FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Diazgranados, N Ibrahim, L Brutsche, NE Newberg, A Kronstein, P Khalife, S Kammerer, WA Quezado, Z Luckenbaugh, DA Salvadore, G Machado-Vieira, R Manji, HK Zarate, CA AF Diazgranados, Nancy Ibrahim, Lobna Brutsche, Nancy E. Newberg, Andrew Kronstein, Phillip Khalife, Sami Kammerer, William A. Quezado, Zenaide Luckenbaugh, David A. Salvadore, Giacomo Machado-Vieira, Rodrigo Manji, Husseini K. Zarate, Carlos A., Jr. TI A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; MESSENGER-RNA; RATING-SCALE; QUETIAPINE MONOTHERAPY; MAJOR DEPRESSION; NMDA ANTAGONIST; MOOD DISORDERS; II DEPRESSION; KETAMINE; LAMOTRIGINE AB Context: Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health. Objective: To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. Design: A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. Setting: Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients: Eighteen subjects with DSM-IV bipolar depression (treatment-resistant). Interventions: Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. Main Outcome Measures: Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. Results: Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d=0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d=0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. Conclusion: In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist. C1 [Zarate, Carlos A., Jr.] NIMH, Expt Therapeut Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv,Clin Res Ctr, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Expt Therapeut Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv,Clin Res Ctr, 10 Ctr Dr,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Quezado, Zenaide/O-4860-2016 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Quezado, Zenaide/0000-0001-9793-4368 FU NIMH; National Institutes of Health; Department of Health and Human Services; National Alliance for Research FX Funding for this work was supported by the Intramural Research Program at the NIMH, National Institutes of Health, Department of Health and Human Services, and by a National Alliance for Research on Schizophrenia and Depression Award (Dr Zarate). NR 49 TC 365 Z9 375 U1 6 U2 37 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2010 VL 67 IS 8 BP 793 EP 802 DI 10.1001/archgenpsychiatry.2010.90 PG 10 WC Psychiatry SC Psychiatry GA 634LC UT WOS:000280581600004 PM 20679587 ER PT J AU Chio, A Calvo, A Moglia, C Restagno, G Ossola, I Brunetti, M Montuschi, A Cistaro, A Ticca, A Traynor, BJ Schymick, JC Mutani, R Marrosu, MG Murru, MR Borghero, G AF Chio, Adriano Calvo, Andrea Moglia, Cristina Restagno, Gabriella Ossola, Irene Brunetti, Maura Montuschi, Anna Cistaro, Angelina Ticca, Anna Traynor, Bryan J. Schymick, Jennifer C. Mutani, Roberto Marrosu, Maria Giovanna Murru, Maria Rita Borghero, Giuseppe TI Amyotrophic Lateral Sclerosis-Frontotemporal Lobar Dementia in 3 Families With p.Ala382Thr TARDBP Mutations SO ARCHIVES OF NEUROLOGY LA English DT Article ID GENE-MUTATIONS; TDP-43; DEGENERATION; CRITERIA; DIAGNOSIS; CONSENSUS; DISEASE; ALS AB Background: TAR DNA-binding protein 43, encoded by the TARDBP gene, has been identified as the major pathological protein of frontotemporal lobar dementia (FTLD) with or without amyotrophic lateral sclerosis (ALS) and sporadic ALS. Subsequently, mutations in the TARDBP gene have been detected in 2% to 3% of patients with ALS (both familial and sporadic ALS). However, to our knowledge, there is only 1 description of 2 patients with FTLD and TARDBP gene mutations who later developed motor neuron disease. Objective: To describe cognitive abnormalities in 3 Italian families with familial ALS and TARDBP gene mutations. Design, Setting, and Participants: Genetic, neuropsychological, and neuroimaging analyses in 36 patients with familial non superoxide dismutase 1 gene (SOD1) ALS and 280 healthy controls. Main Outcome Measure: We identified 3 index cases of familial ALS carrying the p.Ala382Thr missense mutation of the TARDBP gene and with clinical, neuroimaging, and neuropsychological features of FTLD. Results: The p.Ala382Thr missense mutation of the TARDBP gene was absent in the 280 controls. It was present in all affected members of the 3 families for whom DNA was available. All affected members of the 3 families developed FTLD after the onset of ALS, confirmed. by neuropsychological testing and hypometabolism in frontal associative areas assessed with fludeoxyglucose F 18 positron emission tomography and computed tomography. Conclusions: Three apparently unrelated families with familial ALS carrying the p.Ala382Thr TARDBP missense mutation developed FTLD. In these families, FTLD cosegregates with ALS. Patients with ALS carrying TARDBP mutations may develop FTLD. C1 [Chio, Adriano; Calvo, Andrea; Moglia, Cristina; Montuschi, Anna; Mutani, Roberto] Univ Turin, Dept Neurosci, I-10126 Turin, Italy. [Restagno, Gabriella; Ossola, Irene; Brunetti, Maura] Azienda Sanit Osped Osped Infantile Regina Marghe, Mol Genet Lab, Turin, Italy. [Cistaro, Angelina] IRMET Diagnost Imaging Torino, Positron Emiss Tomog Ctr, Turin, Italy. [Ticca, Anna] Azienda Osped San Francesco, Dept Neurol, Nuoro, Italy. [Traynor, Bryan J.; Schymick, Jennifer C.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD USA. [Marrosu, Maria Giovanna; Murru, Maria Rita; Borghero, Giuseppe] Univ Cagliari, Cagliari, Italy. [Marrosu, Maria Giovanna; Murru, Maria Rita; Borghero, Giuseppe] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy. RP Chio, A (reprint author), Univ Turin, Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI Traynor, Bryan/G-5690-2010; Calvo, Andrea/K-4141-2016; Moglia, Cristina/K-4142-2016; OI Calvo, Andrea/0000-0002-5122-7243; Moglia, Cristina/0000-0001-7377-7222; Chio, Adriano/0000-0001-9579-5341; Marrosu, Maria Giovanna/0000-0003-2334-2081 FU Fondazione Vialli e Mauro for ALS Research Onlus; Federazione Italiana Giuoco Calcio; Ministero della Salute; Intramural Research Program [Z01 AG000949-02]; National Institute on Aging; National Institutes of Health FX This work was supported by grants from the Fondazione Vialli e Mauro for ALS Research Onlus, Federazione Italiana Giuoco Calcio, and Ministero della Salute (Ricerca Sanitaria Finalizzata 2007) (Dr Chio); by the Minister della Salute (Ricerca Sanitaria Finalizzata 2007) (Dr Restagno); and by grant Z01 AG000949-02 from the Intramural Research Program and National Institute on Aging, National Institutes of Health. NR 22 TC 32 Z9 35 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2010 VL 67 IS 8 BP 1002 EP 1009 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 637HU UT WOS:000280809000014 PM 20697052 ER PT J AU Kaul, H Riazuddin, SA Qazi, ZA Nasir, IA Zafar, AU Khan, SN Husnain, T Akram, J Hejtmancik, JF Riazuddin, S AF Kaul, Haiba Riazuddin, S. Amer Qazi, Zaheeruddin A. Nasir, Idrees A. Zafar, Ahmad U. Khan, Shaheen N. Husnain, Tayyab Akram, Javed Hejtmancik, J. Fielding Riazuddin, Sheikh TI Ectopia Lentis in a Consanguineous Pakistani Family and a Novel Locus on Chromosome 8q SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RECURRENT FBN1 MUTATION; GENE; FIBRILLIN; LINKAGE AB Objective: To investigate the genetic basis and molecular characteristics of the isolated form of ectopia lentis. Methods: We ascertained a consanguineous Pakistani family with multiple individuals with ectopia lentis. All affected as well as unaffected members with isolated ectopia lentis underwent detailed ophthalmologic and medical examination. Blood samples were collected and DNA was extracted. A genome-wide scan was completed with 382 polymorphic microsatellite markers, and logarithm of odds (LOD) scores were calculated. Results: Maximum 2-point LOD scores of 5.68 and 2.88 at theta=0 were obtained for markers D8S285 and D8S260, respectively, during the genome-wide scan. Additional microsatellite markers refined the disease locus to a 16.96-cM (14.07-Mb) interval flanked by D8S1737 proximally and D8S1117 distally. Conclusions: We report on a new locus for nonsyndromic autosomal recessive ectopia lentis on chromosome 8q11.23-q13.2 in a consanguineous Pakistani family. Clinical Relevance: Identification of genetic loci and genes involved in ectopia lentis will enhance our understanding of the disease at a molecular level, leading to better genetic counseling and family screening and possible future development of better treatment. C1 [Kaul, Haiba; Riazuddin, S. Amer; Nasir, Idrees A.; Zafar, Ahmad U.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Qazi, Zaheeruddin A.] Rehmatullah Benevolent Trust Hosp, Lahore, Pakistan. [Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Iqbal Med Coll, Lahore, Pakistan. [Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM 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 Ministry of Science and Technology, Islamabad, Pakistan. NR 17 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2010 VL 128 IS 8 BP 1046 EP 1049 PG 4 WC Ophthalmology SC Ophthalmology GA 638QJ UT WOS:000280909700013 PM 20697006 ER PT J AU Kim, JW Lee, DK Fishman, M AF Kim, Jonathan W. Lee, Diana K. Fishman, Martin TI Orbital Smooth Muscle Tumor Associated With Epstein-Barr Virus in a Human Immunodeficiency Virus-Positive Patient SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID AIDS C1 [Kim, Jonathan W.; Fishman, Martin] Stanford Med Ctr, Dept Ophthalmol, Palo Alto, CA 94304 USA. [Lee, Diana K.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Kim, JW (reprint author), Stanford Med Ctr, Dept Ophthalmol, 900 Blake Wilbur Dr,W3001, Palo Alto, CA 94304 USA. EM jkim6@stanford.edu NR 4 TC 2 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2010 VL 128 IS 8 BP 1084 EP 1085 PG 2 WC Ophthalmology SC Ophthalmology GA 638QJ UT WOS:000280909700025 PM 20697018 ER PT J AU McCormick, SR McCormick, MJ Grutkoski, PS Ducker, GS Banerji, N Higgins, RR Mendiola, JR Reinartz, JJ AF McCormick, Stanley R. McCormick, Matthew J. Grutkoski, Patricia S. Ducker, Gregory S. Banerji, Nilanjana Higgins, Rodney R. Mendiola, John R. Reinartz, John J. TI FLT3 Mutations at Diagnosis and Relapse in Acute Myeloid Leukemia Cytogenetic and Pathologic Correlations, Including Cuplike Blast Morphology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; MINIMAL RESIDUAL DISEASE; KINASE DOMAIN MUTATIONS; BONE-MARROW SAMPLES; NPM1 MUTATIONS; ADULT PATIENTS; MYELODYSPLASTIC SYNDROME; CONSTITUTIVE ACTIVATION AB Context.-Acquired mutations in the fms-like tyrosine kinase 3 gene (FLT3) adversely impact relapse risk after chemotherapy in patients with acute myeloid leukemia (AML). The FLT3 mutation status may differ at diagnosis and relapse, suggesting a potential role in chemoresistance, yet few reports have addressed the cytogenetic and pathologic correlates of FLT3 mutations in relapsed AML. Objectives.-To determine FLT3 mutations at diagnosis and relapse in a cohort of adult patients with chemoresistant AML and to correlate mutation status with multiple variables. Design.-We retrospectively determined FLT3 internal tandem duplication (FLT3/ITD) and FLT3 tyrosine kinase domain mutations in 50 diagnosis/relapse pairs. We correlated FLT3 status with karyotype, World Health Organization 2008 subtype, white blood cell count, biopsy cellularity, blast percentage, and the presence of invaginated ("cuplike'') blast nuclei. Results.-In 11 of 50 patients (22%) the FLT3 mutation status differed at relapse and diagnosis, with a trend toward gain of FLT3/ITD (n = 7) and loss of FLT3 tyrosine kinase domain (n = 5) mutations. FLT3-mutated AMLs correlated with the World Health Organization 2008 subtype, AML, not otherwise specified, hyperproliferative features at diagnosis and relapse, and cytogenetic evolution. FLT3-wild type AMLs correlated with the subtype AML with myelodysplasia-related changes and frequently had adverse presentation karyotypes. Cuplike blast morphology was associated with FLT3/ITD+ status and with high mutation levels. Four of 7 patients with relapse-only FLT3/ITD mutations exhibited cuplike blasts at relapse after being noncuplike at diagnosis. Conclusions.-In addition to well-known correlates in pretreatment specimens, FLT3 mutation status has pathologic and cytogenetic significance at relapse. A shift to cuplike blast morphology at relapse may herald emergence of a previously undetected FLT3/ITD mutation. (Arch Pathol Lab Med. 2010; 134: 1143-1151) C1 [McCormick, Stanley R.; Reinartz, John J.] United Hosp, Dept Pathol, St Paul, MN 55102 USA. [McCormick, Matthew J.] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. [Grutkoski, Patricia S.; Mendiola, John R.] Abbott NW Hosp, Mol Diagnost Lab, Virginia Piper Canc Inst, Minneapolis, MN 55407 USA. [Ducker, Gregory S.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Higgins, Rodney R.] Abbott NW Hosp, Allina Cytogenet Lab, Minneapolis, MN 55407 USA. RP McCormick, SR (reprint author), United Hosp, Dept Pathol, 333 N Smith Ave, St Paul, MN 55102 USA. EM stan.mccormick@allina.com FU United Hospital Education and Research Committee, United Hospital, St Paul, Minnesota FX This study was funded by the United Hospital Education and Research Committee, United Hospital, St Paul, Minnesota. We acknowledge Kofi Adragni, PhD, for statistical assistance and Mr Lawrence Sobaskie for preparation of the digital images. NR 54 TC 13 Z9 14 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 2010 VL 134 IS 8 BP 1143 EP 1151 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 635DU UT WOS:000280636600011 PM 20670134 ER PT J AU Kirkpatrick, SI McIntyre, L Potestio, ML AF Kirkpatrick, Sharon I. McIntyre, Lynn Potestio, Melissa L. TI Child Hunger and Long-term Adverse Consequences for Health SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID HOUSEHOLD FOOD INSECURITY; LOW FAMILY INCOME; UNITED-STATES; INSUFFICIENCY; OVERWEIGHT; ADOLESCENTS; PRESCHOOL; OUTCOMES; YOUTH AB Objective: To examine the effects of hunger, an extreme manifestation of food insecurity, on subsequent health outcomes using data from the Canadian National Longitudinal Survey of Children and Youth (NLSCY). Design: Longitudinal survey, 1994-2004/2005. Setting: Canada. Participants: A total of 5809 children aged 10 to 15 years and 3333 youth aged 16 to 21 years. Main Exposures: Longitudinal survey data spanning a 10-year period were analyzed using logistic regression. Measures of hunger from NLSCY cycles 1 through 5 were used to differentiate participants who were ever hungry from those who were never hungry. A 3-level variable was created to assess the effect of repeated episodes of hunger. Co-variates included participants' age, sex, baseline health, and household sociodemographic characteristics. Stratified models were used to examine the relation between hunger and health among boys and girls separately. Outcome Measures: The NLCSY cycle 6 outcomes included poor general health, chronic health conditions, and asthma. Results: Among children, both ever being hungry and multiple episodes of hunger were associated with poorer general health but not with chronic conditions or asthma. Higher odds of chronic conditions and of asthma were observed among youth who experienced multiple episodes of hunger compared with those who were never hungry. Associations between hunger and poorer health outcomes persisted among girls in stratified analyses. Conclusions: Children and youth who experience hunger are more likely to have poorer health, and repeated exposure appears to be particularly toxic. Our findings point to the relevance of food insecurity in childhood as a marker of vulnerability, with implications for clinical practice and advocacy. C1 [Kirkpatrick, Sharon I.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kirkpatrick, Sharon I.; McIntyre, Lynn; Potestio, Melissa L.] Univ Calgary, Fac Med, Dept Community Hlth Sci, Calgary, AB, Canada. RP Kirkpatrick, SI (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Executive Blvd, Bethesda, MD 20892 USA. EM sharon.kirkpatrick@nih.gov OI Kirkpatrick, Sharon/0000-0001-9896-5975 FU Alberta Heritage Foundation; Canadian Institutes of Health Research FX The study was supported by the Alberta Heritage Foundation for Medical Research (Dr Kirkpatrick); the Canadian Institutes of Health Research (Dr McIntyre and Ms Potestio). NR 31 TC 62 Z9 63 U1 2 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2010 VL 164 IS 8 BP 754 EP 762 PG 9 WC Pediatrics SC Pediatrics GA 634LE UT WOS:000280581800011 PM 20679167 ER PT J AU Cortesio, CL Wernimont, SA Kastner, DL Cooper, KM Huttenlocher, A AF Cortesio, Christa L. Wernimont, Sarah A. Kastner, Daniel L. Cooper, Kate M. Huttenlocher, Anna TI Impaired podosome formation and invasive migration of macrophages from patients with a PSTPIP1 mutation and PAPA syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID WISKOTT-ALDRICH-SYNDROME; SYNDROME PROTEIN; PTP-PEST; DYNAMICS; WASP C1 [Cortesio, Christa L.; Wernimont, Sarah A.; Huttenlocher, Anna] Univ Wisconsin, Madison, WI 53706 USA. [Kastner, Daniel L.] NIAMSD, Bethesda, MD 20892 USA. [Cooper, Kate M.] Loras Coll, Dubuque, IA USA. RP Cortesio, CL (reprint author), Univ Wisconsin, Madison, WI 53706 USA. FU NCI NIH HHS [R01 CA085862, R01 CA085862-11A1] NR 9 TC 19 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD AUG PY 2010 VL 62 IS 8 BP 2556 EP 2558 DI 10.1002/art.27521 PG 3 WC Rheumatology SC Rheumatology GA 661WA UT WOS:000282762100044 PM 20506269 ER PT J AU Ng, D Spaulding, E Mullikin, JC Biesecker, LG AF Ng, David Spaulding, Emma Mullikin, James C. Biesecker, Leslie G. TI Identification of a novel LDLR mutation (c.261_262invGA, p.Trp87X): Importance of specifying DNA and protein mutations SO ATHEROSCLEROSIS LA English DT Letter DE Familial hypercholesterolemia; LDLR mutation; Large-scale medical sequencing ID FAMILIAL HYPERCHOLESTEROLEMIA; GENE AB ClinSeq is a large-scale medical sequencing (LSMS) project at the National Institutes of Health (NIH), the goal of which is to pilot the feasibility of using high throughput genome sequencing for clinical research and eventually to improve the delivery of healthcare. In phase one, 1000 participants are being clinically evaluated for cardiovascular phenotypes and DNA is being collected for sequencing of 400 candidate genes to identify genetic variants that may predispose to the early development of atherosclerosis. We report on an individual with familial hypercholesterolemia (OMIM #143890) who has a novel mutation, c.261_262invGA that predicts a premature stop (p.Trp87X) in the LDLR gene. Although the p.Trp87X predicted protein mutation has been reported, c.261_262invGA is distinct from mutations reported in prior families and emphasizes the importance of describing mutations at the DNA level. It is important to describe mutations according to the underlying DNA change as multiple nucleotide changes may underlie a single predicted protein change. Published by Elsevier Ireland Ltd. C1 [Ng, David] NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. [Ng, David; Mullikin, James C.] NIH, Intramural Sequencing Ctr, NISC, Bethesda, MD 20892 USA. RP Ng, D (reprint author), NHGRI, GDRB, NIH, 49 Convent Dr,Room 4A80, Bethesda, MD 20892 USA. EM davidng@mail.nih.gov FU Intramural NIH HHS [Z99 HG999999, ZIA HG200359-02] NR 6 TC 2 Z9 2 U1 0 U2 0 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 AUG PY 2010 VL 211 IS 2 BP 397 EP 398 DI 10.1016/j.atherosclerosis.2010.04.011 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634VC UT WOS:000280612700009 PM 20452591 ER PT J AU Hour, TC Lai, YL Kuan, CI Chou, CK Wang, JM Tu, HY Hu, HT Lin, CS Wu, WJ Pu, YS Sterneck, E Huang, AM AF Hour, Tzyh-Chyuan Lai, Yan-Liang Kuan, Ching-I Chou, Chen-Kung Wang, Ju-Ming Tu, Huang-Yao Hu, Huei-Ting Lin, Chang-Shen Wu, Wen-Jeng Pu, Yeong-Shiau Sterneck, Esta Huang, A-Mei TI Transcriptional up-regulation of SOD1 by CEBPD: A potential target for cisplatin resistant human urothelial carcinoma cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE C/EBP transcription factor; Cisplatin drug resistance; Superoxide dismutase; Urothelial carcinoma; SOD inhibitor ID SUPEROXIDE-DISMUTASE GENE; BLADDER-CANCER CELLS; C/EBP-DELTA; RESPONSIVE ELEMENT; TRANSITIONAL CARCINOMA; MULTIPLE TISSUES; MOLECULAR EVENTS; ARSENIC TRIOXIDE; EXPRESSION; MECHANISMS AB Bladder cancer is the fourth most common type of cancer in men (ninth in women) in the United States. Cisplatin is an effective agent against the most common subtype, urothelial carcinoma. However, the development of chemotherapy resistance is a severe clinical problem for the successful treatment of this and other cancers. A better understanding of the cellular and molecular events in response to cisplatin treatment and the development of resistance are critical to impreve the therapeutic options for patients. Here, we report that expression of the CCAAT/enhancer binding protein delta (CEBPD, C/EBP delta, NE-IL6 beta) is induced by cisplatin in the human bladder urothelial carcinoma NTUB1 cell line and is specifically elevated in a cisplatin resistant subline. Expression of CEBPD reduced cisplatin-induced reactive oxygen species (ROS) and apoptosis in NTUB1 cells by inducing the expression of Cu/Zn-superoxide dismutase (SOD1) via direct promoter transactivation. Several reports have implicated CEBPD as a tumor suppressor gene. This study reveals a novel role for CEBPD in conferring drug resistance, suggesting that it can also be pro-oncogenic. Furthermore, our data suggest that SOD inhibitors, which are already used as anti-angiogenic agents, may be suitable for combinatorial chemotherapy to prevent or treat cisplatin resistance in bladder and possibly other cancers. (C) 2010 Elsevier Inc. All rights reserved. C1 [Hour, Tzyh-Chyuan; Lai, Yan-Liang; Kuan, Ching-I; Hu, Huei-Ting; Huang, A-Mei] Kaohsiung Med Univ, Dept Med, Grad Inst Biochem, Kaohsiung 807, Taiwan. [Hour, Tzyh-Chyuan; Huang, A-Mei] Kaohsiung Med Univ, Ctr Excellence Environm Med, Kaohsiung 807, Taiwan. [Chou, Chen-Kung] Chang Gung Univ, Dept Biomed Sci, Tao Yuan, Taiwan. [Wang, Ju-Ming] Natl Cheng Kung Univ, Inst Biosignal Transduct, Tainan 70101, Taiwan. [Tu, Huang-Yao] Kaohsiung Med Univ, Dept Pharm, Coll Pharm, Kaohsiung 807, Taiwan. [Lin, Chang-Shen] Kaohsiung Med Univ, Dept Med, Grad Inst Med, Kaohsiung 807, Taiwan. [Wu, Wen-Jeng] Kaohsiung Med Univ, Dept Urol, Kaohsiung Med Univ Hosp, Kaohsiung 807, Taiwan. [Pu, Yeong-Shiau] Natl Taiwan Univ Hosp, Dept Urol, Taipei, Taiwan. [Sterneck, Esta] NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Huang, AM (reprint author), Kaohsiung Med Univ, Dept Med, Grad Inst Biochem, 100 Shi Chuan 1st Rd, Kaohsiung 807, Taiwan. EM amhuang@kmu.edu.tw RI wang, ju-ming/A-1875-2011; OI PU, YEONG-SHIAU/0000-0002-2859-3966 FU National Science Council, Taipei, Taiwan [NSC95-2320-B-037-048, NSC97-2320-B-037-018-MY3]; Kaohsiung Medical University, Kaohsiung, Taiwan [KMU-Q095018, KMU-Q096009, KMU-M097004, KMU-EM2] FX This work was supported in part by grants from the National Science Council, Taipei, Taiwan (NSC95-2320-B-037-048 and NSC97-2320-B-037-018-MY3) and Kaohsiung Medical University, Kaohsiung, Taiwan (KMU-Q095018, KMU-Q096009, KMU-M097004, and KMU-EM2) to AMH and the Intramural Research Program of the NIH, National Cancer Institute, USA to ES. We thank Dr. Antonio Cuadrado for the SOD1 luciferase reporter constructs. We thank Drs. Lan Chun Tu, Clement Mettling and Yea-Lih Lin for the advice and comments on the article. NR 65 TC 30 Z9 31 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 1 PY 2010 VL 80 IS 3 BP 325 EP 334 DI 10.1016/j.bcp.2010.04.007 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 610DV UT WOS:000278712100005 PM 20385105 ER PT J AU Seibold, SA Singh, BN Zhang, CF Kireeva, M Domecq, C Bouchard, A Nazione, AM Feig, M Cukier, RI Coulombe, B Kashlev, M Hampsey, M Burton, ZF AF Seibold, Steve A. Singh, Badri Nath Zhang, Chunfen Kireeva, Maria Domecq, Celine Bouchard, Annie Nazione, Anthony M. Feig, Michael Cukier, Robert I. Coulombe, Benoit Kashlev, Mikhail Hampsey, Michael Burton, Zachary F. TI Conformational coupling, bridge helix dynamics and active site dehydration in catalysis by RNA polymerase SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Article DE RNA polymerase; Bridge alpha-helix; Trigger loop; Extended fork loop; Induced fit; Molecular dynamics simulation; Fidelity; Hydration/dehydration ID II ELONGATION COMPLEX; STATE KINETIC-ANALYSIS; APO-ADENYLATE KINASE; ESCHERICHIA-COLI; MOLECULAR-DYNAMICS; TRANSCRIPTION ELONGATION; STRUCTURAL BASIS; ALPHA-AMANITIN; TRIGGER LOOP; SACCHAROMYCES-CEREVISIAE AB Molecular dynamics simulation of Thermus thermophilus (Tt) RNA polymerase (RNAP) in a catalytic conformation demonstrates that the active site dNMP-NTP base pair must be substantially dehydrated to support full active site closing and optimum conditions for phosphodiester bond synthesis. In silico mutant beta R428A RNAP, which was designed based on substitutions at the homologous position (Rpb2 R512) of Saccharomyces cerevisiae (Sc) RNAP II, was used as a reference structure to compare to Tt RNAP in simulations. Long range conformational coupling linking a dynamic segment of the bridge alpha-helix, the extended fork loop, the active site, and the trigger loop-trigger helix is apparent and adversely affected in 13 R428A RNAP. Furthermore, bridge helix bending is detected in the catalytic structure, indicating that bridge helix dynamics may regulate phosphodiester bond synthesis as well as translocation. An active site "latch" assembly that includes a key trigger helix residue Tt beta' H1242 and highly conserved active site residues 13 E445 and R557 appears to help regulate active site hydration/dehydration. The potential relevance of these observations in understanding RNAP and DNAP induced fit and fidelity is discussed. (C) 2010 Elsevier B.V. All rights reserved. C1 [Seibold, Steve A.; Zhang, Chunfen; Nazione, Anthony M.; Feig, Michael; Burton, Zachary F.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Seibold, Steve A.; Feig, Michael; Cukier, Robert I.] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. [Singh, Badri Nath; Hampsey, Michael] Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA. [Kireeva, Maria; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. [Domecq, Celine; Bouchard, Annie; Coulombe, Benoit] Inst Rech Clin Montreal, Gene Transcript & Prote Lab, Montreal, PQ H2W 1R7, Canada. RP Burton, ZF (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. EM burton@cns.msu.edu RI Singh, Badri/P-5848-2015 OI Singh, Badri/0000-0002-6100-7092 FU National Institutes of Health [GM57461, GM39484]; National Science Foundation [MCB 0447799]; Michigan State University; Michigan State University Agricultural Experiment Station; Michigan State University College of Osteopathic Medicine; National Science Foundation FX This work was in part supported by the National Institutes of Health grant GM57461 (to Z.F.B.) and GM39484 (to M.H.) and the National Science Foundation MCB 0447799 (to M.F.). Z.F.B. receives support from Michigan State University, the Michigan State University Agricultural Experiment Station, and the Michigan State University College of Osteopathic Medicine. A.M.N. was in part supported by the National Science Foundation Grant sponsored, Michigan State University, Undergraduate Program in Biological Modeling. S.A.S. was supported by the Gene Expression in Development and Disease Initiative, Michigan State University. This project utilized the Michigan State University High Performance Computing Center. The contents of this publication do not necessarily reveal 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. NR 76 TC 16 Z9 17 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD AUG PY 2010 VL 1799 IS 8 BP 575 EP 587 DI 10.1016/j.bbagrm.2010.05.002 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 651MU UT WOS:000281932600007 PM 20478425 ER PT J AU Haughey, NJ Bandaru, VVR Bae, M Mattson, MP AF Haughey, Norman J. Bandaru, Veera V. R. Bae, Mihyun Mattson, Mark P. TI Roles for dysfunctional sphingolipid metabolism in Alzheimer's disease neuropathogenesis SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Alzheimer's disease; Sphingomylein; Ceramide; Sphingosine; Ganglioside; Synapse ID NERVE GROWTH-FACTOR; AMYLOID PRECURSOR PROTEIN; ANTERIOR HYPOTHALAMIC NEURONS; SYNAPTIC VESICLE EXOCYTOSIS; P75 NEUROTROPHIN RECEPTOR; NECROSIS-FACTOR-ALPHA; RAT SENSORY NEURONS; INDUCED CELL-DEATH; LIPID RAFTS; BETA-PEPTIDE AB Sphingolipids in the membranes of neurons play important roles in signal transduction, either by modulating the localization and activation of membrane-associated receptors or by acting as precursors of bioactive lipid mediators. Activation of cytokine and neurotrophic factor receptors coupled to sphingomyelinases results in the generation of ceramides and gangliosides, which in turn, modify the structural and functional plasticity of neurons. In aging and neurodegenerative conditions such as Alzheimer's disease (AD), there are increased membrane-associated oxidative stress and excessive production and accumulation of ceramides. Studies of brain tissue samples from human subjects, and of experimental models of the diseases, suggest that perturbed sphingomyelin metabolism is a pivotal event in the dysfunction and degeneration of neurons that occurs in AD and HIV dementia. Dietary and pharmacological interventions that target sphingolipid metabolism should be pursued for the prevention and treatment of neurodegenerative disorders. (C) 2010 Elsevier B.V. All rights reserved. C1 [Haughey, Norman J.; Bandaru, Veera V. R.; Bae, Mihyun] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Haughey, NJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Meyer 6-109,600 N Wolfe St, Baltimore, MD 21287 USA. EM nhaughe1@jhmi.edu RI Mattson, Mark/F-6038-2012 FU National Institutes of Health [MH077542, AA0174078, AG034849]; National Institute on Aging, NIH FX These studies were supported by National Institutes of Health grants, MH077542, AA0174078 and AG034849 to NJH, and by the Intramural Research Program of the National Institute on Aging, NIH. NR 142 TC 97 Z9 99 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD AUG PY 2010 VL 1801 IS 8 SI SI BP 878 EP 886 DI 10.1016/j.bbalip.2010.05.003 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 620CG UT WOS:000279476000018 PM 20452460 ER PT J AU Hua, X Zhang, H Zhang, H Yang, YN Kuk, AYC AF Hua, Xing Zhang, Han Zhang, Hong Yang, Yaning Kuk, Anthony Y. C. TI Testing multiple gene interactions by the ordered combinatorial partitioning method in case-control studies SO BIOINFORMATICS LA English DT Article ID MULTIFACTOR-DIMENSIONALITY REDUCTION; GENOME-WIDE ASSOCIATION; BREAST-CANCER; ENVIRONMENT INTERACTIONS; DISEASE SUSCEPTIBILITY; CLASSIFICATION TREES; EPISTASIS; POWER; EPIDEMIOLOGY; PROBABILITY AB Motivation: The multifactor-dimensionality reduction (MDR) method has been widely used in multi-locus interaction analysis. It reduces dimensionality by partitioning the multi-locus genotypes into a high-risk group and a low-risk group according to whether the genotype-specific risk ratio exceeds a fixed threshold or not. Alternatively, one can maximize the chi(2) value exhaustively over all possible ways of partitioning the multi-locus genotypes into two groups, and we aim to show that this is computationally feasible. Methods: We advocate finding the optimal MDR (OMDR) that would have resulted from an exhaustive search over all possible ways of partitioning the multi-locus genotypes into two groups. It is shown that this optimal MDR can be obtained efficiently using an ordered combinatorial partitioning (OCP) method, which differs from the existing MDR method in the use of a data-driven rather than fixed threshold. The generalized extreme value distribution (GEVD) theory is applied to find the optimal order of gene combination and assess statistical significance of interactions. Results: The computational complexity of OCP strategy is linear in the number of multi-locus genotypes in contrast with an exponential order for the naive exhaustive search strategy. Simulation studies show that OMDR can be more powerful than MDR with substantial power gain possible when the partitioning of OMDR is different from that of MDR. The analysis results of a breast cancer dataset show that the use of GEVD accelerates the determination of interaction order and reduces the time cost for P-value calculation by more than 10-fold. C1 [Hua, Xing; Zhang, Han; Zhang, Hong; Yang, Yaning] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. [Zhang, Hong] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kuk, Anthony Y. C.] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117546, Singapore. RP Zhang, H (reprint author), Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. EM zhanghan@mail.ustc.edu.cn RI Zhang, Han/K-2118-2016 OI Zhang, Han/0000-0001-7977-9616 FU USTC Innovation Foundation for Graduate Students; National Natural Science Foundation of China FX USTC Innovation Foundation for Graduate Students ( to X. H. and H.Z.); National Natural Science Foundation of China ( to H.Z. and Y.Y.). NR 43 TC 5 Z9 5 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 1 PY 2010 VL 26 IS 15 BP 1871 EP 1878 DI 10.1093/bioinformatics/btq290 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 630HH UT WOS:000280263400009 PM 20538724 ER PT J AU Youn, A Reiss, DJ Stuetzle, W AF Youn, Ahrim Reiss, David J. Stuetzle, Werner TI Learning transcriptional networks from the integration of ChIP-chip and expression data in a non-parametric model SO BIOINFORMATICS LA English DT Article ID YEAST-CELL CYCLE; SACCHAROMYCES-CEREVISIAE; REGULATORY NETWORKS; GENE-EXPRESSION; MODULES; IDENTIFICATION; DISCOVERY; SYSTEMS; GENOME; KINASE AB Results: We have developed LeTICE (Learning Transcriptional networks from the Integration of ChIP-chip and Expression data), an algorithm for learning a transcriptional network from ChIP-chip and expression data. The network is specified by a binary matrix of transcription factor (TF)-gene interactions partitioning genes into modules and a background of genes that are not involved in the transcriptional regulation. We define a likelihood of a network, and then search for the network optimizing the likelihood. We applied LeTICE to the location and expression data from yeast cells grown in rich media to learn the transcriptional network specific to the yeast cell cycle. It found 12 condition-specific TFs and 15 modules each of which is highly represented with functions related to particular phases of cell-cycle regulation. C1 [Youn, Ahrim] NCI, Bethesda, MD 20892 USA. [Reiss, David J.] Univ Washington, Inst Syst Biol, Seattle, WA 98195 USA. [Stuetzle, Werner] Univ Washington, Dept Stat, Seattle, WA 98195 USA. RP Youn, A (reprint author), NCI, Bethesda, MD 20892 USA. EM youna2@mail.nih.gov FU NSF [DMS-9803226] FX NSF grant DMS-9803226. NR 29 TC 10 Z9 12 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 AUG 1 PY 2010 VL 26 IS 15 BP 1879 EP 1886 DI 10.1093/bioinformatics/btq289 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 630HH UT WOS:000280263400010 PM 20525821 ER PT J AU Melis, M Carta, S Fattore, L Tolu, S Yasar, S Goldberg, SR Fratta, W Maskos, U Pistis, M AF Melis, Miriam Carta, Stefano Fattore, Liana Tolu, Stefania Yasar, Sevil Goldberg, Steven R. Fratta, Walter Maskos, Uwe Pistis, Marco TI Peroxisome Proliferator-Activated Receptors-Alpha Modulate Dopamine Cell Activity Through Nicotinic Receptors SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Acetylcholine; dopamine neuron; nicotine; patch-clamp; peroxisome proliferator-activated receptor; ventral tegmental area ID VENTRAL TEGMENTAL AREA; NEURON-FIRING PATTERNS; CENTRAL-NERVOUS-SYSTEM; ACETYLCHOLINE-RECEPTORS; PPAR-ALPHA; RAT-BRAIN; N-ACYLETHANOLAMINE; SUBSTANTIA-NIGRA; KETOGENIC DIET; KINASES AB Background: Modulation of midbrain dopamine neurons by nicotinic acetylcholine receptors (nAChRs) plays an important role in behavior, cognition, motivation, and reward. Specifically, nAChRs containing beta 2 subunits (beta 2-nAChRs) switch dopamine cells from a resting to an excited state. However, how beta 2-nAChRs can be modulated and thereby how dopamine firing activity is affected remains elusive. Because changes in dopamine cell activity are reflected in the dynamics of microcircuits generating altered responses to stimuli and inputs, factors regulating their state are fundamental. Among these, endogenous ligands to the nuclear receptor-transcription factor peroxisome proliferator-activated receptors type-alpha (PPAR alpha) have been recently found to suppress nicotine-induced responses of dopamine neurons. Methods: We used both in vitro and in vivo electrophysiological techniques together with behavioral analysis to investigate on the effects of modulation of PPARa in Sprague Dawley rat and C57BLJ/6 mouse dopamine neurons and their interactions with p2-nAChRs. To this aim, we took advantage of a selective reexpression of beta 2-nAChR exclusively in dopamine cells by stereotaxically injecting a lentiviral vector in the mouse ventral tegmental area. Results: We found that activation of PPAR alpha decreases in vitro both dopamine cell activity and ventral tegmental area net output through negative modulation of beta 2-nAChRs. Additionally, PPARa activation in vivo reduces both the number of spontaneously active dopamine neurons and nicotine-induced increased locomotion. Conclusions: Our combined findings suggest PPARa ligands as important negative modulators of beta 2-nAChRs on dopamine neurons. Thus, PPARa ligands might prove beneficial in treating disorders in which dopamine dysfunction plays a prominent role, such as schizophrenia and nicotine addiction. C1 [Melis, Miriam; Carta, Stefano; Fratta, Walter; Pistis, Marco] Univ Cagliari, Bb Brodie Dept Neurosci, I-09042 Monserrato, CA, Italy. [Fattore, Liana; Fratta, Walter] CNR, Inst Neurosci, Cagliari, Italy. [Tolu, Stefania; Maskos, Uwe] Inst Pasteur, CNRS, Unite Neurobiol Integrat Syst Cholinerg, Paris, France. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. [Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Melis, M (reprint author), Univ Cagliari, Bb Brodie Dept Neurosci, I-09042 Monserrato, CA, Italy. EM myriam@unica.it RI Pistis, Marco/A-3773-2013 OI Pistis, Marco/0000-0002-4622-3205 FU Division of Geriatric Medicine and Gerontology of Johns Hopkins University School of Medicine; National Institute on Drug Abuse, National Institutes of Health FX In loving mempry of Dr. Giuseppe Melis. This study was supported in part by the Division of Geriatric Medicine and Gerontology of Johns Hopkins University School of Medicine and the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. apartment Health and Human Services. UM was supported by the European Commission 7tb framework Programme Neurocypres Project. Agence Nationale de la Recherche Blanc, Agence Nationale de la Recherche Maladies Neurologiques et Psychiatriques 2009. Institut Pasteur, Centre National de la Recherche Scientifique Unitete de Recherche Associee 2182. and Institut National du Cancer BIO-SILC. ST acknowledges support from Fondation pour la Recherche Medicale. NR 55 TC 36 Z9 36 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 2010 VL 68 IS 3 BP 256 EP 264 DI 10.1016/j.biopsych.2010.04.016 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 629NH UT WOS:000280206100007 PM 20570248 ER PT J AU Tedeschi, SK Savani, BN Jagasia, M Engelhardt, B Anasetti, C Barrett, AJ Lee, S AF Tedeschi, Sara K. Savani, Bipin N. Jagasia, Madan Engelhardt, Brian Anasetti, Claudio Barrett, A. John Lee, Stephanie TI Time to Consider HPV Vaccination after Allogeneic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE HPV; Vaccination; Secondary cancer; Squamous cell carcinoma; Transplantation ID HUMAN-PAPILLOMAVIRUS INFECTION; LONG-TERM SURVIVORS; PARTICLE VACCINE; CANCERS; WOMEN; ADOLESCENTS; TYPE-16; IMMUNOGENICITY; RECIPIENTS; RISK AB Squamous cell carcinoma (SCC) is among the most common secondary cancers after allogeneic stem cell transplantation (allo-SCT). Several types of human papillomavirus (HPV) are causally linked with SCC of the genital tract and head and neck, and the incidence of these cancers is higher among immunosuppressed patients compared to immunocompetent patients. In June 2006, a quadrivalent HPV vaccine was approved by the Food and Drug Administration (FDA) for females aged 9 to 26 years to prevent cervical warts and vulvar, vaginal, and cervical cancer. FDA approval was granted in October 2009 for males aged 9 to 26 years to prevent genital warts. The quadrivalent HPV vaccine is now available for off-label use, and may be beneficial to patients after allo-SCT. It is time to evaluate the immunogenicity and efficacy in preventing HPV-related squamous cell carcinoma in this population. Biol Blood Marrow Transplant 16: 1033-1036 (2010) Published by Elsevier Inc. C1 [Tedeschi, Sara K.; Savani, Bipin N.; Jagasia, Madan; Engelhardt, Brian] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect,Dept Med, Long Term Follow Up Transplant Clin,Div Hematol O, Nashville, TN 37232 USA. [Anasetti, Claudio] Univ S Florida, Moffitt Canc Ctr, Dept Blood & Marrow Transplantat, Tampa, FL USA. [Barrett, A. John] NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Lee, Stephanie] Fred Hutchinson Canc Res Ctr, Div Clin Res, Long Term Follow Up Unit, Seattle, WA 98104 USA. RP Savani, BN (reprint author), Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect,Dept Med, Long Term Follow Up Transplant Clin,Div Hematol O, Nashville, TN 37232 USA. EM Bipin.Savani@Vanderbilt.Edu FU Intramural NIH HHS [ZIA HL006105-02, ZIA HL006105-01] NR 24 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1033 EP 1036 DI 10.1016/j.bbmt.2010.03.007 PG 4 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800001 PM 20302962 ER PT J AU Alyea, EP DeAngelo, DJ Moldrem, J Pagel, JM Przepiorka, D Sadelin, M Young, JW Giralt, S Bishop, M Riddell, S AF Alyea, Edwin P. DeAngelo, Daniel J. Moldrem, Jeffrey Pagel, John M. Przepiorka, Donna Sadelin, Michel Young, James W. Giralt, Sergio Bishop, Michael Riddell, Stan TI NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic cell transplantation; Relapse prevention; Acute graft-versus-host disease; Immunotherapy; Resistant leukemia ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; HUMAN T-CELLS; ANTIGEN-PRESENTING CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; REDUCED-INTENSITY TRANSPLANTATION AB Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination, and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance posttransplant, better characterize the T cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify populations at very high risk for relapse to accelerate clinical development and avoid toxicity in patients not at risk for relapse. Biol Blood Marrow Transplant 16: 1037-1069 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Alyea, Edwin P.; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moldrem, Jeffrey; Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pagel, John M.; Riddell, Stan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pagel, John M.; Riddell, Stan] Univ Washington, Seattle, WA 98195 USA. [Przepiorka, Donna] US FDA, Rockville, MD 20857 USA. [Sadelin, Michel; Young, James W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bishop, Michael] NCI, Bethesda, MD 20892 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM edwin_alyea@dfci.harvard.edu FU NCI NIH HHS [P01 CA018029, P01 CA018029-36] NR 280 TC 23 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1037 EP 1069 DI 10.1016/j.bbmt.2010.05.005 PG 33 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800002 PM 20580849 ER PT J AU Pasquini, MC Griffith, LM Arnold, DL Atkins, HL Bowen, JD Chen, JT Freedman, MS Kraft, GH Mancardi, GL Martin, R Muraro, PA Nash, RA Racke, MK Storek, J Saccardi, R AF Pasquini, Marcelo C. Griffith, Linda M. Arnold, Douglas L. Atkins, Harold L. Bowen, James D. Chen, Jacqueline T. Freedman, Mark S. Kraft, George H. Mancardi, Gian Luigi Martin, Roland Muraro, Paolo A. Nash, Richard A. Racke, Michael K. Storek, Jan Saccardi, Riccardo TI Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: Collaboration of the CIBMTR and EBMT to Facilitate International Clinical Studies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic cell transplantation; Autoimmune disease; Autologous hematopoietic cell transplantation; Clinical trial; Multiple sclerosis ID AUTOIMMUNE-DISEASES; OUTCOME MEASURE; FUNCTIONAL COMPOSITE; MULTICENTER TRIAL; INTERFERON-BETA; EUROPEAN GROUP; BRAIN ATROPHY; WORKING PARTY; BLOOD; DISABILITY AB Clinical investigation of autologous hematopoietic stem cell transplantation (HSCT) as therapy for multiple sclerosis (MS) has been ongoing for over a decade. While several phase II studies have been finalized or are in progress, no definitive prospective randomized studies comparing HSCT versus alternative therapies for MS have been completed. In this conference report of North American and European experts who are involved in the care of MS patients, including neurologists and HSCT physicians, and representatives of the Center for International Blood and Marrow Transplant Research (CIBMTR) and European Group for Blood and Marrow Transplantation (EBMT), we ( I) critically review progress to date in HSCT for MS; (2) describe current registry based projects including long-term follow-up studies in HSCT for MS and harmonization of the MS disease-specific research forms that will be used in future by both databases; (3) discuss challenges in study design for a prospective randomized clinical trial of HSCT versus alternative therapy for MS such as feasibility, and the importance of multidisciplinary clinical teams, need for a large sample size and duration of observation required for outcomes assessment; and (4) address future directions in HSCT therapy for MS. To undertake a definitive multicenter clinical trial in autologous HSCT for MS, it will be important to begin well in advance to assemble the team, evaluate proposals for study design, and consider options for the infrastructure and logistical support that will be needed. International collaboration, including partnership with the CIBMTR and EBMT, may be desirable and may in fact be critical for successful completion of a definitive comparative study. Biol Blood Marrow Transplant 16: 1076-1083 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Arnold, Douglas L.; Chen, Jacqueline T.] McGill Univ, Dept Neurol, Montreal, PQ H3A 2T5, Canada. [Atkins, Harold L.] Ottawa Gen Hosp, Blood & Marrow Transplant Program, Ottawa, ON K1H 8L6, Canada. [Bowen, James D.] Swedish Neurosci Inst, Multiple Sclerosis Ctr, Seattle, WA USA. [Chen, Jacqueline T.] Cleveland Clin, Dept Neurosci, Cleveland, OH 44106 USA. [Freedman, Mark S.] Ottawa Gen Hosp, Dept Neurol, Ottawa, ON K1H 8L6, Canada. [Kraft, George H.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Mancardi, Gian Luigi] Univ Genoa, Dept Neurosci Opthalmol & Genet, Genoa, Italy. [Martin, Roland] Univ Med Ctr, Ctr Mol Neurobiol, Inst Neuroimmunol & Clin Multiple Sclerosis Res, Hamburg, Germany. [Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, Dept Neurol, London, England. [Nash, Richard A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Racke, Michael K.] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. [Storek, Jan] Univ Calgary, Dept Med, Calgary, AB, Canada. [Saccardi, Riccardo] Policlin Careggi, Bone Marrow Transplant Unit, UO Ematol, Florence, Italy. RP Griffith, LM (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 6716, Bethesda, MD 20892 USA. EM LGriffith@niaid.nih.gov RI mancardi, giovanni luigi/K-8656-2016 OI Muraro, Paolo/0000-0002-3822-1218; mancardi, giovanni luigi/0000-0001-8427-118X FU Intramural NIH HHS [Z99 AI999999] NR 40 TC 24 Z9 25 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1076 EP 1083 DI 10.1016/j.bbmt.2010.03.012 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800004 PM 20304084 ER PT J AU Le, RQ Bevans, M Savani, BN Mitchell, SA Stringaris, K Koklanaris, E Barrett, AJ AF Le, Robert Quan Bevans, Margaret Savani, Bipin N. Mitchell, Sandra A. Stringaris, Kate Koklanaris, Eleftheria Barrett, A. John TI Favorable Outcomes in Patients Surviving 5 or More Years after Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Leukemia; Hematopoietic stem cell transplantation; Long-term outcome ID BONE-MARROW-TRANSPLANTATION; QUALITY-OF-LIFE; LONG-TERM SURVIVORS; VERSUS-HOST-DISEASE; FUNCTIONAL ASSESSMENT; CHRONIC GVHD; MYELOID-LEUKEMIA; HPV VACCINATION; APLASTIC-ANEMIA; INCREASED RISK AB Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for some hematologic malignancies. As the overall number of survivors continues to increase, studies systematically examining outcomes in long-term survivors are needed. We studied the clinical and quality-of-life outcomes in HSCT recipients surviving 5 or more years from HSCT. Since 1993, 262 patients with hematologic malignancies received a T cell-depleted myeloablative HSCT from an HLA-identical sibling at a single center. Ninety-two survived beyond 5 years from HSCT (median follow-up 9.4 years, range: 5.1-15.3). Median age at transplantation was 35 years (range: 10-56). Twenty-two (24%) received a bone marrow transplant, and 70 (76%) received a peripheral blood HSCT. Of the 92 survivors, 60 completed quality-of-life measures. The main outcomes examined were chronic graft-versus-host-disease, disease relapse, survival, health-related quality-of-life (HRQL) (Functional Assessment of Cancer Therapy-General), physical and mental health (SF-36), and symptom experience (Rotterdam Symptom Checklist). Seventy-five (82%) of 92 survivors no longer required systemic immunosuppressive treatment. Four (4.3%) relapsed with leukemia at a median of 8.5 years (range: 6.2-14.0) after HSCT. Four (4.3%) died between 7.4 and 13.4 years post-HSCT (1 relapse, 1 lung cancer, 1 pneumonia, 1 brain hemorrhage). Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms. Although physical and psychologic symptom distress was low, those with higher symptom distress experienced inferior HRQL. These results show that 5 or more years after T cell-depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL. Biol Blood Marrow Transplant 16: 1162-1170 (2010) Published by Elsevier Inc. C1 [Le, Robert Quan; Savani, Bipin N.; Mitchell, Sandra A.; Stringaris, Kate; Koklanaris, Eleftheria; Barrett, A. John] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Bevans, Margaret; Mitchell, Sandra A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Hematol & Stem Cell Transplantat Sect,Div Hematol, Nashville, TN USA. [Savani, Bipin N.] VAMC, Nashville, TN USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH,Hatfield CRC, Bldg 10,Room 3-5330,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov FU NHLBI; Clinical Center FX This work was supported by the NIH intramural research programs of the NHLBI and the Clinical Center. We also thank Olena Prachenko, MA, at the NTH Clinical Center, for her help with data entry and analysis. NR 45 TC 14 Z9 14 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1162 EP 1170 DI 10.1016/j.bbmt.2010.03.005 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800015 PM 20302959 ER PT J AU Jones, CN Tuleuova, N Lee, JY Ramanculov, E Reddi, AH Zern, MA Revzin, A AF Jones, Caroline N. Tuleuova, Nazgul Lee, Ji Youn Ramanculov, Erlan Reddi, A. Hari Zern, Mark A. Revzin, Alexander TI Cultivating hepatocytes on printed arrays of HGF and BMP7 to characterize protective effects of these growth factors during in vitro alcohol injury SO BIOMATERIALS LA English DT Article DE Protein microarrays; Micropatterned cocultures; Hepatocytes; Growth factor microarrays; Liver injury ID TO-MESENCHYMAL TRANSITION; LIVER FIBROSIS; COMBINATORIAL MICROENVIRONMENTS; CELL-PROLIFERATION; STELLATE CELLS; DNA-SYNTHESIS; STEM-CELLS; APOPTOSIS; MATRIX; RATS AB The goal of the present study was to investigate hepato-protective effects of growth factor (CF) arrays during alcohol injury. Hepatocyte growth factor (HGF) and bone morphogenetic protein (BMP)7 were mixed with collagen (I) and robotically printed onto standard glass slides to create arrays of 500 pm diameter spots. Primary rat hepatocytes were seeded on top of the arrays forming clusters corresponding in size to the underlying protein spots. Cell arrays were then injured in culture by exposure to 100 mm ethanol for 48 h. Hepatocytes residing on CF spots were found to have less apoptosis then cells cultured on collagen-only spots. Least apoptosis (0.3% as estimated by TUNEL assay) was observed on HGF/BMP7/collagen spots whereas most apoptosis (17.3%) was seen on collagen-only arrays. Interestingly, the extent of alcohol-induced apoptosis in hepatocytes varied based on the concentration of printed CF. In addition to preventing apoptosis, printed GFs contributed to maintenance of epithelial phenotype during alcohol injury as evidenced by higher levels of E-cadherin expression in HGF-protected hepatocytes. Importantly, CF microarrays could be used to investigate heterotypic interactions in the context of liver injury. To highlight this, stellate cells - nonparenchymal liver cells involved in fibrosis were added to hepatocytes residing on arrays of either HGF/collagen or collagen-only spots. Exposure of these cocultures to ethanol followed by RT-PCR analysis revealed that stellate cells residing alongside HGF-protected hepatocytes were significantly less activated (less fibrotic) compared to controls. Overall, our results demonstrate that CF microarray format can be used to screen anti-fibrotic and anti-apoptotic effects of growth factors as well as to investigate how signals delivered to a specific cell type modulate heterotypic cellular interactions. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Jones, Caroline N.; Tuleuova, Nazgul; Lee, Ji Youn; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Reddi, A. Hari] Univ Calif Davis, Dept Med, Ctr Tissue Regenerat & Repair, Davis, CA 95616 USA. [Zern, Mark A.] Univ Calif Davis, Dept Med, Transplant Res Inst, Davis, CA 95616 USA. [Tuleuova, Nazgul; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 E Hlth Sci St 2619, Davis, CA 95616 USA. EM arevzin@ucdavis.edu RI Ramanculov, Erlan/E-2823-2013 FU National Center for Biotechnology, Republic of Kazakhstan; NIH [DK073901, EB010131] FX We thank Ms. Dipali Patel for the assistance with primary hepatocyte isolation. We also thank Dr. Jian Wu in the Department of Internal Medicine at UC Davis for helpful discussions and suggestions. NT was supported in part by a fellowship from the National Center for Biotechnology, Republic of Kazakhstan. Financial support for this work was provided by NIH grants (DK073901 and EB010131) awarded to AR. NR 45 TC 22 Z9 25 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD AUG PY 2010 VL 31 IS 23 BP 5936 EP 5944 DI 10.1016/j.biomaterials.2010.04.006 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 623DZ UT WOS:000279719600004 PM 20488537 ER PT J AU Cinelli, MA Morrell, AE Dexheimer, TS Agama, K Agrawal, S Pommier, Y Cushman, M AF Cinelli, Maris A. Morrell, Andrew E. Dexheimer, Thomas S. Agama, Keli Agrawal, Surbhi Pommier, Yves Cushman, Mark TI The structure-activity relationships of A-ring-substituted aromathecin topoisomerase I inhibitors strongly support a camptothecin-like binding mode SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Topoisomerase 1; Aromathecins; Anticancer; Camptothecin-like ID PLANT ANTITUMOR AGENTS; DNA COVALENT COMPLEX; BIOLOGICAL EVALUATION; CLEAVAGE COMPLEXES; NITRATED INDENOISOQUINOLINES; ANTILEUKEMIC ACTIVITY; ORGANIC-SYNTHESIS; ANALOGS; CANCER; CYTOTOXICITY AB Aromathecins are inhibitors of human topoisomerase I (Top1). These compounds are composites of several heteroaromatic systems, namely the camptothecins and indenoisoquinolines, and they possess notable Top1 inhibition and cytotoxicity when substituted at position 14. The SAR of these compounds overlaps with indenoisoquinolines, suggesting that they may intercalate into the Top1-DNA complex similarly. Nonetheless, the proposed binding mode for aromathecins is purely hypothetical, as an X-ray structure is unavailable. In the present communication, we have synthesized eight novel series of A-ring-substituted (positions 1-3) aromathecins, through a simple, modular route, as part of a comprehensive SAR study. Certain groups (such as 2,3-ethylenedioxy) moderately improve Top1 inhibition, and, often, antiproliferative activity, whereas other groups (2,3-dimethoxy and 3-substituents) attenuate bioactivity. Strikingly, these trends are very similar to those previously observed for the A-ring of camptothecins, and this considerable SAR overlap lends further support (in the absence of crystallographic data) to the hypothesis that aromathecins bind in the Top1 cleavage complex as interfacial inhibitors in a 'camptothecin- like' pose. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Cinelli, Maris A.; Morrell, Andrew E.; Cushman, Mark] Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Cinelli, Maris A.; Morrell, Andrew E.; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA. [Dexheimer, Thomas S.; Agama, Keli; Agrawal, Surbhi; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU National Institutes of Health (NIH) [UO1 CA89566]; Lynn and McKeehan; Purdue Research Foundation [203202]; Pfizer Global Research and Development; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; [ST32 CA09634-12] FX This work was facilitated by the National Institutes of Health (NIH) through support with Research Grant UO1 CA89566, Training Grant ST32 CA09634-12, and by the Lynn and McKeehan Fellowships (Purdue University, M.A.C.), and a Purdue Research Foundation Grant (# 203202, M.C. and M.A.C.). This work was also supported in part by an ACS Medicinal Chemistry Pre-doctoral Fellowship sponsored by Pfizer Global Research and Development (A.M.), and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. M.A.C. thanks Drs. Karl Wood, Huaping Mo, and H. Daniel Lee for consultation and valuable discussion and Joe Fornefeld of Midwest Microlab for additional assistance. NR 61 TC 11 Z9 12 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD AUG 1 PY 2010 VL 18 IS 15 BP 5535 EP 5552 DI 10.1016/j.bmc.2010.06.040 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 628JX UT WOS:000280116800010 PM 20630766 ER PT J AU Castle, PE Bulten, J Confortini, M Klinkhamer, P Pellegrini, A Siebers, AG Ronco, G Arbyn, M AF Castle, P. E. Bulten, J. Confortini, M. Klinkhamer, P. Pellegrini, A. Siebers, A. G. Ronco, G. Arbyn, M. TI Age-specific patterns of unsatisfactory results for conventional Pap smears and liquid-based cytology: data from two randomised clinical trials SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Cervical cancer screening; conventional cytology; liquid-based cytology; Pap smear; specimen adequacy ID CERVICAL CYTOLOGY; EUROPEAN GUIDELINES; QUALITY-ASSURANCE; RECOMMENDATIONS; TECHNOLOGIES; PAPANICOLAOU; MANAGEMENT; BETHESDA AB Objective To investigate the rate of unsatisfactory cervical cell samples in liquid-based cytology (LBC) versus conventional cytology (CC) by age. Design Randomised clinical trials. Setting Population-based cervical cancer screening in the Netherlands and Italy. Population Asymptomatic women invited for screening enrolled in two randomised trials: Netherlands ThinPrep (R) versus conventional cytology (NETHCON; 39 010 CC, 46 064 LBC) and New Technologies in Cervical Cancer Screening (NTCC; 22 771 CC, 22 403 LBC). Methods Comparison of categorical variables using Pearson's chi-square test, logistic regression and trend tests. Main outcome measures Proportion of unsatisfactory samples, ratio of LBC versus CC, and variation by 5-year group. Results In NETHCON, a lower percentage of LBC samples were judged to be unsatisfactory compared with CC samples (0.33 versus 1.11%). There was no significant trend in unsatisfactory results by age group for conventional cytology (P(trend) = 0.54), but there was a trend towards an increasing percentage of unsatisfactory results with increasing age for LBC (P(trend) < 0.001). In NTCC, a lower percentage of LBC samples were judged to be unsatisfactory compared with conventional cytology (2.59 versus 4.10%). There was a decrease in the unsatisfactory results by age group with conventional cytology (P(trend) < 0.001) and with LBC (P(trend) = 0.01), although the latter trend arose from the 55-60-years age group (P(trend) = 0.62 when excluding this group). Conclusions The clinical trial in which the results were collected and the cytologic method used were the most important determinants of unsatisfactory cytology. In all situations, the proportion of unsatisfactory samples was lower in LBC compared with CC. The effects of age depended on the criteria used to define unsatisfactory results. C1 [Arbyn, M.] Sci Inst Publ Hlth, Canc Epidemiol Unit, Brussels, Belgium. [Castle, P. E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Bulten, J.; Siebers, A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands. [Confortini, M.] Inst Canc Study & Prevent ISPO, Florence, Italy. [Klinkhamer, P.] PAMM Labs, Pathol Lab, Eindhoven, Netherlands. [Pellegrini, A.] S Giovanni Hosp, Rome, Italy. [Ronco, G.] Ctr Canc Prevent CPO, Canc Epidemiol Unit, Turin, Italy. RP Arbyn, M (reprint author), Sci Inst Publ Hlth, Canc Epidemiol Unit, Brussels, Belgium. EM marc.arbyn@wiv-isp.be RI Siebers, Albert/D-6300-2015; Siebers, Albert/H-6974-2015; Bulten, J./L-4237-2015; OI Siebers, Albert/0000-0002-6085-0678; Siebers, Albert/0000-0002-6085-0678; Siebers, Albert Siebers/0000-0001-5413-9903 FU European Union [SI.2.327046, SPC.2002475]; Italian Ministry of Health [L 138/2004]; Compagnia di S Paolo FIRMS; Regione Piemonte; Regione Toscana; Regione Veneto; Regione Emilia-Romagna; Agenzia di Sanita Pubblica; Regione Lazio; Luxembourg (Grand Duchy of Luxembourg) through the European Network for Cervical Cancer Screening; European Cooperation on Development and Implementation of Cancer Screening and Prevention Guidelines; Dutch Ministry of Health through the National Institute for Public Health and Environment [25141652]; NIH, National Cancer Institute; European Commission (Directorate of SANCO, Luxembourg, Grand-Duchy of Luxembourg), through the ECCG (European Cooperation on development and implementation of Cancer screening and prevention Guidelines, IARC, Lyon, France); Belgian Foundation Against Cancer; Belgian Cancer Centre (Brussels, Belgium); European Commission, DG Research, Brussels, Belgium via the Free University of Amsterdam, the Netherlands FX NTCC was funded by the European Union (Europe against cancer contracts SI.2.327046 and SPC.2002475), Italian Ministry of Health (applied research projects and L 138/2004), Compagnia di S Paolo FIRMS, Regione Piemonte, Regione Toscana, Regione Veneto, Regione Emilia-Romagna, Agenzia di Sanita Pubblica, and Regione Lazio. NETH-CON was funded by grant SPC.2002475 of the European Commission (Directorate General for Health and Consumer), Luxembourg (Grand Duchy of Luxembourg) through the European Network for Cervical Cancer Screening, the European Cooperation on Development and Implementation of Cancer Screening and Prevention Guidelines, and grant 25141652 from the Dutch Ministry of Health through the National Institute for Public Health and Environment.; P Castle was supported by the Intramural Research Program of the NIH, National Cancer Institute. M Arbyn received financial support from the European Commission (Directorate of SANCO, Luxembourg, Grand-Duchy of Luxembourg), through the ECCG (European Cooperation on development and implementation of Cancer screening and prevention Guidelines, IARC, Lyon, France), and the Belgian Foundation Against Cancer and the Belgian Cancer Centre (Brussels, Belgium). M Arbyn and G Ronco are supported by PREHDICT, a research project funded by FP7 (European Commission, DG Research, Brussels, Belgium) via the Free University of Amsterdam, the Netherlands. NR 15 TC 13 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD AUG PY 2010 VL 117 IS 9 BP 1067 EP 1073 DI 10.1111/j.1471-0528.2010.02650.x PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 620WN UT WOS:000279532500005 PM 20604775 ER PT J AU Beydoun, HA Mohan, R Beydoun, MA Davis, J Lance, R Schellhammer, P AF Beydoun, Hind A. Mohan, Ravinder Beydoun, May A. Davis, John Lance, Raymond Schellhammer, Paul TI Development of a scale to assess patient misperceptions about treatment choices for localized prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; diagnosis; treatment; prognosis; patient education; quality of life ID ACTIVE SURVEILLANCE; MEN; INFORMATION; PREFERENCES; KNOWLEDGE; STAGE; LITERACY; SUPPORT; BLACKS; WHITES AB OBJECTIVES To develop a questionnaire to assess a patient's knowledge of his cancer, understanding of treatment choices, and judgement of his survival (KUJ) with and without treatment, as treatment for localized prostate cancer (LPC) can lead to urinary, sexual and bowel side-effects and might not improve survival in 75% of patients. PATIENTS AND METHODS Although > 90% of patients in the USA are diagnosed with LPC, approximate to 94% of them choose treatment, such that newly diagnosed patients need individualized counselling to address misperceptions about the management of LPC. The internal consistency of an 18-item KUJ scale was evaluated among 184 patients recently diagnosed with LPC at a major urology practice. Principal-component analyses were applied for computing a KUJ index. Logistic regression modelling was used to identify predictors of the KUJ index. RESULTS Cronbach's alpha for the KUJ scale was 0.76. Nearly half of the patients provided incorrect answers to most KUJ items. Of the patients, 68% had an income of > US$50 000 and 90% had at least high (or secondary) school literacy level. Quality-of-life measures suggested that most patients were physically, mentally and socially healthy. Higher education, income and functional capacity were associated with worse KUJ. CONCLUSION The KUJ scale is internally consistent and clinicians can use it to identify the educational needs of patients with LPC before treatment selection. Overall, patients who were socioeconomically disadvantaged and those with physical ailments were better informed about the diagnosis, treatment options and prognosis of prostate cancer. C1 [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Mohan, Ravinder] Eastern Virginia Med Sch, Dept Family & Community Med, Norfolk, VA 23501 USA. [Lance, Raymond; Schellhammer, Paul] Eastern Virginia Med Sch, Dept Urol, Norfolk, VA 23501 USA. [Beydoun, May A.] Natl Inst Ageing, Intramural Res Program, Baltimore, MD USA. [Davis, John] Univ Texas Houston, MD Anderson Canc Ctr, Dept Urol Oncol, Houston, TX 77030 USA. RP Beydoun, HA (reprint author), Eastern Virginia Med Sch, Grad Program Publ Hlth, 700 W Olney Rd,POB 1980, Norfolk, VA 23501 USA. EM baydouha@evms.edu FU Norfolk Foundation; US Health Resources Service Administration Department of Health and Human Services; NIH; National Institute on Ageing FX Support for this project was provided in part through grants from the Norfolk Foundation and the US Health Resources Service Administration Department of Health and Human Services. We would like to thank Brian Main for his help in data management. This research was supported in part by the intramural research program of the NIH, National Institute on Ageing. Conflict of Interest: None declared. NR 30 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD AUG PY 2010 VL 106 IS 3 BP 334 EP 341 DI 10.1111/j.1464-410X.2010.09209.