, S.] Banaras Hindu Univ, Varanasi 221005, Uttar Pradesh, India. [Ansari, N. A.; Sacks, D.] NIAID, NIH, Bethesda, MD 20892 USA. [Nylen, S.] Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2011 VL 16 SU 1 SI SI BP 188 EP 188 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 828RC UT WOS:000295519100555 ER PT J AU Akhavan, AA Yaghoobi-Ershadi, MR Khamesipour, A Mirhendi, H Alimohammadian, MH Rassi, Y Bates, P Kamhawi, S Valenzuela, JG Arandian, MH Jafari, R Abdoli, H Shareghi, N Ghanei, M Jalali-Zand, N AF Akhavan, A. A. Yaghoobi-Ershadi, M. R. Khamesipour, A. Mirhendi, H. Alimohammadian, M. H. Rassi, Y. Bates, P. Kamhawi, S. Valenzuela, J. G. Arandian, M. H. Jafari, R. Abdoli, H. Shareghi, N. Ghanei, M. Jalali-Zand, N. TI Leishmania mixed infection in great gerbil populations of endemic areas of zoonotic cutaneous leishmaniasis in central Iran SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Akhavan, A. A.; Yaghoobi-Ershadi, M. R.; Rassi, Y.] Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Entomol & Vector Control, Tehran, Iran. [Khamesipour, A.] Univ Tehran Med Sci, Ctr Res & Training Skin Dis & Leprosy, Tehran, Iran. [Mirhendi, H.] Univ Tehran Med Sci, Sch Publ Hlth, Dept Med Parasitol & Mycol, Tehran, Iran. [Alimohammadian, M. H.] Pasteur Inst Iran, Dept Immunol, Tehran, Iran. [Bates, P.] Univ Lancaster, Sch Hlth & Med, Div Biomed & Life Sci, Lancaster, England. [Kamhawi, S.; Valenzuela, J. G.; Jafari, R.; Abdoli, H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Arandian, M. H.; Shareghi, N.] Univ Tehran Med Sci, Natl Inst Hlth Res, Esfahan Hlth Res Ctr, Tehran, Iran. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2011 VL 16 SU 1 SI SI BP 212 EP 212 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 828RC UT WOS:000295519100628 ER PT J AU Mishra, S Undrovinas, NA Maltsev, VA Reznikov, V Sabbah, HN Undrovinas, A AF Mishra, Sudhish Undrovinas, Nidas A. Maltsev, Victor A. Reznikov, Vitaliy Sabbah, Hani N. Undrovinas, Albertas TI Post-transcriptional silencing of SCN1B and SCN2B genes modulates late sodium current in cardiac myocytes from normal dogs and dogs with chronic heart failure SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE action potential; in silico simulation ID RAT VENTRICULAR MYOCYTES; BETA-SUBUNITS; AUXILIARY SUBUNIT; ACTION-POTENTIALS; CHANNEL BETA-4; FAILING HEART; CANINE MODEL; CARDIOMYOCYTES; NA(V)1.5; CONTRACTION AB Mishra S, Undrovinas NA, Maltsev VA, Reznikov V, Sabbah HN, Undrovinas A. Post-transcriptional silencing of SCN1B and SCN2B genes modulates late sodium current in cardiac myocytes from normal dogs and dogs with chronic heart failure. Am J Physiol Heart Circ Physiol 301: H1596-H1605, 2011. First published June 24, 2011; doi:10.1152/ajpheart.00948.2009.-The emerging paradigm for Na(+) current in heart failure (HF) is that its transient component (I(NaT)) responsible for the action potential (AP) upstroke is decreased, whereas the late component (I(NaL)) involved in AP plateau is augmented. Here we tested whether Na(v)beta(1)- and Na(v)beta(2)-subunits can modulate I(NaL) parameters in normal and failing ventricular cardiomyocytes (VCMs). Chronic HF was produced in nine dogs by multiple sequential coronary artery microembolizations, and six dogs served as a control. I(Na) and APs were measured by the whole cell and perforated patch-clamp in freshly isolated and cultured VCMs, respectively. I(NaL) was augmented with slower decay in HF VCMs compared with normal heart VCMs, and these properties remained unchanged within 5 days of culture. Posttranscriptional silencing SCN1B and SCN2B were achieved by virally delivered short interfering RNA (siRNA) specific to Na(v)beta(1)- and Na(v)beta(2). The delivery and efficiency of siRNA were evaluated by green fluorescent protein expression, by the real-time RT-PCR, and Western blots, respectively. Five days after infection, the levels of mRNA and protein for Na(v)beta(1) and Na(v)beta(2) were reduced by >80%, but mRNA and protein of Na(v)1.5, as well as I(NaT), remained unchanged in HF VCMs. Na(v)beta(1)-siRNA reduced I(NaL) density and accelerated I(NaL) two-exponential decay, whereas Na(v)beta(2)-siRNA produced an opposite effect in VCMs from both normal and failing hearts. Physiological importance of the discovered I(NaL) modulation to affect AP shape and duration was illustrated both experimentally and by numerical simulations of a VCM excitation-contraction coupling model. We conclude that in myocytes of normal and failing dog hearts Na(v)beta(1) and Na(v)beta(2) exhibit oppositely directed modulation of I(NaL). C1 [Mishra, Sudhish; Undrovinas, Nidas A.; Reznikov, Vitaliy; Sabbah, Hani N.; Undrovinas, Albertas] Henry Ford Hosp, Dept Internal Med, Detroit, MI 48202 USA. [Maltsev, Victor A.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Undrovinas, A (reprint author), Henry Ford Hosp, Dept Internal Med, Cardiovasc Res Educ & Res Bldg,Rm 4015,2799 W Gra, Detroit, MI 48202 USA. EM aundrov1@hfhs.org FU National Heart, Lung, and Blood Institute [HL-53819, HL-074238]; American Heart Association [0350472Z]; National Institute on Aging FX This study was supported by National Heart, Lung, and Blood Institute Grants HL-53819 and HL-074238, by a grant-in-aid from the American Heart Association (0350472Z; to A. Undrovinas), and, in part, by the Intramural Research Program of the National Institute on Aging (to V. A. Maltsev; the numerical modeling part). NR 50 TC 17 Z9 17 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2011 VL 301 IS 4 BP H1596 EP H1605 DI 10.1152/ajpheart.00948.2009 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 826NE UT WOS:000295360100042 PM 21705762 ER PT J AU Zhao, H Sun, JH Deschamps, AM Kim, G Liu, CY Murphy, E Levine, RL AF Zhao, Hang Sun, Junhui Deschamps, Anne M. Kim, Geumsoo Liu, Chengyu Murphy, Elizabeth Levine, Rodney L. TI Myristoylated methionine sulfoxide reductase A protects the heart from ischemia-reperfusion injury SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myristoylation; oxidative stress; reactive oxygen species ID OXIDATIVE STRESS; HYDROGEN-PEROXIDE; CARDIAC MYOCYTES; S-NITROSYLATION; A MSRA; MITOCHONDRIAL; PROTEINS; PEPTIDE; CELLS; LOCALIZATION AB Zhao H, Sun J, Deschamps AM, Kim G, Liu C, Murphy E, Levine RL. Myristoylated methionine sulfoxide reductase A protects the heart from ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 301: H1513-H1518, 2011. First published August 12, 2011; doi:10.1152/ajpheart.00441.2011.-Methionine sulfoxide reductase A (MsrA) catalytically scavenges reactive oxygen species and also repairs oxidized methionines in proteins. Increasing MsrA protects cells and organs from a variety of oxidative stresses while decreasing MsrA enhances damage, but the mechanisms of action have not been elucidated. A single gene encodes MsrA of which similar to 25% is targeted to the mitochondria, a major site of reactive oxygen species production. The other similar to 75% is targeted to the cytosol and is posttranslationally modified by myristoylation. To determine the relative importance of MsrA in each compartment in protecting against ischemia-reperfusion damage, we created a series of transgenic mice overexpressing MsrA targeted to the mitochondria or the cytosol. We used a Langendorff model of ischemia-reperfusion and assayed both the rate pressure product and infarct size following ischemia and reperfusion as measures of injury. While the mitochondrially targeted MsrA was expected to be protective, it was not. Notably, the cytosolic form was protective but only if myristoylated. The nonmyristoylated, cytosolic form offered no protection against injury. We conclude that cytosolic MsrA protects the heart from ischemia-reperfusion damage. The requirement for myristoylation suggests that MsrA must interact with a hydrophobic domain to provide protection. C1 [Zhao, Hang; Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Sun, Junhui; Deschamps, Anne M.; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Liu, Chengyu] NHLBI, Transgen Mouse Facil, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Rm 2351,50 South Dr,MSC 8012, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Zhao, Hang/A-2558-2012; Sun, Junhui/C-3499-2011; Levine, Rodney/D-9885-2011; OI Deschamps, Anne/0000-0001-7415-1408 FU National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute. NR 48 TC 20 Z9 20 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2011 VL 301 IS 4 BP H1513 EP H1518 DI 10.1152/ajpheart.00441.2011 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 826NE UT WOS:000295360100033 PM 21841012 ER PT J AU Mason, C Foster-Schubert, KE Imayama, I Kong, A Xiao, LR Bain, C Campbell, KL Wang, CY Duggan, CR Ulrich, CM Alfano, CM Blackburn, GL McTiernan, A AF Mason, Caitlin Foster-Schubert, Karen E. Imayama, Ikuyo Kong, Angela Xiao, Liren Bain, Carolyn Campbell, Kristin L. Wang, Ching-Yun Duggan, Catherine R. Ulrich, Cornelia M. Alfano, Catherine M. Blackburn, George L. McTiernan, Anne TI Dietary Weight Loss and Exercise Effects on Insulin Resistance in Postmenopausal Women SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID DIABETES PREVENTION PROGRAM; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE MODIFICATION; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITIES; FASTING GLUCOSE; OLDER-ADULTS; FOLLOW-UP; OBESITY AB Background: Comprehensive lifestyle interventions are effective in preventing diabetes and restoring glucose regulation; however, the key stimulus for change has not been identified and effects in older individuals are not established. The aim of the study was to investigate the independent and combined effects of dietary weight loss and exercise on insulin sensitivity and restoration of normal fasting glucose in middle-aged and older women. Design: Four-arm RCT, conducted between 2005 and 2009 and data analyzed in 2010. Setting/participants: 439 inactive, overweight/obese postmenopausal women. Interventions: Women were assigned to: dietary weight loss (n=118); exercise (n=117); exercise + diet (n=117); or control (n=87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity. Main outcome measures: 12-month change in serum insulin, C-peptide, fasting glucose, and whole body insulin resistance (HOMA-IR). Results: A significant improvement in HOMA-IR was detected in the diet (-24%, p<0.001) and exercise + diet (-26%, p<0.001) groups but not in the exercise (-9%, p=0.22) group compared with controls (-2%); these effects were similar in middle-aged (50-60 years) and older women (aged 60-75 years). Among those with impaired fasting glucose (5.6-6.9 mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal fasting glucose after adjusting for weight loss and baseline levels were 2.5 (0.8, 8.4); 2.76 (0.8, 10.0); and 3.1 (1.0, 9.9) in the diet, exercise + diet, and exercise group, respectively, compared with controls. Conclusions: Dietary weight loss, with or without exercise, significantly improved insulin resistance. Older women derived as much benefit as did the younger postmenopausal women. C1 [McTiernan, Anne] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Prevent Ctr, Seattle, WA 98109 USA. [Foster-Schubert, Karen E.; Wang, Ching-Yun; McTiernan, Anne] Univ Washington, Div Metab Endocrinol & Nutr, Sch Med, Seattle, WA 98109 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD USA. [Blackburn, George L.] Harvard Univ, Sch Med, Div Nutr, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Campbell, Kristin L.] Univ British Columbia, Dept Physiotherapy, Vancouver, BC V5Z 1M9, Canada. RP McTiernan, A (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Prevent Ctr, M4-B874,POB 19024, Seattle, WA 98109 USA. EM amctiern@fhcrc.org RI Duggan, Catherine/F-9414-2015 OI Duggan, Catherine/0000-0001-7369-4021 FU National Cancer Institute at the NIH [R01 CA102504, U54-CA116847, 5KL2RR025015-03, R25 CA94880, 2R25CA057699-16]; Canadian Institutes of Health Research FX This work was supported by the National Cancer Institute at the NIH (grant number: R01 CA102504, U54-CA116847, and 5KL2RR025015-03 to KFS, R25 CA94880 and 2R25CA057699-16 to AK) and the Canadian Institutes of Health Research (Fellowship to KLC and CM). None of the funding agencies were involved in the trial design or conduct. While working on the trial, CMA was employed at the Ohio State University, and located to NCI following completion of her effort on the NEW trial. NR 39 TC 44 Z9 44 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2011 VL 41 IS 4 BP 366 EP 375 DI 10.1016/j.amepre.2011.06.042 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 832FV UT WOS:000295789300004 PM 21961463 ER PT J AU Stange, KC AF Stange, Kurt C. TI Refocusing Knowledge Generation, Application, and Education Raising Our Gaze to Promote Health Across Boundaries SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID PRIMARY-CARE RESEARCH; PARTICIPATORY RESEARCH; TRANSDISCIPLINARY RESEARCH; COMPLEXITY SCIENCE; POPULATION HEALTH; RESEARCH NETWORKS; TEAM SCIENCE; MULTIMETHOD RESEARCH; FAMILY-PRACTICE; MIXED METHODS C1 [Stange, Kurt C.] Case Western Reserve Univ, Dept Family Med, Cleveland, OH 44106 USA. [Stange, Kurt C.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Stange, Kurt C.] Case Western Reserve Univ, Dept Sociol, Cleveland, OH 44106 USA. [Stange, Kurt C.] Cleveland Clin & Translat Sci Collaborat, Case Comprehens Canc Ctr, Cleveland, OH USA. [Stange, Kurt C.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Stange, KC (reprint author), Case Western Reserve Univ, Dept Family Med, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM kcs@case.edu FU NCRR NIH HHS [UL1 RR024989]; ODCDC CDC HHS [U36 CD319276, 5U36CD319276] NR 99 TC 8 Z9 8 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2011 VL 41 IS 4 SU 3 BP S164 EP S169 DI 10.1016/j.amepre.2011.06.022 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 832SK UT WOS:000295827300006 PM 21961659 ER PT J AU Zhang, W Yang, HC Wang, Q Yang, ZJ Chen, H Wang, SM Pan, ZM Tang, BJ Li, QQ Li, L AF Zhang, Wei Yang, Hsin-Chih Wang, Qi Yang, Zhi-Jun Chen, Hong Wang, Su-Mei Pan, Zhong-Mian Tang, Bu-Jian Li, Qingdi Quentin Li, Li TI Clinical Value of Combined Detection of Serum Matrix Metalloproteinase-9, Heparanase, and Cathepsin for Determining Ovarian Cancer Invasion and Metastasis SO ANTICANCER RESEARCH LA English DT Article DE Ovarian cancer; diagnosis; biomarkers; enzyme-linked immunosorbent assay; cathepsin; matrix metalloproteinase-9; heparanase ID MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; CERVICAL-CANCER; CYSTATIN-C; EXPRESSION; TUMORS; INHIBITORS; CARCINOMA AB Aim: This study evaluated the clinical value of the combined detection of serum cathepsin L (CL), heparanase (Hpa), and matrix metalloproteinase-9 (MMP-9) for determining the degree of ovarian cancer invasion and metastasis before surgery. Patients and Methods: Enzyme-linked immunosorbent assays were used to measure the serum content of CL, Hpa, and MMP-9 in 217 patients with untreated ovarian cancer before surgery, 100 patients with benign ovarian tumors, and 101 healthy women as controls. In addition, the degrees of invasion and metastasis were assessed by the 'gold standard' of clinicopathological diagnosis. The associations of the preoperative serum CL, Hpa, and MMP-9 levels with the clinicopathological factors and metastatic status were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the usefulness of these markers for determining the degree of ovarian cancer invasion before surgery. Results: The serum CL, Hpa, and MMP-9 levels were significantly higher (p=0.001) in patients with malignant ovarian cancer compared with patients with benign ovarian tumors and healthy controls. The serum CL level was significantly higher in patients with epithelial ovarian carcinoma compared with non-epithelial ovarian carcinoma (p=0.048), whereas the serum levels of Hpa (p=0.109) and MMP-9 (p=0.544) did not differ significantly between these two groups. The serum CL, Hpa, and MMP-9 levels correlated with the degree of differentiation and the FIGO staging (p>0.05). The serum CL (p=0.030) and MMP-9 (p=0.010) levels were significantly associated with peritoneal metastasis, and the serum Hpa level (p=0.042) was associated with distant metastasis. A ROC curve analysis revealed sensitivity of 60.9%, 69.6%, and 72.2%, and specificity of 57.4%, 67.2%, and 68.9% for the preoperative serum. levels of CL, Hpa, and MMP-9, respectively, as tumor markers for the degree of extra-pelvic metastasis. Conclusion: Elevated serum CL, Hpa, and MMP-9 levels are correlated with malignant invasion and progression in ovarian cancer. The combined detection of serum CL, Hpa, and MMP-9 may be useful for determining the extent of ovarian cancer metastasis before surgery. C1 [Li, Qingdi Quentin] NIAID, NIH, Bethesda, MD 20892 USA. [Zhang, Wei; Yang, Hsin-Chih; Wang, Qi; Yang, Zhi-Jun; Chen, Hong; Wang, Su-Mei; Pan, Zhong-Mian; Tang, Bu-Jian; Li, Li] Guangxi Med Univ, Canc Hosp, Dept Gynecol Oncol, Nanning 530021, Guangxi, Peoples R China. RP Li, QQ (reprint author), NIAID, NIH, Bldg 10,Room 11N234, Bethesda, MD 20892 USA. EM liquenti@mail.nih.gov; lili_temp@hotmail.com FU Provincial Research Project Funding of Guangxi, China [GSR 9817101] FX This study was supported by a grant from the Provincial Research Project Funding of Guangxi, China (No. GSR 9817101). NR 34 TC 25 Z9 29 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD OCT PY 2011 VL 31 IS 10 BP 3423 EP 3428 PG 6 WC Oncology SC Oncology GA 830PA UT WOS:000295667700041 PM 21965756 ER PT J AU Liang, HS Zhong, YH Luo, ZJ Huang, Y Lin, HD Zhan, S Xie, KQ Li, QQ AF Liang, Huasheng Zhong, Yuhua Luo, Zuojie Huang, Yu Lin, Huade Zhan, Song Xie, Kaiqing Li, Qingdi Quentin TI Diagnostic Value of 16 Cellular Tumor Markers for Metastatic Thyroid Cancer: An Immunohistochemical Study SO ANTICANCER RESEARCH LA English DT Article DE Thyroid cancer; biomarker; diagnosis; sensitivity; specificity; metastasis; immunohistochemistry ID E-CADHERIN EXPRESSION; FOLLICULAR CARCINOMA; GROWTH-FACTOR; PAPILLARY; CXCR4; METALLOPROTEINASE-9; ANGIOGENESIS; INDICATORS; INHIBITORS; FEATURES AB Background: The prognosis for thyroid cancer differs between metastatic and non-metastatic cases. To identify biomarkers useful for thyroid cancer diagnosis and to establish a marker panel for the early detection of metastatic thyroid carcinoma, this study compared histomorphological features and biomarker expression profiles in thyroid carcinomas according to pathological diagnoses. Patients and Methods: Thyroid carcinoma samples were obtained from 113 consecutive patients who underwent resection at multiple centers between 2001 and 2008. These cases included 63 metastatic thyroid tumors (34 papillary carcinomas, 20 follicular carcinomas, 9 undifferentiated carcinomas) and 50 non-metastatic thyroid tumors (36 papillary carcinomas, 14 follicular carcinomas). Tissue microarrays constructed using the 113 samples were analyzed by immunohistochemistry for the expression of 16 protein markers: MMP9, VEGF-C, E-cadherin, MMP2, PPAR gamma, PCNA, CXCR4, PTEN, C-myc, PTTG, HBME-1, p16, p53, FH1T, bFGF and hTERT. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and the predictive values of the identified biomarkers for metastasis in thyroid carcinoma were determined by receiver operating characteristic (ROC) curve analysis. Results: The expression of six proteins, VEGF-C, MMP2, CXCR4, PTTG, HBME-1 and bFGF, was up-regulated in metastatic compared to non-metastatic thyroid carcinoma. Multiple factor binary ordinal logistic regression analysis showed that MMP2, PTTG, VEGF-C, CXCR4 and bFGF were independent factors associated with the metastatic status of thyroid carcinoma. ROC curve analysis of these five proteins revealed that VEGF-C and bFGF were the most useful protein markers for the diagnosis of metastatic thyroid cancer. Conclusion: MMP2, PTTG, VEGF-C, CXCR4 and bFGF are potential cellular tumor markers for identifying thyroid cancer with greater risk for metastasis and the novel combination of VEGF-C and bFGF as biomarkers may improve the accuracy of early detection and the differential diagnosis between metastatic and non-metastatic thyroid carcinoma. C1 [Liang, Huasheng; Zhong, Yuhua] Guangxi Med Univ, Affiliated Hosp 9, Beihai Inst Endocrine & Metab Dis, Beihai 536000, Peoples R China. [Zhan, Song] Guangxi Med Univ, Affiliated Hosp 9, Dept Pathol, Beihai 536000, Peoples R China. [Luo, Zuojie] Guangxi Med Univ, Hosp 1, Dept Endocrinol, Nanning 530021, Peoples R China. [Huang, Yu] Guangxi Prov Hosp, Dept Hepatobiliary & Endocrine Surg, Nanning 530021, Peoples R China. [Lin, Huade] Pingnan Peoples Hosp, Dept Hepatobiliary & Endocrine Surg, Pingnan 537300, Peoples R China. [Xie, Kaiqing] So Med Univ, Nanfang Hosp, Guangzhou 510515, Guangdong, Peoples R China. [Li, Qingdi Quentin] NIH, Bethesda, MD 20892 USA. RP Zhong, YH (reprint author), Guangxi Med Univ, Affiliated Hosp 9, Beihai Inst Endocrine & Metab Dis, Beihai 536000, Peoples R China. EM flowchaos@yahoo.com.cn; zhongyh111@163.com FU Science and Technology Commission Foundation of Guangxi Province [0339080]; Guangxi Provincial Science Foundation for Young Scientists [0728108] FX We are grateful to Xiujiu Liang for her technical assistance and to Su Xuan for helping with the manuscript preparation. This study was supported by grants from the Applied Basic Research Programs of Science and Technology Commission Foundation of Guangxi Province (No. 0339080) and Guangxi Provincial Science Foundation for Young Scientists (No. 0728108). NR 24 TC 13 Z9 13 U1 0 U2 12 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD OCT PY 2011 VL 31 IS 10 BP 3433 EP 3440 PG 8 WC Oncology SC Oncology GA 830PA UT WOS:000295667700043 PM 21965758 ER PT J AU Iqbal, M Naeem, MA Riazuddin, SA Ali, S Farooq, T Qazi, ZA Khan, SN Husnain, T Riazuddin, S Sieving, PA Hejtmancik, JF Riazuddin, S AF Iqbal, Muhammad Naeem, Muhammad Asif Riazuddin, S. Amer Ali, Shahbaz Farooq, Tahir Qazi, Zaheeruddin A. Khan, Shaheen N. Husnain, Tayyab Riazuddin, Saima Sieving, Paul A. Hejtmancik, J. Fielding Riazuddin, Sheikh TI Association of Pathogenic Mutations in TULP1 With Retinitis Pigmentosa in Consanguineous Pakistani Families SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TUBBY-LIKE PROTEIN-1; GENE FAMILY; MEMBERS AB Objective: To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa in 5 consanguineous Pakistani families. Methods: Affected individuals in the families underwent a detailed ophthalmological examination that consisted of fundus photography and electroretinography. Blood samples were collected from all participating family members, and genomic DNA was extracted. A genome-wide linkage scan was performed, followed by exclusion analyses among our cohort of nuclear consanguineous families with microsatellite markers spanning the TULP1 locus on chromosome 6p. Two-point logarithm of odds scores were calculated, and all coding exons of TULP1 were sequenced bidirectionally. Results: The results of ophthalmological examinations among affected individuals in these 5 families were suggestive of retinitis pigmentosa. The genome-wide linkage scan localized the disease interval to chromosome 6p, harboring TULP1 in 1 of 5 families, and sequential analyses identified a single base pair substitution in TULP1 that results in threonine to alanine substitution (p.T380A). Subsequently, we investigated our entire cohort of families with autosomal recessive retinitis pigmentosa and identified 4 additional families with linkage to chromosome 6p, all of them harboring a single base pair substitution in TULP1 that results in lysine to arginine substitution (p.K489R). Results of single-nucleotide polymorphism haplotype analyses were suggestive of a common founder in these 4 families. Conclusion: Pathogenic mutations in TULP1 are responsible for the autosomal recessive retinitis pigmentosa phenotype in these consanguineous Pakistani families, with a single ancestral mutation in TULP1 causing the disease phenotype in 4 of 5 families. Clinical Relevance: Clinical and molecular characterization of pathogenic mutations in TULP1 will increase our understanding of retinitis pigmentosa at a molecular level. Arch Ophthalmol. 2011;129(10):1351-1357 C1 [Iqbal, Muhammad; Riazuddin, S. Amer; Ali, Shahbaz; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Saima; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst Johns Hopkins, Baltimore, MD USA. [Sieving, Paul A.; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD USA. [Riazuddin, Saima] Cincinnati Childrens Hosp Res Fdn, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH USA. [Riazuddin, Saima] Cincinnati Childrens Hosp Res Fdn, Div Ophthalmol, Cincinnati, OH USA. [Farooq, Tahir; Qazi, Zaheeruddin A.] Layton Rahmatulla Benevolent Trust Hosp, Lahore, Pakistan. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@aimrc.org; riaz@aimrc.org RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015 FU Higher Education Commission; Ministry of Science and Technology, Islamabad, Pakistan FX This study was supported in part by the Higher Education Commission and the Ministry of Science and Technology, Islamabad, Pakistan. NR 18 TC 6 Z9 6 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2011 VL 129 IS 10 BP 1351 EP 1357 PG 7 WC Ophthalmology SC Ophthalmology GA 830ZB UT WOS:000295697300013 PM 21987678 ER PT J AU Tsai, CJ Nussinov, R AF Tsai, Chung-Jung Nussinov, Ruth TI Gene-specific transcription activation via long-range allosteric shape-shifting SO BIOCHEMICAL JOURNAL LA English DT Review DE allosteric pathway; allosteric propagation; allostery; enhancer; mediator; transcription initiation; transcription regulation; transcription start site ID RNA-POLYMERASE-II; MEDIATOR SUBUNIT MED1/TRAP220; TUMOR-SUPPRESSOR P53; IN-VIVO; GLUCOCORTICOID-RECEPTOR; YEAST MEDIATOR; FUNCTIONAL-ORGANIZATION; PREINITIATION COMPLEX; STRUCTURAL DISORDER; ENERGY LANDSCAPES AB How is specificity transmitted over long distances at the molecular level? REs (regulatory elements) are often far from transcription start sites. In the present review we discuss possible mechanisms to explain how information from specific REs is conveyed to the basal transcription machinery through TFs (transcription factors) and the Mediator complex. We hypothesize that this occurs through allosteric pathways: binding of a TF to a RE results in changes in the AD (activation domain) of the TF, which binds to Mediator and alters the distribution of the Mediator conformations, thereby affecting transcription initiation/activation. We argue that Mediator is formed by highly disordered proteins with large densely packed interfaces that make efficient long-range signal propagation possible. We suggest two possible general mechanisms for Mediator action: one in which Mediator influences PIC (pre-initiation complex) assembly and transcription initiation, and another in which Mediator exerts its effect on the already assembled but stalled transcription complex. We summarize (i) relevant information from the literature about Mediator composition, organization and structure; (ii) Mediator interaction partners and their effect on Mediator conformation, function and correlation to the RNA Pol II (polymerase II) CTD (C-terminal domain) phosphorylation; and (iii) propose that different allosteric signal propagation pathways in Mediator relate to PIC assembly and polymerase activation of the stalled transcription complex. The emerging picture provides for the first time a mechanistic view of allosteric signalling from the RE sequence to transcription activation, and an insight into how gene specificity and signal transmission can take place in transcription initiation. C1 [Tsai, Chung-Jung; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Sci Program, SAIC Frederick, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov FU National Cancer Institute [HHSN261200800001E]; National Cancer Institute Center for Cancer Research FX The work of the authors has been funded in whole or in part by the National Cancer Institute under contract number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the National Cancer Institute Center for Cancer Research. NR 126 TC 22 Z9 23 U1 0 U2 12 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 2011 VL 439 BP 15 EP 25 DI 10.1042/BJ20110972 PN 1 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831YN UT WOS:000295767100002 PM 21916844 ER PT J AU Neddens, J Fish, KN Tricoire, L Vullhorst, D Shamir, A Chung, W Lewis, DA McBain, CJ Buonanno, A AF Neddens, Joerg Fish, Kenneth N. Tricoire, Ludovic Vullhorst, Detlef Shamir, Alon Chung, Wonjae Lewis, David A. McBain, Chris J. Buonanno, Andres TI Conserved Interneuron-Specific ErbB4 Expression in Frontal Cortex of Rodents, Monkeys, and Humans: Implications for Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Chandelier cell; gamma-aminobutyric acid (GABA); human; inhibition; neuregulin; parvalbumin; primate; schizophrenia ID PARVALBUMIN-POSITIVE INTERNEURONS; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; CORTICAL GABA NEURONS; TYROSINE KINASE; NEURAL DEVELOPMENT; PREFRONTAL CORTEX; KNOCKOUT MICE; NEUREGULIN-1; RECEPTORS AB Background: Neuregulin-1 and ErbB4 are genetically associated with schizophrenia, and detailed knowledge of the cellular and subcellular localization of ErbB4 is important for understanding how neuregulin-1 regulates neuronal network activity and behavior. Expression of ErbB4 is restricted to interneurons in the rodent hippocampus and cortex. However, controversy remains about the cellular expression pattern in primate brain and its subcellular distribution in postsynaptic somatodendritic locations versus presynaptic terminals. Methods: ErbB4 expression was analyzed in pyramidal cells and interneurons in the frontal cortex of five species: C57BL6 mice (n = 3), ErbB4-/- mice (n = 2), Sprague-Dawley rats (n = 3), two macaque species (n = 3 + 2), and humans (normal control subjects, n = 2). We investigated 1) messenger RNA in mice, macaques, and humans; 2) protein expression in all species using highly specific monoclonal antibodies; and 3) specificity tests of several ErbB4 antibodies on brain samples (mouse, macaque, human). Results: ErbB4 RNA is restricted to interneurons in the frontal cortex of mice. ErbB4 protein is undetectable in pyramidal cells of rodents, macaques, and human frontal cortex, whereas most interneurons positive for parvalbumin, calretinin, or cholecystokinin, but only a minority of calbindin-positive cells, co-express ErbB4 in macaques. Importantly, no presynaptic ErbB4 expression was detected in any species. Conclusions: The interneuron-selective somatodendritic expression of ErbB4 is consistent with a primary role of neuregulin-ErbB4 signaling in the postsynaptic modulation of gamma-aminobutyric acidergic function in rodents and primates. Our data validate the use of rodents to analyze effects of abnormal ErbB4 function as a means to model endophenotypes of psychiatric disorders. C1 [Neddens, Joerg; Vullhorst, Detlef; Shamir, Alon; Buonanno, Andres] NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Tricoire, Ludovic; McBain, Chris J.] NICHHD, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. [Fish, Kenneth N.; Chung, Wonjae; Lewis, David A.] Univ Pittsburgh, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA USA. [Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. RP Buonanno, A (reprint author), NICHHD, Mol Neurobiol Sect, NIH, 35 Lincoln Dr, Bethesda, MD 20892 USA. EM buonanno@mail.nih.gov RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health [MH085108, MH051234] FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (AB, CJM), and National Institutes of Health Grants MH085108 (KNF) and MH051234 (DAL). JN is currently affiliated with the Department of Histology, JSW Life Sciences GmbH, Graz-Grambach, Austria. LT is currently affiliated with the Laboratoire de Neurobiologie des processus adaptatifs, Universite Pierre et Marie Curie, Paris, France. NR 48 TC 39 Z9 40 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2011 VL 70 IS 7 BP 636 EP 645 DI 10.1016/j.biopsych.2011.04.016 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 829PI UT WOS:000295595800007 PM 21664604 ER PT J AU Sabichi, AL Lee, JJ Grossman, HB Liu, SY Richmond, E Czerniak, BA De la Cerda, J Eagle, C Viner, JL Palmer, JL Lerner, SP AF Sabichi, Anita L. Lee, J. Jack Grossman, H. Barton Liu, Suyu Richmond, Ellen Czerniak, Bogdan A. De la Cerda, Jorge Eagle, Craig Viner, Jaye L. Palmer, J. Lynn Lerner, Seth P. TI A Randomized Controlled Trial of Celecoxib to Prevent Recurrence of Nonmuscle-Invasive Bladder Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; BACILLUS-CALMETTE-GUERIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; URINARY-BLADDER; CLINICAL-TRIALS; IN-SITU; CARDIOVASCULAR RISK; ADENOMA PREVENTION; COLORECTAL-CANCER; COX-2 INHIBITORS AB Significant morbidity and expense result from frequent recurrences of nonmuscle-invasive bladder cancer (NMIBC) after standard treatment, and carcinoma in situ (Tis) is a poor prognostic factor. Predicated on observational and preclinical data strongly supporting cyclooxygenase-2 (COX-2) in the pathogenesis, and the activity of COX-2 inhibitors, in bladder cancer, we conducted a randomized, double-blind, placebo-controlled trial to determine whether celecoxib could reduce the time-to-recurrence (TTR) in NMIBC patients at high risk for recurrence. A total of 146 patients were randomized to celecoxib (200 mg) or placebo orally twice daily for at least 12 months. The average treatment duration was 1.25 years. Primary intent-to-treat analysis revealed celecoxib did not statistically significantly prolong TTR compared with placebo (P 0.17, log rank) with a median follow-up of 2.49 years. The recurrence-free rate at 12 months with celecoxib was 88% (95% CI: 0.81-0.96) versus 78% (95% CI: 0.69-0.89) with placebo. After controlling for covariates with Cox regression analysis, recurrence rates did not differ between the two study arms (HR 0.69; 95% CI: 0.37-1.29). However, celecoxib had a marginally significant effect on reducing meta-chronous recurrences (vs. placebo) with HR of 0.56 (95% CI: 0.3-1.06; P 0.075). Celecoxib was well tolerated, with similar adverse events and quality-of-life in both arms. Our clinical trial results do not show a clinical benefit for celecoxib in preventing NMIBC recurrence but further investigation of COX-2 inhibitors in this setting is warranted. Cancer Prev Res; 4(10); 1580-9. (C)2011 AACR. C1 [Sabichi, Anita L.] Baylor Coll Med, Dept Med, Div Hematol Oncol, Houston, TX 77030 USA. [Lerner, Seth P.] Baylor Coll Med, Dept Urol, Houston, TX 77030 USA. [Lee, J. Jack; Liu, Suyu; Palmer, J. Lynn] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA. [Grossman, H. Barton; De la Cerda, Jorge] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX USA. [Czerniak, Bogdan A.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Richmond, Ellen; Viner, Jaye L.] NCI, Rockville, MD USA. [Eagle, Craig] Pfizer Pharmaceut Inc, New York, NY USA. [Viner, Jaye L.] Medimmune Inc, Gaithersburg, MD 20878 USA. RP Sabichi, AL (reprint author), Baylor Coll Med, Dept Med, Div Hematol Oncol, 1 Baylor Plaza,MS BCM 187, Houston, TX 77030 USA. EM sabichi@bcm.edu; jjlee@mdanderson.org FU Pfizer; NIH; NCI [N01-CN-85186]; Pfizer Pharmaceuticals; MD Anderson Cancer Center [CA016672] FX This work was funded for the conduct of the study at the satellite accrual sites (but not at the parent site of MDACC or Baylor) by Pfizer. NIH, NCI, N01-CN-85186, Pfizer Pharmaceuticals, MD Anderson Cancer Center Support grant CA016672. NR 54 TC 18 Z9 19 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2011 VL 4 IS 10 BP 1580 EP 1589 DI 10.1158/1940-6207.CAPR-11-0036 PG 10 WC Oncology SC Oncology GA 829XP UT WOS:000295620000010 PM 21881030 ER PT J AU Rotunno, M Hu, N Su, H Wang, CY Goldstein, AM Bergen, AW Consonni, D Pesatori, AC Bertazzi, PA Wacholder, S Shih, J Caporaso, NE Taylor, PR Landi, MT AF Rotunno, Melissa Hu, Nan Su, Hua Wang, Chaoyu Goldstein, Alisa M. Bergen, Andrew W. Consonni, Dario Pesatori, Angela C. Bertazzi, Pier Alberto Wacholder, Sholom Shih, Joanna Caporaso, Neil E. Taylor, Phil R. Landi, Maria Teresa TI A Gene Expression Signature from Peripheral Whole Blood for Stage I Lung Adenocarcinoma SO CANCER PREVENTION RESEARCH LA English DT Article ID MESSENGER-RNA EXPRESSION; PROSTATE-CANCER; MICROARRAY ANALYSIS; ETIOLOGY EAGLE; CELL CARCINOMA; BREAST-CANCER; RUNX3 GENE; RT-PCR; RISK; PROGRESSION AB Affordable early screening in subjects with high risk of lung cancer has great potential to improve survival from this deadly disease. We measured gene expression from lung tissue and peripheral whole blood (PWB) from adenocarcinoma cases and controls to identify dysregulated lung cancer genes that could be tested in blood to improve identification of at-risk patients in the future. Genome-wide mRNA expression analysis was conducted in 153 subjects (73 adenocarcinoma cases, 80 controls) from the Environment And Genetics in Lung cancer Etiology study using PWB and paired snap-frozen tumor and noninvolved lung tissue samples. Analyses were conducted using unpaired t tests, linear mixed effects, and ANOVA models. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the identified biomarkers. We identified 50 dysregulated genes in stage I adenocarcinoma versus control PWB samples (false discovery rate <= 0.1, fold change >= 1.5 or <= 0.66). Among them, eight (TGFBR3, RUNX3, TRGC2, TRGV9, TARP, ACP1, VCAN, and TSTA3) differentiated paired tumor versus noninvolved lung tissue samples in stage I cases, suggesting a similar pattern of lung cancer-related changes in PWB and lung tissue. These results were confirmed in two independent gene expression analyses in a blood-based case-control study (n = 212) and a tumor-nontumor paired tissue study (n 54). The eight genes discriminated patients with lung cancer from healthy controls with high accuracy (AUC = 0.81, 95% CI = 0.74-0.87). Our finding suggests the use of gene expression from PWB for the identification of early detection markers of lung cancer in the future. Cancer Prev Res; 4(10); 1599-608. (C)2011 AACR. C1 [Rotunno, Melissa; Hu, Nan; Su, Hua; Wang, Chaoyu; Goldstein, Alisa M.; Bergen, Andrew W.; Wacholder, Sholom; Caporaso, Neil E.; Taylor, Phil R.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Shih, Joanna] NCI, Div Canc Treatment & Diag, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. [Consonni, Dario; Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, Fdn IRCCS Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy. [Consonni, Dario; Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, Dept Occupat & Environm Hlth, Milan, Italy. RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,MSC 7114, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI bertazzi, pietro alberto/D-5039-2017; OI bertazzi, pietro alberto/0000-0003-3475-2449; Bergen, Andrew/0000-0002-1237-7644; pesatori, angela/0000-0002-0261-3252 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD FX This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD. NR 47 TC 27 Z9 28 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2011 VL 4 IS 10 BP 1599 EP 1608 DI 10.1158/1940-6207.CAPR-10-0170 PG 10 WC Oncology SC Oncology GA 829XP UT WOS:000295620000012 PM 21742797 ER PT J AU Chandra, A Latov, N Wormser, GP Marques, AR Alaedini, A AF Chandra, Abhishek Latov, Norman Wormser, Gary P. Marques, Adriana R. Alaedini, Armin TI Epitope mapping of antibodies to VlsE protein of Borrelia burgdorferi in post-Lyme disease syndrome SO CLINICAL IMMUNOLOGY LA English DT Article DE Lyme disease; Post-Lyme disease syndrome; Chronic Lyme disease; VlsE; Epitope mapping; Antibody ID IMMUNODOMINANT CONSERVED REGION; VARIABLE SURFACE-ANTIGEN; ANTIBIOTIC-TREATMENT; PERSISTENT SYMPTOMS; DIAGNOSIS; HISTORY; PEPTIDE; DOMAIN; VIRUS; TRIAL AB The VlsE lipoprotein of Borrelia burgdorferi elicits a strong immune response during the course of Lyme disease. The present study was aimed at characterization of the epitopes of VlsE targeted by the antibody response in patients with post-Lyme disease syndrome, a condition characterized by persisting symptoms of pain, fatigue, and/or neurocognitive impairment despite antibiotic treatment of B. burgdorferi infection. Epitope mapping was carried out using microarrays that contained synthesized overlapping peptides covering the full sequence of VlsE from B. burgdorferi B31. In addition to the previously characterized IR6 region in the variable domain, specific sequences in the N- and C-terminal invariable domains of VlsE were found to be major B cell epitopes in affected patients. The crystal structure of VlsE indicated that the newly described epitopes form a contiguous region in the surface-exposed membrane-proximal part of the monomeric form of the protein. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chandra, Abhishek; Latov, Norman; Alaedini, Armin] Cornell Univ, Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. [Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. [Marques, Adriana R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Alaedini, A (reprint author), Columbia Univ, Med Ctr, Dept Med, 1130 St Nicholas Ave,Room 937, New York, NY 10032 USA. EM aa819@columbia.edu FU National Institutes of Health (NIH) [AI071180-02, N01-AI-65308] FX This work was supported by the National Institutes of Health (NIH) [grant number AI071180-02 to A. Alaedini] and involved the use of specimens derived from an NIH-supported repository [contract number N01-AI-65308]. It was also supported in part by the Intramural Research Program of the NIH. We are indebted to Dr. Phillip J. Baker at NIH for his invaluable support and guidance throughout this project. We thank Ms. Diane Holmgren, Ms. Donna McKenna, and Ms. Susan Bittker for their assistance with specimen collection and organization. NR 28 TC 10 Z9 10 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD OCT PY 2011 VL 141 IS 1 BP 103 EP 110 DI 10.1016/j.clim.2011.06.005 PG 8 WC Immunology SC Immunology GA 829EC UT WOS:000295558500012 PM 21778118 ER PT J AU Glasier, A Cameron, ST Blithe, D Scherrer, B Mathe, H Levy, D Gainer, E Ulmann, A AF Glasier, Anna Cameron, Sharon T. Blithe, Diana Scherrer, Bruno Mathe, Henri Levy, Delphine Gainer, Erin Ulmann, Andre TI Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel SO CONTRACEPTION LA English DT Article DE Emergency contraception; Ulipristal acetate; Levonorgestrel; Risk factors ID CONCEPTION; RATES; PROBABILITY; INTERCOURSE; FAILURE; REGIMEN; OBESITY; WEIGHT; PILL AB Background: Emergency contraception (EC) does not always work. Clinicians should be aware of potential risk factors for EC failure. Study Design: Data from a meta-analysis of two randomized controlled trials comparing the efficacy of ulipristal acetate (UPA) with levonorgestrel were analyzed to identify factors associated with EC failure. Results: The risk of pregnancy was more than threefold greater for obese women compared with women with normal body mass index (odds ratio (OR), 3.60; 95% confidence interval (CI), 1.96-6.53; p<.0001), whichever EC was taken. However, for obese women, the risk was greater for those taking levonorgestrel (OR, 4.41; 95% CI, 2.05-9.44, p=.0002) than for UPA users (OR, 2.62; 95% CI, 0.89-7.00; ns). For both ECs, pregnancy risk was related to the cycle day of intercourse. Women who had intercourse the day before estimated day of ovulation had a fourfold increased risk of pregnancy (OR, 4.42; 95% CI, 2.33-8.20; p<.0001) compared with women having sex outside the fertile window. For both methods, women who had unprotected intercourse after using EC were more likely to get pregnant than those who did not (OR, 4.64; 95% CI, 2.22-8.96; p=.0002). Conclusions: Women who have intercourse around ovulation should ideally be offered a copper intrauterine device. Women with body mass index >25 kg/m(2) should be offered an intrauterine device or UPA. All women should be advised to start effective contraception immediately after EC. (C) 2011 Elsevier Inc. All rights reserved. C1 [Glasier, Anna; Cameron, Sharon T.] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. [Blithe, Diana] NICHHD, Bethesda, MD 20892 USA. [Scherrer, Bruno; Mathe, Henri; Levy, Delphine; Gainer, Erin; Ulmann, Andre] HRA Phrama, Paris, France. RP Glasier, A (reprint author), Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. EM anna.glasier@ed.ac.uk NR 32 TC 97 Z9 97 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD OCT PY 2011 VL 84 IS 4 BP 363 EP 367 DI 10.1016/j.contraception.2011.02.009 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 829DY UT WOS:000295557900004 PM 21920190 ER PT J AU Frush, S Li, ZW Potts, EN Du, WL Eu, JP Garantziotis, S He, YW Foster, WM Hollingsworth, JW AF Frush, Sarah Li, Zhuowei Potts, Erin N. Du, Wanglei Eu, Jerry P. Garantziotis, Stavros He, You-Wen Foster, W. Michael Hollingsworth, John W. TI The Role of the Extracellular Matrix Protein Mindin in Airway Response to Environmental Airways Injury (Retracted article. See vol. 124, pg. A69, 2016) SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Retracted Publication DE airway smooth muscle; endotoxin; innate immunity; lipopolysaccharide; LPS; lung; mindin; ozone; Tlr4; toll-like receptor ID INDUCED LUNG INFLAMMATION; TOLL-LIKE RECEPTOR-4; OZONE EXPOSURE; GRAIN DUST; FLOW OBSTRUCTION; DAILY MORTALITY; CUTTING EDGE; GUINEA-PIG; MOUSE LUNG; TLR4 AB Background: Our previous work demonstrated that the extracellular matrix protein mindin contributes to allergic airways disease. However, the role of mindin in non-allergic airways disease has not previously been explored. Objectives: We hypothesized that mindin would contribute to airways disease after inhalation of either lipopolysaccharide (LPS) or ozone. Methods: We exposed C57BL/6J and mindin-deficient ((-/-)) mice to aerosolized LPS (0.9 mu g/m(3) for 2.5 hr), saline, ozone (1 ppm for 3 hr), or filtered air (FA). All mice were evaluated 4 hr after LPS/saline exposure or 24 hr after ozone/FA exposure. We characterized the physiological and biological responses by analysis of airway hyperresponsiveness (AHR) with a computer-controlled small-animal ventilator (FlexiVent), inflammatory cellular recruitment, total protein in bronchoalveolar lavage fluid (BALF), pro-inflammatory cytokine profiling, and ex vivo bronchial ring studies. Results: After inhalation of LPS, mindin(-/-) mice demonstrated significantly reduced total cell and neutrophil recruitment into the airspace compared with their wild-type counter-parts. Mindin(-/-) mice also exhibited reduced pro-inflammatory cytokine production and lower AHR to methacholine challenge by FlexiVent. After inhalation of ozone, mice had no detectible differences in cellular inflammation or total BALF protein dependent on mindin. However, mindin(-/-) mice were protected from increased pro-inflammatory cytokine production and AHR compared with their C57BL/6J counter-parts. After ozone exposure, bronchial rings derived from mindin(-/-) mice demonstrated reduced constriction in response to carbachol. Conclusions: These data demonstrate that the extracellular matrix protein mindin modifies the airway response to both LPS and ozone. Our data support a conserved role of mindin in production of pro-inflammatory cytokines and the development of AHR in two divergent models of reactive airways disease, as well as a role of mindin in airway smooth muscle contractility after exposure to ozone. C1 [Frush, Sarah; Li, Zhuowei; Potts, Erin N.; Du, Wanglei; Eu, Jerry P.; Foster, W. Michael; Hollingsworth, John W.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Dept Med, Durham, NC 27710 USA. [Garantziotis, Stavros] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [He, You-Wen; Hollingsworth, John W.] Duke Univ, Dept Immunol, Durham, NC 27710 USA. RP Hollingsworth, JW (reprint author), Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Dept Med, Box 103004, Durham, NC 27710 USA. EM john.hollingsworth@duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU National Institutes of Health [ES016126, ES02046, ES016347, HL081825] FX This work was supported by National Institutes of Health grants to J.W.H. (ES016126, ES02046), W.M.F. (ES016347), and J.P.E. (HL081825). NR 45 TC 6 Z9 7 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2011 VL 119 IS 10 BP 1403 EP 1408 DI 10.1289/ehp.1003339 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 827CA UT WOS:000295402400024 PM 21684833 ER PT J AU Barth, H Rybczynska, J Patient, R Choi, Y Sapp, RK Baumert, TF Krawczynski, K Liang, TJ AF Barth, Heidi Rybczynska, Jolanta Patient, Romuald Choi, Youkyung Sapp, Ronda K. Baumert, Thomas F. Krawczynski, Kris Liang, T. Jake TI Both Innate and Adaptive Immunity Mediate Protective Immunity Against Hepatitis C Virus Infection in Chimpanzees SO HEPATOLOGY LA English DT Article ID RECOVERED CHIMPANZEES; DENDRITIC CELLS; RESPONSES; REINFECTION; RECHALLENGE; INTERFERON; GENOTYPE; PERSISTENCE; CLEARANCE; KINETICS AB Understanding the immunological correlates associated with protective immunity following hepatitis C virus (HCV) reexposure is a prerequisite for the design of effective HCV vaccines and immunotherapeutics. In this study we performed a comprehensive analysis of innate and adaptive immunity following HCV reexposure of two chimpanzees that had previously recovered from HCV-JFH1 infection. One of the chimpanzees, CH10274, became protected from active viremia by repeated challenges with homologous HCV-JFH1 and developed neutralizing antibodies, but was later infected with high-level viremia by a heterologous challenge with the HCV H77 virus that persisted for more than 1 year. The other chimpanzee, CH10273, was protected from a similar, heterologous H77 challenge without any evidence of neutralizing antibodies. Peripheral HCV-specific T-cell responses were present in both chimpanzees after challenges and, interestingly, the overall magnitude of response was lower in uninfected CH10273, which, however, exhibited a more robust CD8+ T-cell response. CH10273 showed higher hepatic expression of CD8 and CD56 (natural killer) markers than CH10274 did shortly after inoculation with H77. The heightened T-cell response was associated with an enhanced hepatic production of interferons (both type I and II) and interferon-stimulated genes (ISGs) in CH10273. Therefore, protection or clearance of HCV reinfection upon heterologous rechallenge depends on the activation of both intrahepatic innate and cellular immune responses. Furthermore, our results suggest that serum neutralizing antibodies may contribute to early control of viral replication and spread after homologous HCV rechallenges but may not be sufficient for a long-term protective immunity. Conclusion: Our study shows that protective immunity against HCV reinfection is orchestrated by a complex network of innate and adaptive immune responses. (HEPATOLOGY 2011;54:1135-1148) C1 [Barth, Heidi; Patient, Romuald; Sapp, Ronda K.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Barth, Heidi; Baumert, Thomas F.] INSERM, U748, Strasbourg, France. [Barth, Heidi; Baumert, Thomas F.] Univ Strasbourg, Strasbourg, France. [Rybczynska, Jolanta; Choi, Youkyung; Krawczynski, Kris] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA. [Patient, Romuald] INSERM, Dept Biol Cellulaire, U966, Tours, France. [Baumert, Thomas F.] Hop Univ Strasbourg, Strasbourg, France. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM kzk1@cdc.gov; JakeL@bdg10.niddk.nih.gov FU Deutsche Forschungsgemeinschaft, Bonn, Germany [BA 3643/1-1]; National Institute of Diabetes and Digestive and Kidney Diseases; NIH; Division of Viral Hepatitis; NCHHSTP; CDC; Agence Nationale de Recherche sur le SIDA et les Hepatites Virales [2010-106, 2010-242]; Inserm, France FX Supported by the Deutsche Forschungsgemeinschaft, Bonn, Germany (BA 3643/1-1 to H.B.), the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, and programmatic support of Division of Viral Hepatitis, NCHHSTP, CDC, and the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (2010-106; 2010-242 to H.B.), and Inserm, France. NR 30 TC 29 Z9 31 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 IS 4 BP 1135 EP 1148 DI 10.1002/hep.24489 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KA UT WOS:000295577200006 PM 21674561 ER PT J AU Baghdasaryan, A Claudel, T Gumhold, J Silbert, D Adorini, L Roda, A Vecchiotti, S Gonzalez, FJ Schoonjans, K Strazzabosco, M Fickert, P Trauner, M AF Baghdasaryan, Anna Claudel, Thierry Gumhold, Judith Silbert, Dagmar Adorini, Luciano Roda, Aldo Vecchiotti, Stefania Gonzalez, Frank J. Schoonjans, Kristina Strazzabosco, Mario Fickert, Peter Trauner, Michael TI Dual Farnesoid X Receptor/TGR5 Agonist INT-767 Reduces Liver Injury in the Mdr2(-/-) (Abcb4(-/-)) Mouse Cholangiopathy Model by Promoting Biliary HCO3- Output SO HEPATOLOGY LA English DT Article ID TRANSMEMBRANE CARBONIC-ANHYDRASE; HUMAN GALLBLADDER EPITHELIUM; BILE-ACID-HOMEOSTASIS; NUCLEAR RECEPTOR; SCLEROSING CHOLANGITIS; CL-/HCO3-EXCHANGER; URSODEOXYCHOLIC ACID; TRANSPORT METABOLON; RAT HEPATOCYTES; KNOCKOUT MICE AB Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. The nuclear farnesoid X receptor (FXR) and the membrane G protein-coupled receptor, TGR5, regulate bile acid (BA) homeostasis and inflammation. Therefore, we hypothesized that activation of FXR and/or TGR5 could ameliorate liver injury in Mdr2(-/-) (Abcb4(-/-)) mice, a model of chronic cholangiopathy. Hepatic inflammation, fibrosis, as well as bile secretion and key genes of BA homeostasis were addressed in Mdr2(-/-) mice fed either a chow diet or a diet supplemented with the FXR agonist, INT-747, the TGR5 agonist, INT-777, or the dual FXR/TGR5 agonist, INT-767 (0.03% w/w). Only the dual FXR/TGR5 agonist, INT-767, significantly improved serum liver enzymes, hepatic inflammation, and biliary fibrosis in Mdr2(-/-) mice, whereas INT-747 and INT-777 had no hepatoprotective effects. In line with this, INT-767 significantly induced bile flow and biliary HCO3- output, as well as gene expression of carbonic anhydrase 14, an important enzyme able to enhance HCO3- transport, in an Fxr-dependent manner. In addition, INT-767 dramatically reduced bile acid synthesis via the induction of ileal Fgf15 and hepatic Shp gene expression, thus resulting in significantly reduced biliary bile acid output in Mdr2(-/-) mice. Conclusion: This study shows that FXR activation improves liver injury in a mouse model of chronic cholangiopathy by reduction of biliary BA output and promotion of HCO3- -rich bile secretion. (HEPATOLOGY 2011;54:1303-1312) C1 [Claudel, Thierry; Trauner, Michael] Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, A-1090 Vienna, Austria. [Baghdasaryan, Anna; Claudel, Thierry; Gumhold, Judith; Silbert, Dagmar; Fickert, Peter; Trauner, Michael] Med Univ Graz, Lab Expt & Mol Hepatol, Div Gastroenterol & Hepatol, Dept Internal Med, Graz, Austria. [Adorini, Luciano] Intercept Pharmaceut, New York, NY USA. [Roda, Aldo; Vecchiotti, Stefania] Univ Bologna, Dept Pharmaceut Sci, Lab Bioanalyt & Analyt Chem, I-40126 Bologna, Italy. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Schoonjans, Kristina] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, Lausanne, Switzerland. [Strazzabosco, Mario] Yale Univ, Sch Med, Dept Internal Med, Sect Digest Dis, New Haven, CT 06510 USA. [Strazzabosco, Mario] Univ Milano Bicocca, Dept Clin Med & Prevent, Milan, Italy. RP Trauner, M (reprint author), Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Internal Med 3, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM michael.trauner@meduniwien.ac.at OI Fickert, Peter/0000-0003-0906-4636 FU Austrian Science Foundation [P18613-B05, P19118, SFB 3008]; Swiss National Science Foundation [SNF 31003A-125487/1]; Medical University of Graz; Intercept FX This work was supported by the Austrian Science Foundation (grant nos. P18613-B05, P19118, and SFB 3008; to M.T.), the Swiss National Science Foundation (grant no. SNF 31003A-125487/1; to K.S.), and by the PhD Program of the Medical University of Graz (to A.B.).; Dr. Adornini owns stock in Intercept. Dr. Trauner is a consultant for Phenex. He is on the speakers' bureau of Falk and received grants from Intercept. NR 65 TC 71 Z9 72 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 IS 4 BP 1303 EP 1312 DI 10.1002/hep.24537 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KA UT WOS:000295577200022 PM 22006858 ER PT J AU Berg, CL Merion, RM Shearon, TH Olthoff, KM Brown, RS Baker, TB Everson, GT Hong, JC Terrault, N Hayashi, PH Fisher, RA Everhart, JE AF Berg, Carl L. Merion, Robert M. Shearon, Tempie H. Olthoff, Kim M. Brown, Robert S., Jr. Baker, Talia B. Everson, Gregory T. Hong, Johnny C. Terrault, Norah Hayashi, Paul H. Fisher, Robert A. Everhart, James E. TI Liver Transplant Recipient Survival Benefit with Living Donation in the Model for Endstage Liver Disease Allocation Era SO HEPATOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; DONOR; MELD AB Receipt of a living donor liver transplant (LDLT) has been associated with improved survival compared with waiting for a deceased donor liver transplant (DDLT). However, the survival benefit of liver transplant has been questioned for candidates with Model for Endstage Liver Disease (MELD) scores <15, and the survival advantage of LDLT has not been demonstrated during the MELD allocation era, especially for low MELD patients. Transplant candidates enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study after February 28, 2002 were followed for a median of 4.6 years. Starting at the time of presentation of the first potential living donor, mortality for LDLT recipients was compared to mortality for patients who remained on the waiting list or received DDLT (no LDLT group) according to categories of MELD score (<15 or >= 15) and diagnosis of hepatocellular carcinoma (HCC). Of 868 potential LDLT recipients (453 with MELD <15; 415 with MELD >= 15 at entry), 712 underwent transplantation (406 LDLT; 306 DDLT), 83 died without transplant, and 73 were alive without transplant at last follow-up. Overall, LDLT recipients had 56% lower mortality (hazard ratio [HR] = 0.44, 95% confidence interval [CI] 0.32-0.60; P < 0.0001). Among candidates without HCC, mortality benefit was seen both with MELD <15 (HR = 0.39; P = 0.0003) and MELD >= 15 (HR = 0.42; P = 0.0006). Among candidates with HCC, a benefit of LDLT was not seen for MELD <15 (HR = 0.82, P = 0.65) but was seen for MELD >= 15 (HR = 0.29, P = 0.043). Conclusion: Across the range of MELD scores, patients without HCC derived a significant survival benefit when undergoing LDLT rather than waiting for DDLT in the MELD liver allocation era. Low MELD candidates with HCC may not benefit from LDLT. (HEPATOLOGY 2011;54:1313-1321) C1 [Berg, Carl L.] Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA 22908 USA. [Merion, Robert M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Merion, Robert M.] Arbor Res Collaborat Hlth, Ann Arbor, MI USA. [Shearon, Tempie H.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Olthoff, Kim M.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Brown, Robert S., Jr.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Baker, Talia B.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Everson, Gregory T.] Univ Colorado, Dept Med, Aurora, CO USA. [Hong, Johnny C.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Terrault, Norah] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hayashi, Paul H.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Fisher, Robert A.] Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. RP Berg, CL (reprint author), Univ Virginia Hlth Syst, Dept Med, POB 800708, Charlottesville, VA 22908 USA. EM CLB7D@hscmail.mcc.virginia.edu FU National Institutes of Health (NIDDK) [U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531]; American Society of Transplant Surgeons; U.S. Department of Health and Human Services, Health Resources and Services Administration FX Supported in part by the National Institutes of Health (NIDDK grant numbers U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531), the American Society of Transplant Surgeons, and the U.S. Department of Health and Human Services, Health Resources and Services Administration. NR 12 TC 46 Z9 46 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 IS 4 BP 1313 EP 1321 DI 10.1002/hep.24494 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KA UT WOS:000295577200023 PM 21688284 ER PT J AU Ghany, MG Nelson, DR Strader, DB Thomas, DL Seeff, LB AF Ghany, Marc G. Nelson, David R. Strader, Doris B. Thomas, David L. Seeff, Leonard B. TI An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases SO HEPATOLOGY LA English DT Editorial Material ID SUSTAINED VIROLOGICAL RESPONSE; PEGINTERFERON ALPHA-2A; GENETIC-VARIATION; PLUS RIBAVIRIN; VIRAL RESPONSE; HCV INFECTION; FOLLOW-UP; TELAPREVIR; COMBINATION; IL28B C1 [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Nelson, David R.] Univ Florida, Sect Hepatobiliary Dis, Gainesville, FL USA. [Strader, Doris B.] Univ Vermont, Coll Med, Div Gastroenterol & Hepatol, Burlington, VT USA. [Thomas, David L.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Seeff, Leonard B.] Hill Grp, Bethesda, MD USA. RP Ghany, MG (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov FU NCI NIH HHS [K24 CA139570] NR 33 TC 728 Z9 768 U1 2 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 IS 4 BP 1433 EP 1444 DI 10.1002/hep.24641 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KA UT WOS:000295577200035 PM 21898493 ER PT J AU Soekadar, SR Witkowski, M Mellinger, J Ramos, A Birbaumer, N Cohen, LG AF Soekadar, Surjo R. Witkowski, Matthias Mellinger, Juergen Ramos, Ander Birbaumer, Niels Cohen, Leonardo G. TI ERD-Based Online Brain-Machine Interfaces (BMI) in the Context of Neurorehabilitation: Optimizing BMI Learning and Performance SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Brain-machine interface; event-related desynchronization; neurorehabilitation; stroke ID COMPUTER INTERFACE; CHRONIC STROKE; BCI SYSTEM; EEG; MOVEMENT; RECOVERY; COMMUNICATION; FMRI; ARM AB Event-related desynchronization (ERD) of sensori-motor rhythms (SMR) can be used for online brain-machine interface (BMI) control, but yields challenges related to the stability of ERD and feedback strategy to optimize BMI learning. Here, we compared two approaches to this challenge in 20 right-handed healthy subjects (HS, five sessions each, S1-S5) and four stroke patients (SP, 15 sessions each, S1-S15). ERD was recorded from a 275-sensor MEG system. During daily training, motor imagery-induced ERD led to visual and proprioceptive feedback delivered through an orthotic device attached to the subjects' hand and fingers. Group A trained with a heterogeneous reference value (RV) for ERD detection with binary feedback and Group B with a homogenous RV and graded feedback (10 HS and 2 SP in each group). HS in Group B showed better BMI performance than Group A and improved BMI control from S1 to S5 while Group A did not. In spite of the small n, SP in Group B showed a trend for a higher BMI performance and learning was significantly better. Using a homogeneous RV and graded feedback led to improved modulation of ipsilesional activity resulting in superior BMI learning relative to use of a heterogeneous RV and binary feedback. C1 [Soekadar, Surjo R.; Witkowski, Matthias; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabilitat Sec, NIH, Bethesda, MD 20892 USA. [Mellinger, Juergen; Ramos, Ander; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol IMP, D-72076 Tubingen, Germany. RP Soekadar, SR (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabilitat Sec, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM surjo@soekadar.com; matthias.witkowski@gmx.de; juergen.mellinger@uni-tuebingen.de; ramos@gmail.com; niels.birbaumer@uni-tuebingen.de; cohenl@ninds.nih.gov OI Soekadar, Surjo R./0000-0003-1280-5538; Ramos-Murguialday, Ander/0000-0002-1549-4029 FU Intramural Research Program (IRP) of the National Institute of Neurological Disorders and Stroke (NINDS), National Institues of Health (NIH); German Federal Ministry of Education and Research (BMBF) [01GQ0831]; Deutsche Forschungsgemeinschaft (DFG); IRP of the NINDS/NIH; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of Health Sciences, Bethesda, MD FX Manuscript received February 01, 2011; revised April 20, 2011; accepted August 06, 2011. Date of current version October 07, 2011. The work of S. Soekadar was supported by the Intramural Research Program (IRP) of the National Institute of Neurological Disorders and Stroke (NINDS), National Institues of Health (NIH), the German Federal Ministry of Education and Research (BMBF # 01GQ0831) and the Deutsche Forschungsgemeinschaft (DFG). The work of M. Witkowski was supported by the IRP of the NINDS/NIH, the DFG and the BMBF (01GQ0831). The work of N. Birbaumer was supported by the BMBF (01GQ0831) and the DFG. The work of L. G. Cohen is supported by the IRP of the NINDS/NIH and the Center for Neuroscience and Regenerative Medicine, Uniformed Services University of Health Sciences, Bethesda, MD. NR 41 TC 25 Z9 25 U1 0 U2 16 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD OCT PY 2011 VL 19 IS 5 BP 542 EP 549 DI 10.1109/TNSRE.2011.2166809 PG 8 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 832GW UT WOS:000295792900010 PM 21984519 ER PT J AU Mezey, E AF Mezey, Eva TI The Therapeutic Potential of Bone Marrow-Derived Stromal Cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE BONE MARROW STROMAL CELLS; TISSUE REPAIR; IMMUNE REGULATION ID MESENCHYMAL STEM-CELLS; SUPPRESS T-LYMPHOCYTE; IN-VIVO; TISSUE-REPAIR; RESPONSES; SECRETION; MIGRATION; EXPRESS; VITRO; TRANSDIFFERENTIATION AB Since the replacement of the hematopoietic system became feasible through bone marrow (BM) transplantation, the idea of how to replace other organs of the body has been in the forefront of medical research. Scientists have been searching for the ideal stem cell that could be manipulated to differentiate into any tissue. Although the embryonal stem cells seemed to have the ability to do this, the difficulties surrounding their use prevented them from becoming therapeutically useful. Thus, the field turned to adult stem cells, particularly stem cells of BM origin. We have learnt a lot during the last decade about the potential of the BM-derived stromal (also called mesenchymal stem) cells (BMSCs). The first studies suggested them as cell replacement tools, but later it turned out that their usefulness is more likely due to paracrine effects due to a large variety of secreted factors that induce growth and differentiation of the tissue-specific stem cells as well as prevent injured cells from apoptotic death. Finally, a whole new field emerged when many groups confirmed that these cells are also capable of regulating immune function in a so far unknown, dynamic manner. When BMSCs are injected they seem to be able to sense the environment and respond according to the actual need of the organism in order to survive. This plasticity can never be done by the use of any drugs and such a "live" cell therapy could open a whole new chapter in clinical care in the future. J. Cell. Biochem. 112: 2683-2687, 2011. (C) 2011 Wiley-Liss, Inc. C1 NIDCR, NIH, Adult Stem Cell Unit, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NIDCR, NIH, Adult Stem Cell Unit, Bldg 49,5A76,49 Convent Dr, Bethesda, MD 20892 USA. EM mezeye@mail.nih.gov FU NIH, DHHS FX This research was supported by the Division of Intramural Research program of NIDCR, in the Intramural Research Program, NIH, DHHS. NR 43 TC 22 Z9 33 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT PY 2011 VL 112 IS 10 BP 2683 EP 2687 DI 10.1002/jcb.23216 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 829YP UT WOS:000295623300005 PM 21678464 ER PT J AU Osada, T Gu, YH Kanazawa, M Tsubota, Y Hawkins, BT Spatz, M Milner, R del Zoppo, GJ AF Osada, Takashi Gu, Yu-Huan Kanazawa, Masato Tsubota, Yoshiaki Hawkins, Brian T. Spatz, Maria Milner, Richard del Zoppo, Gregory J. TI Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by beta(1)-integrins SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE beta(1)-integrins; cerebral endothelial cells; claudin-5; extracellular matrix; matrix adhesion receptors; microvessel permeability ID BLOOD-BRAIN-BARRIER; TIGHT JUNCTION PROTEINS; IN-VITRO; RAT-BRAIN; TYROSINE PHOSPHORYLATION; GLIOBLASTOMA-MULTIFORME; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; ISCHEMIA; PERMEABILITY AB The hypothesis tested by these studies states that in addition to interendothelial cell tight junction proteins, matrix adhesion by beta(1)-integrin receptors expressed by endothelial cells have an important role in maintaining the cerebral microvessel permeability barrier. Primary brain endothelial cells from C57 BL/6 mice were incubated with beta(1)-integrin function-blocking antibody (Ha2/5) or isotype control and the impacts on claudin-5 expression and microvessel permeability were quantified. Both flow cytometry and immunofluorescence studies demonstrated that the interendothelial claudin-5 expression by confluent endothelial cells was significantly decreased in a time-dependent manner by Ha2/5 exposure relative to isotype. Furthermore, to assess the barrier properties, transendothelial electrical resistance and permeability measurements of the monolayer, and stereotaxic injection into the striatum of mice were performed. Ha2/5 incubation reduced the resistance of endothelial cell monolayers significantly, and significantly increased permeability to 40 and 150 kDa dextrans. Ha2/5 injection into mouse striatum produced significantly greater IgG extravasation than the isotype or the control injections. This study demonstrates that blockade of beta(1)-integrin function changes interendothelial claudin-5 expression and increases microvessel permeability. Hence, endothelial cell-matrix interactions via beta(1)-integrin directly affect interendothelial cell tight junction claudin-5 expression and brain microvascular permeability. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1972-1985; doi:10.1038/jcbfm.2011.99; published online 20 July 2011 C1 [Osada, Takashi; Gu, Yu-Huan; Kanazawa, Masato; Hawkins, Brian T.; del Zoppo, Gregory J.] Univ Washington, Sch Med, Div Hematol, Dept Med,Harborview Med Ctr, Seattle, WA 98104 USA. [Osada, Takashi; Gu, Yu-Huan; Kanazawa, Masato; Hawkins, Brian T.; del Zoppo, Gregory J.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA. [Tsubota, Yoshiaki] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Spatz, Maria] NINDS, Stroke Branch, Bethesda, MD 20892 USA. [Milner, Richard; del Zoppo, Gregory J.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP del Zoppo, GJ (reprint author), Univ Washington, Sch Med, Div Hematol, Dept Med,Harborview Med Ctr, Box 359756,325 9th Ave, Seattle, WA 98104 USA. EM grgdlzop@u.washington.edu RI Osada, Takashi/B-2060-2015 FU NIH [NS 053716, NS 038710, NS 036945]; Kanae Foundation for the Promotion of Medical Science FX This study was supported in part by NIH Grants NS 053716, NS 038710, and NS 036945 to Dr del Zoppo. Dr Osada also received funding from the Kanae Foundation for the Promotion of Medical Science. NR 41 TC 42 Z9 44 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2011 VL 31 IS 10 BP 1972 EP 1985 DI 10.1038/jcbfm.2011.99 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 829YB UT WOS:000295621600003 PM 21772312 ER PT J AU Zanotti-Fregonara, P Chen, K Liow, JS Fujita, M Innis, RB AF Zanotti-Fregonara, Paolo Chen, Kewei Liow, Jeih-San Fujita, Masahiro Innis, Robert B. TI Image-derived input function for brain PET studies: many challenges and few opportunities SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE image-derived input function; kinetic modeling; neuroreceptor tracers; PET ID POSITRON-EMISSION-TOMOGRAPHY; INDEPENDENT COMPONENT ANALYSIS; CEREBRAL METABOLIC-RATE; NONINVASIVE QUANTIFICATION; DYNAMIC PET; KINETIC-PARAMETERS; QUANTITATIVE PET; PROSTATE-CANCER; FDG-PET; GLUCOSE AB Quantitative positron emission tomography (PET) brain studies often require that the input function be measured, typically via arterial cannulation. Image-derived input function (IDIF) is an elegant and attractive noninvasive alternative to arterial sampling. However, IDIF is also a very challenging technique associated with several problems that must be overcome before it can be successfully implemented in clinical practice. As a result, IDIF is rarely used as a tool to reduce invasiveness in patients. The aim of the present review was to identify the methodological problems that hinder widespread use of IDIF in PET brain studies. We conclude that IDIF can be successfully implemented only with a minority of PET tracers. Even in those cases, it only rarely translates into a less-invasive procedure for the patient. Finally, we discuss some possible alternative methods for obtaining less-invasive input function. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1986-1998; doi:10.1038/jcbfm.2011.107; published online 3 August 2011 C1 [Zanotti-Fregonara, Paolo; Liow, Jeih-San; Fujita, Masahiro; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Chen, Kewei] Banner Alzheimers Inst, Phoenix, AZ USA. [Chen, Kewei] Banner Good Samaritan PET Ctr, Phoenix, AZ USA. [Chen, Kewei] Arizona State Univ, Dept Math & Stat, Tempe, AZ USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B1D43,31 Ctr Dr,MSC 1026, Bethesda, MD 20892 USA. EM innisr@mail.nih.gov RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS); National Institute of Mental Health, US [RO1 MH57899]; National Institute on Aging, US [R01AG031581-10, P30 AG19610]; state of Arizona FX This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS), by the National Institute of Mental Health, US (RO1 MH57899), the National Institute on Aging, US (R01AG031581-10 and P30 AG19610), and the state of Arizona. NR 93 TC 43 Z9 43 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2011 VL 31 IS 10 BP 1986 EP 1998 DI 10.1038/jcbfm.2011.107 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 829YB UT WOS:000295621600004 PM 21811289 ER PT J AU Onojafe, IF Adams, DR Simeonov, DR Zhang, J Chan, CC Bernardini, IM Sergeev, YV Dolinska, MB Alur, RP Brilliant, MH Gahl, WA Brooks, BP AF Onojafe, Ighovie F. Adams, David R. Simeonov, Dimitre R. Zhang, Jun Chan, Chi-Chao Bernardini, Isa M. Sergeev, Yuri V. Dolinska, Monika B. Alur, Ramakrishna P. Brilliant, Murray H. Gahl, William A. Brooks, Brian P. TI Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TYROSINASE GENE-MUTATIONS; HIMALAYAN MOUSE; 2-(2-NITRO-4-TRIFLUOROMETHYLBENZOYL)-CYCLOHEXANE-1,3-DIONE NTBC; MAMMALIAN TYROSINASE; TISSUE DISTRIBUTION; P GENE; IDENTIFICATION; CATABOLISM; EXPRESSION; PROTEINS AB Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with the latter produce some melanin. We hypothesized that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved inhibitor of tyrosine degradation, could stabilize tyrosinase and improve pigmentation in individuals with OCA1. Here, we tested this hypothesis in mice homozygous for either the Tyr(c-2J) null allele or the Tyr(c-h) allele, which model OCA-1A and OCA-1B, respectively. Only nitisinone-treated Tyr(c-h/c-h) mice manifested increased pigmentation in their fur and irides and had more pigmented melanosomes. High levels of tyrosine improved the stability and enzymatic function of the Tyr(c-h) protein and also increased overall melanin levels in melanocytes from a human with OCA-1B. These results suggest that the use of nitisinone in OCA-1B patients could improve their pigmentation and potentially ameliorate vision loss. C1 [Onojafe, Ighovie F.; Sergeev, Yuri V.; Dolinska, Monika B.; Alur, Ramakrishna P.; Brooks, Brian P.] NEI, Unit Pediat Dev & Genet Eye Dis, NIH, Bethesda, MD 20892 USA. [Adams, David R.; Simeonov, Dimitre R.; Bernardini, Isa M.; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Zhang, Jun; Chan, Chi-Chao] NEI, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. [Brilliant, Murray H.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI USA. RP Brooks, BP (reprint author), Bldg 10,Room 10N226,MSC 1860,10 Ctr Dr, Bethesda, MD 20892 USA. EM brooksb@mail.nih.gov RI Zhang, Jun/K-2424-2012 FU National Eye Institute; National Human Genome Research Institute; National Human Genome Research Institute, NIH; Blind Children's Center FX The authors thank V. Hearing for the gift of alpha PEP7 antiserum and review of the manuscript, J.T. Wroblewski for the gift of CHO cells, and C. Olivares for the gift of the mouse tyrosinase expression construct. We thank the intramural programs of the National Eye Institute and the National Human Genome Research Institute, NIH, for funding this research. B.P. Brooks's lab was partially funded by a 1-year seed grant from the Blind Children's Center. NR 72 TC 10 Z9 10 U1 2 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2011 VL 121 IS 10 BP 3914 EP 3923 DI 10.1172/JCI59372 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000020 PM 21968110 ER PT J AU Akilesh, S Suleiman, H Yu, HY Stander, MC Lavin, P Gbadegesin, R Antignac, C Pollak, M Kopp, JB Winn, MP Shaw, AS AF Akilesh, Shreeram Suleiman, Hani Yu, Haiyang Stander, M. Christine Lavin, Peter Gbadegesin, Rasheed Antignac, Corinne Pollak, Martin Kopp, Jeffrey B. Winn, Michelle P. Shaw, Andrey S. TI Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIN CYTOSKELETON; FILAMIN-A; KIDNEY PODOCYTES; CELL MOTILITY; RHO; DISEASE; PROTEINURIA; DYNAMICS; NEF; REARRANGEMENTS AB The specialized epithelial cell of the kidney, the podocyte, has a complex actin-based cytoskeleton. Dynamic regulation of this cytoskeleton is required for efficient barrier function of the kidney. Podocytes are a useful cell type to study the control of the actin cytoskeleton in vivo, because disruption of components of the cytoskeleton results in podocyte damage, cell loss, and a prototypic injury response called focal segmental glomerulosclerosis (FSGS). Searching for actin regulatory proteins that are expressed in podocytes, we identified a RhoA-activated Rac1 GTPase-activating protein (Rac1-GAP), Arhgap24, that was upregulated in podocytes as they differentiated, both in vitro and in vivo. Increased levels of active Rac1 and Cdc42 were measured in Arhgap24 knockdown experiments, which influenced podocyte cell shape and membrane dynamics. Consistent with a role for Arhgap24 in normal podocyte functioning in vivo, sequencing of the ARHGAP24 gene in patients with FSGS identified a mutation that impaired its Rac1-GAP activity and was associated with disease in a family with FSGS. Thus, Arhgap24 contributes to the careful balancing of RhoA and Rac1 signaling in podocytes, the disruption of which may lead to kidney disease. C1 [Suleiman, Hani; Yu, Haiyang; Stander, M. Christine; Shaw, Andrey S.] Washington Univ, Howard Hughes Med Inst, Div Immunobiol, Dept Pathol & Immunol,Sch Med, St Louis, MO 63110 USA. [Akilesh, Shreeram] Barnes Jewish Hosp, Dept Pathol, St Louis, MO 63110 USA. [Lavin, Peter; Winn, Michelle P.] Duke Univ, Med Ctr, Div Nephrol, Dept Med, Durham, NC USA. [Lavin, Peter; Gbadegesin, Rasheed; Winn, Michelle P.