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 625MC UT WOS:000279898400007 PM 20151969 ER PT J AU Dolan, D Troncoso, J Resnick, SM Crain, BJ Zonderman, AB O'Brien, RJ AF Dolan, David Troncoso, Juan Resnick, Susan M. Crain, Barbara J. Zonderman, Alan B. O'Brien, Richard J. TI Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing SO BRAIN LA English DT Article DE Alzheimer's disease; pathology; ageing; natural history; neurodegenerative mechanisms ID NEUROPATHOLOGY; POPULATION; CONSORTIUM; DIAGNOSIS; MEMORY AB Recent studies suggest that dementia in the most elderly (90 years of age and above) is only modestly related to Alzheimer's disease pathology. This raises the possibility that other, as yet unknown, disease processes may underlie dementia in this rapidly growing demographic group, and that efforts designed to combat Alzheimer's disease may not be appropriate for treating dementia in very elderly subjects. To study this question more closely, we examined the relationship between neocortical Alzheimer-type brain pathology and dementia in consecutive autopsies from 209 participants in the Baltimore Longitudinal Study of Ageing, a prospective longitudinal cohort study of the effect of ageing on cognition. Almost half of the cohort was older than 90 years of age at death. We found that several measures of neocortical Alzheimer's pathology, including the Consortium to Establish a Registry of Alzheimer's Disease neuritic plaque score and the Braak neurofibrillary tangle score, remained significant predictors of dementia, independent of age. In participants older than 90 years of age, intracranial atherosclerosis emerged as an important predictor of dementia in subjects with low Alzheimer's pathology scores, but did not mitigate the importance or population attributable risk of high Alzheimer's pathology scores on the odds of dementia. There was evidence that the threshold score for neurofibrillary pathology to cause dementia increased in the oldest subjects, but this was offset by an overall increase in neurofibrillary pathology in this age group. We conclude that neocortical Alzheimer's disease pathology remains significantly correlated with dementia, independent of age. In the most elderly, atherosclerosis also emerged as a cause of dementia in subjects with low Alzheimer's pathology scores. We found no evidence for a significant number of elderly subjects having dementia without an apparent cause. C1 [Dolan, David; O'Brien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA. [Troncoso, Juan; Crain, Barbara J.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21224 USA. [Resnick, Susan M.; Zonderman, Alan B.] NIA, Intramural Res Program, Lab Personal & Cognit, NIH, Baltimore, MD 21227 USA. [O'Brien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Med, Baltimore, MD 21224 USA. RP O'Brien, RJ (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, Mason F Lord Ctr Tower,Suite 5100,5200 Eastern Av, Baltimore, MD 21224 USA. EM robrien@jhmi.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Ageing [P50 AG05146]; Burroughs Wellcome Fund for Translational Research [1005227]; National Institute on Ageing, National Institutes of Health FX National Institute on Ageing (grant P50 AG05146); The Burroughs Wellcome Fund (grant #1005227) for Translational Research; The Intramural Research Program, National Institute on Ageing, National Institutes of Health. NR 24 TC 45 Z9 47 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2010 VL 133 BP 2225 EP 2231 DI 10.1093/brain/awq141 PN 8 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 639NY UT WOS:000280982700008 PM 20647264 ER PT J AU Wu, T Wang, LA Hallett, M Li, KC Chan, P AF Wu, Tao Wang, Liang Hallett, Mark Li, Kuncheng Chan, Piu TI Neural correlates of bimanual anti-phase and in-phase movements in Parkinson's disease SO BRAIN LA English DT Article DE Parkinson's disease; bimanual movements; fMRI; brain activity; effective connectivity ID SUPPLEMENTARY MOTOR AREA; TRANSCRANIAL MAGNETIC STIMULATION; EXTERNALLY TRIGGERED MOVEMENTS; SEQUENTIAL FINGER MOVEMENTS; CEREBRAL-BLOOD-FLOW; BASAL GANGLIA; FUNCTIONAL MRI; EFFECTIVE CONNECTIVITY; HAND MOVEMENTS; BRAIN-AREAS AB Patients with Parkinson's disease have great difficulty in performing bimanual movements; this problem is more obvious when they perform bimanual anti-phase movements. The underlying mechanism of this problem remains unclear. In the current study, we used functional magnetic resonance imaging to study the bimanual coordination associated changes of brain activity and inter-regional interactions in Parkinson's disease. Subjects were asked to perform right-handed, bimanual in-phase and bimanual anti-phase movements. After practice, normal subjects performed all tasks correctly. Patients with Parkinson's disease performed in-phase movements correctly. However, some patients still made infrequent errors during anti-phase movements; they tended to revert to in-phase movement. Functional magnetic resonance imaging results showed that the supplementary motor area was more activated during anti-phase movement than in-phase movement in controls, but not in patients. In performing anti-phase movements, patients with Parkinson's disease showed less activity in the basal ganglia and supplementary motor area, and had more activation in the primary motor cortex, premotor cortex, inferior frontal gyrus, precuneus and cerebellum compared with normal subjects. The basal ganglia and dorsolateral prefrontal cortex were less connected with the supplementary motor area, whereas the primary motor cortex, parietal cortex, precuneus and cerebellum were more strongly connected with the supplementary motor area in patients with Parkinson's disease than in controls. Our findings suggest that dysfunction of the supplementary motor area and basal ganglia, abnormal interactions of brain networks and disrupted attentional networks are probably important reasons contributing to the difficulty of the patients in performing bimanual anti-phase movements. The patients require more brain activity and stronger connectivity in some brain regions to compensate for dysfunction of the supplementary motor area and basal ganglia in order to perform bimanual movements correctly. C1 [Wu, Tao; Chan, Piu] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr,Dept Neurobiol, Key Lab Neurodegenerat Disorders,Minist Educ, Beijing 100053, Peoples R China. [Wang, Liang; Li, Kuncheng] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 208921428, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, T (reprint author), Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr,Dept Neurobiol, Key Lab Neurodegenerat Disorders,Minist Educ, 45 Changchun St, Beijing 100053, Peoples R China. EM wutao69@gmail.com RI Wang, Liang/E-8652-2011 FU National Science Foundation of China [30870693]; Ministry of Science and Technology [2006AA02A408]; National Institute of Neurological Disorders and Stroke, National Institutes of Health FX The National Science Foundation of China (30870693); Ministry of Science and Technology (2006AA02A408); Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (to M. H.). NR 89 TC 70 Z9 70 U1 2 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2010 VL 133 BP 2394 EP 2409 DI 10.1093/brain/awq151 PN 8 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 639NY UT WOS:000280982700019 PM 20566485 ER PT J AU Berl, MM Duke, ES Mayo, J Rosenberger, LR Moore, EN VanMeter, J Ratner, NB Vaidya, CJ Gaillard, WD AF Berl, Madison M. Duke, Elizabeth S. Mayo, Jessica Rosenberger, Lisa R. Moore, Erin N. VanMeter, John Ratner, Nan Bernstein Vaidya, Chandan J. Gaillard, William Davis TI Functional anatomy of listening and reading comprehension during development SO BRAIN AND LANGUAGE LA English DT Article DE fMRI; Development; Language; Reading; Story comprehension; Lateralization; Supramodal ID BRAIN ACTIVATION PATTERNS; LEFT PREFRONTAL CORTEX; LANGUAGE DOMINANCE; NEURAL-NETWORKS; YOUNG-CHILDREN; FRONTOTEMPORAL INTERACTIONS; SENTENCE COMPREHENSION; SPEECH-PERCEPTION; PARTIAL EPILEPSY; WORKING-MEMORY AB Listening and reading comprehension of paragraph-length material are considered higher-order language skills fundamental to social and academic functioning. Using ecologically relevant language stimuli that were matched for difficulty according to developmental level, we analyze the effects of task, age, neuropsychological skills, and post-task performance on fMRI activation and hemispheric laterality. Areas of supramodal language processing are identified, with the most robust region being left-lateralized activation along the superior temporal sulcus. Functionally, this conjunction has a role in semantic and syntactic processing, leading us to refer to this conjunction as "comprehension cortex." Different from adults, supramodal areas for children include less extensive inferior frontal gyrus but more extensive right cerebellum and right temporal pole. Broader neuroanatomical pathways are recruited for reading, reflecting the more active processing and larger set of cognitive demands needed for reading compared to listening to stories. ROI analyses reveal that reading is a less lateralized language task than listening in inferior frontal and superior temporal areas, which likely reflects the difficulty of the task as children in this study are still developing their reading skills. For listening to stories, temporal activation is stable by age four with no correlations with age, neuropsychological skills or post-task performance. In contrast, frontal activation during listening to stories occurs more often in older children, and frontal activation is positively correlated with better performance on comprehension questions, suggesting that the activation of frontal networks may reflect greater integration and depth of story processing. (C) 2010 Elsevier Inc. All rights reserved. C1 [Berl, Madison M.; Duke, Elizabeth S.; Mayo, Jessica; Rosenberger, Lisa R.; Moore, Erin N.; Vaidya, Chandan J.; Gaillard, William Davis] Childrens Natl Med Ctr, Dept Neurosci, Washington, DC 20010 USA. [Duke, Elizabeth S.; Rosenberger, Lisa R.; Moore, Erin N.; Gaillard, William Davis] NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [VanMeter, John] Georgetown Univ, Ctr Funct & Mol Imaging, Washington, DC USA. [Ratner, Nan Bernstein] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA. [Vaidya, Chandan J.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [VanMeter, John; Gaillard, William Davis] Georgetown Univ, Sch Med, Dept Neurol, Washington, DC USA. RP Gaillard, WD (reprint author), Childrens Natl Med Ctr, Dept Neurosci, 111 Michigan Ave NW, Washington, DC 20010 USA. EM wgaillar@cnmc.org FU NINDS [R01 NS44280]; IDDRC [HD040677-07]; National Center for Research Resources (NCRR), National Institutes of Health (NIH) [M01RR020359]; Partnership for Pediatric Research Epilepsy Foundation; Children's Research Institute Avery Award; NINDS Clinical Epilepsy Section Division of Intramural Research FX This publication was made possible by NINDS R01 NS44280 (WDG), Partnership for Pediatric Research Epilepsy Foundation (MMB); Children's Research Institute Avery Award (MMB), the NINDS Clinical Epilepsy Section Division of Intramural Research, Grant HD040677-07 from the IDDRC, and Grant M01RR020359 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. NR 87 TC 30 Z9 30 U1 8 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD AUG PY 2010 VL 114 IS 2 BP 115 EP 125 DI 10.1016/j.bandl.2010.06.002 PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 639LF UT WOS:000280975600007 PM 20656105 ER PT J AU Lehmann, ML Brachman, RA Listwak, SJ Herkenham, M AF Lehmann, Michael L. Brachman, Rebecca A. Listwak, Samuel J. Herkenham, Miles TI NF-kappa B activity affects learning in aversive tasks: Possible actions via modulation of the stress axis SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE NF-kappa B; Spatial learning and memory; Hypothalamic-pituitary-adrenal axis; Corticosterone; Anxiety; Hippocampus; Barnes maze; Morris water maze ID HIPPOCAMPAL SYNAPTIC PLASTICITY; TRANSCRIPTION FACTOR; SPATIAL MEMORY; MOUSE STRAINS; WATER-MAZE; P50-DEFICIENT MICE; IMMUNE-RESPONSES; KNOCKOUT MICE; BARNES MAZE; P50 SUBUNIT AB The role of altered activity of nuclear factor kappa B (NF-kappa B) in specific aspects of motivated behavior and learning and memory was examined in mice lacking the p50 subunit of the NF-kappa B/rel transcription factor family. Nfkb1-deficient mice are unable to produce p50 and show specific susceptibilities to infections and inflammatory challenges, but the behavioral phenotype of such mice has been largely unexamined, owing in large part to the lack of understanding of the role of NF-kappa B in nervous system function. Here we show that Nfkb1 (p50) knockout mice more rapidly learned to find the hidden platform in the Morris water maze than did wildtype mice. The rise in plasma corticosterone levels after the maze test was greater in p50 knockout than in wildtype mice. In the less stressful Barnes maze, which tests similar kinds of spatial learning, the p50 knockout mice performed similarly to control mice. Adrenalectomy with corticosterone replacement eliminated the differences between p50 knockout and wildtype mice in the water maze. Knockout mice showed increased levels of basal anxiety in the open-field and light/dark box tests, suggesting that their enhanced escape latency in the water maze was due to activation of the stress (hypothalamic-pituitary-adrenal) axis leading to elevated corticosterone production by strongly but not mildly anxiogenic stimuli. The results suggest that, as in the immune system, p50 in the nervous system normally serves to dampen NF-kappa B-mediated intracellular activities, which are manifested physiologically through elevated stress responses to aversive stimuli and behaviorally in the facilitated escape performance in learning tasks. Published by Elsevier Inc. C1 [Lehmann, Michael L.; Brachman, Rebecca A.; Listwak, Samuel J.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA. RP Lehmann, ML (reprint author), NIMH, Funct Neuroanat Sect, NIH, 35 Convent Dr,Bldg 35,Rm 1C911, Bethesda, MD 20892 USA. EM Michael.lehmann@nih.gov OI Brachman, Rebecca/0000-0002-1221-0414; Herkenham, Miles/0000-0003-2228-4238; Lehmann, Michael/0000-0003-4476-8268 FU National Institute of Mental Health FX The work was supported by the Intramural Research Program of the National Institute of Mental Health. We thank Drs. Mu Yang and Jill Silverman for their assistance in the spatial learning tasks utilized in this experiment. NR 47 TC 17 Z9 17 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD AUG PY 2010 VL 24 IS 6 BP 1008 EP 1017 DI 10.1016/j.bbi.2010.04.005 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 627HG UT WOS:000280029500018 PM 20399847 ER PT J AU Gierach, GL Loud, JT Chow, CK Prindiville, SA Eng-Wong, J Soballe, PW Giambartolomei, C Mai, PL Galbo, CE Nichols, K Calzone, KA Vachon, C Gail, MH Greene, MH AF Gierach, Gretchen L. Loud, Jennifer T. Chow, Catherine K. Prindiville, Sheila A. Eng-Wong, Jennifer Soballe, Peter W. Giambartolomei, Claudia Mai, Phuong L. Galbo, Claudia E. Nichols, Kathryn Calzone, Kathleen A. Vachon, Celine Gail, Mitchell H. Greene, Mark H. TI Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Mammographic density; Breast cancer risk; Breast cancer screening; Gene, BRCA1; Gene, BRCA2; Genetic predisposition to disease ID INCREASED GENETIC RISK; PARENCHYMAL PATTERNS; FAMILY-HISTORY; COMPUTERIZED ANALYSIS; FEATURES; CARCINOMA; TISSUE; AGE AB Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institute's Clinical Genetics Branch's Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Center's Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score < 8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score < 1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density. C1 [Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gierach, Gretchen L.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Loud, Jennifer T.; Giambartolomei, Claudia; Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chow, Catherine K.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Prindiville, Sheila A.] NCI, Coordinating Ctr Clin Trials, Off Director, NIH, Bethesda, MD 20892 USA. [Eng-Wong, Jennifer] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Galbo, Claudia E.] Uniformed Serv Univ Hlth Sci, Dept Radiol Sci, Bethesda, MD 20814 USA. [Nichols, Kathryn] WESTAT Corp, Rockville, MD 20850 USA. [Calzone, Kathleen A.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Vachon, Celine] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Galbo, Claudia E.] USN, Natl Med Ctr, Bethesda, MD 20814 USA. RP Gierach, GL (reprint author), 6120 Execut Blvd,Suite 550,Room 5016, Rockville, MD 20892 USA. EM gierachg@mail.nih.gov; loudj@mail.nih.gov; cchow@wrapc.com; prindivs@mail.nih.gov; je95@georgetown.edu; Peter.Soballe@med.navy.mil; clagiamba@yahoo.it; maip@mail.nih.gov; Claudia.galbo@med.navy.mil; kathrynnichols@westat.com; calzonek@mail.nih.gov; vachon.celine@mayo.edu; gailm@mail.nih.gov; greenem@mail.nih.gov RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 FU National Cancer Institute [NO2-CP-11019-50, NO2-CP-65504-50] FX The Breast Imaging Study (NCI Protocol #01-C-009); The Susceptibility to Breast Cancer Study (NCI Protocol #00-C-0079/NNMC Protocol #NNMC.2000.0010). We wish to thank Ruthann Giusti, Christine Mueller, and Paul Han for clinical support; Nicole Dupree, Jason Hu, Beth Mittl, Usha Singh, and Andrea Wilson for their help in data preparation; Pamela Klein for the original design of the NCI/NNMC Susceptibility to Breast Cancer Study; and Fang Fang Wu for the Cumulus density assessments. Special thanks to all our study participants, without whose cooperation this study could not have been done. Financial Support: This project was supported by the Intramural Research Program of the National Cancer Institute, and by contracts NO2-CP-11019-50 and NO2-CP-65504-50 with Westat, Inc. Dr. Gierach was supported by the NCI Cancer Prevention Fellowship Program. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U. S. Government. NR 49 TC 21 Z9 22 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2010 VL 123 IS 1 BP 245 EP 255 DI 10.1007/s10549-010-0749-7 PG 11 WC Oncology SC Oncology GA 627SP UT WOS:000280063200029 PM 20130984 ER PT J AU Huang, L Johnson, KA Mariotto, AB Dignam, JJ Feuer, EJ AF Huang, Lan Johnson, Karen A. Mariotto, Angela B. Dignam, James J. Feuer, Eric J. TI Population-based survival-cure analysis of ER-negative breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Survival; Cure fraction; Breast cancer; ER-; Chemotherapy ID ANNUAL HAZARD RATES; RANDOMIZED-TRIALS; RECURRENCE; CHEMOTHERAPY; THERAPY; MODELS; TIME AB This study investigated the trends over time in age and stage specific population-based survival of estrogen receptor negative (ER-) breast cancer patients by examining the fraction of cured patients and the median survival time for uncured patients. Cause-specific survival data from the Surveillance, Epidemiology, and End Results program for cases diagnosed during 1992-1998 were used in mixed survival cure models to evaluate the cure fraction and the extension in survival for uncured patients. Survival trends were compared with adjuvant chemotherapy data available from an overlapping patterns-of-care study. For stage II N+ disease, the largest increase in cure fraction was 44-60% (P = 0.0257) for women aged a parts per thousand yen70 in contrast to a 7-8% point increase for women aged < 50 or 50-69 (P = 0.056 and 0.038, respectively). For women with stage III disease, the increases in the cure fraction were not statistically significant, although women aged 50-69 had a 10% point increase (P = 0.103). Increases in cure fraction correspond with increases in the use of adjuvant chemotherapy, particularly for the oldest age group. In this article, for the first time, we estimate the cure fraction for ER- patients. We notice that at age a parts per thousand yen70, the accelerated increase in cure fraction from 1992 to 1998 for women with stage II N+ compared with stage III suggests a selective benefit for chemotherapy in the lower stage group. C1 [Huang, Lan] US FDA, CDER OB DBV, Silver Spring, MD 20993 USA. [Johnson, Karen A.] NCI, BGCRG, DCP, Bethesda, MD 20892 USA. [Mariotto, Angela B.; Feuer, Eric J.] NCI, SRAB, DCCPS, Bethesda, MD 20892 USA. [Dignam, James J.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. RP Huang, L (reprint author), US FDA, CDER OB DBV, 10903 New Hampshire Ave,Bldg 21,Rm 3629, Silver Spring, MD 20993 USA. EM lan.huang@fda.hhs.gov FU Susan G. Komen for the Cure Foundation; U.S. National Cancer Institute [NCI-U10-CA-69651, NCI-U10-CA-12027] FX The authors wish to thank the editors, and the referees for comments and suggestions. Work (JJD) was supported in part by a research grant from the Susan G. Komen for the Cure Foundation. The clinical trials data for Fig. 1 generation was obtained under Public Health Service grants NCI-U10-CA-69651 and NCI-U10-CA-12027 from the U.S. National Cancer Institute. NR 15 TC 3 Z9 3 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2010 VL 123 IS 1 BP 257 EP 264 DI 10.1007/s10549-010-0752-z PG 8 WC Oncology SC Oncology GA 627SP UT WOS:000280063200030 PM 20130982 ER PT J AU Mussai, F Campana, D Bhojwani, D Stetler-Stevenson, M Steinberg, SM Wayne, AS Pastan, I AF Mussai, Francis Campana, Dario Bhojwani, Deepa Stetler-Stevenson, Maryalice Steinberg, Seth M. Wayne, Alan S. Pastan, Ira TI Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute lymphoblastic leukaemia; childhood cancer; CD22; immunotoxin; apoptosis ID B-CELL MALIGNANCIES; RFB4(DSFV)-PE38 BL22; HEMATOLOGIC MALIGNANCIES; CHILDHOOD-CANCER; EXOTOXIN-A; RELAPSE; TRIAL; ASSAY; CD22 AB P>Acute lymphoblastic leukaemia (ALL) remains the most frequent cause of cancer-related mortality in paediatrics and outcome is poor for patients who have high-risk ALL or relapse. HA22 (CAT-8015) is an immunotoxin composed of an anti-CD22 variable fragment linked to a 38 kDa truncated protein derived from Pseudomonas exotoxin A. Using a bone marrow mesenchymal cell culture assay to support ALL cell viability, we investigated the in vitro cytotoxicity of HA22 against ALL blasts from newly diagnosed (n = 13) and relapsed patients (n = 22). There was interpatient variability in sensitivity to HA22. Twenty-four of 35 patient samples tested were sensitive (median 50% lethal concentration 3 ng/ml, range 1-80 ng/ml). Blasts from the other 11 patients were not killed by 500 ng/ml HA22. The median 50% lethal concentration was 20 ng/ml for all patients. There was no significant difference in HA22 sensitivity between diagnosis and relapse samples but peripheral blood ALL blasts were more sensitive to HA22 than those from bone marrow (P = 0 center dot 008). Thus, HA22, at concentrations achievable in patients, is highly cytotoxic to B-lineage ALL cells. These results provide a strong rationale for clinical testing of this agent in children with drug-resistant ALL and offers the potential to reduce morbidities of treatment while improving outcome. C1 [Mussai, Francis; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Campana, Dario; Bhojwani, Deepa] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5116, Bethesda, MD 20892 USA. EM waynea@mail.nih.gov; pastani@mail.nih.gov OI Bhojwani, Deepa/0000-0002-7559-7927 FU National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research and was completed in collaboration with MedImmune under a Cooperative Research and Development Agreement. NR 27 TC 41 Z9 42 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 AUG PY 2010 VL 150 IS 3 BP 352 EP 358 DI 10.1111/j.1365-2141.2010.08251.x PG 7 WC Hematology SC Hematology GA 624RE UT WOS:000279836800010 PM 20528877 ER PT J AU Marsh, J Socie, G Tichelli, A Schrezenmeier, H Hochsmann, B Risitano, AM Fuehrer, M Bekassy, AN Korthof, ET Locasciulli, A Ljungman, P Bacigalupo, A Camitta, B Young, NS Passweg, J AF Marsh, Judith Socie, Gerard Tichelli, Andre Schrezenmeier, Hubert Hochsmann, Britta Risitano, Antonio M. Fuehrer, Monika Bekassy, Albert N. Korthof, Elizabeth T. Locasciulli, Anna Ljungman, Per Bacigalupo, Andrea Camitta, Bruce Young, Neal S. Passweg, Jakob CA European Grp Blood Marrow Transpla TI Should irradiated blood products be given routinely to all patients with aplastic anaemia undergoing immunosuppressive therapy with antithymocyte globulin (ATG)? A survey from the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE aplastic anaemia; antithymocyte globulin; antithymocyte globulin; transfusion-associated graft-versus-host disease; irradiated blood products ID VERSUS-HOST-DISEASE; GAMMA-IRRADIATION; TRANSFUSION; ALLOIMMUNIZATION; GUIDELINES C1 [Marsh, Judith] Kings Coll Hosp London, Dept Haematol Med, London, England. [Tichelli, Andre] Univ Basel Hosp, Dept Haematol, CH-4031 Basel, Switzerland. [Socie, Gerard] Hop St Louis, APHP, Paris, France. [Risitano, Antonio M.] Univ Naples Federico II, Dept Biochem & Med Biotechnol, Naples, Italy. [Fuehrer, Monika] Dr von Haunersches Kinderspital, Haematol Oncol BMT, Munich, Germany. [Bekassy, Albert N.] Univ Lund Hosp, Dept Paediat, S-22185 Lund, Sweden. [Korthof, Elizabeth T.] Leiden Univ, Med Ctr, Dept Paediat, Div Haematooncol & Stem Cell Transplantat, Leiden, Netherlands. [Locasciulli, Anna] Osped San Camillo, Rome, Italy. [Ljungman, Per] Karolinska Univ Hosp, Dept Haematol, Stockholm, Sweden. [Bacigalupo, Andrea] Osped San Martino Genova, Div Haematol, Genoa, Italy. [Camitta, Bruce] Med Coll Wisconsin, Dept Pediat, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA. [Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Passweg, Jakob] Univ Hosp Geneva, Div Haematol, Geneva, Switzerland. [Schrezenmeier, Hubert; Hochsmann, Britta] Univ Ulm, Inst Transfus Med, Ulm, Germany. [Schrezenmeier, Hubert; Hochsmann, Britta] Univ Ulm, Inst Clin Transfus Med, Ulm, Germany. [Schrezenmeier, Hubert; Hochsmann, Britta] Univ Ulm, Immunogenet German Red Cross Blood Donor Serv Bad, Ulm, Germany. [Ljungman, Per] Karolinska Inst, Dept Med, Sect Haematol, Stockholm, Sweden. [Camitta, Bruce] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. RP Marsh, J (reprint author), Kings Coll Hosp London, Dept Haematol Med, London, England. EM judith.marsh@kch.nhs.uk FU Intramural NIH HHS [ZIA HL002315-27, Z01 HL002315-26, Z01 HL002315-25] NR 10 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2010 VL 150 IS 3 BP 377 EP 379 DI 10.1111/j.1365-2141.2010.08200.x PG 3 WC Hematology SC Hematology GA 624RE UT WOS:000279836800016 PM 20528874 ER PT J AU Shahzadi, A Riazuddin, SA Ali, S Li, D Khan, SN Husnain, T Akram, J Sieving, PA Hejtmancik, JF Riazuddin, S AF Shahzadi, Amber Riazuddin, S. Amer Ali, Shahbaz Li, David Khan, Shaheen N. Husnain, Tayyab Akram, Javed Sieving, Paul A. Hejtmancik, J. Fielding Riazuddin, Sheikh TI Nonsense mutation in MERTK causes autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RCS RAT; GENE; DYSTROPHY AB Background Retinitis pigmentosa (RP) is one of the most common ophthalmic disorders affecting one in approximately 5000 people worldwide. A nuclear family was recruited from the Punjab province of Pakistan to study the genetic basis of autosomal recessive RP. Methods All affected individuals underwent a thorough ophthalmic examination and the disease was characterised based upon results for fundus photographs and electroretinogram recordings. Genomic DNA was extracted from peripheral leucocytes. Exclusion studies were performed with short tandem repeat (STR) markers flanking reported autosomal recessive RP loci. Haplotypes were constructed and results were statistically evaluated. Results The results of exclusion analyses suggested that family PKRP173 was linked to chromosome 2q harbouring mer tyrosine kinase protooncogene (MERTK), a gene previously associated with autosomal recessive RP. Additional STR markers refined the critical interval and placed it in a 13.4 cM (17 Mb) region flanked by D2S293 proximally and D2S347 distally. Significant logarithm of odds (LOD) scores of 3.2, 3.25 and 3.18 at theta=0 were obtained with markers D2S1896, D2S2269 and D2S160. Sequencing of the coding exons of MERTK identified a mutation, c.718G -> T in exon 4, which results in a premature termination of p.E240X that segregates with the disease phenotype in the family. Conclusion Our results strongly suggest that the nonsense mutation in MERTK, leading to premature termination of the protein, is responsible for RP phenotype in the affected individuals of the Pakistani family. C1 [Shahzadi, Amber; Riazuddin, S. Amer; Ali, Shahbaz; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Li, David; Sieving, Paul A.; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, 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 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 Higher Education Commission and Ministry of Science and Technology Islamabad, Pakistan. NR 13 TC 12 Z9 12 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD AUG PY 2010 VL 94 IS 8 BP 1094 EP 1099 DI 10.1136/bjo.2009.171892 PG 6 WC Ophthalmology SC Ophthalmology GA 634IX UT WOS:000280575400027 PM 20538656 ER PT J AU Zhang, X Maor, Y Wang, JF Kunos, G Groopman, JE AF Zhang, X. Maor, Y. Wang, J. F. Kunos, G. Groopman, J. E. TI Endocannabinoid-like N-arachidonoyl serine is a novel pro-angiogenic mediator SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE endocannabinoids; endothelial cells; angiogenesis; wound healing; G protein-coupled receptor 55; VEGF-C ID CANNABINOID CB1 RECEPTOR; BRAIN CONSTITUENT; REPERFUSION INJURY; VEGF EXPRESSION; CELL-MIGRATION; SITE DISTINCT; GPR55; ANANDAMIDE; 2-ARACHIDONOYLGLYCEROL; ACTIVATION AB BACKGROUND AND PURPOSE N-arachidonoyl serine (ARA-S) is a recently identified endocannabinoid-like lipid with weak affinity for the fully characterized cannabinoid receptors (CB(1) and CB(2)) and the transient receptor potential vanilloid receptor 1 (TRPV-1). ARA-S induces vasodilatation and shows vasoprotective potential via activation of key signalling pathways in endothelial cells. Based on these findings, the effect of ARA-S on endothelial functions was further studied. EXPERIMENTAL APPROACH Primary human dermal microvascular endothelial cells (HMVEC) were used to investigate effects of ARA-S (0-10 mu M) on certain endothelial functions, using cell proliferation, migration and wound repair models in vitro, and angiogenesis assays in vitro and ex vivo. Selective CB receptor antagonists and specific siRNAs were deployed to block individual CB receptors. KEY RESULTS We found that ARA-S stimulated angiogenesis and endothelial wound healing through induction of vascular endothelial growth factor C and its cognate receptor expression in primary HMVEC. Moreover, knock-down of G protein-coupled receptor 55 (GPR55) partly inhibited ARA-S-induced signal transduction and endothelial functions. CONCLUSIONS AND IMPLICATIONS Our results indicate that ARA-S is a pro-angiogenic factor in addition to a vessel dilator. The GPR55 receptor may serve as one target of ARA-S. C1 [Zhang, X.; Maor, Y.; Wang, J. F.; Groopman, J. E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. [Kunos, G.] NIAAA, NIH, Bethesda, MD USA. RP Groopman, JE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, 330 Brookline Ave,RN-325D, Boston, MA 02115 USA. EM jgroopma@bidmc.harvard.edu FU National Institutes of Health [1R01 DA15008-01] FX This work was supported by National Institutes of Health Grants 1R01 DA15008-01. NR 61 TC 35 Z9 35 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 2010 VL 160 IS 7 BP 1583 EP 1594 DI 10.1111/j.1476-5381.2010.00841.x PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 621WM UT WOS:000279616400004 PM 20649563 ER PT J AU Levinson, D Lakoma, MD Petukhova, M Schoenbaum, M Zaslavsky, AM Angermeyer, M Borges, G Bruffaerts, R de Girolamo, G de Graaf, R Gureje, O Haro, JM Hu, CY Karam, AN Kawakami, N Lee, S Lepine, JP Browne, MO Okoliyski, M Posada-Villa, J Sagar, R Viana, MC Williams, DR Kessler, RC AF Levinson, Daphna Lakoma, Matthew D. Petukhova, Maria Schoenbaum, Michael Zaslavsky, Alan M. Angermeyer, Matthias Borges, Guilherme Bruffaerts, Ronny de Girolamo, Giovanni de Graaf, Ron Gureje, Oye Maria Haro, Josep Hu, Chiyi Karam, Aimee N. Kawakami, Norito Lee, Sing Lepine, Jean-Pierre Browne, Mark Oakley Okoliyski, Michail Posada-Villa, Jose Sagar, Rajesh Viana, Maria Carmen Williams, David R. Kessler, Ronald C. TI Associations of serious mental illness with earnings: results from the WHO World Mental Health surveys SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC-DISORDERS; PRIMARY-CARE; DISABILITY; DEPRESSION; PRODUCTIVITY; ORGANIZATION; MANAGEMENT; WORKPLACE; OUTCOMES; PEOPLE AB Background Burden-of-illness data, which are often used in setting healthcare policy-spending priorities, are unavailable for mental disorders in most countries. Aims To examine one central aspect of illness burden, the association of serious mental illness with earnings, in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Method The WMH Surveys were carried out in 10 high-income and 9 low- and middle-income countries. The associations of personal earnings with serious mental illness were estimated. Results Respondents with serious mental illness earned on average a third less than median earnings, with no significant between-country differences (chi(2)(9)=5.5-8.1, P=0.5-0.79). These losses are equivalent to 0.3-0.8% of total national earnings. Reduced earnings among those with earnings and the increased probability of not earning are both important components of these associations: Conclusions These results add to a growing body of evidence that mental disorders have high societal costs. Decisions about healthcare resource allocation should take these costs into consideration. C1 [Petukhova, Maria; Zaslavsky, Alan M.; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Levinson, Daphna] Minist Hlth, Mental Hlth Serv, Jerusalem, Israel. [Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA. [Angermeyer, Matthias] Ctr Publ Mental Hlth, Goesing Am Wagram, Austria. [Borges, Guilherme] Inst Nacl Psiquiatria Ramon de la Fuente, Tlalpan, Mexico. [Bruffaerts, Ronny] Katholieke Univ Leuven, Leuven, Belgium. [de Girolamo, Giovanni] IRCCS Fatebenefratelli, Brescia, Lombardy, Italy. [de Graaf, Ron] Netherlands Inst Mental Hlth & Addict, Utrecht, Netherlands. [Gureje, Oye] Univ Ibadan, Dept Psychiat, Ibadan Oyo, Nigeria. [Maria Haro, Josep] CIBERSAM, Barcelona, Spain. [Hu, Chiyi] Shenzhen Inst Mental Hlth, Shenzhen, Guangdong, Peoples R China. [Karam, Aimee N.] Balamand Univ, Sch Med, Dept Psychiat & Clin Psychol, St George Hosp Univ,Med Ctr, Beirut, Lebanon. [Karam, Aimee N.] Inst Dev Res Advocacy & Appl Care, Beirut, Lebanon. [Kawakami, Norito] Univ Tokyo, Grad Sch Med, Tokyo 1138654, Japan. [Lee, Sing] Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Lepine, Jean-Pierre] Univ Paris Diderot, Hop Lariboisiere Fernand Widal, INSERM, U705, Paris, France. [Browne, Mark Oakley] Univ Tasmania, Sch Med, Discipline Psychiat, Hobart, Tas 7001, Australia. [Okoliyski, Michail] Natl Ctr Publ Hlth Protect, Dept Global Mental Hlth, Sofia, Bulgaria. [Posada-Villa, Jose] OIM COLOMBIA, Asesor Atenc Psicosocial & Salud Mental, Bogota, Colombia. [Sagar, Rajesh] All India Inst Med Sci, New Delhi, India. [Viana, Maria Carmen] Univ Sao Paulo, Sch Med, Inst Psychiat, Sect Psychiat Epidemiol, Sao Paulo, Brazil. [Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu RI Lee, Sing/O-2136-2015; Haro, Josep Maria/D-1423-2011; OI Haro, Josep Maria/0000-0002-3984-277X; Borges, Guilherme/0000-0002-3269-0507; Viana, Maria Carmen/0000-0002-0464-4845 FU Bristol-Myers Squibb; Eli Lilly Company; GlaxoSmithKline; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Pharmaceuticalsc; Pfizer; Sanofi-Aventis; World Health Organization World Mental Health (WMH) Survey Initiative; United States National Institute of Mental Health (NIMH) [R01MH070884]; mental Health Burden Study [HHSN271200700030C]; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; US Public Health Service [R13-MH066849, R01-MH069864, R01 DA016558]; Fogarty International Center [FIRCA R03-TW006481]; Pan American Health Organization (PAHO); Eli Lilly & Company Foundation; Ortho-McNeil Pharmaceutical Inc; Shire; State of Sao Paulo Research Foundation (FAPESP) [03/00204-3]; Ministry of Health of Bulgaria; Shenzhen Bureau of Health; Shenzhen Bureau of Science, Technology, and Information; Ministry of Social Protection; European Commission [QLG5-1999-01042, SANCO 2004123]; Piedmont Region (Italy); Fondo de Investigacion Sanitaria; Institut de Salud Carlos III, Spain [FIS 00/0028, CIBER GB06/0210046, RETICS RD06/0011 REM-TAP]; Ministerio de Ciencia y Tecnologia, Spain [SAF 2000-158-CE]; Departament de Salut, Generalitat de Catalunya, Spain; WHO (India); Ministry of Health; Japan Ministry of Health, Labour and Welfare [H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013]; Lebanese Ministry of Public Health; WHO (Lebanon); Fogarty International; Janssen Cilag; Eli Lilly; Roche; Novartis; National institute of Psychiatry Ramon de la Fuente [INPRFMDIES 4280]; National Council on Science and Technology [CONACyT-G30544-H]; New Zealand Ministry of Health, Alcohol Advisory Council; Health Research Council; WHO (Geneva); WHO (Nigeria); Federal Ministry of Health, Abuja, Nigeria; US NIMH [R01-MH059575]; National Institute of Drug Abuse (NIDA); South African Department of Health; University of Michigan; NIMH [U01-MH60220]; Substance Abuse and Mental Health Services Administration (SAMHSA); Robert Wood Johnson Foundation [044708]; John W. Alden Trust FX R.C.K. has been a consultant for GlaxoSmithKline, Kaiser Permanente, Pfizer, Sanofi-Aventis, Shire Pharmaceuticals and Wyeth-Ayerst; has served on advisory boards for Eli Lilly & Company and Wyeth-Ayerst; and has had research support for his epidemiological studies from Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticalsc, Pfizer and Sanofi-Aventis.; This paper was prepared under the auspices of the World Health Organization World Mental Health (WMH) Survey Initiative. These activities were supported by the United States National Institute of Mental Health (NIMH; R01MH070884), the mental Health Burden Study: Contract number HHSN271200700030C, the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481, the Pan American Health Organization (PAHO), the Eli Lilly & Company Foundation, Ortho-McNeil Pharmaceutical Inc, GlaxoSmithKline, Bristol-Myers Squibb, and Shire. The Sao Paulo Megacity Mental Health Survey is supported by the State of Sao Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204-3. The Epidemiological survey in Bulgaria (EPIBUL) as part of the WMH is supported by the Ministry of Health of Bulgaria in the frame of the National Program for Mental Health 2001-2006. The Chinese WMH Survey Initiative is supported by the Pfizer Foundation. The Shenzhen Mental Health Survey is supported by the Shenzhen Bureau of Health and the Shenzhen Bureau of Science, Technology, and Information. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The ESEMeD project is funded by the European Commission (Contracts QLG5-1999-01042; SANCO 2004123), the Piedmont Region (Italy), Fondo de Investigacion Sanitaria, Institut de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnologia, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER GB06/0210046, RETICS RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. The WMHI was funded by WHO (India) and helped by Dr R Chandrasekaran, JIPMER. The Israel National Health Survey is funded by the Ministry of Health with support from the Israel National Institute for Health Policy and Health Services Research and the National Insurance Institute of Israel. The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The Lebanese National Mental Health Survey (LEBANON) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), Fogarty International, anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from Janssen Cilag, Eli Lilly, GlaxoSmithKline, Roche, and Novartis. The Mexican National Comorbidity Survey (MNCS) is supported by The National institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544-H), with supplemental support from PAHO. Te Rau Hinengaro: The New Zealand Mental Health Survey (NZMHS) is supported by the New Zealand Ministry of Health, Alcohol Advisory Council, and the Health Research Council. The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria), and the Federal Ministry of Health, Abuja, Nigeria. The South Africa Stress and Health Study (SASH) is supported by the US NIMH (R01-MH059575) and National Institute of Drug Abuse (NIDA) with supplemental funding from the South African Department of Health and the University of Michigan.; The US National Comorbidity Survey Replication (NCS-R) is supported by the NIMH (U01-MH60220) with supplemental support from the IDA, the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (Grant 044708) and the John W. Alden Trust. NR 42 TC 45 Z9 45 U1 2 U2 10 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD AUG PY 2010 VL 197 IS 2 BP 114 EP 121 DI 10.1192/bjp.bp.109.073635 PG 8 WC Psychiatry SC Psychiatry GA 638LJ UT WOS:000280896100007 PM 20679263 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Psychopathy, frustration, and reactive aggression: The role of ventromedial prefrontal cortex SO BRITISH JOURNAL OF PSYCHOLOGY LA English DT Article ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; RHESUS-MONKEYS (MACACA-MULATTA)/; CALLOUS-UNEMOTIONAL TRAITS; HUMAN ORBITOFRONTAL CORTEX; RESPONSE REVERSAL; DECISION-MAKING; IMPULSIVE AGGRESSION; FEARFUL EXPRESSIONS; FRONTAL-CORTEX AB Psychopathy is a developmental disorder marked by emotional hyporesponsiveness and an increased risk for instrumental and reactive aggression. The increased risk for reactive aggression is the focus of the current paper. It will be argued that the increased risk for reactive aggression does not relate to an increased sensitivity to threatening stimuli since psychopathy is associated with a reduced sensitivity to threat. Instead, it is argued that the increased risk for reactive aggression relates to an increased risk for frustration; i.e., the emotional state following the performance of an action in the expectation of a particular reward and not receiving this reward. Two impairments seen in psychopathy would increase the risk for frustration and consequent potential reactive aggression; impairments in stimulus-reinforcement learning and reversal learning. It is argued that both are known consequences of impairment in ventromedial prefrontal cortex, one of the regions principally implicated in psychopathy. C1 NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov FU Intramural NIH HHS NR 108 TC 68 Z9 69 U1 14 U2 47 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1269 J9 BRIT J PSYCHOL JI Br. J. Psychol. PD AUG PY 2010 VL 101 BP 383 EP 399 DI 10.1348/000712609X418480 PN 3 PG 17 WC Psychology, Multidisciplinary SC Psychology GA 617WA UT WOS:000279311400001 PM 19321035 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Reactive aggression and functional, not neural, specificity SO BRITISH JOURNAL OF PSYCHOLOGY LA English DT Editorial Material ID VENTROMEDIAL PREFRONTAL CORTEX; EMOTION REGULATION; PSYCHOPATHY; ATTENTION; PREDICT; ADULTS; SYSTEM C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov FU Intramural NIH HHS [ZIA MH002860-09] NR 16 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1269 J9 BRIT J PSYCHOL JI Br. J. Psychol. PD AUG PY 2010 VL 101 BP 407 EP 410 DI 10.1348/000712610X512122 PN 3 PG 4 WC Psychology, Multidisciplinary SC Psychology GA 617WA UT WOS:000279311400003 PM 20594400 ER PT J AU Harlan, LC Zujewski, JA Goodman, MT Stevens, JL AF Harlan, Linda C. Zujewski, Jo Anne Goodman, Marc T. Stevens, Jennifer L. TI Breast Cancer in Men in the United States A Population-Based Study of Diagnosis, Treatment, and Survival SO CANCER LA English DT Article DE breast cancer; men; treatment; diagnosis; survival; hormones; chemotherapy; surgery; radiation ID CARCINOMA IN-SITU; RANDOMIZED-TRIAL; ADJUVANT THERAPY; POSTMENOPAUSAL WOMEN; TAMOXIFEN; MALES AB BACKGROUND: Breast cancer in men is rare, so clinical trials are not practical. Recommendations suggest treating men who are diagnosed with breast cancer using the guidelines for postmenopausal women; however, to date, no population-based studies have evaluated patterns of care. METHODS: To examine characteristics, treatment, and survival among men with newly diagnosed breast cancer, in 2003 and 2004, 512 men were identified from the Surveillance, Epidemiology and End Results Program. Data were reabstracted and therapy was verified through the patients' treating physicians. RESULTS: The majority of men (79%) were diagnosed through discovery of a breast lump or other signs/symptoms. Among men who had invasive disease, 86% underwent mastectomy, 37% received chemotherapy, and 58% received hormone therapy. In multivariate analysis, tumor size (P = .01) and positive lymph node status (P < .0001) were associated positively with the use of chemotherapy, whereas age group (P < .0001) and current unmarried status (P = .01) had negative associations. Among men who had invasive, estrogen receptor (ER)-positive/borderline tumors, the use of tamoxifen or aromatase inhibitors (Als) was associated with age group (P = .05). Among men who had invasive disease, cancer mortality was associated with tumor size (P < .0001). Among men with ER-positive/borderline disease, increased cancer mortality was associated with tumor size (P < .0001), current unmarried status (P = .04), and decreased mortality with tamoxifen (P = .04). CONCLUSIONS: Tumor characteristics and marital status were the primary predictors of therapy and cancer mortality among men with breast cancer. Although Als are not currently recommended, they are commonly prescribed. However, their use did not result in a decrease in cancer mortality. Research must examine the efficacy of Als with and without gonadotropin-releasing hormone analogues. Cancer 2010;116;3558-68. (C) 2010 American Cancer Society. C1 [Harlan, Linda C.] NCI, Appl Res Program, Bethesda, MD 20892 USA. [Zujewski, Jo Anne] NCI, Clin Trials Evaluat Program, Bethesda, MD 20892 USA. [Goodman, Marc T.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Stevens, Jennifer L.] Informat Management Serv Inc, Silver Spring, MD USA. RP Harlan, LC (reprint author), NCI, Appl Res Program, EPN Room 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM lh50w@nih.gov FU [N01-PC-35133]; [N01-PC-35135]; [N01-PC-35141]; [N01-PC-35136]; [N01-PC-35137]; [N01-PC-35138]; [N01-PC-35139]; [N01-PC-35142]; [N01-PC-35143]; [N01-PC-35145]; [N01-PC-54402]; [N01-PC-54403]; [N01-PC-54404]; [N01-PC-54405] FX Supported by grants N01-PC-35133, N01-PC-35135, N01-PC35141, N01-PC-35136, N01-PC-35137, N01-PC-35138, N01-PC-35139, N01-PC-35142, N01-PC-35143, N01-PC-35145, N01-PC-54402, N01-PC-54403, N01-PC-54404, and N01-PC54405. NR 27 TC 14 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2010 VL 116 IS 15 BP 3558 EP 3568 DI 10.1002/cncr.25153 PG 11 WC Oncology SC Oncology GA 629TS UT WOS:000280223200007 PM 20564105 ER PT J AU Dowling, E Yabroff, KR Mariotto, A McNeel, T Zeruto, C Buckman, D AF Dowling, Emily Yabroff, K. Robin Mariotto, Angela McNeel, Timothy Zeruto, Christopher Buckman, Dennis TI Burden of Illness in Adult Survivors of Childhood Cancers Findings From a Population-Based National Sample SO CANCER LA English DT Article DE childhood cancer; survivorship; employment; health limitations; long-term survivors ID LONG-TERM SURVIVORS; QUALITY-OF-LIFE; UNITED-STATES; PROSTATE-CANCER; HEALTH-CARE; SURVEILLANCE; OUTCOMES; EPIDEMIOLOGY; EMPLOYMENT; ADOLESCENT AB BACKGROUND: The number of adult survivors of childhood cancer in the United States is increasing because of effective treatments and improved survival. The purpose of this study was to use a national, population-based sample to estimate the burden of illness in adult survivors of childhood cancer. METHODS: A total of 410 adult survivors of childhood cancer and 294,641 individuals without cancer were identified from multiple years of the National Health Interview Survey. Multiple measures of burden, general health, and lost productivity were compared using multivariate regression analyses including: logistic, polytomous logit, proportional odds, and linear models. RESULTS: Controlling for the effects of age, sex, race/ethnicity, and survey year, adult survivors of childhood cancer reported poorer outcomes across the majority of general health measures and productivity measures than individuals without cancer. Survivors were more likely to report their health status as fair or poor (24.3% vs 10.9%; P < .001); having any health limitation in any way (12.9% vs 3.4%; P < .001); being unable to work because of health problems (20.9% vs 6.3%; P < .001); and being limited in the amount/kind of work because of health problems (30.9% vs 10.6%; P < .001). When categorized by time since diagnosis, cancer survivors had poor health outcomes in every time interval, with the greatest limitations in the initial 4 years after diagnosis and 30 or more years after diagnosis. CONCLUSIONS: Across multiple measures, adult survivors of childhood cancers have poorer health outcomes and more health limitations than similar individuals without cancer. Cancer 2010;116;3712-21. Published 2010 by the American Cancer Society*. C1 [Dowling, Emily; Yabroff, K. Robin] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Mariotto, Angela] NCI, Stat Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [McNeel, Timothy; Zeruto, Christopher; Buckman, Dennis] Informat Management Serv Inc, Silver Spring, MD USA. RP Dowling, E (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, EPN 4005,Execut Blvd, Bethesda, MD 20892 USA. EM dowlinge@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 FU National Cancer Institute FX The National Cancer Institute provided support for this article. NR 42 TC 18 Z9 18 U1 3 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2010 VL 116 IS 15 BP 3712 EP 3721 DI 10.1002/cncr.25141 PG 10 WC Oncology SC Oncology GA 629TS UT WOS:000280223200025 PM 20564096 ER PT J AU Michaud, DS Vrieling, A Jiao, L Mendelsohn, JB Steplowski, E Lynch, SM Wactawski-Wende, J Arslan, AA Bueno-de-Mesquita, HB Fuchs, CS Gross, M Helzlsouer, K Jacobs, EJ LaCroix, A Petersen, G Zheng, W Allen, N Ammundadottir, L Bergmann, MM Boffetta, P Buring, JE Canzian, F Chanock, SJ Clavel-Chapelon, F Clipp, S Freiberg, MS Gaziano, JM Giovannucci, EL Hankinson, S Hartge, P Hoover, RN Hubbell, FA Hunter, DJ Hutchinson, A Jacobs, K Kooperberg, C Kraft, P Manjer, J Navarro, C Peeters, PHM Shu, XO Stevens, V Thomas, G Tjonneland, A Tobias, GS Trichopoulos, D Tumino, R Vineis, P Virtamo, J Wallace, R Wolpin, BM Yu, K Zeleniuch-Jacquotte, A Stolzenberg-Solomon, RZ AF Michaud, Dominique S. Vrieling, Alina Jiao, Li Mendelsohn, Julie B. Steplowski, Emily Lynch, Shannon M. Wactawski-Wende, Jean Arslan, Alan A. Bueno-de-Mesquita, H. Bas Fuchs, Charles S. Gross, Myron Helzlsouer, Kathy Jacobs, Eric J. LaCroix, Andrea Petersen, Gloria Zheng, Wei Allen, Naomi Ammundadottir, Laufey Bergmann, Manuela M. Boffetta, Paolo Buring, Julie E. Canzian, Federico Chanock, Stephen J. Clavel-Chapelon, Francoise Clipp, Sandra Freiberg, Matthew S. Gaziano, J. Michael Giovannucci, Edward L. Hankinson, Susan Hartge, Patricia Hoover, Robert N. Hubbell, F. Allan Hunter, David J. Hutchinson, Amy Jacobs, Kevin Kooperberg, Charles Kraft, Peter Manjer, Jonas Navarro, Carmen Peeters, Petra H. M. Shu, Xiao-Ou Stevens, Victoria Thomas, Gilles Tjonneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Tumino, Rosario Vineis, Paolo Virtamo, Jarmo Wallace, Robert Wolpin, Brian M. Yu, Kai Zeleniuch-Jacquotte, Anne Stolzenberg-Solomon, Rachael Z. TI Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan) SO CANCER CAUSES & CONTROL LA English DT Article DE Alcohol; Pancreatic cancer; Pooled analysis ID BASE-LINE CHARACTERISTICS; GENOME-WIDE ASSOCIATION; LIFE-STYLE FACTORS; WOMENS HEALTH; UNITED-STATES; COFFEE CONSUMPTION; RISK; TOBACCO; DESIGN; SUSCEPTIBILITY AB The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. > 0 to < 5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out. C1 [Michaud, Dominique S.; Peeters, Petra H. M.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Michaud, Dominique S.; Giovannucci, Edward L.; Hankinson, Susan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Vrieling, Alina; Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Jiao, Li; Mendelsohn, Julie B.; Ammundadottir, Laufey; Chanock, Stephen J.; Hartge, Patricia; Hoover, Robert N.; Hutchinson, Amy; Jacobs, Kevin; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Lynch, Shannon M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU Canc Inst, New York, NY USA. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan; Hunter, David J.; Wolpin, Brian M.] Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Jacobs, Eric J.; Stevens, Victoria] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [LaCroix, Andrea; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Allen, Naomi] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Ammundadottir, Laufey; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Bethesda, MD 20892 USA. [Bergmann, Manuela M.] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. [Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, Villejuif, France. [Clavel-Chapelon, Francoise] INSERM, Villejuif, France. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Johns Hopkins Bloomberg Sch Publ Hlth, Hagerstown, MD USA. [Freiberg, Matthew S.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hubbell, F. Allan] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Tumino, Rosario] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. [Tumino, Rosario] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy. [Tumino, Rosario] Civile MP Arezzo Hosp, Dept Histopathol, Ragusa, Italy. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wallace, Robert] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Wallace, Robert] Univ Iowa, Dept Internal Med, Coll Publ Hlth, Iowa City, IA 52242 USA. [Wallace, Robert] Univ Iowa, Coll Med, Dept Epidemiol, Iowa City, IA 52242 USA. [Wallace, Robert] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. RP Michaud, DS (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. EM d.michaud@imperial.ac.uk RI Clavel-Chapelon, Francoise/G-6733-2014; Michaud, Dominique/I-5231-2014; Vrieling, Alina/A-2725-2016; Tobias, Geoffrey/M-4135-2016; OI Tobias, Geoffrey/0000-0002-2878-8253; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI NIH HHS [P01 CA087969, P01 CA087969-12, R01 CA082729, R01 CA124908, R37 CA070867] NR 41 TC 42 Z9 44 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1213 EP 1225 DI 10.1007/s10552-010-9548-z PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400007 PM 20373013 ER PT J AU Han, YY Dinse, GE Umbach, DM Davis, DL Weissfeld, JL AF Han, Yueh-Ying Dinse, Gregg E. Umbach, David M. Davis, Devra L. Weissfeld, Joel L. TI Age-period-cohort analysis of cancers not related to tobacco, screening, or HIV: sex and race differences SO CANCER CAUSES & CONTROL LA English DT Article DE Age-period-cohort model; Cancer incidence, Cancer mortality; Cancer trends; Tobacco; Screening; HIV; SEER; Occupational cancer; Environmental cancer ID SPECIAL SECTION; UNITED-STATES; LUNG-CANCER; NATION; TRENDS AB To identify trends in a residual category of cancers not typically associated with tobacco, screening, or human immunodeficiency virus (HIV) infection. For persons aged 20-84, we used sex- and race-specific age-period-cohort (APC) models to describe temporal patterns of incidence (1975-2004) and mortality (1970-2004) in the U.S. for a residual cancer category that excluded non-Hodgkin lymphoma, Kaposi sarcoma, and cancer of the oral cavity and pharynx, esophagus, pancreas, larynx, lung and bronchus, urinary bladder, kidney and renal pelvis, colon and rectum, prostate, female breast, and cervix uteri. Age-specific incidence rose (0.1-0.9% per year, on average) in every sex-race group, with factors related to both time period and birth cohort membership appearing to accelerate the increases in women. Age-specific mortality fell (0.6-0.9% per year, on average) for black and white men and women, with the declines decelerating in white women but accelerating in the other sex-race groups. Extrapolations of APC models predicted higher age-adjusted incidence rates in white women (11%), black women (5%), and white men (4%) in 2005-2009, relative to 2000-2004, and lower rates in black men (-3%), accompanied by lower age-adjusted mortality rates in every sex-race group (-8% in black men, -3% in black women, -1% in white men, and -1% in white women). The possibility that increased incidence in women over time reflects changes in underlying risks, diagnostic practices, or better case ascertainment should be actively explored. Declining mortality may signify improvements in cancer care. C1 [Weissfeld, Joel L.] UPMC Canc Pavil, Pittsburgh, PA 15232 USA. [Han, Yueh-Ying; Weissfeld, Joel L.] Univ Pittsburgh, Inst Canc, Dept Epidemiol, Pittsburgh, PA 15232 USA. [Dinse, Gregg E.; Umbach, David M.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Davis, Devra L.] Environm Hlth Trust, Mt Sinai Med Ctr, New York, NY USA. RP Weissfeld, JL (reprint author), UPMC Canc Pavil, 4th Floor PLCO,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM weissfeldjl@upmc.edu FU Center for Environmental Oncology of the University of Pittsburgh Cancer Institute; NIH, National Institute of Environmental Health Sciences FX This research was supported in part by the Center for Environmental Oncology of the University of Pittsburgh Cancer Institute and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The authors appreciate the helpful comments provided by Dr. Walter Rogan and Dr. Grace Kissling. NR 23 TC 1 Z9 1 U1 2 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1227 EP 1236 DI 10.1007/s10552-010-9550-5 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400008 PM 20373012 ER PT J AU Flood, A Strayer, L Schairer, C Schatzkin, A AF Flood, Andrew Strayer, Lori Schairer, Catherine Schatzkin, Arthur TI Diabetes and risk of incident colorectal cancer in a prospective cohort of women SO CANCER CAUSES & CONTROL LA English DT Article DE Colorectal cancer; Diabetes; Insulin; Cohort study; Time-dependent variable ID INSULIN-RESISTANCE; METABOLIC SYNDROME; BLOOD-GLUCOSE; COLON-CANCER; MELLITUS; MEN; HEALTH; TYPE-2; HYPERINSULINEMIA; MORTALITY AB To determine whether accounting for the time dynamics of diabetes exposure will change the risk estimates for colorectal cancer. We analyzed data from the 45, 516 women enrolled in the BCDDP follow-up cohort study. We used proportional hazards regression to obtain multivariable-adjusted risk estimates for incident colorectal cancer for prevalent diabetes at baseline and diabetes as a time-dependent variable. Subjects with diabetes had a statistically significant increased risk of colorectal cancer compared to subjects without diabetes (RR = 1.60, 95% CI 1.18-2.18). When we defined exposure as duration of diabetes exposure at cohort exit, we found that in the first 4 years after diagnosis risk was essentially the same as in those never having had a diagnosis of diabetes. For those who had been diagnosed between 4 and 8 years previously, however, we observed a RR of 2.36 (95% CI 0.96-5.79), while longer duration of exposure was associated with smaller and then no change in risk compared to those without a diagnosis of diabetes. These results are consistent with the theory that hyperinsulinemia can explain, at least in part, the association of diabetes with colorectal cancer, but in a time-dependent manner. C1 [Flood, Andrew; Strayer, Lori] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Flood, Andrew] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55454 USA. [Schairer, Catherine; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Flood, A (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM aflood009@umn.edu FU National Institutes of Health [K07 CA108910-01A1]; National Cancer Institute, Bethesda, MD FX Funding for this work was provided by National Institutes of Health (K07 CA108910-01A1 to A. F.) and Intramural Research Program funds from the National Cancer Institute, Bethesda, MD. NR 32 TC 31 Z9 36 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1277 EP 1284 DI 10.1007/s10552-010-9555-0 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400013 PM 20383575 ER PT J AU Jiao, L de Gonzalez, AB Hartge, P Pfeiffer, RM Park, Y Freedman, DM Gail, MH Alavanja, MCR Albanes, D Freeman, LEB Chow, WH Huang, WY Hayes, RB Hoppin, JA Ji, BT Leitzmann, MF Linet, MS Meinhold, CL Schairer, C Schatzkin, A Virtamo, J Weinstein, SJ Zheng, W Stolzenberg-Solomon, RZ AF Jiao, Li de Gonzalez, Amy Berrington Hartge, Patricia Pfeiffer, Ruth M. Park, Yikyung Freedman, D. Michal Gail, Mitchell H. Alavanja, Michael C. R. Albanes, Demetrius Freeman, Laura E. Beane Chow, Wong-Ho Huang, Wen-Yi Hayes, Richard B. Hoppin, Jane A. Ji, Bu-tian Leitzmann, Michael F. Linet, Martha S. Meinhold, Cari L. Schairer, Catherine Schatzkin, Arthur Virtamo, Jarmo Weinstein, Stephanie J. Zheng, Wei Stolzenberg-Solomon, Rachael Z. TI Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts SO CANCER CAUSES & CONTROL LA English DT Article DE Pancreatic cancer; Body mass index; Pooled analysis; Prospective cohort; Effect modification ID FRANCISCO BAY AREA; PHYSICAL-ACTIVITY; MALE SMOKERS; WOMENS HEALTH; UNITED-STATES; US COHORT; OBESITY; METAANALYSIS; MORTALITY; HEIGHT AB To investigate whether the positive association of body mass index (BMI, kg/m(2)) with risk of pancreatic cancer is modified by age, sex, smoking status, physical activity, and history of diabetes. In a pooled analysis of primary data of seven prospective cohorts including 458,070 men and 485,689 women, we identified 2,454 patients with incident pancreatic cancer during an average 6.9 years of follow-up. Cox proportional hazard regression models were used in data analysis. In a random-effects meta-analysis, for every 5 kg/m(2) increment in BMI, the summary relative risk (RR) was 1.06 (95% confidence interval (CI) 0.99-1.13) for men and 1.12 (95% CI 1.05-1.19) for women. The aggregate analysis showed that compared with normal weight (BMI: 18.5 to < 25), the adjusted RR was 1.13 (95% CI 1.03-1.23) for overweight (BMI: 25 to < 30) and 1.19 (95% CI 1.05-1.35) for obesity class I (BMI: 30 to < 35). Tests of interactions of BMI effects by other risk factors were not statistically significant. Every 5 kg/m(2) increment in BMI was associated with an increased risk of pancreatic cancer among never and former smokers, but not among current smokers (P-interaction = 0.08). The present evidence suggests that a high BMI is an independent risk factor of pancreatic cancer. C1 [Jiao, Li] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Zheng, Wei] Vanderbilt Univ, Med Ctr, Div Epidemiol, Nashville, TN USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Jiao, Li; de Gonzalez, Amy Berrington; Hartge, Patricia; Pfeiffer, Ruth M.; Park, Yikyung; Freedman, D. Michal; Gail, Mitchell H.; Alavanja, Michael C. R.; Albanes, Demetrius; Freeman, Laura E. Beane; Chow, Wong-Ho; Huang, Wen-Yi; Hayes, Richard B.; Ji, Bu-tian; Linet, Martha S.; Meinhold, Cari L.; Schairer, Catherine; Schatzkin, Arthur; Weinstein, Stephanie J.; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Leitzmann, Michael F.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany. RP Jiao, L (reprint author), Baylor Coll Med, Dept Med, 2002 Holcombe Blvd,Box 152, Houston, TX 77030 USA. EM jiao@bcm.edu RI Pfeiffer, Ruth /F-4748-2011; Albanes, Demetrius/B-9749-2015; Beane Freeman, Laura/C-4468-2015; Kitahara, Cari/R-8267-2016; OI Beane Freeman, Laura/0000-0003-1294-4124; Park, Yikyung/0000-0002-6281-489X FU National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institute of Environment Health Sciences, Epidemiology Branch, National Institutes of Health FX The funding source of this pooled analysis is the Intramural Research Program of the National Cancer Institute, Division of Cancer Epidemiology and Genetics; and National Institute of Environment Health Sciences, Epidemiology Branch, National Institutes of Health. NR 54 TC 44 Z9 45 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1305 EP 1314 DI 10.1007/s10552-010-9558-x PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400016 PM 20383573 ER PT J AU Koshiol, J Kreimer, AR AF Koshiol, Jill Kreimer, Aimee R. TI Lessons from Australia: Human Papillomavirus Is Not a Major Risk Factor for Esophageal Squamous Cell Carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; CERVICAL-CARCINOMA; PCR CONTAMINATION; FALSE POSITIVES; GENITAL LESIONS; CANCER; HEAD; NECK; INFECTION; SURVIVAL C1 [Koshiol, Jill; Kreimer, Aimee R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Koshiol, J (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7070, Rockville, MD 20852 USA. EM koshiolj@mail.nih.gov RI Kreimer, Aimee/H-1687-2015 FU Intramural NIH HHS [Z99 CA999999] NR 54 TC 9 Z9 9 U1 0 U2 0 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 AUG PY 2010 VL 19 IS 8 BP 1889 EP 1892 DI 10.1158/1055-9965.EPI-10-0506 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 635RY UT WOS:000280675000001 PM 20696658 ER PT J AU Qubaiah, O Devesa, SS Platz, CE Huycke, MM Dores, GM AF Qubaiah, Osama Devesa, Susan S. Platz, Charles E. Huycke, Mark M. Dores, Graca M. TI Small Intestinal Cancer: a Population-Based Study of Incidence and Survival Patterns in the United States, 1992 to 2006 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; SMALL-BOWEL CANCER; B-CELL LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; CARCINOID-TUMORS; GASTROINTESTINAL-TRACT; NEUROENDOCRINE TUMORS; EPIDEMIOLOGY; ENGLAND; TRENDS AB Background: The etiology of cancers of the small intestine is largely unknown. To gain insight into these rare malignancies, we evaluated contemporaneous incidence and survival patterns. Methods: Using small intestine cancer data from 12 population-based registries of the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted and age-specific incidence rates (IRs), IR ratios, and relative survival (RS) rates. Results: In total, 10,945 small intestine cancers (IR = 2.10/100,000 person-years) were diagnosed during 1992 to 2006, including carcinomas (n = 3,412; IR = 0.66), neuroendocrine cancers (n = 4,315; IR = 0.83), sarcomas (n = 1,084; IR = 0.20), and lymphomas (n = 2,023, IR = 0.38). For all histologic groups, males had significantly higher IRs than females, and distinct age-specific gender patterns were limited to intermediate-/high-grade lymphomas. Neuroendocrine cancer rates varied significantly by race, with rates highest among blacks and lowest among Asians/Pacific Islanders. Carcinoma IRs were highest among blacks; sarcoma IRs were highest among Asians/Pacific Islanders; and lymphoma IRs were highest among whites. Age-specific IR patterns were similar across racial/ethnic groups. During 1992 to 2006, duodenal cancer IRs increased more markedly than those for other subsites. RS varied little by gender or race. Neuroendocrine cancers had the most favorable RS, and carcinomas had the least favorable. The greatest improvement in 5-year RS from 1992 to 1998 to 1999 to 2005 was observed for sarcomas and lymphomas. Conclusions: Distinct small intestine cancer IR patterns according to histologic subtype suggest different underlying etiologies and/or disease biology, with susceptibility varying by gender, racial/ethnic groups, and subsite. Temporal patterns support a possible role for diagnostic bias of duodenal cancers. Impact: Future epidemiologic studies of small intestine cancer should consider histologic subtype by gender, race/ethnicity, and subsite. Cancer Epidemiol Biomarkers Prev; 19(8); 1908-18. (C) 2010 AACR. C1 [Qubaiah, Osama; Huycke, Mark M.; Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv 111, Oklahoma City, OK 73104 USA. [Qubaiah, Osama; Huycke, Mark M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Devesa, Susan S.; Dores, Graca M.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Platz, Charles E.] Univ Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA. RP Qubaiah, O (reprint author), Dept Vet Affairs Med Ctr, Med Serv 111, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM osama-qubaiah@ouhsc.edu FU Department of Veterans Affairs Medical Center in Oklahoma City, OK; National Cancer Institute, NIH, Department of Health and Human Services in Bethesda, MD FX Department of Veterans Affairs Medical Center in Oklahoma City, OK and the Intramural Research Program of the National Cancer Institute, NIH, Department of Health and Human Services in Bethesda, MD. NR 43 TC 23 Z9 24 U1 0 U2 0 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 AUG PY 2010 VL 19 IS 8 BP 1908 EP 1918 DI 10.1158/1055-9965.EPI-10-0328 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 635RY UT WOS:000280675000003 PM 20647399 ER PT J AU Kemp, TJ Hildesheim, A Garcia-Pineres, A Williams, MC Shearer, GM Rodriguez, AC Schiffman, M Burk, R Freer, E Bonilla, J Herrero, R Pinto, LA AF Kemp, Troy J. Hildesheim, Allan Garcia-Pineres, Alfonso Williams, Marcus C. Shearer, Gene M. Rodriguez, Ana Cecilia Schiffman, Mark Burk, Robert Freer, Enrique Bonilla, Jose Herrero, Rolando Pinto, Ligia A. TI Elevated Systemic Levels of Inflammatory Cytokines in Older Women with Persistent Cervical Human Papillomavirus Infection SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NORMAL CYTOLOGY; HPV INFECTION; HEPATITIS-C; COSTA-RICA; PREVALENCE; NEOPLASIA; CANCER; DETERMINANTS; GUANACASTE; WORLDWIDE AB Background: Defects in lymphoproliferative responses to mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus (HPV) infection have been reported. Methods: To determine whether these defects were associated with altered cytokine profiles, plasma and peripheral blood mononuclear cell (PBMC) culture supernatants from 50 cases (oversampled for their reduced lymphoproliferative ability) and 50 uninfected controls (oversampled for their robust lymphoproliferative ability) were examined for 24 cytokines using multiplexed bead-based immunoassays and ELISA. Results: The following plasma cytokines were significantly increased in cases relative to controls (cases versus controls; median pg/mL): interleukin (IL)-6, 393.1 versus 14.5; IL-8, 1,128.5 versus 43.9; tumor necrosis factor-alpha (TNF-alpha), 164.1 versus 9.2; macrophage inflammatory protein-1 alpha (MIP-1 alpha), 1,368.9 versus 25.5; granulocyte macrophage colony-stimulating factor (GM-CSF), 13.8 versus 7.3; IL-1 beta, 8.3 versus 1.6 (all P < 0.0001); and IL-1 alpha, 218.2 versus 169.5 (P = 0.02). We focused our analysis on the cytokines IL-6, IL-8, TNF-alpha, and MIP-1 alpha due to their high fold change (>10) and highly statistically significant difference between cases and controls. Length of persistence or type of infection (high risk and low risk) did not affect these differences. IL-6, TNF-alpha, and MIP-1 alpha levels were also increased in unstimulated PBMC culture supernatants from cases compared with controls (P < 0.05), however, the cytokine levels from phytohemagglutinin-stimulated PBMC culture supernatants were significantly lower in the cases (P < 0.0001). Conclusions: Persistent HPV infection in older women with evidence of immune deficit is associated with an increase in systemic inflammatory cytokines. Impact: Future studies are needed to determine whether the inflammatory profile is age dependent and to examine the role that inflammatory cytokines play in HPV-induced progression from infection to cervical cancer. Cancer Epidemiol Biomarkers Prev; 19(8); 1954-9. (C) 2010 AACR. C1 [Kemp, Troy J.; Garcia-Pineres, Alfonso; Williams, Marcus C.; Pinto, Ligia A.] NCI, HPV Immunol Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Hildesheim, Allan; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Shearer, Gene M.] NCI, Expt Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Freer, Enrique; Bonilla, Jose] Univ Costa Rica, Ctr Invest Estruct Microscop, San Jose, Costa Rica. [Freer, Enrique; Bonilla, Jose] Univ Costa Rica, Ctr Invest Biol Celular & Mol, San Jose, Costa Rica. [Burk, Robert] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Pinto, LA (reprint author), NCI, HPV Immunol Lab, Sci Applicat Int Corp Frederick Inc, Bldg 469,Room 205, Frederick, MD 21702 USA. EM pintol@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Cancer Institute, NIH [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under contract no. 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. NR 23 TC 22 Z9 22 U1 1 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 AUG PY 2010 VL 19 IS 8 BP 1954 EP 1959 DI 10.1158/1055-9965.EPI-10-0184 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 635RY UT WOS:000280675000008 PM 20647411 ER PT J AU Cook, MB Dawsey, SM Diaw, L Blaser, MJ Perez-Perez, GI Abnet, CC Taylor, PR Albanes, D Virtamo, J Kamangar, F AF Cook, Michael B. Dawsey, Sanford M. Diaw, Lena Blaser, Martin J. Perez-Perez, Guillermo I. Abnet, Christian C. Taylor, Philip R. Albanes, Demetrius Virtamo, Jarmo Kamangar, Farin TI Serum Pepsinogens and Helicobacter pylori in Relation to the Risk of Esophageal Squamous Cell Carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHRONIC ATROPHIC GASTRITIS; INTESTINAL METAPLASIA; PERNICIOUS-ANEMIA; TRACT CANCERS; REFLUX; INFECTION; ASSOCIATION; POPULATION; HISTOLOGY; STOMACH AB Background: Helicobacter pylori can induce gastric atrophy in humans, which in turn increases gastric cancer risk. Whether H. pylori and gastric atrophy also affect the risk of esophageal squamous cell carcinoma (ESCC), however, remains unresolved. Methods: We performed a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to assess these relationships. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study is composed of 29,133 Finnish male smokers, ages 50 to 69 years, who were recruited during 1985-1988. Using baseline sera, we assessed H. pylori status (via immunoglobulin G antibodies against whole-cell and CagA antigens) and gastric atrophy status [via the biomarkers pepsinogen I (PGI) and pepsinogen II (PGII)] in 79 ESCC cases and 94 controls. Logistic regression with adjustment for age, date of blood draw, education, cigarette smoking, alcohol, body mass index, and fruit and vegetable intake was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Results: Gastric atrophy (PGI/PGII <4) was associated with ESCC (OR, 4.58; 95% CI, 2.00-10.48). There was no evidence for an association between H. pylori and ESCC (OR, 0.94; 95% CI, 0.40-2.24). Conclusions: These results could be explained by misclassification of H. pylori status due to serologic amnesia, ESCC risk being dependent on the functional consequences or interactions of H. pylori rather than the infection per se, gastric atrophy having a different histogenesis in ESCC without being primarily dependent on H. pylori acquisition, or a lack of statistical power to detect an effect. Impact: Validation of these results may warrant mechanistic studies to determine the route of association between gastric atrophy and ESCC. Cancer Epidemiol Biomarkers Prev; 19(8); 1966-75. (C) 2010 AACR. C1 [Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Diaw, Lena] NHLBI, Pulm & Vasc Med Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Blaser, Martin J.; Perez-Perez, Guillermo I.] NYU, Sch Med, Dept Med, New York, NY USA. [Blaser, Martin J.; Perez-Perez, Guillermo I.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Suite 550,Room 5030, Rockville, MD 20852 USA. EM michael.cook@nih.gov RI Cook, Michael/A-5641-2009; Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015 OI Perez Perez, Guillermo /0000-0002-0131-5798; Cook, Michael/0000-0002-0533-7302; Abnet, Christian/0000-0002-3008-7843 FU NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 60 TC 12 Z9 12 U1 0 U2 3 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 AUG PY 2010 VL 19 IS 8 BP 1966 EP 1975 DI 10.1158/1055-9965.EPI-10-0270 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 635RY UT WOS:000280675000010 PM 20647397 ER PT J AU Mahabir, S Forman, MR Dong, YQ Park, Y Hollenbeck, A Schatzkin, A AF Mahabir, Somdat Forman, Michele R. Dong, Young Q. Park, Yikyung Hollenbeck, Albert Schatzkin, Arthur TI Mineral Intake and Lung Cancer Risk in the NIH-American Association of Retired Persons Diet and Health Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DNA-REPAIR CAPACITY; PREVENTION TRIAL; OXIDATIVE STRESS; PROSTATE-CANCER; MAGNESIUM; COHORT; SELENIUM; CALCIUM; DISEASE; WOMEN AB Background: Using data from a case-control study, we previously reported that low dietary intakes of magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), but not selenium (Se) and calcium (Ca), were associated with increased lung cancer risk. Due to dietary recall bias in case-control studies, our objective was to assess whether these findings hold in a prospective cohort study. Methods: We analyzed data from the NIH-American Association of Retired Persons Diet and Health study of 482,875 subjects (288,257 men and 194,618 women) who were cancer-free and completed a food frequency questionnaire at enrollment between 1995 and 2003. Cox proportional hazards models were computed to estimate the relative risk adjusted for potential confounders. Results: During a mean follow-up of 7 years, 7,052 lung cancer cases were identified. For all subjects, we observed no significant associations between total (diet + supplement) Ca, Mg, Fe, Cu, Se, and Zn intakes and lung cancer risk. Total Ca intake was protective (P trend < 0.05) for current smokers and subjects with adenocarcinomas. Total Mg intake increased risk (P trend < 0.05) in men and current smokers. Total Fe intake was inversely associated with risk in women (P trend < 0.01). For dietary minerals, Mg increased risk (P trend < 0.05) in all subjects, among men and current smokers. Increased dietary Ca intake reduced risk in women (P trend = 0.05). Dietary Fe decreased risk in all subjects and among women (P trend < 0.05). Mineral intake from supplements did not affect lung cancer risk. Conclusions: Dietary minerals are risk factors for lung cancer. Impact: Dietary mineral consumption may influence lung cancer risk, but the associations differ by type of mineral and population subgroups. Cancer Epidemiol Biomarkers Prev; 19(8); 1976-83. (C) 2010 AACR. C1 [Mahabir, Somdat] NCI, Modifiable Risk Factors Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Forman, Michele R.; Dong, Young Q.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Hollenbeck, Albert] Amer Assoc Retired Persons, Washington, DC USA. RP Mahabir, S (reprint author), NCI, Modifiable Risk Factors Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 5138, Bethesda, MD 20892 USA. EM mahabir@mail.nih.gov OI Park, Yikyung/0000-0002-6281-489X FU National Cancer Institute, NIH FX Intramural Research Program at the National Cancer Institute, NIH. NR 24 TC 15 Z9 16 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 AUG PY 2010 VL 19 IS 8 BP 1976 EP 1983 DI 10.1158/1055-9965.EPI-10-0067 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 635RY UT WOS:000280675000011 PM 20696660 ER PT J AU Gaudet, MM Yang, HP Bosquet, JG Healey, CS Ahmed, S Dunning, AM Easton, DF Spurdle, AB Ferguson, K O'Mara, T Lambrechts, D Despierre, E Vergote, I Amant, F Lacey, JV Lissowska, J Peplonska, B Brinton, LA Chanock, S Garcia-Closas, M AF Gaudet, Mia M. Yang, Hannah P. Bosquet, Jesus Gonzalez Healey, Catherine S. Ahmed, Shahana Dunning, Alison M. Easton, Doug F. Spurdle, Amanda B. Ferguson, Kaltin O'Mara, Tracy Lambrechts, Diether Despierre, Evelyn Vergote, Ignace Amant, Frederic Lacey, James V., Jr. Lissowska, Jola Peplonska, Beata Brinton, Louise A. Chanock, Stephen Garcia-Closas, Montserrat TI No Association between FTO or HHEX and Endometrial Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENETIC-VARIATION; SUSCEPTIBILITY; VARIANTS AB Introduction: Obesity and diabetes are known risk factors for endometrial cancer; thus, the genetic risk factors of these phenotypes might also be associated with endometrial cancer risk. To evaluate this hypothesis, we genotyped tag-single nucleotide polymorphisms (SNP) and candidate SNPs in FTO and HHEX in a primary set of 417 endometrial cancer cases and 406 population-based controls, and validated significant findings in a replication set of approximately 2,347 cases and 3,140 controls from three additional studies. Methods: We genotyped 189 tagSNPs in FTO (including rs8050136) and five tagSNPs in HHEX (including rs1111875) in the primary set and one SNP each in FTO (rs12927155) and HHEX (rs1111875) in the validation set. Per allele odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the genotypes of each SNPs (as an ordinal variable) and endometrial cancer risk using unconditional logistic regression models, controlling for age and site. Results: In the primary study, the most significant finding in FTO was rs12927155 (OR, 1.56; 95% CI, 1.21-2.01; P = 5.8 x 10(-4)), and in HHEX, it was rs1111875 (OR, 0.80; 95% CI, 0.66-0.97; P = 0.026). In the validation studies, the pooled per allele OR, adjusted for age and study for FTO, was rs12927155 (OR, 0.94; 95% CI, 0.83-1.06; P = 0.29), whereas for HHEX, it was rs1111875 (OR, 1.00; 95% CI, 0.92-1.10; P = 0.96). Conclusion: Our data indicate that common genetic variants in two genes previously related to obesity (FTO) and diabetes (HHEX) by genome-wide association scans were not associated with endometrial cancer risk. Impact: Polymorphisms in FTO and HHEX are unlikely to have large effects on endometrial cancer risk but may have weaker effects. Cancer Epidemiol Biomarkers Prev; 19(8); 2106-9. (C) 2010 AACR. C1 [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Obstet & Gynecol, Bronx, NY 10461 USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Womens Hlth, Bronx, NY 10461 USA. [Yang, Hannah P.; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bosquet, Jesus Gonzalez] Moffitt Canc & Res Ctr, Dept Womens Oncol, Tampa, FL USA. [Healey, Catherine S.; Ahmed, Shahana; Dunning, Alison M.; Easton, Doug F.] Univ Cambridge, Cambridge, England. [Spurdle, Amanda B.; Ferguson, Kaltin; O'Mara, Tracy] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Spurdle, Amanda B.; Ferguson, Kaltin; O'Mara, Tracy] Queensland Inst Med Res, Australian Natl Endometrial Canc Study, Brisbane, Qld 4006, Australia. [O'Mara, Tracy; Lambrechts, Diether] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Despierre, Evelyn; Vergote, Ignace; Amant, Frederic] VIB, Vesalius Res Ctr, Louvain, Belgium. [Lacey, James V., Jr.] Katholieke Univ Leuven, UZ Gasthuisberg, Dept Gynaecol Oncol, Louvain, Belgium. [Lissowska, Jola] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Peplonska, Beata] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Peplonska, Beata] Inst Oncol, Warsaw, Poland. [Chanock, Stephen] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. NCI, Core Genotype Facil, Adv Technol Ctr, Bethesda, MD 20892 USA. RP Gaudet, MM (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Room 1303E,Belfer Bldg,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM mia.gaudet@einstein.yu.edu RI Peplonska, Beata/F-6004-2010; Verdrengh, Evelien/H-4571-2012; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; O'Mara, Tracy/M-7508-2016; Spurdle, Amanda/A-4978-2011; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; O'Mara, Tracy/0000-0002-5436-3232; Spurdle, Amanda/0000-0003-1337-7897; Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166 FU Cancer Research UK [10118, 10124, 11021, C1287/A10118, C1287/A7497, C20/A3084, C490/A11021, C8197/A10123, C8197/A10865]; Intramural NIH HHS [ZIA CP010126-14] NR 8 TC 10 Z9 10 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 AUG PY 2010 VL 19 IS 8 BP 2106 EP 2109 DI 10.1158/1055-9965.EPI-10-0515 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 635RY UT WOS:000280675000025 PM 20647405 ER PT J AU Masuelli, L Marzocchella, L Focaccetti, C Lista, F Nardi, A Scardino, A Mattei, M Turriziani, M Modesti, M Forni, G Schlom, J Modesti, A Bei, R AF Masuelli, Laura Marzocchella, Laura Focaccetti, Chiara Lista, Florigio Nardi, Alessandra Scardino, Antonio Mattei, Maurizio Turriziani, Mario Modesti, Mauro Forni, Guido Schlom, Jeffrey Modesti, Andrea Bei, Roberto TI Local delivery of recombinant vaccinia virus encoding for neu counteracts growth of mammary tumors more efficiently than systemic delivery in neu transgenic mice SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Cancer vaccine; Intratumoral vaccination; Recombinant vaccinia virus; Serum antibodies ID DIVERSIFIED SUBCUTANEOUS/INTRATUMORAL VACCINATION; MULTIPLE COSTIMULATORY MOLECULES; CARCINOEMBRYONIC ANTIGEN CEA; PHASE-I TRIAL; INTRATUMORAL VACCINATION; IMMUNE-RESPONSES; BREAST-CANCER; POXVIRUS VACCINES; DNA VACCINATION; ERBB RECEPTORS AB Recombinant vaccinia virus has been widely employed as a cancer vaccine in several clinical trials. In this study we explored, employing BALB/c mice transgenic for the rat neu oncogene, the ability of the recombinant vaccinia virus neu (rV-neuT) vaccine to inhibit growth of neu+ mammary carcinomas and whether the efficacy of vaccination was dependent on: (a) carcinogenesis stage at which the vaccination was initiated; (b) number of vaccinations and (c) route of delivery (systemic vs. local). BALB-neuT mice were vaccinated one, two and three times by subcutaneous (s.c.) and intramammary gland (im.g.) injection with rV-neuT or V-wt (wild-type vaccinia virus) starting at the stage in which mouse mammary gland displays atypical hyperplasia, carcinoma in situ or invasive carcinoma. We demonstrated that vaccination using rV-neuT was more effective when started at an earlier stage of mammary carcinogenesis and after three vaccinations. The im.g. vaccination was more effective than the s.c. vaccination in inhibiting mammary carcinogenesis, eliciting anti-Neu antibodies, increasing anti-Neu IgG2a/G3 isotypes and inducing antibodies able to trigger mammary tumor cells apoptosis and antibody-dependent cellular cytotoxicity. The better protective ability of rV-neuT im.g. vaccination was associated with its capacity to induce a superior degree of in vivo mammary cancer cells apoptosis. Our research suggests that intratumoral vaccination using recombinant vaccinia virus could be employed to increase the activity of a genetic cancer vaccine. This study may have important implications for the design of cancer vaccine protocols for the treatment of breast cancer and of accessible tumors using recombinant vaccinia virus. C1 [Marzocchella, Laura; Modesti, Andrea; Bei, Roberto] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy. [Masuelli, Laura; Scardino, Antonio] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. [Focaccetti, Chiara; Mattei, Maurizio] Univ Roma Tor Vergata, Dept Biol, STA, I-00133 Rome, Italy. [Lista, Florigio] Ctr Studi & Ric Sanita & Vet Esercito, Rome, Italy. [Nardi, Alessandra] Univ Roma Tor Vergata, Dept Math, I-00133 Rome, Italy. [Turriziani, Mario] Univ Roma Tor Vergata, Dept Internal Med, I-00133 Rome, Italy. [Modesti, Mauro] Univ Roma La Sapienza, Dept Surg, Rome, Italy. [Forni, Guido] Univ Turin, Dept Clin & Biol Sci, Orbassano, Italy. [Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bei, R (reprint author), Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Via Montpellier 1, I-00133 Rome, Italy. EM bei@med.uniroma2.it FU PRIN; AIRC FX This study was supported by grants from PRIN and AIRC. We wish to thank Therion Biologics (Cambridge, MA) and Dr. G. Mazzara, which kindly provided vaccinia viruses, IRBM P. Angeletti (Pomezia, Rome) for peptides, and Dr. Eddi Di Marco (Istituto Tumori di Genova) for providing LTR-Neu cells. The authors thank Debra Weingarten for her editorial assistance in the preparation of the manuscript. NR 52 TC 19 Z9 19 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD AUG PY 2010 VL 59 IS 8 BP 1247 EP 1258 DI 10.1007/s00262-010-0850-0 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA 602AU UT WOS:000278111300011 PM 20364378 ER PT J AU Lund, JL Harlan, LC Yabroff, KR Warren, JL AF Lund, Jennifer L. Harlan, Linda C. Yabroff, K. Robin Warren, Joan L. TI Should Cause of Death From the Death Certificate Be Used to Examine Cancer-Specific Survival? A Study of Patients With Distant Stage Disease SO CANCER INVESTIGATION LA English DT Article DE Cancer survival; Cause of death; Mortality; SEER program; Cancer; Death certificate ID LOCALIZED PROSTATE-CANCER; MORTALITY; ACCURACY; MEN; POPULATION; THERAPY; RATES; TIME AB Death certificates are used to classify cause of death for studies of cancer survival and mortality. Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, we evaluated cause of death (site-specific, cancer cause-specific, or other cause of death) for 229,181 patients with distant stage disease during 1994-2003 who died by 2005. Agreement between coded cause of death and initial diagnosis was 85% in patients with only one primary and 64% in patients with more than one primary. Our findings support the usefulness of site and cancer cause-specific causes of death reported on the death certificate for distant stage patients with a single cancer. C1 [Lund, Jennifer L.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Lund, Jennifer L.; Harlan, Linda C.; Yabroff, K. Robin; Warren, Joan L.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Lund, JL (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, McGavran Greenberg Hall,CB 7435, Chapel Hill, NC 27599 USA. EM jlund@email.unc.edu RI Lund, Jennifer/G-9420-2012; OI Yabroff, K. Robin/0000-0003-0644-5572 FU NIDDK NIH HHS [T32 DK007634, T32 DK007634-09] NR 20 TC 21 Z9 21 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD AUG PY 2010 VL 28 IS 7 BP 758 EP 764 DI 10.3109/07357901003630959 PG 7 WC Oncology SC Oncology GA 634ME UT WOS:000280585300010 PM 20504221 ER PT J AU Yan, HH Pickup, M Pang, YL Gorska, AE Li, ZY Chytil, A Geng, YP Gray, JW Moses, HL Yang, L AF Yan, Hannah H. Pickup, Michael Pang, Yanli Gorska, Agnieszka E. Li, Zhaoyang Chytil, Anna Geng, Yipeng Gray, Jerome W. Moses, Harold L. Yang, Li TI Gr-1+CD11b+ Myeloid Cells Tip the Balance of Immune Protection to Tumor Promotion in the Premetastatic Lung SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER METASTASIS; LYMPHOID-TISSUE IBALT; SUPPRESSOR-CELLS; MAMMARY CARCINOMAS; T-CELLS; BONE; INFLAMMATION; ANGIOGENESIS; RECRUITMENT AB The mechanisms by which a primary tumor affects a selected distant organ before tumor cell arrival remain to be elucidated. This report shows that Gr-1+CD11b+ cells are significantly increased in lungs of mice bearing mammary adenocarcinomas before tumor cell arrival. In the premetastatic lungs, these immature myeloid cells significantly decrease IFN-gamma production and increase proinflammatory cytokines. In addition, they produce large quantities of matrix metalloproteinase 9 (MMP9) and promote vascular remodeling. Deletion of MMP9 normalizes aberrant vasculature in the premetastatic lung and diminishes lung metastasis. The production and activity of MMP9 is selectively restricted to lungs and organs with a large number of Gr-1+CD11b+ cells. Our work reveals a novel protumor mechanism for Gr-1+CD11b+ cells that changes the premetastatic lung into an inflammatory and proliferative environment, diminishes immune protection, and promotes metastasis through aberrant vasculature formation. Thus, inhibition of Gr-1+CD11b+ cells could normalize the premetastatic lung environment, improve host immunosurveillance, and inhibit tumor metastasis. Cancer Res; 70(15); 6139-49. (C) 2010 AACR. C1 [Yan, Hannah H.; Pang, Yanli; Li, Zhaoyang; Yang, Li] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA. [Pickup, Michael; Gorska, Agnieszka E.; Chytil, Anna; Geng, Yipeng; Moses, Harold L.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. [Geng, Yipeng; Gray, Jerome W.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. [Pickup, Michael; Gorska, Agnieszka E.; Chytil, Anna; Moses, Harold L.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 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 FU NIH, NCI, Center for Cancer Research [CA085492, CA102162, U54 CA126505]; Vanderbilt-IngramCancer Center [CA068485] FX Intramural Research Program of the NIH, NCI, Center for Cancer Research (L. Yang); and grants CA085492, CA102162, and U54 CA126505 (H. Moses). The Vanderbilt-IngramCancer Center cores are supported by grant number CA068485. NR 51 TC 117 Z9 120 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2010 VL 70 IS 15 BP 6139 EP 6149 DI 10.1158/0008-5472.CAN-10-0706 PG 11 WC Oncology SC Oncology GA 634CQ UT WOS:000280557500004 PM 20631080 ER PT J AU Shrimali, RK Yu, ZY Theoret, MR Chinnasamy, D Restifo, NP Rosenberg, SA AF Shrimali, Rajeev K. Yu, Zhiya Theoret, Marc R. Chinnasamy, Dhanalakshmi Restifo, Nicholas P. Rosenberg, Steven A. TI Antiangiogenic Agents Can Increase Lymphocyte Infiltration into Tumor and Enhance the Effectiveness of Adoptive Immunotherapy of Cancer SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANTI-VEGF THERAPY; T-CELLS; DENDRITIC CELLS; IN-VIVO; ANGIOGENESIS; BEVACIZUMAB; REGRESSION; EFFICACY; NORMALIZATION AB Adoptive cell transfer (ACT)-based immunotherapies can mediate objective cancer regression in animal models and in up to 70% of patients with metastatic melanoma; however, it remains unclear whether the tumor vasculature impedes the egress of tumor-specific T cells, thus hindering this immunotherapy. Disruption of the proangiogenic interaction of vascular endothelial growth factor (VEGF) with its receptor (VEGFR-2) has been reported to "normalize" tumor vasculature, enhancing the efficacy of chemotherapeutic agents by increasing their delivery to the tumor intersitium. We thus sought to determine whether disrupting VEGF/VEGFR-2 signaling could enhance the effectiveness of ACT in a murine cancer model. The administration of an antibody against mouse VEGF synergized with ACT to enhance inhibition of established, vascularized, B16 melanoma (P = 0.009) and improve survival (P = 0.003). Additive effects of an antibody against VEGFR-2 in conjunction with ACT were seen in this model (P = 0.013). Anti-VEGF, but not anti-VEGFR-2, antibody significantly increased infiltration of transferred cells into the tumor. Thus, normalization of tumor vasculature through disruption of the VEGF/VEGFR-2 axis can increase extravasation of adoptively transferred T cells into the tumor and improve ACT-based immunotherapy. These studies provide a rationale for the exploration of combining antiangiogenic agents with ACT for the treatment of patients with cancer. Cancer Res; 70(15); 6171-80. (C) 2010 AACR. C1 [Shrimali, Rajeev K.; Yu, Zhiya; Theoret, Marc R.; Chinnasamy, Dhanalakshmi; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM SAR@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 SC003811-33] NR 29 TC 149 Z9 153 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2010 VL 70 IS 15 BP 6171 EP 6180 DI 10.1158/0008-5472.CAN-10-0153 PG 10 WC Oncology SC Oncology GA 634CQ UT WOS:000280557500007 PM 20631075 ER PT J AU Bussard, KM Boulanger, CA Booth, BW Bruno, RD Smith, GH AF Bussard, Karen M. Boulanger, Corinne A. Booth, Brian W. Bruno, Robert D. Smith, Gilbert H. TI Reprogramming Human Cancer Cells in the Mouse Mammary Gland SO CANCER RESEARCH LA English DT Article ID IN-VIVO; TERATOCARCINOMA CELLS; EXPRESSION; MICE; DIFFERENTIATION; PHENOTYPE; GENE AB The tissue microenvironment directs stem/progenitor cell behavior. Cancer cells are also influenced by the microenvironment. It has been shown that, when placed into blastocysts, cancer cells respond to embryonic cues and differentiate according to the tissue type encountered during ontological development. Previously, we showed that the mouse mammary gland was capable of redirecting adult mouse testicular and neural stem/progenitor cells toward a mammary epithelial cell fate during gland regeneration. Here, we report that human embryonal carcinoma cells proliferate and produce differentiated mammary epithelial cell progeny when mixed with mouse mammary epithelial cells and inoculated into the epithelium-free mammary fat pads of athymic nude mice. Fluorescence in situ hybridization confirmed the presence of human cell progeny in the mammary outgrowths for human centromeric DNA, as well as immunochemistry for human-specific breast epithelial cytokeratins and human-specific milk proteins in impregnated transplant hosts. It was found that the number of human cells increased by 66- to 660-fold during mammary epithelial growth and expansion as determined by human cytokeratin expression. All features found in primary outgrowths were recapitulated in the secondary outgrowths from chimeric implants. These results show that human embryonal carcinoma-derived progeny interact with mouse mammary cells during mammary gland regeneration and are directed to differentiate into cells that exhibit diverse mammary epithelial cell phenotypes. This is the first demonstration that human cells are capable of recognizing the signals generated by the mouse mammary gland microenvironment present during gland regeneration in vivo. Cancer Res; 70(15); 6336-43. (C) 2010 AACR. C1 [Smith, Gilbert H.] NCI, NIH, MBTL, CCR, Bethesda, MD 20892 USA. [Booth, Brian W.] Clemson Univ, Inst Biol Interfaces Engn, Clemson, SC USA. RP Smith, GH (reprint author), NCI, NIH, MBTL, CCR, Bldg 37,Room 1112,37 Convent Dr, Bethesda, MD 20892 USA. EM gs4d@nih.gov OI Bruno, Robert/0000-0003-3329-9478 FU Center for Cancer Research, NCI, NIH FX The intramural research program of the Center for Cancer Research, NCI, NIH supported this work. NR 16 TC 41 Z9 41 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2010 VL 70 IS 15 BP 6336 EP 6343 DI 10.1158/0008-5472.CAN-10-0591 PG 8 WC Oncology SC Oncology GA 634CQ UT WOS:000280557500024 PM 20647316 ER PT J AU Mirabello, L Berndt, SI Seratti, GF Burdett, L Yeager, M Chowdhury, S Teshome, K Uzoka, A Douglass, C Hayes, RB Hoover, RN Savage, SA AF Mirabello, Lisa Berndt, Sonja I. Seratti, Guillermo F. Burdett, Laurie Yeager, Meredith Chowdhury, Salma Teshome, Kedest Uzoka, Arinze Douglass, Chester Hayes, Richard B. Hoover, Robert N. Savage, Sharon A. CA Natl Osteosarcoma Etiology Study G TI Genetic variation at chromosome 8q24 in osteosarcoma cases and controls SO CARCINOGENESIS LA English DT Article ID PROSTATE-CANCER SUSCEPTIBILITY; GENOME-WIDE ASSOCIATION; FACTOR-H POLYMORPHISM; COLORECTAL-CANCER; MACULAR DEGENERATION; BREAST-CANCER; BONE CANCER; RISK LOCUS; VARIANT; MYC AB Osteosarcoma is a primary bone malignancy that typically occurs during the pubertal growth spurt. Only a few small association studies have evaluated common germ line variation in individuals with osteosarcoma. The 8q24 chromosomal region contains several loci that are associated with risk of many different cancers. We conducted an association study of common single-nucleotide polymorphisms (SNPs) across 8q24 to explore the role this region may play in osteosarcoma risk. We genotyped 214 tag SNPs in 99 osteosarcoma cases and 1430 controls (65 controls from a hospital-based case-control study and 1365 controls from a population-based study). Additive, dominant and recessive genetic models were evaluated using unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses of nine SNPs previously associated with cancer did not show strong statistically significant associations. Of the remaining 205 SNPs, 7 were statistically significant (P < 0.05) in one or more genetic models; the most significant association was observed for the additive effect of the minor allele at rs896324 (OR 1.75, 95% CI 1.13-2.69, P = 0.01). This study suggests that several SNPs in 8q24 may be associated with osteosarcoma, but the susceptibility observed was modest. Future large studies of osteosarcoma genetic risk factors are warranted to improve our understanding of the genetic contribution to this cancer of adolescents and young adults. C1 [Mirabello, Lisa; Berndt, Sonja I.; Seratti, Guillermo F.; Hoover, Robert N.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Seratti, Guillermo F.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Burdett, Laurie; Yeager, Meredith; Chowdhury, Salma; Teshome, Kedest; Uzoka, Arinze] NCI, Core Genotyping Facil, SAIC Frederick, Gaithersburg, MD 20877 USA. [Douglass, Chester] Harvard Univ, Sch Dent Med, Dept Epidemiol, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Div Epidemiol, New York, NY 10016 USA. RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7018, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU National Institutes of Health; National Cancer Institute FX Intramural research program of the National Institutes of Health and the National Cancer Institute. NR 52 TC 10 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2010 VL 31 IS 8 BP 1400 EP 1404 DI 10.1093/carcin/bgq117 PG 5 WC Oncology SC Oncology GA 636BV UT WOS:000280703800013 PM 20530236 ER PT J AU Barnholtz-Sloan, JS Shetty, PB Guan, XW Nyante, SJ Luo, JC Brennan, DJ Millikan, RC AF Barnholtz-Sloan, Jill S. Shetty, Priya B. Guan, Xiaowei Nyante, Sarah J. Luo, Jingchun Brennan, Donal J. Millikan, Robert C. TI FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women SO CARCINOGENESIS LA English DT Article ID SUSCEPTIBILITY LOCI; POPULATION STRATIFICATION; RISK; ANCESTRY; VARIANTS; INFORMATION AB Twenty-nine single-nucleotide polymorphisms (SNPs) from previously published genome-wide association studies (GWAS) and multiple ancestry informative markers were genotyped in the Carolina Breast Cancer Study (CBCS) (742 African-American (AA) cases, 1230 White cases; 658 AA controls, 1118 White controls). In the entire study population, 9/10 SNPs in fibroblast growth factor receptor 2 (FGFR2) were significantly associated with breast cancer after adjusting for age, race and European ancestry [odds ratios (OR) range 1.17-1.81]. Associations were observed for SNPs in FGFR2, LSP1, H19, TLR1/TLR6 and RELN for AA; FGFR2, TNRC9, H19 and MAP3K1 for Whites; FGFR2, TNRC9, Msc5A1 and chromosome 8q for women >= 50 years old and FGFR2 and TNRC9 for women < 50 years old. FGFR2 haplotypes based upon rs11200014, rs2981579, rs1219648 and rs2420946 were associated with increased risk of breast cancer, including the GTGT haplotype in AAs [OR = 1.27, 95% confidence interval (CI) 1.04-1.56] and younger women of either race [OR = 1.35, 95% CI 1.02-1.78) and the ATGT haplotype in Whites (OR = 1.30, 95% CI 1.15-1.46). Recent GWAS hits for breast cancer in Europeans and Whites (i.e. women of European descent) thus showed evidence of replication among AAs and Whites in the CBCS. Several new haplotypes were associated with breast cancer in AA and younger women, particularly the FGFR2 GTGT haplotype. These results highlight the need to conduct GWAS among younger women and in a variety of racial-ethnic populations. C1 [Barnholtz-Sloan, Jill S.; Shetty, Priya B.; Guan, Xiaowei] Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, Cleveland, OH 44106 USA. [Barnholtz-Sloan, Jill S.; Shetty, Priya B.; Guan, Xiaowei] Case Western Reserve Univ, Dept Epidemiol & Biostat, Sch Med, Cleveland, OH 44106 USA. [Nyante, Sarah J.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Rockville, MD 20852 USA. [Luo, Jingchun; Millikan, Robert C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Brennan, Donal J.] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin, Ireland. [Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. RP Barnholtz-Sloan, JS (reprint author), Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, 11100 Euclid Ave,Wearn 152, Cleveland, OH 44106 USA. EM jsb42@case.edu RI Barnholtz-Sloan, Jill/A-4817-2011 FU Research Excellence in Breast Cancer [NIH/NCI P50-CA58223]; Center for Environmental Health and Susceptibility [NIEHS P30-ES10126]; Lineberger Comprehensive Cancer Center [P30-CA16086]; Case Comprehensive Cancer Center [P30-CA043703] FX Specialized Program of Research Excellence in Breast Cancer (NIH/NCI P50-CA58223 to R. C. M.); Center for Environmental Health and Susceptibility (NIEHS P30-ES10126 to R. C. M.); Lineberger Comprehensive Cancer Center Core Grant (P30-CA16086 to R. C. M.); Case Comprehensive Cancer Center Core Grant (P30-CA043703 to J.S.B.-S.). NR 26 TC 63 Z9 64 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2010 VL 31 IS 8 BP 1417 EP 1423 DI 10.1093/carcin/bgq128 PG 7 WC Oncology SC Oncology GA 636BV UT WOS:000280703800016 PM 20554749 ER PT J AU Bosetti, F Choi, SH AF Bosetti, Francesca Choi, Sang-Ho TI Rethinking the role of cyclooxygenase-1 in neuroinflammation More than homeostasis SO CELL CYCLE LA English DT Editorial Material ID INFLAMMATORY RESPONSE; EXPRESSION; LIPOPOLYSACCHARIDE; INHIBITION; STIMULI; BRAIN; MODEL C1 [Bosetti, Francesca; Choi, Sang-Ho] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM frances@mail.nih.gov NR 12 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 1 PY 2010 VL 9 IS 15 BP 2919 EP 2920 DI 10.4161/cc.9.15.12715 PG 2 WC Cell Biology SC Cell Biology GA 642JD UT WOS:000281206300004 PM 20714215 ER PT J AU Moiola, C De Luca, P Gardner, K Vazquez, E De Siervi, A AF Moiola, Cristian De Luca, Paola Gardner, Kevin Vazquez, Elba De Siervi, Adriana TI Cyclin T1 overexpression induces malignant transformation and tumor growth SO CELL CYCLE LA English DT Article DE cyclin T1; CDK9; PTEFb ID RNA-POLYMERASE-II; CARBOXYL-TERMINAL DOMAIN; HEAT-SHOCK GENES; P-TEFB KINASE; IN-VIVO; TRANSCRIPTION ELONGATION; DEPENDENT KINASES; CELL-CYCLE; CANCER-CELL; HIV-1 TAT AB Human PTEFb is a protein kinase composed by CDK9 and Cyclin T that controls the elongation phase of RNA Pol II. This complex also affects the activation and differentiation program of lymphoid cells. In this study we found that several head and neck tumor cell lines overexpress PTEFb. We also established that Cyclin T1 is able to induce transformation in vitro, as we determined by foci and colony formation assays. Nu/nu mice s.c. injected with stable transfected Cyclin T1 cells (NIH 3T3 Cyclin T1) developed tumors faster than animals injected with control cells (NIH 3T3 beta-gal). In vitro, NIH 3T3 Cyclin T1 cells show increased proliferation and CDK4-Rb phosphorylation. Even more, silencing E2F1 expression (shRNA E2F1) in NIH 3T3 cells resulted in a dramatic inhibition of Cyclin T1-induced foci. All these data demonstrate for the first time the Cyclin T1 oncogenic function and suggest a role for this protein in controlling cell cycle probably via Rb/E2F1 pathway. C1 [Moiola, Cristian; De Luca, Paola; Vazquez, Elba; De Siervi, Adriana] Univ Buenos Aires, Sch Sci, Dept Biol Chem, Buenos Aires, DF, Argentina. [Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [De Siervi, Adriana] Natl Inst Dent & Craniofacial Res, Mol Therapeut Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP De Siervi, A (reprint author), Univ Buenos Aires, Sch Sci, Dept Biol Chem, Buenos Aires, DF, Argentina. EM adesiervi@qb.fcen.uba.ar NR 46 TC 14 Z9 14 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 1 PY 2010 VL 9 IS 15 BP 3119 EP 3126 DI 10.4161/cc.9.15.12526 PG 8 WC Cell Biology SC Cell Biology GA 642JD UT WOS:000281206300042 PM 20714219 ER PT J AU Meltzer, JA McArdle, JJ Schafer, RJ Braun, AR AF Meltzer, Jed A. McArdle, Joseph J. Schafer, Robin J. Braun, Allen R. TI Neural Aspects of Sentence Comprehension: Syntactic Complexity, Reversibility, and Reanalysis SO CEREBRAL CORTEX LA English DT Article DE Broca's area; fMRI; language; semantic; syntax ID VERBAL WORKING-MEMORY; EVENT-RELATED FMRI; BROCAS AREA; LANGUAGE COMPREHENSION; RELATIVE CLAUSES; AGRAMMATIC APHASIA; LOCALIZATION; ACTIVATION; DEFICITS; VARIABILITY AB Broca's area is preferentially activated by reversible sentences with complex syntax, but various linguistic factors may be responsible for this finding, including syntactic movement, working-memory demands, and post hoc reanalysis. To distinguish between these, we tested the interaction of syntactic complexity and semantic reversibility in a functional magnetic resonance imaging study of sentence-picture matching. During auditory comprehension, semantic reversibility induced selective activation throughout the left perisylvian language network. In contrast, syntactic complexity (object-embedded vs. subject-embedded relative clauses) within reversible sentences engaged only the left inferior frontal gyrus (LIFG) and left precentral gyrus. Within irreversible sentences, only the LIFG was sensitive to syntactic complexity, confirming a unique role for this region in syntactic processing. Nonetheless, larger effects of reversibility itself occurred in the same regions, suggesting that full syntactic parsing may be a nonautomatic process applied as needed. Complex reversible sentences also induced enhanced signals in LIFG and left precentral regions on subsequent picture selection, but with additional recruitment of the right hemisphere homolog area (right inferior frontal gyrus) as well, suggesting that post hoc reanalysis of sentence structure, compared with initial comprehension, engages an overlapping but larger network of brain regions. These dissociable effects may offer a basis for studying the reorganization of receptive language function after brain damage. C1 [Meltzer, Jed A.; McArdle, Joseph J.; Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. [Schafer, Robin J.] Amer Assoc Advancement Sci, Washington, DC 20005 USA. RP Meltzer, JA (reprint author), Bldg 10,Room 5C-410, Bethesda, MD 20892 USA. EM jed.meltzer@aya.yale.edu FU National Institute on Deafness and Other Communication Disorders, National Institutes of Health FX Intramural Research Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health. NR 60 TC 24 Z9 26 U1 6 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2010 VL 20 IS 8 BP 1853 EP 1864 DI 10.1093/cercor/bhp249 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 634QD UT WOS:000280597100008 PM 19920058 ER PT J AU Brigman, JL Mathur, P Harvey-White, J Izquierdo, A Saksida, LM Bussey, TJ Fox, S Deneris, E Murphy, DL Holmes, A AF Brigman, Jonathan L. Mathur, Poonam Harvey-White, Judith Izquierdo, Alicia Saksida, Lisa M. Bussey, Timothy J. Fox, Stephanie Deneris, Evan Murphy, Dennis L. Holmes, Andrew TI Pharmacological or Genetic Inactivation of the Serotonin Transporter Improves Reversal Learning in Mice SO CEREBRAL CORTEX LA English DT Article DE antidepressant; executive function; gene; reversal; serotonin ID TRYPTOPHAN DEPLETION; ORBITOFRONTAL CORTEX; DECISION-MAKING; COGNITIVE INFLEXIBILITY; BEHAVIORAL FLEXIBILITY; EXECUTIVE FUNCTION; PREFRONTAL CORTEX; FEAR EXTINCTION; BRAIN-SEROTONIN; DEFICIENT MICE AB Growing evidence supports a major contribution of cortical serotonin (5-hydroxytryptamine, 5-HT) to the modulation of cognitive flexibility and the cognitive inflexibility evident in neuropsychiatric disorders. The precise role of 5-HT and the influence of 5-HT gene variation in mediating this process is not fully understood. Using a touch screen-based operant system, we assessed reversal of a pairwise visual discrimination as an assay for cognitive flexibility. Effects of constitutive genetic or pharmacological inactivation of the 5-HT transporter (5-HTT) on reversal were examined by testing 5-HTT null mice and chronic fluoxetine-treated C57BL/6J mice, respectively. Effects of constitutive genetic loss or acute pharmacological depletion of 5-HT were assessed by testing Pet-1 null mice and para-chlorophenylalanine (PCPA)treated C57BL/6J mice, respectively. Fluoxetine-treated C57BL/6J mice made fewer errors than controls during the early phase of reversal when perseverative behavior is relatively high. 5-HTT null mice made fewer errors than controls in completing the reversal task. However, reversal in Pet-1 null and PCPA-treated C57BL/6J mice was not different from controls. These data further support an important role for 5-HT in modulating reversal learning and provide novel evidence that inactivating the 5-HTT improves this process. These findings could have important implications for understanding and treating cognitive inflexibility in neuropsychiatric disease. C1 [Brigman, Jonathan L.; Mathur, Poonam; Izquierdo, Alicia; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Harvey-White, Judith] NIAAA, Lab Physiol Studies, NIH, Rockville, MD 20852 USA. [Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Saksida, Lisa M.; Bussey, Timothy J.] MRC, Cambridge CB2 3EB, England. [Saksida, Lisa M.; Bussey, Timothy J.] Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Fox, Stephanie; Deneris, Evan] Case Western Reserve Univ, Dept Neurosci, Sch Med, Cleveland, OH 44106 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Brigman, JL (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane Room 2N09, Rockville, MD 20852 USA. EM brigmanj@mail.nih.gov RI Brigman, Jonathan/O-4978-2016; Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016 OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041 FU National Institute on Alcohol Abuse and Alcoholism FX Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism. NR 62 TC 84 Z9 85 U1 1 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2010 VL 20 IS 8 BP 1955 EP 1963 DI 10.1093/cercor/bhp266 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 634QD UT WOS:000280597100018 PM 20032063 ER PT J AU Miller, Y Ma, B Nussinov, R AF Miller, Yifat Ma, Buyong Nussinov, Ruth TI Polymorphism in Alzheimer A beta Amyloid Organization Reflects Conformational Selection in a Rugged Energy Landscape SO CHEMICAL REVIEWS LA English DT Review ID SOLID-STATE NMR; MOLECULAR-DYNAMICS SIMULATIONS; YEAST PRION SUP35; ZINC-BINDING SITE; HISTOCHEMICALLY-REACTIVE ZINC; REPLICA EXCHANGE SIMULATIONS; NUCLEAR-MAGNETIC-RESONANCE; ATOMIC-FORCE MICROSCOPY; SIDE-CHAIN INTERACTIONS; RAY FIBER DIFFRACTION C1 [Miller, Yifat; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Ma, Buyong; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Sci Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank current and former group members Drs. Hyunbum Jang, Jie Zheng, and David Zanuy for their computational studies cited here and Drs. Ratnesh Lal and Bruce Kagan for many discussions. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number 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. NR 294 TC 148 Z9 150 U1 2 U2 38 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 J9 CHEM REV JI Chem. Rev. PD AUG PY 2010 VL 110 IS 8 BP 4820 EP 4838 DI 10.1021/cr900377t PG 19 WC Chemistry, Multidisciplinary SC Chemistry GA 639PD UT WOS:000280985800011 PM 20402519 ER PT J AU Raychaudhuri, S Schulz, T Choi, MG Prinz, W AF Raychaudhuri, Sumana Schulz, Tim Choi, Mal-Gi Prinz, Will TI Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Meeting Abstract CT 51st International Conference of the Bioscience of Lipids (ICBL) CY AUG 05, 2010 CL Alhondiga Conf, Bilbao, SPAIN SP Avanti Polar Lipids, Consejo Super Invest Cientificas, Elsevier, Fdn Biofisica Bizkaia, Cobierno Vasco, Ministerio Ciencia Innovacion, Univ Pais Vasco HO Alhondiga Conf C1 [Raychaudhuri, Sumana; Schulz, Tim; Choi, Mal-Gi; Prinz, Will] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD AUG PY 2010 VL 163 SU S BP S11 EP S11 DI 10.1016/j.chemphyslip.2010.05.037 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 633VP UT WOS:000280535200035 ER PT J AU Oner, O Oner, P Bozkurt, OH Odabas, E Keser, N Karadag, H Kizilgun, M AF Oner, Ozgur Oner, Pinar Bozkurt, Ozlem Hekim Odabas, Elif Keser, Nilufer Karadag, Hasan Kizilgun, Murat TI Effects of Zinc and Ferritin Levels on Parent and Teacher Reported Symptom Scores in Attention Deficit Hyperactivity Disorder SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE ADHD; Zinc; Ferritin; Behavioral ratings ID DEFICIT/HYPERACTIVITY DISORDER; IRON-DEFICIENCY; SERUM FERRITIN; CHILDREN; BRAIN; SUPPLEMENTATION; BEHAVIOR; RATINGS AB Objective: It has been suggested that both low iron and zinc levels might be associated with Attention Deficit Hyperactivity Disorder (ADHD) symptoms. However, the association of zinc and iron levels with ADHD symptoms has not been investigated at the same time in a single sample. Method: 118 subjects with ADHD (age = 7-14 years, mean = 9.8, median = 10) were included in the study. The relationship between age, gender, ferritin, zinc, hemoglobin, mean corpuscular volume and reticulosite distribution width and behavioral symptoms of children and adolescents with ADHD were investigated with multiple linear regression analysis. Results: Results showed that subjects with lower zinc level had higher Conners Parent Rating Scale (CPRS) Total, Conduct Problems and Anxiety scores, indicating more severe problems. CPRS Hyperactivity score was associated both with zinc and ferritin levels. Conners Teacher Rating Scale (CTRS) scores were not significantly associated with zinc or ferritin levels. Conclusions: Results indicated that both low zinc and ferritin levels were associated with higher hyperactivity symptoms. Zinc level was also associated with anxiety and conduct problems. Since both zinc and iron are associated with dopamine metabolism, it can be speculated that low zinc and iron levels might be associated with more significant impairment in dopaminergic transmission in subjects with ADHD. C1 [Oner, Ozgur; Oner, Pinar] Dr Sami Ulus Childrens Hosp, Child Psychiat Dept, Ankara, Turkey. [Oner, Ozgur] Childrens Hosp, Fogarty Int Ctr, Mental Hlth & Dev Disabil Program, Boston, MA 02115 USA. [Bozkurt, Ozlem Hekim; Odabas, Elif; Keser, Nilufer] Diskapi Childrens Hosp, Child Psychiat Dept, Ankara, Turkey. [Karadag, Hasan] Diskapi Yildirim Bayazit Training Hosp, Ankara, Turkey. [Kizilgun, Murat] Diskapi Childrens Hosp, Dept Biochem, Ankara, Turkey. RP Oner, O (reprint author), Dr Sami Ulus Childrens Hosp, Child Psychiat Dept, Ankara, Turkey. EM ozgur.oner@yahoo.com FU FIC NIH HHS [D43 TW005807-08, D43 TW005807, D43TW05807, D43 TW005807-09] NR 23 TC 22 Z9 22 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-398X J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD AUG PY 2010 VL 41 IS 4 BP 441 EP 447 DI 10.1007/s10578-010-0178-1 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 589PT UT WOS:000277165300007 PM 20238159 ER PT J AU Tanenbaum, ME Vallenius, T Geers, EF Greene, L Makela, TP Medema, RH AF Tanenbaum, Marvin E. Vallenius, Tea Geers, Erica F. Greene, Lois Makela, Tomi P. Medema, Rene H. TI Cyclin G-associated kinase promotes microtubule outgrowth from chromosomes during spindle assembly SO CHROMOSOMA LA English DT Article ID CLATHRIN-COATED VESICLES; MITOTIC SPINDLE; COMPLEX; PROTEIN; AUGMIN; CELLS; HURP; RECRUITMENT; GENERATION; MITOSIS AB During mitosis, all chromosomes must attach to microtubules of the mitotic spindle to ensure correct chromosome segregation. Microtubule attachment occurs at specialized structures at the centromeric region of chromosomes, called kinetochores. These kinetochores can generate microtubule attachments through capture of centrosome-derived microtubules, but in addition, they can generate microtubules themselves, which are subsequently integrated with centrosome-derived microtubules to form the mitotic spindle. Here, we have performed a large scale RNAi screen and identify cyclin G-associated kinase (GAK) as a novel regulator of microtubule generation at kinetochores/chromatin. This function of GAK requires its C-terminal J-domain, which is essential for clathrin recycling from endocytic vesicles. Consistently, cells lacking GAK show strongly reduced levels of clathrin on the mitotic spindle, and reduction of clathrin levels also inhibits microtubule generation at kinetochores/chromosomes. Finally, we present evidence that association of clathrin with the spindle is promoted by a signal coming from the chromosomes. These results identify a role for GAK and clathrin in microtubule outgrowth from kinetochores/chromosomes and suggest that GAK acts through clathrin to control microtubule outgrowth around chromosomes. C1 [Tanenbaum, Marvin E.; Geers, Erica F.; Medema, Rene H.] Univ Med Ctr Utrecht, Dept Med Oncol, NL-3584 CG Utrecht, Netherlands. [Tanenbaum, Marvin E.; Geers, Erica F.; Medema, Rene H.] Univ Med Ctr Utrecht, Canc Genom Ctr, NL-3584 CG Utrecht, Netherlands. [Vallenius, Tea; Makela, Tomi P.] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland. [Vallenius, Tea; Makela, Tomi P.] Univ Helsinki, Genome Scale Biol Program, FIN-00014 Helsinki, Finland. [Greene, Lois] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Medema, RH (reprint author), Univ Med Ctr Utrecht, Dept Med Oncol, Univ Weg 100,Str 2-118, NL-3584 CG Utrecht, Netherlands. EM r.h.medema@umcutrecht.nl RI makela, tomi/B-3734-2009; OI makela, tomi/0000-0002-4869-8044; Medema, Rene/0000-0002-6754-0381 FU Academy of FInland; EU [LSHG-CT-2005-518254]; Division for Earth and Life Sciences (ALW); Netherlands Genomic Initiative (NGI); Netherlands Organization for Scientific Research (NWO) FX We thank Erich Nigg for the anti-HURP antibody and Don Cleveland for anti-Cenp-E antibody. We also thank the other members of our research groups for helpful discussions and suggestions and Livio Kleij for support with microscopy. We would also like to thank the Biomedicum Helsinki Molecular Imaging Unit for services. This work was supported by Academy of FInland and EU FP6 Program (ENFIN, LSHG-CT-2005-518254). This work was further supported by the Division for Earth and Life Sciences (ALW) and the Netherlands Genomic Initiative (NGI), both with financial aid of the Netherlands Organization for Scientific Research (NWO). NR 32 TC 18 Z9 19 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD AUG PY 2010 VL 119 IS 4 BP 415 EP 424 DI 10.1007/s00412-010-0267-8 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 631VE UT WOS:000280377400008 PM 20237935 ER PT J AU Thanassoulis, G Massaro, JM O'Donnell, CJ Hoffmann, U Levy, D Ellinor, PT Wang, TJ Schnabel, RB Vasan, RS Fox, CS Benjamin, EJ AF Thanassoulis, George Massaro, Joseph M. O'Donnell, Christopher J. Hoffmann, Udo Levy, Daniel Ellinor, Patrick T. Wang, Thomas J. Schnabel, Renate B. Vasan, Ramachandran S. Fox, Caroline S. Benjamin, Emelia J. TI Pericardial Fat Is Associated With Prevalent Atrial Fibrillation The Framingham Heart Study SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; pericardial adipose tissue; obesity; epidemiology; risk factor ID EPICARDIAL ADIPOSE-TISSUE; P-WAVE DISPERSION; CORONARY-ARTERY-DISEASE; VISCERAL ABDOMINAL FAT; LIPOMATOUS HYPERTROPHY; OBESE SUBJECTS; INTERATRIAL SEPTUM; WEIGHT-LOSS; CLINICAL-SIGNIFICANCE; MORPHOLOGIC FEATURES AB Background-Obesity represents an important risk factor for atrial fibrillation (AF). We tested the hypothesis that pericardial fat, a unique fat deposit in close anatomic proximity to cardiac structures and autonomic fibers, is associated with prevalent AF. Methods and Results-Participants from the Framingham Heart Study underwent multidetector computed tomography from 2002 to 2005. We estimated the association between quantitative pericardial, intrathoracic and visceral adipose tissue volumes (per standard deviation of volume) with prevalent AF adjusting for established AF risk factors (age, sex, systolic blood pressure, blood pressure treatment, PR interval, and clinically significant valvular disease). Of the 3217 eligible participants (mean age, 50.6 +/- 10.1 years; 48% women), 54 had a confirmed diagnosis of AF. Pericardial fat but not intrathoracic or visceral abdominal fat was associated with prevalent AF in multivariable-adjusted models (odds ratio per standard deviation of pericardial fat volume, 1.28; 95% confidence intervals, 1.03 to 1.58). Further adjustments for body mass index, heart failure, myocardial infarction, and intrathoracic fat volume did not materially change the association between pericardial fat and AF. Conclusions-Pericardial fat was associated with prevalent AF even after adjustment for AF risk factors, including body mass index. If this association is replicated, further investigations into the mechanisms linking pericardial fat to AF are merited. (Circ Arrhythm Electrophysiol. 2010;3:345-350.) C1 [Thanassoulis, George; O'Donnell, Christopher J.; Levy, Daniel; Schnabel, Renate B.; Vasan, Ramachandran S.; Fox, Caroline S.; Benjamin, Emelia J.] Boston Univ, Framingham, MA 01702 USA. NHLBI, NIH, Framingham, MA 01702 USA. [Thanassoulis, George; Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Massaro, Joseph M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [O'Donnell, Christopher J.; Hoffmann, Udo; Ellinor, Patrick T.; Wang, Thomas J.; Fox, Caroline S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hoffmann, Udo] MGH PET MR CT Program, Boston, MA USA. [O'Donnell, Christopher J.; Levy, Daniel; Fox, Caroline S.] NIH, Div Intramural Res, Bethesda, MD 20892 USA. RP Benjamin, EJ (reprint author), Boston Univ, 73 Mt Wayte Ave,2, Framingham, MA 01702 USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Framingham Heart Study, Boston University; National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC 25195]; Canadian Institute of Health Research; Fonds de Recherche en Sante Quebec; [1R01HL092577]; [RO1 HL076784]; [1RC1HL101056]; [R01 AG028321]; [R01-DK-080739] FX This study was supported by the Framingham Heart Study, Boston University and the National Institutes of Health/National Heart, Lung, and Blood Institute, grant N01-HC 25195. Dr Thanassoulis is supported by a Research Fellowship from the Canadian Institute of Health Research and the Fonds de Recherche en Sante Quebec. Dr Benjamin was supported in part by grants 1R01HL092577, RO1 HL076784, 1RC1HL101056, and R01 AG028321. Dr Vasan was supported in part by grant R01-DK-080739. NR 46 TC 112 Z9 114 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2010 VL 3 IS 4 BP 345 EP 350 DI 10.1161/CIRCEP.109.912055 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 639WI UT WOS:000281006700008 PM 20558845 ER PT J AU Zuberi, Z Nobles, M Sebastian, S Dyson, A Lim, SY Breckenridge, R Birnbaumer, L Tinker, A AF Zuberi, Zia Nobles, Muriel Sebastian, Sonia Dyson, Alex Lim, Shiang Y. Breckenridge, Ross Birnbaumer, Lutz Tinker, Andrew TI Absence of the Inhibitory G-Protein G alpha(i2) Predisposes to Ventricular Cardiac Arrhythmia SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE G(i); inhibitory G-protein; long QT syndrome; ventricular tachycardia; calcium channel ID HEART-RATE DYNAMICS; LONG QT SYNDROME; MYOCARDIAL-INFARCTION; CALCIUM-CHANNEL; ALPHA-SUBUNITS; GENE KNOCKOUT; CA2+ CHANNELS; REPOLARIZATION; FAILURE; TACHYCARDIA AB Background-We explored the role that inhibitory heterotrimeric G-proteins play in ventricular arrhythmia. Methods and Results-Mice with global genetic deletion of G alpha(i2) [G alpha(i2) (-/-)] were studied and found, based on telemetry, to have a prolonged QT interval on surface ECG when awake. In vivo electrophysiology studies revealed that the G alpha(i2) (-/-) mice have a reduced ventricular effective refractory period and a predisposition to ventricular tachycardia when challenged with programmed electrical stimulation. Neither control nor combined global deletion of G alpha(i1) and G alpha(i3) mice showed these abnormalities. There was no evidence for structural heart disease at this time point in the G alpha(i2) (-/-) mice as assessed by cardiac histology and echocardiography. The absence of G alpha(i2) thus leads to a primary electrical abnormality, and we explored the basis for this finding. With patch clamping, single isolated ventricular cells showed that G alpha(i2) (-/-) mice had a prolonged ventricular action potential duration (APD) but steeper action potential shortening as the diastolic interval was reduced in restitution studies. Gene expression studies showed increased expression of L-type Ca-2(+) channel subunits, and patch clamping revealed an increase in these currents in G alpha(i2) (-/-) mice. There were no changes in K+ currents. Conclusions-The absence of inhibitory G-protein signaling mediated through G alpha(i2) is a substrate for ventricular arrhythmias. (Circ Arrhythm Electrophysiol. 2010; 3: 391-400.) C1 [Zuberi, Zia; Nobles, Muriel; Sebastian, Sonia; Dyson, Alex; Breckenridge, Ross; Tinker, Andrew] UCL, Dept Med, London WC1E 6JJ, England. [Lim, Shiang Y.] UCL, Hatter Cardiovasc Inst, London WC1E 6JJ, England. [Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Tinker, A (reprint author), UCL, Dept Med, 5 Univ St, London WC1E 6JJ, England. EM a.tinker@ucl.ac.uk RI Lim, Shiang/E-9640-2011 FU Wellcome Trust; Medical Research Council; British Heart Foundation; National Institutes of Health [Z01-ES101643] FX This work was supported by the Wellcome Trust, Medical Research Council, the British Heart Foundation, and the Intramural Research Program of the National Institutes of Health (project Z01-ES101643 to Dr Birnbaumer). NR 44 TC 9 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2010 VL 3 IS 4 BP 391 EP 400 DI 10.1161/CIRCEP.109.894329 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 639WI UT WOS:000281006700013 PM 20495013 ER PT J AU Barrett, AJ Le Blanc, K AF Barrett, A. J. Le Blanc, K. TI Immunotherapy prospects for acute myeloid leukaemia SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Review DE AML; antibodies; cell therapy; vaccines ID ACUTE MYELOGENOUS LEUKEMIA; NATURAL-KILLER-CELLS; 1ST COMPLETE REMISSION; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ABSOLUTE LYMPHOCYTE COUNT; WT1 PEPTIDE VACCINATION; CYTOTOXIC T-LYMPHOCYTES; DENDRITIC CELLS; GEMTUZUMAB OZOGAMICIN AB P>While chemotherapy is successful at inducing remission of acute myeloid leukaemia (AML), the disease has a high probability of relapse. Strategies to prevent relapse involve consolidation chemotherapy, stem cell transplantation and immunotherapy. Evidence for immunosurveillance of AML and susceptibility of leukaemia cells to both T cell and natural killer (NK) cell attack and justifies the application of immune strategies to control residual AML persisting after remission induction. Immune therapy for AML includes allogeneic stem cell transplantation, adoptive transfer of allogeneic or autologous T cells or NK cells, vaccination with leukaemia cells, dendritic cells, cell lysates, peptides and DNA vaccines and treatment with cytokines, antibodies and immunomodulatory agents. Here we describe what is known about the immunological features of AML at presentation and in remission, the current status of immunotherapy and strategies combining treatment approaches with a view to achieving leukaemia cure. C1 [Barrett, A. J.] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, Clin Res Ctr,NIH, Bethesda, MD 20892 USA. [Le Blanc, K.] Karolinska Univ Hosp, Hematol Ctr, Div Clin Immunol & Transfus Med, Stockholm, Sweden. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, Clin Res Ctr,NIH, Room 3-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM barrettjj@mail.nih.gov NR 107 TC 38 Z9 40 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 2010 VL 161 IS 2 BP 223 EP 232 DI 10.1111/j.1365-2249.2010.04197.x PG 10 WC Immunology SC Immunology GA 625MG UT WOS:000279898800003 PM 20529084 ER PT J AU Tang, SX Zhao, JQ Wang, AF Viswanath, R Harma, H Little, RF Yarchoan, R Stramer, SL Nyambi, PN Lee, S Wood, O Wong, EY Wang, X Hewlett, IK AF Tang, Shixing Zhao, Jiangqin Wang, Aifeng Viswanath, Ragupathy Harma, Harri Little, Richard F. Yarchoan, Robert Stramer, Susan L. Nyambi, Phillipe N. Lee, Sherwin Wood, Owen Wong, Eric Y. Wang, Xue Hewlett, Indira K. TI Characterization of Immune Responses to Capsid Protein p24 of Human Immunodeficiency Virus Type 1 and Implications for Detection SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; HIV-1 P24; SIGNAL AMPLIFICATION; GENETIC DIVERSITY; CORE PROTEIN; ANTIGEN; INFECTION; ASSAY; IMMUNOASSAYS; EPITOPES AB To further refine our current nanoparticle-based HIV-1 p24 antigen assay, we investigated immune responses to p24 to identify diagnostically significant immune dominant epitopes (IDEs) in HIV-infected human sera, to address cross-reactivity of anti-p24 antibodies to different subtypes, and to identify new biomarkers that distinguish acute from chronic HIV infection for more accurate incidence estimation. We identified two major linear epitope regions, located in the CypA binding loop and adjacent helices and at the end of the C-terminal domain. Most sera (86%) from acutely HIV-1-infected individuals reacted with multiple peptides, while 60% and 30% of AIDS patient samples reacted with multiple and single peptides, respectively. In contrast, 46% and 43% of chronically HIV-1-infected individuals reacted with one and none of the peptides, respectively, and only 11% reacted with multiple p24 peptides, indicating a progression of immune responses from polyclone-like during acute infection to monoclone-like or a nonresponse to linear epitopes during chronic infection. Anti-p24 antibodies (subtype B) show broad cross-reactivity to different HIV-1 subtypes, and the synergistic action of different combinations of anti-HIV antibodies improves capture and detection of divergent HIV-1 subtypes. Our results indicate that the modified peptide immunoassay is sensitive and specific for the rapid identification of HIV-1 p24 IDEs and for investigation of immune responses to p24 during natural HIV-1 infection. The data provide the foundation for development and refinement of new assays for improved p24 antigen testing as future tools for rapid and accurate diagnosis as part of early intervention strategies and estimations of incidence. C1 [Tang, Shixing; Zhao, Jiangqin; Wang, Aifeng; Viswanath, Ragupathy; Lee, Sherwin; Wood, Owen; Wong, Eric Y.; Wang, Xue; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Harma, Harri] Univ Turku, Biophys Lab, FIN-20520 Turku, Finland. [Little, Richard F.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Stramer, Susan L.] Amer Red Cross, Biomed Serv Sci Support Off, Gaithersburg, MD 20877 USA. [Nyambi, Phillipe N.] NYU, Sch Med, New York, NY 10010 USA. RP Tang, SX (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN16,8800 Rockville Pike, Bethesda, MD 20892 USA. EM shixing.tang@fda.hhs.gov; indira.hewlett@fda.hhs.gov FU National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID), NIH; National Cancer Institute (NCI), NIH FX This study was funded by an interagency agreement with the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID), NIH, and was supported in part by the Intramural Research Program of the National Cancer Institute (NCI), NIH. NR 38 TC 9 Z9 9 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2010 VL 17 IS 8 BP 1244 EP 1251 DI 10.1128/CVI.00066-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 633XG UT WOS:000280539900012 PM 20534793 ER PT J AU Nesslinger, NJ Ng, A Tsang, KY Ferrara, T Schlom, J Gulley, JL Nelson, BH AF Nesslinger, Nancy J. Ng, Alvin Tsang, Kwong-Yok Ferrara, Theresa Schlom, Jeffrey Gulley, James L. Nelson, Brad H. TI A Viral Vaccine Encoding Prostate-Specific Antigen Induces Antigen Spreading to a Common Set of Self-Proteins in Prostate Cancer Patients SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR-INFILTRATING LYMPHOCYTES; SERUM ANTI-P53 ANTIBODIES; CELL LUNG-CANCER; T-CELL; SEROLOGICAL CLONING; P53 AUTOANTIBODIES; PROLONGED SURVIVAL; PROGNOSTIC-FACTOR; MELANOMA VACCINE AB Purpose: We previously reported a randomized phase II clinical trial combining a poxvirus-based vaccine encoding prostate-specific antigen (PSA) with radiotherapy in patients with localized prostate cancer. Here, we investigate whether vaccination against PSA induced immune responses to additional tumor-associated antigens and how this influenced clinical outcome. Experimental Design: Pretreatment and posttreatment serum samples from patients treated with vaccine + external beam radiation therapy (EBRT) versus EBRT alone were evaluated by Western blot and serologic screening of a prostate cancer cDNA expression library (SEREX) to assess the development of treatment-associated autoantibody responses. Results: Western blotting revealed treatment-associated autoantibody responses in 15 of 33 (45.5%) patients treated with vaccine + EBRT versus 1 of 8 (12.5%) treated with EBRT alone. SEREX screening identified 18 antigens, which were assembled on an antigen array with 16 previously identified antigens. Antigen array screening revealed that 7 of 33 patients (21.2%) treated with vaccine + EBRT showed a vaccine-associated autoantibody response to four ubiquitously expressed self-antigens: DIRC2, NDUFS1, MRFAP1, and MATN2. These responses were not seen in patients treated with EBRT alone, or other control groups. Patients with autoantibody responses to this panel of antigens had a trend toward decreased biochemical-free survival. Conclusions: Vaccine + EBRT induced antigen spreading in a large proportion of patients. A subset of patients developed autoantibodies to a panel of four self-antigens and showed a trend toward inferior outcomes. Thus, cancer vaccines directed against tumor-specific antigens can trigger autoantibody responses to self-proteins, which may influence the efficacy of vaccination. Clin Cancer Res; 16(15); 4046-56. (C) 2010 AACR. C1 [Nesslinger, Nancy J.; Ng, Alvin; Nelson, Brad H.] BC Canc Agcy Vancouver Isl Ctr, Trev & Joyce Deeley Res Ctr, Victoria, BC V8R 6V5, Canada. [Nelson, Brad H.] Univ Victoria, Dept Biochem Microbiol, Victoria, BC, Canada. [Nelson, Brad H.] Univ Victoria, Dept Biol, Victoria, BC V8W 2Y2, Canada. [Nelson, Brad H.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Tsang, Kwong-Yok; Ferrara, Theresa; Schlom, Jeffrey; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Nelson, BH (reprint author), BC Canc Agcy Vancouver Isl Ctr, Deeley Res Ctr, 2410 Lee Ave, Victoria, BC V8R 6V5, Canada. EM bnelson@bccancer.bc.ca RI Nelson, Brad/K-2622-2014; Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU U.S. Department of Defense [W81XWH-07-1-0259]; British Columbia Cancer Foundation; Capital Region Prostate Centre (Victoria, British Columbia); U.S. Army [DAMD17-02-IA-0004]; Center for Cancer Research, National Cancer Institute, NIH FX U.S. Department of Defense; grant no.: W81XWH-07-1-0259, British Columbia Cancer Foundation, The Capital Region Prostate Centre (Victoria, British Columbia), U.S. Army Medical Research and Materiel Command Prostate Cancer Research Program Grant DAMD17-02-IA-0004, Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 54 TC 25 Z9 26 U1 0 U2 2 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 AUG 1 PY 2010 VL 16 IS 15 BP 4046 EP 4056 DI 10.1158/1078-0432.CCR-10-0948 PG 11 WC Oncology SC Oncology GA 633TT UT WOS:000280530300026 PM 20562209 ER PT J AU Diamandis, EP Sidransky, D Laird, PW Cairns, P Bapat, B AF Diamandis, Eleftherios P. Sidransky, David Laird, Peter W. Cairns, Paul Bapat, Bharati TI Epigenomics-Based Diagnostics SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Diamandis, Eleftherios P.] Mt Sinai Hosp, Dept Clin Biochem, Toronto, ON M5G 1X5, Canada. [Diamandis, Eleftherios P.] Univ Hlth Network, Toronto, ON, Canada. [Diamandis, Eleftherios P.] Univ Toronto, Dept Lab Med & Pathobiol, Div Clin Biochem, Toronto, ON, Canada. [Sidransky, David] Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Sidransky, David] Johns Hopkins Univ, Baltimore, MD USA. [Sidransky, David] NCI, Early Detect Res Network, Rockville, MD USA. [Laird, Peter W.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Laird, Peter W.] Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA 90033 USA. [Laird, Peter W.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. [Cairns, Paul] Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. [Cairns, Paul] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. [Bapat, Bharati] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Diamandis, EP (reprint author), Mt Sinai Hosp, Dept Clin Biochem, Toronto, ON M5G 1X5, Canada. RI Bapat, Bharati/B-5839-2014; Laird, Peter/G-8683-2012; OI Diamandis, Eleftherios/0000-0002-1589-820X FU NCI NIH HHS [R01 CA118699, U01 CA084986] NR 0 TC 3 Z9 3 U1 1 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 AUG PY 2010 VL 56 IS 8 BP 1216 EP 1219 DI 10.1373/clinchem.2010.148007 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 633KP UT WOS:000280501400005 PM 20472819 ER PT J AU Milman, G Barnes, AJ Schwope, DM Schwilke, EW Darwin, WD Goodwin, RS Kelly, DL Gorelick, DA Huestis, MA AF Milman, Garry Barnes, Allan J. Schwope, David M. Schwilke, Eugene W. Darwin, William D. Goodwin, Robert S. Kelly, Deanna L. Gorelick, David A. Huestis, Marilyn A. TI Disposition of Cannabinoids in Oral Fluid after Controlled Around-the-Clock Oral THC Administration SO CLINICAL CHEMISTRY LA English DT Article ID METABOLITE 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; DELTA(9)-TETRAHYDROCANNABINOL; PLASMA; MARIJUANA; DRUGS; DELTA-9-TETRAHYDROCANNABINOL; ABUSE; PHARMACOKINETICS; IDENTIFICATION; CANNABIDIOL AB BACKGROUND: Oral fluid, a promising alternative matrix for drug monitoring in clinical and forensic investigations, offers noninvasive sample collection under direct observation. Cannabinoid distribution into oral fluid is complex and incompletely characterized due to the lack of controlled drug administration studies. METHODS: To characterize cannabinoid disposition in oral fluid, we administered around-the-clock oral Delta(9)-tetrahydrocannabinol (THC) (Marinol (R)) doses to 10 participants with current daily cannabis use. We obtained oral fluid samples (n = 440) by use of Quantisal (TM) collection devices before, during, and after 37 20-mg THC doses over 9 days. Samples were extracted with multiple elution solvents from a single SPE column and analyzed by 2-dimensional GC-MS with electron-impact ionization for THC, 11-hydroxy-THC (11-OH-THC), cannabidiol, and cannabinol and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges were 0.5-50 mu g/L, with the exception of cannabinol (1-50 mu g/L) and THCCOOH (7.5-500 ng/L). RESULTS: THCCOOH was the most prevalent analyte in 432 samples (98.2%), with concentrations up to 1117.9 ng/L. In contrast, 11-OH-THC was not identified in any sample; cannabidiol and cannabinol were quantified in 3 and 8 samples, respectively, with maximum concentrations of 2.1 and 13 mu g/L. THC was present in only 20.7% of samples, with highest concentrations near admission (median 4.2 mu g/L, range 0.6-481.9) from previously self-administered smoked cannabis. CONCLUSIONS: Measurement of THCCOOH in OF not only identifies cannabis exposure, but also minimizes the possibility of passive inhalation. THCCOOH may be a better analyte for detection of cannabis use. (C) 2010 American Association for Clinical Chemistry C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Gorelick, David A.] NIDA, Off Sci Director, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Schwilke, Eugene W.] AIT Labs, Indianapolis, IN USA. [Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse(NIDA); NIH; NIDA Residential Research Support Services [HHSN271200599091, N01Da-5-9909]; Sanofi-Aventis, Inc. FX Research Funding: The research was funded by the Intramural Research Program of the National Institute on Drug Abuse(NIDA), NIH, and NIDA Residential Research Support Services Contract HHSN271200599091 CADB Contract No. N01Da-5-9909, and Sanofi-Aventis, Inc. The research was approved by the Institutional Review Board, NIDA. NR 33 TC 28 Z9 28 U1 4 U2 15 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 AUG PY 2010 VL 56 IS 8 BP 1261 EP 1269 DI 10.1373/clinchem.2009.141853 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 633KP UT WOS:000280501400014 PM 20530732 ER PT J AU Kallen, AJ Patel, PR O'Grady, NP AF Kallen, Alexander J. Patel, Priti R. O'Grady, Naomi P. TI Preventing Catheter-Related Bloodstream Infections outside the Intensive Care Unit: Expanding Prevention to New Settings SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CENTRAL VENOUS CATHETERS; CRITICALLY-ILL PATIENTS; SAFETY NETWORK NHSN; CONTROLLED-TRIAL; ACCESS DEVICES; POVIDONE-IODINE; US HOSPITALS; RISK-FACTORS; SURVEILLANCE; HEMODIALYSIS AB With the growing recognition of the preventability of catheter-related bloodstream infections (CRBSIs), reducing the number of CRBSIs acquired in health care facilities has become an important patient safety goal. To date, most prevention efforts have been conducted in intensive care units (ICUs); however, many central venous catheters (CVCs) are found outside the ICU, and rates of catheter-associated bloodstream infections in these settings appear to be similar to rates of these infections in ICUs. CVCs are also used in patients who primarily receive their care as outpatients, including those requiring hemodialysis, undergoing treatment for malignancies, and receiving parenteral nutrition. In some of these patients, CVCs might be used for extended periods, prolonging the patient's time at risk for CRBSIs and highlighting the potential need to look beyond insertion-based interventions to prevent infections. To meet the goal of reducing the number of all CRBSIs associated with health care, further attention on CRBSIs occurring outside the ICU is needed; however, this effort will require a better understanding of the epidemiology and prevention of these infections. C1 [Kallen, Alexander J.; Patel, Priti R.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kallen, AJ (reprint author), 1600 Clifton Rd,MS A-35, Atlanta, GA 30333 USA. EM AKallen@cdc.gov NR 53 TC 51 Z9 51 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2010 VL 51 IS 3 BP 335 EP 341 DI 10.1086/653942 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 629JS UT WOS:000280193800014 PM 20572762 ER PT J AU Uldrick, TS Wang, V O'Mahony, D Aleman, K Wyvill, KM Marshall, V Steinberg, SM Pittaluga, S Maric, I Whitby, D Tosato, G Little, RF Yarchoan, R AF Uldrick, Thomas S. Wang, Victoria O'Mahony, Deirdre Aleman, Karen Wyvill, Kathleen M. Marshall, Vickie Steinberg, Seth M. Pittaluga, Stefania Maric, Irina Whitby, Denise Tosato, Giovanna Little, Richard F. Yarchoan, Robert TI An Interleukin-6-Related Systemic Inflammatory Syndrome in Patients Co-Infected with Kaposi Sarcoma-Associated Herpesvirus and HIV but without Multicentric Castleman Disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PRIMARY EFFUSION LYMPHOMA; VIRAL INTERLEUKIN-6; DNA-SEQUENCES; CELLS; CYTOKINES; HHV-8; REACTIVATION; EXPRESSION; SERUM; KSHV AB Background. Kaposi sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi sarcoma (KS) and multicentric Castleman disease (MCD) in human immunodeficiency virus (HIV)-infected patients. Patients with KSHV-MCD develop fevers, wasting, hypoalbuminemia, cytopenias, and hyponatremia that are related to overproduction of KSHV-encoded viral interleukin (IL)-6 (vIL-6) and human IL-6 (hIL-6). Methods. We identified 6 HIV-infected patients with KS or serological evidence of KSHV infection who had severe inflammatory MCD-like symptoms but in whom we could not diagnose MCD, and we hypothesized that these symptoms resulted from vIL-6 overproduction. Serum vIL-6 levels were assessed in these 6 patients and compared with levels in 8 control patients with symptomatic KSHV-MCD and 32 control patients with KS. KSHV viral load, serum hIL-6 level, and human IL-10 level were also evaluated. Results. Patients with inflammatory MCD-like symptoms but without MCD had elevated vIL-6 levels, comparable with levels in patients with symptomatic KSHV-MCD, and had levels that were significantly greater than those in control patients with KS (P = .003) Elevated hIL-6, IL-10, and KSHV viral loads were also comparable to patients with symptomatic KSHV-MCD and significantly greater than those with KS. Conclusions. A subset of patients with HIV and KSHV co-infection, but without MCD, can develop severe systemic inflammatory symptoms associated with elevated levels of KSHV vIL-6, IL-6, and KSHV viral loads. Excess lytic activation of KSHV, production of the lytic gene product vIL6, and associated immunologic dysregulation may underlie the pathophysiology of these symptoms. This IL-6-related inflammatory syndrome is important to consider in critically ill patients with HIV and KSHV co-infection. C1 [Uldrick, Thomas S.; Wang, Victoria; O'Mahony, Deirdre; Aleman, Karen; Wyvill, Kathleen M.; Little, Richard F.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Ctr Clin, Hematol Serv, Bethesda, MD 20892 USA. [Marshall, Vickie; Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA. RP Yarchoan, R (reprint author), 10 Ctr Dr,Rm 6N106,MSC 1868, Bethesda, MD 20892 USA. EM yarchoan@helix.nih.gov RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 FU National Institutes of Health, National Cancer Institute; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Intramural Research Program of the National Institutes of Health, National Cancer Institute. Additional funding comes from the National Cancer Institute, National Institutes of Health (contract no. HHSN261200800001E). NR 40 TC 71 Z9 73 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2010 VL 51 IS 3 BP 350 EP 358 DI 10.1086/654798 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 629JS UT WOS:000280193800016 PM 20583924 ER PT J AU Powers, JH AF Powers, John H. TI Recommendations for Improving the Design, Conduct, and Analysis of Clinical Trials in Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; NOSOCOMIAL PNEUMONIA; DOUBLE-BLIND; NONINFERIORITY TRIALS; EQUIVALENCE TRIALS; END-POINTS; OPEN-LABEL; MULTICENTER; EFFICACY; THERAPY AB Overall decisions on the clinical use of new antimicrobials depend on the validity and reliability of the evidence from appropriately designed, conducted, and analyzed clinical trials. Because pneumonia is the sixth leading cause of death in the United States and the leading cause of infectious disease-related death, appropriate design of trials in hospital-acquired pneumonia and ventilator-associated pneumonia are an important public health issue. Several issues with the current design of trials in hospital-acquired pneumonia and/or ventilator-associated pneumonia potentially bias their results and raise questions about their validity. These issues are magnified in the context of noninferiority trials, in which bias can make interventions appear more similar, giving false-positive results of safety and effectiveness. The goal of this article is to provide a scientific basis for improving the validity, reliability, and efficiency of clinical trials in hospital-acquired pneumonia and/or ventilator-associated pneumonia to provide better information for decision making for patients, clinicians, regulators, and other stakeholders. C1 [Powers, John H.] NIAID, Sci Applicat Int Corp, Collaborat Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Powers, John H.] George Washington Univ, Sch Med, Bethesda, MD USA. [Powers, John H.] Univ Maryland, Sch Med, Bethesda, MD USA. RP Powers, JH (reprint author), SAIC Frederick, 6700B Rockledge Dr,Rm 1123, Bethesda, MD 20892 USA. EM powersjohn@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Disease; Acureon; Advanced Life Sciences; Astellas; Astra-Zeneca; Basilea; Centegen; Cerexa; Concert; Cubist; Destiny; Forest; Gilead; Great Lakes; Johnson and Johnson; LEO; Merck; Methylgene; MPEX; Pharming; Octoplus; Takeda; Theravance; Wyeth; US Food and Drug Administration; Infectious Diseases Society of America; American College of Chest Physicians; American Thoracic Society; Society of Critical Care Medicine; Pharmaceutical Research and Manufacturers of America; AstraZeneca Pharmaceuticals; Forest Pharmaceuticals FX National Cancer Institute, National Institutes of Health (contract HHSN261200800001E) and the National Institute of Allergy and Infectious Disease.; J.H.P. has received consulting fees from Acureon, Advanced Life Sciences, Astellas, Astra-Zeneca, Basilea, Centegen, Cerexa, Concert, Cubist, Destiny, Forest, Gilead, Great Lakes, Johnson and Johnson, LEO, Merck, Methylgene, MPEX, Pharming, Octoplus, Takeda, Theravance, and Wyeth.; This article was published as part of a supplement entitled "Workshop on Issues in the Design of Clinical Trials for Antibacterial Drugs for Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia," sponsored by the US Food and Drug Administration, Infectious Diseases Society of America, American College of Chest Physicians, American Thoracic Society, and the Society of Critical Care Medicine, with financial support from the Pharmaceutical Research and Manufacturers of America, AstraZeneca Pharmaceuticals, and Forest Pharmaceuticals. NR 61 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 2010 VL 51 SU 1 BP S18 EP S28 DI 10.1086/653036 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 619RO UT WOS:000279448000005 PM 20597667 ER PT J AU Yancey, MA Waxman, AJ Landgren, O AF Yancey, Mary Ann Waxman, Adam J. Landgren, Ola TI A Case Study Progression to Multiple Myeloma SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID INDEPENDENT RISK-FACTOR; LIGHT-CHAIN RATIO; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; CRITERIA; THERAPY; PROGNOSIS AB Multiple myeloma consistently is preceded by precursor states, which often are diagnosed incidentally in the laboratory. This case report illustrates the clinical dilemma of progression from precursor to full malignancy. The article also discusses future directions in management and research focusing on myelomagenesis. C1 [Yancey, Mary Ann; Waxman, Adam J.; Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yancey, MA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. FU National Cancer Institute of the National Institutes of Health FX The authors take full responsibility for the content of the article This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health The content of this article has been reviewed to ensure that it is balanced, objective, and free from commercial bias No financial relationships relevant to the content of this article have been disclosed by the editorial staff. NR 19 TC 1 Z9 1 U1 0 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD AUG PY 2010 VL 14 IS 4 BP 419 EP 422 DI 10.1188/10.CJON.419-422 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 636NK UT WOS:000280743800008 PM 20682498 ER PT J AU Waxman, AJ Kuehl, M Balakumaran, A Weiss, B Landgren, O AF Waxman, Adam J. Kuehl, Michael Balakumaran, Arun Weiss, Brendan Landgren, Ola TI Smoldering (Asymptomatic) Multiple Myeloma: Revisiting the Clinical Dilemma and Looking Into the Future SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Review DE Disease classification; Free light chain; M-protein; MGUS; Precursor disease ID UNDETERMINED SIGNIFICANCE MGUS; LENALIDOMIDE PLUS DEXAMETHASONE; MULTIPARAMETER FLOW-CYTOMETRY; INDEPENDENT RISK-FACTOR; IN-SITU HYBRIDIZATION; MARROW PLASMA-CELLS; TOLL-LIKE RECEPTORS; LIGHT-CHAIN RATIO; FACTOR-KAPPA-B; MONOCLONAL GAMMOPATHY AB Recent studies show that multiple myeloma (MM) is consistently preceded by an asymptomatic precursor state. Smoldering MM (SMM) is a MM precursor defined by an M-protein concentration >= 3 g/dL and/or >= 10% bone marrow plasma cells, in the absence of end-organ damage. Compared with individuals diagnosed with monoclonal gammopathy of undetermined significance (MGUS), patients with SMM have a much higher annual risk of developing MM. However, based on clinical observations, the natural history of SMM varies greatly, from stable MGUS-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into 3 risk groups. Importantly, because of considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Furthermore, until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early MM treatment strategies. Consequently, current clinical guidelines emphasize the application of close clinical monitoring followed by treatment when the patient develops symptomatic MM. This review focuses on novel biomarkers, molecular profiles, and microenvironmental interactions of interest in myelomagenesis. We also discuss how the integration of novel biologic markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future. C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Waxman, Adam J.] NIH Clin Ctr, Clin Res Training Program, Bethesda, MD USA. [Kuehl, Michael] NCI, Genet Branch, Bethesda, MD 20892 USA. [Balakumaran, Arun] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Weiss, Brendan] Walter Reed Army Med Ctr, Dept Med, Hematol Oncol Serv, Washington, DC 20307 USA. RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 9000 Rockville Pike,Bldg 10 Rm 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov FU National Cancer Institute of the National Institutes of Health; The Binding Site, Inc.; National Institutes of Health; Pfizer Inc. FX This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health.; The authors have no relevant relationships to disclose. Dr. Weiss receives research support from The Binding Site, Inc. Adam Waxman is a student in the Clinical Research Training Program at the National Institutes of Health which is made possible through a public-private partnership supported jointly by the National Institutes of Health intramural research program and a grant to the Foundation for NIH from Pfizer Inc. NR 103 TC 16 Z9 17 U1 0 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD AUG PY 2010 VL 10 IS 4 BP 248 EP 257 DI 10.3816/CLML.2010.n.053 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 634OK UT WOS:000280592400002 PM 20709660 ER PT J AU Bai, O Lin, P Huang, DD Fei, DY Floeter, MK AF Bai, Ou Lin, Peter Huang, Dandan Fei, Ding-Yu Floeter, Mary Kay TI Towards a user-friendly brain-computer interface: Initial tests in ALS and PLS patients SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; Brain-computer interface (BCI); Event-related desynchronization (ERD); Event-related synchronization (ERS); User-friendly; Amyotrophic lateral sclerosis (ALS); Primary lateral sclerosis (PLS); Motor control ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOVEMENT BETA-SYNCHRONIZATION; THOUGHT TRANSLATION DEVICE; SUPPORT VECTOR MACHINES; QUALITY-OF-LIFE; MOTOR IMAGERY; PARALYZED PATIENTS; MENTAL PRACTICE; RATING-SCALE; EEG AB Objective: Patients usually require long-term training for effective EEG-based brain-computer interface (BCI) control due to fatigue caused by the demands for focused attention during prolonged BCI operation. We intended to develop a user-friendly BCI requiring minimal training and less mental load. Methods: Testing of BCI performance was investigated in three patients with amyotrophic lateral sclerosis (ALS) and three patients with primary lateral sclerosis (PLS), who had no previous BCI experience. All patients performed binary control of cursor movement. One ALS patient and one PLS patient performed four-directional cursor control in a two-dimensional domain under a BCI paradigm associated with human natural motor behavior using motor execution and motor imagery. Subjects practiced for 510 min and then participated in a multi-session study of either binary control or four-directional control including online BCI game over 1.5-2 h in a single visit. Results: Event-related desynchronization and event-related synchronization in the beta band were observed in all patients during the production of voluntary movement either by motor execution or motor imagery. The online binary control of cursor movement was achieved with an average accuracy about 82.1 +/- 8.2% with motor execution and about 80% with motor imagery, whereas offline accuracy was achieved with 91.4 +/- 3.4% with motor execution and 83.3 +/- 8.9% with motor imagery after optimization. In addition, four-directional cursor control was achieved with an accuracy of 50-60% with motor execution and motor imagery. Conclusion: Patients with ALS or PLS may achieve BCI control without extended training, and fatigue might be reduced during operation of a BCI associated with human natural motor behavior. Significance: The development of a user-friendly BCI will promote practical BCI applications in paralyzed patients. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Bai, Ou; Huang, Dandan; Fei, Ding-Yu] Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, Richmond, VA 23284 USA. [Lin, Peter] Santa Clara Valley Med Ctr, Dept Neurol, San Jose, CA 95128 USA. [Bai, Ou] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Floeter, Mary Kay] NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. RP Bai, O (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, 401 W Main St,Room 1252, Richmond, VA 23284 USA. EM obai@vcu.edu RI Huang, Dandan/I-3108-2013 FU NIH, National Institute of Neurological Disorders and Stroke; State Key Laboratory of Digital Manufacturing, Equipment & Technology, Huazhong University of Science and Technology FX This research was partly supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. O. Bai received partial support from State Key Laboratory of Digital Manufacturing, Equipment & Technology, Huazhong University of Science and Technology. The authors would like to thank Dr. Mark Hallett for his valuable suggestions and Dr. Nobue Iwata for her coordination with patients. NR 62 TC 30 Z9 31 U1 1 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD AUG PY 2010 VL 121 IS 8 BP 1293 EP 1303 DI 10.1016/j.clinph.2010.02.157 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 614OA UT WOS:000279068200017 PM 20347612 ER PT J AU Pinsky, PF Blacka, A Kramer, BS Miller, A Prorok, PC Berg, C AF Pinsky, Paul F. Blacka, Amanda Kramer, Barnett S. Miller, Anthony Prorok, Philip C. Berg, Christine TI Assessing contamination and compliance in the prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial SO CLINICAL TRIALS LA English DT Article ID SELF-REPORT; NONCOMPLIANCE; FEASIBILITY; MORTALITY; PSA AB Background Recently, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial published 7-year complete prostate cancer mortality results, which showed no benefit of screening with prostate specific antigen (PSA) and digital rectal examination (DRE). An issue of concern was the substantial level of 'contamination', or use of PSA and DRE in control arm men. Purpose To provide a detailed description of contamination in PLCO. Methods Surveys inquiring about the most recent PSA and DRE use were given to a sample of control arm men throughout the screening phase of PLCO (years 0-5). A probability model was utilized to translate survey results into actual frequency counts of tests. To assess the impact of contamination, Surveillance, Epidemiology, and End Results (SEER) incidence rates from the pre-screening era (1985-1987) as well as contemporaneous rates, were applied to PLCO person-years of observation. Results Of 38,350 control arm men, 2427 were surveyed. Pre-trial screening and college education were statistically significantly associated with increased contamination rates. The estimated mean number of screening PSAs (DREs) in the control arm was 2.7 (1.1); this compares to 5.0 (3.5) in the screened arm. 1984 and 2538 prostate cancers were observed in the control and screened arms, respectively, during the screening phase. In the absence of screening, 960 and 949 would have been expected; with contemporaneous incidence rates, 1630 and 1611 were expected. Limitations Due to the limitations of the surveys, in terms of both reach and scope, the exact level of PSA and DRE use in control arm men cannot be known. Conclusions Use of prostate screening by control arm men was substantial, but also substantially less than in screened arm men. Detailed quantitative analyses of screening use across arms are critical for understanding current and future findings from the prostate component of PLCO. Clinical Trials 2010; 7: 303-311. http://ctj.sagepub.com C1 [Pinsky, Paul F.; Blacka, Amanda; Prorok, Philip C.; Berg, Christine] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA. [Miller, Anthony] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. EM pinskyp@mail.nih.gov FU National Cancer Institute FX The PLCO Trial was funded by contracts from the National Cancer Institute. The ClinicalTrials.gov identifier for PLCO is NCT00002540. The specific research described here received no additional grant or contract from any funding agency in the public, commercial, or not-for-profit sectors. The authors thank the PLCO PIs and the PLCO participants. NR 14 TC 64 Z9 65 U1 0 U2 3 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 AUG PY 2010 VL 7 IS 4 BP 303 EP 311 DI 10.1177/1740774510374091 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636MV UT WOS:000280741400001 PM 20571134 ER PT J AU Yeh, HC Clark, JM Emmons, KE Moore, RH Bennett, GG Warner, ET Sarwer, DB Jerome, GJ Miller, ER Volger, S Louis, TA Wells, B Wadden, TA Colditz, GA Appel, LJ AF Yeh, Hsin-Chieh Clark, Jeanne M. Emmons, Karen E. Moore, Renee H. Bennett, Gary G. Warner, Erica T. Sarwer, David B. Jerome, Gerald J. Miller, Edgar R., III Volger, Sheri Louis, Thomas A. Wells, Barbara Wadden, Thomas A. Colditz, Graham A. Appel, Lawrence J. TI Independent but coordinated trials: insights from the Practice-based Opportunities for Weight Reduction Trials Collaborative Research Group SO CLINICAL TRIALS LA English DT Article ID UNITED-STATES; RANDOMIZED-TRIAL; OBESITY; INTERVENTIONS; OVERWEIGHT; ADULTS AB Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with similar to 1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. C1 [Yeh, Hsin-Chieh] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Dept Med, Baltimore, MD 21218 USA. [Yeh, Hsin-Chieh; Clark, Jeanne M.; Miller, Edgar R., III; Appel, Lawrence J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Emmons, Karen E.; Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Emmons, Karen E.; Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Moore, Renee H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Moore, Renee H.; Sarwer, David B.; Volger, Sheri; Wadden, Thomas A.] Univ Penn, Dept Psychiat, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Bennett, Gary G.] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. [Warner, Erica T.; Colditz, Graham A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jerome, Gerald J.] Towson Univ, Dept Kinesiol, Towson, MD USA. [Louis, Thomas A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Wells, Barbara] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Appel, Lawrence J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Yeh, HC (reprint author), Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Dept Med, Baltimore, MD 21218 USA. EM hyeh1@jhmi.edu RI Colditz, Graham/A-3963-2009; OI volger, sheri/0000-0002-1689-1173; Colditz, Graham/0000-0002-7307-0291; Jerome, Gerald/0000-0003-0612-2626 FU NHLBI [U01HL087071, U01HL087085, U01HL087072, NCT00661817, NCT00783315, NCT00826774] FX The POWER Trials Collaborative Research Group is supported by NHLBI grants: U01HL087071 (Washington University), U01HL087085 (Johns Hopkins University), and U01HL087072 (University of Pennsylvania). The ClinicalTrials.gov identifiers are NCT00661817 (Washington University), NCT00783315 (Johns Hopkins University), and NCT00826774 (University of Pennsylvania). NR 15 TC 25 Z9 25 U1 0 U2 4 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 AUG PY 2010 VL 7 IS 4 BP 322 EP 332 DI 10.1177/1740774510374213 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636MV UT WOS:000280741400003 PM 20573639 ER PT J AU Zook, PM Jordan, C Adams, B Visness, CM Walter, M Pollenz, K Logan, J Tesson, E Smartt, E Chen, A D'Agostino, J Gern, JE AF Zook, Patricia M. Jordan, Carolina Adams, Bernadette Visness, Cynthia M. Walter, Michelle Pollenz, Kathryn Logan, Jennette Tesson, Elizabeth Smartt, Ernestine Chen, Amy D'Agostino, John Gern, James E. TI Retention strategies and predictors of attrition in an urban pediatric asthma study SO CLINICAL TRIALS LA English DT Article ID LONGITUDINAL RESEARCH; RANDOMIZED-TRIAL; CHILDREN; RECRUITMENT; COHORT; WOMEN; INTERVIEWER; LESSONS AB Background The Urban Environment and Childhood Asthma (URECA) study is a multicenter prospective birth cohort study designed to examine factors related to the development of childhood asthma and allergies in an inner-city population. The retention of these participants has been challenging due to high mobility, inconsistent phone service, custody issues, and stressful life situations. Purpose In this article, we describe the specific retention challenges we encountered during the first 2 years of follow-up in URECA and the strategies we utilized to address them. We also examine how selected maternal characteristics and other factors are related to retention and missed study visits. Methods Strategies implemented to engage participants included: collecting updated and alternative contact information, after-hours phone calls to participants, culturally competent staff, flexible study event scheduling, clinic visit transportation, quarterly newsletters, retention events, drop-in home visits, and cell phone reimbursements. An internally developed web-based data management system enabled close monitoring by site teams and the coordinating center. The rate of deactivations was calculated using survival analysis. Characteristics of active and deactivated participants were compared using the chi-squared test with a Cochran-Mantel - Haenszel adjustment for study site. The proportion of missed visits of the total expected in the first 2 years was calculated and compared by family characteristics using an ANOVA model or a trend test controlling for study site. All analyses were performed using SAS version 9.1 (Cary, NC). Results The 2-year retention rate was 89%. Participation in the first study event predicted subsequent engagement in study activities. Mothers who did not complete the first visit were more likely to miss future events (46.1% vs. 8.9%, p < 0.0001) and to be deactivated (38.5% vs. 4.5%, p < 0.0001). Mothers under 18 years of age were more likely to leave the study compared to older mothers (22.7% vs. 10.1%, p = 0.02). Also, mothers who were married missed fewer events than those not married (8.8% vs. 15.6%, p = 0.01). In addition, deactivations were more common when the child had entered daycare by 3 months of age (10.9% vs. 3.6%, p = 0.05). Limitations The URECA population is predominantly minority, thus our findings might not be generalizable to other populations. Furthermore, we may not be able to observe the effects that might exist in a more diverse population. For example, 86% of the mothers are unmarried, making it difficult to reliably examine the effect of marital status. Conclusion In research, successfully engaging and retaining participants is essential for achieving the study objectives. Identifying factors related to missed visits and deactivations are the initial step in recognizing the potential at-risk participants and can enable the design of targeted strategies to retain participants. Clinical Trials 2010; 7: 400-410. http://ctj.sagepub.com. C1 [Zook, Patricia M.; Jordan, Carolina; Visness, Cynthia M.] Rho Fed Syst Div Inc, Stat & Clin Coordinating Ctr, Chapel Hill, NC USA. [Jordan, Carolina; Pollenz, Kathryn] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Adams, Bernadette; Logan, Jennette] Johns Hopkins Univ, Baltimore, MD USA. [Tesson, Elizabeth] Washington Univ, Sch Med, Pediat Patient Oriented Res Unit, St Louis, MO USA. [Smartt, Ernestine] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Gern, James E.] Univ Wisconsin, Dept Pediat & Med, Madison, WI USA. [Chen, Amy; D'Agostino, John] Columbia Univ, Pediat Pulm Dept, New York, NY USA. RP Zook, PM (reprint author), Rho Fed Syst Div Inc, Stat & Clin Coordinating Ctr, Chapel Hill, NC USA. EM pat_zook@rhoworld.com FU NCRR NIH HHS [1UL1RR025771, M01 RR000052, 5UL1RR024992-02, M01 RR000071, M01 RR000533, UL1 RR024992, UL1 RR024156, M01RR00071, 1UL1RR024156, M01RR00533, RR00052, UL1 RR025771]; NIAID NIH HHS [N01-AI-25482, N01AI25482, N01AI25496, N01-AI-25496, N01 AI025482] NR 19 TC 19 Z9 19 U1 2 U2 11 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 AUG PY 2010 VL 7 IS 4 BP 400 EP 410 DI 10.1177/1740774510373798 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636MV UT WOS:000280741400010 PM 20571137 ER PT J AU Bingley, PJ Williams, AJK Colman, PG Gellert, SA Eisenbarth, G Yu, LP Perdue, LH Pierce, JJ Hilner, JE Nierras, C Akolkar, B Steffes, MW AF Bingley, Polly J. Williams, Alistair J. K. Colman, Peter G. Gellert, Shane A. Eisenbarth, George Yu, Liping Perdue, Letitia H. Pierce, June J. Hilner, Joan E. Nierras, Concepcion Akolkar, Beena Steffes, Michael W. CA T1DGC TI Measurement of islet cell antibodies in the Type 1 Diabetes Genetics Consortium: efforts to harmonize procedures among the laboratories SO CLINICAL TRIALS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; GLUTAMIC-ACID DECARBOXYLASE; STANDARDIZATION PROGRAM; AUTOANTIBODY MARKERS; IA-2; IDENTIFICATION; PREDICTION; IDDM AB Background and Purpose Three network laboratories measured antibodies to islet autoantigens. Antibodies to glutamic acid decarboxylase (GAD65 [GADA]) and the intracellular portion of protein tyrosine phosphatase (IA-2(ic) [IA-2A]) were measured by similar, but not identical, methods in samples from participants in the Type 1 Diabetes Genetics Consortium (T1DGC). Methods All laboratories used radiobinding assays to detect antibodies to in vitro transcribed and translated antigen, but with different local standards, calibrated against the World Health Organization (WHO) reference reagent. Using a common method to calculate WHO units/mL, we compared results reported on samples included in the Diabetes Autoantibody Standardization Program (DASP), and developed standard methods for reporting in WHO units/mL. We evaluated intra-assay and inter-assay coefficient of variation (CV) in blind duplicate samples and assay comparability in four DASP workshops. Results Values were linearly related in the three laboratories for both GADA and IA-2A, and intra-assay technical errors for values within the standard curve were below 13% for GADA and below 8.5% for IA-2A. Correlations in samples tested 1-2 years apart were >97%. Over the course of the study, internal CVs were 10-20% with one exception, and the laboratories concordantly called samples GADA or IA-2A positive or negative in 96.7% and 99.6% of duplicates within the standard curve. Despite acceptable CVs and general concordance in ranking samples, the laboratories differed markedly in absolute values for GADA and IA-2A reported in WHO units/mL in DASP over a large range of values. Limitations With three laboratories using different assay methods (including calibrators), consistent values among them could not be attained. Conclusions Modifications in the assays are needed to improve comparability of results expressed as WHO units/mL across laboratories. It will be essential to retain high intra- and inter-assay precision, sensitivity and specificity and to confirm the accuracy of harmonized methods. Clinical Trials 2010; 7: S56-S64. http://ctj.sagepub.com. C1 [Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Bingley, Polly J.; Williams, Alistair J. K.] Univ Bristol, Dept Clin Sci N Bristol, Bristol, Avon, England. [Colman, Peter G.; Gellert, Shane A.] Royal Melbourne Hosp, Dept Endocrinol & Diabet, Melbourne, Vic, Australia. [Colman, Peter G.; Gellert, Shane A.] Royal Melbourne Hosp, Dept Pathol, Melbourne, Vic, Australia. [Eisenbarth, George; Yu, Liping] Univ Colorado Hlth Sci, Barbara Davis Ctr Childhood Diabet, Denver, CO USA. [Perdue, Letitia H.; Pierce, June J.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Hilner, Joan E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Nierras, Concepcion] Juvenile Diabet Res Fdn Int, New York, NY USA. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. RP Steffes, MW (reprint author), Univ Minnesota, Sch Med, Dept Lab Med & Pathol, 420 Delaware St SE, Minneapolis, MN 55455 USA. EM steff001@umn.edu RI Williams, Alistair/E-7647-2013; Ferry, Robert/O-6107-2016; OI Williams, Alistair/0000-0002-3615-3899 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); [U01 DK062418] FX This research uses resources provided by the Type 1 Diabetes Genetics Consortium (T1DGC), a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. NR 11 TC 15 Z9 16 U1 0 U2 4 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 AUG PY 2010 VL 7 SU 1 BP S56 EP S64 DI 10.1177/1740774510373496 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636DB UT WOS:000280707300004 PM 20693189 ER PT J AU Hall, MA King, NMP Perdue, LH Hilner, JE Akolkar, B Greenbaum, CJ McKeon, C AF Hall, Mark A. King, Nancy M. P. Perdue, Letitia H. Hilner, Joan E. Akolkar, Beena Greenbaum, Carla J. McKeon, Catherine CA T1DGC TI Biobanking, consent, and commercialization in international genetics research: the Type 1 Diabetes Genetics Consortium SO CLINICAL TRIALS LA English DT Article ID INTELLECTUAL PROPERTY; INFORMED-CONSENT; BIOTECHNOLOGY; EXPERIENCE; MULTICENTER; TRIAL AB Background and Purpose This article describes several ethical, legal, and social issues typical of international genetics biobanking, as encountered in the Type 1 Diabetes Genetics Consortium (T1DGC). Methods By studying the examples set and lessons learned from other international biobanking studies and by devoting considerable time and resources to identifying, addressing, and continually monitoring ethical and regulatory concerns, T1DGC was able to minimize the problems reported by some earlier studies. Conclusions Several important conclusions can be drawn based on the experience in this study: (1) Basic international standards for research ethics review and informed consent are broadly consistent across developed countries. (2) When consent forms are adapted locally and translated into different languages, discrepancies are inevitable and therefore require prompt central review and resolution before research is initiated. (3) Providing separate 'check-box' consent for different elements of a study creates confusion and may not be essential. (4) Creating immortalized cell lines to aid future research is broadly acceptable, both in the US and internationally. (5) Imposing some limits on the use of stored samples aids in obtaining ethics approvals worldwide. (6) Allowing potential commercial uses of donated samples is controversial in some Asian countries. (7) Obtaining government approvals can be labor-intensive and time-consuming, and can require legal and diplomatic skills. Clinical Trials 2010; 7: S33-S45. http://ctj.sagepub.com. C1 [Hall, Mark A.; King, Nancy M. P.; Perdue, Letitia H.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Hilner, Joan E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Akolkar, Beena; McKeon, Catherine] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. [Greenbaum, Carla J.] Benaroya Res Inst, Seattle, WA USA. RP Hall, MA (reprint author), Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Med Ctr Blvd,PP-2, Winston Salem, NC 27157 USA. EM mhall@wfubmc.edu RI Ferry, Robert/O-6107-2016 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); [U01 DK062418] FX This research uses resources provided by the Type 1 Diabetes Genetics Consortium (T1DGC), a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and Human Development (NICHD), and the Juvenile Diabetes Research Foundation International (JDRF), and supported by U01 DK062418. NR 24 TC 13 Z9 13 U1 1 U2 5 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 AUG PY 2010 VL 7 SU 1 BP S33 EP S45 DI 10.1177/1740774510373492 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636DB UT WOS:000280707300002 PM 20693188 ER PT J AU Hilner, JE Perdue, LH Sides, EG Pierce, JJ Wagner, AM Aldrich, A Loth, A Albret, L Wagenknecht, LE Nierras, C Akolkar, B AF Hilner, Joan E. Perdue, Letitia H. Sides, Elizabeth G. Pierce, June J. Waegner, Ana M. Aldrich, Alan Loth, Amanda Albret, Lotte Wagenknecht, Lynne E. Nierras, Concepcion Akolkar, Beena CA T1DGC TI Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (T1DGC) SO CLINICAL TRIALS LA English DT Article ID DATA COORDINATING CENTER; GENOME-WIDE ASSOCIATION; MULTIPLEX FAMILIES; CLINICAL-TRIAL; DIG TRIAL; OBJECTIVES; CHALLENGES; EXPERIENCE; RATIONALE; NETWORK AB Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide. Methods T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center. A Steering Committee, with representatives from each network, the Coordinating Center, and the funding organizations, was responsible for T1DGC operations. The Coordinating Center, with regional network representatives, developed study documents and data systems. Each network established laboratories for: DNA extraction and cell line production; human leukocyte antigen genotyping; and autoantibody measurement. Samples were tracked from the point of collection, processed at network laboratories and stored for deposit at National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories. Phenotypic data were collected and entered into the study database maintained by the Coordinating Center. Results T1DGC achieved its original ASP recruitment goal. In response to research design changes, the T1DGC infrastructure also recruited trios, cases, and controls. Results of genetic analyses have identified many novel regions that affect susceptibility to type 1 diabetes. T1DGC created a resource of data and samples that is accessible to the research community. Limitations Participation in T1DGC was declined by some countries due to study requirements for the processing of samples at network laboratories and/or final deposition of samples in NIDDK Central Repositories. Re-contact of participants was not included in informed consent templates, preventing collection of additional samples for functional studies. Conclusions T1DGC implemented a distributed, regional network structure to reach ASP recruitment targets. The infrastructure proved robust and flexible enough to accommodate additional recruitment. T1DGC has established significant resources that provide a basis for future discovery in the study of type 1 diabetes genetics. Clinical Trials 2010; 7: S5-S32. http://ctj.sagepub.com. C1 [Hilner, Joan E.] Univ Alabama, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35294 USA. [Perdue, Letitia H.; Sides, Elizabeth G.; Pierce, June J.; Wagenknecht, Lynne E.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Waegner, Ana M.; Albret, Lotte] Hagedorn Res Inst, Gentofte, Denmark. [Waegner, Ana M.] Hosp Univ Insular Gran Canaria, Dept Endocrinol, Las Palmas De Gran Cana, Spain. [Waegner, Ana M.] Univ Las Palmas Gran Canaria, Dept Med & Surg Sci, Las Palmas Gran Canaria, Spain. [Aldrich, Alan] Univ Alaska, Anchorage Coll Arts & Sci, Anchorage, AK USA. [Loth, Amanda] Walter & Eliza Hall Inst Med Res, Burnet Clin Res Unit, Melbourne, Vic 3050, Australia. [Nierras, Concepcion] Juvenile Diabet Res Fdn Int, New York, NY USA. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. RP Hilner, JE (reprint author), Univ Alabama, Dept Biostat, Sch Publ Hlth, 1665 Univ Blvd,Ryals Publ Hlth Bldg,Suite 514D, Birmingham, AL 35294 USA. EM jhilner@ms.soph.uab.edu RI Argente , Jesus /K-1167-2014; Boehm, Bernhard/F-8750-2015; Mauricio, Didac/B-7951-2009; Tillmann, Vallo/G-8118-2012; Li, Dawei/A-3466-2011; de Bakker, Paul/B-8730-2009; Cameron, Fergus/N-9535-2015; Ferry, Robert/O-6107-2016; Skrha, Jan/C-3095-2017; OI Ludvigsson, Johnny/0000-0003-1695-5234; Battelino, Tadej/0000-0002-0273-4732; Burren, Oliver/0000-0002-3388-5760; Dunger, Professor David/0000-0002-2566-9304; Johannesen, Jesper/0000-0003-2772-2567; Avbelj Stefanija, Magdalena/0000-0002-0836-5114; McLaren, William/0000-0001-6218-1116; Cinek, Ondrej/0000-0002-0526-8714; Castano, Luis/0000-0003-0437-9401; Brismar, Kerstin/0000-0002-5241-514X; Argente , Jesus /0000-0001-5826-0276; Mauricio, Didac/0000-0002-2868-0250; Tillmann, Vallo/0000-0002-5279-4493; de Bakker, Paul/0000-0001-7735-7858; Skrha, Jan/0000-0001-8012-8802; Brodnicki, Thomas/0000-0003-2294-315X; Concannon, Patrick/0000-0002-5801-1859; Schofield, Ellen/0000-0003-0648-1418; Walker, Neil/0000-0001-9796-7688 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); [U01 DK062418] FX This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. NR 30 TC 9 Z9 9 U1 0 U2 11 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 AUG PY 2010 VL 7 SU 1 BP S5 EP S32 DI 10.1177/1740774510373497 PG 28 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636DB UT WOS:000280707300001 PM 20603248 ER PT J AU Mychaleckyj, JC Noble, JA Moonsamy, PV Carlson, JA Varney, MD Post, J Helmberg, W Pierce, JJ Bonella, P Fear, AL Lavant, E Louey, A Boyle, S Lane, JA Sali, P Kim, S Rappner, R Williams, DT Perdue, LH Reboussin, DM Tait, BD Akolkar, B Hilner, JE Steffes, MW Erlich, HA AF Mychaleckyj, Josyf C. Noble, Janelle A. Moonsamy, Priscilla V. Carlson, Joyce A. Varney, Michael D. Post, Jeff Helmberg, Wolfgang Pierce, June J. Bonella, Persia Fear, Anna Lisa Lavant, Eva Louey, Anthony Boyle, Sean Lane, Julie A. Sali, Paul Kim, Samuel Rappner, Rebecca Williams, Dustin T. Perdue, Letitia H. Reboussin, David M. Tait, Brian D. Akolkar, Beena Hilner, Joan E. Steffes, Michael W. Erlich, Henry A. CA T1DGC TI HLA genotyping in the international Type 1 Diabetes Genetics Consortium SO CLINICAL TRIALS LA English DT Article ID MULTIPLEX FAMILIES; SUSCEPTIBILITY; LINKAGE; MELLITUS; GENES; LOCI AB Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers. Purpose In this article, we present the operational strategy of training, classification, reporting, and quality control of HLA genotyping in four laboratories on three continents over nearly 5 years. Methods Methods to standardize HLA genotyping at eight loci included: central training and initial certification testing; the use of uniform reagents, protocols, instrumentation, and software versions; an automated data transfer; and the use of standardized nomenclature and allele databases. We implemented a rigorous and consistent quality control process, reinforced by repeated workshops, yearly meetings, and telephone conferences. Results A total of 15,246 samples have been HLA genotyped at eight loci to four-digit resolution; an additional 6797 samples have been HLA genotyped at two loci. The genotyping repeat rate decreased significantly over time, with an estimated unresolved Mendelian inconsistency rate of 0.21%. Annual quality control exercises tested 2192 genotypes (4384 alleles) and achieved 99.82% intra-laboratory and 99.68% inter-laboratory concordances. Limitations The chosen genotyping platform was unable to distinguish many allele combinations, which would require further multiple stepwise testing to resolve. For these combinations, a standard allele assignment was agreed upon, allowing further analysis if required. Conclusions High-resolution HLA genotyping can be performed in multiple laboratories using standard equipment, reagents, protocols, software, and communication to produce consistent and reproducible data with minimal systematic error. Many of the strategies used in this study are generally applicable to other large multi-center studies. Clinical Trials 2010; 7: S75-S87. http://ctj.sagepub.com. C1 [Moonsamy, Priscilla V.; Post, Jeff; Bonella, Persia; Boyle, Sean; Sali, Paul; Kim, Samuel; Erlich, Henry A.] Roche Mol Syst Inc, Pleasanton, CA 94588 USA. [Mychaleckyj, Josyf C.] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA. [Noble, Janelle A.; Fear, Anna Lisa; Lane, Julie A.; Erlich, Henry A.] Childrens Hosp Oakland Res Inst, Oakland, CA USA. [Carlson, Joyce A.; Rappner, Rebecca] Univ Hosp MAS, Malmo, Sweden. [Varney, Michael D.; Louey, Anthony; Tait, Brian D.] Australian Red Cross Blood Serv, VTIS, Melbourne, Vic, Australia. [Helmberg, Wolfgang] Med Univ, Dept Blood Grp Serol & Transfus Med, Graz, Austria. [Pierce, June J.; Williams, Dustin T.; Perdue, Letitia H.; Reboussin, David M.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. [Hilner, Joan E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Erlich, HA (reprint author), Roche Mol Syst Inc, 4300 Hacienda Dr, Pleasanton, CA 94588 USA. EM henry.erlich@roche.com RI Ferry, Robert/O-6107-2016 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); [U01 DK062418] FX This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and is supported by U01 DK062418. NR 17 TC 25 Z9 26 U1 0 U2 4 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 AUG PY 2010 VL 7 SU 1 BP S75 EP S87 DI 10.1177/1740774510373494 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636DB UT WOS:000280707300006 PM 20595243 ER PT J AU Perdue, LH Albret, L Aldrich, A Loth, A Sides, EG Dove, A Wagner, AM Waterman, R Pierce, JJ Akolkar, B Steffes, MW Hilner, JE AF Perdue, Letitia H. Albret, Lotte Aldrich, Alan Loth, Amanda Sides, Elizabeth G. Dove, Angela Waegner, Ana M. Waterman, Rebecca Pierce, June J. Akolkar, Beena Steffes, Michael W. Hilner, Joan E. CA T1DGC TI Quality control of phenotypic forms data in the Type 1 Diabetes Genetics Consortium SO CLINICAL TRIALS LA English DT Article ID TRIAL; RATIONALE; DESIGN AB Background When collecting phenotypic data in clinics across the globe, the Type 1 Diabetes Genetics Consortium (T1DGC) used several techniques that ensured consistency, completeness, and accuracy of the data. Purpose The aim of this article is to describe the procedures used for collection, entry, processing, and management of the phenotypic data in this international study. Methods The T1DGC ensured the collection of high quality data using the following procedures throughout the entire study period. The T1DGC used centralized and localized training, required a pilot study, certified all data entry personnel, created standardized data collection forms, reviewed a sample of form sets quarterly throughout the duration of the study, and used a data entry system that provided immediate feedback to those entering the data. Results Due to the intensive procedures in developing the forms, the study was able to uphold consistency among all clinics and minimal changes were required after implementation of the forms. The train-the-trainer model was efficient and only a small number of clinics had to repeat a pilot study. The study was able to maintain a low percentage of missing data (<0.001%) and low duplicate data entry error rate (0.10%). Conclusions It is critical to provide immediate follow-up in order to reinforce training and ensure the quality of the data collected and entered. Clinical Trials 2010; 7: S46-S55. http://ctj.sagepub.com. C1 [Perdue, Letitia H.; Sides, Elizabeth G.; Pierce, June J.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Albret, Lotte; Waegner, Ana M.] Hagedorn Res Inst, Gentofte, Denmark. [Aldrich, Alan] Univ Alaska, Anchorage Coll Arts & Sci, Anchorage, AK USA. [Loth, Amanda; Waterman, Rebecca] Walter & Eliza Hall Inst Med Res, Burnet Clin Res Unit, Melbourne, Vic 3050, Australia. [Dove, Angela] Benaroya Res Inst, Seattle, WA USA. [Waegner, Ana M.] Hosp Univ Insular Gran Canaria, Dept Endocrinol, Las Palmas Gran Canaria, Spain. [Waegner, Ana M.] Univ Las Palmas Gran Canaria, Dept Med & Surg Sci, Las Palmas Gran Canaria, Spain. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. [Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Hilner, Joan E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. RP Perdue, LH (reprint author), Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Med Ctr Blvd,WC-22, Winston Salem, NC 27157 USA. EM lperdue@wfubmc.edu RI Ferry, Robert/O-6107-2016 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); [U01 DK062418] FX This research uses resources provided by the T1DGC, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and supported by U01 DK062418. NR 11 TC 3 Z9 3 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 AUG PY 2010 VL 7 SU 1 BP S46 EP S55 DI 10.1177/1740774510373495 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636DB UT WOS:000280707300003 PM 20603249 ER PT J AU Rosinger, S Nutland, S Mickelson, E Varney, MD Boehm, BO Olsem, GJ Hansen, JA Nicholson, I Hilner, JE Perdue, LH Pierce, JJ Akolkar, B Nierras, C Steffes, MW AF Rosinger, Silke Nutland, Sarah Mickelson, Eric Varney, Michael D. Boehm, Bernard O. Olsem, Gary J. Hansen, John A. Nicholson, Ian Hilner, Joan E. Perdue, Letitia H. Pierce, June J. Akolkar, Beena Nierras, Concepcion Steffes, Michael W. CA T1DGC TI Collection and processing of whole blood for transformation of peripheral blood mononuclear cells and extraction of DNA: the Type 1 Diabetes Genetics Consortium SO CLINICAL TRIALS LA English DT Article ID FAMILIES AB Background and Purpose To yield large amounts of DNA for many genotype analyses and to provide a renewable source of DNA, the Type 1 Diabetes Genetics Consortium (T1DGC) harvested DNA and peripheral blood mononuclear cells (PBMCs) from individuals with type 1 diabetes and their family members in several regions of the world. Methods DNA repositories were established in Asia-Pacific, Europe, North America, and the United Kingdom. To address region-specific needs, different methods and sample processing techniques were used among the laboratories to extract and to quantify DNA and to establish Epstein-Barr virus transformed cell lines. Results More than 98% of the samples of PBMCs were successfully transformed. Approximately 20-25 mu g of DNA were extracted per mL of whole blood. Extraction of DNA from the cell pack ranged from 92 to 165 mu g per cell pack. In addition, the extracted DNA from whole blood or transformed cells was successfully utilized in each regional human leukocyte antigen genotyping laboratory and by several additional laboratories performing consortium-wide genotyping projects. Limitations Although the isolation of PBMCs was consistent among sites, the measurement of DNA was difficult to harmonize. Conclusions DNA repositories can be established in different regions of the world and produce similar amounts of high-quality DNA for a variety of high-throughput genotyping techniques. Furthermore, even with the distances and time necessary for transportation, highly efficient transformation of PBMCs is possible. For future studies/trials involving several laboratories in different locations, the T1DGC experience includes examples of protocols that may be applicable. In summary, T1DGC has developed protocols that would be of interest to any scientific organization attempting to overcome the logistical problems associated with studies/trials spanning multiple research facilities, located in different regions of the world. Clinical Trials 2010; 7: S65-S74. http://ctj.sagepub.com C1 [Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Rosinger, Silke; Boehm, Bernard O.] Univ Ulm, Dept Internal Med, Div Endocrinol & Diabet, D-7900 Ulm, Germany. [Nutland, Sarah] Univ Cambridge, Cambridge Inst Med Res, JDRF Wellcome Trust Diabet & Inflammat Lab, Cambridge, England. [Mickelson, Eric; Olsem, Gary J.; Hansen, John A.] Fred Hutchinson Canc Res Ctr, Human Immunogenet Program, Seattle, WA 98104 USA. [Varney, Michael D.; Nicholson, Ian] Australian Red Cross Blood Serv, VTIS, Melbourne, Vic, Australia. [Hilner, Joan E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Perdue, Letitia H.; Pierce, June J.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. [Nierras, Concepcion] Juvenile Diabet Res Fdn Int, New York, NY USA. RP Steffes, MW (reprint author), Univ Minnesota, Sch Med, Dept Lab Med & Pathol, 420 Delaware St SE, Minneapolis, MN 55455 USA. EM steff001@umn.edu RI Boehm, Bernhard/F-8750-2015 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); [U01 DK062418] FX This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD), and Juvenile Diabetes Research Foundation International (JDRF) and is supported by U01 DK062418. NR 11 TC 11 Z9 11 U1 0 U2 3 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 AUG PY 2010 VL 7 SU 1 BP S65 EP S74 DI 10.1177/1740774510373493 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636DB UT WOS:000280707300005 PM 20595244 ER PT J AU Doo, EC Ghany, MG AF Doo, Edward C. Ghany, Marc G. TI Hepatitis B Virology for Clinicians SO CLINICS IN LIVER DISEASE LA English DT Article DE Hepatitis B virus; Polymerase; Antiviral Therapy; cccDNA ID CLOSED CIRCULAR DNA; GENOMIC RNA ENCAPSIDATION; VIRUS-INFECTION; LAMIVUDINE THERAPY; ANTIVIRAL THERAPY; E-ANTIGEN; HEPADNAVIRUS INFECTION; REVERSE TRANSCRIPTION; POLYMERASE-ACTIVITY; TYROSINE RESIDUE AB A basic understanding of the molecular events involved in the hepatitis B virus (HBV) life cycle is essential to better appreciate the natural history and atypical presentations of the disease and to develop individual management plans based on readily available virologic tests. With the improved knowledge gained from studying the molecular biology of HBV, novel approaches to inhibition of viral replication are being explored, such as viral entry inhibitors, nucleocapsid inhibitors, and inhibitors of viral assembly. However, the ultimate goal of therapy is to identify strategies to eliminate covalently closed circular DNA from infected hepatocytes. This article serves to introduce the clinically relevant aspects of the HBV life cycle as they pertain to patient management. C1 [Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Doo, Edward C.] NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDKD, 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 National Institutes of Health, Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases. NR 52 TC 5 Z9 5 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 1089-3261 J9 CLIN LIVER DIS JI Clin. Liver Dis. PD AUG PY 2010 VL 14 IS 3 BP 397 EP + DI 10.1016/j.cld.2010.05.001 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639OP UT WOS:000280984400003 PM 20638021 ER PT J AU Dording, CM Mischoulon, D Goodness, TM Baer, L Clain, A Stewart, JW Matthews, JD McGrath, PJ Nierenberg, AA Fava, M Papakostas, GI AF Dording, Christina M. Mischoulon, David Goodness, Tracie M. Baer, Lee Clain, Alisabet Stewart, Jonathan W. Matthews, John D. McGrath, Patrick J. Nierenberg, Andrew A. Fava, Maurizio Papakostas, George I. TI Psychoticism and Paranoid Ideation in Patients With Nonpsychotic Major Depressive Disorder: Prevalence, Response to Treatment, and Impact on Short- and Long-Term Treatment Outcome SO CNS SPECTRUMS LA English DT Article AB Objective/Introduction: We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute antidepressant response and on relapse prevention. Methods: Subjects with Structured Clinical Interview for DSM Disorders-diagnosed non psychotic MDD were recruited into a clinical trial of open-label fluoxetine 10-60 mg/day for 12 weeks, followed by double-blind randomization of responders (n=262) to fluoxetine continuation or placebo for 12 months. PI and P were assessed with the patient-rated SCL-90. The association of these symptoms with response to treatment was assessed by logistic regression. Results: We found significant decreases in PI and P during acute treatment phase for fluoxetine responders and nonresponders, although only 10.3% and 7.5% of patients experienced a >50% reduction in PI and P scores, respectively. Neither PI nor P scores significantly predicted time to relapse. P scores predicted a lower response rate to treatment with fluoxetine. Discussion:The results of the present study suggest that there is a significant relationship between the presence of psychoticism in patients with nonpsychotic MDD, and the likelihood of overall depressive symptom improvement following a trial of monotherapy with fluoxetine. Conclusion: An increased burden of psychoticism in depressed subjects may confer poorer response to fluoxetine, but not increased risk of relapse among fluoxetine responders. C1 [Dording, Christina M.] Harvard Univ, Sch Med, Sexual Behav Studies, Boston, MA USA. [Dording, Christina M.; Mischoulon, David; Nierenberg, Andrew A.; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Mischoulon, David] Massachusetts Gen Hosp, Res, Boston, MA 02114 USA. [Mischoulon, David] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Goodness, Tracie M.; Clain, Alisabet; Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Baer, Lee] Harvard Univ, Sch Med, Psychol, Boston, MA USA. [Baer, Lee] Massachusetts Gen Hosp, Dept Psychiat, Psychol, Boston, MA 02114 USA. [Stewart, Jonathan W.; McGrath, Patrick J.] Columbia Univ Coll Phys & Surg, Psychiat Clin, 630 W 168th St, New York, NY 10032 USA. [Stewart, Jonathan W.