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. [Gbadegesin, Rasheed] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Antignac, Corinne] Hop Necker Enfants Malades Tour Lavoisier, INSERM, U423, Paris, France. [Pollak, Martin] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA. [Pollak, Martin] Harvard Univ, Sch Med, Boston, MA USA. [Kopp, Jeffrey B.] NIH, Kidney Dis Sect, Bethesda, MD 20892 USA. RP Shaw, AS (reprint author), Washington Univ, Howard Hughes Med Inst, Div Immunobiol, Dept Pathol & Immunol,Sch Med, Campus Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. EM shaw@pathology.wustl.edu RI Yu, Haiyang/J-2810-2013; OI Akilesh, Shreeram/0000-0003-3152-7991; Yu, Haiyang/0000-0003-3460-6716; Kopp, Jeffrey/0000-0001-9052-186X FU Washington University George M. O'Brien Center for Kidney Disease Research [P30 DK079333]; NIDDK [RO1DK058366]; Howard Hughes Medical Institute; Medical Scientist Training Program FX We are grateful for the support of Washington University George M. O'Brien Center for Kidney Disease Research (P30 DK079333) for some of the patient specimens. We would like to thank Jeffrey Miner for helpful discussions and Jiancheng Hu for technical assistance and reagents for the GTPase activity pull-down assays. This work was supported in part by the NIDDK Intramural (to J.B. Kopp) and Extramural Research Programs (RO1DK058366, to A.S. Shaw), Howard Hughes Medical Institute, and the Medical Scientist Training Program Grant to Washington University School of Medicine. NR 33 TC 84 Z9 87 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2011 VL 121 IS 10 BP 4127 EP 4137 DI 10.1172/JCI46458 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000038 PM 21911940 ER PT J AU Xiang, Y Shen, J AF Xiang, Yun Shen, Jun TI Windowed Stochastic Proton Decoupling for In Vivo C-13 Magnetic Resonance Spectroscopy with Reduced RF Power Deposition SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE in vivo C-13 MRS; carboxylic/amide carbons; stochastic decoupling scheme; RF power deposition ID HUMAN BRAIN; 11.7 TESLA; RAT-BRAIN; METABOLISM; HUMANS; CYCLE; NMR; MRS AB Purpose: To propose a strategy for reducing radiofrequency (RF) power deposition by stochastic proton decoupiing based on Rayleigh's theorem. Materials and Methods: Rayleigh's theorem was used to remove frequency components of stochastic decoupling over the 3.90-6.83 ppm range. (2-C-13] or [2,5-C-13(2)]glucose was infused intravenously to anesthetized rats. C-13 labeling of brain metabolites was detected in the carboxylic/amide spectral region at 11.7 T using either the original stochastic decoupling method developed by Ernst or the proposed windowed stochastic decoupling method. Results: By restricting frequency components of stochastic decoupling to 1.91-3.90 ppm and 6.83-7.60 ppm spectral regions decoupling power deposition was reduced by approximate to 50%. The proposed windowed stochastic decoupling scheme is experimentally demonstrated for in vivo C-13 MRS of rat brain at 11.7 T. Conclusion: The large reduction in decoupling power deposition makes it feasible to perform stochastic proton decoupling at very high magnetic fields for human brain C-13 MRS studies. C1 [Xiang, Yun; Shen, Jun] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU NIH, NIMH FX Contract grant sponsor: Intramural Research Program of the NIH, NIMH. NR 18 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD OCT PY 2011 VL 34 IS 4 BP 968 EP 972 DI 10.1002/jmri.22667 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 826ZP UT WOS:000295394400031 PM 21769967 ER PT J AU Bang, H Park, S Hwang, J Jin, H Cho, E Kim, DY Song, T Shamputa, IC Via, LE Barry, CE Cho, SN Lee, H AF Bang, Hyeeun Park, Sangjung Hwang, Joohwan Jin, Hyunwoo Cho, Eunjin Kim, Dae Yoon Song, Taeksun Shamputa, Isdore Chola Via, Laura E. Barry, Clifton E., III Cho, Sang-Nae Lee, Hyeyoung TI Improved rapid molecular diagnosis of multidrug-resistant tuberculosis using a new reverse hybridization assay, REBA MTB-MDR SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID LINE PROBE ASSAY; MYCOBACTERIUM-TUBERCULOSIS; ISONIAZID RESISTANCE; RPOB GENE; RIFAMPIN RESISTANCE; MUTATIONS; STRAINS; BEACONS; LEVEL; KATG AB Rapid diagnosis of multidrug-resistant tuberculosis (MDR-TB) is essential for the prompt initiation of effective second-line therapy to improve treatment outcome and limit transmission of this obstinate disease. A variety of molecular methods that enable the rapid detection of mutations implicated in MDR-TB have been developed. The sensitivity of the methods is dependent, in principle, on the repertoire of mutations being detected, which is typically limited to mutations in the genes rpoB, katG and the promoter region of inhA. In this study, a new reverse hybridization assay, REBA MTB-MDR (M&D), that probes mutations in the oxyR-ahpC intergenic region, in addition to those in rpoB, katG and the inhA promoter region, was evaluated. A set of 240 Mycobacterium tuberculosis clinical isolates from patients receiving retreatment regimens was subjected to conventional phenotypic drug-susceptibility testing (DST) and the REBA MTB-MDR assay. The nucleotide sequences of the loci known to be involved in drug resistance were determined for comparison. In brief, the results showed that the REBA MTB-MDR assay efficiently recognized nucleotide changes in the oxyR-ahpC intergenic region as well as those in rpoB, katG and the inhA promoter region with higher sensitivity, resulting in an 81.0% detection rate for isoniazid resistance. Inclusion of the oxyR-ahpC intergenic region in the REBA MTB-MDR assay improved the overall sensitivity of molecular DST for MDR-TB from 73.1 to 79.9%. C1 [Bang, Hyeeun; Park, Sangjung; Hwang, Joohwan; Jin, Hyunwoo; Lee, Hyeyoung] Yonsei Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Wonju 220710, South Korea. [Cho, Eunjin; Song, Taeksun] Int TB Res Ctr, Chang Won 631710, South Korea. [Kim, Dae Yoon] Mokpo Natl Hosp, Mokpo 530828, South Korea. [Shamputa, Isdore Chola; Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20852 USA. [Cho, Sang-Nae] Yonsei Univ, Genome Res Ctr Resp Pathogens, Coll Med, Seoul 120752, South Korea. RP Lee, H (reprint author), Yonsei Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Wonju 220710, South Korea. EM hyelee@yonsei.ac.kr RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU National Institutes of Health, National Institute of Allergy and Infectious Disease FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Disease. NR 22 TC 10 Z9 11 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD OCT PY 2011 VL 60 IS 10 BP 1447 EP 1454 DI 10.1099/jmm.0.032292-0 PG 8 WC Microbiology SC Microbiology GA 833CW UT WOS:000295860400005 PM 21596910 ER PT J AU Kimura, Y Fujita, M Hong, JS Lohith, TG Gladding, RL Zoghbi, SS Tauscher, JA Goebl, N Rash, KS Chen, ZG Pedregal, C Barth, VN Pike, VW Innis, RB AF Kimura, Yasuyuki Fujita, Masahiro Hong, Jinsoo Lohith, Talakad G. Gladding, Robert L. Zoghbi, Sami S. Tauscher, Johannes A. Goebl, Nancy Rash, Karen S. Chen, Zhaogen Pedregal, Concepcion Barth, Vanessa N. Pike, Victor W. Innis, Robert B. TI Brain and Whole-Body Imaging in Rhesus Monkeys of C-11-NOP-1A, a Promising PET Radioligand for Nociceptin/Orphanin FQ Peptide Receptors SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE molecular imaging; positron emission tomography; nociceptin/orphanin peptide ID POSITRON-EMISSION-TOMOGRAPHY; ANTI-OPIOID PEPTIDE; IN-VIVO; PHARMACOLOGICAL CHARACTERIZATION; ANTAGONIST SB-612111; ORPHANIN FQ; BINDING; LOCALIZATION; EXPRESSION; MODEL AB Our laboratory developed (S)-3-(2'-fluoro-6',7'-dihydrospiro [piperidine-4,4'-thieno[3,2-c]pyran]-1-yl)-2-(2-fluorobenzyl)-N-methylpropanamide (C-11-NOP-1A), a new radioligand for the nociceptin/orphanin FQ peptide (NOP) receptor, with high affinity (K-i, 0.15 nM) and appropriate lipophilicity (measured logD, 3.4) for PET brain imaging. Here, we assessed the utility of C-11-NOP-1A for quantifying NOP receptors in the monkey brain and estimated the radiation safety profile of this radioligand based on its biodistribution in monkeys. Methods: Baseline and blocking PET scans were acquired from head to thigh for 3 rhesus monkeys for approximately 120 min after C-11-NOP-1A injection. These 6 PET scans were used to quantify NOP receptors in the brain and to estimate radiation exposure to organs of the body. In the blocked scans, a selective nonradioactive NOP receptor antagonist (SB-612111; 1 mg/kg intravenously) was administered before C-11-NOP-1A. In all scans, arterial blood was sampled to measure the parent radioligand C-11-NOP-1A. Distribution volume (V-T; a measure of receptor density) was calculated with a compartment model using brain and arterial plasma data. Radiation-absorbed doses were calculated using the MIRD Committee scheme. Results: After C-11-NOP-1A injection, peak uptake of radioactivity in the brain had a high concentration (similar to 5 standardized uptake value), occurred early (similar to 12 min), and thereafter washed out quickly. V-T (mL . cm(-3)) was highest in the neocortex (similar to 20) and lowest in hypothalamus and cerebellum (similar to 13). SB-612111 blocked approximately 50%-70% of uptake and reduced V-T in all brain regions to approximately 7 mL . cm(-3). Distribution was well identified within 60 min of injection and stable for the remaining 60 min, consistent with only parent radioligand and not radiometabolites entering the brain. Whole-body scans confirmed that the brain had specific (i.e., displaceable) binding but could not detect specific binding in peripheral organs. The effective dose for humans estimated from the baseline scans in monkeys was 5.0 mSv/MBq. Conclusion: C-11-NOP-1A is a useful radioligand for quantifying NOP receptors in the monkey brain, and its radiation dose is similar to that of other C-11-labeled ligands for neuroreceptors. C-11-NOP-1A appears to be a promising candidate for measuring NOP receptors in the human brain. C1 [Kimura, Yasuyuki; Fujita, Masahiro; Hong, Jinsoo; Lohith, Talakad G.; Gladding, Robert L.; Zoghbi, Sami S.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Kimura, Yasuyuki] Natl Inst Radiol Sci, Dept Mol Neuroimaging, Mol Imaging Ctr, Chiba 260, Japan. [Tauscher, Johannes A.; Goebl, Nancy; Rash, Karen S.; Chen, Zhaogen; Pedregal, Concepcion; Barth, Vanessa N.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Kimura, Yasuyuki/D-4459-2016; Tauscher, Johannes/M-5976-2016 OI Kimura, Yasuyuki/0000-0002-7927-9483; FU National Institute of Mental Health, National Institutes of Health; Eli Lilly FX We thank Kacey Anderson, Leah P. Dickstein, Kimberly Jenko, Nobuyo Kimura, Cheryl L. Wallisch, Jeih-San Liow, Harushige Ozaki, and the staff of the PET Department for assistance in completing these studies and PMOD Technologies (Zurich, Switzerland) for providing its image analysis and modeling software. Ioline Henter provided invaluable editorial assistance. Garth Terry created the table for scaling factors for organs in monkey and man. This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, and by a Cooperative Research and Development Agreement with Eli Lilly. No other potential conflict of interest relevant to this article was reported. NR 27 TC 19 Z9 19 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT 1 PY 2011 VL 52 IS 10 BP 1638 EP 1645 DI 10.2967/jnumed.111.091181 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 828XM UT WOS:000295537800024 PM 21880575 ER PT J AU Sutin, AR Stockdale, GD AF Sutin, Angelina R. Stockdale, Gary D. TI Trait Dissociation and the Subjective Affective, Motivational, and Phenomenological Experience of Self-Defining Memories SO JOURNAL OF PERSONALITY LA English DT Article ID AUTOBIOGRAPHICAL MEMORIES; NONCLINICAL POPULATION; INDIVIDUAL-DIFFERENCES; COGNITIVE-PROCESSES; PERSONAL STRIVINGS; SCALE; RELIABILITY; VALIDITY; DISTURBANCES; TENDENCIES AB The present research reports 2 studies that examine the relation between nonpathological trait dissociation and the subjective affect, motivation, and phenomenology of self-defining memories. In Study 1 (N = 293), participants retrieved and rated the emotional and motivational experience of a general and a positive and negative achievement-related memory. Study 2 (N = 449) extended these ratings to relationship-related memories and the phenomenological experience of the memory. Dissociation was associated with incongruent affect in valenced memories (e. g., positive affect in a negative memory) and memories that were visually incoherent and saturated with power motivation, hubristic pride, and shame, regardless of valence or domain. The present findings demonstrate that autobiographical memories, which integrate emotional, motivational, and phenomenological components, reflect the emotional and motivational processes inherent to dissociation. C1 [Sutin, Angelina R.] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA. [Stockdale, Gary D.] Univ Calif Davis, Davis, CA 95616 USA. RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sutina@mail.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 51 TC 5 Z9 5 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3506 J9 J PERS JI J. Pers. PD OCT PY 2011 VL 79 IS 5 BP 939 EP 963 DI 10.1111/j.1467-6494.2010.00708.x PG 25 WC Psychology, Social SC Psychology GA 824UN UT WOS:000295227800003 PM 21204840 ER PT J AU Yadav, PN Kroeze, WK Farrell, MS Roth, BL AF Yadav, Prem N. Kroeze, Wesley K. Farrell, Martilias S. Roth, Bryan L. TI Antagonist Functional Selectivity: 5-HT2A Serotonin Receptor Antagonists Differentially Regulate 5-HT2A Receptor Protein Level In Vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID 5-HYDROXYTRYPTAMINE(2A) RECEPTOR; NEUROLEPTIC AGENTS; DRUG DISCOVERY; RAT-BRAIN; BINDING; VITRO; MIANSERIN; AGONIST; INTERNALIZATION; SCHIZOPHRENIA AB Dysregulation of the 5-HT2A receptor is implicated in both the etiology and treatment of schizophrenia. Although the essential role of 5-HT2A receptors in atypical antipsychotic drug actions is widely accepted, the contribution of 5-HT2A down-regulation to their efficacy is not known. We hypothesized that down-regulation of cortical 5-HT2A receptors contributes to the therapeutic action of atypical antipsychotic drugs. To test this hypothesis, we assessed the effect of chronically administered antipsychotics (clozapine, olanzapine, and haloperidol) and several 5-HT2A antagonists [ketanserin, altanserin, alpha-(2,3-dimethoxyphenyl)-1-[ 2-(4-fluorophenylethyl)]-4-piperidinemethanol (M100907), alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethano (M11939), 4-[(2Z)-3-{[2-(dimethylamino)ethoxy]amino}-3-(2-fluorophenyl)prop-2-en-1-ylidene]cyclohexa-2,5-dien-1-one (SR46349B), and pimavanserin], on the phencyclidine (PCP)-induced hyperlocomotor response and cortical 5-HT2A receptor levels in C57BL/6J mice. Clozapine and olanzapine, but not haloperidol, induced receptor down-regulation and attenuated PCP-induced locomotor responses. Of the selective 5-HT2A antagonists tested, only ketanserin caused significant receptor protein down-regulation, whereas SR46349B up-regulated 5-HT2A receptors and potentiated PCP-hyperlocomotion; the other 5-HT2A receptor antagonists were without effect. The significance of these findings with respect to atypical antipsychotic drug action is discussed. C1 [Yadav, Prem N.; Kroeze, Wesley K.; Farrell, Martilias S.; Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Dept Med Chem, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Dept Psychiat, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Program Neurosci, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. RP Roth, BL (reprint author), Univ N Carolina, Chapel Hill Med Sch, Dept Pharmacol, 4072 Genet Med Bldg,120 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU National Institutes of Health National Institute of Mental Health [U19-MH82441, R01-MH61887]; Michael Hooker Chair FX This work was supported by the National Institutes of Health National Institute of Mental Health [Grants U19-MH82441, R01-MH61887] (to B.L.R.) and the Michael Hooker Chair. NR 39 TC 28 Z9 29 U1 1 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2011 VL 339 IS 1 BP 99 EP 105 DI 10.1124/jpet.111.183780 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 821UC UT WOS:000294998900011 PM 21737536 ER PT J AU Jutkiewicz, EM Brooks, EA Kynaston, AD Rice, KC Woods, JH AF Jutkiewicz, Emily M. Brooks, Emily A. Kynaston, Adam D. Rice, Kenner C. Woods, James H. TI Patterns of Nicotinic Receptor Antagonism: Nicotine Discrimination Studies SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DIHYDRO-BETA-ERYTHROIDINE; APPARENT PA(2) ANALYSIS; DRUG DISCRIMINATION; STIMULUS PROPERTIES; SMOKING-CESSATION; ACETYLCHOLINE-RECEPTORS; SUBSTITUTION PATTERNS; LABORATORY-ANIMALS; INTRINSIC EFFICACY; DEPOT NALTREXONE AB Evaluation of the discriminative stimulus effects of drugs is a useful procedure for identification of receptor mediation of in vivo drug effects. This assay can be enhanced when the stimulus effects of different doses of agonist are evaluated. In the present study, rats were trained to discriminate small or large doses of nicotine from saline, and interactions of these effects with nicotinic receptor antagonists and partial agonists were determined. The insurmountable nicotine antagonist mecamylamine blocked both the discriminative stimulus and response rate-reducing effects of nicotine but was less effective against the large dose of nicotine. The alpha 4 beta 2*-selective, competitive antagonist dihydro-beta-erythrodine (DH beta E) antagonized the discriminative stimulus effects of both doses but was less effective against the larger training dose of nicotine. Schild analyses of DH beta E suggested that different nicotinic receptor populations may be mediating the stimulus effects of large and small doses of nicotine. This suggestion was supported by observations that the discriminative stimulus effects of the partial agonist cytisine were more like those of the large dose than of the small dose of nicotine and that cytisine antagonized the effects of only the small nicotine dose. Varenicline produced nicotine-like effects in both training dose groups but reduced the discriminative stimulus effects of intermediate doses of nicotine in the group trained to the small dose of nicotine. Overall, these results suggest that small doses of nicotine produce their stimulus effects via alpha 4 beta 2* nicotine receptors, whereas larger doses of nicotine recruit additional nicotine receptor subtypes, as revealed by drug discrimination assays in rats. C1 [Jutkiewicz, Emily M.; Brooks, Emily A.; Kynaston, Adam D.; Woods, James H.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Woods, James H.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Woods, JH (reprint author), Univ Michigan, Dept Pharmacol, 1301 MSRB III,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM jhwoods@umich.edu FU National Institutes of Health National Institute on Drug Abuse [T32-DA007268]; National Institute on Alcohol Abuse and Alcoholism; University of Michigan Tobacco Research Network FX This work was supported in part by the Intramural Research Programs of the National Institutes of Health National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism; the National Institutes of Health National Institute on Drug Abuse [Grant T32-DA007268]; and the University of Michigan Tobacco Research Network. NR 56 TC 23 Z9 23 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2011 VL 339 IS 1 BP 194 EP 202 DI 10.1124/jpet.111.182170 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 821UC UT WOS:000294998900021 PM 21730011 ER PT J AU Kulyyassov, A Shoaib, M Pichugin, A Kannouche, P Ramanculov, E Lipinski, M Ogryzko, V AF Kulyyassov, Arman Shoaib, Muhammad Pichugin, Andrei Kannouche, Patricia Ramanculov, Erlan Lipinski, Marc Ogryzko, Vasily TI PUB-MS: A Mass Spectrometry-based Method to Monitor Protein-Protein Proximity in vivo SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE protein-protein interactions; biotinylation; proximity; multiplexing; pulse-chase; SILAC ID RESONANCE ENERGY-TRANSFER; INACTIVE X-CHROMOSOME; FRAGMENT COMPLEMENTATION ASSAYS; CHROMATIN IMMUNOPRECIPITATION; SELF-ORGANIZATION; HISTONE H2A; BIOTINYLATION; COMPLEX; CELLS; DNA AB The common techniques to study protein-protein proximity in vivo are not well adapted to the capabilities and the expertise of a standard proteomics laboratory, typically based on the use of mass spectrometry. With the aim of closing this gap, we have developed PUB-MS (for proximity utilizing biotinylation and mass spectrometry), an approach to monitor protein-protein proximity, based on biotinylation of a protein fused to a biotin-acceptor peptide (BAP) by a biotin-ligase, BirA, fused to its interaction partner. The biotinylation status of the BAP can be further detected by either Western analysis or mass spectrometry. The BAP sequence was redesigned for easy monitoring of the biotinylation status by LC-MS/MS. In several experimental models, we demonstrate that the biotinylation in vivo is specifically enhanced when the BAP- and BirA-fused proteins are in proximity to each other. The advantage of mass spectrometry is demonstrated by using BAPs with different sequences in a single experiment (allowing multiplex analysis) and by the use of stable isotopes. Finally, we show that our methodology can be also used to study a specific subfraction of a protein of interest that was in proximity with another protein at a predefined time before the analysis. C1 [Kulyyassov, Arman; Shoaib, Muhammad; Pichugin, Andrei; Kannouche, Patricia; Lipinski, Marc; Ogryzko, Vasily] Inst Gustave Roussy, F-94805 Villejuif, France. [Kulyyassov, Arman; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana 01000, Kazakhstan. RP Ogryzko, V (reprint author), Inst Gustave Roussy, 39 Rue Camilles Desmoulin, F-94805 Villejuif, France. EM vogryzko@gmail.com RI Ramanculov, Erlan/E-2823-2013; Ogryzko, Vasily/M-6665-2015; OI Ogryzko, Vasily/0000-0002-8548-1389; Kulyyassov, Arman/0000-0002-7932-5689 FU La Ligue Contre le Cancer [9ADO1217/1B1-BIOCE]; Institut National du Cancer [247343/1B1-BIOCE]; Centre National de la Recherche Scientifique [CNRS-INCA-MSHE] [3037987]; NCB Kazakhstan [0103_00404] FX We thank Dr. M. Lechner (Drexel University, Philadelphia) for the KAP1-HP1BDwt and KAP1-HP1BDwt plasmids, Drs H. Willard and M. Chadwick (Case Western Reserve University, Cleveland) for the ORFs of the H2A.BBD and macroH2A, and Dr. L. L. Pritchard for critical reading of the manuscript. We also thank Chloe Robin for the Figure 2C. This work was supported by grants from "La Ligue Contre le Cancer" (9ADO1217/1B1-BIOCE), the "Institut National du Cancer" (247343/1B1-BIOCE) and Centre National de la Recherche Scientifique [CNRS-INCA-MSHE Franco-Pologne #3037987) to VO, by NCB Kazakhstan (0103_00404) to AK and by a travel grant to AK. from the Cooperation Universitaire et Scientifique Department of the French Embassy in Astana, Kazakhstan. NR 37 TC 7 Z9 8 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT PY 2011 VL 10 IS 10 BP 4416 EP 4427 DI 10.1021/pr200189p PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 829RT UT WOS:000295602700006 PM 21842862 ER PT J AU Avital, I AF Avital, Itzhak TI Regional Chemotherapy for Pancreatic Cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Editorial Material ID STATISTICS C1 NCI, USUHS, Head GI & Hepatobiliary Malignancies Sect, Surg Branch,NIH, Bethesda, MD 20892 USA. RP Avital, I (reprint author), NCI, USUHS, Head GI & Hepatobiliary Malignancies Sect, Surg Branch,NIH, 10 Ctr Dr,CRC Room 4-3961, Bethesda, MD 20892 USA. EM avitali@mail.nih.gov NR 4 TC 1 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT PY 2011 VL 104 IS 5 BP 453 EP 453 DI 10.1002/jso.21975 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 828WR UT WOS:000295535400001 PM 21618244 ER PT J AU Kreimer, AR Rodriguez, AC Hildesheim, A Herrero, R Porras, C Schiffman, M Gonzalez, P Solomon, D Jimenez, S Schiller, JT Lowy, DR Quint, W Sherman, ME Schussler, J Wacholder, S AF Kreimer, Aimee R. Cecilia Rodriguez, Ana Hildesheim, Allan Herrero, Rolando Porras, Carolina Schiffman, Mark Gonzalez, Paula Solomon, Diane Jimenez, Silvia Schiller, John T. Lowy, Douglas R. Quint, Wim Sherman, Mark E. Schussler, John Wacholder, Sholom CA CVT Vaccine Grp TI Proof-of-Principle Evaluation of the Efficacy of Fewer Than Three Doses of a Bivalent HPV16/18 Vaccine SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-PAPILLOMAVIRUS; BROAD-SPECTRUM; PCR; INFECTION; TRIAL; ASSAY AB Background Three-dose regimens for human papillomavirus (HPV) vaccines are expensive and difficult to complete, especially in settings where the need for cervical cancer prevention is greatest. Methods We evaluated the vaccine efficacy of fewer than three doses of the HPV16/18 vaccine Cervarix in our Costa Rica Vaccine Trial. Women were randomly assigned to receive three doses of the HPV16/18 vaccine or to a control vaccine and were followed for incident HPV16 or HPV18 infection that persisted in visits that were 10 or more months apart (median follow-up 4.2 years). After excluding women who had no follow-up or who were HPV16 and HPV18 DNA positive at enrollment, 5967 women received three vaccine doses (2957 HPV vaccine vs 3010 control vaccine), 802 received two doses (422 HPV vs 380 control), and 384 received one dose (196 HPV vs 188 control). Reasons for receiving fewer doses and other pre- and post-randomization characteristics were balanced within each dosage group between women receiving the HPV and control vaccines. Results Incident HPV16 or HPV18 infections that persisted for 1 year were unrelated to dosage of the control vaccine. Vaccine efficacy was 80.9% for three doses of the HPV vaccine (95% confidence interval [CI] = 71.1% to 87.7%; 25 and 133 events in the HPV and control arms, respectively), 84.1% for two doses (95% CI = 50.2% to 96.3%; 3 and 17 events), and 100% for one dose (95% CI = 66.5% to 100%; 0 and 10 events). Conclusion Four years after vaccination of women who appeared to be uninfected, this nonrandomized analysis suggests that two doses of the HPV16/18 vaccine, and maybe even one dose, are as protective as three doses. C1 [Kreimer, Aimee R.; Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Wacholder, Sholom] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Solomon, Diane] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, NIH, Rockville, MD 20852 USA. [Schiller, John T.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Rockville, MD 20852 USA. [Cecilia Rodriguez, Ana; Herrero, Rolando; Porras, Carolina; Gonzalez, Paula; Jimenez, Silvia] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Quint, Wim] DDL Diagnost Lab, Voorburg, Netherlands. [Schussler, John] Informat Management Syst, Rockville, MD USA. [Herrero, Rolando] Int Agcy Res Canc, Early Detect & Prevent Sect, F-69372 Lyon, France. RP Kreimer, AR (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7084, Rockville, MD 20852 USA. EM kreimera@mail.nih.gov RI Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015 OI Hildesheim, Allan/0000-0003-0257-2363; FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on Women's Health; Ministry of Health of Costa Rica FX The Costa Rica HPV Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the US National Cancer Institute (NCI). The trial is sponsored and funded by the NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women's Health.; This study was conducted with the support from the Ministry of Health of Costa Rica. Vaccine was provided for our trial by GlaxoSmithKline Biologicals (GSK), under a Clinical Trials Agreement with the NCI. GSK also provided support for aspects of the trial associated with regulatory submission needs of the company under FDA BB-IND 7920. SchillerJ. T. Schiller and D. R. Lowy report that they are named inventors on US government-owned HPV vaccine patents that are licensed to GSK and Merck and for which the NCI receives licensing fees. J. T. Schiller and D. R. Lowy are entitled to limited royalties as specified by federal law. No other financial disclosures were reported. NR 19 TC 170 Z9 170 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT PY 2011 VL 103 IS 19 BP 1444 EP 1451 DI 10.1093/jnci/djr319 PG 8 WC Oncology SC Oncology GA 830UX UT WOS:000295683800008 PM 21908768 ER PT J AU Schiffman, M Wentzensen, N Wacholder, S Kinney, W Gage, JC Castle, PE AF Schiffman, Mark Wentzensen, Nicolas Wacholder, Sholom Kinney, Walter Gage, Julia C. Castle, Philip E. TI Re: Human Papillomavirus Testing in the Prevention of Cervical Cancer Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Schiffman, Mark; Wentzensen, Nicolas; Wacholder, Sholom; Gage, Julia C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. [Castle, Philip E.] Amer Soc Clin Pathologists, Washington, DC USA. RP Schiffman, M (reprint author), Rm 7012,6120 Execut Blvd, Rockville, MD 20852 USA. EM schiffmm@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT PY 2011 VL 103 IS 19 BP 1483 EP U73 DI 10.1093/jnci/djr309 PG 2 WC Oncology SC Oncology GA 830UX UT WOS:000295683800016 ER PT J AU Brewinski, M Megazzini, K Hance, LF Cruz, MC Pavia-Ruz, N Della Negra, M Ferreira, FGF Marques, H Hazra, R AF Brewinski, Margaret Megazzini, Karen Hance, Laura Freimanis Cashat Cruz, Miguel Pavia-Ruz, Noris Della Negra, Marinella Faleiro Ferreira, Flavia Gomes Marques, Heloisa Hazra, Rohan CA NISDI Pediat Study Grp 2010 TI Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy* SO JOURNAL OF TROPICAL PEDIATRICS LA English DT Article DE HIV; cholesterol; triglycerides; pediatric ID CARDIOVASCULAR RISK-FACTORS; PROTEASE INHIBITORS; YOUNG; ASSOCIATION; CHILDHOOD; ATHEROSCLEROSIS; DISEASE; OBESITY AB In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3-5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9-6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART. C1 [Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. [Brewinski, Margaret] US Agcy Int Dev, Off HIV AIDS, Washington, DC 20005 USA. [Megazzini, Karen; Hance, Laura Freimanis] Westat Corp, Rockville, MD 20850 USA. [Cashat Cruz, Miguel; Pavia-Ruz, Noris] Hosp Infantil Mexico Dr Federico Gomez, Dept Infectol, Clin Inmunodeficiencias, Federico Gomez 06720, Mexico. [Della Negra, Marinella] Inst Infectol Emilio Ribas, BR-02146900 Sao Paulo, Brazil. [Faleiro Ferreira, Flavia Gomes] Univ Fed Minas Gerais, Sch Med, BR-30130100 Belo Horizonte, MG, Brazil. [Marques, Heloisa] Univ Sao Paulo, Inst Crianca HCFM, BR-05403900 Sao Paulo, Brazil. RP Hazra, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA. EM hazrar@mail.nih.gov RI Mussi-Pinhata, Marisa/G-6568-2012 FU National Institutes of Health (NICHD) [HHSN2672008 00001C, N01-HD-3-3345, N01-HD-8-0001] FX This work was supported by the National Institutes of Health (NICHD Contract # HHSN2672008 00001C [NICHD Control #: N01-HD-3-3345 and N01-HD-8-0001]). NR 26 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0142-6338 J9 J TROP PEDIATRICS JI J. Trop. Pediatr. PD OCT PY 2011 VL 57 IS 5 BP 324 EP 332 DI 10.1093/tropej/fmq089 PG 9 WC Pediatrics; Tropical Medicine SC Pediatrics; Tropical Medicine GA 828VU UT WOS:000295532600003 PM 20889625 ER PT J AU Ballyns, JJ Shah, JP Hammond, J Gebreab, T Gerber, LH Sikdar, S AF Ballyns, Jeffrey J. Shah, Jay P. Hammond, Jennifer Gebreab, Tadesse Gerber, Lynn H. Sikdar, Siddhartha TI Objective Sonographic Measures for Characterizing Myofascial Trigger Points Associated With Cervical Pain SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE color Doppler imaging; elastography; myofascial trigger points; sonography ID SKELETAL-MUSCLE; BLOOD-FLOW; SOFT-TISSUE; ANGIOGENESIS; INFLAMMATION; PRESSURE; REMOTE; MTRPS AB Objectives-The purpose of this study was to determine whether the physical properties and vascular environment of active myofascial trigger points associated with acute spontaneous cervical pain, asymptomatic latent trigger points, and palpably normal muscle differ in terms of the trigger point area, pulsatility index, and resistivity index, as measured by sonoelastography and Doppler imaging. Methods-Sonoelastography was performed with an external 92-Hz vibration in the upper trapezius muscles in patients with acute cervical pain and at least 1 palpable trigger point (n = 44). The area of reduced vibration amplitude was measured as an estimate of the size of the stiff myofascial trigger points. Patients also underwent triplex Doppler imaging of the same region to analyze blood flow waveforms and calculate the pulsatility index of blood flow in vessels at or near the trigger points. Results On sonoelastography, active sites (spontaneously painful with palpable myofascial trigger points) had larger trigger points (mean +/- SD, 0.57 +/- 0.20 cm(2)) compared to latent sites (palpable trigger points painful on palpation; 0.36 +/- 0.16 cm(2)) and palpably normal sites (0.17 +/- 0.22 cm(2); P <.01). Analysis of receiver operating characteristic curves showed that area measurements could robustly distinguish between active, latent, and normal sites (areas under the curve, 0.9 for active versus latent, 0.8 for active versus normal, and 0.8 for latent versus normal, respectively). Doppler spectral waveform data showed that vessels near active sites had a significantly higher pulsatility index (median, 8.3) compared to normal sites (median, 3.0; P <.05). Conclusions-The results presented in this study show that myofascial trigger points may be classified by area using sonoelastography. Furthermore, monitoring the trigger point area and pulsatility index may be useful in evaluating the natural history of myofascial pain syndrome. C1 [Ballyns, Jeffrey J.; Sikdar, Siddhartha] George Mason Univ, Dept Elect & Comp Engn, Fairfax, VA 22030 USA. [Gerber, Lynn H.] George Mason Univ, Coll Hlth & Human Serv, Fairfax, VA 22030 USA. [Shah, Jay P.; Hammond, Jennifer; Gebreab, Tadesse] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Sikdar, S (reprint author), George Mason Univ, Dept Elect & Comp Engn, 4400 Univ Dr,MS 1G5, Fairfax, VA 22030 USA. EM ssikdar@gmu.edu FU National Institutes of Health (NIH); Clinical Center and Office of the Director, NIH [1R01-AR057348]; National Institutes of Arthritis and Musculoskeletal and Skin Diseases, NIH FX This research was supported in part by the Intramural Research Program, National Institutes of Health (NIH), the Clinical Center and Office of the Director, NIH, and grant 1R01-AR057348 from the National Institutes of Arthritis and Musculoskeletal and Skin Diseases, NIH. NR 36 TC 36 Z9 37 U1 0 U2 4 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD OCT PY 2011 VL 30 IS 10 BP 1331 EP 1340 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 829BW UT WOS:000295551300003 PM 21968483 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. [Gipson, Chester] USDA, APHIS, AC, Washington, DC USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 2011 VL 40 IS 10 BP 297 EP 297 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 830ZQ UT WOS:000295698800016 PM 22358204 ER PT J AU Guardiani, E Zalewski, C Brewer, C Merideth, M Introne, W Smith, ACM Gordon, L Gahl, W Kim, HJ AF Guardiani, Elizabeth Zalewski, Christopher Brewer, Carmen Merideth, Melissa Introne, Wendy Smith, Ann C. M. Gordon, Leslie Gahl, William Kim, H. Jeffrey TI Otologic and Audiologic Manifestations of Hutchinson-Gilford Progeria Syndrome SO LARYNGOSCOPE LA English DT Article DE Hutchinson-Gilford Progeria syndrome; hearing loss; progeria; middle ear; external ear ID SENSORINEURAL HEARING-LOSS; PHENOTYPE; RECURRENT; CHILDREN AB Objectives/Hypothesis: To define the audiologic and otologic phenotype of Hutchinson-Gilford progeria syndrome (HGPS). Study Design: Prospective case series. Methods: Fifteen patients with HGPS were enrolled in a prospective natural history study; 14 were evaluated in the neurotology clinic, and 11 received audiologic evaluations. The physical exam and audiologic findings of these patients were reviewed to define an otologic and audiologic phenotype for HGPS in the largest series of subjects in the literature. Results: All patients were noted to have stiff auricular cartilages, small or absent lobules, and hypoplasia of the lateral soft-tissue portion of the external ear canal leading to a shortened canal. Ten of 14 patients (71%) had dry cerumen impaction, and four of 14 patients (29%) reported a history of recurrent otitis media. Nineteen of 22 ears (86.4%) demonstrated low-frequency conductive hearing loss in the 250 to 500 Hz range. Sixteen of 22 ears (73%) had type A tympanograms; three of 22 ears (14%) displayed bimodal or "W" peaked tympanograms; two of 22 ears (9%) had type B tympanograms; one of 22 ears (4%) had a type C tympanogram. Nine of 10 patients had distortion product otoacoustic emissions consistent with normal peripheral hearing sensitivity. Conclusions: HGPS is caused by a mutation in the LMNA gene resulting in the production of an abnormal nuclear protein; this in turn affects nuclear structure and function. Patients with HGPS have characteristic otologic features due to cartilaginous and subcutaneous tissue abnormalities and typically demonstrate low-frequency conductive hearing loss despite largely normal tympanometry. It is important to be aware of these conditions in managing these patients. C1 [Guardiani, Elizabeth; Kim, H. Jeffrey] Georgetown Univ Hosp, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA. [Zalewski, Christopher; Brewer, Carmen; Kim, H. Jeffrey] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. [Merideth, Melissa; Introne, Wendy; Smith, Ann C. M.; Gahl, William] NHGRI, Bethesda, MD 20892 USA. [Gordon, Leslie] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Gordon, Leslie] Hasbro Childrens Hosp, Dept Pediat, Providence, RI USA. [Gordon, Leslie] Harvard Univ, Sch Med, Dept Anesthesia, Childrens Hosp Boston, Boston, MA 02115 USA. RP Kim, HJ (reprint author), Georgetown Univ Hosp, Dept Otolaryngol Head & Neck Surg, 1st Floor Gorman Bldg,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM hk7@georgetown.edu RI SMITH, ANN C.M./C-1122-2008 FU National Human Genome Research Institute; National Institute on Deafness and Other Communication Disorders FX This work was supported by the intramural research programs of the National Human Genome Research Institute and the National Institute on Deafness and Other Communication Disorders. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 25 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2011 VL 121 IS 10 BP 2250 EP 2255 DI 10.1002/lary.22151 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 824UX UT WOS:000295228800036 PM 21898437 ER PT J AU Shevtsov, AB Kushugulova, AR Tynybaeva, IK Kozhakhmetov, SS Abzhalelov, AB Momynaliev, KT Stoyanova, LG AF Shevtsov, A. B. Kushugulova, A. R. Tynybaeva, I. K. Kozhakhmetov, S. S. Abzhalelov, A. B. Momynaliev, K. T. Stoyanova, L. G. TI Identification of phenotypically and genotypically related Lactobacillus strains based on nucleotide sequence analysis of the groEL, rpoB, rplB, and 16S rRNA genes SO MICROBIOLOGY LA English DT Article DE national fermented milk drinks; identification; genotyping; Lactobacillus; 16S rRNA genes; groEL; rplB; rpoB genes ID ALIGNMENT; BACTERIA; PRODUCTS AB Sixty-eight cultures of lactic acid bacteria were isolated and identified from national fermented milk drinks (airan, koumiss, kurunga, shubat) home-made in different regions of the Republic of Kazakhstan and the Buryat Republic of Russia. The cultures of lactic acid bacteria of the genus Lactobacillus were identified as L. paracasei and L. rhamnosus related to the L. casei group and as L. brevis, L. buchneri, L. diolivorans, and L. parabuchneri (the L. buchneri group) using the classical microbiological methods and on the basis of the 16S rRNA gene sequence analysis. The polymorphism of the nucleotide sequences of the genes groEL, rpoB, and rplB encoding specific proteins was studied for intraspecific differentiation of the lactobacilli. The analysis of these genes allowed a more accurate identification of the lactobacilli that are genetically and phenotypically related to the L. casei group as L. paracasei subsp. paracasei and L. paracasei subsp. tolerans. The gene nucleotide sequences of all the genotyped strains were deposited in the GenBank database. C1 [Stoyanova, L. G.] Moscow MV Lomonosov State Univ, Fac Biol, Dept Microbiol, Moscow 119992, Russia. [Shevtsov, A. B.; Momynaliev, K. T.] Republ Kazakhstan Natl Ctr Biotechnol, Astana, Kazakhstan. [Kushugulova, A. R.; Tynybaeva, I. K.; Kozhakhmetov, S. S.; Abzhalelov, A. B.] Republican Collect Microorganisms, Astana, Kazakhstan. RP Stoyanova, LG (reprint author), Moscow MV Lomonosov State Univ, Fac Biol, Dept Microbiol, Moscow 119992, Russia. EM stoyanovamsu@mail.ru RI Kushugulova, Almagul/C-7185-2012; OI Kushugulova, Almagul/0000-0001-9479-0899; Shevtsov, Alexandr/0000-0002-7576-2750 NR 23 TC 2 Z9 2 U1 2 U2 23 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0026-2617 EI 1608-3237 J9 MICROBIOLOGY+ JI Microbiology PD OCT PY 2011 VL 80 IS 5 BP 672 EP 681 DI 10.1134/S0026261711050134 PG 10 WC Microbiology SC Microbiology GA 830UI UT WOS:000295682300010 ER PT J AU Enewold, L Zhou, J Devesa, SS Erickson, RL Zhu, KM McGlynn, KA AF Enewold, Lindsey Zhou, Jing Devesa, Susan S. Erickson, Ralph L. Zhu, Kangmin McGlynn, Katherine A. TI Trends in Testicular Germ Cell Tumors Among US Military Servicemen, 1990-2003 SO MILITARY MEDICINE LA English DT Article ID UNITED-STATES; CANCER; RATES AB Objective: To determine the incidence of testicular germ cell tumors among active duty males and compare it with the incidence in the general U.S. population. Methods: The Automated Cancer Tumor Registry and the Surveillance, Epidemiology, and End Results Program data from 1990 to 2003 were analyzed for men aged between 20 and 59 years by histology and stage at diagnosis. Rates were age adjusted using the male active duty military population as the standard. Results: Nonseminoma incidence was significantly lower in the military than in the general population (incidence rate ratio = 0.90, 95% confidence interval = 0.82-0.98). Trends in incidence tended to be similar in both the populations. Increases were observed for both histologic types but were only significant for seminoma (Automated Cancer Tumor Registry: 21% and Surveillance, Epidemiology, and End Results program: 16%; p < 0.05). Increases in incidence were only observed for localized tumors of both histologic types. Conclusions: The lower incidence of non-seminoma in the military and the increased incidence of localized tumors in both populations remain unexplained. C1 [Enewold, Lindsey; Zhou, Jing; Zhu, Kangmin] Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA. [Devesa, Susan S.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Erickson, Ralph L.] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. [Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Enewold, L (reprint author), Walter Reed Army Med Ctr, US Mil Canc Inst, 6900 Georgia Ave NW,Bldg 1,Suite A 109, Washington, DC 20307 USA. FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; United States Military Cancer Institute via the Uniformed Services University of the Health Sciences under Henry M. Jackson Foundation for the Advancement of Military Medicine FX This study was partly supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by the United States Military Cancer Institute via the Uniformed Services University of the Health Sciences under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine. NR 15 TC 4 Z9 5 U1 0 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2011 VL 176 IS 10 BP 1184 EP 1187 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 831EK UT WOS:000295711300019 PM 22128656 ER PT J AU Dozmorov, IM Jarvis, J Saban, R Benbrook, DM Wakeland, E Aksentijevich, I Ryan, J Chiorazzi, N Guthridge, JM Drewe, E Tighe, PJ Centola, M Lefkovits, I AF Dozmorov, Igor M. Jarvis, James Saban, Ricardo Benbrook, Doris M. Wakeland, Edward Aksentijevich, Ivona Ryan, John Chiorazzi, Nicholas Guthridge, Joel M. Drewe, Elizabeth Tighe, Patrick J. Centola, Michael Lefkovits, Ivan TI Internal standard-based analysis of microarray data2-Analysis of functional associations between HVE-genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; JUVENILE RHEUMATOID-ARTHRITIS; LNCAP CELL-PROLIFERATION; EXPRESSION; PATHWAYS; CANCER; 5-ALPHA-ANDROSTANE-3-ALPHA; SUSCEPTIBILITY; INFLAMMATION; RECEPTORS AB In this work we apply the Internal Standard-based analytical approach that we described in an earlier communication and here we demonstrate experimental results on functional associations among the hypervariably-expressed genes (HVE-genes). Our working assumption was that those genetic components, which initiate the disease, involve HVE-genes for which the level of expression is un-distinguishable among healthy individuals and individuals with pathology. We show that analysis of the functional associations of the HVE-genes is indeed suitable to revealing disease-specific differences. We show also that another possible exploit of HVE-genes for characterization of pathological alterations is by using multivariate classification methods. This in turn offers important clues on naturally occurring dynamic processes in the organism and is further used for dynamic discrimination of groups of compared samples. We conclude that our approach can uncover principally new collective differences that cannot be discerned by individual gene analysis. C1 [Dozmorov, Igor M.; Guthridge, Joel M.; Centola, Michael] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Jarvis, James; Saban, Ricardo; Benbrook, Doris M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Wakeland, Edward] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Aksentijevich, Ivona; Ryan, John] NIAMSD, Bethesda, MD 20892 USA. [Chiorazzi, Nicholas] N Shore Univ Hosp, Feinstein Inst Med Res, Manhasset, NY USA. [Chiorazzi, Nicholas] N Shore Univ Hosp, Dept Med, Manhasset, NY USA. [Chiorazzi, Nicholas] N Shore Univ Hosp, Dept Cell Biol, Manhasset, NY USA. [Chiorazzi, Nicholas] Albert Einstein Coll Med, Manhasset, NY USA. [Drewe, Elizabeth; Tighe, Patrick J.] Univ Nottingham, Nottingham NG7 2RD, England. [Lefkovits, Ivan] Univ Clin Basel, Dept Biomed, CH-4051 Basel, Switzerland. RP Dozmorov, IM (reprint author), Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. EM igor-dozmorov@omrf.org RI Lefkovits, Ivan/B-9777-2009 OI Lefkovits, Ivan/0000-0003-1783-8881 FU National Institutes of Health [P20 RR020143, R01 AI045050, P30 AR053483, P20RR016478, R01 AI084200, CA106713]; Royal College of Pathology UK; Journal of Experimental Pathology; Jones Charitable Trust FX The National Institutes of Health (P20 RR020143 to I. D., R01 AI045050 to I. D., P30 AR053483 to I. D. and J.G., P20RR016478 to I. D., R01 AI084200 to I. D. and J.J., CA106713 to D. B.); The Royal College of Pathology UK and The Journal of Experimental Pathology (to E. D. and P.J.T.); and The Jones Charitable Trust (to E. D. and P.J.T.). Funding for open access charge: P20RR016478. NR 35 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 18 BP 7881 EP 7899 DI 10.1093/nar/gkr503 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 830WC UT WOS:000295687700009 PM 21715372 ER PT J AU McNeill, DR Lin, PC Miller, MG Pistell, PJ de Souza-Pinto, NC Fishbein, KW Spencer, RG Liu, Y Pettan-Brewer, C Ladiges, WC Wilson, DM AF McNeill, Daniel R. Lin, Ping-Chang Miller, Marshall G. Pistell, Paul J. de Souza-Pinto, Nadja C. Fishbein, Kenneth W. Spencer, Richard G. Liu, Yie Pettan-Brewer, Christina Ladiges, Warren C. Wilson, David M., III TI XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; STRAND BREAK REPAIR; DNA-LIGASE-III; DAMAGE; DISEASE; PROTEIN; CANCER; MOUSE; GENE; POLYMORPHISMS AB Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median lifespan of similar to 26 months and a nearly identical maximal life expectancy of similar to 37 months. However, a number of HZ animals (7 of 92) showed a propensity for abdominal organ rupture, which may stem from developmental abnormalities given the prominent role of XRCC1 in endoderm and mesoderm formation. For other end-points evaluated-weight, fat composition, blood chemistries, condition of major organs, tissues and relevant cell types, behavior, brain volume and function, and chromosome and telomere integrity-HZ mice exhibited by-and-large a normal phenotype. Treatment of animals with the alkylating agent azoxymethane resulted in both liver toxicity and an increased incidence of precancerous lesions in the colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals has little effect on chronological longevity and many key biological markers of aging in the absence of environmental challenges, but may adversely affect normal animal development or increase disease susceptibility to a relevant genotoxic exposure. C1 [McNeill, Daniel R.; Liu, Yie; Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, IRP,Biomed Res Ctr, Baltimore, MD 21224 USA. [Lin, Ping-Chang; Fishbein, Kenneth W.; Spencer, Richard G.] NIA, Clin Invest Lab, NIH, IRP,Biomed Res Ctr, Baltimore, MD 21224 USA. [Miller, Marshall G.] Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Pistell, Paul J.] Towson Univ, Dept Psychol, Towson, MD 21252 USA. [de Souza-Pinto, Nadja C.] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo, Brazil. [Pettan-Brewer, Christina; Ladiges, Warren C.] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, IRP,Biomed Res Ctr, Baltimore, MD 21224 USA. EM wladiges@u.washington.edu; wilsonda@mail.nih.gov RI Souza-Pinto, Nadja/C-3462-2013; 3, INCT/H-4497-2013; Redoxoma, Inct/H-9962-2013; OI Souza-Pinto, Nadja/0000-0003-4206-964X; Lin, Ping-Chang/0000-0003-0918-4072; Fishbein, Kenneth/0000-0002-6353-4603 FU National Institute on Aging; National Institute of Environmental Health Sciences [R21ES016572] FX Funding for open access charge: Intramural Research Program of the National Institute on Aging and National Institute of Environmental Health Sciences grant R21ES016572 (to W.L.). NR 35 TC 13 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2011 VL 39 IS 18 BP 7992 EP 8004 DI 10.1093/nar/gkr280 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 830WC UT WOS:000295687700017 PM 21737425 ER PT J AU Molino-Lova, R Macchi, C Gori, AM Marcucci, R Polcaro, P Cecchi, F Lauretani, F Bandinelli, S Abbate, R Beghi, E Guralnik, JM Ferrucci, L AF Molino-Lova, R. Macchi, C. Gori, A. M. Marcucci, R. Polcaro, P. Cecchi, F. Lauretani, F. Bandinelli, S. Abbate, R. Beghi, E. Guralnik, J. M. Ferrucci, L. TI High sensitivity C-reactive protein predicts the development of new carotid artery plaques in older persons SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Article DE C-reactive protein; Atherosclerosis; Carotid arteries; Risk factors; Older persons ID INTIMA-MEDIA THICKNESS; GLOBAL CARDIOVASCULAR RISK; ATHEROSCLEROSIS PROGRESSION; MONOCYTE COUNT; INFLAMMATION; CORONARY; ROTTERDAM; POPULATION; MEN; INTERLEUKIN-6 AB Background and Aim: Previous studies have shown that increased levels of C-reactive protein (CRP) predict cardiovascular events, including stroke, myocardial infarction and death from cardiovascular causes. Previous studies have also shown that increased levels of CRP are strong predictors of the progression of pre-existing carotid artery plaques. However, whether CRP is involved in the development of new plaques, that may or may not be associated with clinical events, in subjects with clean carotid arteries has been scarcely investigated. Methods and Results: 486 "InCHIANTI'' Study participants (200 men and 286 women, 72% aged 65 years and over) free from carotid artery plaques at baseline, also underwent carotid artery scan three years later. We tested the association of baseline characteristics, cardiovascular risk factors and inflammatory markers with the development of new carotid artery plaques. Older participants were significantly more likely to develop new plaques. Independent of age, the relative risks of developing new plaques associated with heavy smoking and family history of atherosclerosis were 1.7 (95% CI 1.5-1.9) and 1.9 (95% CI 1.2-3.1), respectively.Participants with high (> 3 mu g/mL) and moderate (>= 1 and <= 3 mu g/mL) CRP levels had a relative risk of 2.2 (95% CI 1.9-2.6) and 1.9 (95% CI 1.6-2.3) respectively, when compared with subjects with low (<1 mu g/mL) CRP levels. Surprisingly, risk factors such as hypertension, diabetes, dyslipidemia and overweight/obesity were not significant predictors of the development of new carotid artery plaques. Conclusions: High CRP levels independently predict the development of new plaques in older persons with carotid arteries free from atherosclerotic lesions. (C) 2010 Elsevier B.V. All rights reserved. C1 [Molino-Lova, R.; Macchi, C.; Gori, A. M.; Polcaro, P.; Cecchi, F.] Fdn Don C Gnocchi, Dept Cardiovasc Rehabil, I-50020 Florence, Italy. [Molino-Lova, R.] Fdn Don C Gnocchi, Dept Cardiopulm Rehabil, Massa, Italy. [Gori, A. M.; Marcucci, R.] Univ Florence, Dept Med & Surg Crit Care, Ctr Study Mol & Clin Level Chron Degenerat & Neop, Florence, Italy. [Lauretani, F.] Tuscany Hlth Reg Agcy, Florence, Italy. [Bandinelli, S.] ASF, Geriatr Rehabil Unit, Florence, Italy. [Beghi, E.] Mario Negri Inst Pharmacol Res, Lab Neurol Disorders, Milan, Italy. [Guralnik, J. M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. RP Molino-Lova, R (reprint author), Fdn Don C Gnocchi, Dept Cardiovasc Rehabil, Via Imprunetana 124, I-50020 Florence, Italy. EM rmolino@dongnocchi.it RI Lauretani, Fulvio/K-5115-2016; OI Gori, annamaria.gori@unifi.it/0000-0001-6857-5861; Marcucci, Rossella/0000-0001-9549-7176; Lauretani, Fulvio/0000-0002-5287-9972; Cecchi, Franco/0000-0002-2035-5621 FU NIA NIH HHS [N01 AG916413] NR 39 TC 9 Z9 11 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD OCT PY 2011 VL 21 IS 10 BP 776 EP 782 DI 10.1016/j.numecd.2010.02.003 PG 7 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA 830DS UT WOS:000295638100004 PM 20554169 ER PT J AU Apud, JA AF Apud, Jose A. TI The extraction, isolation and purification of an endogenous regulator for the 5-HT2 receptor SO PHARMACOLOGICAL RESEARCH LA English DT Review DE Endocoids; 5-HT2 receptor; H-3-Ketanserin; PI turnover; 293 cells AB Early studies indicated that serotonin, a primary transmitter in the central nervous system, may not represent the primary endogenous regulator for the 5-HT2 receptor labeled by [H-3]-ketanserin. Instead, an endogenous ligand may be responsible for modulating the [H-3]-ketanserin site. Through different isolation and purification procedures, a pronase-sensitive peptide with activity on [H-3]-ketanserin binding was identified in the rat brain. This peptide seems specific for the 5-HT2 receptor since it does not displace the binding of [H-3]-mipramine or [H-3]-mianserin from rat cortical membranes and is able to stimulate PI turnover in a ketanserin sensitive fashion. Given the role of 5-HT2 receptors in the action of antidepressants, this finding may help understand some of the molecular mechanisms involved in antidepressant effect. Published by Elsevier Ltd. C1 NIMH, Clin Brain Disorders Branch, GCAP, NIH, Bethesda, MD 20892 USA. RP Apud, JA (reprint author), NIMH, Clin Brain Disorders Branch, GCAP, NIH, Bldg 10,CRC 7-3342,10 Ctr Dr, Bethesda, MD 20892 USA. EM apudj@mail.nih.gov NR 4 TC 1 Z9 1 U1 1 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD OCT PY 2011 VL 64 IS 4 BP 312 EP 313 DI 10.1016/j.phrs.2011.05.022 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 831YO UT WOS:000295767200003 PM 21683793 ER PT J AU Armstrong, D AF Armstrong, David TI Age- and disease-related neuroplasticity of chemically identified neuronal circuits: A tribute to Professor Erminio Costa SO PHARMACOLOGICAL RESEARCH LA English DT Review DE Alzheimer's disease; NMDA; Hippocampus; AMPA; Glutamate ID RECEPTOR SUBTYPE IMMUNOREACTIVITY; ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; ENTORHINAL CORTEX; PLAQUES AB The following review highlights a small portion of the research ongoing in my laboratory at the Fidia Georgetown Institute of Neuroscience (FGIN) during the years 1989-1994. Specifically, this work focused on the selective vulnerability of neurons in Alzheimer's disease. At the time, it was known that alpha-amino3-hydroxy-5-methyl-4-isoaxolepropionate (AMPA) receptors were composed of one or more subunits (GluR1-4). Furthermore, the presence of the GluR2 subunit was known to substantially reduce Ca(2+) through AMPA receptors in response to ligand binding. This finding led us to hypothesize that the presence or absence of the GluR2 subunit in the AMPA receptor may have a profound influence on the ability of the cell to gate extracellular Ca(2+) and maintain intracellular calcium homeostasis. Furthermore, in Alzheimer's disease we hypothesized that cells at risk for developing AD neuropathology will express certain combinations of glutamate receptor subunits that form channels with increased permeability to Ca(2+). In turn, these cells may become more vulnerable to the pathologic consequences of increased intracellular Ca(2+) and destabilized intracellular Ca(2+) homeostasis. To test this hypothesis we employed anatomical techniques and examined post mortem materials from patients with AD. The results of these studies are summarized in this review. Notably, this review also highlights the valuable collaborations established during my five years at FGIN and pays tribute to the intellectually rich and supportive environment provided by Dr. Costa and colleagues. (C) 2011 Published by Elsevier Ltd. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Armstrong, D (reprint author), NIMH, NIH, Neurosci Bldg,Room 6138,6001 Execut Blvd,MSC 9606, Bethesda, MD 20892 USA. EM armstrda@mail.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD OCT PY 2011 VL 64 IS 4 BP 336 EP 338 DI 10.1016/j.phrs.2011.05.023 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 831YO UT WOS:000295767200012 PM 21704164 ER PT J AU Schwandt, ML Lindell, SG Higley, JD Suomi, SJ Heilig, M Barr, CS AF Schwandt, Melanie L. Lindell, Stephen G. Higley, James D. Suomi, Stephen J. Heilig, Markus Barr, Christina S. TI OPRM1 gene variation influences hypothalamic-pituitary-adrenal axis function in response to a variety of stressors in rhesus macaques SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Opioids; Hypothalamic-pituitary-adrenal (HPA) axis; Cortisol; Stress; Nonhuman primate; Separation; Alcohol; Postpartum depression ID MU-OPIOID-RECEPTOR; SINGLE NUCLEOTIDE POLYMORPHISM; ENDOGENOUS OPIOIDS; HPA AXIS; PHYSIOLOGICAL-RESPONSES; MORPHINE CONSUMPTION; ALCOHOL DEPENDENCE; A118G POLYMORPHISM; PLASMA-CORTISOL; RESPIRATORY DEPRESSION AB The endogenous opioid system is involved in modulating a number of behavioral and physiological systems, including the hypothalamic pituitary adrenal (HPA) axis. In humans, a functional variant in the OPRM1 gene (OPRM1 A118G) is associated with a number of outcomes, including attenuated HPA axis responses to stress. A nonsynonymous variant (OPRM1 C77G) in the rhesus macaque has been shown to have similar effects in vivo to the human variant. The current study investigated whether OPRM1 C77G influences HPA axis response to stress in rhesus macaques. We analyzed plasma adrenocorticotropic hormone (ACTH) and cortisol levels measured in response to three different stressors: (1) maternal separation in infant subjects at 6 months of age, (2) acute ethanol administration in adolescent subjects at 4 years of age, and (3) postpartum HPA axis function in adult rhesus macaque females. For the maternal separation paradigm, ACTH and cortisol levels were determined at baseline as well as peak levels during each of 4 consecutive separation episodes. For the acute ethanol administration paradigm, hormone levels were determined at baseline and again at 5 min, 10 min, and 60 min following the ethanol infusion. For postpartum sampling, hormone levels were determined at postpartum days 7, 14, 21, 30, 60, 90, 120, and 150. Infants carrying the 77G allele exhibited lower levels of cortisol across all 4 separation episodes. Furthermore, adolescents carrying the 77G allele exhibited lower cortisol levels at 5 and 10 min following acute ethanol administration. Adult females with prior reproductive experience and who carry the 77G allele exhibited lower cortisol levels across the postpartum period. No significant genotype effects were found for ACTH, although there were some trends for lower ACTH levels in 77G allele carriers. These data are consistent with human studies that have demonstrated attenuated cortisol responses to stress among carriers of the OPRM1 118G allele, lending further support to the argument that the rhesus and human allelic variants are functionally similar. Our results also suggest that OPRM1 variation may influence coping style, as well as alcohol-induced and postpartum levels of HPA axis activity and, as such, may modify vulnerability to alcohol use disorders and postpartum depression. Published by Elsevier Ltd. C1 [Schwandt, Melanie L.; Lindell, Stephen G.; Heilig, Markus; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Lindell, Stephen G.; Barr, Christina S.] NIAAA, Sect Comparat Behav Genom, LNG, NIH, Rockville, MD 20852 USA. [Higley, James D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, Stephen J.] NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. RP Schwandt, ML (reprint author), 10 Ctr Dr,10CRC 1-5330, Bethesda, MD 20892 USA. EM melanies@mail.nih.gov RI Schwandt, Melanie/L-9866-2016; OI Heilig, Markus/0000-0003-2706-2482 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Child Health and Human Development (NICHD) FX Funding for this study was provided by the intramural programs of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute of Child Health and Human Development (NICHD). The NIAAA and NICHD had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 88 TC 18 Z9 18 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD OCT PY 2011 VL 36 IS 9 BP 1303 EP 1311 DI 10.1016/j.psyneuen.2011.03.002 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 829TZ UT WOS:000295608500005 PM 21459516 ER PT J AU de Gonzalez, AB Brenner, A Hartge, P Lee, C Morton, L Rajaraman, P AF de Gonzalez, Amy Berrington Brenner, Alina Hartge, Patricia Lee, Choonsik Morton, Lindsay Rajaraman, Preetha TI Evolving Strategies in Epidemiologic Research on Radiation and Cancer SO RADIATION RESEARCH LA English DT Editorial Material ID US RADIOLOGIC TECHNOLOGISTS; ATOMIC-BOMB SURVIVORS; BREAST-CANCER; IONIZING-RADIATION; CHILDHOOD-CANCER; LUNG-CANCER; HODGKINS-LYMPHOMA; POOLED ANALYSIS; THYROID-CANCER; RISK C1 [de Gonzalez, Amy Berrington; Brenner, Alina; Hartge, Patricia; Lee, Choonsik; Morton, Lindsay; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP de Gonzalez, AB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM berringtona@mail.nih.gov RI Morton, Lindsay/B-5234-2015; Lee, Choonsik/C-9023-2015 OI Morton, Lindsay/0000-0001-9767-2310; Lee, Choonsik/0000-0003-4289-9870 NR 35 TC 1 Z9 1 U1 1 U2 3 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2011 VL 176 IS 4 BP 527 EP 532 DI 10.1667/RRXX37.1 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 829SV UT WOS:000295605500011 PM 21823973 ER PT J AU Linet, M Kleinerman, R Mabuchi, K AF Linet, Martha Kleinerman, Ruth Mabuchi, Kiyohiko TI IN MEMORIAM Elaine Ron 1943-2010 SO RADIATION RESEARCH LA English DT Biographical-Item C1 [Linet, Martha; Kleinerman, Ruth; Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Linet, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2011 VL 176 IS 4 BP 533 EP 534 DI 10.1667/RRXX36.1 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 829SV UT WOS:000295605500012 ER PT J AU Abdel-Rahman, A Anyangwe, N Carlacci, L Casper, S Danam, RP Enongene, E Erives, G Fabricant, D Gudi, R Hilmas, CJ Hines, F Howard, P Levy, D Lin, Y Moore, RJ Pfeiler, E Thurmond, TS Turujman, S Walker, NJ AF Abdel-Rahman, Ali Anyangwe, Njwen Carlacci, Louis Casper, Steve Danam, Rebecca P. Enongene, Evaristus Erives, Gladys Fabricant, Daniel Gudi, Ramadevi Hilmas, Corey J. Hines, Fred Howard, Paul Levy, Dan Lin, Ying Moore, Robert J. Pfeiler, Erika Thurmond, T. Scott Turujman, Saleh Walker, Nigel J. TI The Safety and Regulation of Natural Products Used as Foods and Food Ingredients SO TOXICOLOGICAL SCIENCES LA English DT Article DE botanicals; dietary supplements; food; food ingredients; safety; regulation ID CHINESE HERBS NEPHROPATHY; GREEN TEA; STEVIA-REBAUDIANA; ARISTOLOCHIC ACID; REBAUDIOSIDE-A; EPIGALLOCATECHIN GALLATE; DIETARY-SUPPLEMENTS; RATS; STEVIOSIDE; EXTRACT AB The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements. C1 [Danam, Rebecca P.; Erives, Gladys; Thurmond, T. Scott] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 21029 USA. [Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Enongene, Evaristus; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J.; Hines, Fred; Levy, Dan; Lin, Ying; Moore, Robert J.; Turujman, Saleh] US FDA, Div Dietary Supplement Programs, Off Nutr Labeling & Dietary Supplements, College Pk, MD 21029 USA. [Howard, Paul] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Pfeiler, Erika] US FDA, Off Commissioner, Off Chief Scientist, Laurel, MD 20708 USA. [Walker, Nigel J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Thurmond, TS (reprint author), US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 265, College Pk, MD 21029 USA. EM scott.thurmond@fda.hhs.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 55 TC 38 Z9 43 U1 2 U2 62 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2011 VL 123 IS 2 BP 333 EP 348 DI 10.1093/toxsci/kfr198 PG 16 WC Toxicology SC Toxicology GA 828VW UT WOS:000295532900002 PM 21821733 ER PT J AU Shpyleva, SI Muskhelishvili, L Tryndyak, VP Koturbash, I Tokar, EJ Waalkes, MP Beland, FA Pogribny, IP AF Shpyleva, Svitlana I. Muskhelishvili, Levan Tryndyak, Volodymyr P. Koturbash, Igor Tokar, Erik J. Waalkes, Michael P. Beland, Frederick A. Pogribny, Igor P. TI Chronic Administration of 2-Acetylaminofluorene Alters the Cellular Iron Metabolism in Rat Liver SO TOXICOLOGICAL SCIENCES LA English DT Article DE 2-acetylaminofluorene; carcinogenesis; iron metabolism; liver; rat ID HEPATOCELLULAR-CARCINOMA; HEPATIC IRON; REGULATORY GENES; TRANSFERASE-P; CANCER; HEPCIDIN; HEPATOCARCINOGENESIS; CARCINOGENESIS; EXPRESSION; DISEASE AB Dysregulated intracellular iron homeostasis has been found not only in rodent and human hepatocellular carcinomas but also in several preneoplastic pathological states associated with hepatocarcinogenesis; however, the precise underlying mechanisms of metabolic iron disturbances in preneoplastic liver and the role of these disturbances remain unexplored. In the present study, using an in vivo model of rat hepatocarcinogenesis induced by 2-acetylaminofluorene, we found extensive alterations in cellular iron metabolism at preneoplastic stages of liver carcinogenesis. These were characterized by a substantial decrease in the levels of cytoplasmic non-heme iron in foci of initiated hepatocytes and altered expression of the major genes responsible for the proper maintenance of intracellular iron homeostasis. Gene expression analysis revealed that the decreased intracellular levels of iron in preneoplastic foci might be attributed to increased iron export from the cells, driven by upregulation of ferroportin (Fpn1), the only known non-heme iron exporter. Likewise, increased Fpn1 gene expression was found in vitro in TRL1215 rat liver cells with an acquired malignant phenotype, suggesting that upregulation of Fpn1 might be a specific feature of neoplastically transformed cells. Other changes observed in vivo included the downregulation of hepcidin (Hamp) gene, a key regulator of Fpn1, and this was accompanied by decreased levels of CCAAT/enhancer binding proteins alpha and beta, especially at the Hamp promoter. In conclusion, our results demonstrate the significance of altered intracellular iron metabolism in the progression of liver carcinogenesis and suggest that correction of these alterations could possibly affect liver cancer development. C1 [Shpyleva, Svitlana I.; Tryndyak, Volodymyr P.; Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Shpyleva, Svitlana I.; Tryndyak, Volodymyr P.] RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapy, UA-03022 Kiev, Ukraine. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program, Res Triangle Pk, NC 27713 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Bldg 14C,Off 101, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) FX National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). NR 42 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2011 VL 123 IS 2 BP 433 EP 440 DI 10.1093/toxsci/kfr193 PG 8 WC Toxicology SC Toxicology GA 828VW UT WOS:000295532900011 PM 21785164 ER PT J AU La Maestra, S Kisby, GE Micale, RT Johnson, J Kow, YW Bao, GB Sheppard, C Stanfield, S Tran, H Woltjer, RL D'Agostini, F Steele, VE De Flora, S AF La Maestra, Sebastiano Kisby, Glen E. Micale, Rosanna T. Johnson, Jessica Kow, Yoke W. Bao, Gaobin Sheppard, Clayton Stanfield, Sarah Huong Tran Woltjer, Randall L. D'Agostini, Francesco Steele, Vernon E. De Flora, Silvio TI Cigarette Smoke Induces DNA Damage and Alters Base-Excision Repair and Tau Levels in the Brain of Neonatal Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE cigarette smoke; brain; neonatal mice; DNA damage; base-excision repair; tau; neurodegenerative disorders ID OXIDATIVE STRESS; ALZHEIMERS-DISEASE; N-ACETYLCYSTEINE; BIRTH OUTCOMES; TOBACCO-SMOKE; PROTEIN-TAU; CANCER; MOUSE; SCLEROSIS; EXPOSURE AB The prenatal and perinatal periods of brain development are especially vulnerable to insults by environmental agents. Early life exposure to cigarette smoke (CS), which contains both genotoxicants and oxidants, is considered an important risk factor for both neurodevelopmental and neurodegenerative disorders. Yet, little is known regarding the underlying pathogenetic mechanisms. In the present study, neonatal Swiss ICR (CD-1) albino mice were exposed to various concentrations of CS for 4 weeks and the brain examined for lipid peroxides, DNA damage, base-excision repair (BER) enzymes, apoptosis, and levels of the microtubule protein tau. CS induced a dose-dependent increase in both malondialdehyde and various types of DNA damage, including single-strand breaks, double-strand breaks, and DNA-protein cross-links. However, the CS-induced DNA damage in the brain returned to basal levels 1 week after smoking cessation. CS also modulated the activity and distribution of the BER enzymes 8-oxoguanine-DNA-glycosylase (OGG1) and apyrimidinic/apurinic endonuclease (APE1) in several brain regions. Normal tau (i.e., three-repeat tau, 3R tau) and various pathological forms of tau were also measured in the brain of CS-exposed neonatal mice, but only 3R tau and tau phosphorylated at serine 199 were significantly elevated. The oxidative stress, genomic dysregulation, and alterations in tau metabolism caused by CS during a critical period of brain development could explain why CS is an important risk factor for both neurodevelopmental and neurodegenerative disorders appearing in later life. C1 [La Maestra, Sebastiano; Micale, Rosanna T.; D'Agostini, Francesco; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Kisby, Glen E.; Johnson, Jessica] Oregon Hlth & Sci Univ, CROET, Portland, OR 97239 USA. [Kow, Yoke W.; Bao, Gaobin; Sheppard, Clayton] Emory Univ, Dept Radiat Oncol, Sch Med, Atlanta, GA 30322 USA. [Stanfield, Sarah; Huong Tran; Woltjer, Randall L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Steele, Vernon E.] NCI, Canc Prevent Div, Rockville, MD 20892 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. EM sdf@unige.it FU U.S. National Cancer Institute [NO1-CN53301, CA90860]; Department of Defense [DAMD17-98-1-8625] FX U.S. National Cancer Institute (NO1-CN53301, CA90860); Department of Defense (DAMD17-98-1-8625). NR 49 TC 11 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2011 VL 123 IS 2 BP 471 EP 479 DI 10.1093/toxsci/kfr187 PG 9 WC Toxicology SC Toxicology GA 828VW UT WOS:000295532900014 PM 21778470 ER PT J AU Oakley, MS Gerald, N McCutchan, TF Aravind, L Kumar, S AF Oakley, Miranda S. Gerald, Noel McCutchan, Thomas F. Aravind, L. Kumar, Sanjai TI Clinical and molecular aspects of malaria fever SO TRENDS IN PARASITOLOGY LA English DT Review ID PLASMODIUM-FALCIPARUM; FEBRILE TEMPERATURES; HOST ERYTHROCYTE; CEREBRAL MALARIA; PARASITES; GLYCOSYLPHOSPHATIDYLINOSITOL; RESPONSES; PIGMENT; RECEPTORS; INFECTION AB Although clinically benign, malaria fever is thought to have significant relevance in terms of parasite growth and survival and its virulence which in turn may alter the clinical course of illness. In this article, the historical literature is reviewed, providing some evolutionary perspective on the genesis and biological relevance of malaria fever, and the available molecular data on the febrile-temperature-inducible parasite factors that may contribute towards the regulation of parasite density and alteration of virulence in the host is also discussed. The potential molecular mechanisms that could be responsible for the induction and regulation of cyclical malaria fevers caused by different species of Plasmodiurn are also discussed. C1 [Gerald, Noel; McCutchan, Thomas F.; Kumar, Sanjai] US FDA, Div Emerging Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. [Oakley, Miranda S.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), US FDA, Div Emerging Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. EM sanjai.kumar@fda.hhs.gov NR 49 TC 12 Z9 12 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD OCT PY 2011 VL 27 IS 10 BP 442 EP 449 DI 10.1016/j.pt.2011.06.004 PG 8 WC Parasitology SC Parasitology GA 831RN UT WOS:000295748900005 PM 21795115 ER PT J AU Chen, M Wang, YR Hou, TT Zhang, HL Qu, AJ Wang, XH AF Chen, Min Wang, Yanru Hou, Tingting Zhang, Huiliang Qu, Aijuan Wang, Xianhua TI Differential mitochondrial calcium responses in different cell types detected with a mitochondrial calcium fluorescent indicator, mito-GCaMP2 SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA English DT Article DE fluorescent indicator; mitochondria; calcium; cardiomyocyte ID RABBIT CARDIAC MYOCYTES; IN-VIVO; CA2+ SIGNALS; TRANSIENTS; PROTEINS; MECHANISMS AB Mitochondrial calcium plays a crucial role in mitochondrial metabolism, cell calcium handling, and cell death. However, some mechanisms concerning mitochondrial calcium regulation are still unknown, especially how mitochondrial calcium couples with cytosolic calcium. In this work, we constructed a novel mitochondrial calcium fluorescent indicator (mito-GCaMP2) by genetic manipulation. Mito-GCaMP2 was imported into mitochondria with high efficiency and the fluorescent signals co-localized with that of tetramethyl rhodamine methyl ester, a mitochondrial membrane potential indicator. The mitochondrial inhibitors specifically decreased the signals of mito-GCaMP2. The apparent K(d) of mito-GCaMP2 was 195.0 nmol/L at pH 8.0 in adult rat cardiomyocytes. Furthermore, we observed that mito-GCaMP2 preferred the alkaline pH surrounding of mitochondria. In HeLa cells, we found that mitochondrial calcium ([Ca(2+)](mito)) responded to the changes of cytosolic calcium ([Ca(2+)](cyto)) induced by histamine or thapasigargin. Moreover, external Ca(2+) (100 mu mol/L) directly induced an increase of [Ca(2+)](mito) in permeabilized HeLa cells. However, in rat cardiomyocytes [Ca(2+)](mito) did not respond to cytosolic calcium transients stimulated by electric pacing or caffeine. In permeabilized cardiomyocytes, 600 nmol/L free Ca(2+) repeatedly increased the fluorescent signals of mito-GCaMP2, which excluded the possibility that mito-GCaMP2 lost its function in cardiomyocytes mitochondria. These results showed that the response of mitochondrial calcium is diverse in different cell lineages and suggested that mitochondria in cardiomyocytes may have a special defense mechanism to control calcium flux. C1 [Chen, Min] Yunnan Ctr Dis Prevent & Control, Kunming 650022, Peoples R China. [Chen, Min; Wang, Yanru; Hou, Tingting; Zhang, Huiliang; Wang, Xianhua] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. [Qu, Aijuan] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chen, M (reprint author), Yunnan Ctr Dis Prevent & Control, Kunming 650022, Peoples R China. EM chenminyx@gmail.com; xianhua@pku.edu.cn FU National Natural Science Foundation of China [30800371] FX This work was supported by a grant from the National Natural Science Foundation of China (30800371). NR 36 TC 10 Z9 10 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1672-9145 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophys. Sin. PD OCT PY 2011 VL 43 IS 10 BP 822 EP 830 DI 10.1093/abbs/gmr075 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 827EU UT WOS:000295411300010 PM 21880604 ER PT J AU Aue, G Lozier, JN Tian, X Cullinane, AM Soto, S Samsel, L Mccoy, P Wiestner, A AF Aue, Georg Lozier, Jay Nelson Tian, Xin Cullinane, Ann M. Soto, Susan Samsel, Leigh McCoy, Philip Wiestner, Adrian TI Inflammation, TNF alpha and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID MULTIPLE-MYELOMA; THALIDOMIDE; THROMBOEMBOLISM; RISK; COMPLICATIONS; ASPIRIN; MALIGNANCIES; PREVENTION; CANCER; CELLS AB Patients receiving lenalidomide are at an increased risk for deep venous thrombosis (DVT). Here, we prospectively investigated the DVT risk in patients with relapsed chronic lymphocytic leukemia (CLL) treated with lenalidomide (n = 32). Five patients developed six incidents of DVT over 1 year for an annual incidence of 16%. Three of these were considered drug-related. Median time to DVT was 105 days (range 56-259 days). No pulmonary embolism was detected. Hypercoagulability screen before study entry was negative in all patients who subsequently developed DVTs. Compared to normal volunteers CLL patients had increased baseline levels of D-dimer, thrombin-antithrombin, soluble vascular endothelial adhesion molecule 1 (sVCAM-1), and thrombomodulin (p < 0.001). After 1 week on lenalidomide D-dimer, thrombomodulin, sVCAM-1, factor VIII, TNF alpha, and C-reactive protein were significantly increased while protein C was decreased (p < 0.001). In patients with lenalidomide-related DVTs, TNF alpha, and sVCAM-1 were more strongly upregulated than in all other patients (p < 0.05) and TNF alpha and sVCAM-1 levels were significantly correlated (r = 0.65, p < 0.001). These data link lenalidomide associated DVTs with TNF alpha upregulation and endothelial cell dysfunction and suggest that aspirin may have a role for DVT prophylaxis in these patients. Am. J. Hematol. 86: 835-840, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Aue, Georg; Soto, Susan; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Lozier, Jay Nelson; Cullinane, Ann M.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Samsel, Leigh; McCoy, Philip] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bld 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM wiestnera@mail.nih.gov FU NIH FX This research was supported by NIH Intramural Research program. NR 30 TC 14 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2011 VL 86 IS 10 BP 835 EP 840 DI 10.1002/ajh.22114 PG 6 WC Hematology SC Hematology GA 824WB UT WOS:000295231800003 PM 21812019 ER PT J AU Rabkin, CS Engels, EA Landgren, O Schuurman, R Camargo, MC Pfeiffer, R Goedert, JJ AF Rabkin, Charles S. Engels, Eric A. Landgren, Ola Schuurman, Rob Camargo, M. Constanza Pfeiffer, Ruth Goedert, James J. TI Circulating cytokine levels, Epstein-Barr viremia, and risk of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ELEVATED SERUM-LEVELS; B-CELL LYMPHOMA; HOMOSEXUAL-MEN; AIDS; EXPRESSION; INTERLEUKIN-5; INFECTION; SEQUENCE; CANCER AB Cytokine dysregulation and decontrol of Epstein-Barr virus (EBV) latency by human immunodeficiency virus (HIV) infection are potential mechanisms for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). We therefore assessed circulating blood levels in pre-diagnosis plasma or serum from 63 AIDS-related NHL cases 0.1-2.0 (median 1.0) years pre-NHL and 181 controls matched for CD4+ T-cell count. Cytokines were measured by Millipore 30-plex Luminex assays and cell-free EBV DNA detected by polymerase chain reaction (PCR). Correlations in multiplex cytokine levels were summarized by factor analysis. Individual cytokines and their principal factors were analyzed for associations with NHL by conditional logistic regression. Cases had higher levels for 25 of the 30 cytokines. In analyses of cytokine profiles, cases had significantly higher scores for a principal factor primarily reflecting levels of interleukin (IL)-4, IL-5, IL-13, and granulocyte-macrophage colony stimulating factor (four gene products with coordinated transcription in vitro), as well as IL-1alpha. Epstein-Barr viremia was not significantly associated based on 113 evaluable samples without PCR inhibition. We found increases of T-helper Type 2 interleukins and generalized elevations of other inflammatory cytokines and growth factors up to 2 years before AIDS-NHL. Cytokine-mediated hyperstimulation of B-cell proliferation may play a role in AIDS-related lymphomagenesis. C1 [Rabkin, Charles S.; Engels, Eric A.; Camargo, M. Constanza; Pfeiffer, Ruth; Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Landgren, Ola] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Schuurman, Rob] Univ Med Ctr Utrecht, Dept Virol, Utrecht, Netherlands. RP Rabkin, CS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 7082, Rockville, MD 20852 USA. EM rabkinc@mail.nih.gov RI Camargo, M. Constanza/R-9891-2016 FU Intramural NIH HHS [ZIA CP010212-01] NR 24 TC 10 Z9 10 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2011 VL 86 IS 10 BP 875 EP 878 DI 10.1002/ajh.22119 PG 4 WC Hematology SC Hematology GA 824WB UT WOS:000295231800014 PM 22022727 ER PT J AU O'Seaghdha, CM Fox, CS AF O'Seaghdha, Conall M. Fox, Caroline S. TI In Reply to 'Does High or Low Urinary Connective Tissue Growth Factor Predict CKD?' SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] Brigham & Womens Hosp, NHLBI, Boston, MA 02115 USA. RP O'Seaghdha, CM (reprint author), Brigham & Womens Hosp, NHLBI, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2011 VL 58 IS 4 BP 681 EP 682 DI 10.1053/j.ajkd.2011.08.007 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 826UE UT WOS:000295379600030 ER PT J AU Gripp, KW Hopkins, E Johnston, JJ Krause, C Dobyns, WB Biesecker, LG AF Gripp, Karen W. Hopkins, Elizabeth Johnston, Jennifer J. Krause, Caitlin Dobyns, William B. Biesecker, Leslie G. TI Long-Term Survival in TARP Syndrome and Confirmation of RBM10 as the Disease-Causing Gene SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE ASD; cryptorchidism; persistent left superior vena cava; Pierre-Robin sequence; RBM10; talipes equinovarus; X-linked AB TARP syndrome, comprising Talipes equinovarus, atrial septal defect (ASD), Robin sequence (micrognathia, glossoptosis, and cleft palate), and persistence of the left superior vena cava, is an X-linked condition with pre- or postnatal lethality in affected males. Based on linkage studies and massively parallel sequencing of X-chromosome exons in two families, the disease-causing gene was identified as RBM10. We identified a maternally inherited frameshift mutation in an unrelated patient, confirming RBM10 as the disease gene. This is the first reported individual with TARP syndrome who survived past early infancy, thus expanding the phenotypic spectrum of this disorder. In addition to the characteristic cleft palate, ASD, and persistent superior vena cava, he had low-set and posteriorly angulated ears, upslanting palpebral fissures, cryptorchidism, and structural brain abnormalities including partial agenesis of the corpus callosum, dysplastic enlarged caudate, and cerebellar hypoplasia with megacisterna magna. Preterm delivery, suspected pulmonary hypoplasia, and pulmonary hypertension resulted in chronic lung disease. At the age of 3 7/12 years, he remained ventilator-dependent at night, and he was fed exclusively through a gastro-jejunal tube. Sensorineural hearing loss required a hearing aid. Optic atrophy and cortical visual impairment were noted. He was unable to sit independently, was non-communicative and he had severe intellectual disability. Atrial flutter required recurrent ablation of intra-atrial re-entry pathways. The mother's hetero-zygosity for the RBM10 mutation underscored the importance of accurate diagnosis and counseling for TARP syndrome. (C) 2011 Wiley-Liss, Inc. C1 [Gripp, Karen W.; Hopkins, Elizabeth] Alfred I DuPont Hosp Children, Div Med Genet, Wilmington, DE 19803 USA. [Johnston, Jennifer J.; Krause, Caitlin; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Dobyns, William B.] Seattle Childrens Res Inst, Seattle, WA USA. RP Gripp, KW (reprint author), Alfred I DuPont Hosp Children, Div Med Genet, Wilmington, DE 19803 USA. EM kgripp@nemours.org OI Dobyns, William/0000-0002-7681-2844 FU National Human Genome Research Institute of the National Institutes of Health FX Grant sponsor: Intramural Program of the National Human Genome Research Institute of the National Institutes of Health.; We appreciate the family's generosity in allowing us to share this information. This work was supported in part by funding from the Intramural Program of the National Human Genome Research Institute of the National Institutes of Health. NR 3 TC 14 Z9 14 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2011 VL 155A IS 10 BP 2516 EP 2520 DI 10.1002/ajmg.a.34190 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 826BL UT WOS:000295326300029 PM 21910224 ER PT J AU Lieu, TA Au, D Krishnan, JA Moss, M Selker, H Harabin, A Taggart, V Connors, A AF Lieu, Tracy A. Au, David Krishnan, Jerry A. Moss, Marc Selker, Harry Harabin, Andrea Taggart, Virginia Connors, Alfred CA Comparative Effectiveness Res Lung TI Comparative Effectiveness Research in Lung Diseases and Sleep Disorders Recommendations from the National Heart, Lung, and Blood Institute Workshop SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE randomized controlled trials; observational studies; implementation; study designs; methodology ID UNITED-STATES; TIME-SERIES; CARE; SAFETY; NETWORK; ASTHMA; TRIAL AB The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed. C1 [Harabin, Andrea; Taggart, Virginia] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. [Connors, Alfred] Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Cleveland, OH USA. [Lieu, Tracy A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Lieu, Tracy A.