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Matthews, John D.] Massachusetts Gen Hosp, Inpatient Res & Training, Boston, MA USA. [Matthews, John D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [McGrath, Patrick J.] New York State Psychiat Inst & Hosp, Depress Evaluat Serv, New York, NY 10032 USA. [Nierenberg, Andrew A.] NIMH, Bipolar Trials Network, Bethesda, MD USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. [Papakostas, George I.] Massachusetts Gen Hosp, Treatment Resistant Depress Studies, Boston, MA 02114 USA. RP Dording, CM (reprint author), Massachusetts Gen Hosp, 50 Staniford St,401, Boston, MA 02114 USA. EM cdording@partners.org NR 34 TC 0 Z9 0 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD AUG PY 2010 VL 15 IS 8 BP 515 EP 521 DI 10.1017/S1092852900000468 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V44BS UT WOS:000209725100006 PM 20703198 ER PT J AU Balagopalan, L Coussens, NP Sherman, E Samelson, LE Sommers, CL AF Balagopalan, Lakshmi Coussens, Nathan P. Sherman, Eilon Samelson, Lawrence E. Sommers, Connie L. TI The LAT Story: A Tale of Cooperativity, Coordination, and Choreography SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID T-CELL-RECEPTOR; C-CBL PROTOONCOGENE; PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; PLASMA-MEMBRANE MICRODOMAINS; MEDIATED SIGNALING PATHWAYS; HOMOLOGY 2 DOMAIN; FC-EPSILON-RI; ANTIGEN RECEPTOR; ADAPTER PROTEIN; LIPID RAFTS AB The adapter molecule LAT is a nucleating site for multiprotein signaling complexes that are vital for the function and differentiation of T cells. Extensive investigation of LAT in multiple experimental systems has led to an integrated understanding of the formation, composition, regulation, dynamic movement, and function of LAT-nucleated signaling complexes. This review discusses interactions of signaling molecules that bind directly or indirectly to LAT and the role of cooperativity in stabilizing LAT-nucleated signaling complexes. In addition, it focuses on how imaging studies visualize signaling assemblies as signaling clusters and demonstrate their dynamic nature and cellular fate. Finally, this review explores the function of LAT based on the interpretation of mouse models using various LAT mutants. C1 [Balagopalan, Lakshmi; Coussens, Nathan P.; Sherman, Eilon] NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov RI Sherman, Eilon /B-3688-2014 OI Sherman, Eilon /0000-0002-7403-6036 NR 160 TC 73 Z9 75 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD AUG PY 2010 VL 2 IS 8 AR a005512 DI 10.1101/cshperspect.a005512 PG 20 WC Cell Biology SC Cell Biology GA 634MY UT WOS:000280588200003 PM 20610546 ER PT J AU Misteli, T AF Misteli, Tom TI Higher-order Genome Organization in Human Disease SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; DE-LANGE-SYNDROME; BECKWITH-WIEDEMANN-SYNDROME; SISTER-CHROMATID COHESION; SILVER-RUSSELL-SYNDROME; DNA-DAMAGE RESPONSE; GENE-EXPRESSION; NUCLEAR ARCHITECTURE; CHROMOSOME TERRITORIES; NIPPED-B AB Genomes are organized into complex higher-order structures by folding of the DNA into chromatin fibers, chromosome domains, and ultimately chromosomes. The higher-order organization of genomes is functionally important for gene regulation and control of gene expression programs. Defects in how chromatin is globally organized are relevant for physiological and pathological processes. Mutations and transcriptional misregulation of several global genome organizers are linked to human diseases and global alterations in chromatin structure are emerging as key players in maintenance of genome stability, aging, and the formation of cancer translocations. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 103 TC 88 Z9 89 U1 4 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD AUG PY 2010 VL 2 IS 8 AR a000794 DI 10.1101/cshperspect.a000794 PG 17 WC Cell Biology SC Cell Biology GA 634MY UT WOS:000280588200012 PM 20591991 ER PT J AU Yu, BB AF Yu, Binbing TI A Bayesian MCMC approach to survival analysis with doubly-censored data SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE AIDS; Dementia; Doubly censored data; Incubation period; MCMC; Midpoint imputation ID FAILURE TIME DATA; REGRESSION-ANALYSIS; HAZARDS MODEL; AIDS; DEMENTIA; IMPUTATION; DISEASE AB Doubly-censored data refers to time to event data for which both the originating and failure times are censored. In studies involving AIDS incubation time or survival after dementia onset, for example, data are frequently doubly-censored because the date of the originating event is interval-censored and the date of the failure event usually is right-censored. The primary interest is in the distribution of elapsed times between the originating and failure events and its relationship to exposures and risk factors. The estimating equation approach Sun et al. (1999). Regression analysis of doubly censored failure time data with applications to AIDS studies. Biometrics 55, 909-914] and its extensions assume the same distribution of originating event times for all subjects. This paper demonstrates the importance of utilizing additional covariates to impute originating event times, i.e., more accurate estimation of originating event times may lead to less biased parameter estimates for elapsed time. The Bayesian MCMC method is shown to be a suitable approach for analyzing doubly-censored data and allows a rich class of survival models. The performance of the proposed estimation method is compared to that of other conventional methods through simulations. Two examples, an AIDS cohort study and a population-based dementia study, are used for illustration. Sample code is shown in Appendix. Published by Elsevier B.V. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov FU Intramural Research Program of the National Institute on Aging FX The author was supported in part by the Intramural Research Program of the National Institute on Aging. NR 26 TC 5 Z9 7 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD AUG 1 PY 2010 VL 54 IS 8 BP 1921 EP 1929 DI 10.1016/j.csda.2010.02.025 PG 9 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 602QY UT WOS:000278155100003 PM 20514348 ER PT J AU Lobanov, AV Turanov, AA Hatfield, DL Gladyshev, VN AF Lobanov, Alexey V. Turanov, Anton A. Hatfield, Dolph L. Gladyshev, Vadim N. TI Dual functions of codons in the genetic code SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Selenocysteine; pyrrolysine; genetic code; codon reassignment ID YEAST CANDIDA-CYLINDRACEA; TRANSFER-RNA; PROTEIN SYNTHESIS; STOP-CODON; AMINO-ACID; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; MESSENGER-RNA; EVOLUTIONARY IMPLICATIONS; SELENOCYSTEINE INSERTION AB The discovery of the genetic code provided one of the basic foundations of modern molecular biology. Most organisms use the same genetic language, but there are also well-documented variations representing codon reassignments within specific groups of organisms (such as ciliates and yeast) or organelles (such as plastids and mitochondria). In addition, duality in codon function is known in the use of AUG in translation initiation and methionine insertion into internal protein positions as well as in the case of selenocysteine and pyrrolysine insertion (encoded by UGA and UAG, respectively) in competition with translation termination. Ambiguous meaning of CUG in coding for serine and leucine is also known. However, a recent study revealed that codons in any position within the open reading frame can serve a dual function and that a change in codon meaning can be achieved by availability of a specific type of RNA stem-loop structure in the 3'-untranslated region. Thus, duality of codon function is a more widely used feature of the genetic code than previously known, and this observation raises the possibility that additional recoding events and additional novel features have evolved in the genetic code. C1 [Lobanov, Alexey V.; Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Lobanov, Alexey V.; Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD USA. RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Div Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu RI Gladyshev, Vadim/A-9894-2013 FU National Institutes of Health; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by National Institutes of Health grants to VNG and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research to DLH. NR 65 TC 21 Z9 21 U1 3 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD AUG PY 2010 VL 45 IS 4 BP 257 EP 265 DI 10.3109/10409231003786094 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636TJ UT WOS:000280763700001 PM 20446809 ER PT J AU Niu, G Chen, XY AF Niu, Gang Chen, Xiaoyuan TI Vascular Endothelial Growth Factor as an Anti-Angiogenic Target for Cancer Therapy SO CURRENT DRUG TARGETS LA English DT Review DE Vascular endothelial growth factor; VEGF; targeted therapy; molecular imaging ID RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; HUMANIZED MONOCLONAL-ANTIBODY; METASTATIC COLORECTAL-CANCER; G-RICH OLIGONUCLEOTIDES; HEPARIN-BINDING DOMAIN; HUMAN OVARIAN-CANCER; IN-VITRO SELECTION; TUMOR ANGIOGENESIS; BONE-MARROW AB New blood vessel formation (angiogenesis) is fundamental to tumor growth, invasion, and metastatic dissemination. The vascular endothelial growth factor (VEGF) signaling pathway plays pivotal roles in regulating tumor angiogenesis. VEGF as a therapeutic target has been validated in various types of human cancers. Different agents including antibodies, aptamers, peptides, and small molecules have been extensively investigated to block VEGF and its pro-angiogenic functions. Some of these agents have been approved by FDA and some are currently in clinical trials. Combination therapies are also being pursued for better tumor control. By providing comprehensive real-time information, molecular imaging of VEGF pathway may accelerate the drug development process. Moreover, the imaging will be of great help for patient stratification and therapeutic effect monitoring, which will promote effective personalized molecular cancer therapy. This review summarizes the current status of tumor therapeutic agents targeting to VEGF and the applications of VEGF related molecular imaging. C1 [Niu, Gang] NIH, Imaging Sci Training Program, Ctr Clin, Bethesda, MD 20892 USA. [Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, LOMIN, NIH, Bethesda, MD 20892 USA. RP Niu, G (reprint author), NIH, Imaging Sci Training Program, Ctr Clin, 9 Mem Dr,9-1W111, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU Radiology and Imaging Sciences Department, NIH Clinical Center; NIBIB, NIH FX Dr. Niu currently is an Imaging Sciences Training Fellowship jointly supported by the Radiology and Imaging Sciences Department, NIH Clinical Center and the Intramural Research Program, NIBIB, NIH. NR 222 TC 58 Z9 62 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD AUG PY 2010 VL 11 IS 8 BP 1000 EP 1017 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 632XS UT WOS:000280463500013 PM 20426765 ER PT J AU Hegde, RS Ploegh, HL AF Hegde, Ramanujan S. Ploegh, Hidde L. TI Quality and quantity control at the endoplasmic reticulum SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID ER-ASSOCIATED DEGRADATION; HMG COA REDUCTASE; ANCHORED UBIQUITIN LIGASE; SIGNAL PEPTIDE PEPTIDASE; N-LINKED GLYCANS; MISFOLDED GLYCOPROTEINS; PROTEIN-DEGRADATION; UNCONVENTIONAL SECRETION; RETRO-TRANSLOCATION; COMPLEX AB The endoplasmic reticulum (ER) is the site of maturation for secretory and membrane proteins that together make up about one third of the cellular proteome. Cells carefully control the synthetic output of this organelle to regulate both quality and quantity of proteins that emerge. Here, we synthesize current concepts underlying the pathways that mediate protein degradation from the ER and their deployment under physiologic and pathologic conditions. C1 [Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Ploegh, Hidde L.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov; ploegh@wi.mit.edu OI Hegde, Ramanujan/0000-0001-8338-852X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health; National Institutes of Health FX RSH's laboratory is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health. HLP's laboratory is supported by grants from the National Institutes of Health. NR 78 TC 80 Z9 81 U1 1 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 2010 VL 22 IS 4 BP 437 EP 446 DI 10.1016/j.ceb.2010.05.005 PG 10 WC Cell Biology SC Cell Biology GA 639BJ UT WOS:000280945500004 PM 20570125 ER PT J AU Akhmanova, A Hammer, JA AF Akhmanova, Anna Hammer, John A., III TI Linking molecular motors to membrane cargo SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID END-DIRECTED TRANSPORT; PROTEIN-KINASE-II; MYOSIN-VI; INTRACELLULAR-TRANSPORT; CYTOPLASMIC DYNEIN; ANTEROGRADE TRANSPORT; MELANOSOME TRANSPORT; AXONAL-TRANSPORT; PLASMA-MEMBRANE; RAB11 FAMILY AB Three types of motors, myosins, kinesins, and cytoplasmic dynein, cooperate to transport intracellular membrane organelles. Transport of each cargo is determined by recruitment of specific sets of motors and their regulation. Targeting of motors to membranes often depends on the formation of large multiprotein assemblies and can be influenced by membrane lipid composition. Motor activity can be regulated by cargo-induced conformational changes such as unfolding or dimerization. The architecture and function of motor: cargo complexes can also be controlled by phosphorylation, calcium signaling, and proteolysis. The complexity of transport systems is further increased by mechanical and functional cross-talk between different types of motors on the same cargo and by participation of the same motor in the movement of different organelles. C1 [Akhmanova, Anna] Erasmus MC, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands. [Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Akhmanova, A (reprint author), Erasmus MC, Dept Cell Biol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM a.akhmanova@erasmusmc.nl; hammerj@nhlbi.nih.gov RI Akhmanova, Anna/B-8896-2011 OI Akhmanova, Anna/0000-0002-9048-8614 FU Netherlands Organisation for Scientific Research FX We thank Xufeng Wu for assistance in preparing Figure 2. We apologize for not citing many important references owing to space limitations. A.A. is supported by the Netherlands Organisation for Scientific Research grants ALW-VICI and ZonMW-TOP. NR 80 TC 94 Z9 95 U1 1 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 2010 VL 22 IS 4 BP 479 EP 487 DI 10.1016/j.ceb.2010.04.008 PG 9 WC Cell Biology SC Cell Biology GA 639BJ UT WOS:000280945500009 PM 20466533 ER PT J AU Barry, CE Blanchard, JS AF Barry, Clifton E., III Blanchard, John S. TI The chemical biology of new drugs in the development for tuberculosis SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID MULTIDRUG-RESISTANT TUBERCULOSIS; NONREPLICATING MYCOBACTERIUM-TUBERCULOSIS; BETA-LACTAM ANTIBIOTICS; ATP SYNTHASE INHIBITOR; IN-VIVO ACTIVITIES; MURINE MODEL; ANTIMYCOBACTERIAL ACTIVITY; ANTITUBERCULOSIS ACTIVITY; NITROIMIDAZOPYRAN PA-824; BACTERICIDAL ACTIVITY AB With the worldwide emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (Mtb), there are serious concerns about the continued ability to contain this disease. We discuss the most promising new drugs in late-stage development that might be useful in treating MDR and XDR forms of the disease. These agents have novel mechanisms of action that are not targeted by the standard drugs used presently to treat susceptible strains. C1 [Barry, Clifton E., III; Blanchard, John S.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Barry, Clifton E., III; Blanchard, John S.] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. RP Blanchard, JS (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM blanchar@aecom.yu.edu RI Barry, III, Clifton/H-3839-2012 FU NIAID NIH HHS [R01 AI033696, R01 AI033696-18] NR 95 TC 37 Z9 37 U1 2 U2 13 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 AUG PY 2010 VL 14 IS 4 BP 456 EP 466 DI 10.1016/j.cbpa.2010.04.008 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 642CJ UT WOS:000281180600004 PM 20452813 ER PT J AU Taub, DD Murphy, WJ Longo, DL AF Taub, Dennis D. Murphy, William J. Longo, Dan L. TI Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; T-CELL DEVELOPMENT; PROINFLAMMATORY CYTOKINE EXPRESSION; FASTED PLASMA GHRELIN; NECROSIS-FACTOR-ALPHA; IMMUNE-SYSTEM; FACTOR-I; ANTIRETROVIRAL THERAPY; LYMPHOCYTE DEVELOPMENT; HIV-1-INFECTED ADULTS AB One of the major fundamental causes for the aging of the immune system is the structural and functional involution of the thymus, and the associated decline in de novo naive T-lymphocyte output. This loss of naive T-cell production weakens the ability of the adaptive immune system to respond to new antigenic stimuli and eventually leads to a peripheral T-cell bias to the memory phenotype. While the precise mechanisms responsible for age-associated thymic involution remain unknown, a variety of theories have been forwarded including the loss of expression of various growth factors and hormones that influence the lymphoid compartment and promote thymic function. Extensive studies examining two hormones, namely growth hormone (GH) and ghrelin (GRL), have demonstrated their contributions to thymus biology. In the current review, we discuss the literature supporting a role for these hormones in thymic physiology and age-associated thymic involution and their potential use in the restoration of thymic function in aged and immunocompromised individuals. C1 [Taub, Dennis D.; Longo, Dan L.] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Murphy, William J.] Univ Calif Davis, Med Ctr, Dept Dermatol, Sacramento, CA 95817 USA. RP Taub, DD (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Taubd@grc.nia.nih.gov FU National Institute on Aging, National Institutes of Health FX We wish to thank former NIA post-doctoral fellows, Drs. Dixit and Yang, and our excellent technical staff members, Ana Lustig, Arnell Carter and Gary Collins for their significant efforts in the studies shown here for both the GH and GRL infusions. This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 129 TC 47 Z9 49 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD AUG PY 2010 VL 10 IS 4 BP 408 EP 424 DI 10.1016/j.coph.2010.04.015 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641OV UT WOS:000281138700011 PM 20595009 ER PT J AU Song, BJ Moon, KH Upreti, VV Eddington, ND Lee, IJ AF Song, Byoung-Joon Moon, Kwan-Hoon Upreti, Vijay V. Eddington, Natalie D. Lee, Insong J. TI Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE MDMA; metabolism; oxidative/nitrosative stress; protein oxidation; functional redox proteomics; mitochondrial dysfunction; organ damage ID ALCOHOLIC FATTY LIVER; CULTURED RAT HEPATOCYTES; NITRIC-OXIDE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; ALDEHYDE DEHYDROGENASE; GEL-ELECTROPHORESIS; REACTIVE OXYGEN; SEROTONERGIC NEUROTOXICITY; TRYPTOPHAN-HYDROXYLASE; PROTEIN MODIFICATIONS AB Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. C1 [Song, Byoung-Joon; Moon, Kwan-Hoon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Upreti, Vijay V.; Eddington, Natalie D.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Lee, Insong J.] Coll Notre Dame Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21210 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bj.song@nih.gov FU National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism. We are grateful to Drs. Timothy D. Veenstra, Li-Rong Yu, and Xiaoying Ye at the Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Inc. for determining the protein sequences of oxidatively-modified mitochondrial proteins, as described [44]. The authors do not have any conflict of interest. NR 107 TC 21 Z9 22 U1 0 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD AUG PY 2010 VL 11 IS 5 BP 434 EP 443 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 633BF UT WOS:000280473800004 PM 20420575 ER PT J AU Chen, XY AF Chen, Xiaoyuan (Shawn) TI The Medicinal Chemistry of Targeted Tumor Imaging (I) SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD AUG PY 2010 VL 10 IS 11 BP 1046 EP 1047 PG 2 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 615EU UT WOS:000279117100001 PM 20681945 ER PT J AU Jacobson, O Chen, XY AF Jacobson, Orit Chen, Xiaoyuan TI PET Designated Flouride-18 Production and Chemistry SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; N-SUCCINIMIDYL 4-FLUOROBENZOATE; ANION-EXCHANGE RESIN; F-18 FLUOROMISONIDAZOLE; AUTOMATED SYNTHESIS; LABELING PROTEINS; IMAGING AGENTS; RGD PEPTIDE; ELEMENTAL FLUORINE; TERMINAL ALKYNES AB Positron emission tomography (PET) is a nuclear medicine imaging technology which allows for four-dimensional, quantitative determination of the distribution of labeled biological compounds within the human body. PET is becoming an increasingly important tool for the measurement of physiological, biochemical and pharmacological functions at the molecular level in healthy and pathological conditions. This review will focus on Flouride-18, one of the common isotopes used for PET imaging, which has a half life of 109.8 minutes. This isotope can be produced with an efficient yield in a cyclotron as a nucleophile or as an electrophile. Flouride-18 can be thereafter introduced into small molecules or biomolecules using various chemical synthetic routes, to give the desired imaging agent. C1 [Jacobson, Orit; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-01] NR 106 TC 19 Z9 20 U1 0 U2 23 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD AUG PY 2010 VL 10 IS 11 BP 1048 EP 1059 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 615EU UT WOS:000279117100002 PM 20388116 ER PT J AU Lee, S Xie, J Chen, XY AF Lee, Seulki Xie, Jin Chen, Xiaoyuan TI Activatable Molecular Probes for Cancer Imaging SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID RESONANCE ENERGY-TRANSFER; CELL-PENETRATING PEPTIDES; INFRARED FLUORESCENT-PROBES; IN-VIVO; PROTEASE ACTIVITY; QUANTUM DOTS; LIVING SUBJECTS; APOPTOSIS; NANOPARTICLES; THERAPEUTICS AB The development of highly sensitive and specific molecular probes for cancer imaging still remains a daunting challenge. Recently, interdisciplinary research at the interface of imaging sciences and bionanoconjugation chemistry has generated novel activatable imaging probes that can provide high-resolution imaging with ultra-low background signals. Activatable imaging probes are designed to amplify output imaging signals in response to specific biomolecular recognition or environmental changes in real time. This review introduces and highlights the unique design strategies and applications of various activatable imaging probes in cancer imaging. C1 [Lee, Seulki; Xie, Jin; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. RP Lee, S (reprint author), NIBIB, LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM Seulki.Lee@nih.gov; Shawn.Chen@nih.gov RI Xie, Jin/E-8193-2010 FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-01] NR 72 TC 40 Z9 42 U1 4 U2 32 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-5294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD AUG PY 2010 VL 10 IS 11 BP 1135 EP 1144 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 615EU UT WOS:000279117100006 PM 20388112 ER PT J AU Gao, JH Chen, XY Cheng, Z AF Gao, Jinhao Chen, Xiaoyuan Cheng, Zhen TI Near-Infrared Quantum Dots as Optical Probes for Tumor Imaging SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Quantum dots; near-infrared; tumor imaging; fluorescence imaging; perspective ID RESONANCE ENERGY-TRANSFER; GROWTH-FACTOR RECEPTOR; IN-VIVO; NON-CADMIUM; MAGNETIC NANOPARTICLES; PHOSPHOLIPID MICELLES; LIVING SUBJECTS; DRUG-DELIVERY; NANOCRYSTALS; CANCER AB Molecular imaging plays a key role in personalized medicine, which is the goal and future of patient management. Among the various molecular imaging modalities, optical imaging may be the fastest growing area for bioanalysis, and the major reason is the research on fluorescence semiconductor quantum dots (QDs) and dyes have evolved over the past two decades. The great efforts on the synthesis of QDs with fluorescence emission from UV to near-infrared (NIR) regions speed up the studies of QDs as optical probes for in vitro and in vivo molecular imaging. For in vivo applications, the fluorescent emission wavelength ideally should be in a region of the spectrum where blood and tissue absorb minimally and tissue penetration reach maximally, which is NIR region (typically 700-1000 nm). The goal of this review is to provide readers the basics of NIR-emitting QDs, the bioconjugate chemistry of QDs, and their applications for diagnostic tumor imaging. We will also discuss the benefits, challenges, limitations, perspective, and the future scope of NIR-emitting QDs for tumor imaging applications. C1 [Gao, Jinhao; Cheng, Zhen] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Gao, Jinhao; Cheng, Zhen] Stanford Univ, Sch Med, Bio X Program, Stanford, CA 94305 USA. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Gao, JH (reprint author), Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, 1201 Welch Rd, Stanford, CA 94305 USA. EM gaojh@stanford.edu RI Gao, Jinhao/F-5092-2010; Cheng, Zhen/K-2843-2012 OI Gao, Jinhao/0000-0003-3215-7013; FU NCI/NIH [R21 CA121842, U54 CA119367] FX This work was partially supported by NCI/NIH R21 CA121842 and U54 CA119367. NR 89 TC 39 Z9 40 U1 4 U2 75 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD AUG PY 2010 VL 10 IS 12 BP 1147 EP 1157 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 615FB UT WOS:000279117800002 PM 20388111 ER PT J AU Chen, K Chen, XY AF Chen, Kai Chen, Xiaoyuan TI Design and Development of Molecular Imaging Probes SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Molecular imaging; imaging probe design; imaging probe development strategies ID POSITRON-EMISSION-TOMOGRAPHY; STIMULATING HORMONE ANALOG; SMALL-ANIMAL PET; INTEGRIN ALPHA(V)BETA(3) EXPRESSION; PROTEIN-SYNTHESIS RATE; IN-VIVO; CLICK CHEMISTRY; TUMOR XENOGRAFTS; LIVING SUBJECTS; PROTEOMIC TECHNOLOGIES AB Molecular imaging, the visualization, characterization and measurement of biological processes at the cellular, subcellular level, or even molecular level in living subjects, has rapidly gained importance in the dawning era of personalized medicine. Molecular imaging takes advantage of the traditional diagnostic imaging techniques and introduces molecular imaging probes to determine the expression of indicative molecular markers at different stages of diseases and disorders. As a key component of molecular imaging, molecular imaging probe must be able to specifically reach the target of interest in vivo while retaining long enough to be detected. A desirable molecular imaging probe with clinical translation potential is expected to have unique characteristics. Therefore, design and development of molecular imaging probe is frequently a challenging endeavor for medicinal chemists. This review summarizes the general principles of molecular imaging probe design and some fundamental strategies of molecular imaging probe development with a number of illustrative examples. C1 [Chen, Kai] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Chen, Xiaoyuan] Univ So Calif, Keck Sch Med, Dept Radiol, Mol Imaging Ctr, Los Angeles, CA 90033 USA. RP Chen, K (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM chenkai@usc.edu; shawn.chen@nih.gov FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-01] NR 96 TC 42 Z9 45 U1 2 U2 45 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD AUG PY 2010 VL 10 IS 12 BP 1227 EP 1236 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 615FB UT WOS:000279117800007 PM 20388106 ER PT J AU Wisner, KL AF Wisner, Katherine L. TI SSRI TREATMENT DURING PREGNANCY: ARE WE ASKING THE RIGHT QUESTIONS? SO DEPRESSION AND ANXIETY LA English DT Article ID SEROTONIN-REUPTAKE INHIBITORS; PERSISTENT PULMONARY-HYPERTENSION; ANTIDEPRESSANT TREATMENT; CHILD-DEVELOPMENT; MAJOR DEPRESSION; BIRTH-DEFECTS; RISK; POSTPARTUM; WOMEN; NEWBORN AB Katherine L. Wisner M.D., M.S., is Professor of Psychiatry, Obstetrics/Gynecology and Reproductive Sciences, Epidemiology and Women's Studies at the University of Pittsburgh School of Medicine, and director of the Women's Behavioral HealthCare program at the Western Psychiatric Institute and Clinic (WPIC) of the University Pittsburgh Medical Center. She also serves as an investigator at the Magee-Womens Research Institute. Dr. Wisner obtained an M.S. in Nutrition and an M.D. from Case Western Reserve University, followed by a categorical pediatric internship and general and child psychiatry residency at Children's Hospital of Pittsburgh and WPIC. She completed a post-doctoral fellow in Epidemiology at the University of Pittsburgh Graduate School of Public Health and a fellowship in Professional Ethics at Case Western Reserve University in 1996. Dr. Wisner's research is focused on the psychiatric evaluation and treatment of women of childbearing age. She is recognized as an expert in the treatment of mood disorders during pregnancy and the postpartum period. She is the principal investigator on several National Institute of Mental Health and foundation-funded research projects. As the current President of the Marce International Society (for the understanding, prevention, and treatment of mental illness related to childbearing), Dr. Wisner is hosting a conference in October 2010 (www.marcesodety.com). She has authored more than 150 peer-reviewed articles and book chapters. C1 [Wisner, Katherine L.] Univ Pittsburgh, Womens Behav HealthCARE, Western Psychiat Inst & Clin, Womens Behav HealthCare Program,Med Ctr, Pittsburgh, PA 15213 USA. [Wisner, Katherine L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Wisner, Katherine L.] Magee Womens Res Inst, Pittsburgh, PA USA. [Wisner, Katherine L.] NIMH, Bethesda, MD 20892 USA. RP Wisner, KL (reprint author), Univ Pittsburgh, Womens Behav HealthCARE, Western Psychiat Inst & Clin, Womens Behav HealthCare Program,Med Ctr, 3811 OHara St, Pittsburgh, PA 15213 USA. EM WisnerKL@upmc.edu FU National Institute of Mental Health [R01 MH60335, R01 MH071825, R01 MH075921] FX The author discloses the following financial relationships within the past 3 years: Dr. Wisner's effort was supported primarily by National Institute of Mental Health R01 MH60335; also by National Institute of Mental Health R01 MH071825 and R01 MH075921. Dr. Wisner has participated on an Advisory Board for Eli Lilly Co. and received a donation of active and placebo transdermal estradiol patches from Novartis for an NIMH funded randomized trial. NR 20 TC 6 Z9 6 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD AUG PY 2010 VL 27 IS 8 BP 695 EP 698 DI 10.1002/da.20729 PG 4 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 635ZE UT WOS:000280696000001 PM 20694964 ER PT J AU Yamamoto, M Morita, R Mizoguchi, T Matsuo, H Isoda, M Ishitani, T Chitnis, AB Matsumoto, K Crump, JG Hozumi, K Yonemura, S Kawakami, K Itoh, M AF Yamamoto, Mai Morita, Ryoko Mizoguchi, Takamasa Matsuo, Hiromi Isoda, Miho Ishitani, Tohru Chitnis, Ajay B. Matsumoto, Kunihiro Crump, J. Gage Hozumi, Katsuto Yonemura, Shigenobu Kawakami, Koichi Itoh, Motoyuki TI Mib-Jag1-Notch signalling regulates patterning and structural roles of the notochord by controlling cell-fate decisions SO DEVELOPMENT LA English DT Article DE Mind bomb; Notch signalling; Notochord; Basement membrane; Muscle patterning; Zebrafish ID ZEBRAFISH EMBRYOS; MIND BOMB; ALAGILLE-SYNDROME; SEGMENT POLARITY; UBIQUITIN LIGASE; SONIC HEDGEHOG; NOTCH; GENE; SPECIFICATION; DELTA AB In the developing embryo, cell-cell signalling is necessary for tissue patterning and structural organization. During midline development, the notochord plays roles in the patterning of its surrounding tissues while forming the axial structure; however, how these patterning and structural roles are coordinated remains elusive. Here, we identify a mechanism by which Notch signalling regulates the patterning activities and structural integrity of the notochord. We found that Mind bomb (Mib) ubiquitylates Jagged 1 (Jag1) and is essential in the signal-emitting cells for Jag1 to activate Notch signalling. In zebrafish, loss- and gain-of-function analyses showed that Mib-Jag1-Notch signalling favours the development of non-vacuolated cells at the expense of vacuolated cells in the notochord. This leads to changes in the peri-notochordal basement membrane formation and patterning surrounding the muscle pioneer cells. These data reveal a previously unrecognized mechanism regulating the patterning and structural roles of the notochord by Mib-Jag1-Notch signalling-mediated cell-fate determination. C1 [Yamamoto, Mai; Mizoguchi, Takamasa; Matsuo, Hiromi; Itoh, Motoyuki] Nagoya Univ, Inst Adv Res, Aichi 4648602, Japan. [Yamamoto, Mai; Morita, Ryoko; Isoda, Miho; Ishitani, Tohru; Matsumoto, Kunihiro; Itoh, Motoyuki] Nagoya Univ, Grad Sch Sci, Aichi 4648602, Japan. [Chitnis, Ajay B.] NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Crump, J. Gage] Univ So Calif, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90033 USA. [Hozumi, Katsuto] Tokai Univ, Dept Immunol, Sch Med, Kanagawa 2591193, Japan. [Yonemura, Shigenobu] RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. [Kawakami, Koichi] Natl Inst Genet, Div Mol & Dev Biol, Shizuoka 4118540, Japan. RP Itoh, M (reprint author), Nagoya Univ, Inst Adv Res, Aichi 4648602, Japan. EM mito@iar.nagoya-u.ac.jp RI Ishitani, Tohru/E-9781-2014 FU NICHD; Astellas Foundation for Research on Metabolic Disorders; MEXT of Japan FX We thank T. Honjo, H, Yagita, T. Oda, S. C. Chandrasekharappa, M. Hibi and S. Chiba for providing plasmid vectors, antibodies and cultured cells; the Zebrafish National BioResource Project in Japan for providing zebrafish strains; R. Inaba for technical assistance; and M. Hibi for helpful discussions. This study was supported in part by the NICHD intramural program. This research was supported by the Astellas Foundation for Research on Metabolic Disorders (M. I.), the Program for Improvement of Research Environment for Young Researchers from SCF commissioned by MEXT of Japan (M. I.), and Grants-in-Aid for Scientific Research programs in Japan (K. M. and M. I.). Deposited in PMC for release after 12 months. NR 49 TC 32 Z9 32 U1 2 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG 1 PY 2010 VL 137 IS 15 BP 2527 EP 2537 DI 10.1242/dev.051011 PG 11 WC Developmental Biology SC Developmental Biology GA 624OK UT WOS:000279828300010 PM 20573700 ER PT J AU Pei, WH Kratz, LE Bernardini, I Sood, R Yokogawa, T Dorward, H Ciccone, C Kelley, RI Anikster, Y Burgess, HA Huizing, M Feldman, B AF Pei, Wuhong Kratz, Lisa E. Bernardini, Isa Sood, Raman Yokogawa, Tohei Dorward, Heidi Ciccone, Carla Kelley, Richard I. Anikster, Yair Burgess, Harold A. Huizing, Marjan Feldman, Benjamin TI A model of Costeff Syndrome reveals metabolic and protective functions of mitochondrial OPA3 SO DEVELOPMENT LA English DT Article DE Zebrafish; OPA3; Costeff Syndrome; 3-Methylglutaconic aciduria; Mitochondria; Metabolic disorder ID 3-METHYLGLUTACONIC ACIDURIA; OPTIC ATROPHY; STEROL BIOSYNTHESIS; BARTH-SYNDROME; MOUSE MODEL; ZEBRAFISH; GENE; MUTATION; MEVALONATE; DISORDERS AB Costeff Syndrome, which is caused by mutations in the OPTIC ATROPHY 3 (OPA3) gene, is an early-onset syndrome characterized by urinary excretion of 3-methylglutaconic acid (MGC), optic atrophy and movement disorders, including ataxia and extrapyramidal dysfunction. The OPA3 protein is enriched in the inner mitochondrial membrane and has mitochondrial targeting signals, but a requirement for mitochondrial localization has not been demonstrated. We find zebrafish opa3 mRNA to be expressed in the optic nerve and retinal layers, the counterparts of which in humans have high mitochondrial activity. Transcripts of zebrafish opa3 are also expressed in the embryonic brain, inner ear, heart, liver, intestine and swim bladder. We isolated a zebrafish opa3 null allele for which homozygous mutants display increased MGC levels, optic nerve deficits, ataxia and an extrapyramidal movement disorder. This correspondence of metabolic, ophthalmologic and movement abnormalities between humans and zebrafish demonstrates a phylogenetic conservation of OPA3 function. We also find that delivery of exogenous Opa3 can reduce increased MGC levels in opa3 mutants, and this reduction requires the mitochondrial localization signals of Opa3. By manipulating MGC precursor availability, we infer that elevated MGC in opa3 mutants derives from extra-mitochondrial HMG-CoA through a non-canonical pathway. The opa3 mutants have normal mitochondrial oxidative phosphorylation profiles, but are nonetheless sensitive to inhibitors of the electron transport chain, which supports clinical recommendations that individuals with Costeff Syndrome avoid mitochondria-damaging agents. In summary, this paper introduces a faithful Costeff Syndrome model and demonstrates a requirement for mitochondrial OPA3 to limit HMG-CoA-derived MGC and protect the electron transport chain against inhibitory compounds. C1 [Pei, Wuhong; Bernardini, Isa; Dorward, Heidi; Ciccone, Carla; Huizing, Marjan; Feldman, Benjamin] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Kratz, Lisa E.; Kelley, Richard I.] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21205 USA. [Sood, Raman] NHGRI, Zebrafish Core Facil, Bethesda, MD 20892 USA. [Yokogawa, Tohei; Burgess, Harold A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, Bethesda, MD 20892 USA. [Anikster, Yair] Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Metabol Dis Unit,Safra Childrens Hosp, IL-52621 Tel Hashomer, Israel. RP Feldman, B (reprint author), NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. EM bfeldman@mail.nih.gov RI Burgess, Harold/B-8474-2015; OI Burgess, Harold/0000-0003-1966-7801; Feldman, Benjamin/0000-0003-4838-8641 FU National Human Genome Research Institute, the National Institutes of Health FX We thank Forbes D. Porter, Christopher A. Wassif and Lien Ly for assistance with pilot studies; Kevin Bittman, Sung-Kook Hong, Huaibin Cai, Jorge L. Velez and Stephen Wincovitch for technical assistance; Charles P. Venditti and Erich Roessler for helpful discussions. This work was supported by the Intramural Research Program of the National Human Genome Research Institute, the National Institutes of Health. Deposited in PMC for release after 12 months. NR 39 TC 19 Z9 19 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG 1 PY 2010 VL 137 IS 15 BP 2587 EP 2596 DI 10.1242/dev.043745 PG 10 WC Developmental Biology SC Developmental Biology GA 624OK UT WOS:000279828300016 PM 20627962 ER PT J AU Brown, JL Kassis, JA AF Brown, J. Lesley Kassis, Judith A. TI Spps, a Drosophila Sp1/KLF family member, binds to PREs and is required for PRE activity late in development SO DEVELOPMENT LA English DT Article DE Sp1/Klf family members; Gene expression; Polycomb group genes ID HISTONE METHYLTRANSFERASE ACTIVITY; GROUP PROTEIN COMPLEXES; POLYCOMB-GROUP PROTEINS; GROUP RESPONSE ELEMENT; DNA-BINDING; TRANSCRIPTION FACTORS; ENGRAILED GENE; GERMLINE MOSAICS; HOMEOTIC GENE; SEX COMB AB The Polycomb group of proteins (PcG) is important for transcriptional repression and silencing in all higher eukaryotes. In Drosophila, PcG proteins are recruited to the DNA by Polycomb-group response elements (PREs), regulatory sequences whose activity depends on the binding of many different sequence-specific DNA-binding proteins. We previously showed that a binding site for the Sp1/KLF family of zinc-finger proteins is required for PRE activity. Here, we report that the Sp1/KLF family member Spps binds specifically to Ubx and engrailed PREs, and that Spps binds to polytene chromosomes in a pattern virtually identical to that of the PcG protein, Psc. A deletion of the Spps gene causes lethality late in development and a loss in pairing-sensitive silencing, an activity associated with PREs. Finally, the Spps mutation enhances the phenotype of pho mutants. We suggest that Spps may work with, or in parallel to, Pho to recruit PcG protein complexes to PREs. C1 [Brown, J. Lesley; Kassis, Judith A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA. EM jkassis@mail.nih.gov OI Kassis, Judith/0000-0001-9268-3213 FU NIH, NICHD FX We thank Jim Kennison for helpful discussions, Monica Cooper and Jim Kennison for the PRED-mw line, and Yuzhong Cheng and Melissa Cunningham for comments on this paper. We also thank Kris Langlais, Karl Pfeifer and Cameron Johnson for help with the larval ChIP and qPCR, and the Bloomington stock center for fly stocks. This research was supported by the Intramural Research Program of the NIH, NICHD. Deposited in PMC for release after 12 months. NR 51 TC 16 Z9 16 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG 1 PY 2010 VL 137 IS 15 BP 2597 EP 2602 DI 10.1242/dev.047761 PG 6 WC Developmental Biology SC Developmental Biology GA 624OK UT WOS:000279828300017 PM 20627963 ER PT J AU Feldman, B Hong, SK Brown, JL AF Feldman, Benjamin Hong, Sung-Kook Brown, Jamie L. TI A role for Mxtx2 in mesendoderm induction SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Feldman, Benjamin; Hong, Sung-Kook; Brown, Jamie L.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 51 BP 430 EP 430 DI 10.1016/j.ydbio.2010.05.084 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400085 ER PT J AU Zhang, Y Poplawski, NJ Glazier, JA AF Zhang, Ying Poplawski, Nikodem J. Glazier, James A. TI The Role of FGF Gradients in the Regulation of Early Limb Growth SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Zhang, Ying] NCI, Genet Vertebrate Dev Sect, Canc & Dev Biol Lab, Frederick Canc & Dev Ctr, Frederick, MD 21702 USA. [Zhang, Ying; Poplawski, Nikodem J.; Glazier, James A.] Indiana Univ, Brocomplex Inst, Bloomington, IN 47405 USA. [Zhang, Ying; Poplawski, Nikodem J.; Glazier, James A.] Indiana Univ, Dept Phys, Bloomington, IN 47405 USA. RI Zhang, Ying/Q-6956-2016 OI Zhang, Ying/0000-0002-8045-3821 NR 0 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 93 BP 444 EP 444 DI 10.1016/j.ydbio.2010.05.132 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400128 ER PT J AU Matsuda, M Chitnis, A AF Matsuda, Miho Chitnis, Ajay TI Notch-restricted Atoh1 expression regulates morphogenesis of the posterior lateral line in zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Matsuda, Miho; Chitnis, Ajay] NICHD, LMG, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 111 BP 449 EP 449 DI 10.1016/j.ydbio.2010.05.150 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400146 ER PT J AU Hill, JK Gan, L Wu, DK AF Hill, Jennifer K. Gan, Lin Wu, Doris K. TI Genetic interaction of Lmx1a and Lmo4 in the mouse inner ear SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Hill, Jennifer K.; Wu, Doris K.] Natl Inst Deafness & Other Commun Disorders, Rockville, MD USA. [Gan, Lin] Univ Rochester, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 133 BP 455 EP 455 DI 10.1016/j.ydbio.2010.05.173 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400168 ER PT J AU Range, R Angerer, R Angerer, L AF Range, Ryan Angerer, Robert Angerer, Lynne TI Complex control of Wnt signaling determines the size of the initial neurogenic territory at the animal pole of the sea urchin embryo SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Range, Ryan; Angerer, Robert; Angerer, Lynne] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 183 BP 469 EP 469 DI 10.1016/j.ydbio.2010.05.224 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400218 ER PT J AU Coate, TM Crenshaw, EB Kelley, MW AF Coate, Thomas M. Crenshaw, E. Bryan Kelley, Matthew W. TI The fasciculation of spiral ganglion peripheral axons in the mouse cochlea is dependent on Pou3F4 SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Coate, Thomas M.; Kelley, Matthew W.] NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Crenshaw, E. Bryan] U Penn, Childrens Hosp, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 192 BP 472 EP 472 DI 10.1016/j.ydbio.2010.05.234 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400227 ER PT J AU Tanigawa, S Wang, HH Yang, YL Sharma, N Yamaguchi, T Perantoni, A AF Tanigawa, Shunsuke Wang, Honghe Yang, Yili Sharma, Nirmala Yamaguchi, Terry Perantoni, Alan TI Wnt4 induces tubule formation in metanephric mesenchyme by a non-canonical mechanism SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Tanigawa, Shunsuke; Wang, Honghe; Yang, Yili; Sharma, Nirmala; Yamaguchi, Terry; Perantoni, Alan] NCI, Canc Dev Biol Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 220 BP 479 EP 479 DI 10.1016/j.ydbio.2010.05.264 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400252 ER PT J AU Wang, AB Ma, XF Conti, MA Liu, CY Kawamoto, S Adelstein, RS AF Wang, Aibing Ma, Xuefei Conti, Mary Anne Liu, Chengyu Kawamoto, Sachiyo Adelstein, Robert S. TI Isoform and domain dependence of nonmuscle myosin II in vivo and in vitro SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Wang, Aibing; Ma, Xuefei; Conti, Mary Anne; Kawamoto, Sachiyo; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Liu, Chengyu] NHLBI, Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 223 BP 480 EP 480 DI 10.1016/j.ydbio.2010.05.267 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400255 ER PT J AU Dutta, S Brooks, BP Dawid, IB AF Dutta, Sunit Brooks, Brian P. Dawid, Igor B. TI Kctd15 inhibits neural crest formation by modulating Wnt signaling SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Dutta, Sunit; Dawid, Igor B.] NICHD, Sect Dev Biol, Bethesda, MD USA. [Dutta, Sunit; Brooks, Brian P.] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 304 BP 501 EP 501 DI 10.1016/j.ydbio.2010.05.313 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400333 ER PT J AU Kersey, RK Brodigan, T Fukushige, T Krause, M AF Kersey, Rossio K. Brodigan, Thomas Fukushige, Tetsu Krause, Mike TI Transcriptional control of dorsal-ventral polarity cues in C. elegans SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Kersey, Rossio K.; Brodigan, Thomas; Fukushige, Tetsu; Krause, Mike] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 315 BP 503 EP 504 DI 10.1016/j.ydbio.2010.05.324 PG 2 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400344 ER PT J AU Nakatake, Y Ko, M AF Nakatake, Yuki Ko, Minoru TI Combinational differentiation by environmental manipulation and transgene with NIA ES cell bank SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Nakatake, Yuki; Ko, Minoru] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009; Nakatake, Yuhki/K-5405-2013 OI Ko, Minoru/0000-0002-3530-3015; NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 385 BP 522 EP 523 DI 10.1016/j.ydbio.2010.05.464 PG 2 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400407 ER PT J AU Bhatwadekar, AD Guerin, EP Jarajapu, YPR Caballero, S Sheridan, C Kent, D Kennedy, L Lansang, MC Ruscetti, FW Pepine, CJ Higgins, PJ Bartelmez, SH Grant, MB AF Bhatwadekar, Ashay D. Guerin, E. P. Jarajapu, Yagna P. R. Caballero, Sergio Sheridan, Carl Kent, David Kennedy, Laurence Lansang, M. Cecilia Ruscetti, Frank W. Pepine, Carl J. Higgins, Paul J. Bartelmez, Stephen H. Grant, Maria B. TI Transient Inhibition of Transforming Growth Factor-beta 1 in Human Diabetic CD34(+) Cells Enhances Vascular Reparative Functions SO DIABETES LA English DT Article ID GROWTH-FACTOR-BETA; HEMATOPOIETIC STEM-CELLS; ENDOTHELIAL PROGENITOR CELLS; NITRIC-OXIDE SYNTHASE; CHOROIDAL NEOVASCULARIZATION; MONONUCLEAR-CELLS; ISCHEMIA; MOBILIZATION; MECHANISM; MICE AB OBJECTIVE-Peripheral blood CD34(+) cells from diabetic patients demonstrate reduced vascular reparative function due to decreased proliferation and diminished migratory prowess, largely resulting from decreased nitric oxide (NO) bioavailability. The level of TGF-beta, a key factor that modulates stem cell quiescence, is increased in the serum of type 2 diabetic patients We asked whether transient TGF-beta 1 inhibition in CD34(+) cells would improve their reparative ability. RESEARCH DESIGN AND METHODS-To inhibit TGF-beta 1 protein expression, CD34(+) cells were treated ex vivo with antisense phosphorodiamidate morpholino oligomers (TGF-beta 1-PMOs) and analyzed for cell surface CXCR4 expression, cell survival in the absence of added growth factors, SDF-1-induced migration, NO release, and in vivo retinal vascular reparative ability. RESULTS-TGF-beta 1-PMO treatment of diabetic CD34(+) cells resulted in increased expression of CXCR4, enhanced survival in the absence of growth factors, and increased migration and NO release as compared with cells treated with control PMO Using a retinal ischemia reperfusion injury model in mice, we observed that recruitment of diabetic CD34(+) cells to injured acellular retinal capillaries was greater after TGF-beta 1-PMO treatment compared with control PMO-treated cells. CONCLUSIONS-Transient inhibition of TGF-beta 1 may represent a promising therapeutic strategy for restoring the reparative capacity of dysfunctional diabetic CD34(+) cells. Diabetes 59:2010-2019, 2010 C1 [Kennedy, Laurence; Lansang, M. Cecilia; Grant, Maria B.] Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32611 USA. [Pepine, Carl J.] Univ Florida, Div Cardiol, Gainesville, FL USA. [Guerin, E. P.; Kent, David] Vis Clin, Kilkenny, Ireland. [Sheridan, Carl] Univ Liverpool, Sch Clin Sci, Liverpool L69 3BX, Merseyside, England. [Ruscetti, Frank W.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Higgins, Paul J.] Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. [Bartelmez, Stephen H.] BetaStem Therapeut Inc, San Francisco, CA USA. RP Grant, MB (reprint author), Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32611 USA. FU National Institutes of Health [EY-007739, EY-012601]; Juvenile Diabetes Research Foundation; American Heart Association; BetaStem Therapeutics Inc.; [U01-HL-087366] FX This work was supported by grants to M.B.G. from the National Institutes of Health (EY-007739 and EY-012601), U01-HL-087366, the Loftus family, and the Juvenile Diabetes Research Foundation and to A.D.B. from the American Heart Association. S.H.B. received a grant from BetaStem Therapeutics Inc. No other potential conflicts of interest relevant to this article were reported. NR 47 TC 14 Z9 16 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2010 VL 59 IS 8 BP 2010 EP 2019 DI 10.2337/db10-0287 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636PA UT WOS:000280749100020 PM 20460428 ER PT J AU Muller, YL Hanson, RL Bian, L Mack, J Shi, XL Pakyz, R Shuldiner, AR Knowler, WC Bogardus, C Baier, LJ AF Muller, Yunhua L. Hanson, Robert L. Bian, Li Mack, Janel Shi, Xiaolian Pakyz, Ruth Shuldiner, Alan R. Knowler, William C. Bogardus, Clifton Baier, Leslie J. TI Functional Variants in MBL2 Are Associated With Type 2 Diabetes and Pre-Diabetes Traits in Pima Indians and the Old Order Amish SO DIABETES LA English DT Article ID MANNOSE-BINDING LECTIN; INSULIN-RESISTANCE; GENE POLYMORPHISMS; AMERICAN-INDIANS; PROTEIN; LOCI; REPLICATION; DISEASE; MELLITUS; OBESITY AB OBJECTIVE-MBL2 encodes the mannose-binding learn, which is a key player in the innate immune system and has recently been found to play a role in insulin resistance and development of type 1 diabetes and gestational diabetes mellitus To assess the role of MBL2 in diabetes susceptibility, this gene was analyzed in the Pima Indian population, which has a high prevalence of type 2 diabetes. RESEARCH DESIGN AND METHODS-Nineteen tag single nucleotide polymorphisms (SNPs) were genotyped in a population-based sample of 3,501 full-heritage Pima Indians, and selected SNPs were further genotyped in independent samples of Native American (n = 3,723) and Old Order Amish (n = 486) subjects. RESULTS-Two variants, a promoter SNP (rs11003125) at -550 bp with a risk allele frequency of 0 77 and a Gly54Asp (rs1800450) with a risk allele frequency of 0.83, were associated with type 2 diabetes in the full-heritage Pima Indians (odds ratio 1 30 per copy of the G allele for rs1103125, P = 0.0007, and 1.30 per copy of the glycine allele for rs1800450, P = 0 002, adjusted for age, sex, birth year, and family membership). These associations replicated in an independent Native American sample (1.19, P = 004, for rs11003125) and a Caucasian sample, the Old Order Amish (1 51, P = 0.004, for rs1103125 and 2 38, P = 0.003, for rs1800450). Among Pima Indians with normal glucose tolerance, the diabetes risk allele glycine of Gly54Asp was associated with a decreased acute insulin response to an intravenous glucose bolus infusion (P = 0 004, adjusted for age, sex, percent body fat, glucose disposal under physiological insulin stimulation, and family membership). CONCLUSIONS-Our data suggest that the functional variants in MBL2 contribute to type 2 diabetes susceptibility in both Native Americans and the Old Order Amish. Diabetes 59: 2080-2085, 2010 C1 [Muller, Yunhua L.; Hanson, Robert L.; Bian, Li; Mack, Janel; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Diabet Mol Genet Sect, NIH, Phoenix, AZ USA. [Muller, Yunhua L.; Hanson, Robert L.; Bian, Li; Mack, Janel; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. [Shi, Xiaolian; Pakyz, Ruth; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. RP Baier, LJ (reprint author), NIDDK, Diabet Mol Genet Sect, NIH, Phoenix, AZ USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Digestive and Kidney Disease; National Institutes of Health; National Insitutes of Health [R01 DK54261, P30 DK072488, P60 DK079637]; ADA FX This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Disease, the National Institutes of Health. The Amish study was supported by National Insitutes of Health grants R01 DK54261 and P30 DK072488 (to the Clinical Nutrition Research Unit of Maryland) and P60 DK079637 (to the Baltimore Diabetes Research and Training Center). Li Bian was supported by an ADA mentor grant awarded to Clifton Bogardus. NR 31 TC 10 Z9 13 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2010 VL 59 IS 8 BP 2080 EP 2085 DI 10.2337/db09-1593 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 636PA UT WOS:000280749100029 PM 20522590 ER PT J AU Penesova, A Bunt, JC Bogardus, C Krakoff, J AF Penesova, Adela Bunt, Joy C. Bogardus, Clifton Krakoff, Jonathan TI Effect of Paternal Diabetes on Pre-Diabetic Phenotypes in Adult Offspring SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LOW-BIRTH-WEIGHT; PIMA-INDIANS; INSULIN ACTION; METABOLIC CHARACTERISTICS; BETA-CELL; ASSOCIATION; TRANSMISSION; INDIVIDUALS; INTOLERANCE AB OBJECTIVE Paternal and maternal type 2 diabetes, exclusive of gestational diabetes, may influence risk factors in the offspring differently (through possible epigenetic effects of parental diabetes) and are difficult to identify without accurate dates of diagnosis. We aimed to examine a metabolic phenotype in three different groups of offspring to see distinct paternal versus maternal effects. RESEARCH DESIGN AND METHODS We examined body composition and insulin action (M) in nondiabetic subjects and insulin secretion tested via acute insulin response (AIR) in normal glucose-tolerant full-heritage Pima Indian adults categorized by disparate parental diabetes status: 1) offspring of fathers with early-onset diabetes (age <35 years) and nondiabetic mothers (ODF; n = 10), 2) offspring of mothers with early-onset diabetes (age <35 years), not exposed to diabetes in utero with nondiabetic fathers (OMED; n = 11), and 3) a control group of offspring of parents without diabetes until >50 years of age (CON; n = 15). RESULTS ODFs were leaner than CONs and OMEDs (percent of body fat [%BF]: least-squares means adjusted for age and sex [95% CI]: 27.3 [23.3-31.3] in ODFs vs. 35.4 [32.2-38.5] in CONs and 32.4 [28.8-36.1] in OMEDs, P = 0.04). ODFs were more insulin sensitive (had a higher M) than OMEDs or CONs, but not after adjustment for age, sex, and %BF. AIR adjusted for M, age, sex, and %BF was lower in ODFs versus CONs and OMEDs (P < 0.05). CONCLUSIONS Adult ODFs were leaner and had lower early insulin secretion, despite being equally insulin sensitive after adjustment for body fat compared to the other groups, indicating a paternal imprinted effect. C1 [Penesova, Adela; Bunt, Joy C.; Krakoff, Jonathan] NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ USA. RP Penesova, A (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ USA. EM adela.penesova@savba.sk FU National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NR 25 TC 6 Z9 9 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2010 VL 33 IS 8 BP 1823 EP 1828 DI 10.2337/dc10-0664 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 645AF UT WOS:000281422600025 PM 20519666 ER PT J AU Nandagopal, R Brown, RJ Rother, KI AF Nandagopal, Radha Brown, Rebecca J. Rother, Kristina I. TI Resolution of Type 2 Diabetes Following Bariatric Surgery: Implications for Adults and Adolescents SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Review ID Y GASTRIC BYPASS; CARDIOVASCULAR RISK-FACTORS; BODY-MASS INDEX; BILIOPANCREATIC DIVERSION; MORBID-OBESITY; WEIGHT-LOSS; METABOLIC SYNDROME; SLEEVE GASTRECTOMY; GLUCOSE-TOLERANCE; MELLITUS AB Bariatric surgery is now widely reported to ameliorate or resolve type 2 diabetes mellitus in adults. Some clinical investigators even suggest its use as an early therapeutic intervention for type 2 diabetes in patients not meeting standard criteria for bariatric surgery. However, little is known about the exact mechanisms explaining the metabolic consequences, and much active investigation is underway to identify hormonal changes leading to diabetes resolution. This review includes a detailed description of various bariatric surgical procedures, including the latest less-invasive techniques, and a summary of current data providing insight into the short- and long-term metabolic effects. We outline current hypotheses regarding the mechanisms by which these surgical procedures affect diabetes and report on morbidity and mortality. Finally, we discuss the available data on bariatric surgery in adolescent patients, including special considerations in this potentially vulnerable population. C1 [Nandagopal, Radha; Brown, Rebecca J.; Rother, Kristina I.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Rother, KI (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,Room 8C 432A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kr58q@nih.gov FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. We thank Leann Sutphin for her contributions to this manuscript. NR 66 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 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD AUG PY 2010 VL 12 IS 8 BP 671 EP 677 DI 10.1089/dia.2010.0037 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 622EB UT WOS:000279642000012 PM 20615109 ER PT J AU Rubin, RR Gaussoin, SA Peyrot, M DiLillo, V Miller, K Wadden, TA West, DS Wing, RR Knowler, WC AF Rubin, R. R. Gaussoin, S. A. Peyrot, M. DiLillo, V. Miller, K. Wadden, T. A. West, D. S. Wing, R. R. Knowler, W. C. CA Look AHEAD Res Grp TI Cardiovascular disease risk factors, depression symptoms and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes SO DIABETOLOGIA LA English DT Article DE Antidepressant medication; CVD risk; Depression symptoms; Look AHEAD trial ID ANKLE-BRACHIAL INDEX; MYOCARDIAL-INFARCTION; PREVENTION PROGRAM; MORTALITY; CARE; INDIVIDUALS; ASSOCIATION; MEDICATION; EVENTS; ADULTS AB To determine the associations of baseline depression symptoms and use of antidepressant medicines (ADMs) with baseline cardiovascular disease (CVD) risk factors in Look AHEAD (Action for Health in Diabetes) trial participants. Look AHEAD participants (n = 5,145; age 58.7 +/- 6.8 years; BMI 35.8 +/- 5.8 kg/m(2)) were assessed for CVD risk factors (elevated HbA(1c) or insulin use, elevated BP or antihypertensive use, elevated lipid levels or lipid-lowering medication, current smoking, BMI a parts per thousand yen30 kg/m(2), lower peak exercise capacity assessed as metabolic equivalents [METs], and ankle-brachial index < 0.9 or > 1.3). Participants also completed the Beck Depression Inventory (BDI) and reported their use of ADMs. Of the participants, 14.7% had BDI scores a parts per thousand yen11, consistent with mild-moderate depression, and 16.5% took ADMs; 4.4% had both depression markers (i.e. elevated symptom scores and took ADMs). In logistic regression analyses of CVD risk (elevated risk factor or use of medication to control the risk factor), controlled for demographic factors, continuous BDI scores and ADM use were each independently associated with elevated BP (or medication), current smoking, BMI a parts per thousand yen30 kg/m(2) and lower MET values. ADM use was also associated with elevated serum lipids or use of lipid-lowering medication. Among Look AHEAD participants, depression symptoms or ADM use on entry to the study were each independently associated with a wide range of CVD risk factors. Future research should assess the temporal dynamics of the relationships of depression symptoms and ADM use with CVD risk factors. Clinicaltrials.gov NCT00017953 This study is funded by the National Institutes of Health with additional support from the Centers for Disease Control and Prevention. C1 [Rubin, R. R.; Peyrot, M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA. [Rubin, R. R.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. [Gaussoin, S. A.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Peyrot, M.] Loyola Univ Maryland, Dept Sociol, Baltimore, MD USA. [DiLillo, V.] Ohio Wesleyan Univ, Dept Psychol, Delaware, OH 43015 USA. [Miller, K.] Univ N Carolina, Dept Educ, Chapel Hill, NC USA. [Wadden, T. A.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [West, D. S.] Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. [Wing, R. R.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Knowler, W. C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. RP Rubin, RR (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 600 N Wolfe St, Baltimore, MD 21287 USA. EM rrubin4@jhmi.edu FU National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992, DK 046204]; 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; Centers for Disease Control and Prevention; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01-RR-02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01-RR-01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01 RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR00211-40]; University of Pittsburgh General Clinical Research Center [M01 RR000056 44]; University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs FX 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; and the Centers for Disease Control and Prevention. 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. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01-RR-02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01-RR-01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01 RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR00211-40); the University of Pittsburgh General Clinical Research Center (M01 RR000056 44) and NIH grant (DK 046204); and the University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs. The following organisations have committed to make major contributions to Look AHEAD: Federal Express; Health Management Resources; Johnson & Johnson; LifeScan; Optifast-Novartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; Slim-Fast Foods Company; and Unilever. NR 24 TC 32 Z9 32 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2010 VL 53 IS 8 BP 1581 EP 1589 DI 10.1007/s00125-010-1765-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 616FG UT WOS:000279193800008 PM 20422396 ER PT J AU Green, TC Kershaw, T Lin, HQ Heimer, R Goulet, JL Kraemer, KL Gordon, AJ Maisto, SA Day, NL Bryant, K Fiellin, DA Justice, AC AF Green, Traci C. Kershaw, Trace Lin, Haiqun Heimer, Robert Goulet, Joseph L. Kraemer, Kevin L. Gordon, Adam J. Maisto, Steve A. Day, Nancy L. Bryant, Kendall Fiellin, David A. Justice, Amy C. TI Patterns of drug use and abuse among aging adults with and without HIV: A latent class analysis of a US Veteran cohort SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Aging; Veterans; HIV; Substance-related disorders; Latent class analysis; Illicit drugs; Cohort studies ID ACTIVE ANTIRETROVIRAL THERAPY; SUBSTANCE USE DISORDERS; VIRUS-INFECTED VETERANS; HEALTH-CARE UTILIZATION; NEW-YORK-CITY; DEVELOPMENTAL TRAJECTORIES; YOUNG ADULTHOOD; UNITED-STATES; MARIJUANA USE; OLDER-ADULTS AB This study characterized the extent and patterns of self-reported drug use among aging adults with and without HIV, assessed differences in patterns by HIV status, and examined pattern correlates. Data derived from 6351 HIV-infected and uninfected adults enrolled in an eight-site matched cohort, the Veterans Aging Cohort Study (VACS). Using clinical variables from electronic medical records and socio-demographics, drug use consequences, and frequency of drug use from baseline surveys, we performed latent class analyses (LCA) stratified by HIV status and adjusted for clinical and socio-demographic covariates. Participants were, on average, age 50 (range 22-86), primarily male (95%) and African-American (64%). Five distinct patterns emerged: non-users, past primarily marijuana users, past multidrug users, current high consequence multidrug users, and current low consequence primarily marijuana users. HIV status strongly influenced class membership. Non-users were most prevalent among HIV uninfected (36.4%) and current high consequence multidrug users (25.5%) were most prevalent among HIV-infected. While problems of obesity marked those not currently using drugs, current users experienced higher prevalences of medical or mental health disorders. Multimorbidity was highest among past and current multidrug users. HIV-infected participants were more likely than HIV-uninfected participants to be current low consequence primarily marijuana users. In this sample, active drug use and abuse were common. HIV-infected and uninfected Veterans differed on extent and patterns of drug use and on important characteristics within identified classes. Findings have the potential to inform screening and intervention efforts in aging drug users with and without HIV. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Green, Traci C.; Kershaw, Trace] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Green, Traci C.; Kershaw, Trace; Heimer, Robert; Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [Lin, Haiqun] Yale Univ, Sch Publ Hlth, Div Biostat, New Haven, CT USA. [Heimer, Robert] Yale Univ, Sch Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT USA. [Goulet, Joseph L.; Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Kraemer, Kevin L.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr Comorbid VISN, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Maisto, Steve A.] Syracuse Univ, Dept Psychol, Ctr Hlth & Behav, Syracuse, NY USA. [Day, Nancy L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Bryant, Kendall] NIAAA, Bethesda, MD USA. [Fiellin, David A.] Yale Univ, Sch Med, Investigat Med Program, New Haven, CT USA. RP Green, TC (reprint author), 111 Plain St Bldg,Rm 111, Providence, RI 02903 USA. EM traci.c.green@brown.edu RI Day, Nancy/H-3171-2016; OI Goulet, Joseph/0000-0002-0842-804X; Fiellin, David/0000-0002-4006-010X FU National Institutes of Health, National Institute on Drug Abuse [1F31DA023862-01A1]; National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]; VHA Public Health Strategic Health Core Group FX Research for this manuscript was supported by the National Institutes of Health, National Institute on Drug Abuse grant 1F31DA023862-01A1 to TCG. The Veterans Aging Cohort Study funded by: National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566) and VHA Public Health Strategic Health Core Group. The funding sources had no further involvement in the study design, data collection, analysis, writing, preparation or decision to submit this manuscript for publication. NR 94 TC 37 Z9 37 U1 2 U2 11 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 AUG 1 PY 2010 VL 110 IS 3 BP 208 EP 220 DI 10.1016/j.drugalcdep.2010.02.020 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 634ZU UT WOS:000280626200005 PM 20395074 ER PT J AU Dohse, M Scharenberg, C Shukla, S Robey, RW Volkmann, T Deeken, JF Brendel, C Ambudkar, SV Neubauer, A Bates, SE AF Dohse, Marius Scharenberg, Christian Shukla, Suneet Robey, Robert W. Volkmann, Thorsten Deeken, John F. Brendel, Cornelia Ambudkar, Suresh V. Neubauer, Andreas Bates, Susan E. TI Comparison of ATP-Binding Cassette Transporter Interactions with the Tyrosine Kinase Inhibitors Imatinib, Nilotinib, and Dasatinib SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; HIGH-AFFINITY INTERACTION; HEMATOPOIETIC STEM-CELLS; MEDIATED DRUG EFFLUX; P-GLYCOPROTEIN; BCR-ABL; IN-VITRO; MULTIDRUG TRANSPORTER; PRIMARY CML; RESISTANCE AB Although the development of tyrosine kinase inhibitors (TKIs) to control the unregulated activity of BCR-ABL revolutionized the therapy of chronic myeloid leukemia, resistance to TKIs is a clinical reality. Among the postulated mechanisms of resistance is the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), which mediate reduced intracellular drug accumulation. We compared the interactions of the TKIs imatinib, nilotinib, and dasatinib with ABCB1 and ABCG2 in ex vivo and in vitro systems. The TKIs inhibited rhodamine 123 and Hoechst 33342 efflux mediated by endogenous expression of the transporters in murine and human hematopoietic stem cells with potency order nilotinib >> imatinib >> dasatinib. Studies with ABCB1-, ABCG2-, and ABCC1-transfected human embryonic kidney 293 cells verified that nilotinib was the most potent inhibitor of ABCB1 and ABCG2. Cytotoxicity assays in stably transduced K562-ABCG2 and K562-ABCB1 cells confirmed that the TKIs were also substrates for the two transporters. Like imatinib, both nilotinib and dasatinib decreased ABCG2 surface expression in K562-ABCG2 cells. Finally, we found that all TKIs were able to compete labeling of ABCB1 and ABCG2 by the photo-cross-linkable prazosin analog [(125)I] iodoarylazidoprazosin, suggesting interaction at the prazosin-binding site of both proteins. Our experiments support the hypothesis that all three TKIs are substrates of ABC transporters and that, at higher concentrations, TKIs overcome transporter function. Taken together, the results suggest that therapeutic doses of imatinib and nilotinib may diminish the potential of ABCB1 and ABCG2 to limit oral absorption or confer resistance. Clinical data are required to definitively answer the latter question. C1 [Dohse, Marius; Shukla, Suneet; Robey, Robert W.; Ambudkar, Suresh V.; Bates, Susan E.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dohse, Marius; Scharenberg, Christian; Volkmann, Thorsten; Brendel, Cornelia; Neubauer, Andreas] Univ Marburg, Dept Hematol Oncol & Immunol, Marburg, Germany. [Scharenberg, Christian] Karolinska Inst, Dept Med, Ctr Expt Hematol, Karolinska Univ Hosp Huddinge, Stockholm, Sweden. [Deeken, John F.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. RP Bates, SE (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov RI shukla, suneet/B-4626-2012 FU National Institutes of Health National Cancer Institute FX This work was supported in part by the Intramural Research Program of the National Institutes of Health National Cancer Institute; and the Kind-Phillip-Foundation for Leukemia Research (to M.D.). NR 41 TC 81 Z9 84 U1 1 U2 13 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD AUG PY 2010 VL 38 IS 8 BP 1371 EP 1380 DI 10.1124/dmd.109.031302 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 626HG UT WOS:000279956400014 PM 20423956 ER PT J AU Negishi, M AF Negishi, Masahiko TI CAR and Gene Regulation: Mechanism and Action SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics(ISSX) CY SEP 04-08, 2010 CL Istanbul, TURKEY SP Int Soc Study Xenobiot C1 [Negishi, Masahiko] NIEHS, Pharmacogenet Sect, LRDT, NIH, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD AUG PY 2010 VL 42 SU 1 BP 10 EP 11 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641RP UT WOS:000281147700021 ER PT J AU Surapureddi, S Rana, R Goldstein, J AF Surapureddi, Sailesh Rana, Ritu Goldstein, Joyce TI Med25 as a coactivator of HNF4 alpha, reveals vital role in RNA Polymerase II recruitment and defective drug metabolism in human liver SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics(ISSX) CY SEP 04-08, 2010 CL Istanbul, TURKEY SP Int Soc Study Xenobiot C1 [Surapureddi, Sailesh; Rana, Ritu; Goldstein, Joyce] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD AUG PY 2010 VL 42 SU 1 BP 157 EP 158 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641RP UT WOS:000281147700279 ER PT J AU Bourdi, M Davies, JS Raghavachari, N Liu, DLN Sendide, K Munson, PJ Pohl, LR AF Bourdi, Mohammed Davies, John S. Raghavachari, Nalini Liu, Delong N. Sendide, Khalid Munson, Peter J. Pohl, Lance R. TI Confounding Effects of C57BL/6 Substrains in Toxicology SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics(ISSX) CY SEP 04-08, 2010 CL Istanbul, TURKEY SP Int Soc Study Xenobiot C1 [Bourdi, Mohammed; Davies, John S.; Sendide, Khalid; Pohl, Lance R.] NHLBI, Lab Mol Immunol, NIH, DHHS, Bethesda, MD 20892 USA. [Raghavachari, Nalini] NHLBI, Genom Core Facil, Bethesda, MD 20892 USA. [Liu, Delong N.; Munson, Peter J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD AUG PY 2010 VL 42 SU 1 BP 257 EP 257 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641RP UT WOS:000281147700456 ER PT J AU Cadenhead, KS Addington, J Cannon, T Cornblatt, B McGlashan, T Perkins, D Seidman, L Tsuang, M Walker, E Woods, S Heinssen, R AF Cadenhead, Kristin S. Addington, Jean Cannon, Tyrone Cornblatt, Barbara McGlashan, Thomas Perkins, Diana Seidman, Larry Tsuang, Ming Walker, Elaine Woods, Scott Heinssen, Robert TI Reshaping an enduring sense of self: the process of recovery from a first episode of schizophrenia SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Article DE qualitative research; recovery of function; schizophrenia; self-concept ID ULTRA-HIGH-RISK; PRODROMAL SCHIZOPHRENIA; PSYCHOSIS; SCALE; INTERVENTIONS; DISORDERS; SERVICES; PEOPLE; TRIAL AB Aim: Although advances in the treatment of schizophrenia have been made, little is known about the process of recovery from first episode of schizophrenia (FES). To date, the study of recovery in the field of mental health has focused on long-term mental illness. This qualitative study addresses ways in which individuals with FES describe their process of recovery and how identified individuals (e.g. family members) describe their perceptions of and roles in the participant's process of recovery. Methods: Charmaz's constructivist grounded theory methodology was used to interview 10 young adults twice who self-identified as recovering from FES. In addition, 10 individuals were identified who had influenced their recovery and were interviewed once, for a total of 30 interviews. Data collection sources included in-depth semi-structured interviews. Data analysis methods were consistent with Charmaz's methodology and included coding, and constant comparison of data. Results: The results provide a substantive theory of the process of recovery from FES that is comprised of the following phases: 'Who they were prior to the illness', 'Lives interrupted: Encountering the illness', 'Engaging in services and supports', 'Re-engaging in life', 'Envisioning the future'; and the core category, 'Re-shaping an enduring sense of self', that occurred throughout all phases. A prominent feature of this model is that participants' enduring sense of self were reshaped rather than reconstructed throughout their recovery. Conclusions: This model of recovery from FES is unique, and as such, provides implications for clinical care, research and policy development for these young adults and their families. C1 [Cadenhead, Kristin S.; Tsuang, Ming] UCSD, Dept Psychiat & Biobehav Sci, San Diego, CA USA. [Cannon, Tyrone] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cannon, Tyrone] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Cornblatt, Barbara] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [McGlashan, Thomas; Woods, Scott] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Perkins, Diana] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Walker, Elaine] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Schizophrenia Spectrum Disorders Res Program, Div Adult Translat Res, Bethesda, MD USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. RP Cadenhead, KS (reprint author), Univ Calif San Diego, Dept Psychiat, 0810,9500 Gilman Dr, La Jolla, CA 92093 USA. EM kcadenhead@ucsd.edu FU National Institute of Mental Health [R01 MH60720, K24 MH76191, U01 MH066134, R01 MH065079, R01 MH061523, K05MH01654, U01 MH066069, P50 MH064065, R01 MH065562, P50 MH080272, R21MH075027, RO1MH062066, U01 MH066160]; Donaghue Foundation; Eli Lilly Co FX This work was supported by the National Institute of Mental Health R01 MH60720 and K24 MH76191 to KSC, U01 MH066134 to JA, R01 MH065079 to TDC, R01 MH061523 to BAC, K05MH01654 to THM, U01 MH066069 and P50 MH064065 to DOP, R01 MH065562 and P50 MH080272 to LJS, R21MH075027 to MTT, RO1MH062066 to EFW, U01 MH066160 to SWW, Donaghue Foundation to SWW and Eli Lilly & Co to THM, JA, and DOP. NR 20 TC 28 Z9 28 U1 2 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD AUG PY 2010 VL 4 IS 3 BP 220 EP 226 DI 10.1111/j.1751-7893.2010.00183.x PG 7 WC Psychiatry SC Psychiatry GA 639SY UT WOS:000280996000005 PM 20712727 ER PT J AU Wiench, M Hager, GL AF Wiench, Malgorzata Hager, Gordon L. TI Expanding horizons for nuclear receptors SO EMBO REPORTS LA English DT Editorial Material ID GLUCOCORTICOID-RECEPTOR C1 [Wiench, Malgorzata; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Wiench, M (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD AUG PY 2010 VL 11 IS 8 BP 569 EP 571 DI 10.1038/embor.2010.111 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 630YS UT WOS:000280313400006 PM 20634803 ER PT J AU Constantin, S Klenke, U Wray, S AF Constantin, Stephanie Klenke, Ulrike Wray, Susan TI The Calcium Oscillator of GnRH-1 Neurons Is Developmentally Regulated SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; EMBRYONIC OLFACTORY PLACODE; GREEN FLUORESCENT PROTEIN; LHRH NEURONS; RHESUS-MONKEY; FUNCTIONAL EXPRESSION; CA2+ OSCILLATIONS; MOLECULAR-CLONING; EXPLANT CULTURES; A RECEPTOR AB Oscillations in intracellular calcium levels have been described in GnRH-1 neurons in both prenatal and adult cells. However, differences have been reported in the mechanisms underlying these [Ca(2+)](i) oscillations, dependent on the model used. The goal of this study was to address whether these changes depend on the maturation status of GnRH-1 neurons by assaying prenatal GnRH-1 cells maintained in explants, at two different developmental stages. This report documents an increase in the frequency of [Ca(2+)](i) oscillations between 1 and 3 wk of in vitro maturation. During the early stage, [Ca(2+)](i) oscillations are blocked by tetrodotoxin and are mainly triggered by excitatory neurotransmitters, gamma-aminobutyric acid (GABA), and glutamate. In contrast, in the later stage, some cells exhibit residual tetrodotoxin-insensitive [Ca(2+)](i) oscillations, which are sustained by action potential-independent GABA and glutamate release. The strength of these two excitatory inputs remained relatively constant during the maturation process, and the increase in frequency of [Ca(2+)](i) oscillations observed at the later stage is due to a novel excitatory input carried by cholecystokinin. Together, these data indicate developmentally regulated release and interactions of neurotransmitters (known regulators of GnRH-1 cells in adults) and point to extrinsic factors regulating GnRH-1 cellular physiology. (Endocrinology 151: 3863-3873, 2010) C1 [Constantin, Stephanie; Klenke, Ulrike; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Constantin, Stephanie] Univ Otago, Dept Physiol, Ctr Neuroendocrinol, Dunedin 9054, New Zealand. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, 9000 Rock Pike 36 5W21,Bldg 36,Room 5A-25, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov RI Constantin, Stephanie/C-5264-2009; OI Constantin, Stephanie/0000-0003-0596-9737; wray, susan/0000-0001-7670-3915 FU National Institutes of Health, National Institute of Neurological Disorders and Stroke FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. NR 53 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2010 VL 151 IS 8 BP 3863 EP 3873 DI 10.1210/en.2010-0118 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 629CH UT WOS:000280171100038 PM 20555030 ER PT J AU Shen, HCJ Ylaya, K Pechhold, K Wilson, A Adem, A Hewitt, SM Libutti, SK AF Shen, H. -C. Jennifer Ylaya, Kris Pechhold, Klaus Wilson, Arianne Adem, Asha Hewitt, Stephen M. Libutti, Steven K. TI Multiple Endocrine Neoplasia Type 1 Deletion in Pancreatic alpha-Cells Leads to Development of Insulinomas in Mice SO ENDOCRINOLOGY LA English DT Article ID MEN1 GENE; CONDITIONAL INACTIVATION; MOUSE MODEL; TUMORS; IDENTIFICATION; ISLETS; VHL AB The pancreatic alpha- and beta-cells are critical components in regulating blood glucose homeostasis via secretion of glucagon and insulin, respectively. Both cell types are typically localized in the islets of Langerhans. However, little is known about the roles of paracrine interactions that contribute to their physiological functions. The lack of suitable cell lines to study alpha- and beta-cells interactions have led us to develop an alpha-cell-specific Cre-expressing transgenic line utilizing a glucagon promoter sequence, the Glu-Cre transgenic mouse. Here, we demonstrate that the Glu-Cre could specifically and efficiently excise floxed target genes in adult islet alpha-cells. We further showed that deletion of the tumor suppressor gene, multiple endocrine neoplasia type 1 (Men1), in alpha-cells led to tumorigenesis. However, to our surprise, the lack of Men1 in alpha-cells did not result in glucagonomas but rather beta-cell insulinomas. Because deletion of the Men1 alleles was only present in alpha-cells, our data suggested that cross communication between alpha- and beta-cells contributes to tumorigenesis in the absence of Men1. Together, we believed that the new model systems described here will allow future studies to decipher cellular interactions between islet alpha- and beta-cells in a physiological context. (Endocrinology 151: 4024-4030, 2010) C1 [Shen, H. -C. Jennifer; Ylaya, Kris; Wilson, Arianne; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Pechhold, Klaus] NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA. EM slibutti@montefiore.org OI Hewitt, Stephen/0000-0001-8283-1788 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by funds from the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 25 TC 13 Z9 13 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2010 VL 151 IS 8 BP 4024 EP 4030 DI 10.1210/en.2009-1251 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 629CH UT WOS:000280171100053 PM 20555035 ER PT J AU Scherubl, H Cadiot, G Jensen, RT Rosch, T Stolzel, U Kloppel, G AF Scheruebl, H. Cadiot, G. Jensen, R. T. Roesch, T. Stoelzel, U. Kloeppel, G. TI Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems? SO ENDOSCOPY LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; ENDOCRINE NEOPLASIA TYPE-1; GASTROENTEROPANCREATIC TUMORS; ENDOSCOPIC ULTRASONOGRAPHY; GASTROINTESTINAL TUMORS; SOMATOSTATIN ANALOGS; CELL CHANGES; MANAGEMENT; DIAGNOSIS; PATHOGENESIS AB Well differentiated neuroendocrine tumors (NETs) of the stomach (gastric carcinoid tumors) are observed more often, with a tenfold increase in the US in the last 30-35 years, and the prognosis has improved greatly in that time. Nowadays most carcinoids of the stomach are diagnosed at an early stage. Four types of gastric NETs have been proposed and recognition of the type is important for defining the diagnostic approach and treatment. Often gastric NETs (especially type 1) are found incidentally during a gastroscopy performed for other reasons; most of these NETs are smaller than 20 mm in size. Conservative management and endoscopic surveillance is adequate for well differentiated, multifocal gastric carcinoids (type 1 or type 2 gastric NETs) that are less than 10-20 mm in diameter, unless they show angioinvasion, infiltrate the muscular wall, or have a proliferation rate above 2%. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. It is essential to distinguish between multifocal (types 1 and 2) and unifocal type 3 or type 4 gastric NETs, since surgery is indicated for type 3 gastric NETs larger than 10 mm in diameter and for poorly differentiated (localized) neuroendocrine gastric carcinomas (type 4 gastric NET). For optimal management, the type, biology, and stage of the tumor as well as the individual situation of the patient must be considered. Most patients with well differentiated gastric NETs can be treated conservatively and be followed up with endoscopic surveillance. C1 [Scheruebl, H.] Vivantes Klinikum Urban, Klin Innere Med Gastroenterol & Gastrointestinale, D-10967 Berlin, Germany. [Cadiot, G.] Hop Robert Debre, Serv Hepatogastroenterol, Reims, France. [Jensen, R. T.] NIH, Digest Dis Branch, Bethesda, MD 20892 USA. [Roesch, T.] Univ Klinikum Hamburg Eppendorf, Klin Interdisziplinare Endoskopie, Hamburg, Germany. [Stoelzel, U.] Klinikum Chemnitz, Klin Gastroenterol & GI Onkol, Chemnitz, Germany. [Kloeppel, G.] Tech Univ Munich, Klinikum Rechts Isar, Inst Pathol, D-8000 Munich, Germany. RP Scherubl, H (reprint author), Vivantes Klinikum Urban, Klin Innere Med Gastroenterol & Gastrointestinale, Dieffenbachstr 1, D-10967 Berlin, Germany. EM hans.scheruebl@vivantes.de NR 64 TC 44 Z9 49 U1 0 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD AUG PY 2010 VL 42 IS 8 BP 664 EP 671 DI 10.1055/s-0030-1255564 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 633HK UT WOS:000280492300010 PM 20669078 ER PT J AU Pommier, Y Sordet, O Redon, C Das, B Regairaz, M AF Pommier, Y. Sordet, O. Redon, C. Das, B. Regairaz, M. TI Promotion of Genomic Stability by DNA Topoisomerase I by Coordination of Transcription and Replication SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Pommier, Y.; Sordet, O.; Redon, C.; Das, B.; Regairaz, M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 686 EP 686 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600009 ER PT J AU Stumpf, JD Bailey, CM Spell, D Stillwagon, M Anderson, KS Copeland, WC AF Stumpf, J. D. Bailey, C. M. Spell, D. Stillwagon, M. Anderson, K. S. Copeland, W. C. TI Evidence that mtDNA Depletion but Not Point Mutations or Deletions Causes DNA Polymerase Gamma-Related Mitochondrial Diseases SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Stumpf, J. D.; Spell, D.; Stillwagon, M.; Copeland, W. C.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Bailey, C. M.; Anderson, K. S.] Yale Univ, Dept Pharmacol, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 695 EP 695 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600046 ER PT J AU Lubet, RA AF Lubet, R. A. TI Chemopreventive Efficacy of Agents that Interact with the Antioxidant Response Element and Agents that Induce the Ah Receptor SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Lubet, R. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 698 EP 698 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600055 ER PT J AU Beckel-Mitchener, A AF Beckel-Mitchener, A. TI Pre-Clinical Drug Development Studies in Fragile-X: The NIH Perspective SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Beckel-Mitchener, A.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 701 EP 701 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600068 ER PT J AU Momot, D Nostrand, TA Ward, Y John, K Poirier, MC Olivero, OA AF Momot, D. Nostrand, T. A. Ward, Y. John, K. Poirier, M. C. Olivero, O. A. TI Role of Nucleotide Excision Repair (NER) in Manifestation of Zidovudine (AZT)-Induced Aneuploidy and Centrosomal Dysregulation SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Momot, D.; Nostrand, T. A.; Ward, Y.; John, K.; Poirier, M. C.; Olivero, O. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 704 EP 704 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600082 ER PT J AU Marchetti, F Polyzos, A William, A Bishop, J Yauk, C AF Marchetti, F. Polyzos, A. William, A. Bishop, J. Yauk, C. TI Mainstream and Sidestream Tobacco Smoke Induce Mutations in Male Germ Cells But Not Micronuclei in Erythrocytes in the Mouse SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Marchetti, F.; Polyzos, A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. [William, A.; Yauk, C.] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Bishop, J.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 705 EP 705 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600083 ER PT J AU Hernandez, REE John, K Woodward, RA Poiner, M AF Hernandez, Ramon E. E. John, K. Woodward, R. A. Poiner, M. TI Detection of Tamoxifen (TAM)-DNA Adduct Formation in Primates and Patients SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Hernandez, Ramon E. E.; John, K.; Woodward, R. A.; Poiner, M.] NCI, NIH, Bethesda, MD 20892 USA. [Woodward, R. A.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 714 EP 714 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600121 ER PT J AU Yamanaka, K Eoff, RL Egli, M Dorjsuren, D Jadhav, A Simeonov, A Lloyd, RS AF Yamanaka, K. Eoff, R. L. Egli, M. Dorjsuren, D. Jadhav, A. Simeonov, A. Lloyd, R. S. TI Small Molecule Inhibitors of DNA Polymerase Kappa SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Yamanaka, K.; Lloyd, R. S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Eoff, R. L.; Egli, M.] Vanderbilt Univ, Nashville, TN USA. [Dorjsuren, D.; Jadhav, A.; Simeonov, A.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 716 EP 716 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600127 ER PT J AU Cline, SD Marnett, LJ Copeland, WC AF Cline, S. D. Marnett, L. J. Copeland, W. C. TI Disruption of Human Mitochondrial DNA Polymerase y Replication by the Endogenous Aldehyde Adduct of DNA, M(1)dG SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Cline, S. D.] Mercer Univ, Sch Med, Macon, GA 31207 USA. [Marnett, L. J.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Copeland, W. C.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 717 EP 717 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600132 ER PT J AU Swartz, CD Lentz, CA Green, AS Prajapati, MH Recio, L Witt, KL AF Swartz, C. D. Lentz, C. A. Green, A. S. Prajapati, M. H. Recio, L. Witt, K. L. TI Mutagenicity of Three Herbal Products, Pulegone, Senna, and Milk Thistle Extract, in the Ames Salmonella Mutagenicity Assay SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Swartz, C. D.; Lentz, C. A.; Green, A. S.; Prajapati, M. H.; Recio, L.] Integrated Syst Lab, Res Triangle Pk, NC USA. [Witt, K. L.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 718 EP 718 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600137 ER PT J AU Bacolla, A Wang, G Jain, A Chuzhanova, NA Cooper, DN Bohr, VA Vasquez, KM AF Bacolla, A. Wang, G. Jain, A. Chuzhanova, N. A. Cooper, D. N. Bohr, V. A. Vasquez, K. M. TI Non-B DNA-Forming Sequences and WRN Deficiency Independently Increase the Frequency of Spontaneous Base Substitution in Human Cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Chuzhanova, N. A.; Vasquez, K. M.] Nottingham Trent Univ, Sch Sci & Technol, Nottingham, England. [Cooper, D. N.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff, S Glam, Wales. [Bohr, V. A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Bacolla, A.; Wang, G.; Jain, A.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Smithville, TX USA. RI Bacolla, Albino/N-3877-2013; Cooper, David/H-4384-2011 OI Bacolla, Albino/0000-0003-0206-8423; Cooper, David/0000-0002-8943-8484 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 720 EP 720 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600146 ER PT J AU John, K Churchwell, MI Beland, FA Pratt, MM McMullen, G Poiner, MC AF John, K. Churchwell, M., I Beland, F. A. Pratt, M. M. McMullen, G. Poiner, M. C. TI Chlorophyllin (CHL) Differentially Modulates Benzo(a)pyrene-DNA (BP-DNA) Adduct Formation in C57BL16 Mice Chronically Fed BP and CHL in the Diet SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [John, K.; Pratt, M. M.; McMullen, G.; Poiner, M. C.] NCI, NIH, Bethesda, MD 20892 USA. [Churchwell, M., I; Beland, F. A.] NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 720 EP 720 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600143 ER PT J AU Kasiviswanathan, R Minko, IG Lloyd, RS Copeland, WC AF Kasiviswanathan, R. Minko, I. G. Lloyd, R. S. Copeland, W. C. TI Translesion Synthesis Past an Acrolein-Derived DNA Adduct, Gamma-Hydroxypropano-Deoxyguanosine, by Human Mitochondrial DNA Polymerase Gamma SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Kasiviswanathan, R.; Copeland, W. C.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Minko, I. G.; Lloyd, R. S.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 721 EP 721 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600148 ER PT J AU Dutra, A Pak, E Wincovitch, S John, K Poiner, MC Olivero, OA AF Dutra, A. Pak, E. Wincovitch, S. John, K. Poiner, M. C. Olivero, O. A. TI Nuclear Bud Formation: A Novel Manifestation of Zidovudine Genotoxicity SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [John, K.; Poiner, M. C.; Olivero, O. A.] NCI, Bethesda, MD 20892 USA. [Dutra, A.; Pak, E.; Wincovitch, S.] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 727 EP 727 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600171 ER PT J AU Hobbs, CA Recio, L Shepard, K Green, A Winters, J Baldetti, C Streicker, M Witt, KL AF Hobbs, C. A. Recio, L. Shepard, K. Green, A. Winters, J. Baldetti, C. Streicker, M. Witt, K. L. TI Genotoxicity of Hydroxyurea in Mice Measured at Doses Relevant to Pediatric Sickle Cell Anemia Patients SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Hobbs, C. A.; Recio, L.; Shepard, K.; Green, A.; Winters, J.; Baldetti, C.] Integrated Lab Syst Inc, Genet & Mol Toxicol Div, Res Triangle Pk, NC USA. [Streicker, M.] Integrated Lab Syst Inc, Investigat Toxicol Div, Res Triangle Pk, NC USA. [Witt, K. L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 727 EP 727 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600173 ER PT J AU Levy, DD McDaniel, LP Witt, KL AF Levy, D. D. McDaniel, L. P. Witt, K. L. TI Sensitivity and Specificity of the In Vivo Rodent Micronucleus Assay towards the Detection of Rodent Carcinogens. An Updated Analysis of National Toxicology Program Data. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Levy, D. D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [McDaniel, L. P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Witt, K. L.] US NIH Natl Toxicol Program, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 731 EP 731 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600188 ER PT J AU Vandenberg, LN Chahoud, I Heindel, JJ Padmanabhan, V Paumgartten, FJR Schoenfelder, G AF Vandenberg, Laura N. Chahoud, Ibrahim Heindel, Jerrold J. Padmanabhan, Vasantha Paumgartten, Francisco J. R. Schoenfelder, Gilbert TI Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE endocrine disruptor; human exposure; PBPK/PBTK model; pregnancy; risk assessment; toxicokinetics ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; TANDEM MASS-SPECTROMETRY; HPLC-MS/MS METHOD; ENVIRONMENTAL PHENOLS; ESTROGEN-RECEPTOR; ADIPOSE-TISSUE; HUMAN SERUM; FLUORESCENCE DETECTION; DISRUPTING CHEMICALS AB BACKGROUND: Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. Importantly, results from a large number of biomonitoring studies are at odds with the results from two toxicokinetic studies. OBJECTIVE: We examined several possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. DATA SOURCES: We examined > 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism. DATA EXTRACTION AND SYNTHESIS: The > 80 biomonitoring studies examined included measurements in thousands of individuals from several different countries, and these studies overwhelmingly detected BPA in individual adults, adolescents, and children. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Some regulatory agencies have relied solely on these toxicokinetic models in their risk assessments. CONCLUSIONS: Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes. C1 [Vandenberg, Laura N.] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Vandenberg, Laura N.] Tufts Univ, Tufts Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Chahoud, Ibrahim] Charite, Inst Klin Pharmakol & Toxikol, D-13353 Berlin, Germany. [Heindel, Jerrold J.] NIEHS, Div Extramural Res & Training, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Padmanabhan, Vasantha] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Padmanabhan, Vasantha] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Padmanabhan, Vasantha] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Paumgartten, Francisco J. R.] Fundacao Oswaldo Cruz, Natl Sch Publ Hlth, Lab Environm Toxicol, Rio De Janeiro, Brazil. [Schoenfelder, Gilbert] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany. RP Vandenberg, LN (reprint author), Tufts Univ, Dept Biol, 200 Boston Ave,Suite 4600, Medford, MA 02155 USA. EM laura.vandenberg@tufts.edu RI Padmanabhan, Vasantha/C-8558-2017; OI Padmanabhan, Vasantha/0000-0002-8443-7212; Schonfelder, Gilbert/0000-0001-6134-1990 FU National Institutes of Health (NIH) [1F32GM087107-01, R01 ES016541, R01 ES017005]; National Research Council-Brazil FX This work was supported by grants 1F32GM087107-01 (L.N.V.) and R01 ES016541 and R01 ES017005 (V. P.) from the National Institutes of Health (NIH) and by a research fellowship from the National Research Council-Brazil (F.J.R.P.). NR 129 TC 460 Z9 477 U1 15 U2 171 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 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2010 VL 118 IS 8 BP 1055 EP 1070 DI 10.1289/ehp.0901716 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 634LR UT WOS:000280583500019 PM 20338858 ER PT J AU Dietert, RR DeWitt, JC Germolec, DR Zelikoff, JT AF Dietert, Rodney R. DeWitt, Jamie C. Germolec, Dori R. Zelikoff, Judith T. TI Breaking Patterns of Environmentally Influenced Disease for Health Risk Reduction: Immune Perspectives SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE asthma; developmental immunotoxicity; health risks; immune dysfunction; inflammation; intervention; metabolic syndrome; patterns of disease; prevention; safety testing ID INFANT-DEATH-SYNDROME; NECROSIS-FACTOR-ALPHA; REGULATORY T-CELLS; METABOLIC SYNDROME; ADIPOSE-TISSUE; DEVELOPMENTAL IMMUNOTOXICITY; CRITICAL WINDOWS; INSULIN-RESISTANCE; PRENATAL EXPOSURE; CIGARETTE-SMOKE AB BACKGROUND: Diseases rarely, if ever, occur in isolation. Instead, most represent part of a more complex web or "pattern" of conditions that are connected via underlying biological mechanisms and processes, emerge across a lifetime, and have been identified with the aid of large medical databases. OBJECTIVE: We have described how an understanding of patterns of disease may be used to develop new strategies for reducing the prevalence and risk of major immune-based illnesses and diseases influenced by environmental stimuli. FINDINGS: Examples of recently defined patterns of diseases that begin in childhood include not only metabolic syndrome, with its characteristics of inflammatory dysregulation, but also allergic, autoimmune, recurrent infection, and other inflammatory patterns of disease. The recent identification of major immune-based disease patterns beginning in childhood suggests that the immune system may play an even more important role in determining health status and health care needs across a lifetime than was previously understood. CONCLUSIONS: Focusing on patterns of disease, as opposed to individual conditions, offers two important venues for environmental health risk reduction. First, prevention of developmental immunotoxicity and pediatric immune dysfunction can be used to act against multiple diseases. Second, pattern-based treatment of entryway diseases can be tailored with the aim of disrupting the entire disease pattern and reducing the risk of later-life illnesses connected to underlying immune dysfunction. Disease-pattern-based evaluation, prevention, and treatment will require a change from the current approach for both immune safety testing and pediatric disease management. C1 [Dietert, Rodney R.] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. [DeWitt, Jamie C.] E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA. [Germolec, Dori R.] NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Zelikoff, Judith T.] NYU, Langone Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY USA. RP Dietert, RR (reprint author), Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, C5 135 VMC,N Tower Rd, Ithaca, NY 14853 USA. EM rrd1@cornell.edu OI DeWitt, Jamie/0000-0002-0440-4059 FU Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health; Institute for Science and Health; National Institute of Environmental Health Sciences, National Institutes of Health [ES00260]; Department of Pharmacology and Toxicology; East Carolina University Division of Research and Graduate Studies FX This work was supported in part by funding to D. R. G. from the Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health; by a grant to J. T. Z. from the Institute for Science and Health and the National Institute of Environmental Health Sciences, National Institutes of Health (ES00260); and by a faculty startup award to J. C. D. from the Department of Pharmacology and Toxicology and the East Carolina University Division of Research and Graduate Studies. NR 76 TC 36 Z9 38 U1 1 U2 10 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 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2010 VL 118 IS 8 BP 1091 EP 1099 DI 10.1289/ehp.1001971 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 634LR UT WOS:000280583500022 PM 20483701 ER PT J AU Birnbaum, LS Jung, P AF Birnbaum, Linda S. Jung, Paul TI Evolution in Environmental Health: Incorporating the Infectious Disease Paradigm SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Birnbaum, Linda S.; Jung, Paul] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Birnbaum, LS (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov NR 8 TC 3 Z9 3 U1 0 U2 0 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 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2010 VL 118 IS 8 BP A327 EP A328 DI 10.1289/ehp.1002661 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 634LR UT WOS:000280583500002 PM 20675264 ER PT J AU Cupul-Uicab, LA Hernandez-Avila, M Terrazas-Medina, EA Pennell, ML Longnecker, MP AF Cupul-Uicab, Lea A. Hernandez-Avila, Mauricio Terrazas-Medina, Efrain A. Pennell, Michael L. Longnecker, Matthew P. TI Prenatal exposure to the major DDT metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and growth in boys from Mexico SO ENVIRONMENTAL RESEARCH LA English DT Article DE Body height; Body mass index; Child; Preschool; Growth and development; Infant; Longitudinal study; pp '-DDE ID BODY-MASS INDEX; DICHLORODIPHENYL DICHLOROETHENE DDE; POLYCHLORINATED-BIPHENYLS PCBS; BRITISH BIRTH COHORT; ANOGENITAL DISTANCE; CHILDHOOD GROWTH; MALARIA CONTROL; MALE NEWBORNS; HUMAN-MILK; FOLLOW-UP AB Recent data suggest that prenatal exposure to p,p'-DDE may reduce height and increase body mass index (BMI) in childhood, thus potentially raising the risk of adult health problems. The association between prenatal DDE exposure and growth was evaluated in 788 boys from Chiapas, an area of Mexico where DDT was recently used. The median DDE levels in maternal serum at birth (2002-2003) were 2.7 mu g/g lipid. 2633 measurements of height (cm) and weight (kg) were obtained in 2004-2005. The median age of the children during follow-up was 18 months (quartiles 14 and 22 months). Height and body mass index (kg/m(2)) were age-standardized and expressed as standard deviation scores (SDS). Multivariate random-effect models for longitudinal data were fitted and predicted height and BMI SDS were estimated from the adjusted models. Overall, associations between prenatal DDE level and height or BMI SOS at any given age were not observed. For example, the predicted values showed that children with the highest exposure (DDE: > 9.00 mu g/g) compared to those least exposed (DDE: < 3.01 mu g/g) grew similarly and they had a BMI SDS similar to the referent group. The results do not support the prior findings of an association of DDE exposure with childhood height or BMI. Published by Elsevier Inc. C1 [Cupul-Uicab, Lea A.; Longnecker, Matthew P.] Natl Inst Environm Hlth Sci Natl, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Hernandez-Avila, Mauricio] Minist Hlth, Subsecretaria Promoc & Prevenc Salud, Mexico City 06696, DF, Mexico. [Terrazas-Medina, Efrain A.] Natl Inst Publ Hlth, Ctr Invest Salud Poblac, Cuernavaca 62508, Morelos, Mexico. [Pennell, Michael L.] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA. RP Cupul-Uicab, LA (reprint author), Natl Inst Environm Hlth Sci Natl, Epidemiol Branch, NIH, Dept Hlth & Human Serv, MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cupuluicabl@niehs.nih.gov RI CUPUL UICAB, LEA/C-8699-2014; OI CUPUL UICAB, LEA/0000-0001-6190-4474; Longnecker, Matthew/0000-0001-6073-5322 FU National Institute of Environmental Health Sciences, National Institutes of Health [N01-ES-15467]; National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; Instituto Nacional de Salud Cuernavaca, Morelos, Mexico FX This work was supported in part by a contract from the National Institute of Environmental Health Sciences, National Institutes of Health [N01-ES-15467], in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, and in part by the Instituto Nacional de Salud Cuernavaca, Morelos, Mexico. NR 59 TC 23 Z9 23 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD AUG PY 2010 VL 110 IS 6 SI SI BP 595 EP 603 DI 10.1016/j.envres.2010.06.001 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 634HN UT WOS:000280571600009 PM 20566194 ER PT J AU Judson, RS Martin, MT Reif, DM Houck, KA Knudsen, TB Rotroff, DM Xia, MH Sakamuru, S Huang, RL Shinn, P Austin, CP Kavlock, RJ Dix, DJ AF Judson, Richard S. Martin, Matthew T. Reif, David M. Houck, Keith A. Knudsen, Thomas B. Rotroff, Daniel M. Xia, Menghang Sakamuru, Srilatha Huang, Ruili Shinn, Paul Austin, Christopher P. Kavlock, Robert J. Dix, David J. TI Analysis of Eight Oil Spill Dispersants Using Rapid, In Vitro Tests for Endocrine and Other Biological Activity SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID CHEMICAL LIBRARIES; HUMAN RELEVANCE; PPAR; ALPHA; HEPATOCARCINOGENESIS; CARCINOGENICITY; NONYLPHENOL; PROGRAM; ASSAYS; VIVO AB The Deepwater Horizon oil spill has led to the use of >1 M gallons of oil spill dispersants, which are mixtures of surfactants and solvents. Because of this large scale use there is a critical need to understand the potential for toxicity of the currently used dispersant and potential alternatives, especially given the limited toxicity testing information that is available. In particular, some dispersants contain nonylphenol ethoxylates (NPEs), which can degrade to nonylphenol (NP), a known endocrine disruptor. Given the urgent need to generate toxicity data, we carried out a series of in vitro high-throughput assays on eight commercial dispersants. These assays focused on the estrogen and androgen receptors (ER and AR), but also included a larger battery of assays probing other biological pathways. Cytotoxicity in mammalian cells was also quantified. No activity was seen in any AR assay. Two dispersants showed a weak ER signal in one assay (EC50 of 16 ppm for Nokomis 3-F4 and 25 ppm for ZI-400). NPs and NPEs also had a weak signal in this same ER assay. Note that Corexit 9500, the currently used product, does not contain NPEs and did not show any ER activity. Cytotoxicity values for six of the dispersants were statistically indistinguishable, with median LC50 values similar to 100 ppm. Two dispersants, JD 2000 and SAF-RON GOLD, were significantly less cytotoxic than the others with LC50 values approaching or exceeding 1000 ppm. C1 [Judson, Richard S.; Martin, Matthew T.; Reif, David M.; Houck, Keith A.; Knudsen, Thomas B.; Rotroff, Daniel M.; Kavlock, Robert J.; Dix, David J.] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Xia, Menghang; Sakamuru, Srilatha; Huang, Ruili; Shinn, Paul; Austin, Christopher P.] NIH, Chem Genom Ctr, US Dept HHS, Bethesda, MD 20892 USA. RP Judson, RS (reprint author), US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA. EM judson.richard@epa.gov RI Martin, Matthew/A-1982-2013; OI Martin, Matthew/0000-0002-8096-9908; Judson, Richard/0000-0002-2348-9633; Reif, David/0000-0001-7815-6767 FU Intramural NIH HHS [ZIA HG200319-06] NR 29 TC 71 Z9 76 U1 4 U2 67 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD AUG 1 PY 2010 VL 44 IS 15 BP 5979 EP 5985 DI 10.1021/es102150z PG 7 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 631SD UT WOS:000280367200051 PM 20602530 ER PT J AU Jeong, SH Yim, HW Yoon, SH Jee, YM Bae, SH Lee, WC AF Jeong, S. H. Yim, H. W. Yoon, S. H. Jee, Y. M. Bae, S. H. Lee, W. C. TI Changes in the intrafamilial transmission of hepatitis B virus after introduction of a hepatitis B vaccination programme in Korea SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Hepatitis B virus; intrafamilial transmission; vertical transmission ID HEPATOCELLULAR-CARCINOMA; INFECTION; TAIWAN; TURKEY; ADULTS; HEALTH AB Hepatitis B virus (HBV) infections are endemic in Korea. The aims of this study were to determine the prevalence of HBsAg positivity in Korea and to evaluate the changes in intrafamilial transmission after introduction of HBV vaccination in 1983. This study was based on the 2001 Korea National Health and Nutrition Examination Survey. A total of 2512 study subjects, aged 10-29 years, were selected from across Korea using a stratified multi-stage probability sampling design. To identify the changes in intrafamilial transmission after the introduction of the HBV vaccination programme, 1850 subjects with parental serological markers were selected. These subjects were then grouped into two birth cohorts (cohort I: born before 1983; cohort 2: born after 1983). Appropriate sampling weights were used for all analyses. The weighted age-specific prevalence of HBsAg was 4.9% in participants in their 20s and 1.9% in adolescents; the combined weighted prevalence was 3.2%. Of subjects with HBsAg positivity in either parent, 17.5% were HBsAg-seropositive. Of subjects with two HBsAg-negative parents, 1.5% were HBsAg-seropositive. The HBsAg positivity rate of offspring with HBsAg-positive mothers was higher than those with HBsAg-positive fathers (27.3% vs. 4.8%, P < 0.001). The weighted HBsAg positivity rate of offspring with HBsAg-negative mothers was 2.3% for cohort 1 and 0.4% for cohort 2 (P < 0.01), and for those offspring with HBsAg-positive mothers it was also significantly decreased compared to cohorts 1 and 2 (40.2% vs. 16.4%, P < 0.01). However, the weighted HBsAg positivity rate of offspring with HBsAg-positive mothers was still high. Our results showed that introduction of HBV vaccination has resulted in a decline in the overall HBsAg positivity rate and a reduction in intrafamilial transmission in Korea, but further preventive measures for maternal intrafamilial transmission are needed. C1 [Jeong, S. H.; Yim, H. W.; Yoon, S. H.; Lee, W. C.] Catholic Univ, Dept Prevent Med, Coll Med, Seoul 137701, South Korea. [Bae, S. H.] Catholic Univ, Dept Internal Med, Coll Med, Seoul 137701, South Korea. [Jee, Y. M.] Ctr Dis Control & Prevent, Div Enter & Hepatitis Viruses, Natl Inst Hlth, Atlanta, GA 30333 USA. RP Yim, HW (reprint author), Catholic Univ, Dept Prevent Med, Coll Med, 505 Banpo Dong, Seoul 137701, South Korea. EM y1693@catholic.ac.kr RI Jeong, Sook-Hyang/D-5726-2012 FU Ministry of Health & Welfare, Republic of Korea [A060093] FX This study was supported by a grant from the Korea Health 21 R&D Project (A060093), Ministry of Health & Welfare, Republic of Korea. NR 26 TC 5 Z9 5 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD AUG PY 2010 VL 138 IS 8 BP 1090 EP 1095 DI 10.1017/S0950268809991324 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 628QW UT WOS:000280136700002 PM 19951454 ER PT J AU Gasior, M Yankura, J Hartman, AL French, A Rogawski, MA AF Gasior, Maciej Yankura, Jessica Hartman, Adam L. French, Amy Rogawski, Michael A. TI Anticonvulsant and proconvulsant actions of 2-deoxy-d-glucose SO EPILEPSIA LA English DT Article DE 2-Deoxy-d-glucose; 3-Methyl-glucose; Glucose metabolism; Glycolysis; Pentose phosphate pathway; Ketogenic diet; Kindling ID KETOGENIC DIET; IN-VIVO; GLUCOSE-TRANSPORT; ADULT RATS; SEIZURES; EPILEPSY; HYPOGLYCEMIA; THRESHOLDS; METABOLISM; MECHANISMS AB P>Purpose: 2-Deoxy-d-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2-DG was also tested in fully amygdala-kindled rats. Results: 2-DG (125-500 mg/kg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6-Hz seizure test. 2-DG (250-500 mg/kg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3-MG had no effect on seizure threshold in the 6-Hz test but, like 2-DG, decreased seizure threshold in the i.v. PTZ test. 2-DG (250 and 500 mg/kg, i.p., 30 min before testing) had no effect on amygdala-kindled seizures. Conclusions: Although 2-DG protects against seizures in the 6-Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway. C1 [Rogawski, Michael A.] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [Rogawski, Michael A.] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. [Gasior, Maciej; Yankura, Jessica; Hartman, Adam L.; French, Amy; Rogawski, Michael A.] NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. [Hartman, Adam L.] Johns Hopkins Univ Hosp, John M Freeman Pediat Epilepsy Ctr, Baltimore, MD 21287 USA. RP Rogawski, MA (reprint author), Univ Calif Davis, Dept Neurol, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA. EM rogawski@ucdavis.edu RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NINDS; UC Davis Clinical and Translational Science Center (NCRR) [UL1 RR024146]; Epilepsy Research Foundation; Epilepsy Foundation FX This work was supported by NINDS (MAR); the UC Davis Clinical and Translational Science Center (NCRR Grant UL1 RR024146); the Epilepsy Research Foundation (MAR); and the Epilepsy Foundation through the generous support of Pfizer, Inc. (ALH). NR 53 TC 20 Z9 21 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2010 VL 51 IS 8 BP 1385 EP 1394 DI 10.1111/j.1528-1167.2010.02593.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 635PW UT WOS:000280669600006 PM 20491877 ER PT J AU Roberts, JD Davies, RW Lubitz, SA Thibodeau, IL Nery, PB Birnie, DH Benjamin, EJ Lemery, R Ellinor, PT Gollob, MH AF Roberts, Jason D. Davies, Robert W. Lubitz, Steven A. Thibodeau, Isabelle L. Nery, Pablo B. Birnie, David H. Benjamin, Emelia J. Lemery, Robert Ellinor, Patrick T. Gollob, Michael H. TI Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation SO EUROPACE LA English DT Article DE Atrial fibrillation; Atrial natriuretic peptide; Single nucleotide polymorphism; Genetics ID OF-FUNCTION MUTATION; BLOOD-PRESSURE PROGRESSION; NATRIURETIC-PEPTIDE; FAMILIAL AGGREGATION; INCIDENT HYPERTENSION; GENE POLYMORPHISMS; ISCHEMIC-STROKE; HEART-DISEASE; RISK-FACTOR; VARIANTS AB Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important cause of morbidity and mortality. A genetic mutation in the NPPA gene, which encodes the atrial natriuretic peptide, has been identified as the putative causative factor in a family with an autosomal dominant pattern of inheritance for AF. Two common single nucleotide polymorphisms (SNPs) in NPPA, rs5063 and rs5065, result in amino acid changes of the primary peptide and have been previously implicated in conditions associated with AF, including stroke and hypertension. Recently, the rs5063 SNP has been reported to confer an increased risk of AF development in a Chinese population. We sought to examine the associations of both rs5063 and rs5065 with AF in two separate North American cohorts of European ancestry. Patients with early-onset AF, along with healthy controls, were recruited at the University of Ottawa Heart Institute (UOHI) and the Massachusetts General Hospital (MGH). Study participants were genotyped for rs5063 and rs5065 using a combination of restriction fragment length polymorphism analysis and DNA microarrays. The study genotyped a total of 620 AF cases and 2446 healthy controls. The UOHI arm of the study identified an odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.42-1.24] for rs5063, whereas an OR of 1.33 (95% CI: 0.80-2.21) was observed in the MGH arm. The combined OR approximated unity (OR 0.99; 95% CI: 0.54-1.80). Analysis of rs5065 revealed an OR of 1.12 (95% CI: 0.84-1.48) in UOHI, 1.08 (95% CI 0.80-1.45) in MGH, and 1.10 (95% CI 0.90-1.35) when combined. Common non-synonymous genetic variants within NPPA in these two large North American cohorts of European ancestry are not associated with the development of AF. C1 [Roberts, Jason D.; Thibodeau, Isabelle L.; Gollob, Michael H.] Univ Ottawa, Inst Heart, Arrhythmia Res Lab, Ottawa, ON K1Y 4W7, Canada. [Davies, Robert W.] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON K1Y 4W7, Canada. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Nery, Pablo B.; Birnie, David H.; Lemery, Robert; Gollob, Michael H.] Univ Ottawa, Inst Heart, Arrhythmia Serv, Ottawa, ON K1Y 4W7, Canada. [Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol & Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Gollob, MH (reprint author), Univ Ottawa, Inst Heart, Arrhythmia Res Lab, 40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM mgollob@ottawaheart.ca RI Nery, Pablo/D-1754-2011; OI Benjamin, Emelia/0000-0003-4076-2336 FU Heart and Stroke Foundation of Ontario; Canadian Institutes of Health Research; NIH [HL092577, RC1-HL01056, DA027021, T32HL00757] FX This work was supported by grants from the Heart and Stroke Foundation of Ontario and Canadian Institutes of Health Research to M.H.G. and grants from the NIH: HL092577 to P.T.E. and E.J.B.; RC1-HL01056 to E.J.B.; and DA027021 to P.T.E.; S.A.L. was supported by a training grant from the NIH (T32HL00757). NR 42 TC 13 Z9 13 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD AUG PY 2010 VL 12 IS 8 BP 1078 EP 1083 DI 10.1093/europace/euq161 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633VV UT WOS:000280535800009 PM 20543198 ER PT J AU Thayer, JF Verkuil, B Brosschot, JF Kampschroer, K West, A Sterling, C Christie, IC Abernethy, DR Sollers, JJ Cizza, G Marques, AH Sternberg, EM AF Thayer, Julian F. Verkuil, Bart Brosschot, Jos F. Kampschroer, Kevin West, Anthony Sterling, Carolyn Christie, Israel C. Abernethy, Darrell R. Sollers, John J. Cizza, Giovanni Marques, Andrea H. Sternberg, Esther M. TI Effects of the physical work environment on physiological measures of stress SO EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION LA English DT Article DE cortisol; heart rate variability; work stress ID HEART-RATE-VARIABILITY; JOB STRAIN; DISEASE; EVENTS; RISK; SLEEP; SATISFACTION; METAANALYSIS; ASSOCIATION; QUALITY AB Aims In this study we investigated the effects of the physical work environment on two physiological measures of the stress response. Methods and results Circadian variations in vagally mediated heart rate variability (HRV) and the morning rise in cortisol were evaluated in 60 participants working in a government building either in a traditional (individual offices and old cubicles; n = 40) or a modern workspace (individualized cubicles with improved views and lighting; n = 20). Results revealed significant linear (B = - 1.03; confidence interval: - 1.05 to - 1.01, P < 0.05) and quadratic (B = 1.001; confidence interval: 1.0004 - 1.002, P < 0.05) trends by office type interactions for indices of vagally mediated HRV. Individuals in the old office space had flatter slopes and thus less circadian variation including less HRV at night, and a larger rise in cortisol upon awakening compared with those in the new office space. Conclusion These results indicate that physical features of the work environment may affect two aspects of the physiological stress response: circadian variations in HRV and the morning rise in cortisol. These findings have important social, economic, and public health implications for work environment risk factors on health. Eur J Cardiovasc Prev Rehabil 17:431-439 (C) 2010 The European Society of Cardiology C1 [Sternberg, Esther M.] NIMH, Integrat Neural Immune Program, NIH, Rockville, MD 20892 USA. [Abernethy, Darrell R.] NIA, NIH, Baltimore, MD 21224 USA. [Cizza, Giovanni] NIDDKD, NIH, Bethesda, MD 20892 USA. [Thayer, Julian F.; Sollers, John J.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Kampschroer, Kevin] US Gen Serv Adm, Denver, CO USA. [West, Anthony] Radiant Res, Denver, CO USA. [Christie, Israel C.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. [Abernethy, Darrell R.] US Pharmacopeia, Rockville, MD USA. [Thayer, Julian F.] Univ Heidelberg, Mannheim Inst Publ Hlth, D-6800 Mannheim, Germany. [Verkuil, Bart; Brosschot, Jos F.] Leiden Univ, Inst Psychol, Leiden, Netherlands. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, NIH, 5625 Fishers Lane,MSC 9401,Rm 4N-13B, Rockville, MD 20892 USA. EM sternbee@mail.nih.gov OI Verkuil, Bart/0000-0002-9991-0690 FU United States General Services Administration; National Institute of Mental Health; National Institutes of Health FX This study was funded by the United States General Services Administration, the Intramural Research Program of the National Institute of Mental Health and National Institutes of Health. NR 24 TC 17 Z9 17 U1 4 U2 30 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1741-8267 J9 EUR J CARDIOV PREV R JI Eur. J. Cardiovasc. Prev. Rehabil. PD AUG PY 2010 VL 17 IS 4 BP 431 EP 439 DI 10.1097/HJR.0b013e328336923a PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 634AP UT WOS:000280550200009 PM 20404733 ER PT J AU Dhingra, R Gona, P Benjamin, EJ Wang, TJ Aragam, J D'Agostino, RB Kannel, WB Vasan, RS AF Dhingra, Ravi Gona, Philimon Benjamin, Emelia J. Wang, Thomas J. Aragam, Jayashri D'Agostino, Ralph B., Sr. Kannel, William B. Vasan, Ramachandran S. TI Relations of serum phosphorus levels to echocardiographic left ventricular mass and incidence of heart failure in the community SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Phosphorus; Congestive heart failure; Ventricle; Epidemiology; Risk factors ID PARATHYROID-HORMONE SECRETION; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; PHOSPHATE LEVEL; RISK; ASSOCIATION; FRAMINGHAM; 1,25-DIHYDROXYVITAMIN-D; HYPERPHOSPHATEMIA; SUPPLEMENTATION AB Aims To evaluate the association of serum phosphorus with cardiac structure/function and incident heart failure. Methods and results We related serum phosphorus to echocardiographic left ventricular (LV) measurements cross-sectionally, and to incident heart failure prospectively in 3300 participants (mean age 44 years, 51% women) free of heart failure, myocardial infarction, and chronic kidney disease (estimated glomerular filtration rate [eGFR]<60 mL/min/1.73 m(2)). Cross-sectionally, serum phosphorus was related positively to LV mass, internal dimensions, and systolic dysfunction. On follow-up (mean 17.4 years), 157 individuals developed heart failure. In models adjusting for established risk factors as time-varying covariates, each mg/dL increment in serum phosphorus was associated with a 1.74-fold risk of heart failure [95% confidence intervals (CI) 1.17-2.59]. Individuals in the highest serum phosphorus quartile experienced a two-fold (95% CI 1.28-3.40) risk of heart failure compared with participants in the lowest quartile. These relations were maintained upon additional adjustment for LV mass/dimensions and systolic dysfunction. In analyses restricted to individuals with eGFR >90 mUmin/1.73 m(2), no proteinuria and serum phosphorus <4.5 mg/dL, the association of serum phosphorus with heart failure remained robust. Conclusion In our community-based sample, higher serum phosphorus was associated with greater LV mass cross-sectionally, and with an increased risk of heart failure prospectively. C1 [Dhingra, Ravi; Gona, Philimon; Benjamin, Emelia J.; Wang, Thomas J.; D'Agostino, Ralph B., Sr.; Kannel, William B.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Dhingra, Ravi] Dartmouth Hitchcock Med Ctr, Div Cardiol, Lebanon, NH 03766 USA. [Dhingra, Ravi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gona, Philimon; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Aragam, Jayashri] Vet Affairs Hosp, W Roxbury, MA USA. [Benjamin, Emelia J.; Kannel, William B.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect EJB RSV, Boston, MA 02118 USA. [Benjamin, Emelia J.; Kannel, William B.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NIH/NHLBI [N01-HC-25195, HL080124, 2K24HL4334] FX This work was supported by the NIH/NHLBI Contract No. N01-HC-25195; HL080124, and 2K24HL4334 (Dr R.S.V.). NR 34 TC 44 Z9 46 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD AUG PY 2010 VL 12 IS 8 BP 812 EP 818 DI 10.1093/eurjhf/hfq106 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 642HR UT WOS:000281200100008 PM 20675668 ER PT J AU Kastenmuller, W Gerner, MY Germain, RN AF Kastenmueller, Wolfgang Gerner, Michael Y. Germain, Ronald N. TI The in situ dynamics of dendritic cell interactions SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; LYMPH-NODES; CD8-T-CELL MEMORY; CD4-T-CELL HELP; VIVO; IMMUNITY; ACTIVATION; RESPONSES; DISTINCT; TRAFFICKING AB DC regulate T-cell function by promoting either tolerance or activation, and in the latter case, by directing the quality of the ensuing response. New imaging tools now permit direct visualization of the relevant DC-T-cell interactions in vivo and have provided a new perspective on the dynamics of these crucial cellular contacts. In this Viewpoint, we discuss the insights generated by direct visualization of DC-T-cell interactions and the controversies/unanswered questions that need to be addressed in future work. C1 [Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, Natl Inst Hlth,DHHS, Bethesda, MD 20892 USA. [Germain, Ronald N.] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, Natl Inst Hlth,DHHS, Bldg 10,Rm 11N311,10 Ctr Dr,MSC-1892, Bethesda, MD 20892 USA. EM rgermain@nih.gov FU Intramural NIH HHS [ZIA AI000545-23, ZIA AI001034-04] NR 34 TC 15 Z9 15 U1 0 U2 0 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 AUG PY 2010 VL 40 IS 8 BP 2103 EP 2106 DI 10.1002/eji.201040482 PG 4 WC Immunology SC Immunology GA 643OH UT WOS:000281305900005 PM 20853494 ER PT J AU Che, KF Sabado, RL Shankar, EM Tjomsland, V Messmer, D Bhardwaj, N Lifson, JD Larsson, M AF Che, Karlhans F. Sabado, Rachel L. Shankar, Esaki M. Tjomsland, Veronica Messmer, Davorka Bhardwaj, Nina Lifson, Jeffrey D. Larsson, Marie TI HIV-1 impairs in vitro priming of naive T cells and gives rise to contact-dependent suppressor T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE DC; HIV-1; Immune responses; Suppressor T-cells ID REVERSIBLE IMMUNE DYSFUNCTION; DENDRITIC CELLS; UP-REGULATION; LIGAND TRAIL; DISEASE PROGRESSION; PD-1 EXPRESSION; DC-SIGN; VIRUS; ACTIVATION; RESPONSES AB Priming of T cells in lymphoid tissues of HIV-infected individuals occurs in the presence of HIV-1. DC in this milieu activate T cells and disseminate HIV-1 to newly activated T cells, the outcome of which may have serious implications in the development of optimal antiviral responses. We investigated the effects of HIV-1 on DC-naive T-cell interactions using an allogeneic in vitro system. Our data demonstrate a dramatic decrease in the primary expansion of naive T cells when cultured with HIV-1-exposed DC. CD4(+) and CD8(+) T cells showed enhanced expression of PD-1 and TRAIL, whereas CTLA-4 expression was observed on CD4(+) T cells. It is worth noting that T cells primed in the presence of HIV-1 suppressed priming of other naive T cells in a contact-dependent manner. We identified PD-1, CTLA-4, and TRAIL pathways as responsible for this suppresion, as blocking these negative molecules restored T-cell proliferation to a higher degree. In conclusion, the presence of HIV-1 during DC priming produced cells with inhibitory effects on T-cell activation and proliferation, i.e. suppressor T cells, a mechanism that could contribute to the enhancement of HIV-1 pathogenesis. C1 [Che, Karlhans F.; Shankar, Esaki M.; Tjomsland, Veronica; Larsson, Marie] Linkoping Univ, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. [Sabado, Rachel L.; Bhardwaj, Nina] NYU, Sch Med, New York, NY USA. [Messmer, Davorka] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Che, KF (reprint author), Linkoping Univ, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. EM karlhans.fru.che@liu.se RI Muthu , Shankar/G-6444-2011; OI Esaki Muthu, Shankar/0000-0002-7866-9818 FU Swedish Research Council; Swedish, Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University; CALF; Swedish Society of Medicine; National Cancer Institute, National Institutes of Health [NO1-CO-124000, HHSN266200400088C]; [ML: AI52731] FX The authors thank the Biological Products Core of the AIDS and Cancer Virus Program, SAIC Frederick, Inc., NCI, Frederick, MD, USA, for generously providing infectious and AT-2-inactivated HIV-1. This work has been supported by grants through: ML: AI52731, The Swedish Research Council, The Swedish, Physicians against AIDS Research Foundation, The Swedish International Development Cooperation Agency; SIDA SARC, VINNMER for Vinnova, Linkoping University Hospital Research Fund, CALF, and The Swedish Society of Medicine. J. D. L.: in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under contracts NO1-CO-124000 and HHSN266200400088C. NR 46 TC 26 Z9 26 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2010 VL 40 IS 8 BP 2248 EP 2258 DI 10.1002/eji.201040377 PG 11 WC Immunology SC Immunology GA 643OH UT WOS:000281305900024 PM 20455275 ER PT J AU Michaelides, M Pascau, J Gispert, JD Delis, F Grandy, DK Wang, GJ Desco, M Rubinstein, M Volkow, ND Thanos, PK AF Michaelides, Michael Pascau, Javier Gispert, Juan-Domingo Delis, Foteini Grandy, David K. Wang, Gene-Jack Desco, Manuel Rubinstein, Marcelo Volkow, Nora D. Thanos, Panayotis K. TI Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE 2-[18F]-fluoro-2-deoxy-d-glucose; attention deficit hyperactivity disorder; mice; micro-positron emission tomography; positron emission tomography ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; FUNCTIONAL MAGNETIC-RESONANCE; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; WORKING-MEMORY; D-4 RECEPTOR; ANTERIOR CINGULATE; FRONTAL-CORTEX; COGNITIVE TASK AB Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D(4)) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [18F]2-fluoro-2-deoxy-d-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D(4). Images were analyzed using a novel automated image registration procedure. Baseline D(4)-/- mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D(4)+/+ and D(4)+/- mice; when given MP, D(4)-/- mice increased metabolism in the PFC and decreased it in the CBV, whereas in D(4)+/+ and D(4)+/- mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D(4) polymorphisms. C1 [Michaelides, Michael; Thanos, Panayotis K.] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Michaelides, Michael] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Pascau, Javier; Desco, Manuel] Univ Gregorio Maranon, Gen Hosp, Madrid, Spain. [Gispert, Juan-Domingo; Thanos, Panayotis K.] Inst Alta Tecnol, Barcelona, Spain. [Delis, Foteini; Wang, Gene-Jack; Volkow, Nora D.; Thanos, Panayotis K.