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [Au, David] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Au, David] Dept Vet Affairs, Seattle, WA USA. [Krishnan, Jerry A.] Univ Chicago, Dept Med, Asthma & COPD Ctr, Chicago, IL 60637 USA. [Krishnan, Jerry A.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Moss, Marc] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Selker, Harry] Tufts Univ, Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Clin & Translat Sci Inst, Boston, MA 02111 USA. RP Taggart, V (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM taggartv@nih.gov FU Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health; HSR&D, VA Puget Sound Health Care System FX Supported by the Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health.; D.A. was funded by HSR&D, VA Puget Sound Health Care System. The views expressed in this manuscript are those of the authors and do not necessarily represent the opinions of the Department of Veterans Affairs. NR 42 TC 23 Z9 24 U1 1 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2011 VL 184 IS 7 BP 848 EP 856 DI 10.1164/rccm.201104-0634WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 827DM UT WOS:000295407300020 PM 21965016 ER PT J AU Miller, FG AF Miller, Franklin G. TI Dispensing With Equipoise SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Clinical equipoise; Informed consent; Clinical research; Research ethics ID RANDOMIZED CLINICAL-TRIALS; PLACEBO-CONTROLLED TRIALS; ETHICS; HYPERPLASIA; DISORDER; CRITIQUE; BENEFIT; CANCER AB Equipoise is widely endorsed as a necessary requirement for ethical design and conduct of randomized controlled trials. Nevertheless, I argue in this article that the equipoise principle suffers from fundamental defects. In particular, equipoise provides flawed ethical guidance for placebo-controlled trials and for decisions to terminate trials early based on interim data relating to benefit. The problems with equipoise are traced to a "therapeutic orientation to clinical trials," which conflates the ethics of clinical research with the ethics of medical care. Because of this mistaken therapeutic orientation, equipoise fails to adequately account for the central purpose of randomized trials in providing evidence sufficient to guide health policy decisions relating to licensing new treatments and insurance coverage. I conclude that it is time to dispense with equipoise. The principles of research ethics are sufficient to provide adequate guidance to protect subjects and to promote socially valuable research without any appeal to equipoise. C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 26 TC 2 Z9 2 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD OCT PY 2011 VL 342 IS 4 BP 276 EP 281 DI 10.1097/MAJ.0b013e318227e871 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 825ZN UT WOS:000295321000004 PM 21804362 ER PT J AU Colbert, RA Cronstein, BN AF Colbert, Robert A. Cronstein, Bruce N. TI Biosimilars: The Debate Continues SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material C1 [Colbert, Robert A.] NIAMSD, Pediat Translat Res Branch, NIH, CRC, Bethesda, MD 20892 USA. [Cronstein, Bruce N.] NYU, Sch Med, New York, NY USA. RP Colbert, RA (reprint author), NIAMSD, Pediat Translat Res Branch, NIH, CRC, 10 Ctr Dr,Room 1-5142,MSC 1102, Bethesda, MD 20892 USA. EM colbertr@mail.nih.gov FU Intramural NIH HHS [ZIA AR041184-02]; NCRR NIH HHS [UL1 RR029893, UL1-RR-029893]; NIAMS NIH HHS [AR-54897, AR-56672, AR-56672S1, R01 AR054897, R56 AR056672, R01 AR056672] NR 6 TC 10 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 BP 2848 EP 2850 DI 10.1002/art.30505 PG 3 WC Rheumatology SC Rheumatology GA 825PN UT WOS:000295293000002 PM 21702015 ER PT J AU Greenwell-Wild, T Moutsopoulos, NM Gliozzi, M Kapsogeorgou, E Rangel, Z Munson, PJ Moutsopoulos, HM Wahl, SM AF Greenwell-Wild, Teresa Moutsopoulos, Niki M. Gliozzi, Maria Kapsogeorgou, Efstathia Rangel, Zoila Munson, Peter J. Moutsopoulos, Haralampos M. Wahl, Sharon M. TI Chitinases in the Salivary Glands and Circulation of Patients With Sjogren's Syndrome Macrophage Harbingers of Disease Severity SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; T-CELLS; IN-VIVO; EXPRESSION; STAT4; INTERLEUKIN-17; ACTIVATION; INTERFERON; INVOLVEMENT AB Objective. Sjogren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that targets salivary and lacrimal glands and may be accompanied by multiorgan systemic manifestations. To further the understanding of immunopathology associated with SS and identify potential therapeutic targets, we undertook the present study comparing the gene expression profiles of salivary glands with severe inflammation versus those of salivary glands with mild or no disease. Methods. Using microarray profiling of salivary gland tissue from patients with SS and control subjects, we identified target genes, which were further characterized in tissue, serum, and cultured cell populations by real-time polymerase chain reaction and protein analysis. Results. Among the most highly expressed SS genes were those associated with myeloid cells, including members of the mammalian chitinase family, which had not previously been shown to be associated with exocrinopathies. Both chitinase 3-like protein 1 and chitinase 1, highly conserved chitinase-like glycoproteins (one with enzymatic activity and one lacking enzymatic activity), were evident at the transcriptome level and were detected within inflamed tissue. Chitinases were expressed during monocyte-to-macrophage differentiation and their levels augmented by stimulation with cytokines, including interferon-alpha (IFN alpha). Conclusion. Because elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, the present observations suggest that macrophages have potential immunopathologic involvement in SS and that the tissue macrophage transcription profile reflects multiple genes induced by IFN alpha. C1 [Wahl, Sharon M.] Natl Inst Dent & Craniofacial Res, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. [Kapsogeorgou, Efstathia; Moutsopoulos, Haralampos M.] Natl Univ Athens, Sch Med, Athens, Greece. [Rangel, Zoila; Munson, Peter J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Oral Infect & Immun Branch, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM SMWahl@mail.nih.gov FU NIH, National Institute of Dental and Craniofacial Research FX Supported in part by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research. NR 55 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 BP 3103 EP 3115 DI 10.1002/art.30465 PG 13 WC Rheumatology SC Rheumatology GA 825PN UT WOS:000295293000032 PM 21618203 ER PT J AU Xu, MY Weinberg, CR Umbach, DM Li, LP AF Xu, Mengyuan Weinberg, Clarice R. Umbach, David M. Li, Leping TI coMOTIF: a mixture framework for identifying transcription factor and a coregulator motif in ChIP-seq Data SO BIOINFORMATICS LA English DT Article ID FACTOR-BINDING SITES; EXPECTATION MAXIMIZATION; EM ALGORITHM; BAYESIAN MODELS; DISCOVERY; GIBBS; SEQUENCE; ALIGNMENT; ELEMENTS; IDENTIFICATION AB Motivation: ChIP-seq data are enriched in binding sites for the protein immunoprecipitated. Some sequences may also contain binding sites for a coregulator. Biologists are interested in knowing which coregulatory factor motifs may be present in the sequences bound by the protein ChIP'ed. Results: We present a finite mixture framework with an expectation-maximization algorithm that considers two motifs jointly and simultaneously determines which sequences contain both motifs, either one or neither of them. Tested on 10 simulated ChIP-seq datasets, our method performed better than repeated application of MEME in predicting sequences containing both motifs. When applied to a mouse liver Foxa2 ChIP-seq dataset involving similar to 12 000 400-bp sequences, coMOTIF identified co-occurrence of Foxa2 with Hnf4a, Cebpa, E-box, Ap1/Maf or Sp1 motifs in similar to 6-33% of these sequences. These motifs are either known as liver-specific transcription factors or have an important role in liver function. C1 [Xu, Mengyuan; Weinberg, Clarice R.; Umbach, David M.; Li, Leping] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Li, LP (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. FU National Institutes of Health; National Institute of Environmental Health Sciences [ES101765-05] FX Funding: Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences (ES101765-05). NR 37 TC 4 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2011 VL 27 IS 19 BP 2625 EP 2632 DI 10.1093/bioinformatics/btr397 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 827FC UT WOS:000295412200002 PM 21775309 ER PT J AU Han, HY Qiu, L Wang, XH Qiu, F Wong, YC Yao, XS AF Han, Huiying Qiu, Li Wang, Xianghong Qiu, Feng Wong, Yongchuan Yao, Xinsheng TI Physalins A and B Inhibit Androgen-Independent Prostate Cancer Cell Growth through Activation of Cell Apoptosis and Downregulation of Androgen Receptor Expression SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE physalin A; physalin B; androgen-independent prostate cancer; apoptosis; androgen receptor ID SIGNAL-TRANSDUCTION PATHWAYS; PROTEIN-KINASE; DEATH; GENE; P38; PROGRESSION; CARCINOMA; ANTIGEN AB Androgen deprivation therapy is a common treatment strategy for advanced prostate cancer. Though effective initially, the tumor often progresses to androgen independent stage in most patients eventually after a period of remission. One of the key factors of development of resistance is reflected in expression of androgen receptor (AR). In this study, we showed that two natural compounds, physalins A and B, both secosteriods from Physalisalkekengi var. franchetii, significantly inhibited the growth of two androgen-independent cell lines CWR22Rv1 and C42B, induced apoptosis via c-Jun N-terminal kinase (JNK) and/or extracellular signal-regulated kinase (ERK) activation, and decreased AR expression. In addition, physalins A and B down-regulated the expression of prostate specific antigen (PSA) in C42B cells which is a target gene of AR. Our results suggest that physalin A and B might be useful agents in preventing the growth of androgen-independent prostate cancer (AI-PCa). C1 [Wang, Xianghong; Wong, Yongchuan] Univ Hong Kong, Fac Med, Dept Anat, Canc Biol Grp, Hong Kong, Hong Kong, Peoples R China. [Han, Huiying] NCI, Extracellular Matrix Pathol Sect, Radiat Oncol Branch, Ctr Canc Res,NIH,Adv Technol Ctr, Bethesda, MD 20892 USA. [Qiu, Li] Guangxi Inst Med Plant, Nanning 530023, Guangxi, Peoples R China. [Qiu, Feng; Yao, Xinsheng] Shenyang Pharmaceut Univ, Coll Tradit Chinese Mat Med, Shenyang 110015, Peoples R China. [Yao, Xinsheng] Jinan Univ, Inst Tradit Chinese Med & Nat Prod, Guangzhou 510632, Guangdong, Peoples R China. RP Wong, YC (reprint author), Univ Hong Kong, Fac Med, Dept Anat, Canc Biol Grp, 21 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. EM ycwong@hkucc.hku.hk; tyaoxs@jnu.edu.cn NR 33 TC 7 Z9 7 U1 0 U2 4 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD OCT PY 2011 VL 34 IS 10 BP 1584 EP 1588 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 826YI UT WOS:000295391100010 PM 21963499 ER PT J AU Pearl, PL Shukla, L Theodore, WH Jakobs, C Gibson, KM AF Pearl, Phillip L. Shukla, Lovy Theodore, William H. Jakobs, Cornelis Gibson, K. Michael TI Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism SO BRAIN & DEVELOPMENT LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the Infantile-Seizure-Society/International Symposium on Epilepsy in Neurometabolic Diseases (ISENMD) CY MAR 26-28, 2010 CL Taipei, TAIWAN SP Infantile Seizure Soc ID GAMMA-HYDROXYBUTYRIC ACID; SSADH DEFICIENCY; MICE DEFICIENT; ABSENCE SEIZURES; VIGABATRIN; CHILDREN; MECHANISMS; DISEASE; PATIENT; ADULTS AB Objectives: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a gamma-aminobutyric acid (GABA) degradative defect. Epilepsy affects half of patients. The murine model is associated with a transition from absence to convulsive seizures in the third week, with fatal status epilepticus. Methods: The clinical phenotype is reported from a patient database. Flumazenil-Positron Emission Topography (FMZ-PET) and Transcranial Magnetic Stimulation (TMS) were used to study GABA neurotransmission. Electrocorticography, single cell electrophysiology, and radioligand binding studies are reported from animal studies. Results: Generalized seizures predominate, including tonic clonic, atypical absence, and myoclonic. EEG discharges are typically generalized spike-wave. MRI shows a dentatopallidoluysian pattern. Sudden Unexpected Death in Epilepsy Patients (SUDEP) has occurred and the associated neuropathology reveals chronic excitotoxic injury in gloubus pallidus. Investigations using FMZ-PET and TMS support downregulation of GABA(A) and GABA(B) activity, respectively, in patients. Gamma-hydroxybutyrate (GHB) induces spike-wave discharges in homozygous null mice via GHB and GABA(B)-mediated mechanisms. These resemble absence seizures and are abolished by a GABA(B) receptor antagonist. Decreased binding of GABA(A) and GABA(B) receptor antagonists has been demonstrated in P19 and P14 null mice, respectively. Downregulation of GABA(A) and GABA(B) receptor subunits is observed by P14. GABA(A) and GABA(B) mediated potentials are reduced from P8-P14. Conclusion: Generalized epilepsy and epileptiform discharges are characteristic of SSADH deficiency. Spontaneous absence seizures appear in null mice by the third week, which may be induced by GHB or GABA(B) activity. Subsequent overuse dependent downregulation of GABA(A) and GABA(B) receptor activity may be associated with hyperexcitability concomitant with the transition to generalized seizures. (C) 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. C1 [Pearl, Phillip L.; Shukla, Lovy] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Pearl, Phillip L.; Theodore, William H.] Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Branch, NIH, Bethesda, MD USA. [Jakobs, Cornelis] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Metab Unit, Amsterdam, Netherlands. [Gibson, K. Michael] Michigan Technol Univ, Dept Biol Sci, Houghton, MI 49931 USA. RP Pearl, PL (reprint author), George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM ppearl@cnmc.org FU NICHD NIH HHS [NS 40270/HD58553, R01 HD058553]; NINDS NIH HHS [R01 NS040270] NR 35 TC 20 Z9 20 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD OCT PY 2011 VL 33 IS 9 BP 796 EP 805 DI 10.1016/j.braindev.2011.04.013 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 827QN UT WOS:000295443100013 PM 21664777 ER PT J AU Amodio, E Goedert, JJ Barozzi, P Riva, G Firenze, A Bonura, F Viviano, E Romano, N Luppi, M AF Amodio, Emanuele Goedert, James J. Barozzi, Patrizia Riva, Giovanni Firenze, Alberto Bonura, Filippa Viviano, Enza Romano, Nino Luppi, Mario TI Differences in Kaposi sarcoma-associated herpesvirus-specific and herpesvirus-non-specific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily SO CANCER SCIENCE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; SWISS HIV COHORT; T-CELL RESPONSES; PERIPHERAL-BLOOD; INFECTED INDIVIDUALS; RISK-FACTORS; HUMAN-HERPESVIRUS-8; VIRUS AB Kaposi sarcoma (KS) might develop because of incompetent immune responses, both non-specifically and specifically against the KS-associated herpesvirus (KSHV). Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV seropositives (without KS) and 15 KSHV-seronegative controls were tested for interferon-c T-cell (enzyme-linked immunospot [Elispot]) responses to KSHV-latency-associated nuclear antigen (LANA), KSHV-K8.1 and CMV/Epstein-Barr virus (EBV) peptide pools. The forearm and thigh of each participant was also tested for delayed-type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS) and two (13%) seronegative controls. All four cases with KSHV-LANA responses had current KS lesions, whereas five of six cases with KSHV-K8.1 responses had no lesions (P = 0.048). No case responded to both LANA and K8.1. Compared with the seronegative controls, the risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55-0.94, P = 0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02-1.80, P = 0.04) and tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86-30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for classic KS was reduced fivefold (OR 0.20, CI 0.03-0.77, P = 0.04) per KSHV response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV-specific and KSHV-non-specific immunity is associated with classic KS. This might clarify why Kaposi sarcoma responds to immune reconstitution. (Cancer Sci 2011; 102: 1769-1773) C1 [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Amodio, Emanuele; Firenze, Alberto; Bonura, Filippa; Viviano, Enza; Romano, Nino] Univ Palermo, Dept Sci Hlth Promot G DAlessandro, Sect Hyg, Palermo, Italy. [Barozzi, Patrizia; Riva, Giovanni; Luppi, Mario] Univ Modena & Reggio Emilia, Dept Oncol, Modena, Italy. [Barozzi, Patrizia; Riva, Giovanni; Luppi, Mario] Univ Modena & Reggio Emilia, Dept Hematol, Modena, Italy. [Barozzi, Patrizia; Riva, Giovanni; Luppi, Mario] Univ Modena & Reggio Emilia, Dept Resp Dis, Modena, Italy. RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. EM goedertj@mail.nih.gov RI Luppi, Mario/J-3668-2016; Barozzi, Patrizia/Q-2638-2016 OI Luppi, Mario/0000-0002-0373-1154; Barozzi, Patrizia/0000-0002-8936-1114 FU National Cancer Institute, National Institutes of Health; Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy; Programma di ricerca Regione-Universita (PRU), Regione Emilia Romagna; European Commission [LSHC-CT-2005-018704]; Associazione Italiana Lotta alle Leucemie, Linfoma e Mieloma (AIL)-Sezione "Luciano Pavarotti"-Modena-ONLUS FX The authors thank Liliana Preiss, RTI International, for computer programming and analysis, as well as the study participants. This study was supported in part by: the Intramural Research Program of the National Cancer Institute, National Institutes of Health (J. J. G.); the Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy (M. L.); the Programma di ricerca Regione-Universita (PRU) 2007-2009, Regione Emilia Romagna (M. L.); the European Commission's FP6 Life-Science-Health Programme (INCA project; LSHC-CT-2005-018704) (M. L.); and the Associazione Italiana Lotta alle Leucemie, Linfoma e Mieloma (AIL)-Sezione "Luciano Pavarotti"-Modena-ONLUS (M. L.). NR 30 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD OCT PY 2011 VL 102 IS 10 BP 1769 EP 1773 DI 10.1111/j.1349-7006.2011.02032.x PG 5 WC Oncology SC Oncology GA 826CK UT WOS:000295328800001 PM 21740480 ER PT J AU Wong, HL Rabkin, CS Shu, XO Pfeiffer, RM Cai, Q Ji, BT Yang, G Li, HL Rothman, N Gao, YT Zheng, W Chow, WH AF Wong, Hui-Lee Rabkin, Charles S. Shu, Xiao-Ou Pfeiffer, Ruth M. Cai, Qiuyin Ji, Bu-Tian Yang, Gong Li, Hong-Lan Rothman, Nathaniel Gao, Yu-Tang Zheng, Wei Chow, Wong-Ho TI Systemic cytokine levels and subsequent risk of gastric cancer in Chinese Women SO CANCER SCIENCE LA English DT Article ID HELICOBACTER-PYLORI INFECTION; NECROSIS-FACTOR-ALPHA; ELEVATED LEVELS; INTERLEUKIN-6; HEALTH; POPULATION; REPRODUCIBILITY; POLYMORPHISMS; INFLAMMATION; METASTASIS AB Although control of the host cytokine network is known to influence gastric cancer susceptibility, the specific inflammatory responses in gastric carcinogenesis remain unclear. We prospectively examined the relationships between gastric cancer risk and plasma levels of interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha in a nested case control study within The Shanghai Women's Health Study. Two controls were matched to each case on the basis of age, menopausal status, and sample collection parameters. The associations between gastric cancer risk and tertiles of cytokine levels were estimated by odds ratios (OR) and 95% confidence intervals (CI) from conditional logistic regression, adjusting for education. During a median follow-up period of 4 years (range 0.1-8 years), 141 women developed gastric cancer and were matched to 282 cancer-free study participants. Elevated levels of plasma IL-6 were associated with an increased risk of gastric cancer (P-trend = 0.04). Risk increased 70% (OR = 1.7; 95% CI 1.0, 3.0) for women in the highest tertile (>4 pg/mL) of IL-6 compared with those in the lowest tertile (<1.8 pg/mL). The association between gastric cancer risk and IL-6 was stronger after 4 years of follow-up (OR = 2.6 [95% CI 1.0, 6.7] for highest versus lowest tertile) compared with an OR of 1.4 (95% CI 0.7, 2.9) for those diagnosed within 1-4 years of follow-up. No associations were observed with the other pro-inflammatory cytokines examined, namely IL-1 beta, IL-8, and TNF-alpha. Systemic plasma IL-6 levels may inform long-term gastric cancer risk. This novel finding awaits confirmation in future studies with sequential plasma collection. (Cancer Sci 2011; 102: 1911-1915) C1 [Wong, Hui-Lee] US FDA, Silver Spring, MD USA. [Rabkin, Charles S.; Pfeiffer, Ruth M.; Ji, Bu-Tian; Rothman, Nathaniel; Chow, Wong-Ho] NCI, US NIH, Rockville, MD USA. [Shu, Xiao-Ou; Cai, Qiuyin; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Nashville, TN USA. [Li, Hong-Lan; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. RP Wong, HL (reprint author), US FDA, Silver Spring, MD USA. EM huilee.wong@fda.hhs.gov FU National Institutes of Health [R37 CA70867]; Intramural Research Program [N02 CP1101066]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX The work was supported by a grant from the National Institutes of Health (R37 CA70867) and an Intramural Research Program contract (N02 CP1101066). The authors thank the Shanghai residents who participated in the study and the research staff of the Shanghai Women's Health Study. The authors also thank Regina Courtney for plasma sample preparation at the Survey and Biospecimen Shared Resources supported, in part, by the Vanderbilt-Ingram Cancer Center (P30 CA68485). NR 31 TC 10 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD OCT PY 2011 VL 102 IS 10 BP 1911 EP 1915 DI 10.1111/j.1349-7006.2011.02033.x PG 5 WC Oncology SC Oncology GA 826CK UT WOS:000295328800010 PM 21740481 ER PT J AU Liu, F Hsing, AW Wang, X Shao, Q Qi, J Ye, Y Wang, ZY Chen, HY Gao, X Wang, GZ Chu, LW Ding, Q OuYang, J Gao, X Huang, YC Chen, YB Gao, YT Zhang, ZF Rao, J Shi, R Wu, QJ Wang, ML Zhang, ZD Zhang, YY Jiang, HW Zheng, J Hu, YL Guo, L Lin, XL Tao, S Jin, GF Sun, JL Lu, DR Zheng, SL Sun, YH Mo, ZN Xu, JF AF Liu, Fang Hsing, Ann W. Wang, Xiang Shao, Qiang Qi, Jun Ye, Yu Wang, Zhong Chen, Hongyan Gao, Xin Wang, Guozeng Chu, Lisa W. Ding, Qiang OuYang, Jun Gao, Xu Huang, Yichen Chen, Yanbo Gao, Yu Tang Zhang, Zuo-Feng Rao, Jianyu Shi, Rong Wu, Qijun Wang, Meilin Zhang, Zhengdong Zhang, Yuanyuan Jiang, Haowen Zheng, Jie Hu, Yanlin Guo, Ling Lin, Xiaoling Tao, Sha Jin, Guangfu Sun, Jielin Lu, Daru Zheng, S. Lilly Sun, Yinghao Mo, Zengnan Xu, Jianfeng TI Systematic confirmation study of reported prostate cancer risk-associated single nucleotide polymorphisms in Chinese men SO CANCER SCIENCE LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; VARIANTS; MULTIPLE; IDENTIFICATION; REPLICATION; POPULATIONS; 8Q24 AB More than 30 prostate cancer (PCa) risk-associated loci have been identified in populations of European descent by genome-wide association studies. We hypothesized that a subset of these loci might be associated with PCa risk in Chinese men. To test this hypothesis, 33 single nucleotide polymorphisms (SNP), one each from the 33 independent PCa risk-associated loci reported in populations of European descent, were investigated for their associations with PCa risk in a case-control study of Chinese men (1108 cases and 1525 controls). We found that 11 of the 33 SNP were significantly associated with PCa risk in Chinese men (P < 0.05). The reported risk alleles were associated with increased risk for PCa, with allelic odds ratios ranging from 1.12 to 1.44. The most significant locus was located on 8q24 region 2 (rs16901979, P = 5.14 x 10(-9)) with a genome-wide significance (P < 10(-8)), and three loci reached the Bonferroni correction significance level (P < 1.52 x 10(-3)), including 8q24 region 1 (rs1447295, P = 7.04 x 10(-6)), 8q24 region 5 (rs10086908, P = 9.24 x 10(-4)) and 8p21 (rs1512268, P = 9.39 x 10(-4)). Our results suggest that a subset of the PCa risk-associated SNP discovered by genome-wide association studies among men of European descent is also associated with PCa risk in Chinese men. This finding provides evidence of ethnic differences and similarity in genetic susceptibility to PCa. Genome-wide association studies in Chinese men are needed to identify Chinese-specific PCa risk-associated SNP. (Cancer Sci 2011; 102: 1916-1920) C1 [Gao, Xu; Sun, Yinghao] Second Mil Med Univ, Changhai Hosp, Dept Urol, Shanghai, Peoples R China. [Liu, Fang; Chen, Hongyan; Lin, Xiaoling; Sun, Jielin; Lu, Daru; Zheng, S. Lilly; Xu, Jianfeng] Fudan Univ, Sch Life Sci, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China. [Hsing, Ann W.; Chu, Lisa W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Wang, Xiang; Ding, Qiang; Jiang, Haowen; Zheng, Jie; Xu, Jianfeng] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200433, Peoples R China. [Shao, Qiang] Suchow Univ, Affiliated Hosp 1, Suzhou Municipal Hosp, Dept Urol, Suzhou, Peoples R China. [Qi, Jun; Huang, Yichen] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Urol, Shanghai 200030, Peoples R China. [Ye, Yu; Hu, Yanlin; Mo, Zengnan] Guangxi Med Univ, Affiliated Hosp 1, Dept Urol, Guangxi, Peoples R China. [Wang, Zhong; Chen, Yanbo] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Urol, Shanghai 200030, Peoples R China. [Chen, Hongyan; Lu, Daru; Xu, Jianfeng] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China. [Gao, Xin] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Urol, Guangzhou 510275, Guangdong, Peoples R China. [Wang, Guozeng] Pudong Gongli Hosp, Dept Urol, Shanghai, Peoples R China. [OuYang, Jun] Suzhou Univ, Peoples Hosp 1, Dept Urol, Suzhou 215006, Peoples R China. [Gao, Yu Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Rao, Jianyu] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. [Shi, Rong; Wu, Qijun] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200030, Peoples R China. [Wang, Meilin; Zhang, Zhengdong] Nanjing Med Univ, Sch Publ Hlth, Ctr Canc, Dept Mol & Genet Toxicol, Nanjing, Peoples R China. [Zhang, Yuanyuan] Wake Forest Univ, Bowman Gray Sch Med, Dept Urol, Winston Salem, NC 27103 USA. [Jin, Guangfu; Sun, Jielin; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC 27103 USA. [Guo, Ling; Tao, Sha; Xu, Jianfeng] Van Andel Res Inst, Grand Rapids, MI USA. RP Sun, YH (reprint author), Second Mil Med Univ, Changhai Hosp, Dept Urol, Shanghai, Peoples R China. EM sunyh@medmail.com.cn; mozengnan@gmail.com; jxu@wfubmc.edu RI tao, sha/B-7750-2012 FU National Cancer Institute [R01CA129684] FX This study was partially funded by the National Cancer Institute (R01CA129684 to J. X.). NR 25 TC 26 Z9 31 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1349-7006 J9 CANCER SCI JI Cancer Sci. PD OCT PY 2011 VL 102 IS 10 BP 1916 EP 1920 DI 10.1111/j.1349-7006.2011.02036.x PG 5 WC Oncology SC Oncology GA 826CK UT WOS:000295328800011 PM 21756274 ER PT J AU Srikantan, S Gorospe, M Abdelmohsen, K AF Srikantan, Subramanya Gorospe, Myriam Abdelmohsen, Kotb TI Senescence-associated microRNAs linked to tumorigenesis SO CELL CYCLE LA English DT Editorial Material ID APOPTOSIS C1 [Srikantan, Subramanya; Gorospe, Myriam; Abdelmohsen, Kotb] NIA IRP, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA IRP, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 NR 10 TC 5 Z9 5 U1 0 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2011 VL 10 IS 19 BP 3211 EP 3212 DI 10.4161/cc.10.19.17050 PG 2 WC Cell Biology SC Cell Biology GA 827FB UT WOS:000295412100001 PM 21941082 ER PT J AU Bai, YW Zhou, Z Feng, HQ Zhou, BR AF Bai, Yawen Zhou, Zheng Feng, Hanqiao Zhou, Bing-Rui TI Recognition of centromeric histone variant CenH3s by their chaperones Structurally conserved or not SO CELL CYCLE LA English DT Editorial Material C1 [Bai, Yawen; Zhou, Zheng; Feng, Hanqiao; Zhou, Bing-Rui] NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov RI Zhou, Bing-Rui/D-4766-2009 NR 11 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2011 VL 10 IS 19 BP 3217 EP 3218 DI 10.4161/cc.10.19.17077 PG 2 WC Cell Biology SC Cell Biology GA 827FB UT WOS:000295412100004 PM 21926476 ER PT J AU Fer, N Melillo, G AF Fer, Nicole Melillo, Giovanni TI The HIF-1 alpha-c-Myc pathway and tumorigenesis: Evading the apoptotic gatekeeper SO CELL CYCLE LA English DT Editorial Material ID HYPOXIA; CANCER; CELLS; MYC C1 [Fer, Nicole; Melillo, Giovanni] NCI, Frederick, MD 21701 USA. RP Fer, N (reprint author), NCI, Frederick, MD 21701 USA. EM melillog@mail.nih.gov NR 8 TC 5 Z9 5 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2011 VL 10 IS 19 BP 3228 EP 3228 DI 10.4161/cc.10.19.17049 PG 1 WC Cell Biology SC Cell Biology GA 827FB UT WOS:000295412100010 PM 21971179 ER PT J AU Sackett, DL Fojo, T AF Sackett, Dan L. Fojo, Tito TI Taccalonolides: A microtubule stabilizer poses a new puzzle with old pieces SO CELL CYCLE LA English DT Editorial Material ID PACLITAXEL; TUBULIN; AGENTS C1 [Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Fojo, Tito] NCI, NIH, Bethesda, MD 20892 USA. RP Sackett, DL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM ds1k@nih.gov; fojot@mail.nih.gov NR 6 TC 4 Z9 4 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2011 VL 10 IS 19 BP 3233 EP 3234 DI 10.4161/cc.10.19.17126 PG 2 WC Cell Biology SC Cell Biology GA 827FB UT WOS:000295412100015 PM 21946521 ER PT J AU Cui, CY Kunisada, M Childress, V Michel, M Schlessinger, D AF Cui, Chang-Yi Kunisada, Makoto Childress, Victoria Michel, Marc Schlessinger, David TI Shh is required for Tabby hair follicle development SO CELL CYCLE LA English DT Article DE Eda; Shh; Wnt; hair follicle subtypes; Tabby ID HEDGEHOG SIGNALING PATHWAY; SWEAT GLAND DEVELOPMENT; SONIC-HEDGEHOG; ECTODERMAL DYSPLASIA; SALIVARY-GLANDS; INDUCTION; ECTODYSPLASIN; MICE; EDA; EXPRESSION AB In embryonic Eda mutant ("Tabby") mice, the development of one of the two major types of hair, "primary" hair fails, but other "secondary" hairs develop in normal numbers, though shorter and slightly aberrant. In Tabby mice, Shh is undetectable in skin early on, but is activated during secondary hair formation. We inferred that Shh may be involved in primary hair formation, activated normally by Eda, and also possibly in secondary hair formation, activated by an Eda-independent pathway. Varying the dosage of Shh now supports these inferences. In Shh knockout mice, mice were totally hairless: primary and secondary hair follicle germs were formed, but further progression failed. Consistent with these findings, when Shh loss was restricted to the skin, secondary hair follicle germs were initiated on time in Tabby mice, but their subsequent development (down-growth) failed. An Shh transgene expressed in Tabby skin could not restore induction of primary hair follicles, but restored normal length to the somewhat aberrant secondary hair that was formed and prolonged the anagen phase of hair cycling. Thus, Shh is required for primary and secondary hair down-growth and full secondary hair length, but is not itself sufficient to replace Eda or make fully normal secondary hair. C1 [Cui, Chang-Yi; Childress, Victoria; Michel, Marc; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Kunisada, Makoto] Kobe Univ, Div Dermatol, Dept Internal Med Related, Grad Sch Med, Kobe, Hyogo 657, Japan. RP Cui, CY (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM CuiC@mail.nih.gov FU National Institute on Aging, National Institutes of Health FX The authors thank David Richardson and Anna Butler for helping with animal management. This work was entirely supported by the Intramural Research Program of National Institute on Aging, National Institutes of Health. NR 32 TC 9 Z9 9 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2011 VL 10 IS 19 BP 3379 EP 3386 DI 10.4161/cc.10.19.17669 PG 8 WC Cell Biology SC Cell Biology GA 827FB UT WOS:000295412100036 PM 21926481 ER PT J AU Begaye, A Trostel, S Zhao, ZM Taylor, RE Schriemer, DC Sackett, DL AF Begaye, Adrian Trostel, Shana Zhao, Zhiming Taylor, Richard E. Schriemer, David C. Sackett, Dan L. TI Mutations in the beta-tubulin binding site for peloruside A confer resistance by targeting a cleft significant in side chain binding SO CELL CYCLE LA English DT Article DE peloruside A; laulimalide; paclitaxel; drug resistance; mitotic arrest; binding site; beta-tubulin ID MICROTUBULE-STABILIZING AGENTS; TAXOID SITE; CELLS RESISTANT; ALPHA-TUBULIN; LAULIMALIDE; PACLITAXEL; DRUGS; COLCHICINE; MUTANTS; MITOSIS AB Peloruside A is a microtubule-stabilizing macrolide that binds to beta-tubulin at a site distinct from the taxol site. The site was previously identified by H-D exchange mapping and molecular docking as a region close to the outer surface of the microtubule and confined in a cavity surrounded by a continuous loop of protein folded so as to center on Y340. We have isolated a series of peloruside A-resistant lines of the human ovarian carcinoma cell line A2780( 1A9) to better characterize this binding site and the consequences of altering residues in it. Four resistant lines (Pel A-D) are described with singlebase mutations in class I beta-tubulin that result in the following substitutions: R306H, Y340S, N337D and A296S in various combinations. The mutations are localized to peptides previously identified by Hydrogen-Deuterium exchange mapping, and center on a cleft in which the drug side chain appears to dock. The Pel lines are 10-15-fold resistant to peloruside A and show cross resistance to laulimalide but not to any other microtubule stabilizers. They show no cross-sensitivity to any microtubule destabilizers, nor to two drugs with targets unrelated to microtubules. Peloruside A induces G(2)/M arrest in the Pel cell lines at concentrations 10-15 times that required in the parental line. The cells show notable changes in morphology compared with the parental line. C1 [Begaye, Adrian; Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA. [Trostel, Shana] NCI, NIH, Bethesda, MD 20892 USA. [Zhao, Zhiming; Taylor, Richard E.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Schriemer, David C.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada. RP Sackett, DL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA. EM sackettd@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health; Human Development, NIH FX This work was supported in part by funding from the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 35 TC 18 Z9 18 U1 0 U2 13 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2011 VL 10 IS 19 BP 3387 EP 3396 DI 10.4161/cc.10.19.17706 PG 10 WC Cell Biology SC Cell Biology GA 827FB UT WOS:000295412100037 PM 21926482 ER PT J AU Hawkins, RD Hon, GC Yang, CH Antosiewicz-Bourget, JE Lee, LK Ngo, QM Klugman, S Ching, KA Edsall, LE Ye, Z Kuan, S Yu, PZ Liu, H Zhang, XM Green, RD Lobanenkov, VV Stewart, R Thomson, JA Ren, B AF Hawkins, R. David Hon, Gary C. Yang, Chuhu Antosiewicz-Bourget, Jessica E. Lee, Leonard K. Ngo, Que-Minh Klugman, Sarit Ching, Keith A. Edsall, Lee E. Ye, Zhen Kuan, Samantha Yu, Pengzhi Liu, Hui Zhang, Xinmin Green, Roland D. Lobanenkov, Victor V. Stewart, Ron Thomson, James A. Ren, Bing TI Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency SO CELL RESEARCH LA English DT Article DE hESCs; epigenomics; histone modifications; enhancers ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; HUMAN GENOME; HISTONE MODIFICATIONS; TRANSCRIPTION FACTORS; SELF-RENEWAL; DEVELOPMENTAL REGULATORS; DEFINED FACTORS; PROTEIN CTCF; ENHANCERS AB Pluripotency, the ability of a cell to differentiate and give rise to all embryonic lineages, defines a small number of mammalian cell types such as embryonic stem (ES) cells. While it has been generally held that pluripotency is the product of a transcriptional regulatory network that activates and maintains the expression of key stem cell genes, accumulating evidence is pointing to a critical role for epigenetic processes in establishing and safeguarding the pluripotency of ES cells, as well as maintaining the identity of differentiated cell types. In order to better understand the role of epigenetic mechanisms in pluripotency, we have examined the dynamics of chromatin modifications genome-wide in human ES cells (hESCs) undergoing differentiation into a mesendodermal lineage. We found that chromatin modifications at promoters remain largely invariant during differentiation, except at a small number of promoters where a dynamic switch between acetylation and methylation at H3K27 marks the transition between activation and silencing of gene expression, suggesting a hierarchy in cell fate commitment over most differentially expressed genes. We also mapped over 50 000 potential enhancers, and observed much greater dynamics in chromatin modifications, especially H3K4me1 and H3K27ac, which correlate with expression of their potential target genes. Further analysis of these enhancers revealed potentially key transcriptional regulators of pluripotency and a chromatin signature indicative of a poised state that may confer developmental competence in hESCs. Our results provide new evidence supporting the role of chromatin modifications in defining enhancers and pluripotency. C1 [Antosiewicz-Bourget, Jessica E.; Yu, Pengzhi; Thomson, James A.] Univ Wisconsin, Genome Ctr Wisconsin, Madison, WI 53706 USA. [Hawkins, R. David; Hon, Gary C.; Lee, Leonard K.; Ngo, Que-Minh; Klugman, Sarit; Ching, Keith A.; Edsall, Lee E.; Ye, Zhen; Kuan, Samantha; Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Yang, Chuhu; Stewart, Ron] Morgridge Inst Res, Madison, WI 53707 USA. [Liu, Hui; Zhang, Xinmin; Green, Roland D.] Roche NimbleGen, Madison, WI 53719 USA. [Lobanenkov, Victor V.] NIAID, Rockville, MD 20892 USA. RP Thomson, JA (reprint author), Univ Wisconsin, Genome Ctr Wisconsin, Madison, WI 53706 USA. EM thomson@primate.wisc.edu; biren@ucsd.edu RI Yu, Pengzhi/I-3182-2016; OI Yu, Pengzhi/0000-0001-7637-404X; Lobanenkov, Victor/0000-0001-6665-3635; Edsall, Lee Elizabeth/0000-0002-0326-2829 FU California Institute of Regenerative Medicine [RS1-00292-1, RN2-00905-1]; NIH [U01 ES017166-01]; Ludwig Institute for Cancer Research FX This work is supported, in part, by funding from the California Institute of Regenerative Medicine (to BR; RS1-00292-1 and RN2-00905-1), the NIH (U01 ES017166-01) and the Ludwig Institute for Cancer Research. NR 78 TC 50 Z9 53 U1 0 U2 12 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD OCT PY 2011 VL 21 IS 10 BP 1393 EP 1409 DI 10.1038/cr.2011.146 PG 17 WC Cell Biology SC Cell Biology GA 827VN UT WOS:000295457400005 PM 21876557 ER PT J AU Pezzolo, A Parodi, F Marimpietri, D Raffaghello, L Cocco, C Pistorio, A Mosconi, M Gambini, C Cilli, M Deaglio, S Malavasi, F Pistoia, V AF Pezzolo, Annalisa Parodi, Federica Marimpietri, Danilo Raffaghello, Lizzia Cocco, Claudia Pistorio, Angela Mosconi, Manuela Gambini, Claudio Cilli, Michele Deaglio, Silvia Malavasi, Fabio Pistoia, Vito TI Oct-4(+)/Tenascin C+ neuroblastoma cells serve as progenitors of tumor-derived endothelial cells SO CELL RESEARCH LA English DT Article DE neuroblastoma; vascular mimicry; tumor-derived endothelium; progenitor cells; Tenascin C ID STEM-LIKE CELLS; TENASCIN-C; SELF-RENEWAL; DIFFERENTIAL-DIAGNOSIS; STEM/PROGENITOR CELLS; PERIVASCULAR NICHE; INITIATING CELLS; GANGLIOSIDE GD2; CANCER; EXPRESSION AB Neuroblastoma (NB)-associated endothelial microvessels (EMs) may be lined by tumor-derived endothelial cells (TECs), that are genetically unstable and chemoresistant. Here we have addressed the identification of TEC progenitors in NB by focusing on Octamer-binding transcription factor 4 (Oct-4) as a putative marker. Oct-4(+) cells were detected in primary NB samples (n = 23), metastatic bone marrow aspirates (n = 10), NB cell lines (n = 4), and orthotopic tumors (n = 10) formed by the HTLA-230 NB cell line in immunodeficient mice. Most Oct-4(+) cells showed a perivascular distribution, with 5% of them homing in perinecrotic areas. All Oct-4(+) cells were tumor-derived since they shared amplification of MYCN oncogene with malignant cells. Perivascular Oct-4(+) cells expressed stem cell-related, neural progenitor-related and NB-related markers, including surface Tenascin C (TNC), that was absent from perinecrotic Oct-4(+) cells and bulk tumor cells. TNC+ but not TNC-HTLA-230 cells differentiated in vitro into endothelial-like cells expressing vascular-endothelial-cadherin, prostate-specific membrane antigen and CD31 upon culture in medium containing vascular endothelial growth factor (VEGF). TNC+ but not TNC-HTLA-230 cells formed neurospheres when cultured in serum-free medium. Both cell fractions were tumorigenic, but only tumors formed by TNC+ cells contained EMs lined by TECs. In conclusion, we have identified in NB tumors two putative niches containing Oct-4(+) tumor cells. Oct-4(+)/TNC+ perivascular NB cells displayed a high degree of plasticity and served as progenitors of TECs. Therapeutic targeting of Oct4(+)/TNC+ progenitors may counteract the contribution of NB-derived ECs to tumor relapse and chemoresistance. C1 [Pezzolo, Annalisa; Parodi, Federica; Marimpietri, Danilo; Raffaghello, Lizzia; Pistoia, Vito] Ist Giannina Gaslini, Lab Oncol, I-16147 Genoa, Italy. [Cocco, Claudia] Ist Giannina Gaslini, AIRC Tumor Immunol Unit, I-16147 Genoa, Italy. [Pistorio, Angela] Ist Giannina Gaslini, Epidemiol & Biostat Unit, I-16147 Genoa, Italy. [Mosconi, Manuela; Gambini, Claudio] IRCCS G Gaslini Hosp, Dept Expt & Lab Med, Pathol Lab, Genoa, Italy. [Cilli, Michele] Natl Canc Inst, Anim Res Facil, Genoa, Italy. [Deaglio, Silvia; Malavasi, Fabio] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. RP Pezzolo, A (reprint author), Ist Giannina Gaslini, Lab Oncol, Largo G Gaslini 5, I-16147 Genoa, Italy. EM annalisapezzolo@ospedale-gaslini.ge.it RI Deaglio, Silvia/G-4814-2011; OI Raffaghello, Lizzia/0000-0003-2357-0607 FU Fondazione Italiana Neuroblastoma, Fondazione; Ministero della Salute Progetto Strategico Oncologico; Associazione Italiana per la Ricerca sul Cancro (AIRC) FX We thank the late Dr Giorgio Corte for reading the manuscript. Special thanks go to Dr Paolo Bianco for discussion and suggestions. This work was supported by Fondazione Italiana Neuroblastoma, Fondazione "Guido Berlucchi", Fondazione "Bianca e Wilma Querci", Progetto di Ricerca Regione Liguria "Endotelio di derivazione tumorale: caratterizzazione e targeting immunologico a fini terapeutici" and Ministero della Salute Progetto Strategico Oncologico 2006 "Microambiente tumorale: ruolo nella progressione neoplastica sulle difese dell'ospite. Identificazione di nuovi bersagli per lo sviluppo di terapie innovative". CC was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC). NR 78 TC 22 Z9 24 U1 0 U2 5 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD OCT PY 2011 VL 21 IS 10 BP 1470 EP 1486 DI 10.1038/cr.2011.38 PG 17 WC Cell Biology SC Cell Biology GA 827VN UT WOS:000295457400010 PM 21403679 ER PT J AU Roberts, DD AF Roberts, David D. TI Emerging functions of matricellular proteins SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review ID EXTRACELLULAR-MATRIX; THROMBOSPONDIN-1; INTEGRIN; DISEASE; MICE; ABNORMALITIES; COLLAGEN C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Center for Cancer Research, National Cancer Institute, NIH FX Cited work in the author's laboratory was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. Conference support was provided by DK089753-01, the Center for Cancer Research, and the NIH Office of Rare Diseases Research. NR 26 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD OCT PY 2011 VL 68 IS 19 BP 3133 EP 3136 DI 10.1007/s00018-011-0779-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 826BX UT WOS:000295327500001 PM 21833584 ER PT J AU Gemoll, T Roblick, UJ Szymczak, S Braunschweig, T Becker, S Igl, BW Bruch, HP Ziegler, A Hellman, U Difilippantonio, MJ Ried, T Jornvall, H Auer, G Habermann, JK AF Gemoll, Timo Roblick, Uwe J. Szymczak, Silke Braunschweig, Till Becker, Susanne Igl, Bernd-Wolfgang Bruch, Hans-Peter Ziegler, Andreas Hellman, Ulf Difilippantonio, Michael J. Ried, Thomas Jornvall, Hans Auer, Gert Habermann, Jens K. TI HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE Colon cancer; Genomic instability; Two-dimensional gel electrophoresis; Mass spectrometry; Aneuploidy; HDAC2 ID COMPARATIVE GENOMIC HYBRIDIZATION; CHROMOSOMAL INSTABILITY; COLON-CANCER; GEL-ELECTROPHORESIS; TISSUE MICROARRAYS; CELL-LINES; EXPRESSION; CARCINOMA; THIOREDOXIN; BINDING AB DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n = 19), diploid (n = 31), and aneuploid (n = 47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers. C1 [Gemoll, Timo; Roblick, Uwe J.; Bruch, Hans-Peter; Habermann, Jens K.] Med Univ Lubeck, Surg Res Lab, Dept Surg, D-23538 Lubeck, Germany. [Gemoll, Timo; Roblick, Uwe J.; Jornvall, Hans; Habermann, Jens K.] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden. [Gemoll, Timo; Becker, Susanne; Auer, Gert] Karolinska Inst, Karolinska Biom Ctr, S-17176 Stockholm, Sweden. [Braunschweig, Till] Univ Clin RWTH Aachen, Inst Pathol, D-52074 Aachen, Germany. [Szymczak, Silke; Igl, Bernd-Wolfgang; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometry & Stat, D-23538 Lubeck, Germany. [Hellman, Ulf] Canc Res Ltd, Ludwig Inst, S-75124 Uppsala, Sweden. [Difilippantonio, Michael J.; Ried, Thomas] NCI, Dept Genet, Ctr Canc Res, NIH, Bethesda, MD 20814 USA. RP Habermann, JK (reprint author), Med Univ Lubeck, Surg Res Lab, Dept Surg, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM Jens.Habermann@gmail.com RI Szymczak, Silke/C-6625-2013; Habermann, Jens/E-2968-2010; OI Ziegler, Andreas/0000-0002-8386-5397 FU Swedish Cancer Society (Cancerfonden); Cancer Society Stockholm (Cancerforeningen); Swedish Research Council; Wallenberg Consortium North; Knut and Alice Wallenberg Foundation; Ad Infinitum Foundation; Werner and Clara Kreitz Foundation FX Grants from the Swedish Cancer Society (Cancerfonden), the Cancer Society Stockholm (Cancerforeningen), the Swedish Research Council, the Wallenberg Consortium North, the Knut and Alice Wallenberg Foundation, the Ad Infinitum Foundation, and the Werner and Clara Kreitz Foundation are gratefully acknowledged. We thank Elke Gheribi and Regina Kaatz for assistance with clinical sample collection, Gisela Grosser-Pape for support with ploidy assessment, and Claudia Killaitis for clinical data administration. This study was performed in collaboration with the North German Tumor Bank of Colorectal Cancer (DKH #108446) and the Surgical Center for Translational Oncology-Lubeck (SCTO-L). NR 41 TC 4 Z9 4 U1 0 U2 6 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD OCT PY 2011 VL 68 IS 19 BP 3261 EP 3274 DI 10.1007/s00018-011-0628-3 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 826BX UT WOS:000295327500011 PM 21290163 ER PT J AU Pan, Q Qiao, F Gao, C Norman, B Optican, L Zelenka, PS AF Pan, Q. Qiao, F. Gao, C. Norman, B. Optican, L. Zelenka, Peggy S. TI Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75) SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE Cdk5; Src; Signal transduction; Ubiquitination; Kinase activity ID TYROSINE KINASE; C-SRC; CELL-MATRIX; ACTIVATION; MITOSIS; SITE; PP60(C-SRC); MORPHOLOGY; PP60C-SRC; ADHESION AB The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity. C1 [Pan, Q.; Qiao, F.; Gao, C.; Norman, B.; Zelenka, Peggy S.] NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. [Optican, L.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NEI, Lab Mol & Dev Biol, NIH, 5635 Fishers Lane,Room 1127, Bethesda, MD 20892 USA. EM zelenkap@nei.nih.gov FU National Eye Institute [Z01-EY000238-25] FX We thank Dr. John Reddan of Oakland University for the human lens epithelial cell line (FHL124), Drs. Xiao Dong Jiao and J. Fielding Hejtmancik for generously sequencing DNA clones, and Ms. Andrea Elfstrom for technical assistance. This work was supported by the National Eye Institute Intramural Research Program Z01-EY000238-25. NR 30 TC 17 Z9 19 U1 0 U2 7 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD OCT PY 2011 VL 68 IS 20 BP 3425 EP 3436 DI 10.1007/s00018-011-0638-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 826BS UT WOS:000295327000010 PM 21442427 ER PT J AU Zaidi, MR Merlino, G AF Zaidi, M. Raza Merlino, Glenn TI The Two Faces of Interferon-gamma in Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; MAJOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; IFN-GAMMA; T-CELLS; IN-VIVO; INDOLEAMINE 2,3-DIOXYGENASE; CUTANEOUS MELANOMA; INDUCED ARTHRITIS; IMMUNE ESCAPE AB Interferon-gamma is a cytokine whose biological activity is conventionally associated with cytostatic/cytotoxic and antitumor mechanisms during cell-mediated adaptive immune response. It has been used clinically to treat a variety of malignancies, albeit with mixed results and side effects that can be severe. Despite ample evidence implicating a role for IFN-gamma in tumor immune surveillance, a steady flow of reports has suggested that it may also have protumorigenic effects under certain circumstances. We propose that, in fact, IFN-gamma treatment is a double-edged sword whose anti-and protumorigenic activities are dependent on the cellular, microenvironmental, and/or molecular context. As such, inhibition of the IFN-gamma/IFN-gamma receptor pathway may prove to be a viable new therapeutic target for a subset of malignancies. Clin Cancer Res; 17(19); 6118-24. (C) 2011 AACR. C1 [Zaidi, M. Raza; Merlino, Glenn] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zaidi, MR (reprint author), 37 Convent Dr,5002, Bethesda, MD 20892 USA. EM zaidir@mail.nih.gov RI Zaidi, M. Raza/H-1386-2016 OI Zaidi, M. Raza/0000-0003-0480-3188 FU Center for Cancer Research, NCI, NIH FX This work was supported in part by the Intramural Research Program of the Center for Cancer Research, NCI, NIH. NR 85 TC 139 Z9 144 U1 0 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2011 VL 17 IS 19 BP 6118 EP 6124 DI 10.1158/1078-0432.CCR-11-0482 PG 7 WC Oncology SC Oncology GA 827VR UT WOS:000295457900003 PM 21705455 ER PT J AU Parkhurst, MR Riley, JP Dudley, ME Rosenberg, SA AF Parkhurst, Maria R. Riley, John P. Dudley, Mark E. Rosenberg, Steven A. TI Adoptive Transfer of Autologous Natural Killer Cells Leads to High Levels of Circulating Natural Killer Cells but Does Not Mediate Tumor Regression SO CLINICAL CANCER RESEARCH LA English DT Article ID KIR LIGAND INCOMPATIBILITY; NK CELLS; INHIBITORY RECEPTORS; METASTATIC MELANOMA; CANCER REGRESSION; SELF-TOLERANCE; BREAST-CANCER; IMMUNOTHERAPY; TRANSPLANTATION; THERAPY AB Purpose: Adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate regression of metastatic melanoma. However, many patients with cancer are ineligible for such treatment because their TIL do not expand sufficiently or because their tumors have lost expression of antigens and/or MHC molecules. Natural killer (NK) cells are large granular lymphocytes that lyse tumor cells in a non-MHC-restricted manner. Therefore, we initiated in a clinical trial to evaluate the efficacy of adoptively transferred autologous NK cells to treat patients with cancers who were ineligible for treatment with TIL. Experimental Design: Patients with metastatic melanoma or renal cell carcinoma were treated with adoptively transferred in vitro activated autologous NK cells after the patients received a lymphodepleting but nonmyeloablative chemotherapy regimen. Clinical responses and persistence of the adoptively transferred cells were evaluated. Results: Eight patients were treated with an average of 4.7 x 10(10) (+/- 2.1 x 10(10)) NK cells. The infused cells exhibited high levels of lytic activity in vitro. Although no clinical responses were observed, the adoptively transferred NK cells seemed to persist in the peripheral circulation of patients for at least one week posttransfer and, in some patients, for several months. However, the persistent NK cells in the circulation expressed significantly lower levels of the key activating receptor NKG2D and could not lyse tumor cell targets in vitro unless reactivated with IL-2. Conclusions: The persistent NK cells could mediate antibody-dependent cell-mediated cytotoxicity without cytokine reactivation in vitro, which suggests that coupling adoptive NK cell transfer with monoclonal antibody administration deserves evaluation. Clin Cancer Res; 17(19); 6287-97. (C) 2011 AACR. C1 [Parkhurst, Maria R.; Riley, John P.; Dudley, Mark E.; Rosenberg, Steven A.] NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RP Parkhurst, MR (reprint author), NCI, NIH, Surg Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Maria_Parkhurst@nih.gov FU NCI FX This work was funded through the NCI intramural program. NR 34 TC 98 Z9 104 U1 3 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2011 VL 17 IS 19 BP 6287 EP 6297 DI 10.1158/1078-0432.CCR-11-1347 PG 11 WC Oncology SC Oncology GA 827VR UT WOS:000295457900019 PM 21844012 ER PT J AU Hoofnagle, AN Aebersold, R Anderson, NL Felsenfeld, A Liebler, DC AF Hoofnagle, Andrew N. Aebersold, Ruedi Anderson, N. Leigh Felsenfeld, Adam Liebler, Daniel C. TI Painting a Moving Picture: Large-Scale Proteomics Efforts and Their Potential for Changing Patient Care SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Aebersold, Ruedi] Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, Zurich, Switzerland. [Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC USA. [Felsenfeld, Adam] NHGRI, Bethesda, MD 20892 USA. [Liebler, Daniel C.] Vanderbilt Univ, Jim Ayers Inst Precance Detect & Diag, Nashville, TN USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Hoofnagle, AN (reprint author), Univ Washington, Dept Lab Med, 1959 NE Pacific,Campus Box 357110, Seattle, WA 98195 USA. EM ahoof@u.washington.edu OI Liebler, Daniel/0000-0002-7873-3031 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 2011 VL 57 IS 10 BP 1357 EP 1360 DI 10.1373/clinchem.2010.158311 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 825ZX UT WOS:000295322000004 PM 21540400 ER PT J AU Hutchison, CA Landgren, O AF Hutchison, Colin A. Landgren, Ola TI Polyclonal Immunoglobulin Free Light Chains as a Potential Biomarker of Immune Stimulation and Inflammation SO CLINICAL CHEMISTRY LA English DT Article ID C-REACTIVE PROTEIN; SERUM; CATABOLISM; DISORDERS; DISEASE; RISK C1 [Hutchison, Colin A.] Univ Hosp Birmingham, Dept Nephrol, Birmingham B15 2TH, W Midlands, England. [Hutchison, Colin A.] Univ Birmingham, Dept Nephrol, Renal Inst Birmingham, Birmingham, W Midlands, England. [Landgren, Ola] NCI, Multiple Myeloma Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Hutchison, CA (reprint author), Univ Hosp Birmingham, Dept Nephrol, Birmingham B15 2TH, W Midlands, England. EM c.a.hutchison@bham.ac.uk NR 18 TC 30 Z9 31 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 2011 VL 57 IS 10 BP 1387 EP 1389 DI 10.1373/clinchem.2011.169433 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 825ZX UT WOS:000295322000010 PM 21836076 ER PT J AU Schwope, DM Karschner, EL Gorelick, DA Huestis, MA AF Schwope, David M. Karschner, Erin L. Gorelick, David A. Huestis, Marilyn A. TI Identification of Recent Cannabis Use: Whole-Blood and Plasma Free and Glucuronidated Cannabinoid Pharmacokinetics following Controlled Smoked Cannabis Administration SO CLINICAL CHEMISTRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; ORAL FLUID; DELTA-9-TETRAHYDROCANNABINOL THC; TEMPORAL INDICATION; HEPATIC MICROSOMES; HUMAN-URINE; METABOLISM; DELTA(9)-TETRAHYDROCANNABINOL; MARIJUANA; TETRAHYDROCANNABINOL AB BACKGROUND: Delta(9)-Tetrahydrocannabinol (THC) is the most frequently observed illicit drug in investigations of accidents and driving under the influence of drugs. THC-glucuronide has been suggested as a marker of recent cannabis use, but there are no blood data following controlled THC administration to test this hypothesis. Furthermore, there are no studies directly examining whole-blood cannabinoid pharmacokinetics, although this matrix is often the only available specimen. METHODS: Participants (9 men, 1 woman) resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. We quantified THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide and THCCOOH-glucuronide directly in whole blood and plasma by liquid chromatography/tandem mass spectrometry within 24 h of collection to obviate stability issues. RESULTS: Median whole blood (plasma) observed maximum concentrations (C(max)) were 50 (76), 6.4 (10), 41 (67), 1.3 (2.0), 2.4 (3.6), 89 (190), and 0.7 (1.4) mu g/L 0.25 h after starting smoking for THC, 11-OH-THC, THCCOOH, CBD, CBN, and THCCOOH-glucuronide, respectively, and 0.5 h for THCglucuronide. At observed C(max), whole-blood (plasma) detection rates were 60% (80%), 80% (90%), and 50% (80%) for CBD, CBN, and THC-glucuronide, respectively. CBD and CBN were not detectable after 1 h in either matrix (LOQ 1.0 mu g/L). CONCLUSIONS: Human whole-blood cannabinoid data following cannabis smoking will assist whole blood and plasma cannabinoid interpretation, while furthering identification of recent cannabis intake. (C) 2011 American Association for Clinical Chemistry C1 [Schwope, David M.; Karschner, Erin L.; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, NIH FX D.M. Schwope, Intramural Research Program, National Institute on Drug Abuse, NIH; M.A. Huestis, Intramural Research Program, National Institute on Drug Abuse, NIH. NR 37 TC 49 Z9 50 U1 6 U2 26 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 2011 VL 57 IS 10 BP 1406 EP 1414 DI 10.1373/clinchem.2011.171777 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 825ZX UT WOS:000295322000013 PM 21836075 ER PT J AU Matsumoto, RR Li, SM Katz, JL Fantegrossi, WE Coop, A AF Matsumoto, Rae R. Li, Su-Min Katz, Jonathan L. Fantegrossi, William E. Coop, Andrew TI Effects of the selective sigma receptor ligand, 1-(2-phenethyl)piperidine oxalate (AC927), on the behavioral and toxic effects of cocaine SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cocaine; Conditioned place preference; Drug discrimination; Locomotor activity; Self-administration; Sigma receptors ID CONDITIONED PLACE PREFERENCE; PHEOCHROMOCYTOMA PC12 CELLS; RHESUS-MONKEYS; PROTEIN EXPRESSION; GUINEA-PIG; IN-VIVO; RAT; DOPAMINE; INVOLVEMENT; BINDING AB Background: Sigma receptors represent a unique structural class of proteins and they have become increasingly studied as viable medication development targets for neurological and psychiatric disorders, including drug abuse. Earlier studies have shown that cocaine and many other abused substances interact with sigma receptors and that antagonism of these proteins can mitigate their actions. Methods: In the present study, AC927 (1-(2-phenethyl)piperidine oxalate), a selective sigma receptor ligand, was tested against the behavioral and toxic effects of cocaine in laboratory animals. Results: Acute administration of AC927 in male, Swiss Webster mice significantly attenuated cocaine-induced convulsions, lethality, and locomotor activity, at doses that alone had no significant effects on behavior. Subchronic administration of AC927 also attenuated cocaine-induced conditioned place preference in mice, at doses that alone had no effects on place conditioning. In drug discrimination studies in male, Sprague-Dawley rats, AC927 partially substituted for the discriminative stimulus effects of cocaine. When it was administered with cocaine, AC927 shifted the cocaine dose-response curve to the left, suggesting an enhancement of the discriminative stimulus effects of cocaine. In non-human primates, AC927 was self-administered, maintaining responding that was intermediate between contingent saline and a maintenance dose of cocaine. Conclusion: The ability of AC927 to elicit some cocaine-like appetitive properties and to also reduce many cocaine-induced behaviors suggests that it is a promising lead for the development of a medication to treat cocaine abuse. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Matsumoto, Rae R.] W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. [Matsumoto, Rae R.] Univ Oklahoma, Hlth Sci Ctr, Dept Pharmaceut Sci, Coll Pharm, Norman, OK 73019 USA. [Li, Su-Min; Katz, Jonathan L.] Natl Inst Drug Abuse, Psychobiol Sect, Lexington, KY USA. [Fantegrossi, William E.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Fantegrossi, William E.] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. [Coop, Andrew] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, College Pk, MD 20742 USA. RP Matsumoto, RR (reprint author), W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA. EM rmatsumoto@hsc.wvu.edu OI Katz, Jonathan/0000-0002-1068-1159 FU National Institute on Drug Abuse (NIDA) [DA11979, DA13978, DA05018, DA19634]; College on Problems of Drug Dependence (CPDD) FX Funding for this study was provided by the National Institute on Drug Abuse (NIDA, DA11979, DA13978, and DA05018) and the College on Problems of Drug Dependence (CPDD). Andrew Coop is the recipient of a K02 award from NIDA (DA19634). The NIDA and CPDD had no further role in study design; in the collection, analysis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication. NR 52 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2011 VL 118 IS 1 BP 40 EP 47 DI 10.1016/j.drugalcdep.2011.02.017 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 826ZN UT WOS:000295394200007 PM 21420799 ER PT J AU Edin, ML Wang, ZJ Bradbury, JA Graves, JP Lih, FB DeGraff, LM Foley, JF Torphy, R Ronnekleiv, OK Tomer, KB Lee, CR Zeldin, DC AF Edin, Matthew L. Wang, ZhongJing Bradbury, J. Alyce Graves, Joan P. Lih, Fred B. DeGraff, Laura M. Foley, Julie F. Torphy, Robert Ronnekleiv, Oline K. Tomer, Kenneth B. Lee, Craig R. Zeldin, Darryl C. TI Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart SO FASEB JOURNAL LA English DT Article DE CYP2J2; EETs; reactive oxygen species; leukotoxin; Langendorff ID SOLUBLE EPOXIDE HYDROLASE; EPOXYEICOSATRIENOIC ACIDS; ARACHIDONIC-ACID; LINOLEIC-ACID; MYOCARDIAL-INFARCTION; POSTISCHEMIC RECOVERY; ATHEROSCLEROSIS RISK; CONTRACTILE FUNCTION; GENETIC-VARIATION; DISEASE RISK AB Cytochrome P450 (CYP) epoxygenases CYP2C8 and CYP2J2 generate epoxyeicosatrienoic acids (EETs) from arachidonic acid. Mice with expression of CYP2J2 in cardiomyocytes (alpha MHC-CYP2J2 Tr) or treated with synthetic EETs have increased functional recovery after ischemia/reperfusion (I/R); however, no studies have examined the role of cardiomyocyte-vs. endothelial-derived EETs or compared the effects of different CYP epoxygenase isoforms in the ischemic heart. We generated transgenic mice with increased endothelial EET biosynthesis (Tie2-CYP2C8 Tr and Tie2-CYP2J2 Tr) or EET hydrolysis (Tie2-sEH Tr). Compared to wild-type (WT), alpha MHC-CYP2J2 Tr hearts showed increased recovery of left ventricular developed pressure (LVDP) and decreased infarct size after I/R. In contrast, LVDP recovery and infarct size were unchanged in Tie2-CYP2J2 Tr and Tie2-sEH Tr hearts. Surprisingly, compared to WT, Tie2-CYP2C8 Tr hearts had significantly reduced LVDP recovery (from 21 to 14%) and increased infarct size after I/R (from 51 to 61%). Tie2-CYP2C8 Tr hearts also exhibited increased reactive oxygen species (ROS) generation, dihydroxyoctadecenoic acid (DiHOME) formation, and coronary resistance after I/R. ROS scavengers and CYP2C8 inhibition reversed the detrimental effects of CYP2C8 expression in Tie2-CYP2C8 Tr hearts. Treatment of WT hearts with 250 nM 9,10-DiHOME decreased LVDP recovery compared to vehicle (16 vs. 31%, respectively) and increased coronary resistance after I/R. These data demonstrate that increased ROS generation and enhanced DiHOME synthesis by endothelial CYP2C8 impair functional recovery and mask the beneficial effects of increased EET production following I/R.-Edin, M. L., Wang, Z. J., Bradbury, J. A., Graves, J. P., Lih, F. B., DeGraff, L. M., Foley, J. F., Torphy, R., Ronnekleiv, O. K., Tomer, K. B., Lee, C. R., Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart. FASEB J. 25, 3436-3447 (2011). www.fasebj.org C1 [Edin, Matthew L.; Wang, ZhongJing; Bradbury, J. Alyce; Graves, Joan P.; Lih, Fred B.; DeGraff, Laura M.; Foley, Julie F.; Torphy, Robert; Tomer, Kenneth B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Ronnekleiv, Oline K.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Ronnekleiv, Oline K.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Lee, Craig R.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), 111 TW Alexander Dr,Bldg 101,Rm A222, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013; OI Edin, Matthew/0000-0002-7042-500X; Lee, Craig/0000-0003-3595-5301 FU NIH, NIEHS [Z01 ES050167, Z01 ES025034, R01 GM088199] FX The authors thank Dr. Bruce Hammock (University of California, Davis, CA, USA) for providing the sEH antibody, Dr. Joyce Goldstein [U.S. National Institutes of Health (NIH)/National Institute for Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA] for providing the CYP2C8 antibody, and Dr. Tom Sato (University of Texas Southwestern Medical Center, Dallas, TX, USA) for providing the Tie2 promoter construct. The authors also thank staff at Xenogen Biosciences (Cranberry, NJ, USA) for assistance with pronuclear injections and staff in the NIEHS Laboratory of Experimental Pathology (Natasha Clayton and Tiwanda Masinde) for assistance with immunohistochemistry. This work was supported with funds from the Intramural Research Program of the NIH, NIEHS, to K.B.T. (Z01 ES050167), D.C.Z. (Z01 ES025034), and C.R.L. (R01 GM088199). NR 56 TC 56 Z9 56 U1 1 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2011 VL 25 IS 10 BP 3436 EP 3447 DI 10.1096/fj.11-188300 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 826LU UT WOS:000295356400015 PM 21697548 ER PT J AU Kashimada, K Svingen, T Feng, CW Pelosi, E Bagheri-Fam, S Harley, VR Schlessinger, D Bowles, J Koopman, P AF Kashimada, Kenichi Svingen, Terje Feng, Chun-Wei Pelosi, Emanuele Bagheri-Fam, Stefan Harley, Vincent R. Schlessinger, David Bowles, Josephine Koopman, Peter TI Antagonistic regulation of Cyp26b1 by transcription factors SOX9/SF1 and FOXL2 during gonadal development in mice SO FASEB JOURNAL LA English DT Article DE Forkhead box protein L2; germ cells; meiosis; retinoic acid; sex determination ID STEROIDOGENIC FACTOR-I; GERM-CELL FATE; SEX DETERMINATION; RETINOIC-ACID; GENE-TRANSCRIPTION; TESTIS DEVELOPMENT; NUCLEAR RECEPTOR; MOUSE; DIFFERENTIATION; EXPRESSION AB Sex determination in fetal germ cells depends on a balance between exposure to retinoic acid (RA) and the degradation of RA achieved by the testis-specific expression of the catabolic cytochrome P450 enzyme, CYP26B1. Therefore, identification of factors regulating the expression of the Cyp26b1 gene is an important goal in reproductive biology. We used in situ hybridization to demonstrate that Cyp26b1 and transcription factor genes steroidogenic factor-1 (Sf1) and Sry-related HMG box 9 (Sox9) are coexpressed in Sertoli cells, whereas Cyp26b1 and Sf1 are coexpressed in Leydig cells in mouse fetal testes. In the mouse gonadal somatic cell line TM3, transfection of constructs expressing SOX9 and SF1 activated Cyp26b1 expression, independently of the positive regulator RA. In embryonic gonads deficient in SOX9 or SF1, Cyp26b1 expression was decreased relative to wild-type (WT) controls, as measured by quantitative RT-PCR (qRT-PCR). Furthermore, qRT-PCR showed that Cyp26b1 up-regulation by SOX9/SF1 was attenuated by the ovarian transcription factor Forkhead box L2 (FOXL2) in TM3 cells, whereas in Foxl2-null mice, Cyp26b1 expression in XX gonads was increased similar to 20-fold relative to WT controls. These data support the hypothesis that SOX9 and SF1 ensure the male fate of germ cells by up-regulating Cyp26b1 and that FOXL2 acts to antagonize Cyp26b1 expression in ovaries.-Kashimada, K., Svingen, T., Feng, C.-W., Pelosi, E., Bagheri-Fam, S., Harley, V. R., Schlessinger, D., Bowles, J., Koopman, P. Antagonistic regulation of Cyp26b1 by transcription factors SOX9/SF1 and FOXL2 during gonadal development in mice. FASEB J. 25, 3561-3569 (2011). www.fasebj.org C1 [Kashimada, Kenichi; Svingen, Terje; Feng, Chun-Wei; Bowles, Josephine; Koopman, Peter] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. [Pelosi, Emanuele; Schlessinger, David] NIA, NIH, Biomed Res Ctr, Intramural Res Program,Lab Genet, Baltimore, MD 21224 USA. [Bagheri-Fam, Stefan; Harley, Vincent R.] Prince Henrys Inst Med Res, Clayton, Vic, Australia. RP Koopman, P (reprint author), Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. EM p.koopman@imb.uq.edu.au RI Svingen, Terje/A-5283-2010; Koopman, Peter /C-9416-2009; Bowles, Josephine/B-6583-2013; OI Svingen, Terje/0000-0003-4650-7651; Koopman, Peter /0000-0001-6939-0914; Bowles, Josephine/0000-0003-2867-7438; Harley, Vincent/0000-0002-2405-1262; Pelosi, Emanuele/0000-0003-1890-9821; Kashimada, Kenichi/0000-0003-2505-5932 FU Australian Research Council (ARC); National Health and Medical Research Council of Australia; U.S. National Institutes of Health, National Institute on Aging FX The authors thank R. Chandraratna and K. Yin Tsang (Vitae Pharmaceuticals, Fort Washington, PA, USA) for providing AGN193109, Ken-Ichirou Morohashi (Kyushu University, Fukuoka, Japan) for providing SF1 antibody, and Sally L. Dunwoodie (Victor Chang Cardiac Research Institute, Sydney, NSW, Australia) for providing Cited2-knockout mice. The authors also thank C. Spiller and C. Harris for technical support. This work was supported by research grants from the Australian Research Council (ARC), the National Health and Medical Research Council of Australia, and the Intramural Research Program of the U.S. National Institutes of Health, National Institute on Aging. P.K. is a Federation Fellow of the ARC. NR 56 TC 36 Z9 38 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2011 VL 25 IS 10 BP 3561 EP 3569 DI 10.1096/fj.11-184333 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 826LU UT WOS:000295356400026 PM 21757499 ER PT J AU An, J Golech, S Klaewsongkram, J Zhang, YQ Subedi, K Huston, GE Wood, WH Wersto, RP Becker, KG Swain, SL Weng, NP AF An, Jie Golech, Susanne Klaewsongkram, Jettanong Zhang, Yongqing Subedi, Kalpana Huston, Gail E. Wood, William H., III Wersto, Robert P. Becker, Kevin G. Swain, Susan L. Weng, Nanping TI Kruppel-like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL-17 expression during Th17 differentiation SO FASEB JOURNAL LA English DT Article DE transcription factor; T-cell homeostasis; autoimmune disease ID T-CELL DEVELOPMENT; ROR-GAMMA-T; EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR; DOWN-REGULATION; T-H-17 CELLS; TGF-BETA; LINEAGE; SURVIVAL; ALPHA AB Kruppel-like factor 4 (KLF4), a transcription factor, plays a key role in the pluripotency of stem cells. We sought to determine the function of KLF4 in T-cell development and differentiation by using T-cell-specific Klf4-knockout (KO) mice. We found that KLF4 was highly expressed in thymocytes and mature T cells and was rapidly down-regulated in mature T cells after activation. In Klf4-KO mice, we observed a modest reduction of thymocytes (27%) due to the reduced proliferation of double-negative (DN) thymocytes. We demonstrated that a direct repression of Cdkn1b by KLF4 was a cause of decreased DN proliferation. During in vitro T-cell differentiation, we observed significant reduction of IL-17-expressing CD4(+) T cells (Th17; 24%) but not in other types of Th differentiation. The reduction of Th17 cells resulted in a significant attenuation of the severity (35%) of experimental autoimmune encephalomyelitis in vivo in Klf4-KO mice as compared with the Klf4 wild-type littermates. Finally, we demonstrated that KLF4 directly binds to the promoter of Il17a and positively regulates its expression. In summary, these findings identify KLF4 as a critical regulator in T-cell development and Th17 differentiation.-An, J., Golech, S., Klaewsongkram, J., Zhang, Y., Subedi, K., Huston, G. E., Wood, W. H., III, Wersto, R. P., Becker, K. G., Swain, S. L., Weng, N. Kruppel-like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL-17 expression during Th17 differentiation. FASEB J. 25, 3634-3645 (2011). www.fasebj.org C1 [An, Jie; Golech, Susanne; Klaewsongkram, Jettanong; Subedi, Kalpana; Weng, Nanping] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Zhang, Yongqing; Wood, William H., III; Becker, Kevin G.] NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. [Wersto, Robert P.] NIA, Flow Cytometry Unit, NIH, Baltimore, MD 21224 USA. [Huston, Gail E.] Trudeau Inst, New York, NY USA. [Swain, Susan L.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. RP Weng, NP (reprint author), 251 Bayview Blvd,Ste 100, Baltimore, MD 21224 USA. EM wengn@mail.nih.gov OI Klaewsongkram, Jettanong/0000-0001-6063-2403; Becker, Kevin/0000-0002-6794-6656 FU National Institute on Aging; National Institute on Aging, National Institutes of Health FX The authors thank Drs. Richard Hodes and Joyti Sen for critical reading of the manuscript, Andrea Wurster and Qing Yu for help with Th2- and Th17-cell differentiation, Jun Ho Lee for help with the EAE mouse model, Cuong Nguyen and Tonya Wolf of the Flow Cytometry Unit for cell sorting, the staff of the National Institute on Aging animal facility for support and assistance, and Ana Lustig for proofreading the manuscript. This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. J.A and S. G. designed and performed experiments, analyzed the data, and contributed to the writing of the manuscript. J.K., Y.Z., K.S., G.E.H., W.H.W., R.P.W., and K.G.B. contributed to some of the experiments and data analysis. S.L.S and N.W. directed the experiments and wrote the manuscript. N.W. conceived the research, designed the experiments, and funded the research. The authors declare no competing financial interests. NR 51 TC 23 Z9 30 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2011 VL 25 IS 10 BP 3634 EP 3645 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 826LU UT WOS:000295356400033 PM 21685331 ER PT J AU Allen, MD Neumann, S Gershengorn, MC AF Allen, Michael D. Neumann, Susanne Gershengorn, Marvin C. TI Occupancy of both sites on the thyrotropin (TSH) receptor dimer is necessary for phosphoinositide signaling SO FASEB JOURNAL LA English DT Article DE GPCR; inositolphosphates; IP1; G(q/11) coupling ID PHOSPHOLIPASE-C; FLUORESCENT PROTEIN; CYTOSOLIC CA-2+; PHARMACOLOGY; DIMERIZATION; TRANSDUCIN; MUTATIONS; RHODOPSIN; FAMILIES; PEPTIDE AB The thyroid-stimulating hormone (TSH) receptor signals via Gs to produce cAMP and via G(q/11) to produce inositol-1,4,5-trisphosphate, which is degraded to inositol monophosphate (IP1; phosphoinositide signaling). The potency of TSH for cAMP signaling is higher than for phosphoinositide signaling, and it was suggested that there are "spare receptors" for cAMP signaling. In a human embryonic kidney macrophage scavenger receptor-expressing (HEK-EM) 293 model system, there are no spare receptors, but the cells still exhibited 100-fold differences in potencies. Dose responses for TSH-stimulated dissociation of prebound 125I-TSH (negative cooperativity; EC50 = 70 mU/ml), which requires TSH binding to both sites of the TSH receptor (TSHR) homodimer, and TSH-stimulated IP1 production (EC50 = 50 mU/ml) were indistinguishable. Fluorescence resonance energy transfer (FRET) using tagged receptors showed that TSHR formed homodimers and heterodimers with two binding-deficient mutant TSHRs, L252P and C41S. When L252P or C41S was expressed with TSHR, that is, when TSHR/L252P or TSHR/C41S heterodimers could only bind one TSH, TSH-stimulated IP1 production was decreased relative to cAMP production. The slopes of linear regression analyses comparing fold stimulation by TSH of IP1 vs. cAMP production were 0.044 +/- 0.0047, 0.0043 +/- 0.0041, and 0.0059 +/- 0.0014 for cells expressing TSHR alone, TSHR and L252P, or TSHR and C41S, respectively. We suggest that TSHR coupling to phosphoinositide signaling is dependent on binding 2 molecules of TSH to TSHR homodimer, causing a conformational change allowing coupling to G(q/11).Allen, M. D., Neumann, S., Gershengorn, M. C. Occupancy of both sites on the thyrotropin (TSH) receptor dimer is necessary for phosphoinositide signaling. FASEB J. 25, 3687-3694 (2011). www.fasebj.org C1 [Allen, Michael D.; Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, CEB, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDK, CEB, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, U.S. National Institutes of Health [Z01-DK011006] FX The authors thank Stefano Costanzi and Jurgen Wess for helpful comments. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (Z01-DK011006), U.S. National Institutes of Health. NR 27 TC 18 Z9 18 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD OCT PY 2011 VL 25 IS 10 BP 3687 EP 3694 DI 10.1096/fj.11-188961 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 826LU UT WOS:000295356400037 PM 21705666 ER PT J AU Appella, E Johansson, J AF Appella, Ettore Johansson, Jan TI Special Issue: Protein Structure and Proteomics Introduction SO FEBS JOURNAL LA English DT Editorial Material C1 [Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Johansson, Jan] Karolinska Inst, KI Alzheimers Dis Res Ctr, NVS Dept, Stockholm, Sweden. RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD OCT PY 2011 VL 278 IS 20 SI SI BP 3795 EP 3795 DI 10.1111/j.1742-4658.2011.08313.x PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 826EW UT WOS:000295335500001 PM 21883927 ER PT J AU Auttachoat, W Germolec, DR Smith, MJ White, KL Guo, TL AF Auttachoat, Wimolnut Germolec, Dori R. Smith, Matthew J. White, Kimber L., Jr. Guo, Tai L. TI Contact sensitizing potential of annatto extract and its two primary color components, cis-bixin and norbixin, in female BALB/c mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Annatto; Bixin; Norbixin; LLNA; MEST ID LOCAL LYMPH-NODE; ASSAY; ALLERGENS; HYPERSENSITIVITY; IRRITANTS; CHEMICALS; IDENTIFICATION; DISCRIMINATE; URTICARIA; RESPONSES AB The present studies were performed to examine the contact allergenic effects of an annatto extract (ANT) in female BALB/c mice. ANT at 5-10% induced a greater than threefold increase in lymph node cell proliferation when compared to the control in the LLNA. Moreover, a significant increase in the percent ear swelling at 24 h after ANT challenge was observed in the MEST. A significant increase in the percentage of B cells was also observed. To determine which of the two predominant coloring components (norbixin and bixin) in ANT was responsible for the sensitizing effects of ANT, norbixin was subsequently examined, with negative results being observed in both the LLNA and MEST following treatment with norbixin (1-20%). These findings suggested that perhaps bixin was responsible for the positive responses in both the LLNA and MEST following exposure to ANT. Therefore, further studies using a partially purified cis-bixin extract were conducted. Positive responses in both the LLNA and MEST were observed in mice treated with cis-bixin at the concentrations as low as 0.1-0.5%. These results have demonstrated that cis-bixin, but not norbixin, is likely a contact sensitizer and contributes to the contact hypersensitivity effects observed following dermal exposure to ANT in mice. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Auttachoat, Wimolnut; Smith, Matthew J.; White, Kimber L., Jr.; Guo, Tai L.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Germolec, Dori R.] NIEHS, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. EM klwhite@vcu.edu FU NIEHS [ES 55538] FX This work was supported by the NIEHS Contract ES 55538. "This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH or the United States government". NR 46 TC 9 Z9 9 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD OCT PY 2011 VL 49 IS 10 BP 2638 EP 2644 DI 10.1016/j.fct.2011.07.009 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 824ZW UT WOS:000295241700021 PM 21777644 ER PT J AU Hu, GQ Schones, DE Cui, KR Ybarra, R Northrup, D Tang, QS Gattinoni, L Restifo, NP Huang, SM Zhao, KJ AF Hu, Gangqing Schones, Dustin E. Cui, Kairong Ybarra, River Northrup, Daniel Tang, Qingsong Gattinoni, Luca Restifo, Nicholas P. Huang, Suming Zhao, Keji TI Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1 SO GENOME RESEARCH LA English DT Article ID CHROMATIN REMODELING COMPLEXES; GENOME-WIDE ANALYSIS; BAF COMPLEX; GENE-EXPRESSION; DNA; PROMOTER; PROTEIN; CELLS; OCCUPANCY; INDUCTION AB Enhancers of transcription activate transcription via binding of sequence-specific transcription factors to their target sites in chromatin. In this report, we identify GATA1-bound distal sites genome-wide and find a global reorganization of the nucleosomes at these potential enhancers during differentiation of hematopoietic stem cells (HSCs) to erythrocytes. We show that the catalytic subunit BRG1 of BAF complexes localizes to these distal sites during differentiation and generates a longer nucleosome linker region surrounding the GATA1 sites by shifting the flanking nucleosomes away. Intriguingly, we find that the nucleosome shifting specifically facilitates binding of TAL1 but not GATA1 and is linked to subsequent transcriptional regulation of target genes. C1 [Hu, Gangqing; Schones, Dustin E.; Cui, Kairong; Northrup, Daniel; Tang, Qingsong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Ybarra, River; Huang, Suming] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32611 USA. [Gattinoni, Luca; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zhao, KJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov RI HU, GANGQING/K-5849-2012; Restifo, Nicholas/A-5713-2008; cheng, yong/I-4270-2012; Gattinoni, Luca/A-2281-2008 OI Restifo, Nicholas P./0000-0003-4229-4580; Gattinoni, Luca/0000-0003-2239-3282 FU Division of Intramural Research Program of the National Heart, Lung and Blood Institute, NIH [R01HL090589, R01HL091929, K22HL101950] FX This work was supported by the Division of Intramural Research Program of the National Heart, Lung and Blood Institute, NIH (K.Z.), R01HL090589 and R01HL091929 (S.H.), and K22HL101950 (D.E.S.). NR 53 TC 80 Z9 80 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2011 VL 21 IS 10 BP 1650 EP 1658 DI 10.1101/gr.121145.111 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 827DQ UT WOS:000295407800009 PM 21795385 ER PT J AU Cox, S Kuo, C Jamieson, DJ Kourtis, AP McPheeters, ML Meikle, SF Posner, SF AF Cox, Shanna Kuo, Cassie Jamieson, Denise J. Kourtis, Athena P. McPheeters, Melissa L. Meikle, Susan F. Posner, Samuel F. TI Poisoning hospitalisations among reproductive-aged women in the USA, 1998-2006 SO INJURY PREVENTION LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; ATTEMPTED-SUICIDE; NONMEDICAL USE; UNITED-STATES; INJURY; ASSOCIATION; DRUGS AB Objective To describe poisoning hospitalisations among reproductive-aged women from 1998 to 2006. Methods 1998-2006 data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilisation Project were used to identify hospitalisations for poisonings among US women aged 15-44 years. Differences in hospitalisation characteristics were compared by intent using chi(2) statistics. Trends in poisoning hospitalisation rates were calculated overall and by subgroup. Results There were approximately 636 000 poisoning hospitalisations in women aged 15-44 years during 1998-2006. Hospitalisations for intentionally self-inflicted poisonings had a higher proportion of women aged 15-24 years and privately insured women than did unintentional poisonings (p<0.001). Poisoning hospitalisations in rural areas and those that resulted in death were more likely to be of undetermined intent than those for which intent was specified (p<0.001). Co-diagnoses of substance abuse (34.5%) or mental disorders (66.5%) were high. The rate of poisoning hospitalisations overall and unintentional poisoning hospitalisations increased 6% and 22%, respectively, during this period (p<0.001). The most frequently diagnosed poisoning agent was acetaminophen. Poisonings attributable to acetaminophen, opioids, central nervous system stimulants and benzodiazepines increased, while poisonings attributable to antidepressants decreased (p<0.05). Conclusions The increase in unintentional poisoning hospitalisations among women aged 15-44 years and the changing profile of poisoning agents should inform the healthcare community's poisoning prevention strategies. Poisoning prevention strategies should include a component to address substance abuse and mental health disorders among reproductive-age women. C1 [Cox, Shanna; Kuo, Cassie; Jamieson, Denise J.; Kourtis, Athena P.; Posner, Samuel F.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [McPheeters, Melissa L.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA. [Meikle, Susan F.] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Cox, S (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway MS K-20, Atlanta, GA 30341 USA. EM shanna.cox@cdc.hhs.gov OI Posner, Samuel/0000-0003-1574-585X NR 36 TC 8 Z9 8 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD OCT PY 2011 VL 17 IS 5 BP 332 EP 337 DI 10.1136/ip.2010.029793 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 823MB UT WOS:000295125300010 PM 21296799 ER PT J AU Twardoski, B Feldmann, H Bloom, ME Ward, J AF Twardoski, Barri Feldmann, Heinz Bloom, Marshall E. Ward, Joe TI Modern dosimetric tools for Co-60 irradiation at high containment laboratories SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article DE Microbiology; radiation chemistry; radiation physics; dose-response curve; dosimetry; radiation ID FLUORESCENT FILM DOSIMETER AB Purpose: To evaluate an innovative photo-fluorescent film as a routine dosimetric tool during 1.0 SD on each test) was analyzed with logistic regression. Results: Older adults with high pentosidine level had worse baseline DSST score (p = 0.05) but not different 3MS score (p = 0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall < 0.001; DSST 5.9, 7.4, and 4.5 point decline, p = 0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio = 1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio = 1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. Conclusion: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes. Neurology (R) 2011;77:1351-1356 C1 [Yaffe, K.; Vitartas, C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, K.; Schwartz, A. V.; Vittinghoff, E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Lindquist, K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Yaffe, K.; Vitartas, C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Satterfield, S.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Launer, L.; Harris, T.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA. [Rosano, C.; Cauley, J. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Cauley, Jane A/0000-0003-0752-4408 FU NIH, National Institute of Aging; American Health Assistance Foundation [A201-0029]; Amgen; Merck Serono; GlaxoSmithKline; Anonymous Foundation; Alzheimer Association; NIH (NIA, NIDDK, NIMH); Department of Defense; NIH (NIDDK, NIA); Medtronic, Inc.; Zoll Medical Corporation; NIH (NIA, NIDDK, NHLBI, NIAID, NIMH); NIH/NIA; Novartis; NIH; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX NIA contract nos. N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Aging, and by a grant from the American Health Assistance Foundation, grant no. A201-0029.; Dr. Yaffe has served on data safety monitoring boards for Pfizer Inc, Medivation, Inc. and the NIH (NIMH and NIA trials); and has received research support from the NIH (NIA, NIDDK, NIMH), the Department of Defense, American Health Assistance Foundation, Anonymous Foundation, and the Alzheimer Association. K. Lindquist reports no disclosures. Dr. Schwartz serves on a scientific advisory board for GlaxoSmithKline; has received speaker honoraria from Amgen and Merck Serono; has received funding for travel from Amgen; and receives research support from Merck Serono, GlaxoSmithKline, the NIH (NIDDK, NIA). C. Vitartas reports no disclosures. Dr. Vittinghoff receives publishing royalties for Regression Methods in Biostatistics: Linear, Logistic, Survival and Repeated Measures Models (Springer Verlag, 2005); and receives research support from Medtronic, Inc., Zoll Medical Corporation, Amgen, and the NIH (NIA, NIDDK, NHLBI, NIAID, NIMH). Dr. Satterfield receives research support from the NIH/NIA. Dr. Simonsick serves as an Associate Editor for the Journal of Gerontology Medical Sciences and on the editorial board of the Journal of Aging and Health. Dr. Launer receives research support from the NIH/NIA Intramural Research Program. Dr. Rosano reports no disclosures. Dr. Cauley receives research support from Novartis. Dr. Harris receives research support from the NIH. NR 31 TC 48 Z9 48 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 2011 VL 77 IS 14 BP 1351 EP 1356 DI 10.1212/WNL.0b013e3182315a56 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 828XV UT WOS:000295539000010 PM 21900628 ER PT J AU Zheng, CY Seabold, GK Horak, M Petralia, RS AF Zheng, Chan-Ying Seabold, Gail K. Horak, Martin Petralia, Ronald S. TI MAGUKs, Synaptic Development, and Synaptic Plasticity SO NEUROSCIENTIST LA English DT Review DE SAP97; MAGI; CASK; PSD-95; SAP102 ID ADHESION-LIKE MOLECULES; DENDRITIC SPINE MORPHOGENESIS; RECEPTOR SURFACE EXPRESSION; DENSITY PROTEIN PSD-95; D-ASPARTATE RECEPTORS; NMDA RECEPTOR; POSTSYNAPTIC DENSITY; AMPA RECEPTORS; EXCITATORY SYNAPSES; IN-VIVO AB MAGUKs are proteins that act as key scaffolds in surface complexes containing receptors, adhesion proteins, and various signaling molecules. These complexes evolved prior to the appearance of multicellular animals and play key roles in cell-cell intercommunication. A major example of this is the neuronal synapse, which contains several presynaptic and postsynaptic MAGUKs including PSD-95, SAP102, SAP97, PSD-93, CASK, and MAGIs. Here, they play roles in both synaptic development and in later synaptic plasticity events. During development, MAGUKs help to organize the postsynaptic density via associations with other scaffolding proteins, such as Shank, and the actin cytoskeleton. They affect the clustering of glutamate receptors and other receptors, and these associations change with development. MAGUKs are involved in long-term potentiation and depression (e.g., via their phosphorylation by kinases and phosphorylation of other proteins associated with MAGUKs). Importantly, synapse development and function are dependent on the kind of MAGUK present. For example, SAP102 shows high mobility and is present in early synaptic development. Later, much of SAP102 is replaced by PSD-95, a more stable synaptic MAGUK; this is associated with changes in glutamate receptor types that are characteristic of synaptic maturation. C1 [Zheng, Chan-Ying; Seabold, Gail K.; Horak, Martin; Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Petralia, RS (reprint author), NIDCD, NIH, 50-4142,50 S Dr,MSC 8027, Bethesda, MD 20892 USA. EM petralia@nidcd.nih.gov RI Horak, Martin/F-9819-2010 FU National Institute on Deafness and Other Communication Disorders (NIDCD) at the National Institutes of Health (NIH) FX The authors thank Drs. Katherine W. Roche and Elizabeth Webber for critical review of the article. This work was supported by the Intramural Program of the National Institute on Deafness and Other Communication Disorders (NIDCD) at the National Institutes of Health (NIH). NR 119 TC 72 Z9 77 U1 8 U2 24 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2011 VL 17 IS 5 BP 493 EP 512 DI 10.1177/1073858410386384 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 827HR UT WOS:000295420100009 PM 21498811 ER PT J AU Wadden, TA Neiberg, RH Wing, RR Clark, JM Delahanty, LM Hill, JO Krakoff, J Otto, A Ryan, DH Vitolins, MZ AF Wadden, Thomas A. Neiberg, Rebecca H. Wing, Rena R. Clark, Jeanne M. Delahanty, Linda M. Hill, James O. Krakoff, Jonathan Otto, Amy Ryan, Donna H. Vitolins, Mara Z. CA Look AHEAD Res Grp TI Four-Year Weight Losses in the Look AHEAD Study: Factors Associated With Long-Term Success SO OBESITY LA English DT Article ID LIFE-STYLE INTERVENTION; DIABETES-PREVENTION-PROGRAM; LOSS MAINTENANCE; CARDIOVASCULAR-DISEASE; BEHAVIORAL TREATMENT; PHYSICAL-ACTIVITY; OBESE-PATIENTS; ACTIVITY GOALS; RISK-FACTORS; MANAGEMENT AB This report provides a further analysis of the year 4 weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with long-term success. A total of 5,145 overweight/obese men and women with type 2 diabetes were randomly assigned to an intensive lifestyle intervention (ILI) or a usual care group, referred to as Diabetes Support and Education (DSE). ILI participants were provided approximately weekly group or individual treatment in year 1; continued but less frequent contact was provided in years 2-4. DSE participants received three group educational sessions in all years. As reported previously, at year 4, ILI participants lost an average of 4.7% of initial weight, compared with 1.1% for DSE (P < 0.0001). More ILI than DSE participants lost >= 5% (46% vs. 25%, P < 0.0001) and >= 10% (23% vs. 10%, P < 0.0001) of initial weight. Within the ILI, achievement of both the 5% and 10% categorical weight losses at year 4 was strongly related to meeting these goals at year 1. A total of 887 participants in ILI lost >= 10% at year 1, of whom 374 (42.2%) achieved this loss at year 4. Participants who maintained the loss, compared with those who did not, attended more treatment sessions and reported more favorable physical activity and food intake at year 4. These results provide critical evidence that a comprehensive lifestyle intervention can induce clinically significant weight loss (i.e., >= 5%) in overweight/obese participants with type 2 diabetes and maintain this loss in more than 45% of patients at 4 years. C1 [Wadden, Thomas A.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Neiberg, Rebecca H.] Wake Forest Univ, Dept Biostatist Sci, Winston Salem, NC 27109 USA. [Wing, Rena R.] Miriam Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI USA. [Clark, Jeanne M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Delahanty, Linda M.] Harvard Univ, Sch Med, Boston, MA USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hill, James O.] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. [Krakoff, Jonathan] NIDDK, NIH, Phoenix, AZ USA. [Otto, Amy] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA. [Ryan, Donna H.] Pennington Biomed Res Ctr, Dept Clin Res, Baton Rouge, LA USA. [Vitolins, Mara Z.] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. RP Wadden, TA (reprint author), Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. EM Wadden@mail.med.upenn.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; Centers for Disease Control and Prevention; Department of Health and Human Services; National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Department of Veterans Affairs FX Federal sponsors; National Institute of Diabetes and Digestive and Kidney Diseases. Mary Evans, PhD; Barbara Harrison, MS; Van S. Hubbard, MD, PhD; Susan Z. Yanovski, MD; Robert Kuczmarski, PhD; National Heart, Lung, and Blood Institute. Lawton S. Cooper, MD, MPH; Peter Kaufman, PhD, FABMR; Centers for Disease Control and Prevention. Edward W. Gregg, PhD; David F. Williamson, PhD; Ping Zhang, PhD; This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; the Centers for Disease Control and Prevention; and the Department of Veterans Affairs. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the IHS or other funding sources. NR 53 TC 149 Z9 154 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2011 VL 19 IS 10 BP 1987 EP 1998 DI 10.1038/oby.2011.230 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 825IX UT WOS:000295266700010 PM 21779086 ER PT J AU Cohen, SS Gammon, MD North, KE Millikan, RC Lange, EM Williams, SM Zheng, W Cai, QY Long, JR Smith, JR Signorello, LB Blot, WJ Matthews, CE AF Cohen, Sarah S. Gammon, Marilie D. North, Kari E. Millikan, Robert C. Lange, Ethan M. Williams, Scott M. Zheng, Wei Cai, Qiuyin Long, Jirong Smith, Jeffrey R. Signorello, Lisa B. Blot, William J. Matthews, Charles E. TI ADIPOQ, ADIPOR1, and ADIPOR2 Polymorphisms in Relation to Serum Adiponectin Levels and BMI in Black and White Women SO OBESITY LA English DT Article ID GENOME-WIDE ASSOCIATION; APM1 GENE; CARDIOVASCULAR-DISEASE; QUANTITATIVE TRAITS; INSULIN-RESISTANCE; HEALTHY CAUCASIANS; METABOLIC SYNDROME; HERITAGE FAMILY; IRAS FAMILY; OBESITY AB Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single-nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study (SCCS) from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and BMI using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, P = 0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI. C1 [Cohen, Sarah S.; Gammon, Marilie D.; North, Kari E.; Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Cohen, Sarah S.; Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Lange, Ethan M.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Williams, Scott M.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Sch Med, Nashville, TN 37232 USA. [Zheng, Wei; Cai, Qiuyin; Long, Jirong; Signorello, Lisa B.; Blot, William J.] Vanderbilt Univ, Dept Med, Div Epidemiol,Vanderbilt Ingram Cancer Ctr, Vanderbilt Epidemiol Ctr,Sch Med, Nashville, TN USA. [Smith, Jeffrey R.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Rockville, MD USA. RP Cohen, SS (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. EM sarah@ieixmail.com RI Williams, Scott/B-9491-2012; Smith, Jeff/C-3484-2012; matthews, Charles/E-8073-2015 OI matthews, Charles/0000-0001-8037-3103 FU Susan G. Komen for the Cure [OP05-0927-DR1]; National Cancer Institute (NCI) [R01 CA092447, T32 CA09330-26, 5-R25-CA057726]; National Institute of Environmental Health Sciences [P30ES10126]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX This project was funded in part by grant OP05-0927-DR1 from Susan G. Komen for the Cure. The Southern Community Cohort Study is funded by grant R01 CA092447 from the National Cancer Institute (NCI). S. S. C. also received support from NCI Training Grants T32 CA09330-26 and 5-R25-CA057726. M. D. G. is supported in part from P30ES10126 from the National Institute of Environmental Health Sciences. Sample preparation was conducted at the Survey and Biospecimen Shared Resource that is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). We thank Regina Courtney and the late Qing Wang for serum and DNA sample preparation, and Kevin Bradley and Joan Breyer for genotyping assistance, including contributing to the design of gene targets. We also thank Heather Munro at the International Epidemiology Institute for her statistical review. NR 42 TC 14 Z9 16 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2011 VL 19 IS 10 BP 2053 EP 2062 DI 10.1038/oby.2010.346 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 825IX UT WOS:000295266700019 PM 21273992 ER PT J AU Malhotra, A Kobes, S Knowler, WC Baier, LJ Bogardus, C Hanson, RL AF Malhotra, Alka Kobes, Sayuko Knowler, William C. Baier, Leslie J. Bogardus, Clifton Hanson, Robert L. TI A Genome-Wide Association Study of BMI in American Indians SO OBESITY LA English DT Article ID BODY-MASS INDEX; PIMA-INDIANS; OBESITY; VARIANTS; LOCI; POPULATIONS; EXTREME; FAMILY; ONSET; RISK AB Numerous studies have been done to understand genetic contributors to BMI, but only a limited number of studies have been done in nonwhite groups such as American Indians. A genome-wide association study (GWAS) for BMI was therefore performed in Pima Indians. BMI measurements from a longitudinal study of 1,120 Pima Indians and 454,194 single-nucleotide polymorphisms (SNPs) from the 1 million Affymetrix SNP panel were used (35% of SNPs were excluded due to minor allele frequency < 0.05). Data included BMI measured at multiple examinations collected from 1965 to 2004, as well as the maximum BMI at one of these visits. General and within-family tests were performed using a maximum-likelihood based mixed model procedure. No SNP reached a genome-wide significance level (estimated at P < 4.94 x 10(-7)). For repeated measures analyses, the strongest associations for general and within-family tests mapped to two different regions on chromosome 6 (rs9342220 (P = 1.39 x 10(-6)) and rs7758764 (P = 2.51 x 10(-6)), respectively). For maximum BMI, the strongest association for the general tests mapped to chromosome 4 (rs17612333; P = 1.98 x 10(-6)) and to chromosome 3 (rs11127958; P = 1.53 x 10(-6)) for the within-family tests. Further analysis is important because only a few of these regions have been previously implicated in a GWAS and genetic susceptibility may differ by ethnicity. C1 [Malhotra, Alka; Kobes, Sayuko; Knowler, William C.; Baier, Leslie J.; Bogardus, Clifton; Hanson, Robert L.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. RP Malhotra, A (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. EM alka@niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Digestive and Kidney Diseases FX The authors thank the study participants and staff of the Diabetes Epidemiology and Clinical Research Section and of the Diabetes Molecular Genetics Section for performing the studies generating these data. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 21 TC 20 Z9 21 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2011 VL 19 IS 10 BP 2102 EP 2106 DI 10.1038/oby.2011.178 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 825IX UT WOS:000295266700027 PM 21701565 ER PT J AU Sekine, Y Osei-Hwedieh, D Matsuda, K Raghavachari, N Liu, DL Furuya, Y Koike, H Suzuki, K Remaley, AT AF Sekine, Yoshitaka Osei-Hwedieh, David Matsuda, Kant Raghavachari, Nalini Liu, Delong Furuya, Yosuke Koike, Hidekazu Suzuki, Kazuhiro Remaley, Alan T. TI High Fat Diet Reduces the Expression of Glutathione Peroxidase 3 in Mouse Prostate SO PROSTATE LA English DT Article DE high fat diet; prostate; GPx3; cholesterol; mouse ID CANCER CELL-LINES; OXIDATIVE STRESS; NUDE-MICE; GROWTH; GLUTATHIONE-PEROXIDASE-3; CARCINOGENESIS; INFLAMMATION; CHOLESTEROL; CARCINOMA; LNCAP AB BACKGROUND. High fat diets are known to be a risk factor for prostate cancer. In this study, we investigated the effect of high fat diet on mouse prostate gene expression. METHODS. C57BL/6J mice were fed either a control or high fat diet for 12 weeks. Microarray analyses were performed on mouse ventral prostate (VP) and dorsolateral prostate (DLP), followed by canonical pathway analysis and regulatory network identification. mRNA changes were confirmed by real time PCR. RESULTS. Approximately 2,125, and 1,194 genes responded significantly to the high fat diet in VP, DLP, respectively. Pathways and networks related to oxidative stress, glutathione metabolism, NRF-mediated oxidative stress response and NF-kappaB were all differentially regulated by high fat diet. Glutathione peroxidase 3 (GPx3) mRNA levels were decreased by approximately twofold by high fat diet in all three prostate lobes. In human non-transformed prostate cells (PrSC, PrEC, and BPH-1), cholesterol loading decreased GPx3 expression, and increased H(2)O(2) levels of culture medium. Troglitazone increased GPx3 expression in three normal prostate cells, and decreased H(2)O(2) levels. In addition, troglitazone attenuated cholesterol-induced H(2)O(2) increase. Tissue from prostate cancer biopsies had decreased GPx3 mRNA and its level was inversely related to the Gleason score. CONCLUSIONS. High fat diet alters pathways related to many genes concerned with oxidative stress. GPx3, a gene identified by this analysis, was found to be down-regulated by high fat diet and appears be decreased in human prostate cancers, suggesting that GPx3 may have a possible role in modulating carcinogenesis. Prostate 71: 1499-1509, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Sekine, Yoshitaka; Osei-Hwedieh, David; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Matsuda, Kant] NCI, Tissue Array Res Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Raghavachari, Nalini] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA. [Liu, Delong] NHLBI, Math & Stat Comp Lab, CIT, NIH, Bethesda, MD 20892 USA. [Liu, Delong] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA. [Sekine, Yoshitaka; Furuya, Yosuke; Koike, Hidekazu; Suzuki, Kazuhiro] Gunma Univ, Grad Sch Med, Dept Urol, Gunma, Japan. RP Sekine, Y (reprint author), NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bldg 10,Room 8N224,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ysekine@showa.gunma-u.ac.jp FU Intramural NHBLI National Institutes of Health FX Grant sponsor: Intramural NHBLI National Institutes of Health. NR 40 TC 8 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD OCT 1 PY 2011 VL 71 IS 14 BP 1499 EP 1509 DI 10.1002/pros.21365 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 827CR UT WOS:000295404400003 PM 21374652 ER PT J AU Fesinmeyer, MD Kwon, EM Fu, R Ostrander, EA Stanford, JL AF Fesinmeyer, Megan D. Kwon, Erika M. Fu, Rong Ostrander, Elaine A. Stanford, Janet L. TI Genetic Variation in RNASEL and Risk for Prostate Cancer in a Population-Based Case-Control Study SO PROSTATE LA English DT Article DE prostate cancer; RNASEL; Gleason grade; prostatitis ID RIBONUCLEASE-L; ASSOCIATION; VARIANTS; POLYMORPHISMS; INFLAMMATION; MUTATIONS; FAMILIES; GENOME; HPC1 AB BACKGROUND. Linkage studies have implicated chromosome 1q24 as a putative locus for hereditary prostate cancer. The RNASEL gene maps to 1q24 and has been associated with prostate cancer risk in multiple family-based linkage studies. The RNASEL gene product combats viral infection by degrading viral RNA and inducing apoptosis of infected cells. Few studies have evaluated the role of RNASEL variants in unselected or sporadic prostate cancer, or have considered the potential interaction between RNASEL variants and patient characteristics associated with past infection. METHODS. Ten SNPs in the RNASEL gene were genotyped in 1,308 prostate cancer cases and 1,267 age-matched controls from prior population-based, case-control studies. The association between each SNP and haplotype with prostate cancer risk was calculated using logistic regression. Associations stratified by Gleason score were evaluated using polytomous regression. The likelihood ratio test was used to investigate effect modification. RESULTS. Two RNASEL SNPs were associated with overall increases in prostate cancer risk (OR = 1.13 for each variant allele of rs12723593; OR = 1.88 for any variant allele of rs56250729). Risk estimates did not vary substantially by Gleason score, but there was effect modification for the variant allele of rs635261 by history of prostatitis (P = 0.02). CONCLUSIONS. This study identified three RNASEL variants that are associated with risk for prostate cancer. Further research is required to confirm these results and to better understand the potential role RNASEL variants may play in the etiology of sporadic prostate cancer. Prostate 71: 1538-1547, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Fesinmeyer, Megan D.; Fu, Rong; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Fu, Rong] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU NIH [RO1 CA056678, RO1 CA092579, P50 CA097186] FX Grant sponsor: NIH; Grant numbers: RO1 CA056678; RO1 CA092579; P50 CA097186; Additional support provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute. NR 34 TC 3 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD OCT 1 PY 2011 VL 71 IS 14 BP 1538 EP 1547 DI 10.1002/pros.21370 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 827CR UT WOS:000295404400007 PM 21360564 ER PT J AU Hari, D Xin, HW Jaiswal, K Wiegand, G Kim, BK Ambe, C Burka, D Koizumi, T Ray, S Garfield, S Thorgeirsson, S Avital, I AF Hari, Danielle Xin, Hong-Wu Jaiswal, Kshama Wiegand, Gordon Kim, Bo-Kyu Ambe, Che Burka, Douglas Koizumi, Tomotake Ray, Satyajit Garfield, Susan Thorgeirsson, Snorri Avital, Itzhak TI Isolation of Live Label-Retaining Cells and Cells Undergoing Asymmetric Cell Division via Nonrandom Chromosomal Cosegregation from Human Cancers SO STEM CELLS AND DEVELOPMENT LA English DT Article ID IMMORTAL STRAND HYPOTHESIS; HEMATOPOIETIC STEM-CELLS; TEMPLATE DNA STRANDS; SELECTIVE SEGREGATION; IN-VITRO; IDENTIFICATION; GENOME; VIVO; SKIN AB The ability to retain DNA labels over time is a property proposed to be associated with adult stem cells. Recently, label retaining cells (LRC) were indentified in cancer. LRC were suggested to be the result of either slow-cycling or asymmetric-cell-division with nonrandom-chromosomal-cosegregation (ACD-NRCC). ACD-NRCC is proposed to segregate the older template DNA strands into daughter stem cells and newly synthesized DNA into daughter cells destined for differentiation. The existence of cells undergoing ACD-NRCC and the stem-like nature of LRC remain controversial. Currently, to detect LRC and ACD-NRCC, cells need to undergo fixation. Therefore, testing the stem-cell nature and other functional traits of LRC and cells undergoing ACD-NRCC has been limited. Here, we show a method for labeling DNA with single and dual-color nucleotides in live human liver cancer cells avoiding the need for fixation. We describe a novel methodology for both the isolation of live LRC and cells undergoing ACD-NRCC via fluorescence-activated cell sorting with confocal microscopy validation. This has the potential to be a powerful adjunct to stem-cell and cancer research. C1 [Hari, Danielle; Xin, Hong-Wu; Jaiswal, Kshama; Wiegand, Gordon; Kim, Bo-Kyu; Ambe, Che; Burka, Douglas; Koizumi, Tomotake; Ray, Satyajit; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hari, Danielle] Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Garfield, Susan; Thorgeirsson, Snorri] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Avital, I (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM avitali@mail.nih.gov FU NCI [1ZIABC011005-02] FX We thank L. Liam and P. Mannan for the confocal microscopy and surface rendering work. A. Mixon and S. Farid for help with the FACS analysis experiments. This work was supported by an NCI intramural grant (1ZIABC011005-02). NR 32 TC 19 Z9 19 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD OCT PY 2011 VL 20 IS 10 BP 1649 EP 1658 DI 10.1089/scd.2010.0455 PG 10 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 826AX UT WOS:000295324900001 PM 21294632 ER PT J AU Casson, PR Krawetz, SA Diamond, MP Zhang, HP Legro, RS Schlaff, WD Coutifaris, C Brzyski, RG Christman, GM Santoro, N Eisenberg, E AF Casson, Peter R. Krawetz, Stephen A. Diamond, Michael P. Zhang, Heping Legro, Richard S. Schlaff, William D. Coutifaris, Christos Brzyski, Robert G. Christman, Gregory M. Santoro, Nanette Eisenberg, Esther CA Reprod Med Network TI Proactively Establishing a Biologic Specimens Repository for Large Clinical Trials: An Idea Whose Time has Come SO SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE LA English DT Article DE biorepository; repository; Reproductive Medicine Network AB Large randomized clinical trials are becoming more costly, and resources to support them increasingly scarce. Biologic materials, such as blood, DNA, body fluids, or tissue samples collected and stored as a component of these studies represent an invaluable resource, to answer immediate secondary hypotheses, but also as archived material, linked to the study data, for the use of investigators long into the future. The regulatory climate surrounding the storage and future unconstrained utilization of biologic materials is evolving quickly. It is no longer acceptable simply to store samples and use them in an unbridled and unregulated fashion. Thus, to fully utilize the tremendous potential of biologic samples generated from large clinical trials and their related databases, investigators should consider proactively creating a biologic specimen repository, or biorepository. A repository likely assures appropriate subject consent, sample provenance, secure storage, and codified procedures for sample and data retrieval and sharing that protect the subject's confidentiality, the investigator's need for accurate data, and the limited resource. Importantly, the biorepository specimens/samples are typically collected in addition to local and core specimens obtained for the parent study that provide baseline assessments for safety and efficacy outcomes. C1 [Casson, Peter R.] Univ Vermont, Dept Med & Obstet & Gynecol, Burlington, VT 05401 USA. [Krawetz, Stephen A.; Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Zhang, Heping] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. [Schlaff, William D.; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA. [Coutifaris, Christos] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Christman, Gregory M.] Univ Michigan, Dept Obstet & Gynecol, Reprod Sci Program, Ann Arbor, MI 48109 USA. [Eisenberg, Esther] NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Casson, PR (reprint author), Univ Vermont, Div Reprod Endocrinol & Infertil, Dept Obstet Gynecol & Reprod Sci, MCHV Fletcher Allen Hlth Care, Smith 401,111 Colchester Ave, Burlington, VT 05401 USA. EM Peter.casson@vtmednet.org OI Diamond, Michael/0000-0001-6353-4489 FU NICHD NIH HHS [U10 HD055936, U10 HD055942, U10 HD038992] NR 8 TC 5 Z9 5 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1939-6368 J9 SYST BIOL REPROD MED JI Syst. Biol. Reprod. Med. PD OCT PY 2011 VL 57 IS 5 BP 217 EP 221 DI 10.3109/19396368.2011.604818 PG 5 WC Andrology; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA 825KT UT WOS:000295273900002 PM 21951166 ER PT J AU Krawetz, SA Casson, PR Diamond, MP Zhang, HP Legro, RS Schlaff, WD Coutifaris, C Brzyski, RG Christman, GM Santoro, N Eisenberg, E AF Krawetz, Stephen A. Casson, Peter R. Diamond, Michael P. Zhang, Heping Legro, Richard S. Schlaff, William D. Coutifaris, Christos Brzyski, Robert G. Christman, Gregory M. Santoro, Nanette Eisenberg, Esther CA Reprod Med Network TI Establishing a Biologic Specimens Repository for Reproductive Clinical Trials: Technical Aspects SO SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE LA English DT Article DE biorepository; protocol; Reproductive Medicine Network; sample collection ID HUMAN-SPERMATOZOA; BUFFER SYSTEMS; BLOOD-CLOTS; BIOMARKERS; COLLECTION; GENOME; FROZEN; RNA; DNA AB The individual research group or independent investigator often requires access to samples from a unique well characterized subject population. Cohorts of such samples from a well-defined comparative population are rare and limited access can impede progress. This bottleneck can be removed by accessing the samples provided by biorepositories such as the NIH/NICHD Cooperative Reproductive Medicine Network (RMN) Biorepository (detailed in the preceeding manuscript in this issue. In those cases where the individual research group or independent investigator already has access to a unique population, comparisons between well-defined groups are often sought to contextualize the data. In both cases seamless integration of data resources associated with the samples is required to ensure optimal comparisons. At the most basic level this requires standardization of sample collection and storage, as well as a de-identified data base containing demographic, clinical, and laboratory values. To facilitate such interoperability, the reagents and protocols that have been adopted by the RMN Biorepository for the collection and storage of serum, blood, saliva and sperm are described. C1 [Krawetz, Stephen A.; Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Casson, Peter R.] Univ Vermont, Dept Med & Obstet & Gynecol, Burlington, VT USA. [Zhang, Heping] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. [Schlaff, William D.; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA. [Coutifaris, Christos] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Christman, Gregory M.] Univ Michigan, Dept Obstet & Gynecol, Reprod Sci Program, Ann Arbor, MI 48109 USA. [Eisenberg, Esther] NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Krawetz, SA (reprint author), Ctr Mol Med & Genet, Dept Obstet & Gynecol, CS Mott Ctr Human Grwoth & Dev, 275 E Hancock, Detroit, MI 48201 USA. EM steve@compbio.med.wayne.edu OI Diamond, Michael/0000-0001-6353-4489 FU NIH/NICHD [U10HD055925, U10 HD038992, U10 HD038998, U10 HD027049, U10 HD039005, U10 HD055936, U10 HD055942, H10 HD055944] FX This work was supported in part by NIH/NICHD grants U10HD055925 (HZ), U10 HD038992 (RL), U10 HD038998 (WS), U10 HD027049 (CC), U10 HD039005 (MD), U10 HD055936 (GC), U10 HD055942 (RB), and H10 HD055944 (PC). The authors would like to thank the other members of the RMN for their invaluable assistance in developing the RMN biorepository. NR 33 TC 5 Z9 5 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1939-6368 J9 SYST BIOL REPROD MED JI Syst. Biol. Reprod. Med. PD OCT PY 2011 VL 57 IS 5 BP 222 EP 227 DI 10.3109/19396368.2011.604819 PG 6 WC Andrology; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA 825KT UT WOS:000295273900003 PM 21899384 ER PT J AU Goldstein, AM AF Goldstein, Alisa M. TI Germline BAP1 mutations and tumor susceptibility SO NATURE GENETICS LA English DT Editorial Material ID SOMATIC MUTATIONS; CANCER; LOSSES; BREAST C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Goldstein, AM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM goldstea@mail.nih.gov FU Intramural NIH HHS [Z01 CP004410-31] NR 15 TC 21 Z9 21 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2011 VL 43 IS 10 BP 925 EP 926 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200003 PM 21956388 ER PT J AU Hyde, RK Liu, PP AF Hyde, R. Katherine Liu, P. Paul TI GATA2 mutations lead to MDS and AML SO NATURE GENETICS LA English DT Editorial Material ID SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; MYELOID-LEUKEMIA; MYELODYSPLASIA C1 [Hyde, R. Katherine; Liu, P. Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA. RP Hyde, RK (reprint author), NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA. EM pliu@mail.nih.gov RI Liu, Paul/A-7976-2012; OI Liu, Paul/0000-0002-6779-025X; Hyde, R. Katherine/0000-0003-2808-1749 NR 14 TC 14 Z9 14 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2011 VL 43 IS 10 BP 926 EP 927 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200004 PM 21956389 ER PT J AU Zenatti, PP Ribeiro, D Li, WQ Zuurbier, L Silva, MC Paganin, M Tritapoe, J Hixon, JA Silveira, AB Cardoso, BA Sarmento, LM Correia, N Toribio, ML Kobarg, J Horstmann, M Pieters, R Brandalise, SR Ferrando, AA Meijerink, JP Durum, SK Yunes, JA Barata, JT AF Zenatti, Priscila P. Ribeiro, Daniel Li, Wenqing Zuurbier, Linda Silva, Milene C. Paganin, Maddalena Tritapoe, Julia Hixon, Julie A. Silveira, Andre B. Cardoso, Bruno A. Sarmento, Leonor M. Correia, Nadia Toribio, Maria L. Kobarg, Joerg Horstmann, Martin Pieters, Rob Brandalise, Silvia R. Ferrando, Adolfo A. Meijerink, Jules P. Durum, Scott K. Yunes, J. Andres Barata, Joao T. TI Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia SO NATURE GENETICS LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; INTERLEUKIN-7 RECEPTOR; MULTIPLE-SCLEROSIS; GENE-EXPRESSION; PRECURSOR-B; ACTIVATION; NOTCH1; PTEN; IL-7; MICE AB Interleukin 7 (IL-7) and its receptor, formed by IL-7R alpha (encoded by IL7R) and gamma c, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL). We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Ra subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, gamma c or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL. C1 [Ribeiro, Daniel; Silva, Milene C.; Cardoso, Bruno A.; Sarmento, Leonor M.; Correia, Nadia; Barata, Joao T.] Univ Lisbon, Fac Med, Inst Med Mol, Canc Biol Unit, P-1699 Lisbon, Portugal. [Zenatti, Priscila P.; Silveira, Andre B.; Brandalise, Silvia R.; Yunes, J. Andres] Ctr Infantil Boldrini, Lab Biol Mol, Campinas, SP, Brazil. [Li, Wenqing; Tritapoe, Julia; Hixon, Julie A.; Durum, Scott K.] NCI, Immunol Cytokine Grp, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Zuurbier, Linda; Meijerink, Jules P.] Erasmus Med Ctr MC Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. [Paganin, Maddalena; Ferrando, Adolfo A.] Columbia Univ Med Ctr, Inst Canc Genet, New York, NY USA. [Toribio, Maria L.] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, Madrid, Spain. [Kobarg, Joerg] CNPEM, LNBio, Campinas, SP, Brazil. [Horstmann, Martin] German Cooperat Study Grp Childhood Acute Lymphob, Hamburg, Germany. [Horstmann, Martin] Univ Med Ctr Hamburg Eppendorf, Clin Pediat Hematol & Oncol, Childrens Canc Ctr Hamburg, Res Inst, Hamburg, Germany. [Brandalise, Silvia R.] Univ Estadual Campinas, Serv Hematol Oncol Pediat, Campinas, SP, Brazil. [Ferrando, Adolfo A.] Columbia Univ Med Ctr, Dept Pathol, New York, NY USA. [Yunes, J. Andres] Univ Estadual Campinas, Fac Ciencias Med, Dept Genet Med, Campinas, SP, Brazil. RP Barata, JT (reprint author), Univ Lisbon, Fac Med, Inst Med Mol, Canc Biol Unit, P-1699 Lisbon, Portugal. EM joao_barata@fm.ul.pt RI Barata, Joao/D-9181-2015; Toribio, Maria L/C-2039-2017; Meijerink, Jules/D-4393-2017; Silveira, Andre/I-8859-2012; OI Barata, Joao/0000-0002-4826-8976; Toribio, Maria L/0000-0002-8637-0373; Meijerink, Jules/0000-0002-6860-798X; Silveira, Andre/0000-0003-3375-1081; Cardoso, Bruno/0000-0002-6521-7257; Sarmento, Leonor/0000-0002-3692-0592 FU Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/SAU-OBD/104816/2008]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [08/10034-1]; National Cancer Institute, US National Institutes of Health (NIH); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Bolsa de Investigacao (BI); FCT; foundation Children Cancer-Free (Stichting Kinderen Kankervrij; KiKa) [2007-012] FX We are grateful to the subjects and their families for providing the specimens for this study. We thank S. Walsh (University of Maryland) for helpful discussions on the IL7R transmembrane domain; K. Czarra and M. Karwan for animal technical assistance; A. Silva, I. Antunes, A. Melao and J. Buijs-Gladdines for experimental support; P. Vandenabeele for kindly providing the WEHI3B cell line; and J. O'Shea for providing Jak3-/- bone marrow and CP-690550. This work was supported by grants from Fundacao para a Ciencia e a Tecnologia (FCT; PTDC/SAU-OBD/104816/2008, J. T. B.), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; 08/10034-1, J.A.Y.) and the intramural program of the National Cancer Institute, US National Institutes of Health (NIH) (S. K. D.). P.P.Z. and A. B. S. have Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) PhD scholarships. L. M. S. has a postdoctoral fellowship; D. R., B. A. C. and N.C. have PhD scholarships, and M. C. S. had a Bolsa de Investigacao (BI) fellowship, all from the FCT. L.Z. was supported by a grant (2007-012) from the foundation Children Cancer-Free (Stichting Kinderen Kankervrij; KiKa). NR 51 TC 132 Z9 136 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2011 VL 43 IS 10 BP 932 EP U31 DI 10.1038/ng.924 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200006 PM 21892159 ER PT J AU Bis, JC Kavousi, M Franceschini, N Isaacs, A Abecasis, GR Schminke, U Post, WS Smith, AV Cupples, LA Markus, HS Schmidt, R Huffman, JE Lehtimaki, T Baumert, J Munzel, T Heckbert, SR Dehghan, A North, K Oostra, B Bevan, S Stoegerer, EM Hayward, C Raitakari, O Meisinger, C Schillert, A Sanna, S Volzke, H Cheng, YC Thorsson, B Fox, CS Rice, K Rivadeneira, F Nambi, V Halperin, E Petrovic, KE Peltonen, L Wichmann, HE Schnabel, RB Dorr, M Parsa, A Aspelund, T Demissie, S Kathiresan, S Reilly, MP Taylor, K Uitterlinden, A Couper, DJ Sitzer, M Kahonen, M Illig, T Wild, PS Orru, M Ludemann, J Shuldiner, AR Eiriksdottir, G White, CC Rotter, JI Hofman, A Seissler, J Zeller, T Usala, G Ernst, F Launer, LJ D'Agostino, RB O'Leary, DH Ballantyne, C Thiery, J Ziegler, A Lakatta, EG Chilukoti, RK Harris, TB Wolf, PA Psaty, BM Polak, JF Li, X Rathmann, W Uda, M Boerwinkle, E Klopp, N Schmidt, H Wilson, JF Viikari, J Koenig, W Blankenberg, S Newman, AB Witteman, J Heiss, G van Duijn, C Scuteri, A Homuth, G Mitchell, BD Gudnason, V O'Donnell, CJ AF Bis, Joshua C. Kavousi, Maryam Franceschini, Nora Isaacs, Aaron Abecasis, Goncalo R. Schminke, Ulf Post, Wendy S. Smith, Albert V. Cupples, L. Adrienne Markus, Hugh S. Schmidt, Reinhold Huffman, Jennifer E. Lehtimaki, Terho Baumert, Jens Muenzel, Thomas Heckbert, Susan R. Dehghan, Abbas North, Kari Oostra, Ben Bevan, Steve Stoegerer, Eva-Maria Hayward, Caroline Raitakari, Olli Meisinger, Christa Schillert, Arne Sanna, Serena Voelzke, Henry Cheng, Yu-Ching Thorsson, Bolli Fox, Caroline S. Rice, Kenneth Rivadeneira, Fernando Nambi, Vijay Halperin, Eran Petrovic, Katja E. Peltonen, Leena Wichmann, H. Erich Schnabel, Renate B. Doerr, Marcus Parsa, Afshin Aspelund, Thor Demissie, Serkalem Kathiresan, Sekar Reilly, Muredach P. Taylor, Kent Uitterlinden, Andre Couper, David J. Sitzer, Matthias Kahonen, Mika Illig, Thomas Wild, Philipp S. Orru, Marco Luedemann, Jan Shuldiner, Alan R. Eiriksdottir, Gudny White, Charles C. Rotter, Jerome I. Hofman, Albert Seissler, Jochen Zeller, Tanja Usala, Gianluca Ernst, Florian Launer, Lenore J. D'Agostino, Ralph B., Sr. O'Leary, Daniel H. Ballantyne, Christie Thiery, Joachim Ziegler, Andreas Lakatta, Edward G. Chilukoti, Ravi Kumar Harris, Tamara B. Wolf, Philip A. Psaty, Bruce M. Polak, Joseph F. Li, Xia Rathmann, Wolfgang Uda, Manuela Boerwinkle, Eric Klopp, Norman Schmidt, Helena Wilson, James F. Viikari, Jorma Koenig, Wolfgang Blankenberg, Stefan Newman, Anne B. Witteman, Jacqueline Heiss, Gerardo van Duijn, Cornelia Scuteri, Angelo Homuth, Georg Mitchell, Braxton D. Gudnason, Vilmundur O'Donnell, Christopher J. CA CARDIoGRAM Consortium TI Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque SO NATURE GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; SINGLE NUCLEOTIDE POLYMORPHISMS; URIC-ACID LEVELS; HEART-DISEASE; MYOCARDIAL-INFARCTION; GENETIC-LOCI; LIPID-LEVELS; ATHEROSCLEROSIS; RISK; POPULATION AB Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 x 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events. C1 [Bis, Joshua C.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kavousi, Maryam; Dehghan, Abbas; Uitterlinden, Andre; Hofman, Albert; Witteman, Jacqueline] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Kavousi, Maryam; Dehghan, Abbas; Rivadeneira, Fernando; Uitterlinden, Andre; Hofman, Albert; Witteman, Jacqueline; van Duijn, Cornelia] Sponsored Netherlands Consortium Healthy Aging NC, NGI, Rotterdam, Netherlands. [Franceschini, Nora; Li, Xia; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Isaacs, Aaron; van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Isaacs, Aaron; Oostra, Ben; van Duijn, Cornelia] Ctr Med Syst Biol, Leiden, Netherlands. [Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Schminke, Ulf] Ernst Moritz Arndt Univ Greifswald, Dept Neurol, Greifswald, Germany. [Post, Wendy S.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Smith, Albert V.; Thorsson, Bolli; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Cupples, L. Adrienne; Demissie, Serkalem; White, Charles C.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Cupples, L. Adrienne; Fox, Caroline S.; Wolf, Philip A.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Markus, Hugh S.; Bevan, Steve] St Georges Univ London, Ctr Clin Neurosci, London, England. [Schmidt, Reinhold; Stoegerer, Eva-Maria] Med Univ Graz, Dept Neurol, Graz, Austria. [Huffman, Jennifer E.; Hayward, Caroline] Western Gen Hosp, Human Genet Unit, Inst Genet & Mol Med, MRC, Edinburgh EH4 2XU, Midlothian, Scotland. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, Terho; Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [Baumert, Jens; Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Muenzel, Thomas; Schnabel, Renate B.; Wild, Philipp S.; Zeller, Tanja; Blankenberg, Stefan] Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [North, Kari] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Schillert, Arne; Ziegler, Andreas] Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany. [Sanna, Serena; Orru, Marco; Usala, Gianluca; Uda, Manuela] CNR, IRGB, Cagliari, Italy. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Cheng, Yu-Ching] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rivadeneira, Fernando; Uitterlinden, Andre] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Nambi, Vijay; Ballantyne, Christie] Baylor Coll Med, Houston, TX 77030 USA. [Nambi, Vijay] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Prevent, Houston, TX USA. [Nambi, Vijay] Ben Taub Gen Hosp, Houston, TX 77030 USA. [Halperin, Eran] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Petrovic, Katja E.] Med Univ Graz, Graz, Austria. [Petrovic, Katja E.] Gen Hosp, Dept Neurol, Graz, Austria. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England. [Peltonen, Leena] Univ Helsinki, Biomedicum, Inst Mol Med Finland, Helsinki, Finland. [Peltonen, Leena] Natl Inst Hlth & Welf, Helsinki, Finland. [Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Parsa, Afshin; Shuldiner, Alan R.; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Taylor, Kent; Rotter, Jerome I.] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Sitzer, Matthias] Klinikum Herford, Dept Neurol, Herford, Germany. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Illig, Thomas; Klopp, Norman] German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Muenchen, Neuherberg, Germany. [Illig, Thomas] Hannover Med Sch, Biobank Hannover Med Sch, D-3000 Hannover, Germany. [Orru, Marco] Santa Barbara Hosp, Div Med, Cardiol Operating Unit, Santa Barbara, CA, Italy. [Luedemann, Jan] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Seissler, Jochen] Univ Munich, Med Clin Innenstadt, Ctr Diabet, Munich, Germany. [Ernst, Florian; Chilukoti, Ravi Kumar; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Launer, Lenore J.; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [O'Leary, Daniel H.] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Boston, MA 02111 USA. [Thiery, Joachim] Univ Hosp Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany. [Thiery, Joachim] Univ Leipzig, Fac Med, Leipzig Res Ctr Civilizat Dis, Leipzig, Germany. [Lakatta, Edward G.; Scuteri, Angelo] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Polak, Joseph F.] Tufts Univ, Sch Med, Dept Radiol, Boston, MA 02111 USA. [Rathmann, Wolfgang] Univ Dusseldorf, Inst Biometr & Epidemiol, German Diabet Ctr, Leibniz Ctr Diabet Res, Dusseldorf, Germany. [Boerwinkle, Eric] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. RP Bis, JC (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM joshbis@uw.edu; odonnellc@nhlbi.nih.gov RI Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Hayward, Caroline/M-8818-2016; Aspelund, Thor/C-5983-2008; Abecasis, Goncalo/B-7840-2010; Rice, Kenneth/A-4150-2013; Newman, Anne/C-6408-2013; Meisinger, Christine/B-5358-2014; Schnabel, Renate/F-6527-2014; Gudnason, Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; OI Meisinger, Christa/0000-0002-9026-6544; sanna, serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825; Ziegler, Andreas/0000-0002-8386-5397; Bevan, Steve/0000-0003-0490-6830; Mitchell, Braxton/0000-0003-4920-4744; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Hayward, Caroline/0000-0002-9405-9550; Cupples, L. Adrienne/0000-0003-0273-7965; Aspelund, Thor/0000-0002-7998-5433; Rice, Kenneth/0000-0001-5779-4495; Newman, Anne/0000-0002-0106-1150; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; Dehghan, Abbas/0000-0001-6403-016X FU US National Institutes of Health (NIH) [N01-AG-12100]; National Institute on Aging (NIA) Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); NIH [R01 AG18728, R01 HL088119, U01 GM074518-04, U01 HL072515-06]; University of Maryland General Clinical Research Center [M01 RR 16500]; Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center; Paul Beeson Physician Faculty Scholars in Aging Program; National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; US National Institutes of Health [HHSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research; Netherlands Organisation for Scientific Research; Erasmus Medical Center; Centre for Medical Systems Biology (CMSB); National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute of Aging [AG-023629, AG-15928, AG-20098, AG-027058, AG08122, AG16495, AG033193]; National Center for Research Resources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; National Institute of Neurological Disorders and Stroke [NS17950]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Netherlands Organisation of Scientific Research (NWO, De Nederlandse Organisatie voor Wetenschappelijk Onderzoek) [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; NWO [918-76-619]; Erasmus Medical Center and Erasmus University; Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Bundesministeriumfuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; National Institute on Aging, NIH; National Institute on Aging [NO1-AG-1-2109]; National Institute on Aging to the University of Michigan [263-MA-410953]; National Institutes of Health [HG005581, HL084729]; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; Austrian Science Fond (FWF) [P20545-P05, P13180]; Medical University of Graz; European Community [201668]; government of Rheinland-Pfalz ('Stiftung Rheinland Pfalzfur Innovation') [AZ 961-386261/733]; Wissenschafft Zukunft; 'Schwerpunkt Vaskulare Pravention' of the Johannes Gutenberg-University of Mainz; BoehringerIngelheim; Philips Medical Systems; Gutenberg Heart Study; National Genome Network 'NGFNplus' [A3 01GS0833]; Federal Ministry of Education and Research, Germany; Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research (BMBF); German National Genome Research Network (NGFNplus) [01GS0834]; University of Ulm; Munich Center of Health Sciences (MC Health); Karl-Wilder Foundation; German Diabetes Center; German Federal Ministry of Health; Ministry of Innovation, Science, Research and Technology of the State of North Rhine Westphalia; Office of the Scottish Government; Royal Society; European Union [LSHG-CT-2006-018947]; Academy of Finland [117797, 121584, 126925]; Social Insurance Institution of Finland; University Hospital Medical funds to Tampere; Turku University Hospitals; Finnish Foundation of Cardiovascular Research FX The Age, Gene/Environment Susceptibility (AGES) Reykjavik Study was funded by US National Institutes of Health (NIH) contract N01-AG-12100, the National Institute on Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament).; The Old Order Amish Studies were supported by grants and contracts from the NIH including R01 AG18728 (Amish Longevity Study), R01 HL088119 (Amish Calcification Study), U01 GM074518-04 (The Amish Pharmacogenomics of Anti-Platelet Intervention (PAPI) study) and U01 HL072515-06 (the Heredity and Phenotype Intervention (HAPI) heart study), the University of Maryland General Clinical Research Center grant M01 RR 16500, the Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center and the Paul Beeson Physician Faculty Scholars in Aging Program. We thank our Amish research volunteers for their long-standing partnership in research and the research staff at the Amish Research Clinic for their hard work and dedication.; The Atherosclerosis Risk in Communities Study (ARIC) was carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and US National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Study infrastructure was partly supported by grant number UL1RR025005, a component of the US National Institutes of Health and NIH Roadmap for Medical Research.; The Erasmus Rucphen Family Study was supported by grants from The Netherlands Organisation for Scientific Research, Erasmus Medical Center and the Centre for Medical Systems Biology (CMSB). We are grateful to all study participants and their relatives, the general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work and P. Snijders for his help in data collection.; The Cardiovascular Health Study research reported in this article was supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grants HL080295, HL075366, HL087652, HL105756 with additional contribution from National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098 and AG-027058 from the National Institute of Aging. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00069 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the US National Institutes of Health and Boston University School of Medicine was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278) and by grants from the National Institute of Neurological Disorders and Stroke (NS17950, P. A. W.) and the National Institute of Aging (AG08122, AG16495, P. A. W. and AG033193, S. S.). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project.; Rotterdam Study I and II (RS I and RS II): The Rotterdam GWAS was funded by the Netherlands Organisation of Scientific Research (NWO, De Nederlandse Organisatie voor Wetenschappelijk Onderzoek) Investments (number 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project number 050-060-810. This study was further supported by an NWO grant (vici, 918-76-619). The Rotterdam Study was funded by the Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are very grateful to the participants and staff from the Rotterdam Study, the participating general practioners and the pharmacists. We thank P. Arp, M. Jhamai, M. Moorhouse, M. Verkerk and S. Bervoets for their help in creating the GWAS database. We would like to thank T. A. Knoch, L. V. de Zeeuw, A. Abuseiris and R. de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the National German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministeriumfuer Forschung und Technology under grants #01 AK 803 A-H and #01 IG 07015 G, for access to their grid resources.; The SardiNIA Study: This work was supported by the Intramural Research Program of the National Institute on Aging, NIH. The SardiNIA ('Progenia') team was supported by Contract NO1-AG-1-2109 from the National Institute on Aging. The efforts of G. R. A. were supported in part by contract 263-MA-410953 from the National Institute on Aging to the University of Michigan and by research grants HG005581 and HL084729 from the National Institutes of Health (to G.R.A.).; The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants number 01ZZ9603, 01ZZ0103 and 01ZZ0403), and the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The SHIP authors are grateful to the contribution of A. Teumer, A. Hoffmann and A. Petersmann in generating the SNP data. The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG.; The Austrian Stroke Prevention Study (ASPS): The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS.; The Coronary Artery Progression Study: Research leading these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 201668; AtheroRemo.; The Gutenberg Heart Study was funded through the government of Rheinland-Pfalz ('Stiftung Rheinland Pfalzfur Innovation', contract number AZ 961-386261/733), the research programs 'Wissenschafft Zukunft' and 'Schwerpunkt Vaskulare Pravention' of the Johannes Gutenberg-University of Mainz and its contract with BoehringerIngelheim and Philips Medical Systems, including an unrestricted grant for the Gutenberg Heart Study. Specifically, the research reported in this article was supported by the National Genome Network 'NGFNplus' (contract number project A3 01GS0833) by the Federal Ministry of Education and Research, Germany.; Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF). Part of this work was financed by the German National Genome Research Network (NGFNplus, project number 01GS0834) and through additional funds from the University of Ulm. Furthermore, the research was supported within the Munich Center of Health Sciences (MC Health) as part of Ludwig-Maximilians-Universitat Munich (LMU) innovative. IMT measurement of the KORA cohort was funded by a grant of the Karl-Wilder Foundation. Finally, part of this work was financed by the German Diabetes Center, which is funded by the German Federal Ministry of Health and the Ministry of Innovation, Science, Research and Technology of the State of North Rhine Westphalia.; The Orkney Complex Disease Study (ORCADES) was supported by the Chief Scientist Office of the Scottish Government, the Royal Society and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We would like to acknowledge the invaluable contributions of L. Anderson and the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney.; The Cardiovascular Risk in Young Finns Study was supported by the Academy of Finland (grant numbers 117797, 121584 and 126925), the Social Insurance Institution of Finland, University Hospital Medical funds to Tampere, and Turku University Hospitals, the Finnish Foundation of Cardiovascular Research. NR 37 TC 92 Z9 92 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2011 VL 43 IS 10 BP 940 EP U40 DI 10.1038/ng.920 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200007 PM 21909108 ER PT J AU Ripke, S Sanders, AR Kendler, KS Levinson, DF Sklar, P Holmans, PA Lin, DY Duan, J Ophoff, RA Andreassen, OA Scolnick, E Cichon, S Clair, DS Corvin, A Gurling, H Werge, T Rujescu, D Blackwood, DHR Pato, CN Malhotra, AK Purcell, S Dudbridge, F Neale, BM Rossin, L Visscher, PM Posthuma, D Ruderfer, DM Fanous, A Stefansson, H Steinberg, S Mowry, BJ Golimbet, V De Hert, M Jonsson, EG Bitter, I Pietilainen, OPH Collier, DA Tosato, S Agartz, I Albus, M Alexander, M Amdur, RL Amin, F Bass, N Bergen, SE Black, DW Borglum, AD Brown, MA Bruggeman, R Buccola, NG Byerley, WF Cahn, W Cantor, RM Carr, VJ Catts, SV Choudhury, K Cloninger, CR Cormican, P Craddock, N Danoy, PA Datta, S De Haan, L Demontis, D Dikeos, D Djurovic, S Donnelly, P Donohoe, G Duong, L Dwyer, S Fink-Jensen, A Freedman, R Freimer, NB Friedl, M Georgieva, L Giegling, I Gill, M Glenthoj, B Godard, S Hamshere, M Hansen, M Hansen, T Hartmann, AM Henskens, FA Hougaard, DM Hultman, CM Ingason, A Jablensky, AV Jakobsen, KD Jay, M Jurgens, G Kahn, R Keller, MC Kenis, G Kenny, E Kim, Y Kirov, GK Konnerth, H Konte, B Krabbendam, L Krasucki, R Lasseter, VK Laurent, C Lawrence, J Lencz, T Lerer, FB Liang, KY Lichtenstein, P Lieberman, JA Linszen, DH Lonnqvist, J Loughland, CM Maclean, AW Maher, BS Maier, W Mallet, J Malloy, P Mattheisen, M Mattingsdal, M McGhee, KA McGrath, JJ McIntosh, A McLean, DE McQuillin, A Melle, I Michie, PT Milanova, V Morris, DW Mors, O Mortensen, PB Moskvina, V Muglia, P Myin-Germeys, I Nertney, DA Nestadt, G Nielsen, J Nikolov, I Nordentoft, M Norton, N Nothen, MM O'Dushlaine, CT Olincy, A Olsen, L O'Neill, FA Orntoft, TF Owen, MJ Pantelis, C Papadimitriou, G Pato, MT Peltonen, L Petursson, H Pickard, B Pimm, J Pulver, AE Puri, V Quested, D Quinn, EM Rasmussen, HB Rethelyi, JM Ribble, R Rietschel, M Riley, BP Ruggeri, M Schall, U Schulze, TG Schwab, SG Scott, RJ Shi, JX Sigurdsson, E Silverman, JM Spencer, CCA Stefansson, K Strange, A Strengman, E Stroup, TS Suvisaari, J Terenius, L Thirumalai, S Thygesen, JH Timm, S Toncheva, D van den Oord, E van Os, J van Winkel, R Veldink, J Walsh, D Wang, AG Wiersma, D Wildenauer, DB Williams, HJ Williams, NM Wormley, B Zammit, S Sullivan, PF O'Donovan, MC Daly, MJ Gejman, PV AF Ripke, Stephan Sanders, Alan R. Kendler, Kenneth S. Levinson, Douglas F. Sklar, Pamela Holmans, Peter A. Lin, Dan-Yu Duan, Jubao Ophoff, Roel A. Andreassen, Ole A. Scolnick, Edward Cichon, Sven Clair, David St. Corvin, Aiden Gurling, Hugh Werge, Thomas Rujescu, Dan Blackwood, Douglas H. R. Pato, Carlos N. Malhotra, Anil K. Purcell, Shaun Dudbridge, Frank Neale, Benjamin M. Rossin, Lizzy Visscher, Peter M. Posthuma, Danielle Ruderfer, Douglas M. Fanous, Ayman Stefansson, Hreinn Steinberg, Stacy Mowry, Bryan J. Golimbet, Vera De Hert, Marc Jonsson, Erik G. Bitter, Istvan Pietilainen, Olli P. H. Collier, David A. Tosato, Sarah Agartz, Ingrid Albus, Margot Alexander, Madeline Amdur, Richard L. Amin, Farooq Bass, Nicholas Bergen, Sarah E. Black, Donald W. Borglum, Anders D. Brown, Matthew A. Bruggeman, Richard Buccola, Nancy G. Byerley, William F. Cahn, Wiepke Cantor, Rita M. Carr, Vaughan J. Catts, Stanley V. Choudhury, Khalid Cloninger, C. Robert Cormican, Paul Craddock, Nicholas Danoy, Patrick A. Datta, Susmita De Haan, Lieuwe Demontis, Ditte Dikeos, Dimitris Djurovic, Srdjan Donnelly, Peter Donohoe, Gary Duong, Linh Dwyer, Sarah Fink-Jensen, Anders Freedman, Robert Freimer, Nelson B. Friedl, Marion Georgieva, Lyudmila Giegling, Ina Gill, Michael Glenthoj, Birte Godard, Stephanie Hamshere, Marian Hansen, Mark Hansen, Thomas Hartmann, Annette M. Henskens, Frans A. Hougaard, David M. Hultman, Christina M. Ingason, Andres Jablensky, Assen V. Jakobsen, Klaus D. Jay, Maurice Juergens, Gesche Kahn, Renes Keller, Matthew C. Kenis, Gunter Kenny, Elaine Kim, Yunjung Kirov, George K. Konnerth, Heike Konte, Bettina Krabbendam, Lydia Krasucki, Robert Lasseter, Virginia K. Laurent, Claudine Lawrence, Jacob Lencz, Todd Lerer, F. Bernard Liang, Kung-Yee Lichtenstein, Paul Lieberman, Jeffrey A. Linszen, Don H. Lonnqvist, Jouko Loughland, Carmel M. Maclean, Alan W. Maher, Brion S. Maier, Wolfgang Mallet, Jacques Malloy, Pat Mattheisen, Manuel Mattingsdal, Morten McGhee, Kevin A. McGrath, John J. McIntosh, Andrew McLean, Duncan E. McQuillin, Andrew Melle, Ingrid Michie, Patricia T. Milanova, Vihra Morris, Derek W. Mors, Ole Mortensen, Preben B. Moskvina, Valentina Muglia, Pierandrea Myin-Germeys, Inez Nertney, Deborah A. Nestadt, Gerald Nielsen, Jimmi Nikolov, Ivan Nordentoft, Merete Norton, Nadine Noethen, Markus M. O'Dushlaine, Colm T. Olincy, Ann Olsen, Line O'Neill, F. Anthony Orntoft, Torben F. Owen, Michael J. Pantelis, Christos Papadimitriou, George Pato, Michele T. Peltonen, Leena Petursson, Hannes Pickard, Ben Pimm, Jonathan Pulver, Ann E. Puri, Vinay Quested, Digby Quinn, Emma M. Rasmussen, Henrik B. Rethelyi, Janos M. Ribble, Robert Rietschel, Marcella Riley, Brien P. Ruggeri, Mirella Schall, Ulrich Schulze, Thomas G. Schwab, Sibylle G. Scott, Rodney J. Shi, Jianxin Sigurdsson, Engilbert Silverman, Jeremy M. Spencer, Chris C. A. Stefansson, Kari Strange, Amy Strengman, Eric Stroup, T. Scott Suvisaari, Jaana Terenius, Lars Thirumalai, Srinivasa Thygesen, Johan H. Timm, Sally Toncheva, Draga van den Oord, Edwin van Os, Jim van Winkel, Ruud Veldink, Jan Walsh, Dermot Wang, August G. Wiersma, Durk Wildenauer, Dieter B. Williams, Hywel J. Williams, Nigel M. Wormley, Brandon Zammit, Stan Sullivan, Patrick F. O'Donovan, Michael C. Daly, Mark J. Gejman, Pablo V. CA Schizophrenia Psychiat Genome-Wide TI Genome-wide association study identifies five new schizophrenia loci SO NATURE GENETICS LA English DT Article ID COMMON SNPS EXPLAIN; BIPOLAR DISORDER; HUMAN HEIGHT; LARGE PROPORTION; MICRORNA; VARIANTS; SUSCEPTIBILITY; HERITABILITY; INDIVIDUALS; ANCESTRY AB We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)). C1 [Sanders, Alan R.; Duan, Jubao; Gejman, Pablo V.] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL USA. [Ripke, Stephan; Sklar, Pamela; Rossin, Lizzy; Ruderfer, Douglas M.; Bergen, Sarah E.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sanders, Alan R.; Duan, Jubao; Gejman, Pablo V.] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA. [Kendler, Kenneth S.; Maher, Brion S.; Ribble, Robert; Riley, Brien P.; Wormley, Brandon] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Kendler, Kenneth S.; Fanous, Ayman; Maher, Brion S.; Ribble, Robert; Riley, Brien P.; Wormley, Brandon] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA USA. [Kendler, Kenneth S.; Maher, Brion S.; Ribble, Robert; Riley, Brien P.; Wormley, Brandon] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA USA. [Levinson, Douglas F.; Alexander, Madeline] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Sklar, Pamela; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Holmans, Peter A.; Craddock, Nicholas; Dwyer, Sarah; Georgieva, Lyudmila; Hamshere, Marian; Kirov, George K.; Moskvina, Valentina; Nikolov, Ivan; Norton, Nadine; Owen, Michael J.; Williams, Hywel J.; Williams, Nigel M.; Zammit, Stan; O'Donovan, Michael C.] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Gen, Sch Med, Cardiff, S Glam, Wales. [Holmans, Peter A.; Craddock, Nicholas; Dwyer, Sarah; Georgieva, Lyudmila; Hamshere, Marian; Kirov, George K.; Moskvina, Valentina; Nikolov, Ivan; Norton, Nadine; Owen, Michael J.; Williams, Hywel J.; Williams, Nigel M.; Zammit, Stan; O'Donovan, Michael C.] Cardiff Univ, Dept Psychol Med & Neurol, Sch Med, Cardiff, S Glam, Wales. [Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Ophoff, Roel A.; Strengman, Eric] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Ophoff, Roel A.; Strengman, Eric] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Ophoff, Roel A.; Cantor, Rita M.; Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. [Ophoff, Roel A.; Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Andreassen, Ole A.; Agartz, Ingrid; Djurovic, Srdjan; Mattingsdal, Morten; Melle, Ingrid] Univ Oslo, Inst Clin Med, Psychiat Sect, Oslo, Norway. [Andreassen, Ole A.; Melle, Ingrid] Oslo Univ Hosp, Dept Psychiat, Oslo, Norway. [Scolnick, Edward; Purcell, Shaun; Neale, Benjamin M.] Broad Inst, Cambridge, MA USA. [Cichon, Sven; Mattheisen, Manuel; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Cichon, Sven; Mattheisen, Manuel; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Clair, David St.] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland. [Corvin, Aiden; Cormican, Paul; Donohoe, Gary; Gill, Michael; Kenny, Elaine; Morris, Derek W.; O'Dushlaine, Colm T.; Quinn, Emma M.] Trinity Coll Dublin, Neuropsychiat Genet Res Grp, Dublin, Ireland. [Gurling, Hugh; Bass, Nicholas; Choudhury, Khalid; Datta, Susmita; Krasucki, Robert; Lawrence, Jacob; McQuillin, Andrew; Pimm, Jonathan; Puri, Vinay] UCL, Sch Med, Windeyer Inst Med Sci, Mol Psychiat Lab,Res Dept Mental Hlth Sci, London W1N 8AA, England. [Werge, Thomas; Duong, Linh; Hansen, Thomas; Ingason, Andres; Jakobsen, Klaus D.; Olsen, Line; Rasmussen, Henrik B.; Thygesen, Johan H.] Copenhagen Univ Hosp, Inst Biol Psychiat, Mental Hlth Ctr MHC Sct Hans, Roskilde, Denmark. [Rujescu, Dan; Friedl, Marion; Giegling, Ina; Hartmann, Annette M.; Konnerth, Heike; Konte, Bettina] Univ Munich, Dept Psychiat, D-8000 Munich, Germany. [Blackwood, Douglas H. R.; Maclean, Alan W.; Malloy, Pat; McGhee, Kevin A.; McIntosh, Andrew] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland. [Pato, Carlos N.; Pato, Michele T.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Malhotra, Anil K.; Lencz, Todd] Zucker Hillside Hosp, Div N Shore Long Isl Jewish Hlth Syst, Div Res, Dept Psychiat, Glen Oaks, NY USA. [Malhotra, Anil K.; Lencz, Todd] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Malhotra, Anil K.; Lencz, Todd] Yeshiva Univ, Albert Einstein Coll Med, Dept Psychiat & Behav Sci, New York, NY 10033 USA. [Dudbridge, Frank] London Sch Hyg & Trop Med, Dept Non Communicable Dis Epidemiol, London WC1, England. [Visscher, Peter M.] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. [Posthuma, Danielle] Vrije Univ Amsterdam, CNCR, Dept Funct Gen, Amsterdam, Netherlands. [Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, Dept Med Genom, Amsterdam, Netherlands. [Fanous, Ayman; Amdur, Richard L.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Fanous, Ayman; Amdur, Richard L.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Stefansson, Hreinn; Steinberg, Stacy; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Mowry, Bryan J.; McGrath, John J.; Nertney, Deborah A.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Mowry, Bryan J.; McGrath, John J.; Nertney, Deborah A.] Univ Queensland, Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia. [Golimbet, Vera] Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia. [De Hert, Marc; van Winkel, Ruud] Katholieke Univ Leuven, Univ Psychiat Ctr, Kortenberg, Belgium. [Jonsson, Erik G.; Terenius, Lars] Karolinska Hosp & Inst, Human Brain Informat HUBIN Project, Dept Clin Neurosci, Stockholm, Sweden. [Bitter, Istvan; Rethelyi, Janos M.] Semmelweis Univ, Dept Psychiat & Psychotherapy, Budapest, Hungary. [Pietilainen, Olli P. H.; Peltonen, Leena] Univ Helsinki, FIMM, Helsinki, Finland. [Pietilainen, Olli P. H.; Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Collier, David A.] Kings Coll London, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. [Tosato, Sarah; Ruggeri, Mirella] Univ Verona, Sect Psychiat & Clin Psychol, I-37100 Verona, Italy. [Agartz, Ingrid] Diakonhjemmet Hosp, Dept Res, Oslo, Norway. [Albus, Margot] State Mental Hosp, Haar, Germany. [Amin, Farooq] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Amin, Farooq] Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Black, Donald W.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Borglum, Anders D.; Demontis, Ditte] Univ Aarhus, Inst Human Genet, Aarhus, Denmark. [Borglum, Anders D.; Mors, Ole] Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark. [Brown, Matthew A.; Danoy, Patrick A.] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld, Australia. [Bruggeman, Richard; Wiersma, Durk] Univ Groningen, Dept Psychiat, Univ Med Ctr Groningen, NL-9712 TS Groningen, Netherlands. [Buccola, Nancy G.] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA. [Byerley, William F.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Byerley, William F.] NCIRE, San Francisco, CA USA. [Cahn, Wiepke; Kahn, Renes] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Carr, Vaughan J.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Carr, Vaughan J.; Michie, Patricia T.; Schall, Ulrich] Schizophrenia Res Inst, Sydney, NSW, Australia. [Catts, Stanley V.] Univ Queensland, Dept Psychiat, Royal Brisbane Hosp, Brisbane, Qld, Australia. [Cloninger, C. Robert] Washington Univ, Dept Psychiat, St Louis, MO USA. [De Haan, Lieuwe; Linszen, Don H.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Dikeos, Dimitris; Papadimitriou, George] Univ Athens, Sch Med, Dept Psychiat, GR-11527 Athens, Greece. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Donnelly, Peter; Spencer, Chris C. A.; Strange, Amy] Wellcome Trust Ctr Human Genet, Oxford, England. [Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Fink-Jensen, Anders] Copenhagen Univ Hosp, Mental Hlth Ctr Copenhagen, Copenhagen, Denmark. [Freedman, Robert; Olincy, Ann] Univ Colorado Denver, Dept Psychiat, Aurora, CO USA. [Glenthoj, Birte] Copenhagen Univ Hosp, Mental Hlth Ctr Glostrup, Ctr Clin Intervent & Neuropsychiat Schizophrenia, Glostrup, Denmark. [Godard, Stephanie] Hop La Pitie Salpetriere, INSERM, Inst Myol, Paris, France. [Hansen, Mark] Illumina Inc, La Jolla, CA USA. [Henskens, Frans A.] Univ Newcastle, School Elect Engn & Comp Sci, Newcastle, NSW 2300, Australia. [Hougaard, David M.] State Serum Inst, Dept Clin Chem & Immunol, Sect Neonatal Screening & Hormones, Copenhagen, Denmark. [Hultman, Christina M.; Lichtenstein, Paul; Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Jablensky, Assen V.] Univ Western Australia, Ctr Clin Res Neuropsychiat, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. [Jay, Maurice; Laurent, Claudine] Pierre & Marie Curie Fac Med, Dept Child & Adolescent Psychiat, Paris, France. [Juergens, Gesche] Bispebjerg Hosp, Dept Clin Pharmacol, Copenhagen, Denmark. [Keller, Matthew C.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Kenis, Gunter; van Winkel, Ruud] Maastricht Univ Med Ctr, S Limburg Mental Hlth Res & Teaching Network SEAR, European Grad Sch Neurosci EURON, Dept Psychiat & Psychol,Sch Mental Hlth & Neurosc, Maastricht, Netherlands. [Kim, Yunjung; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Krabbendam, Lydia; Myin-Germeys, Inez; van Os, Jim] Maastricht Univ Med Ctr, S Limburg Mental Hlth Res & Teaching Network, Maastricht, Netherlands. [Lasseter, Virginia K.; Nestadt, Gerald; Pulver, Ann E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Lerer, F. Bernard] Hadassah Hebrew Univ Med Ctr, Dept Psychiat, Jerusalem, Israel. [Liang, Kung-Yee] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Lieberman, Jeffrey A.; Stroup, T. Scott] Columbia Univ, Dept Psychiat, New York, NY USA. [Lonnqvist, Jouko; Suvisaari, Jaana] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland. [Loughland, Carmel M.] Univ Newcastle, Schizophrenia Res Inst, Sydney & Ctr Brain & Mental Hlth Res, Newcastle, NSW 2300, Australia. [Maier, Wolfgang; Rietschel, Marcella] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. [Mallet, Jacques] Hop La Pitie Salpetriere, CNRS, Lab Genet Mol Neurotransmiss & Proc Neurodegener, Paris, France. [Mattheisen, Manuel] Univ Bonn, IMBIE, D-5300 Bonn, Germany. [Mattingsdal, Morten] Sorlandet Hosp, Dept Res, Kristiansand, Norway. [McLean, Duncan E.] Pk Ctr Mental Hlth, Queensland Ctr Mental Hlth Res, Queensland, Australia. [Michie, Patricia T.] Univ Newcastle, Sch Psychol, Funct NeuroImaging Lab, Sydney, NSW, Australia. [Milanova, Vihra] Alexander Univ Hosp, Psychiat Clin 1, Dept Psychiat, Sofia, Bulgaria. [Mortensen, Preben B.] Univ Aarhus, Natl Ctr Register Based Res, Aarhus, Denmark. [Muglia, Pierandrea] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Muglia, Pierandrea] NeuroSearch AS, Ballerup, Denmark. [Nielsen, Jimmi] Aalborg Psychiat Hosp, Unit Psychiat Res, Aalborg, Denmark. [Nordentoft, Merete] Copenhagen Univ Hosp, Psychiat Ctr Copenhagen, Copenhagen, Denmark. [O'Neill, F. Anthony] Queens Univ, Dept Psychiat, Belfast, Antrim, North Ireland. [Orntoft, Torben F.] ARoS Appl Biotechnol AS, Skejby, Denmark. [Orntoft, Torben F.] Aarhus Univ Hosp, Dept Mol Med, DK-8000 Aarhus, Denmark. [Pantelis, Christos] Univ Melbourne & Melbourne Hlth, Dept Psychiat, Melbourne Neuropsychiat Ctr, Melbourne, Australia. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England. [Petursson, Hannes; Sigurdsson, Engilbert] Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland. [Pickard, Ben] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland. [Quested, Digby] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. [Rietschel, Marcella; Schulze, Thomas G.] Univ Heidelberg, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Schall, Ulrich] Univ Newcastle, Prior Ctr Brain & Mental Hlth Res, Sydney, NSW, Australia. [Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany. [Schwab, Sibylle G.; Wildenauer, Dieter B.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. [Schwab, Sibylle G.] Univ Erlangen Nurnberg, Dept Psychiat, Erlangen, Germany. [Schwab, Sibylle G.] Univ Western Australia, Western Australian Inst Med Res, Ctr Med Res, Perth, WA 6009, Australia. [Scott, Rodney J.] Univ Newcastle, Ctr Informat Based Med, Hunter Med Res Inst, Newcastle & Schizophrenia Res Inst, Sydney, NSW, Australia. [Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sigurdsson, Engilbert] Univ Iceland, Dept Psychiat, Reykjavik, Iceland. [Silverman, Jeremy M.] Vet Affairs Med Ctr, Dept Psychiat, New York, NY USA. [Thirumalai, Srinivasa] W Berkshire Natl Hlth Serv NHS Trust, Reading, Berks, England. [Timm, Sally] Copenhagen Univ Hosp, Mental Hlth Ctr Frederiksberg, Copenhagen, Denmark. [Toncheva, Draga] Univ Hosp Maichin Dom, Dept Med Genet, Sofia, Bulgaria. [van den Oord, Edwin] Virginia Commonwealth Univ, Dept Pharm, Richmond, VA USA. [Veldink, Jan] Univ Medisch Ctr UMC Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Walsh, Dermot] Hlth Res Board, Dublin, Ireland. [Wang, August G.] Copenhagen Univ Hosp, Mental Hlth Ctr Amager, Copenhagen, Denmark. [Wildenauer, Dieter B.] Graylands Hosp, Ctr Clin Res Neuropsychiat, Mt Claremont, WA, Australia. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Gejman, PV (reprint author), NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL USA. EM pgejman@gmail.com RI Melle, Ingrid /B-4858-2011; Ruderfer, Douglas/M-5795-2016; Lencz, Todd/J-3418-2014; McQuillin, Andrew/C-1623-2008; Stroup, Thomas/F-9188-2014; Demontis, Ditte/M-4515-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Sigurdsson, Engilbert/D-2486-2014; Myin-Germeys, Inez /L-5106-2014; Jablensky, Assen/H-5116-2014; Pickard, Benjamin/K-3923-2014; Hansen, Thomas/O-5965-2014; Holmans, Peter/F-4518-2015; Mortensen, Preben/D-2358-2015; SCHALL, ULRICH/G-7452-2013; Mattheisen, Manuel/B-4949-2012; Pantelis, Christos/H-7722-2014; Liang, Kung-Yee/F-8299-2011; Tosato, Sarah /E-6045-2010; Cloninger, Claude/F-5357-2012; Ingason, Andres/G-6817-2012; Bergen, Sarah/I-8313-2012; McIntosh, Andrew/B-9379-2008; McGrath, John/G-5493-2010; Cahn , Wiepke /B-5743-2013; Catts, Stanley/G-6917-2013; Schulze, Thomas/H-2157-2013; Gurling, Hugh/A-5029-2010; Maher, Brion/F-9185-2010; Nielsen, Jimmi /G-2990-2010 OI Andreassen, Ole A./0000-0002-4461-3568; Henskens, Frans/0000-0003-2358-5630; Visscher, Peter/0000-0002-2143-8760; Suvisaari, Jaana/0000-0001-7167-0990; Bruggeman, Richard/0000-0002-3238-8471; O'Neill, Francis Anthony/0000-0002-7531-7657; Stefansson, Hreinn/0000-0002-9331-6666; Escott-Price, Valentina/0000-0003-1784-5483; Golimbet, Vera/0000-0002-9960-7114; Agartz, Ingrid/0000-0002-9839-5391; Jonsson, Erik/0000-0001-8368-6332; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Morris, Derek/0000-0002-3413-570X; Rethelyi, Janos/0000-0002-3641-012X; Myin-Germeys, Inez/0000-0002-3731-4930; KELLER, MATTHEW/0000-0002-6075-9882; Gill, Michael/0000-0003-0206-5337; Buccola, Nancy/0000-0003-1378-4636; lichtenstein, paul/0000-0003-3037-5287; Thygesen, Johan H/0000-0002-7479-3459; Melle, Ingrid /0000-0002-9783-548X; Ruderfer, Douglas/0000-0002-2365-386X; Lencz, Todd/0000-0001-8586-338X; McQuillin, Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Zammit, Stanley/0000-0002-2647-9211; Stroup, Thomas/0000-0002-3123-0672; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Sigurdsson, Engilbert/0000-0001-9404-7982; Pickard, Benjamin/0000-0002-2374-6329; Hansen, Thomas/0000-0001-6703-7762; Holmans, Peter/0000-0003-0870-9412; Mortensen, Preben/0000-0002-5230-9865; Mattheisen, Manuel/0000-0002-8442-493X; Pantelis, Christos/0000-0002-9565-0238; Cloninger, Claude/0000-0003-3096-4807; McIntosh, Andrew/0000-0002-0198-4588; McGrath, John/0000-0002-4792-6068; FU US National Institutes of Health FX We thank the study participants and the research staff at the many study sites. Over 40 US National Institutes of Health grants and similar numbers of government grants from other countries, along with substantial private and foundation support, enabled this work. We greatly appreciate the sustained efforts of T. Lehner (National Institute of Mental Health) on behalf of the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC). Detailed acknowledgments, including grant support, are listed in the Supplementary Note. NR 32 TC 535 Z9 547 U1 11 U2 155 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2011 VL 43 IS 10 BP 969 EP U77 DI 10.1038/ng.940 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200011 ER EF