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD USA. [Grandy, David K.] Oregon Hlth & Sci Univ, Portland, OR USA. [Rubinstein, Marcelo] Univ Buenos Aires, Dept Biol, Buenos Aires, DF, Argentina. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, 30 Bell Ave, Upton, NY 11973 USA. EM thanos@bnl.gov RI Pascau, Javier/B-5734-2013; Michaelides, Michael/K-4736-2013; Desco, Manuel/D-2822-2009; OI Pascau, Javier/0000-0003-1484-731X; Michaelides, Michael/0000-0003-0398-4917; Desco, Manuel/0000-0003-0989-3231; Gispert, Juan Domingo/0000-0002-6155-0642 FU NIAAA [AA 11 034, AA07574, AA07611] FX This work was supported by the NIAAA (AA 11 034, AA07574 and AA07611). NR 95 TC 13 Z9 15 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD AUG PY 2010 VL 32 IS 4 BP 668 EP 676 DI 10.1111/j.1460-9568.2010.07319.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 639TD UT WOS:000280996500017 PM 20646063 ER PT J AU Terry, GE Hirvonen, J Liow, JS Seneca, N Tauscher, JT Schaus, JM Phebus, L Felder, CC Morse, CL Pike, VW Halldin, C Innis, RB AF Terry, Garth E. Hirvonen, Jussi Liow, Jeih-San Seneca, Nicholas Tauscher, Johannes T. Schaus, John M. Phebus, Lee Felder, Christian C. Morse, Cheryl L. Pike, Victor W. Halldin, Christer Innis, Robert B. TI Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE C-11-MePPEP; F-18-FMPEP-d(2); Dosimetry; PET ID RADIATION-DOSIMETRY; RADIOLIGAND; ENDOCANNABINOIDS; EXPRESSION; SYSTEM; TARGET AB Cannabinoid subtype 1 (CB1) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB1 receptors with two PET radioligands: C-11-MePPEP and F-18-FMPEP-d (2). Here we describe the biodistribution and dosimetry estimates for these two radioligands. Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with C-11-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with F-18-FMPEP-d (2). Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for F-18-FMPEP-d (2). The effective doses of C-11-MePPEP and F-18-FMPEP-d (2) are 4.6 and 19.7 mu Sv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of C-11-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from F-18-FMPEP-d (2) showed both hepatobiliary and urinary excretion. C-11-MePPEP and F-18-FMPEP-d (2) yield an effective dose similar to other PET radioligands labeled with either C-11 or F-18. The high uptake in brain confirms the utility of these two radioligands to image CB1 receptors in brain, and both may also be useful to image CB1 receptors in the periphery. C1 [Terry, Garth E.; Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Terry, Garth E.; Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. RP Terry, GE (reprint author), NIMH, Mol Imaging Branch, 31 Ctr Dr, Bethesda, MD 20892 USA. EM gartht@mail.nih.gov; robert.innis@nih.gov RI Tauscher, Johannes/M-5976-2016 FU Eli Lilly; NIMH [Z01-MH-002852-04, Z01-MH-002793-06]; Academy of Finland; Finnish Cultural Foundation; Finnish Foundation for Alcohol Studies; Finnish Medical Foundation; Instrumentarium Foundation; Jalmari and Rauha Ahokas Foundation; Paulo Foundation; Research Foundation of Orion Corporation; Yrjo Jahnsson Foundation FX We thank Maria D. Ferraris Araneta, William C. Kreisl, Barbara Scepura, Gerald Hodges, Amanda Farris, and Leah Dickstein for subject recruitment and care; Robert Gladding for his assistance in image processing; the NIH PET Department for imaging; and PMOD Technologies for providing its image analysis and modeling software. This research was supported by a Cooperative Research and Development Agreement with Eli Lilly and by the Intramural Program of NIMH (projects # Z01-MH-002852-04 and # Z01-MH-002793-06). Jussi Hirvonen was supported by personal grants from The Academy of Finland, The Finnish Cultural Foundation, The Finnish Foundation for Alcohol Studies, The Finnish Medical Foundation, The Instrumentarium Foundation, The Jalmari and Rauha Ahokas Foundation, The Paulo Foundation, The Research Foundation of Orion Corporation, and The Yrjo Jahnsson Foundation. NR 25 TC 10 Z9 10 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD AUG PY 2010 VL 37 IS 8 BP 1499 EP 1506 DI 10.1007/s00259-010-1411-7 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 635EW UT WOS:000280639400008 PM 20333514 ER PT J AU Beer, AJ Chen, XY AF Beer, Ambros J. Chen, Xiaoyuan TI Imaging of angiogenesis: from morphology to molecules and from bench to bedside SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material ID DRUG DEVELOPMENT; CANCER; THERAPY C1 [Beer, Ambros J.] Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-8000 Munich, Germany. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Beer, AJ (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-8000 Munich, Germany. EM ambros.beer@tum.de; Shawn.Chen@nih.gov FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-01] NR 22 TC 5 Z9 6 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD AUG PY 2010 VL 37 SU 1 BP S1 EP S3 DI 10.1007/s00259-010-1501-6 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 635EV UT WOS:000280639300001 PM 20640419 ER PT J AU Haubner, R Beer, AJ Wang, H Chen, XY AF Haubner, Roland Beer, Ambros J. Wang, Hui Chen, Xiaoyuan TI Positron emission tomography tracers for imaging angiogenesis SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Angiogenesis; Vascular endothelial growth factor; Fibronectin ED-B domain; Integrin alpha(v)beta(3); Matrix metalloproteinase; Imaging; Positron emission tomography ID ENDOTHELIAL GROWTH-FACTOR; MATRIX-METALLOPROTEINASE INHIBITORS; ALPHA(V)BETA(3) INTEGRIN EXPRESSION; CYCLIC RGD PEPTIDES; ED-B DOMAIN; CANCER ALPHA(V)-INTEGRIN EXPRESSION; SMALL-ANIMAL PET; GLY-ASP PEPTIDE; TUMOR ANGIOGENESIS; ALPHA-V-BETA-3 INTEGRIN AB Position emission tomography imaging of angiogenesis may provide non-invasive insights into the corresponding molecular processes and may be applied for individualized treatment planning of antiangiogenic therapies. At the moment, most strategies are focusing on the development of radiolabelled proteins and antibody formats targeting VEGF and its receptor or the ED-B domain of a fibronectin isoform as well as radiolabelled matrix metalloproteinase inhibitors or alpha(v)beta(3) integrin antagonists. Great efforts are being made to develop suitable tracers for different target structures. All of the major strategies focusing on the development of radiolabelled compounds for use with positron emission tomography are summarized in this review. However, because the most intensive work is concentrated on the development of radiolabelled RGD peptides for imaging alpha(v)beta(3) expression, which has successfully made its way from bench to bedside, these developments are especially emphasized. C1 [Haubner, Roland] Med Univ Innsbruck, Dept Nucl Med, Innsbruck, Austria. [Beer, Ambros J.] Tech Univ Munich, Dept Nucl Med, Munich, Germany. [Wang, Hui] Sichuan Univ, W China Hosp, Dept Radiol, Chengdu 610064, Peoples R China. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Haubner, R (reprint author), Med Univ Innsbruck, Dept Nucl Med, Innsbruck, Austria. EM Roland.Haubner@i-med.ac.at FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-01] NR 142 TC 61 Z9 67 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD AUG PY 2010 VL 37 SU 1 BP S86 EP S103 DI 10.1007/s00259-010-1503-4 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 635EV UT WOS:000280639300007 PM 20559632 ER PT J AU Peng, XH Li, H Seidman, M AF Peng, Xiaohua Li, Hong Seidman, Michael TI A Template-Mediated Click-Click Reaction: PNA-DNA, PNA-PNA (or Peptide) Ligation, and Single Nucleotide Discrimination SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article DE Peptide nucleic acids; Chemical Ligation; Click chemistry; Nucleotides; DNA ID AZIDE-ALKYNE CYCLOADDITION; TERMINAL ALKYNES; NUCLEIC-ACIDS; CHEMISTRY; OLIGONUCLEOTIDES; RECOGNITION; CHIMERAS; THYMINE AB A highly efficient chemical ligation was developed for quantitative conjugation of PNA with DNA (PNA or peptide) by using the copper-catalyzed azide-alkyne cycloaddition reaction Whereas PNAs with an alkyne at the C-terminus and an oxide at the N-terminus have been used, an efficient click-click reaction occurs. The PNA click ligation is sequence specific and capable of single nucleotide discrimination C1 [Peng, Xiaohua] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53211 USA. [Li, Hong; Seidman, Michael] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Peng, XH (reprint author), Univ Wisconsin, Dept Chem & Biochem, 3210 N Cramer St, Milwaukee, WI 53211 USA. FU University of Wisconsin-Milwaukee (UWM); National Institutes of Health; National Institute on Aging FX We are grateful for the financial support of this research by the University of Wisconsin-Milwaukee (UWM start-up fund) This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. We thank Prof K K Surerus for generously shining hei lab space/equipment NR 28 TC 22 Z9 22 U1 2 U2 35 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1434-193X J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD AUG PY 2010 IS 22 BP 4194 EP 4197 DI 10.1002/ejoc.201000615 PG 4 WC Chemistry, Organic SC Chemistry GA 640MB UT WOS:000281054600005 PM 23504541 ER PT J AU Cirulli, F Aloe, L Francia, N Berry, A Alleva, E Suomi, SJ AF Cirulli, F. Aloe, L. Francia, N. Berry, A. Alleva, E. Suomi, S. J. TI NGF and BDNF as neuroendocrine factors involved in the response to early life stress and susceptibility to psychopathology: evidence from animal models SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Cirulli, F.] Ist Super Sanita, Sect Behav Neurosci, Dept Cell Biol, I-00161 Rome, Italy. [Aloe, L.] Inst Neurobiol & Mol Med, CNR EBRI, Rome, Italy. [Francia, N.; Berry, A.; Alleva, E.] Ist Super Sanita, Sect Behav Neurosci, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Suomi, S. J.] NICHD, Comparat Ethol Lab, Poolesville, MD USA. RI Cirulli, Francesca/B-1581-2013; Alleva, Enrico/B-1630-2013 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S170 EP S171 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800030 ER PT J AU Huf, W Pail, G Hartinger, B Kasess, C Kasper, S Mattay, VS Meyer-Lindenberg, A Moser, E Weinberger, DR Pezawas, L AF Huf, W. Pail, G. Hartinger, B. Kasess, C. Kasper, S. Mattay, V. S. Meyer-Lindenberg, A. Moser, E. Weinberger, D. R. Pezawas, L. TI Emotion cognition interaction located using surface-based versus volume-based analysis SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Huf, W.; Pail, G.; Hartinger, B.; Kasper, S.; Pezawas, L.] Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria. [Kasess, C.; Moser, E.] Med Univ Vienna, MR Ctr Excellence, Vienna, Austria. [Mattay, V. S.; Weinberger, D. R.] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Meyer-Lindenberg, A.] Cent Inst Mental Hlth, Dept Psychiatty & Psychotherapy, D-6800 Mannheim, Germany. RI Moser, Ewald/B-3666-2013 OI Moser, Ewald/0000-0001-8278-9583 NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S296 EP S297 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800281 ER PT J AU Kashkin, VA Belozertseva, IV Shekunova, EV Zvartau, EE Bagrov, AY AF Kashkin, V. A. Belozertseva, I. V. Shekunova, E. V. Zvartau, E. E. Bagrov, A. Y. TI Marinobufagenin, an endogenous Na pump inhibitor, is implicated in social behavior of mice SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol ID WITHDRAWAL; RATS C1 [Kashkin, V. A.; Shekunova, E. V.; Zvartau, E. E.] Pavlov State Med Univ, St Petersburg, Russia. [Belozertseva, I. V.] Almazou Fed Heart Blood & Endocrinol Ctr, St Petersburg, Russia. [Bagrov, A. Y.] NIA, NIH, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RI Belozertseva, Irina/K-7259-2015 OI Belozertseva, Irina/0000-0001-8572-3600 NR 3 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S274 EP S274 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800242 ER PT J AU Pail, G Huf, W Kasess, C Kasper, S Moser, E Brocke, B Meyer-Lindenberg, A Mattay, V Weinberger, DR Pezawas, L AF Pail, G. Huf, W. Kasess, C. Kasper, S. Moser, E. Brocke, B. Meyer-Lindenberg, A. Mattay, Vs. Weinberger, D. R. Pezawas, L. TI Fronto-limbic interaction of working memory and emotion in the medial prefrontal cortex SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Pail, G.; Huf, W.; Kasess, C.; Kasper, S.; Moser, E.; Pezawas, L.] Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria. [Brocke, B.] Tech Univ Dresden, Neurobiol Personal & Neurogenet Lab, D-8027 Dresden, Germany. [Meyer-Lindenberg, A.] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. [Mattay, Vs.; Weinberger, D. R.] NIMH, NIH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RI Moser, Ewald/B-3666-2013 OI Moser, Ewald/0000-0001-8278-9583 NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S294 EP S294 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800277 ER PT J AU Bauer, AK Travis, EL Malhotra, SS Rondini, EA Walker, C Cho, HY Trivedi, S Gladwell, W Reddy, S Kleeberger, SR AF Bauer, A. K. Travis, E. L. Malhotra, S. S. Rondini, E. A. Walker, C. Cho, H-Y Trivedi, S. Gladwell, W. Reddy, S. Kleeberger, S. R. TI Identification of novel susceptibility genes in ozone-induced inflammation in mice SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Inflammation; lymphotoxin alpha; major histocompatibility complex; mouse; susceptibility; tumour necrosis factor ID NECROSIS-FACTOR-ALPHA; MAJOR HISTOCOMPATIBILITY COMPLEX; INDUCED LUNG INFLAMMATION; PULMONARY INFLAMMATION; MOUSE STRAINS; POLYMORPHISMS; CHILDREN; DISEASE; ASSOCIATION; ASTHMA AB Ozone (O(3)) remains a prevalent air pollutant and public health concern. Inf2 is a significant quantitative trait locus on murine chromosome 17 that contributes to susceptibility to O(3)-induced infiltration of polymorphonuclear leukocytes (PMNs) into the lung, but the mechanisms of susceptibility remain unclear. The study objectives were to confirm and restrict Inf2, and to identify and test novel candidate susceptibility gene(s). Congenic strains of mice that contained overlapping regions of Inf2 and their controls, and mice deficient in either major histocompatibility complex (MHC) class II genes or the Tnf cluster, were exposed to air or O(3). Lung inflammation and gene expression were assessed. Inf2 was restricted from 16.42 Mbp to 0.96 Mbp, and bioinformatic analysis identified MHC class II, the Tnf cluster and other genes in this region that contain potentially informative single nucleotide polymorphisms between the susceptible and resistant mice. Furthermore, O(3)-induced inflammation was significantly reduced in mice deficient in MHC class II genes or the Tnf cluster genes, compared with wild-type controls. Gene expression differences were also observed in MHC class II and Tnf cluster genes. This integrative genetic analysis of Inf2 led to identification of novel O(3) susceptibility genes that may provide important, new therapeutic targets in susceptible individuals. C1 [Bauer, A. K.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, Ctr Integrat Toxicol, E Lansing, MI 48824 USA. [Travis, E. L.; Malhotra, S. S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Walker, C.; Cho, H-Y; Trivedi, S.; Gladwell, W.; Kleeberger, S. R.] NIEHS, Biol Res Lab, Res Triangle Pk, NC 27709 USA. [Reddy, S.] Johns Hopkins Univ, Baltimore, MD USA. RP Bauer, AK (reprint author), Michigan State Univ, Dept Pathobiol & Diagnost Invest, Ctr Integrat Toxicol, B43 Food Safety & Toxicol Bldg, E Lansing, MI 48824 USA. EM akbauer@msu.edu FU National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services; Michigan State University FX This research was supported by the Intramural Research program of the National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services (S.R. Kleeberger, H-Y. Cho, C. Walker, S. Tivedi, W. Gladwell) and Michigan State University (A.K. Bauer and E.A. Rondini). NR 30 TC 10 Z9 10 U1 0 U2 7 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD AUG PY 2010 VL 36 IS 2 BP 428 EP 437 DI 10.1183/09031936.00145309 PG 10 WC Respiratory System SC Respiratory System GA 647EY UT WOS:000281601800029 PM 20032013 ER PT J AU Min-Oo, G Ayi, K Bongfen, SE Tam, M Radovanovic, I Gauthier, S Santiago, H Rothfuchs, AG Roffe, E Sher, A Mullick, A Fortin, A Stevenson, MM Kain, KC Gros, P AF Min-Oo, Gundula Ayi, Kodjo Bongfen, Silayuv E. Tam, Mifong Radovanovic, Irena Gauthier, Susan Santiago, Helton Rothfuchs, Antonio Gigliotti Roffe, Ester Sher, Alan Mullick, Alaka Fortin, Anny Stevenson, Mary M. Kain, Kevin C. Gros, Philippe TI Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Apicomplexa; Plasmodium; Cysteamine; Mouse model; Anti-parasitic ID PYRUVATE-KINASE DEFICIENCY; COMPLEX GENETIC-CONTROL; NEPHROPATHIC CYSTINOSIS; FALCIPARUM-MALARIA; TRYPANOSOMA-CRUZI; CANDIDA-ALBICANS; RESISTANCE; MICE; SUSCEPTIBILITY; GLUTATHIONE AB In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection. (C) 2010 Elsevier Inc. All rights reserved. C1 [Min-Oo, Gundula; Bongfen, Silayuv E.; Radovanovic, Irena; Gauthier, Susan; Fortin, Anny; Gros, Philippe] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. [Ayi, Kodjo; Kain, Kevin C.] Univ Toronto, Dept Med, UHN, McLaughlin Rotman Ctr Global Hlth, Toronto, ON, Canada. [Ayi, Kodjo; Kain, Kevin C.] Univ Toronto, McLaughlin Ctr Mol Med, Toronto, ON, Canada. [Tam, Mifong; Stevenson, Mary M.] Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. [Santiago, Helton] George Washington Univ, Ctr Hlth, Dept Microbiol Immunol & Trop Med, Washington, DC USA. [Santiago, Helton; Rothfuchs, Antonio Gigliotti] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Roffe, Ester; Sher, Alan] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Mullick, Alaka] Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada. RP Gros, P (reprint author), McGill Univ, Dept Biochem, 3655 Promenade Sir William Osler,Room 910, Montreal, PQ H3G 1Y6, Canada. EM philippe.gros@mcgill.ca RI Santiago, Helton/F-8704-2012; Roffe, Ester/H-4688-2012; Rothfuchs, Antonio/F-5981-2013; Vacinas, Inct/J-9431-2013 OI Santiago, Helton/0000-0002-5695-8256; Rothfuchs, Antonio/0000-0001-6001-7240; FU CIHR [MOP-79343, POP2, MT-13721]; Genome Canada through the Ontario Genomics Institute FX This work was supported by CIHR Team Grant in Malaria(K.C.K., PG., M.M.S.), operating grant MOP-79343 and POP2 (PG.), MT-13721 (K.C.K.), Genome Canada through the Ontario Genomics Institute (K.C.K.), CIHR Canada Research Chair (K.C.K.). NR 53 TC 11 Z9 11 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD AUG PY 2010 VL 125 IS 4 BP 315 EP 324 DI 10.1016/j.exppara.2010.02.009 PG 10 WC Parasitology SC Parasitology GA 606LE UT WOS:000278425700001 PM 20219464 ER PT J AU Himer, L Csoka, B Selmeczy, Z Koscso, B Pocza, T Pacher, P Nemeth, ZH Deitch, EA Vizi, ES Cronstein, BN Hasko, G AF Himer, Leonora Csoka, Balazs Selmeczy, Zsolt Koscso, Balazs Pocza, Timea Pacher, Pal Nemeth, Zoltan H. Deitch, Edwin A. Vizi, E. Sylvester Cronstein, Bruce N. Hasko, Gyoergy TI Adenosine A(2A) receptor activation protects CD4(+) T lymphocytes against activation-induced cell death SO FASEB JOURNAL LA English DT Article DE inflammation; apoptosis; anergy ID FAS-LIGAND EXPRESSION; VASOACTIVE-INTESTINAL-PEPTIDE; DEFICIENT MICE REVEALS; FACTOR-KAPPA-B; EXTRACELLULAR ADENOSINE; ADENYLATE-CYCLASE; DEAMINASE DEFICIENCY; MEDIATED ACTIVATION; DNA FRAGMENTATION; MOUSE THYMOCYTES AB Activation-induced cell death (AICD) is initiated by T-cell receptor (TCR) restimulation of already activated and expanded peripheral T cells and is mediated through Fas/Fas ligand (FasL) interactions. Adenosine is a purine nucleoside signaling molecule, and its immunomodulatory effects are mediated by 4 G-protein-coupled receptors: A(1), A(2A), A(2B), and A(3). In this study, we investigated the role of A(2A) receptors in regulating CD4(+) T lymphocyte AICD. Our results showed that the selective A(2A) receptor agonist CGS21680 (EC50 = 15.2-32.6 nM) rescued mouse CD4(+) hybridomas and human Jurkat cells from AICD and that this effect was reversed by the selective A(2A) receptor antagonist ZM241385 (EC50 = 2.3 nM). CGS21680 decreased phosphatidylserine exposure on the membrane, as well as the cleavage of caspase-3, caspase-8 and poly(ADP-ribose) polymerase indicating that A2A receptor stimulation blocks the extrinsic apoptotic pathway. In addition, CGS21680 attenuated both Fas and FasL mRNA expression. This decrease in FasL expression was associated with decreased activation of the transcription factor systems NF-kappa B, NF-ATp, early growth response (Egr)-1, and Egr-3. The antiapoptotic effect of A(2A) receptor stimulation was mediated by protein kinase A. Together, these results demonstrate that A(2A) receptor activation suppresses the AICD of peripheral T cells.-Himer, L., Csoka, B., Selmeczy, Z., Koscso, B., Pocza, T., Pacher, P., Nemeth, Z. H., Deitch, E. A., Vizi, E. S., Cronstein, B. N., Hasko, G. Adenosine A(2A) receptor activation protects CD4(+) T lymphocytes against activation-induced cell death. FASEB J. 24, 2631-2640 (2010). www.fasebj.org C1 [Csoka, Balazs; Nemeth, Zoltan H.; Deitch, Edwin A.; Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Himer, Leonora; Selmeczy, Zsolt; Koscso, Balazs; Pocza, Timea; Vizi, E. Sylvester] Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, Budapest, Hungary. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. [Nemeth, Zoltan H.] Morristown Mem Hosp, Dept Surg, Morristown, NJ USA. [Cronstein, Bruce N.] NYU, Sch Med, Dept Med, Div Clin Pharmacol, New York, NY USA. [Hasko, Gyoergy] Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, H-4012 Debrecen, Hungary. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130 FU U.S. National Institutes of Health (NIH) [R01 GM66189]; NIH, National Institute on Alcohol Abuse and Alcoholism; OTKA [73110, 78275] FX This work was supported by the U.S. National Institutes of Health (NIH; grant R01 GM66189), the Intramural Research Program of NIH, National Institute on Alcohol Abuse and Alcoholism, and the Hungarian Research Fund OTKA (73110 and 78275). NR 63 TC 34 Z9 35 U1 0 U2 5 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 AUG PY 2010 VL 24 IS 8 BP 2631 EP 2640 DI 10.1096/fj.10-155192 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LD UT WOS:000285005400005 PM 20371613 ER PT J AU Lui, JC Forcinito, P Chang, M Chen, WP Barnes, KM Baron, J AF Lui, Julian C. Forcinito, Patricia Chang, Maria Chen, Weiping Barnes, Kevin M. Baron, Jeffrey TI Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth SO FASEB JOURNAL LA English DT Article DE organ size; microarray; histone modification; proliferation ID HUMAN GENOME; CELLULAR MEMORY; SOMATIC GROWTH; GROUP PROTEINS; FETAL-RAT; LIVER; SIZE; POLYCOMB; DIFFERENTIATION; TRANSPLANTS AB Children grow, but adults do not. The cessation of growth in multiple organs is the end result of a progressive decline in cell proliferation beginning in early life. The mechanisms responsible for this growth deceleration are largely unknown. Using expression microarray and real-time PCR, we identified a common program of gene expression in lung, kidney, and liver during growth deceleration in juvenile rats. Gene ontology analyses and siRNA-mediated knockdown in vitro indicated that many of the down-regulated genes are growth promoting. Down-regulated genes in the program showed declining histone H3K4 trimethylation with age, implicating underlying epigenetic mechanisms. To investigate the physiological processes driving the genetic program, a tryptophan-deficient diet was used to temporarily inhibit juvenile growth in newborn rats for 4 wk. Afterward, microarray analysis showed that the genetic program had been delayed, implying that it is driven by body growth itself rather than age. Taken together, the findings suggest that growth in early life induces progressive down-regulation of a large set of proliferation-stimulating genes, causing organ growth to slow and eventually cease.-Lui, J. C., Forcinito, P., Chang, M., Chen, W., Barnes, K. M., Baron, J. Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth. FASEB J. 24, 3083-3092 (2010). www.fasebj.org C1 [Lui, Julian C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Bethesda, MD 20892 USA. [Chen, Weiping] NIDDKD, Microarray Core Facil, NIH, Bethesda, MD 20892 USA. RP Lui, JC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM luichunk@mail.nih.gov RI Lui, Chun Kin Julian/E-2253-2012 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 36 TC 25 Z9 26 U1 0 U2 4 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 AUG PY 2010 VL 24 IS 8 BP 3083 EP 3092 DI 10.1096/fj.09-152835 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LD UT WOS:000285005400044 PM 20371622 ER PT J AU M'ikanatha, NM Sandt, CH Localio, AR Tewari, D Rankin, SC Whichard, JM Altekruse, SF Lautenbach, E Folster, JP Russo, A Chiller, TM Reynolds, SM McDermott, PF AF M'ikanatha, Nkuchia M. Sandt, Carol H. Localio, A. Russell Tewari, Deepanker Rankin, Shelley C. Whichard, Jean M. Altekruse, Sean F. Lautenbach, Ebbing Folster, Jason P. Russo, Anthony Chiller, Tom M. Reynolds, Stanley M. McDermott, Patrick F. TI Multidrug-Resistant Salmonella Isolates from Retail Chicken Meat Compared with Human Clinical Isolates SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID UNITED-STATES; NONTYPHOIDAL SALMONELLA; ESCHERICHIA-COLI; FOOD ANIMALS; BETA-LACTAMASE; INFECTIONS; PLASMIDS; MEXICO; CMY-2 AB Aim: To examine the prevalence of antimicrobial-resistant Salmonella in chicken meat and correlate with isolates from ill humans. Methods: We isolated Salmonella from raw chicken purchased from a randomly selected sample of retail outlets in central Pennsylvania during 2006-2007. Salmonella isolates from meat were compared, using pulsed-field gel electrophoresis, to isolates in the PulseNet database of Salmonella recovered from humans. Results: Of 378 chicken meat samples, 84 (22%) contained Salmonella. Twenty-six (31%) of the Salmonella isolates were resistant to >= 3 antimicrobials and 18 (21%) were resistant to ceftiofur. All ceftiofur-resistant isolates exhibited reduced susceptibility (minimum inhibitory concentration >2 mg/mu L) to ceftriaxone and carried a blaCMY gene, as detected by polymerase chain reaction. Among the 28 Salmonella serovar Typhimurium isolates, 20 (71.4%) were resistant to >= 3 antimicrobials and 12 (42.9%) were resistant to ceftiofur. One ceftiofur-resistant Salmonella serovar Typhimurium poultry isolate exhibited a rare pulsed-field gel electrophoresis pattern indistinguishable from a human isolate in PulseNet; both isolates carried the bla(CMY-2) gene. Conclusions: These data demonstrate the presence of multidrug-resistant Salmonella in poultry meat, including blaCMY plasmid-mediated genes that confer resistance to both ceftiofur, used in poultry, and ceftriaxone, used for treating salmonellosis in humans. This study illustrates the potential for molecular subtyping databases to identify related Salmonella isolates from meat and ill humans, and suggests that chicken could be a source for multidrug-resistant salmonellosis in humans. C1 [M'ikanatha, Nkuchia M.] Penn Dept Hlth, Div Infect Dis Epidemiol, Harrisburg, PA 17120 USA. [M'ikanatha, Nkuchia M.; Localio, A. Russell; Rankin, Shelley C.; Lautenbach, Ebbing] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Sandt, Carol H.; Reynolds, Stanley M.] Penn Dept Hlth Bur Labs, Exton, PA USA. [Tewari, Deepanker; Russo, Anthony] Penn Dept Agr, Harrisburg, PA USA. [Whichard, Jean M.; Folster, Jason P.; Chiller, Tom M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Altekruse, Sean F.] NIH, Bethesda, MD 20892 USA. [Folster, Jason P.] Atlanta Res & Educ Fdn, Atlanta, GA USA. [McDermott, Patrick F.] US FDA, Ctr Vet Med, Laurel, MD USA. RP M'ikanatha, NM (reprint author), Penn Dept Hlth, Div Infect Dis Epidemiol, Harrisburg, PA 17120 USA. EM nmikanatha@state.pa.us FU Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics [U18-HS10399]; Pennsylvania Department of Health through Centers for Disease Control and Prevention [ELC-04040] FX This study was supported in part by the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics cooperative agreement (U18-HS10399) and by the Pennsylvania Department of Health through Centers for Disease Control and Prevention grant (ELC-04040) for National Antimicrobial Resistance Monitoring. NR 27 TC 23 Z9 24 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD AUG PY 2010 VL 7 IS 8 BP 929 EP 934 DI 10.1089/fpd.2009.0499 PG 6 WC Food Science & Technology SC Food Science & Technology GA 631UK UT WOS:000280374900009 PM 20443729 ER PT J AU Lee, JH Wada, T Febbraio, M He, JH Matsubara, T Lee, MJ Gonzalez, FJ Xie, W AF Lee, Jung Hoon Wada, Taira Febbraio, Maria He, Jinhan Matsubara, Tsutomu Lee, Min Jae Gonzalez, Frank J. Xie, Wen TI A Novel Role for the Dioxin Receptor in Fatty Acid Metabolism and Hepatic Steatosis SO GASTROENTEROLOGY LA English DT Article DE Aryl Hydrocarbon Receptor; Fatty Acid Metabolism; Steatosis; Gene Regulation ID ARYL-HYDROCARBON RECEPTOR; PEROXISOMAL BETA-OXIDATION; LIVER-X-RECEPTOR; AH RECEPTOR; GENE-EXPRESSION; DEFICIENT MICE; PPAR-GAMMA; SYSTEM; CD36; IDENTIFICATION AB BACKGROUND & AIMS: The aryl hydrocarbon receptor (AhR) also known as the dioxin receptor or xenobiotic receptor is a member of the basic helix-loop-helix/period AhR nuclear translocator single minded family. The goal of this study was to determine the endobiotic role of AhR in hepatic steatosis. METHODS: Wild-type, constitutively activated AhR transgenic, AhR null and CD36/fatty acid translocase null mice were used to investigate the role of AhR in steatosis and the involvement of CD36 in the steatotic effect of AhR. The promoters of the mouse and human CD36 genes were cloned and their regulation by AhR was analyzed. RESULTS: Activation of AhR induced spontaneous hepatic steatosis characterized by the accumulation of triglycerides. The steatotic effect of AhR likely is owing to the combined up-regulation of CD36 and fatty acid transport proteins, suppression of fatty acid oxidation, inhibition of hepatic export of triglycerides, increase in peripheral fat mobilization, and increased hepatic oxidative stress. Promoter analysis established CD36 as a novel transcriptional target of AhR. Activation of AhR in liver cells induced CD36 gene expression and enhanced fatty acid uptake. The steatotic effect of an AhR agonist was inhibited in CD36(-/-) mice. CONCLUSIONS: Our study reveals a novel link between AhR-induced steatosis and the expression of CD36. Industrial or military exposures to dioxin and related compounds have been linked to increased prevalence of fatty liver in human beings. Results from this study may help to establish AhR and its target CD36 as novel therapeutic and preventive targets for fatty liver disease. C1 [Lee, Jung Hoon; Wada, Taira; He, Jinhan; Lee, Min Jae; Xie, Wen] Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA. [Lee, Jung Hoon; Wada, Taira; He, Jinhan; Lee, Min Jae; Xie, Wen] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Xie, Wen] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Febbraio, Maria] Cleveland Clin, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44106 USA. [Matsubara, Tsutomu; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD USA. RP Xie, W (reprint author), Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA. EM wex6@pitt.edu RI Xie, Wen/M-1768-2016; Lee, Min Jae/C-9814-2015 OI Lee, Min Jae/0000-0002-3252-6467 FU National Institutes of Health [DK083952, DK076962, N01-DK-7-0004/HHSN267200700004C]; American Heart Association [09P0ST2280546] FX This work was supported in part by National Institutes of Health grants DK083952 and DK076962 (W.X.), and by an American Heart Association postdoctoral fellowship 09P0ST2280546 (J.H.). Normal human hepatocytes were obtained through the Liver Tissue Cell Distribution System, Pittsburgh, Pennsylvania, which was funded by National Institutes of Health contract #N01-DK-7-0004/HHSN267200700004C. NR 33 TC 72 Z9 73 U1 0 U2 9 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 AUG PY 2010 VL 139 IS 2 BP 653 EP 663 DI 10.1053/j.gastro.2010.03.033 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 633DG UT WOS:000280479100036 PM 20303349 ER PT J AU Dakshinamurthy, A Nyswaner, KM Farabaugh, PJ Garfinkel, DJ AF Dakshinamurthy, Arun Nyswaner, Katherine M. Farabaugh, Philip J. Garfinkel, David J. TI BUD22 Affects Ty1 Retrotransposition and Ribosome Biogenesis in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID VIRUS-LIKE PARTICLES; SMALL NUCLEAR-RNA; YEAST; PROTEIN; GENES; TRANSPOSITION; ELEMENT; CLEAVAGE; GENOME; SITE AB A variety of cellular factors affect the movement of the retrovirus-like transposon Ty1. To identify genes involved in Ty1 virus-like particle (VLP) function, the level of the major capsid protein (Gag-p45) and its proteolytic precursor (Gag-p49p) was monitored in a subset of Ty1 cofactor mutants. Twenty-nine of 87 mutants contained alterations in the level of Gag; however, only bud22 Delta showed a striking defect in Gag processing. BUD22 affected the +1 translational frameshifting event required to express the Pol proteins protease, integrase, and reverse transcriptase. Therefore, it is possible that the bud22 Delta mutant may not produce enough functional Ty1 protease to completely process Gag-p49 to p45. Furthermore, BUD22 is required for 18S rRNA processing and 40S subunit biogenesis and influences polysome density. Together our results suggest that BUD22 is involved in a step in ribosome biogenesis that not only affects general translation, but also may alter the frameshifting efficiency of ribosomes, an event central to Ty1 retrotransposition. C1 [Dakshinamurthy, Arun; Nyswaner, Katherine M.; Garfinkel, David J.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Dakshinamurthy, Arun; Farabaugh, Philip J.] Univ Maryland, Dept Biol Sci, Program Mol & Cell Biol, Baltimore, MD 21250 USA. RP Garfinkel, DJ (reprint author), Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. EM djgarf@bmb.uga.edu OI Farabaugh, Philip/0000-0002-5658-7141 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Mary-Ann Checkley, Amar Klar, Emiko Matsuda, Sharon Moore, Dwight Nissley, Gurjeet Singh, Karen Stafanisko, and Jeffrey Strathern for helpful discussions. This work is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. NR 64 TC 13 Z9 13 U1 0 U2 2 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 2010 VL 185 IS 4 BP 1193 EP U99 DI 10.1534/genetics.110.119115 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA 651EM UT WOS:000281907700006 PM 20498295 ER PT J AU White, DB Koehly, LM Omogbehin, A McBride, CM AF White, Della Brown Koehly, Laura M. Omogbehin, Adedamola McBride, Colleen M. TI African Americans' responses to genetic explanations of lung cancer disparities and their willingness to participate in clinical genetics research SO GENETICS IN MEDICINE LA English DT Article DE African Americans; lung cancer disparities; willingness to participate; clinical genetics research; psychosocial factors ID NONPOLYPOSIS COLORECTAL-CANCER; RACIAL-DIFFERENCES; UNITED-STATES; PUBLIC UNDERSTANDINGS; MINORITY RECRUITMENT; OVARIAN-CANCER; INCREASED RISK; HEALTH-CARE; RACE; SMOKING AB Purpose: To assess whether reactions to genetic explanations for disparities in lung cancer incidence among family members of African American patients with lung cancer are associated with willingness to participate in clinical genetics research. Methods: Data are reported for 67 self-identified African Americans aged 18 to 55 years who completed a telephone survey assessing reactions to explanations (i.e., genetics, toxin exposure, menthol cigarettes, and race-related stress) for lung cancer disparities. Majority were female (70%), current smokers (57%), and patients' biological relatives (70%). Results: Family members rated the four explanations similarly, each as believable, fair, and not too worrisome. Participants also indicated a high level of willingness to participate in genetics research (M = 4.1 +/- 1.0; scale: 1-5). Endorsements of genetics explanations for disparities as believable and fair, and toxin exposure as believable were associated significantly with willingness to participate in genetics research. Conclusion: These results suggest that strategies to encourage African Americans' participation in genetics research would do well to inform potential participants of how their involvement might be used to better understand important environmental factors that affect health disparities. Genet Med 2010: 12(8):496-502. C1 [White, Della Brown; Koehly, Laura M.; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Omogbehin, Adedamola] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. RP White, DB (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,Bldg 31,Room B1B36H, Bethesda, MD 20892 USA. EM whitede@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 60 TC 4 Z9 4 U1 1 U2 4 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 AUG PY 2010 VL 12 IS 8 BP 496 EP 502 DI 10.1097/GIM.0b013e3181e5e513 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 641FY UT WOS:000281111400005 PM 20613544 ER PT J AU Hoffman, BG Robertson, G Zavaglia, B Beach, M Cullum, R Lee, S Soukhatcheva, G Li, LP Wederell, ED Thiessen, N Bilenky, M Cezard, T Tam, A Kamoh, B Birol, I Dai, D Zhao, YJ Hirst, M Verchere, CB Helgason, CD Marra, MA Jones, SJM Hoodless, PA AF Hoffman, Brad G. Robertson, Gordon Zavaglia, Bogard Beach, Mike Cullum, Rebecca Lee, Sam Soukhatcheva, Galina Li, Leping Wederell, Elizabeth D. Thiessen, Nina Bilenky, Mikhail Cezard, Timothee Tam, Angela Kamoh, Baljit Birol, Inanc Dai, Derek Zhao, Yongjun Hirst, Martin Verchere, C. Bruce Helgason, Cheryl D. Marra, Marco A. Jones, Steven J. M. Hoodless, Pamela A. TI Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver SO GENOME RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR FOXA; GENE-EXPRESSION; HUMAN GENOME; HISTONE MODIFICATIONS; NITRIC-OXIDE; IN-VIVO; CHROMATIN IMMUNOPRECIPITATION; PANCREAS DEVELOPMENT; HOMEODOMAIN PROTEIN AB The liver and pancreas share a common origin and coexpress several transcription factors. To gain insight into the transcriptional networks regulating the function of these tissues, we globally identify binding sites for FOXA2 in adult mouse islets and liver, PDXI in islets, and HNF4A in liver. Because most eukaryotic transcription factors bind thousands of loci, many of which are thought to be inactive, methods that can discriminate functionally active binding events are essential for the interpretation of genome-wide transcription factor binding data. To develop such a method, we also generated genome-wide H3K4me1 and H3K4me3 localization data in these tissues. By analyzing our binding and histone methylation data in combination with comprehensive gene expression data, we show that H3K4me1 enrichment profiles discriminate transcription factor occupied loci into three classes: those that are functionally active, those that are poised for activation, and those that reflect pioneer-like transcription factor activity. Furthermore, we demonstrate that the regulated presence of H3K4me1-marked nucleosomes at transcription factor occupied promoters and enhancers controls their activity, implicating both tissue-specific transcription factor binding and nucleosome remodeling complex recruitment in determining tissue-specific gene expression. Finally, we apply these approaches to generate novel insights into how FOXA2, PDX1, and HNF4A cooperate to drive islet- and liver-specific gene expression. C1 [Hoffman, Brad G.; Zavaglia, Bogard; Beach, Mike; Helgason, Cheryl D.] British Columbia Canc Agcy, Dept Canc Endocrinol, Vancouver, BC V5Z 1L3, Canada. [Hoffman, Brad G.; Soukhatcheva, Galina; Dai, Derek; Verchere, C. Bruce] British Columbia Childrens Hosp, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Hoffman, Brad G.; Soukhatcheva, Galina; Dai, Derek; Verchere, C. Bruce] Sunny Hill Hlth Ctr, Vancouver, BC V5Z 4H4, Canada. [Hoffman, Brad G.; Helgason, Cheryl D.] Univ British Columbia, Dept Surg, Vancouver, BC V5Z 4E3, Canada. [Robertson, Gordon; Thiessen, Nina; Bilenky, Mikhail; Cezard, Timothee; Tam, Angela; Kamoh, Baljit; Birol, Inanc; Zhao, Yongjun; Hirst, Martin; Marra, Marco A.; Jones, Steven J. M.] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada. [Cullum, Rebecca; Lee, Sam; Wederell, Elizabeth D.; Hoodless, Pamela A.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Li, Leping] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Marra, Marco A.; Jones, Steven J. M.; Hoodless, Pamela A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada. RP Hoffman, BG (reprint author), British Columbia Canc Agcy, Dept Canc Endocrinol, Vancouver, BC V5Z 1L3, Canada. EM brad.hoffman@ubc.ca RI Tang, Macy/B-9798-2014; Hirst, Martin/B-7684-2016; Jones, Steven/C-3621-2009; Marra, Marco/B-5987-2008; Birol, Inanc/G-5440-2011; OI Birol, Inanc/0000-0003-0950-7839; Hoodless, Pamela/0000-0003-1371-0725 FU NIH, National Institute of Environmental Health Sciences [Z01-ES-101765]; Genome Canada; Genome British Columbia; Juvenile Diabetes Research Foundation; Canadian Institutes for Health Research FX We acknowledge the Genome Sciences Centre sequencing, bio-informatics, and SAGE library construction teams, and Joanne Johnson and Amanda Kotzer for project management M A M, P.A H, and S J M J are Senior Scholars of the Michael Smith Foundation for Health Research L.L was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-101765) Funding was provided by Genome Canada, Genome British Columbia, the Juvenile Diabetes Research Foundation and the Canadian Institutes for Health Research, with infrastructure support provided by the British Columbia Cancer Foundation NR 60 TC 68 Z9 68 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD AUG PY 2010 VL 20 IS 8 BP 1037 EP 1051 DI 10.1101/gr.104356.109 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 636EA UT WOS:000280709800004 PM 20551221 ER PT J AU Broadhead, ML Becerra, SP Choong, PFM Dass, CR AF Broadhead, Matthew L. Becerra, S. Patricia Choong, Peter F. M. Dass, Crispin R. TI The applied biochemistry of PEDF and implications for tissue homeostasis SO GROWTH FACTORS LA English DT Article DE Pigment epithelium-derived factor; structure; receptor; biochemistry; healing; repair ID EPITHELIUM-DERIVED FACTOR; ENDOTHELIAL GROWTH-FACTOR; ORTHOTOPIC OSTEOSARCOMA GROWTH; BINDING-SITE; NEUROTROPHIC ACTIVITY; PROSTATE-CANCER; OVARIAN-CANCER; CELL-GROWTH; IN-VITRO; ANGIOGENESIS AB Pigment epithelium-derived factor (PEDF) is an endogenously produced glycoprotein with a spectrum of biological roles across diverse pathologies. Recent research has focused on the biochemical properties of PEDF and its associated receptors. This review discusses the recent developments in PEDF biochemistry and how this new knowledge will help progress our understanding of PEDF as a molecular mediator for anti-angiogenesis and -tumorigenesis. Additionally, pathophysiological roles for PEDF in healing and tissue homeostasis are being revealed and our enhanced understanding of the interactions between PEDF and its receptors may yet prove useful in propelling PEDF towards clinical application. C1 [Broadhead, Matthew L.; Choong, Peter F. M.; Dass, Crispin R.] Univ Melbourne, Dept Orthopaed, St Vincents Hosp, Melbourne, Vic, Australia. [Broadhead, Matthew L.; Choong, Peter F. M.; Dass, Crispin R.] Univ Melbourne, Dept Surg, St Vincents Hosp, Melbourne, Vic, Australia. [Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Choong, Peter F. M.] Peter MacCallum Canc Inst, Sarcoma Serv, Melbourne, Vic, Australia. RP Dass, CR (reprint author), SVHM, Dept Orthopaed, L3,Daly Wing,35 Victoria Parade, Fitzroy, Vic 3065, Australia. EM matthew.broadhead@gmail.com; becerras@nei.nih.go; sarcoma@bigpond.net.au; crispin.dass@svhm.org.au FU National Health and Medical Research Council (NHMRC); St Vincent's Research FX Dr M. L. Broadhead is supported by a Postgraduate Scholarship awarded by the National Health and Medical Research Council (NHMRC). The authors would also like to acknowledge the continuing support of the Royal Australasian College of Surgeons, the Australian Orthopaedic Association and the St Vincent's Research Endowment Fund. NR 53 TC 15 Z9 15 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PD AUG PY 2010 VL 28 IS 4 BP 280 EP 285 DI 10.3109/08977191003604513 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 645OJ UT WOS:000281471800006 PM 20166889 ER PT J AU Rodriguez, S Eiriksdottir, G Gaunt, TR Harris, TB Launer, LJ Gudnason, V Day, INM AF Rodriguez, S. Eiriksdottir, G. Gaunt, T. R. Harris, T. B. Launer, L. J. Gudnason, V. Day, I. N. M. TI IGF2BP1, IGF2BP2 and IGF2BP3 genotype, haplotype and genetic model studies in metabolic syndrome traits and diabetes SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE Insulin-like growth factor binding proteins; Genotype; Haplotype; Genetic model; Metabolic syndrome traits; Type 2 diabetes ID GENOME-WIDE ASSOCIATION; INSULIN SENSITIVITY; PROINSULIN CONVERSION; SUSCEPTIBILITY LOCI; NULL ALLELES; RISK LOCI; TYPE-2; VARIANTS; CDKAL1; POLYMORPHISMS AB Objective: Genetic variation at the insulin-like binding protein 2 (IGF2BP2) gene has been associated with type 2 diabetes (T2D) by genome-wide association studies and by replication analyses. Our aim was to explore the underlying genetic model and mechanism of action, factors accounting for non-replications of the associations, and the effect of variation from pathway-related genes IGF2BP1 and IGF2BP3. Method: We analysed here the association between T2D (and related traits) and rs4402960 and rs1470579 in IGF2BP2, and rs46522 and rs6949019 (marking IGF2BP1 and IGF2BP3 respectively) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study (N similar to 2500 aged 65-96 years). We undertook a retrospective analysis of the deviations from the multiplicative model in previous studies and the present study. Results: We replicated an association between rs4402960 and T2D status, and reported significant associations with anthropometric traits, fasting insulin. HOMA-IR and HOMA-%B. These associations were also observed for rs1470579, but not for the SNPs marking IGF2BP1 and IGF2BP3. Conclusions: The lower fasting insulin levels and the impaired beta-cell function associated with IGF2BP2 SNPs are independent of obesity phenotypes. The action of these SNPs on T2D may result from an effect on beta-cell function. This could lead to lower insulin levels, the association with anthropometric traits being secondary. We discuss possible mechanisms of action relating IGF2BP2 with T2D traits. The occurrence of null alleles, the inclusion of T2D patients in analyses of metabolic syndrome risk traits and the genetic model, are possible factors accounting for non-replications of IGF2BP2 associations with T2D. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved. C1 [Rodriguez, S.; Gaunt, T. R.; Day, I. N. M.] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol CAiTE, Bristol BS8 2BN, Avon, England. [Rodriguez, S.; Gaunt, T. R.; Day, I. N. M.] Univ Bristol, Bristol Genet Epidemiol Labs, Bristol BS8 2BN, Avon, England. [Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Harris, T. B.; Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Gudnason, V.] Univ Iceland, Fac Med, Reykjavik, Iceland. RP Rodriguez, S (reprint author), Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol CAiTE, Oakfield House, Bristol BS8 2BN, Avon, England. EM santi.rodriguez@bristol.ac.uk RI Gaunt, Tom/O-3918-2014; Gudnason, Vilmundur/K-6885-2015 OI Gaunt, Tom/0000-0003-0924-3247; Gudnason, Vilmundur/0000-0001-5696-0084 FU NIH [N01-AG-12100]; NIA; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament) FX The Age, Gene/Environment Susceptibility Reykjavik Study is funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). NR 51 TC 10 Z9 13 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD AUG PY 2010 VL 20 IS 4 BP 310 EP 318 DI 10.1016/j.ghir.2010.04.002 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 643AT UT WOS:000281265300007 PM 20627640 ER PT J AU von Rosenvinge, EC Koh, C Holland, SM Heller, T AF von Rosenvinge, Erik C. Koh, Christopher Holland, Steven M. Heller, Theo TI When to leave a stone unturned ... SO GUT LA English DT Editorial Material C1 [von Rosenvinge, Erik C.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP von Rosenvinge, EC (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-101, Bethesda, MD 20892 USA. EM vonroe@yahoo.com NR 3 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD AUG PY 2010 VL 59 IS 8 BP 1036 EP + DI 10.1136/gut.2009.188276 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 626PA UT WOS:000279976700009 PM 20542868 ER PT J AU Broering, R Zhang, XZ Kottilil, S Trippler, M Jiang, M Lu, MJ Gerken, G Schlaak, JF AF Broering, Ruth Zhang, Xiaozhen Kottilil, Shyam Trippler, Martin Jiang, Min Lu, Mengji Gerken, Guido Schlaak, Joerg F. TI The interferon stimulated gene 15 functions as a proviral factor for the hepatitis C virus and as a regulator of the IFN response SO GUT LA English DT Article ID PLUS RIBAVIRIN; ANTIVIRAL MOLECULE; INFECTION; REPLICATION; EXPRESSION; PROTEIN; ISG15; UBIQUITIN; UBP43; CELLS AB Background Non-response to combination therapy by patients with hepatitis C virus (HCV) has previously been associated with a strong hepatic upregulation of interferon stimulated genes (ISGs) including ISG15. Therefore, the aim of this study was to further elucidate the functional role of this molecule. Methods ISG15 expression was suppressed by siRNAs or enhanced by over-expression in genomic and subgenomic human or murine HCV replicon systems. In addition, ISG15 expression was analysed in liver samples of patients with HCV prior to antiviral therapy and correlated with clinical and virological parameters. Results Short- or long-term knockdown of ISG15 expression suppressed HCV replication comparable to IFNs without evidence for the induction of resistant mutations. Triple therapy consisting of ISG15 knockdown, interferon alpha (IFN alpha) and ribavirin led to complete suppression of the HCV NS5A protein, corresponding to 99% suppression of HCV-RNA compared to 75% suppression by IFN alpha and ribavirin only. Combination treatment of ISG15 knockdown and IFN was associated with enhanced and prolonged expression of selected ISGs. Consistent with these in vitro data, high hepatic ISG15 levels correlated with the unfavourable HCV genotype 1, a high hepatic HCV load and a low antiviral response to IFN during the initial phase of treatment. Conclusions ISG15 plays an important role in the HCV replication cycle. Therefore, therapies based on the suppression of ISG15 may provide a promising strategy to overcome non-response to standard combination treatment in the future. Furthermore, analysis of ISG15 prior to therapy may be useful to predict short-term and long-term outcome and thus tailor antiviral therapy with pegIFN and ribavirin. C1 [Broering, Ruth; Trippler, Martin; Jiang, Min; Gerken, Guido; Schlaak, Joerg F.] Univ Hosp Essen, Dept Gastroenterol & Hepatol, D-45122 Essen, Germany. [Zhang, Xiaozhen; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Lu, Mengji] Univ Hosp Essen, Inst Virol, D-45122 Essen, Germany. RP Schlaak, JF (reprint author), Univ Hosp Essen, Dept Gastroenterol & Hepatol, Hufelandstr 55, D-45122 Essen, Germany. EM joerg.schlaak@uni-due.de OI Schlaak, Joerg/0000-0002-9499-1014; Gerken, Guido/0000-0001-6734-5001 FU Deutsche Forschungsgemeinschaft [SCHL377/2-4, 6-2]; NIH, (National Institute of Allergy and Infectious Diseases) FX JFS is supported by the Deutsche Forschungsgemeinschaft (SCHL377/2-4 & 6-2). This research was supported by the Intramural Research Program of the NIH, (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 39 TC 49 Z9 53 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD AUG PY 2010 VL 59 IS 8 BP 1111 EP 1119 DI 10.1136/gut.2009.195545 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 626PA UT WOS:000279976700019 PM 20639253 ER PT J AU Tamary, H Nishri, D Yacobovich, J Zilber, R Dgany, O Krasnov, T Aviner, S Stepensky, P Ravel-Vilk, S Bitan, M Kaplinsky, C Ben Barak, A Elhasid, R Kapelusnik, J Koren, A Levin, C Attias, D Laor, R Yaniv, I Rosenberg, PS Alter, BP AF Tamary, Hannah Nishri, Daniella Yacobovich, Joanne Zilber, Rama Dgany, Orly Krasnov, Tanya Aviner, Shraga Stepensky, Polina Ravel-Vilk, Shoshana Bitan, Menachem Kaplinsky, Chaim Ben Barak, Ayelet Elhasid, Ronit Kapelusnik, Joseph Koren, Ariel Levin, Carina Attias, Dina Laor, Ruth Yaniv, Isaac Rosenberg, Philip S. Alter, Blanche P. TI Frequency and natural history of inherited bone marrow failure syndromes: the Israeli Inherited Bone Marrow Failure Registry SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE inherited bone marrow failure syndromes; Fanconi anemia; stem cell transplantation ID DIAMOND-BLACKFAN ANEMIA; SEVERE CONGENITAL NEUTROPENIA; FANCONI-ANEMIA; DYSKERATOSIS-CONGENITA; CANCER; PATHOPHYSIOLOGY; RISKS AB Background Inherited bone marrow failure syndromes are rare genetic disorders characterized by bone marrow failure, congenital anomalies, and cancer predisposition. Available single disease registries provide reliable information regarding natural history, efficacy and side effects of treatments, and contribute to the discovery of the causative genes. However, these registries could not shed light on the true incidence of the various syndromes. We, therefore, established an Israeli national registry in order to investigate the relative frequency of each of these syndromes and their complications. Design and Methods Patients were registered by their hematologists in all 16 medical centers in Israel. We included patients with Fanconi anemia, severe congenital neutropenia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, dyskeratosis congenita, Shwachman-Diamond syndrome, and thrombocytopenia with absent radii. Results One hundred and twenty-seven patients diagnosed between 1966 and 2007 were registered. Fifty-two percent were found to have Fanconi anemia, 17% severe congenital neutropenia, 14% Diamond-Blackfan anemia, 6% congenital amegakaryocytic thrombocytopenia, 5% dyskeratosis congenita, 2% Shwachman-Diamond syndrome, and 2% thrombocytopenia with absent radii. No specific diagnosis was made in only 2 patients. Of the thirty patients (24%) developing severe bone marrow failure, 80% had Fanconi anemia. Seven of 9 patients with leukemia had Fanconi anemia, as did all 6 with solid tumors. Thirty-four patients died from their disease; 25 (74%) had Fanconi anemia and 6 (17%) had severe congenital neutropenia. Conclusions This is the first comprehensive population-based study evaluating the incidence and complications of the different inherited bone marrow failure syndromes. By far the most common disease was Fanconi anemia, followed by severe congenital neutropenia and Diamond-Blackfan anemia. Fanconi anemia carried the worst prognosis, with severe bone marrow failure and cancer susceptibility. Diamond-Blackfan anemia had the best prognosis. The data presented provide a rational basis for prevention programs and longitudinal surveillance of the complications of inherited bone marrow failure syndromes. C1 [Tamary, Hannah; Yacobovich, Joanne; Zilber, Rama; Yaniv, Isaac] Schneider Childrens Med Ctr Israel, Pediat Hematol Oncol Dept, Tel Aviv, Israel. [Nishri, Daniella] Schneider Childrens Med Ctr Israel, Dept Pediat C, Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Dgany, Orly; Krasnov, Tanya] Felsenstein Med Res Ctr, Pediat Hematol Lab, Petah Tiqwa, Israel. [Aviner, Shraga] Barzilai Govt Hosp, Dept Pediat, Ashqelon, Israel. [Stepensky, Polina; Ravel-Vilk, Shoshana] Hadassah Med Ctr, Pediat Hematol Oncol Unit, IL-91120 Jerusalem, Israel. [Bitan, Menachem] Hadassah Med Ctr, Bone Marrow Transplant Unit, IL-91120 Jerusalem, Israel. [Kaplinsky, Chaim] Chaim Sheba Med Ctr, Pediat Hematol Oncol Dept, IL-52621 Tel Hashomer, Israel. [Ben Barak, Ayelet; Elhasid, Ronit] Rambam Med Ctr, Pediat Hematol Oncol Dept, Haifa, Israel. [Kapelusnik, Joseph] Soroka Med Ctr, Pediat Hematol Oncol Unit, Beer Sheva, Israel. [Koren, Ariel; Levin, Carina] HaEmek Med Ctr, Pediat Hematol Unit, Afula, Israel. [Rosenberg, Philip S.] NCI, Biostat Branch, Bethesda, MD 20892 USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tamary, H (reprint author), Schneider Childrens Med Ctr Israel, Pediat Hematol Oncol Dept, 14 Kaplan St,Petah Tiqva 49,202, Tel Aviv, Israel. EM htamary@post.tau.ac.il FU Israel Cancer Association; National Institutes of Health; National Cancer Institute of the United States FX this work was supported in part by a grant from the Israel Cancer Association, and by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute of the United States. NR 23 TC 24 Z9 26 U1 0 U2 2 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 AUG PY 2010 VL 95 IS 8 BP 1300 EP 1307 DI 10.3324/haematol.2009.018119 PG 8 WC Hematology SC Hematology GA 646UH UT WOS:000281568000011 PM 20435624 ER PT J AU DaSilva, AF Love, T dos Santos, MH Martella, A Enoch, MA Hodgkinson, C Goldman, D Stohler, C Zubieta, JK AF DaSilva, A. F. Love, T. dos Santos, M. Henriques Martella, A. Enoch, M.-A. Hodgkinson, C. Goldman, D. Stohler, C. Zubieta, J. -K. TI BDNF Val66Met Is Associated with Functional and Structural Brain Changes in Dopaminergic Pathways in Relation to the Human Trigeminal Pain Experience SO HEADACHE LA English DT Meeting Abstract CT 52nd Annual Scientific Meeting of the American-Headache-Society CY JUN 24-27, 2010 CL Los Angeles, CA SP Amer Headache Soc C1 [DaSilva, A. F.; dos Santos, M. Henriques; Martella, A.] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Love, T.; Zubieta, J. -K.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Enoch, M.-A.; Hodgkinson, C.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. [Stohler, C.] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. RI Hodgkinson, Colin/F-9899-2010 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 0017-8748 J9 HEADACHE JI Headache PD AUG PY 2010 VL 50 SU 1 BP S6 EP S6 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 613YT UT WOS:000279022000012 ER PT J AU Simon, SL Bouville, A Land, CE Beck, HL AF Simon, Steven L. Bouville, Andre Land, Charles E. Beck, Harold L. TI RADIATION DOSES AND CANCER RISKS IN THE MARSHALL ISLANDS ASSOCIATED WITH EXPOSURE TO RADIOACTIVE FALLOUT FROM BIKINI AND ENEWETAK NUCLEAR WEAPONS TESTS: SUMMARY SO HEALTH PHYSICS LA English DT Article DE cancer; fallout; Marshall Islands; nuclear weapons ID THYROID NEOPLASIA; DETONATION; HISTORY AB Nuclear weapons testing conducted at Bikini and Enewetak Atolls during 1946-1958 resulted in exposures of the resident population of the present-day Republic of the Marshall Islands to radioactive fallout. This paper summarizes the results of a thorough and systematic reconstruction of radiation doses to that population, by year, age at exposure, and atoll of residence, and the related cancer risks. Detailed methods and results are presented in a series of companion papers in this volume. From our analysis, we concluded that 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall Islands. In this work, we estimated deposition densities (kBq m(-2)) of all important dose-contributing radionuclides at each of the 32 atolls and separate reef islands of the Marshall Islands. Quantitative deposition estimates were made for 63 radionuclides from each test at each atoll. Those estimates along with reported measurements of exposure rates at various times after fallout were used to estimate radiation absorbed doses to the red bone marrow, thyroid gland, stomach wall, and colon wall of atoll residents from both external and internal exposure. Annual doses were estimated for six age groups ranging from newborns to adults. We found that the total deposition of Cs-137, external dose, internal organ doses, and cancer risks followed the same geographic pattern with the large population of the southern atolls receiving the lowest doses. Permanent residents of the southern atolls who were of adult age at the beginning of the testing period received external doses ranging from 5 to 12 mGy on average; the external doses to adults at the mid-latitude atolls ranged from 22 to 59 mGy on average, while the residents of the northern atolls received external doses in the hundreds to over 1,000 mGy. Internal doses varied significantly by age at exposure, location, and organ. Except for internal doses to the thyroid gland, external exposure was generally the major contributor to organ doses, particularly for red bone marrow and stomach wall. Internal doses to the stomach wall and red bone marrow were similar in magnitude, about 1 mGy to 7 mGy for permanent residents of the southern and mid-latitude atolls. However, adult residents of Utrik and Rongelap Island, which are part of the northern atolls, received much higher internal doses because of intakes of short-lived radionuclides leading to doses from 20 mGy to more than 500 mGy to red bone marrow and stomach wall. In general, internal doses to the colon wall were four to ten times greater than those to the red bone marrow and internal doses to the thyroid gland were 20 to 30 times greater than to the red bone marrow. Adult internal thyroid doses for the Utrik community and for the Rongelap Island community were about 760 mGy and 7,600 mGy, respectively. The highest doses were to the thyroid glands of young children exposed on Rongelap at the time of the Castle Bravo test of 1 March 1954 and were about three times higher than for adults. Internal doses from chronic intakes, related to residual activities of long-lived radionuclides in the environment, were, in general, low in comparison with acute exposure resulting from the intakes of radionuclides immediately or soon after the deposition of fallout. The annual doses and the population sizes at each atoll in each year were used to develop estimates of cancer risks for the permanent residents of all atolls that were inhabited during te testing period as well as for the Marshallese population groups that were relocated prior to the testing or after it had begun. About 170 excess cancers (radiation-related cases) are projected to occur among more than 25,000 Marshallese, half of whom were born before 1948. All but about 65 of those cancers are estimated to have already been expressed. The 170 excess cancers are in comparison to about 10,600 cancers that would spontaneously arise, unrelated to radioactive fallout, among the same cohort of Marshallese people. Health Phys. 99(2):105-123; 2010 C1 [Simon, Steven L.; Bouville, Andre; Land, Charles E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-Al-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. The authors express appreciation to their colleagues who assisted with companion papers in this volume, Dunstana Melo, Payne Harris, Shawki Ibrahim, Robert Weinstock, Iulian Apostoaei, and Brian Moroz, as well as to the numerous investigators who preceded us in documenting and understanding the consequences of nuclear testing in the Marshall Islands and whose work we have cited here and in the companion papers. NR 34 TC 19 Z9 19 U1 2 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 105 EP 123 DI 10.1097/HP.0b013e3181dc523c PG 19 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500001 PM 20622547 ER PT J AU Beck, HL Bouville, A Moroz, BE Simon, SL AF Beck, Harold L. Bouville, Andre Moroz, Brian E. Simon, Steven L. TI FALLOUT DEPOSITION IN THE MARSHALL ISLANDS FROM BIKINI AND ENEWETAK NUCLEAR WEAPONS TESTS SO HEALTH PHYSICS LA English DT Article DE Cs-137; fallout; Marshall Islands; nuclear weapons ID CS-137; DETONATION AB Deposition densities (Bq m(-2)) of all important dose-contributing radionuclides occurring in nuclear weapons testing fallout from tests conducted at Bikini and Enewetak Atolls (1946-1958) have been estimated on a test-specific basis for 32 atolls and separate reef islands of the Marshall Islands. A complete review of various historical and contemporary data, as well as meteorological analysis, was used to make judgments regarding which tests deposited fallout in the Marshall Islands and to estimate fallout deposition density. Our analysis suggested that only 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in substantial fallout deposition on any of the 23 inhabited atolls. This analysis was confirmed by the fact that the sum of our estimates of Cs-137 deposition from these 20 tests at each atoll is in good agreement with the total Cs-137 deposited as estimated from contemporary soil sample analyses. The monitoring data and meteorological analyses were used to quantitatively estimate the deposition density of 63 activation and fission products for each nuclear test, plus the cumulative deposition of Pu239+240 at each atoll. Estimates of the degree of fractionation of fallout from each test at each atoll, as well as of the fallout transit times from the test sites to the atolls were used in this analysis. The estimates of radionuclide deposition density, fractionation, and transit times reported here are the most complete available anywhere and are suitable for estimations of both external and internal dose to representative persons as described in companion papers. Health Phys. 99(2):124-142; 2010 C1 [Bouville, Andre; Moroz, Brian E.; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Beck, Harold L.] US DOE, New York, NY 10014 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-Al-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. NR 53 TC 15 Z9 15 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 124 EP 142 DI 10.1097/HP.0b013e3181bbbfbd PG 19 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500002 PM 20622548 ER PT J AU Bouville, A Beck, HL Simon, SL AF Bouville, Andre Beck, Harold L. Simon, Steven L. TI DOSES FROM EXTERNAL IRRADIATION TO MARSHALL ISLANDERS FROM BIKINI AND ENEWETAK NUCLEAR WEAPONS TESTS SO HEALTH PHYSICS LA English DT Article DE Cs-137; dose; external; fallout; Marshall Islands AB Annual doses from external irradiation resulting from exposure to fallout from the 65 atmospheric nuclear weapons tests conducted in the Marshall Islands at Bikini and Enewetak between 1946 and 1958 have been estimated for the first time for Marshallese living on all inhabited atolls. All tests that deposited fallout on any of the 23 inhabited atolls or separate reef islands have been considered. The methodology used to estimate the radiation doses at the inhabited atolls is based on test- and location-specific radiation survey data, deposition density estimates of Cs-137, and fallout times-of-arrival provided in a companion paper (Beck et al.), combined with information on the radionuclide composition of the fallout at various times after each test. These estimates of doses from external irradiation have been combined with corresponding estimates of doses from internal irradiation, given in a companion paper (Simon et al.), to assess the cancer risks among the Marshallese population (Land et al.) resulting from exposure to radiation from the nuclear weapons tests. Health Phys. 99(2):143-156; 2010 C1 [Bouville, Andre; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Beck, Harold L.] US DOE, New York, NY 10014 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-Al-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. The authors are indebted to several individuals whose analyses and research have made substantial contributions to this work. They include William Robison for various data and publications on measurements made in the Marshall Islands, Brian Moroz for meteorological analysis and graphic support, Robert Weinstock for computer programming support, Dunstana Melo for the review of the manuscript, as well as other scientists who have added to our understanding of the contamination and consequences in the Marshall Islands through their scientific publications, many of which are cited here. NR 24 TC 10 Z9 10 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 143 EP 156 DI 10.1097/HP.0b013e3181dc521d PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500003 PM 20622549 ER PT J AU Simon, SL Bouville, A Melo, D Beck, HL Weinstock, RM AF Simon, Steven L. Bouville, Andre Melo, Dunstana Beck, Harold L. Weinstock, Robert M. TI ACUTE AND CHRONIC INTAKES OF FALLOUT RADIONUCLIDES BY MARSHALLESE FROM NUCLEAR WEAPONS TESTING AT BIKINI AND ENEWETAK AND RELATED INTERNAL RADIATION DOSES SO HEALTH PHYSICS LA English DT Article DE dose; internal; fallout; Marshall Islands; nuclear weapons ID ISLANDS; IODINE; INGESTION; CS-137; ENVIRONMENT; PLUTONIUM; DOSIMETRY; EXPOSURE; HISTORY; I-131 AB Annual internal radiation doses resulting from both acute and chronic intakes of all important dose-contributing radionuclides occurring in fallout from nuclear weapons testing at Bikini and Enewetak from 1946 through 1958 have been estimated for the residents living on all atolls and separate reef islands of the Marshall Islands. Internal radiation absorbed doses to the tissues most at risk to cancer induction (red bone marrow, thyroid, stomach, and colon) have been estimated for representative persons of all population communities for all birth years from 1929 through 1968, and for all years of exposure from 1948 through 1970. The acute intake estimates rely on a model using, as its basis, historical urine bioassay data, for members of the Rongelap Island and Ailinginae communities as well as for Rongerik residents. The model also utilizes fallout times of arrival and radionuclide deposition densities estimated for all tests and all atolls. Acute intakes of 63 radionuclides were estimated for the populations of the 20 inhabited atolls and for the communities that were relocated during the testing years for reasons of safety and decontamination. The model used for chronic intake estimates is based on reported whole-body, urine, and blood counting data for residents of Utrik and Rongelap. Dose conversion coefficients relating intake to organ absorbed dose were developed using internationally accepted models but specifically tailored for intakes of particulate fallout by consideration of literature-based evidence to choose the most appropriate alimentary tract absorption fraction (f(1)) values. Dose estimates were much higher for the thyroid gland than for red marrow, stomach wall, or colon. The highest thyroid doses to adults were about 7,600 mGy for the people exposed on Rongelap; thyroid doses to adults were much lower, by a factor of 100 or more, for the people exposed on the populated atolls of Kwajalein and Majuro. The estimates of radionuclide intake and internal radiation dose to the Marshallese that are presented in this paper are the most complete available anywhere and were used to make projections of lifetime cancer risks to the exposed populations, which are presented in a companion paper in this volume. Health Phys. 99(2):157-200; 2010 C1 [Simon, Steven L.; Bouville, Andre; Melo, Dunstana] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Beck, Harold L.] US DOE, New York, NY USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-Al-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency Agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. NR 81 TC 12 Z9 12 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 157 EP 200 DI 10.1097/HP.0b013e3181dc4e51 PG 44 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500004 PM 20622550 ER PT J AU Land, CE Bouville, A Apostoaei, I Simon, SL AF Land, Charles E. Bouville, Andre Apostoaei, Iulian Simon, Steven L. TI PROJECTED LIFETIME CANCER RISKS FROM EXPOSURE TO REGIONAL RADIOACTIVE FALLOUT IN THE MARSHALL ISLANDS SO HEALTH PHYSICS LA English DT Article DE cancer; fallout; Marshall Islands; nuclear weapons ID ATOMIC-BOMB SURVIVORS; THYROID NEOPLASIA; SOLID CANCER; DISEASE AB Radioactive fallout from nuclear test detonations during 1946-1958 at Bikini and Enewetak Atolls in the Marshall Islands (MI) exposed populations living elsewhere in the MI archipelago. A comprehensive analysis, presented in seven companion papers, has produced estimates of tissue-specific radiation absorbed dose to MI residents at all historically inhabited atolls from internal (ingested) and external irradiation resulting from exposure to radioactive fallout, by calendar year, and by age of the population at time of exposure. The present report deals, for the first time, with the implications of these doses for cancer risk among exposed members of the MI population. Radiation doses differed by geographic location and year of birth, and radiation-related cancer risk depends upon age at exposure and age at observation for risk. Using dose-response models based on committee reports published by the National Research Council and the National Institutes of Health, we project that, during the lifetimes of members of the MI population potentially exposed to ionizing radiation from weapons test fallout deposited during the testing period (1948-1958) and from residual radioactive sources during the subsequent 12 y (1959-1970), perhaps 1.6% (with 90% uncertainty range 0.4% to 3.4%) of all cancers might be attributable to fallout-related radiation exposures. By sub-population, the projected proportion of cancers attributable to radiation from fallout from all nuclear tests conducted in the Marshall Islands is 55% (28% to 69%) among 82 persons exposed in 1954 on Rongelap and Ailinginae, 10% (2.4% to 22%) for 157 persons exposed on Utrik, and 2.2% (0.5% to 4.8%) and 0.8% (0.2% to 1.8%), respectively, for the much larger populations exposed in mid-latitude locations including Kwajalein and in southern locations including Majuro. By cancer type, point estimates of attributable risk varied, by location, between 12% and 95% for thyroid cancer, between 2% and 78% for leukemia, and between 0.8% and 55% for all cancers combined. The largest projected risks pertain to the Rongelap Island community and the lowest risks pertain to the populations resident on the southern-most atolls. While the projected cancer risks are smaller than those estimated by the National Cancer Institute in a more simplistic analysis conducted in 2004, these estimates of cancer risk are the best available as they are based on the most detailed dose reconstruction to date and comprehensively include populations at all locations and dose contributions from all nuclear tests. Health Phys. 99(2):201-215; 2010 C1 [Land, Charles E.; Bouville, Andre; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Apostoaei, Iulian] SENES Oak Ridge Inc, Oak Ridge, TN USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-A1-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency Agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-A1-5077 and NCI agreement #Y3-CO-5117. NR 31 TC 12 Z9 12 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 201 EP 215 DI 10.1097/HP.0b013e3181dc4e84 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500005 PM 20622551 ER PT J AU Simon, SL AF Simon, Steven L. TI DEDICATION: PAYNE S. HARRIS (1922-2010) SO HEALTH PHYSICS LA English DT Biographical-Item C1 NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 216 EP 216 DI 10.1097/HP.0b013e3181e28c02 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500006 PM 20622552 ER PT J AU Harris, PS Simon, SL Ibrahim, SA AF Harris, Payne S. Simon, Steven L. Ibrahim, Shawki A. TI URINARY EXCRETION OF RADIONUCLIDES FROM MARSHALLESE EXPOSED TO FALLOUT FROM THE 1954 BRAVO NUCLEAR TEST SO HEALTH PHYSICS LA English DT Article DE excretion; urinary; fallout; I-131; Marshall Islands ID IODINE; METABOLISM; SWEAT AB Soon after the Bravo nuclear test at Bikini Atoll in the Marshall Islands on 1 March 1954, urine samples were collected for analysis of excreted radioactivity from native residents exposed to radioactive fallout on two atolls as well as from U. S. military personnel on a third atoll. The earliest acquired samples, obtained by the Los Alamos Scientific Laboratory (LASL), were assayed for various radionuclides and provided the first known measurements of I-131 in urine following exposure to fallout from a nuclear test. Over the course of 1954, many additional samples were collected by the LASL, as well as by the Atomic Energy Commission New York Operations Office's Health and Safety Laboratory and the Naval Radiological Defense Laboratory. Collectively, the groups sampled included Marshallese exposed on Rongelap and Ailinginae Atolls, American military weather observers temporarily resident on Rongerik Atoll, and sailors from the Japanese fishing vessel, the Lucky Dragon. While the bioassay measurement data and individual urine volumes have been crucial to various attempts to assess intakes of radioactivity and the related internal radiation doses among the Marshallese, those data have never been published in any peer-reviewed journal, but have been restricted to agency memoranda, laboratory reports, and summaries in some publications and book chapters. Reconstructions of internal doses to Marshallese in 1954 and in later years have depended on these data and, hence, they have considerable historical importance as well as importance to ongoing health risk projections for Marshallese. This paper presents much of the original data on urine volumes and radioactivity from the various assays of urine for radionuclides, and compares estimates of I-131 intakes made in 1954, 1985, 1987, and 2008. Health Phys. 99(2):217-232; 2010 C1 [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Ibrahim, Shawki A.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. [Harris, Payne S.] Los Alamos Sci Lab, Santa Fe, NM USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-A1-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency Agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-A1-5077 and NCI agreement #Y3-CO-5117. The authors appreciate the helpful comments of their colleagues, Andre Bouville, Harold Beck, and Dunstana Melo. NR 36 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 217 EP 232 DI 10.1097/HP.0b013e3181dc50a4 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500007 PM 20622553 ER PT J AU Ibrahim, SA Simon, SL Bouville, A Melo, D Beck, HL AF Ibrahim, Shawki A. Simon, Steven L. Bouville, Andre Melo, Dunstana Beck, Harold L. TI ALIMENTARY TRACT ABSORPTION (f(1) VALUES) FOR RADIONUCLIDES IN LOCAL AND REGIONAL FALLOUT FROM NUCLEAR TESTS SO HEALTH PHYSICS LA English DT Article DE fallout; Marshall Islands; radionuclide; nuclear weapons ID GASTROINTESTINAL ABSORPTION; MARSHALL-ISLANDS; SEA-WATER; RETENTION; URANIUM; PLUTONIUM; METABOLISM; INGESTION; HUMANS; HISTORY AB This paper presents gastrointestinal absorption fractions (f(1) values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f(1) values are based on specific circumstances of weapons test conditions and a review of reported f(1) values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f(1) values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f(1) values for different circumstances where persons are exposed to radioactive fallout (e. g., local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f(1) values are similar to those adopted by the International Commission on Radiological Protection (ICRP) (e.g., iodine and most actinides). However, f(1) values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f(1) values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively). The f(1) values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout. Health Phys. 99(2):233-251; 2010 C1 [Simon, Steven L.; Bouville, Andre; Melo, Dunstana] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Ibrahim, Shawki A.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-A1-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-A1-5077 and NCI agreement #Y3-CO-5117. The authors would like to thank J. D. Harrison of the Health Protection Agency (HPA), UK, for his review and comments on an earlier draft of this paper. NR 85 TC 3 Z9 3 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 233 EP 251 DI 10.1097/HP.0b013e3181b186ff PG 19 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500008 PM 20622554 ER PT J AU Moroz, BE Beck, HL Bouville, A Simon, SL AF Moroz, Brian E. Beck, Harold L. Bouville, Andre Simon, Steven L. TI PREDICTIONS OF DISPERSION AND DEPOSITION OF FALLOUT FROM NUCLEAR TESTING USING THE NOAA-HYSPLIT METEOROLOGICAL MODEL SO HEALTH PHYSICS LA English DT Article DE Marshall Islands; nuclear weapons; fallout; modeling; meteorological ID CONTINENTAL UNITED-STATES; RADIOACTIVE PLUME; TEST-SITE; DOLON AB The NOAA Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT) was evaluated as a research tool to simulate the dispersion and deposition of radioactive fallout from nuclear tests. Model-based estimates of fallout can be valuable for use in the reconstruction of past exposures from nuclear testing, particularly where little historical fallout monitoring data are available. The ability to make reliable predictions about fallout deposition could also have significant importance for nuclear events in the future. We evaluated the accuracy of the HYSPLIT-predicted geographic patterns of deposition by comparing those predictions against known deposition patterns following specific nuclear tests with an emphasis on nuclear weapons tests conducted in the Marshall Islands. We evaluated the ability of the computer code to quantitatively predict the proportion of fallout particles of specific sizes deposited at specific locations as well as their time of transport. In our simulations of fallout from past nuclear tests, historical meteorological data were used from a reanalysis conducted jointly by the National Centers for Environmental Prediction (NCEP) and the National Center for Atmospheric Research (NCAR). We used a systematic approach in testing the HYSPLIT model by simulating the release of a range of particle sizes from a range of altitudes and evaluating the number and location of particles deposited. Our findings suggest that the quantity and quality of meteorological data are the most important factors for accurate fallout predictions and that, when satisfactory meteorological input data are used, HYSPLIT can produce relatively accurate deposition patterns and fallout arrival times. Furthermore, when no other measurement data are available, HYSPLIT can be used to indicate whether or not fallout might have occurred at a given location and provide, at minimum, crude quantitative estimates of the magnitude of the deposited activity. A variety of simulations of the deposition of fallout from atmospheric nuclear tests conducted in the Marshall Islands (mid-Pacific), at the Nevada Test Site (U.S.), and at the Semipalatinsk Nuclear Test Site (Kazakhstan) were performed. The results of the Marshall Islands simulations were used in a limited fashion to support the dose reconstruction described in companion papers within this volume. Health Phys. 99(2):252-269; 2010 C1 [Moroz, Brian E.; Bouville, Andre; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov FU National Institute of Allergy and Infectious Diseases [Y2-Al-5077]; National Cancer Institute [Y3-CO-5117] FX This work was supported by the Intra-Agency agreement between the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. The authors are indebted to Roland Draxler and Barbara Stunder of the NOAA Air Resources Laboratory in Silver Spring, MD, for their willingness and generosity in providing instruction and information about the operation and theory of the HYSPLIT model (http://ready.arl.noaa.gov/HYSPLIT.php). NR 33 TC 9 Z9 11 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2010 VL 99 IS 2 BP 252 EP 269 DI 10.1097/HP.0b013e3181b43697 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 622QN UT WOS:000279678500009 PM 20622555 ER PT J AU Liu, W Yan, M Liu, Y Wang, R Li, C Deng, C Singh, A Coleman, WG Rodgers, GP AF Liu, W. Yan, M. Liu, Y. Wang, R. Li, C. Deng, C. Singh, A. Coleman, W. G., Jr. Rodgers, G. P. TI Olfactomedin 4 down-regulates innate immunity against H-pylori infection SO HELICOBACTER LA English DT Meeting Abstract CT 23rd International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 16-18, 2010 CL Rotterdam, NETHERLANDS C1 [Liu, W.; Yan, M.; Liu, Y.; Wang, R.; Li, C.; Deng, C.; Singh, A.; Coleman, W. G., Jr.; Rodgers, G. P.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2010 VL 15 IS 4 BP 318 EP 318 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 626SC UT WOS:000279986200023 ER PT J AU Yang, Z Zhou, Y Jin, D AF Yang, Z. Zhou, Y. Jin, D. TI Polyphosphate Binds to the Principal Sigma Factor of RNA Polymerase during Starvation Response in H. pylori SO HELICOBACTER LA English DT Meeting Abstract CT 23rd International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 16-18, 2010 CL Rotterdam, NETHERLANDS C1 [Yang, Z.; Zhou, Y.; Jin, D.] NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2010 VL 15 IS 4 BP 331 EP 331 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 626SC UT WOS:000279986200057 ER PT J AU Lodish, MB Gartner, LA Albini, P Sabnis, G Brodie, A Meck, JM Meloni-Ehrig, AM Hill, S Tsilou, E Valera, VA Walter, BA Merino, MJ Stratakis, CA AF Lodish, M. B. Gartner, L. A. Albini, P. Sabnis, G. Brodie, A. Meck, J. M. Meloni-Ehrig, A. M. Hill, S. Tsilou, E. Valera, V. A. Walter, B. A. Merino, M. J. Stratakis, C. A. TI Intrauterine Growth Retardation Associated with Precocious Puberty and Sertoli Cell Hyperplasia SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE genetic syndrome; hyper androgenemia; disorder of puberty; testicular tumor; aromatase ID SILVER-RUSSELL-SYNDROME; TRISOMY-8 MOSAICISM; UNIPARENTAL DISOMY; CHROMOSOME-ABNORMALITIES; PREPUBERTAL GYNECOMASTIA; TUMORS; SEX AB The original description of patients with Russell-Silver syndrome included precocious puberty, the mechanism of which was unclear. We describe a child with a Russell-Silver syndrome-like phenotype who presented with precocious puberty that was associated with hyperplasia of the Sertoli cells. The patient was found to have an immature cryptorchid testicle; hyperplastic Sertoli cells were also aneuploid carrying trisomy 8. This chromosomal abnormality was present in Sertoli cells only and could not be detected in peripheral lymphocytes, tunica vaginalis, or other, normal, testicular tissue. Sertoli cells in culture showed excess aromatization providing an explanation for the rapid advancement of the patient's bone age. We conclude that in a patient with a Russell-Silver syndrome-like phenotype, Sertoli cell hyperplasia was associated with somatic trisomy 8, increased aromatization, and gonadotropin-independent precocious puberty. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol Genet, Program Dev Endocrinol Genet, Bethesda, MD USA. NIH, Pediat Endocrinol Inter Inst Training Program, Bethesda, MD 20892 USA. SUNY Buffalo, Sch Med, Childrens Hosp Buffalo, Buffalo, NY 14260 USA. Univ Maryland, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. Quest Diagnost Nichols Inst, Dept Cytogenet, Chantilly, VA USA. NIH, Ctr Clin, Dept Diagnost Imaging, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lodish, MB (reprint author), 10 Ctr Dr,CRC Room 1-3330, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU United States National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [Z01-HD-000642-04] FX We thank our patient and his family and acknowledge the great help that we received for this study from the nursing and other support staff of the NIH Clinical Center outpatient clinics and the 1NW ward. This work was supported by the United States National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) intramural project Z01-HD-000642-04 (to Dr. C. A. Stratakis). NR 33 TC 3 Z9 3 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD AUG PY 2010 VL 42 IS 9 BP 682 EP 688 DI 10.1055/s-0030-1252021 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631TG UT WOS:000280370400011 PM 20411478 ER PT J AU Pawlyk, BS Bulgakov, OV Liu, XQ Xu, XY Adamian, M Sun, X Khani, SC Berson, EL Sandberg, MA Li, TS AF Pawlyk, Basil S. Bulgakov, Oleg V. Liu, Xiaoqing Xu, Xiaoyun Adamian, Michael Sun, Xun Khani, Shahrokh C. Berson, Eliot L. Sandberg, Michael A. Li, Tiansen TI Replacement Gene Therapy with a Human RPGRIP1 Sequence Slows Photoreceptor Degeneration in a Murine Model of Leber Congenital Amaurosis SO HUMAN GENE THERAPY LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; REGULATOR (RPGR)-INTERACTING PROTEIN; RETINITIS-PIGMENTOSA; ROD PHOTORECEPTOR; RESTORES VISION; MUTATIONS; IDENTIFICATION; MORPHOGENESIS; LOCALIZATION; TRANSDUCTION AB RPGR-interacting protein-1 (RPGRIP1) is localized in the photoreceptor-connecting cilium, where it anchors the RPGR (retinitis pigmentosa GTPase regulator) protein, and its function is essential for photoreceptor maintenance. Genetic defect in RPGRIP1 is a known cause of Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. We evaluated the efficacy of replacement gene therapy in a murine model of LCA carrying a targeted disruption of RPGRIP1. The replacement construct, packaged in an adeno-associated virus serotype 8 (AAV8) vector, used a rhodopsin kinase gene promoter to drive RPGRIP1 expression. Both promoter and transgene were of human origin. After subretinal delivery of the replacement gene in the mutant mice, human RPGRIP1 was expressed specifically in photoreceptors, localized correctly in the connecting cilia, and restored the normal localization of RPGR. Electroretinogram and histological examinations showed better preservation of rod and cone photoreceptor function and improved photoreceptor survival in the treated eyes. This study demonstrates the efficacy of human gene replacement therapy and validates a gene therapy design for future clinical trials in patients afflicted with this condition. Our results also have therapeutic implications for other forms of retinal degenerations attributable to a ciliary defect. C1 [Pawlyk, Basil S.; Bulgakov, Oleg V.; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Berson, Eliot L.; Sandberg, Michael A.; Li, Tiansen] Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. [Pawlyk, Basil S.; Bulgakov, Oleg V.; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Berson, Eliot L.; Sandberg, Michael A.; Li, Tiansen] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Khani, Shahrokh C.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Li, TS (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. EM Tiansen.Li@nih.gov FU National Eye Institute [EY10581]; NEI [P30EY14104]; Foundation Fighting Blindness; Foundation for Retina Research; Massachusetts Lions Eye Research Fund FX The authors thank Dr. Jeng-Shin Lee at the Research Vector Core of Harvard Medical School for AAV vector packaging, the National Disease Research Interchange for providing human retinal tissue, and Norman Michaud for select tissue processing for light microscopy. This work was supported by National Eye Institute grant EY10581, an NEI core grant for Vision Research (P30EY14104), the Foundation Fighting Blindness, the Foundation for Retina Research, and the Massachusetts Lions Eye Research Fund. NR 43 TC 41 Z9 42 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 AUG PY 2010 VL 21 IS 8 BP 993 EP 1004 DI 10.1089/hum.2009.218 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 636RK UT WOS:000280757200009 PM 20384479 ER PT J AU Chen, SF Wang, HW Lu, XF Liu, DP Chen, J Jaquish, CE Rao, DC Hixson, JE Kelly, TN Hou, LP Wang, LY Huang, JF Chen, CS Rice, TK Whelton, PK He, JA Gu, DF AF Chen, Shufeng Wang, Hongwei Lu, Xiangfeng Liu, De-Pei Chen, Jing Jaquish, Cashell E. Rao, Dabeeru C. Hixson, James E. Kelly, Tanika N. Hou, Liping Wang, Laiyuan Huang, Jianfeng Chen, Chung-Shiuan Rice, Treva K. Whelton, Paul K. He, Jiang Gu, Dongfeng TI Polymorphisms in the GNB3 and ADD1 genes and blood pressure in a Chinese population SO HUMAN GENETICS LA English DT Article ID BETA-3 SUBUNIT GENE; ESSENTIAL-HYPERTENSION; ALPHA-ADDUCIN; JAPANESE POPULATION; NO ASSOCIATION; VARIANTS; RENIN AB A large proportion of the phenotypic variation in blood pressure (BP) appears to be inherited as a polygenic trait. This study examined the association between 12 single nucleotide polymorphisms (SNPs) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) and adducin 1 alpha (ADD1) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP. A total of 3,142 individuals from 636 families were recruited from rural north China, and 2,746 met the eligibility criteria for analysis. BP measurements were obtained using a random-zero sphygmomanometer. Genetic variants were determined using SNPlex assays on an automated DNA Sequencer. A mixed linear model was used to estimate the association between each SNP and BP level. After Bonferroni correction, marker rs4963516 of the GNB3 gene remained significantly associated with DBP (corrected P values = 0.006, 0.007 and 0.002 for co-dominant, additive, and recessive models, respectively) and MAP (corrected P values = 0.02, 0.049, and 0.005, respectively). Compared to carriers of the major A allele, CC homozygotes had higher mean DBP (75.81 +/- A 0.62 vs. 73.46 +/- A 0.25 mmHg, P = 0.0002) and MAP (91.87 +/- A 0.68 vs. 89.42 +/- A 0.28 mmHg, P = 0.0004) after adjusting for covariates of age, gender, BMI, study site, and room temperature during BP measurement. In summary, these data support a role for the GNB3 gene in BP regulation in the Chinese population. Future studies aimed at replicating these novel findings are warranted. C1 [Chen, Shufeng; Wang, Hongwei; Lu, Xiangfeng; Hou, Liping; Wang, Laiyuan; Huang, Jianfeng; Gu, Dongfeng] Chinese Acad Med Sci, Peking Union Med Coll, Div Populat Genet,Dept Evidence Based Med, Cardiovasc Inst,Fu Wai Hosp, Beijing 100037, Peoples R China. [Gu, Dongfeng] Chinese Natl Human Genome Ctr, Beijing, Peoples R China. [Liu, De-Pei] Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100037, Peoples R China. [Chen, Jing; Kelly, Tanika N.; Chen, Chung-Shiuan; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. [Chen, Jing; He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Jaquish, Cashell E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Rao, Dabeeru C.; Rice, Treva K.] Washington Univ, Sch Med, St Louis, MO USA. [Hixson, James E.] Univ Texas Sch Publ Hlth, Houston, TX USA. [Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP Gu, DF (reprint author), Chinese Acad Med Sci, Peking Union Med Coll, Div Populat Genet,Dept Evidence Based Med, Cardiovasc Inst,Fu Wai Hosp, 167 Beilishi Rd, Beijing 100037, Peoples R China. EM gudf@yahoo.com RI Hou, Liping/G-1648-2011 OI Hou, Liping/0000-0003-3972-245X FU National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD [U01HL072507] FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is supported by a cooperative agreement project Grant (U01HL072507) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. NR 29 TC 6 Z9 6 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 2010 VL 128 IS 2 BP 137 EP 143 DI 10.1007/s00439-010-0834-3 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 627WR UT WOS:000280075200003 PM 20473689 ER PT J AU Schumacher, FR Cheng, I Freedman, ML Mucci, L Allen, NE Pollak, MN Hayes, RB Stram, DO Canzian, F Henderson, BE Hunter, DJ Virtamo, J Manjer, J Gaziano, JM Kolonel, LN Tjonneland, A Albanes, D Calle, EE Giovannucci, E Crawford, ED Haiman, CA Kraft, P Willett, WC Thun, MJ Marchand, LL Kaaks, R Feigelson, HS Bueno-De-Mesquita, HB Palli, D Riboli, E Lund, E Amiano, P Andriole, G Dunning, AM Trichopoulos, D Stampfer, MJ Key, TJ Ma, J AF Schumacher, Fredrick R. Cheng, Iona Freedman, Matthew L. Mucci, Lorelei Allen, Naomi E. Pollak, Michael N. Hayes, Richard B. Stram, Daniel O. Canzian, Frederico Henderson, Brian E. Hunter, David J. Virtamo, Jarmo Manjer, Jonas Gaziano, J. Michael Kolonel, Laurence N. Tjonneland, Anne Albanes, Demetrius Calle, Eugenia E. Giovannucci, Edward Crawford, E. David Haiman, Christopher A. Kraft, Peter Willett, Walter C. Thun, Michael J. Marchand, Loic Le Kaaks, Rudolf Feigelson, Heather Spencer Bueno-de-Mesquita, H. Bas Palli, Domenico Riboli, Elio Lund, Eliv Amiano, Pilar Andriole, Gerald Dunning, Alison M. Trichopoulos, Dimitrios Stampfer, Meir J. Key, Timothy J. Ma, Jing TI A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among SO HUMAN MOLECULAR GENETICS LA English DT Article ID GROWTH-FACTOR-I; GENOME-WIDE ASSOCIATION; FACTOR-BINDING PROTEIN-3; BREAST-CANCER; MULTIETHNIC COHORT; CIRCULATING LEVELS; FACTOR (IGF)-I; SERUM-LEVELS; MENDELIAN RANDOMIZATION; MISSING HERITABILITY AB The insulin-like growth factor (IGF) pathway has been implicated in prostate development and carcinogenesis. We conducted a comprehensive analysis, utilizing a resequencing and tagging single-nucleotide polymorphism (SNP) approach, between common genetic variation in the IGF1, IGF binding protein (BP) 1, and IGFBP3 genes with IGF-I and IGFBP-3 blood levels, and prostate cancer (PCa) risk, among Caucasians in the NCI Breast and Prostate Cancer Cohort Consortium. We genotyped 14 IGF1 SNPs and 16 IGFBP1/IGFBP3 SNPs to capture common [minor allele frequency (MAF) >= 5%] variation among Caucasians. For each SNP, we assessed the geometric mean difference in IGF blood levels (N = 5684) across genotypes and the association with PCa risk (6012 PCa cases/6641 controls). We present two-sided statistical tests and correct for multiple comparisons. A non-synonymous IGFBP3 SNP in exon 1, rs2854746 (Gly32Ala), was associated with IGFBP-3 blood levels (P-adj = 8.8 x 10(-43)) after adjusting for the previously established IGFBP3 promoter polymorphism A-202C (rs2854744); IGFBP-3 blood levels were 6.3% higher for each minor allele. For IGF1 SNP rs4764695, the risk estimates among heterozygotes was 1.01 (99% CI: 0.90-1.14) and 1.20 (99% CI: 1.06-1.37) for variant homozygotes with overall PCa risk. The corrected allelic P-value was 8.7 x 10(-3). IGF-I levels were significantly associated with PCa risk (P-trend = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile. We have identified SNPs significantly associated with IGFBP-3 blood levels, but none of these alter PCa risk; however, a novel IGF1 SNP, not associated with IGF-I blood levels, shows preliminary evidence for association with PCa risk among Caucasians. C1 [Mucci, Lorelei; Hunter, David J.; Giovannucci, Edward; Stampfer, Meir J.; Ma, Jing] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. [Schumacher, Fredrick R.; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Cheng, Iona; Kolonel, Laurence N.; Marchand, Loic Le] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mucci, Lorelei; Giovannucci, Edward; Willett, Walter C.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02115 USA. [Allen, Naomi E.; Key, Timothy J.] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7BN, England. [Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Med & Oncol,Canc Prevent Res Unit, Montreal, PQ H3T 1E2, Canada. [Hayes, Richard B.] NYU, Sch Med, New York, NY 10016 USA. [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FIN-00300 Helsinki, Finland. [Manjer, Jonas] Malmo Univ Hosp, Dept Surg, S-20502 Malmo, Sweden. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. [Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Calle, Eugenia E.; Thun, Michael J.; Feigelson, Heather Spencer] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Crawford, E. David] Univ Colorado, Denver Hlth Sci Ctr, Denver, CO 80045 USA. [Feigelson, Heather Spencer] Kaiser Permanente, Denver, CO 80237 USA. [Bueno-de-Mesquita, H. Bas; Amiano, Pilar] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. [Palli, Domenico] ISPO Canc Res & Prevent Inst, Mol & Nutrit Epidemiol Unit, I-50139 Florence, Italy. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London SW7 2AZ, England. [Lund, Eliv] Univ Tromso, Inst Community Med, N-9019 Tromso, Norway. [Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens 11527, Greece. RP Ma, J (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015; OI Pollak, Michael/0000-0003-3047-0604; Dunning, Alison Margaret/0000-0001-6651-7166; PALLI, Domenico/0000-0002-5558-2437 FU National Cancer Institute (NCI) [U01 CA098216, U01 CA098233, U01 CA098758, U01 CA098710, CA-34944, CA-40360, CA-097193]; National Research Service Award Training Program in Cancer Epidemiology [T32 CA009001-32]; NHLBI [HL-26490, HL-34595]; Department of Health and Human Services, National Cancer Institute [N01-CN-45165, N01-RC-45035, N01-RC-37004]; [CA54281]; [CA63464] FX This work was funded by National Cancer Institute (NCI) grants U01 CA098216 (EPIC), U01 CA098233 (Harvard), U01 CA098758 (MEC) and U01 CA098710 (ACS). F. R. S. was supported by the National Research Service Award Training Program in Cancer Epidemiology (T32 CA009001-32). The Physicians' Health Study was supported by the NCI (CA-34944, CA-40360 and CA-097193) and the NHLBI (HL-26490 and HL-34595). The Multiethnic Cohort was supported by CA54281 and CA63464. The ATBC Study was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035 and N01-RC-37004 from the Department of Health and Human Services, National Cancer Institute. NR 97 TC 32 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2010 VL 19 IS 15 BP 3089 EP 3101 DI 10.1093/hmg/ddq210 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 633HA UT WOS:000280491200015 PM 20484221 ER PT J AU Sommer, WH Lidstrom, J Sun, H Passer, D Eskay, R Parker, SCJ Witt, SH Zimmermann, US Nieratschker, V Rietschel, M Margulies, EH Palkovits, M Laucht, M Heilig, M AF Sommer, Wolfgang H. Lidstroem, Jessica Sun, Hui Passer, Derek Eskay, Robert Parker, Stephen C. J. Witt, Stephanie H. Zimmermann, Ulrich S. Nieratschker, Vanessa Rietschel, Marcella Margulies, Elliott H. Palkovits, Miklos Laucht, Manfred Heilig, Markus TI Human NPY Promoter Variation rs16147:T > C as a Moderator of Prefrontal NPY Gene Expression and Negative Affect SO HUMAN MUTATION LA English DT Article DE NPY; promoter variant; brain; gene expression; stress coping ID NEUROPEPTIDE-Y GENE; SEROTONIN TRANSPORTER GENE; DEPRESSED SUICIDE VICTIMS; GREATER-THAN-T; MAJOR DEPRESSION; NERVOUS-SYSTEM; NO ASSOCIATION; SCHIZOPHRENIA; POLYMORPHISM; STRESS AB Studies in humans and animals suggest a role for NPY in the mediation of behavioral stress responses. Here, we examined whether the NPY promoter variant rs16147:T>C is functional for expression of NPY in a brain region relevant for behavioral control, anxiety and depression, the anterior cingulate cortex. In silico analysis of DNA structural profile changes produced by rs16147 variation suggests allelic differences in protein binding at the rs16147 site. This was confirmed by electrophoretic mobility shift assay, demonstrating that the rs16147 C-allele has strongly reduced affinity for a yet unknown factor compared to the T-allele. Analyzing 107 human post-mortem brain samples we show that allelic variation at rs16147 contributes to regulation of NPY mRNA and peptide levels in this region. Specifically, the C-allele leads to increased gene expression. In agreement with the molecular findings, rs16147: T>C is associated with anxiety and depressive symptoms in 314 young adults via a gene x environment interaction with early childhood adversity, replicating the recent finding of rs16147-C as a risk factor for stress related psychopathology. Our results show the importance of rs16147: T>C for regulation of NPY gene expression and brain function. (C) 2010 Wiley-Liss, Inc. C1 [Sommer, Wolfgang H.; Witt, Stephanie H.; Zimmermann, Ulrich S.; Nieratschker, Vanessa; Rietschel, Marcella; Laucht, Manfred] Cent Inst Mental Hlth, D-68159 Mannheim, Germany. [Sommer, Wolfgang H.; Lidstroem, Jessica; Sun, Hui; Passer, Derek; Eskay, Robert; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Parker, Stephen C. J.; Margulies, Elliott H.] NHGRI, Genome Informat Sect, NIH, Bethesda, MD 20892 USA. [Palkovits, Miklos] Semmelweis Univ, Neuromorphol Lab, H-1085 Budapest, Hungary. [Palkovits, Miklos] Hungarian Acad Sci, Budapest, Hungary. RP Sommer, WH (reprint author), Cent Inst Mental Hlth, Sq J5, D-68159 Mannheim, Germany. EM wolfgang.sommer@zi-mannheim.de RI Zimmermann, Ulrich/B-9357-2011; Palkovits, Miklos/F-2707-2013; OI Heilig, Markus/0000-0003-2706-2482; Sommer, Wolfgang/0000-0002-5903-6521; Palkovits, Miklos/0000-0003-0578-0387 FU NIAAA; Karolinska Institute; EU [LSHM-CT-2004-503039]; German Research Foundation (DFG); Federal Ministry for Education and Research [NGFN+01GS08152] FX Contract grant sponsor: Intramural funding from NIAAA and Karolinska Institute, EU Grant FP6 BNEII (LSHM-CT-2004-503039) to M. P., grants from the German Research Foundation (DFG) and the Federal Ministry for Education and Research as part of the 'National Genome Research Network' (NGFN+01GS08152). NR 61 TC 52 Z9 53 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD AUG PY 2010 VL 31 IS 8 BP E1594 EP E1608 DI 10.1002/humu.21299 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 636SJ UT WOS:000280760300013 PM 20648632 ER PT J AU Goto, M O'Brien, DA Eddy, EM AF Goto, M. O'Brien, D. A. Eddy, E. M. TI Speriolin is a novel human and mouse sperm centrosome protein SO HUMAN REPRODUCTION LA English DT Article DE centriole; flagellum; fertilization; paternal inheritance; zygote ID GAMMA-TUBULIN; FINE-STRUCTURE; MICROTUBULE ORGANIZATION; CHROMOSOME SEGREGATION; MAMMALIAN SPERMATOZOON; HUMAN OOCYTES; CENTRIOLES; FERTILIZATION; INHERITANCE; EMBRYOS AB Oocytes in humans, mice and other mammals lack identifiable centrioles. The proximal centriole brought in by the fertilizing sperm in humans and most other mammals appears to gives rise to the centrioles at the spindle poles in the zygote, and is believed to indicate that centrioles are inherited through the paternal lineage. However, both the proximal and distal sperm centrioles degenerate in mice and other rodents. A bipolar mitotic spindle nucleates from multiple centrosome-like structures in the mouse zygote and centrioles are not seen until the blastocyst stage, suggesting that centrioles are inherited through the maternal lineage in mice. We previously identified speriolin as a spermatogenic cell-specific binding partner of Cdc20 that co-localizes with pericentrin in mouse spermatocytes and is present in the centrosome in round spermatids. The nature and localization of speriolin in mouse and human sperm and the fate of speriolin following fertilization in the mouse were determined using immunofluorescence microscopy, immunoelectron microscopy and western blotting. Speriolin surrounds the intact proximal centriole in human sperm, but is localized at the periphery of the disordered distal centriole in mouse sperm. Human speriolin contains an internal 163-amino acid region not present in mouse that may contribute to localization differences. Speriolin is carried into the mouse oocyte during fertilization and remains associated with the decondensing sperm head in zygotes. The speriolin spot appears to undergo duplication or splitting during the first interphase and is detectable in 2-cell embryos. Speriolin is a novel centrosomal protein present in the connecting piece region of mouse and human sperm that is transmitted to the mouse zygote and can be detected throughout the first mitotic division. C1 [Goto, M.; O'Brien, D. A.] Univ N Carolina, Dept Cell & Dev Biol, Sch Med, Chapel Hill, NC 27599 USA. [Goto, M.; Eddy, E. M.] NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP O'Brien, DA (reprint author), Univ N Carolina, Dept Cell & Dev Biol, Sch Med, Chapel Hill, NC 27599 USA. EM dao@med.unc.edu FU NIH, National Institute of Environmental Health Sciences [R01 HD045655]; Eunice Kennedy Shriver/National Institute of Child Health and Human Development FX These studies were supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (E.M.E.) and in part by NIH grant R01 HD045655 (D.A.O.) from the Eunice Kennedy Shriver/National Institute of Child Health and Human Development. NR 69 TC 21 Z9 23 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD AUG PY 2010 VL 25 IS 8 BP 1884 EP 1894 DI 10.1093/humrep/deq138 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 630NP UT WOS:000280280500006 PM 20542897 ER PT J AU Ellis, RD Sagara, I Doumbo, O Wu, YM AF Ellis, Ruth D. Sagara, Issaka Doumbo, Ogobara Wu, Yimin TI Blood stage vaccines for Plasmodium falciparum Current status and the way forward SO HUMAN VACCINES LA English DT Review DE malaria; vaccine; blood stage; falciparum; merozoite ID APICAL MEMBRANE ANTIGEN-1; PAPUA-NEW-GUINEA; MALARIA VACCINE; ANTIBODY-RESPONSES; IMMUNOGENICITY TRIAL; ACQUIRED-IMMUNITY; CLINICAL-TRIAL; SAFETY; CANDIDATE; PROTEIN AB Since the recent call for a shift from malaria control to eradication, the role of asexual blood stage vaccines for falciparum malaria, which are not expected to prevent infection, has become less clear. However, blood stage antigens remain likely to be a critical component of a highly effective malaria vaccine. The inclusion of a blood stage component in a multistage malaria vaccine would not only prevent disease caused by "leaky" pre-erythrocytic immunity, but would also protect against epidemics in newly vulnerable populations. Recent clinical results of blood stage vaccine candidates have shown strain specific and partial efficacy, although no protection against clinical outcomes has been demonstrated in experimental infection or field trials to date. The current status of Plasmodium falciparum blood stage vaccine development is summarized and the potential role of these vaccines in the changed malaria landscape is discussed. Alternative preclinical and clinical development paths will speed iterative development. C1 [Ellis, Ruth D.; Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA. [Sagara, Issaka; Doumbo, Ogobara] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. RP Ellis, RD (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA. EM ellisru@niaid.nih.gov FU NIAID/NIH FX This work was supported by the Intramural Program of NIAID/NIH. Thanks to Louis Miller for his thoughtful review and comments on the manuscript and to Alemush Imeru for her help with manuscript preparation. NR 71 TC 28 Z9 28 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8600 J9 HUM VACCINES JI Hum. Vaccines PD AUG PY 2010 VL 6 IS 8 BP 627 EP 634 DI 10.4161/hv.6.8.11446 PG 8 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 661VC UT WOS:000282756200004 PM 20519960 ER PT J AU Xu, M Wang, F Gildersleeve, JC Achilefu, S AF Xu, Mai Wang, Fan Gildersleeve, Jeffrey C. Achilefu, Samuel TI MAb L9E10 to Blood Group H2 Antigen Binds to Colon Cancer Stem Cells and Inhibits Tumor Cell Migration and Invasion SO HYBRIDOMA LA English DT Article ID MONOCLONAL-ANTIBODIES; HELICOBACTER-PYLORI; EXPRESSION; H-TYPE-2; TYPE-2; CARCINOMAS; TISSUES AB The functions of the precursor H antigen for ABO blood group antigens are still not fully understood, particularly in cancer cells. In this study, we used hybridoma technology and NSY human colon cancer cells as an immunogen to generate a monoclonal antibody designated as MAb L9E10. The binding antigen of MAb L9E10 was identified as blood group (BG) H2 antigen using carbohydrate array and erythrocyte agglutination assays. In immunofluorescence study, we found that BG-H2 was expressed on the surfaces of both colon cancer stem cells and their differentiated progeny. In a functional study, we observed that MAb L9E10 inhibited tumor cell migration and invasion at a concentration of 10 mg/mL in vitro. This result suggests that MAb L9E10 could be used to study cancer biology, particularly cancer stem cell biology. In addition, it is potentially useful for studying gastric diseases caused by Helicobacter pylori bacteria, with attachment to human gastric epithelial cells mediated by blood group antigens Lewis b and H2. Finally, MAb L9E10 is an ideal biological reagent for identifying Bombay blood type in which erythrocytes have no BG-H2 antigen expression. C1 [Xu, Mai; Achilefu, Samuel] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Achilefu, Samuel] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. [Wang, Fan] Peking Univ, Med Isotopes Res Ctr, Beijing 100871, Peoples R China. [Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Achilefu, S (reprint author), Washington Univ, Sch Med, Dept Radiol, 4525 Scott Ave, St Louis, MO 63110 USA. EM xum@mir.wustl.edu; achilefus@mir.wustl.edu RI Achilefu, Samuel/A-3681-2012; Gildersleeve, Jeffrey/N-3392-2014; OI Achilefu, Samuel/0000-0002-3133-6717 FU NIH; NCI; Elsa U. Pardee Foundation FX This work was supported in part by Intramural Research Program of the NIH, NCI, and the Elsa U. Pardee Foundation. We are grateful to Ms. Gail Sudlow for assistance in the manuscript preparation. NR 32 TC 4 Z9 4 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1554-0014 J9 HYBRIDOMA JI Hybridoma PD AUG PY 2010 VL 29 IS 4 BP 355 EP 359 DI 10.1089/hyb.2010.0020 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 639QX UT WOS:000280990500013 PM 20715995 ER PT J AU Huang, H Tang, QZ Wang, AB Chen, MY Yan, L Liu, C Jiang, H Yang, QL Bian, ZY Bai, X Zhu, LH Wang, L Li, HL AF Huang, He Tang, Qi-Zhu Wang, Ai-Bing Chen, Manyin Yan, Ling Liu, Chen Jiang, Hong Yang, Qinglin Bian, Zhou-Yan Bai, Xue Zhu, Li-Hua Wang, Lang Li, Hongliang TI Tumor Suppressor A20 Protects Against Cardiac Hypertrophy and Fibrosis by Blocking Transforming Growth Factor-beta-Activated Kinase 1-Dependent Signaling SO HYPERTENSION LA English DT Article DE A20; cardiac remodeling; inflammation; apoptosis ID UBIQUITIN-EDITING ENZYME; HEART-FAILURE; TRANSDUCTION PATHWAYS; PRESSURE-OVERLOAD; TRANSGENIC MICE; ANGIOTENSIN-II; KAPPA-B; APOPTOSIS; TAK1; OVEREXPRESSION AB A20 or tumor necrosis factor-induced protein 3 is a negative regulator of nuclear factor kappa B signaling. A20 has been shown previously to attenuate cardiac hypertrophy in vitro and postmyocardial infarction remodeling in vivo. In the present study, we tested the hypothesis that overexpression of A20 in the murine heart would protect against cardiac hypertrophy in vivo. The effects of constitutive human A20 expression on cardiac hypertrophy were investigated using in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding in A20 transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by echocardiography, as well as by pathological and molecular analyses of heart samples. Constitutive overexpression of human A20 in the murine heart attenuated the hypertrophic response and markedly reduced inflammation, apoptosis, and fibrosis. Cardiac function was also preserved in hearts with increased A20 levels in response to hypertrophic stimuli. Western blot experiments further showed A20 expression markedly blocked transforming growth factor-beta-activated kinase 1-dependent c-Jun N-terminal kinase/p38 signaling cascade but with no difference in either extracellular signal-regulated kinase 1/2 or AKT activation in vivo and in vitro. In cultured neonatal rat cardiac myocytes, [3H]proline incorporation and Western blot assays revealed that A20 expression suppressed transforming growth factor-beta-induced collagen synthesis and transforming growth factor-beta-activated kinase 1-dependent Smad 2/3/4 activation. In conclusion, A20 improves cardiac functions and inhibits cardiac hypertrophy, inflammation, apoptosis, and fibrosis by blocking transforming growth factor-beta-activated kinase 1-dependent signaling. (Hypertension. 2010;56:232-239.) C1 [Huang, He; Tang, Qi-Zhu; Yan, Ling; Jiang, Hong; Bian, Zhou-Yan; Bai, Xue; Zhu, Li-Hua; Wang, Lang; Li, Hongliang] Wuhan Univ, Dept Cardiol, Renmin Hosp, Wuhan 430060, Peoples R China. [Huang, He; Tang, Qi-Zhu; Yan, Ling; Jiang, Hong; Bian, Zhou-Yan; Bai, Xue; Zhu, Li-Hua; Wang, Lang; Li, Hongliang] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430072, Peoples R China. [Wang, Ai-Bing] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Chen, Manyin] Guangzhou Med Coll, Affiliated Hosp 1, Dept Cardiothorac Surg, Guangzhou, Guangdong, Peoples R China. [Liu, Chen] Sun Yat Sen Univ, Dept Cardiol, Affiliated Hosp 1, Guangzhou 510275, Guangdong, Peoples R China. [Yang, Qinglin] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. RP Li, HL (reprint author), Wuhan Univ, Dept Cardiol, Renmin Hosp, JieFang Rd 238, Wuhan 430060, Peoples R China. EM lihl@whu.edu.cn FU National Natural Science Foundation of China [30900524, 30972954, 30770733]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry [2006-331] FX This research was supported by the National Natural Science Foundation of China (30900524, 30972954, and 30770733) and by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (2006-331). NR 36 TC 39 Z9 41 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 2010 VL 56 IS 2 BP 232 EP U111 DI 10.1161/HYPERTENSIONAHA.110.149963 PG 27 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 625FM UT WOS:000279880200013 PM 20585109 ER PT J AU Wollny, G Ledesma-Carbayo, MJ Kellman, P Santos, A AF Wollny, Gert Ledesma-Carbayo, Maria J. Kellman, Peter Santos, Andres TI Exploiting Quasiperiodicity in Motion Correction of Free-Breathing Myocardial Perfusion MRI SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Heart; image registration; myocardial perfusion ID NONRIGID REGISTRATION; IMAGE REGISTRATION; ELASTIC REGISTRATION; MUTUAL INFORMATION; QUANTIFICATION; DEFORMATION AB Free-breathing image acquisition is desirable in first-pass gadolinium-enhanced magnetic resonance imaging (MRI), but the breathing movements hinder the direct automatic analysis of the myocardial perfusion and qualitative readout by visual tracking. Nonrigid registration can be used to compensate for these movements but needs to deal with local contrast and intensity changes with time. We propose an automatic registration scheme that exploits the quasiperiodicity of free breathing to decouple movement from intensity change. First, we identify and register a subset of the images corresponding to the same phase of the breathing cycle. This registration step deals with small differences caused by movement but maintains the full range of intensity change. The remaining images are then registered to synthetic references that are created as a linear combination of images belonging to the already registered subset. Because of the quasiperiodic respiratory movement, the subset images are distributed evenly over time and, therefore, the synthetic references exhibit intensities similar to their corresponding unregistered images. Thus, this second registration step needs to account only for the movement. Validation experiments were performed on data obtained from six patients, three slices per patient, and the automatically obtained perfusion profiles were compared with profiles obtained by manually segmenting the myocardium. The results show that our automatic approach is well suited to compensate for the free-breathing movement and that it achieves a significant improvement in the average Pearson correlation coefficient between manually and automatically obtained perfusion profiles before (0.87 +/- 0.18) and after (0.96 +/- 0.09) registration. C1 [Wollny, Gert] Univ Politech, ETSI Telecomunicac, Grp Biomed Imaging Technol, Dept Elect Engn, Madrid 28040, Spain. [Wollny, Gert; Ledesma-Carbayo, Maria J.; Santos, Andres] Ciber BBN, Zaragoza 50018, Spain. [Ledesma-Carbayo, Maria J.; Santos, Andres] Univ Politecn Madrid, Dept Elect Engn, ETSIT, Grp Biomed Imaging Technol, E-28040 Madrid, Spain. [Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Wollny, G (reprint author), Univ Politech, ETSI Telecomunicac, Grp Biomed Imaging Technol, Dept Elect Engn, Madrid 28040, Spain. EM gert@die.upm.es; mledesma@die.upm.es; andres@die.upm.es RI Ledesma-Carbayo, Maria /D-5529-2009; Santos, Andres/C-4012-2009 OI Ledesma-Carbayo, Maria /0000-0001-6846-3923; Wollny, Gert/0000-0002-3611-0100; Santos, Andres/0000-0001-7423-9135 FU Spain's Ministry of Science and Innovation [TIN2007-68048-C02-01, PS-010000-2008-1]; Comunidad de Madrid; European Social Fund; National Institutes of Health, National Heart, Lung and Blood Institute FX This work was supported in part by Spain's Ministry of Science and Innovation under research projects TIN2007-68048-C02-01, and SINBAD (PS-010000-2008-1), and by the project ARTEMIS Comunidad de Madrid, and by the European Social Fund.; Experimental data were provided with the support of the Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute. NR 29 TC 14 Z9 14 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD AUG PY 2010 VL 29 IS 8 BP 1516 EP 1527 DI 10.1109/TMI.2010.2049270 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 694XS UT WOS:000285335800007 PM 20442043 ER PT J AU Liu, XF Prince, JL AF Liu, Xiaofeng Prince, Jerry L. TI Shortest Path Refinement for Motion Estimation From Tagged MR Images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Dijkstra's algorithm; harmonic phase (HARP); magnetic resonance (MR) tagging; motion tracking; shortest path ID MYOCARDIAL DEFORMATIONS; SPATIAL MODULATION; STRAIN MAPS; TRACKING; RECONSTRUCTION; MODEL; MAGNETIZATION; DENSE AB Magnetic resonance tagging makes it possible to measure the motion of tissues such as muscles in the heart and tongue. The harmonic phase (HARP) method largely automates the process of tracking points within tagged MR images, permitting many motion properties to be computed. However, HARP tracking can yield erroneous motion estimates due to 1) large deformations between image frames, 2) through-plane motion, and 3) tissue boundaries. Methods that incorporate the spatial continuity of motion-so-called refinement or flood-filling methods-have previously been reported to reduce tracking errors. This paper presents a new refinement method based on shortest path computations. The method uses a graph representation of the image and seeks an optimal tracking order from a specified seed to each point in the image by solving a single source shortest path problem. This minimizes the potential errors for those path dependent solutions that are found in other refinement methods. In addition to this, tracking in the presence of through-plane motion is improved by introducing synthetic tags at the reference time (when the tissue is not deformed). Experimental results on both tongue and cardiac images show that the proposed method can track the whole tissue more robustly and is also computationally efficient. C1 [Liu, Xiaofeng] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. [Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Liu, XF (reprint author), NCI, Ctr Clin, Bethesda, MD 20892 USA. EM xiaofeng.liu@gmail.edu; prince@jhu.edu RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 FU NIH/NHLBI [R01HL047405] FX This work was supported by the NIH/NHLBI under Grant R01HL047405. NR 34 TC 23 Z9 23 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD AUG PY 2010 VL 29 IS 8 BP 1560 EP 1572 DI 10.1109/TMI.2010.2045509 PG 13 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 694XS UT WOS:000285335800010 PM 20304720 ER PT J AU Kim, YC Kim, KK Shevach, EM AF Kim, Yong Chan Kim, Kee Kwang Shevach, Ethan M. TI Simvastatin induces Foxp3+T regulatory cells by modulation of transforming growth factor-beta signal transduction SO IMMUNOLOGY LA English DT Article DE Foxp3; geranylgeranylation; simvastatin; Smad6; Smad7; transforming growth factor-beta; T regulatory cells ID TRANSCRIPTION FACTOR FOXP3; VERSUS-HOST-DISEASE; T-CELLS; GENE-EXPRESSION; DNA METHYLATION; CUTTING EDGE; INDUCTION; AUTOIMMUNITY; ATORVASTATIN; RECEPTOR AB P>Statins are widely used drugs for the treatment of hypercholesterolaemia. A number of recent studies have suggested that statins also have pleiotropic effects on immune responses and statins have proven to be effective in the treatment of autoimmune diseases in animal models. Foxp3+ T regulatory cells are a unique subset of CD4+ T cells that mediate immunosuppression. Foxp3+ T cells develop in the thymus, but can also be induced in peripheral sites in the presence of transforming growth factor-beta (TGF-beta). We demonstrate here that simvastatin blockade of the mevalonate pathway can mediate induction of mouse Foxp3+ T cells and that simvastatin can synergize with low levels of TGF-beta to induce Foxp3+ T cells. The effects of simvastatin are secondary to a blockade of protein geranylgeranylation, are mediated at late time-points after T-cell activation, and are associated with demethylation of the Foxp3 promoter. One major effect of simvastatin was inhibition of the induction of Smad6 and Smad7, inhibitory Smads that inhibit TGF-beta signalling. Our results suggest that one mechanism responsible for the immunosuppressive effects of statins is the ability to promote the generation of Foxp3+ T regulatory cells. C1 [Kim, Yong Chan; Shevach, Ethan M.] NIAID, Immunol Lab, Cellular Immunol Sect, Bethesda, MD 20892 USA. [Kim, Kee Kwang] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, Cellular Immunol Sect, Bldg 10, Bethesda, MD 20892 USA. EM Eshevach@niaid.nih.gov RI Kim, Kee/F-8784-2011 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (Bethesda, MD) FX This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (Bethesda, MD). NR 22 TC 43 Z9 46 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD AUG PY 2010 VL 130 IS 4 BP 484 EP 493 DI 10.1111/j.1365-2567.2010.03269.x PG 10 WC Immunology SC Immunology GA 623JM UT WOS:000279735800004 PM 20408897 ER PT J AU Browne, SK Holland, SM AF Browne, Sarah K. Holland, Steven M. TI Anti-cytokine autoantibodies explain some chronic mucocutaneous candidiasis SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Editorial Material ID HYPER-IGE SYNDROME; PULMONARY ALVEOLAR PROTEINOSIS; RED-CELL APLASIA; AUTOIMMUNE-DISEASE; FUNGAL-INFECTIONS; IFN-GAMMA; MUTATIONS; RITUXIMAB; STAT3; ERYTHROPOIETIN C1 [Browne, Sarah K.; Holland, Steven M.] NIAID, Lab Clincial Infect Dis, NIH, Bethesda, MD 20892 USA. RP Browne, SK (reprint author), NIAID, Lab Clincial Infect Dis, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU Intramural NIH HHS [Z01 AI000646-16] NR 24 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD AUG PY 2010 VL 88 IS 6 BP 614 EP 615 DI 10.1038/icb.2010.72 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 637PN UT WOS:000280830700002 PM 20548324 ER PT J AU Howe, D Shannon, JG Winfree, S Dorward, DW Heinzen, RA AF Howe, Dale Shannon, Jeffrey G. Winfree, Seth Dorward, David W. Heinzen, Robert A. TI Coxiella burnetii Phase I and II Variants Replicate with Similar Kinetics in Degradative Phagolysosome-Like Compartments of Human Macrophages SO INFECTION AND IMMUNITY LA English DT Article ID Q-FEVER; PHAGOSOME MATURATION; PERITONEAL-MACROPHAGES; CHLAMYDIA-TRACHOMATIS; LYSOSOMAL RESPONSE; CELL-LINES; HOST-CELL; LIPOPOLYSACCHARIDE; INFECTION; IMMUNOFLUORESCENCE AB Coxiella burnetii infects mononuclear phagocytes, where it directs biogenesis of a vacuolar niche termed the parasitophorous vacuole (PV). Owing to its lumenal pH (similar to 5) and fusion with endolysosomal vesicles, the PV is considered phagolysosome-like. However, the degradative properties of the mature PV are unknown, and there are conflicting reports on the maturation state and growth permissiveness of PV harboring virulent phase I or avirulent phase II C. burnetii variants in human mononuclear phagocytes. Here, we employed infection of primary human monocyte-derived macrophages (HMDMs) and THP-1 cells as host cells to directly compare the PV maturation kinetics and pathogen growth in cells infected with the Nine Mile phase I variant (NMI) or phase II variant (NMII) of C. burnetii. In both cell types, phase variants replicated with similar kinetics, achieving roughly 2 to 3 log units of growth before they reached stationary phase. HMDMs infected by either phase variant secreted similar amounts of the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha. In infected THP-1 cells, equal percentages of NMI and NMII PVs decorate with the early endosomal marker Rab5, the late endosomal/lysosomal markers Rab7 and CD63, and the lysosomal marker cathepsin D at early (8 h) and late (72 h) time points postinfection (p.i.). Mature PVs (2 to 4 days p.i.) harboring NMI or NMII contained proteolytically active cathepsins and quickly degraded Escherichia coli. These data suggest that C. burnetii does not actively inhibit phagolysosome function as a survival mechanism. Instead, NMI and NMII resist degradation to replicate in indistinguishable digestive PVs that fully mature through the endolysosomal pathway. C1 [Howe, Dale; Shannon, Jeffrey G.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Shannon, Jeffrey G.] NIAID, Salmonella Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Dorward, David W.] NIAID, Intracellular Parasites Lab, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Dorward, David W.] NIAID, Microscopy Unit, Res Technol Sect, Rocky Mt Labs,Res Technol Branch,NIH, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 56 TC 65 Z9 66 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2010 VL 78 IS 8 BP 3465 EP 3474 DI 10.1128/IAI.00406-10 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 626TQ UT WOS:000279990400015 PM 20515926 ER PT J AU Chia, VM Li, Y Quraishi, SM Graubard, BI Figueroa, JD Weber, JP Chanock, SJ Rubertone, MV Erickson, RL McGlynn, KA AF Chia, V. M. Li, Y. Quraishi, S. M. Graubard, B. I. Figueroa, J. D. Weber, J-P. Chanock, S. J. Rubertone, M. V. Erickson, R. L. McGlynn, K. A. TI Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes SO INTERNATIONAL JOURNAL OF ANDROLOGY LA English DT Article DE hormone-metabolizing genes; persistent organochlorine pesticides; polychlorinated biphenyls; testicular germ cell tumours ID BREAST-CANCER RISK; CHLORINATED-HYDROCARBON LEVELS; POLYCHLORINATED-BIPHENYLS; CYTOCHROME-P450 1A1; HUMAN-SERUM; POLYMORPHISMS; HEXACHLOROBENZENE; HEALTH; TRENDS; BLOOD AB P>It has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p'-dichlorodiphenyldichloroethylene, chlordane-related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01-3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p-interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45-55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions < 0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values > 0.2, however, caution is advisable when interpreting the findings of this study. C1 [McGlynn, K. A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Weber, J-P.] Inst Natl Sante Publ Quebec, Toxicol Ctr, Quebec City, PQ, Canada. [Rubertone, M. V.] USA, Ctr Hlth Promot & Prevent Med, Washington, DC 20310 USA. [Erickson, R. L.] Walter Reed Army Inst Res, Silver Spring, MD USA. RP McGlynn, KA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, EPS Suite 550,6120 Execut Blvd, Rockville, MD 20892 USA. EM mcglynnk@mail.nih.gov FU NIH, National Cancer Institute FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 29 TC 19 Z9 19 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-6263 J9 INT J ANDROL JI Int. J. Androl. PD AUG PY 2010 VL 33 IS 4 BP 588 EP 596 DI 10.1111/j.1365-2605.2009.00975.x PG 9 WC Andrology SC Endocrinology & Metabolism GA 622MZ UT WOS:000279669200004 PM 19627379 ER PT J AU Caccavale, LJ Farhat, T Iannotti, RJ AF Caccavale, Laura J. Farhat, Tilda Iannotti, Ronald J. TI ADOLESCENT PEER SUPPORT MODERATES THE RELATIONSHIP BETWEEN WEIGHT STATUS AND BODY IMAGE SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Caccavale, Laura J.; Farhat, Tilda; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Washington, DC 20008 USA. EM caccavalel@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 42 EP 43 PG 2 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500093 ER PT J AU Farhat, T Iannotti, RJ Caccavale, LJ AF Farhat, Tilda Iannotti, Ronald J. Caccavale, Laura J. TI ADOLESCENT OVERWEIGHT/OBESITY AND PHYSICAL ACTIVITY: MEDIATION BY BODY IMAGE SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Farhat, Tilda; Iannotti, Ronald J.; Caccavale, Laura J.] NICHD, NIH, Bethesda, MD USA. EM farhatti@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 43 EP 43 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500095 ER PT J AU O'Neill, S Lipkus, IM Sanderson, SC Shepperd, J Docherty, S McBride, CM AF O'Neill, Suzanne Lipkus, Isaac M. Sanderson, Saskia C. Shepperd, James Docherty, Sharron McBride, Colleen M. TI RELIABILITY AND PREDICTIVE VALIDITY OF A MEASURE OF MOTIVATIONS FOR GENETIC TESTING FOR COMMON DISEASE RISK SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [O'Neill, Suzanne] Georgetown Univ, Washington, DC 20007 USA. [Lipkus, Isaac M.; Docherty, Sharron] Duke Univ, Sch Nursing, Durham, NC USA. [Sanderson, Saskia C.] Mt Sinai Sch Med, New York, NY USA. [Shepperd, James] Univ Florida, Gainesville, FL USA. [McBride, Colleen M.] NHGRI, Soc & Behav Res Branch, Bethesda, MD 20892 USA. EM sco4@georgetown.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 63 EP 63 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500143 ER PT J AU Biesecker, BB Wade, C Shiloh, S Woolford, S Roberts, JS Alford, S Marteau, TM AF Biesecker, Barbara B. Wade, Christopher Shiloh, Shoshana Woolford, Samuel Roberts, J. Scott Alford, Sharon Marteau, Theresa M. TI MODELING DECISIONS TO UNDERGO GENETIC TESTING FOR SUSCEPTIBILITY TO COMMON HEALTH CONDITIONS: AN ANCILLARY STUDY OF THE MULTIPLEX INITIATIVE SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Biesecker, Barbara B.; Wade, Christopher] NHGRI, NIH, Bethesda, MD 20892 USA. [Shiloh, Shoshana] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. [Woolford, Samuel] Bentley Univ, Dept Math Sci, Bentley, MA USA. [Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Alford, Sharon] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. [Marteau, Theresa M.] Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England. EM barbarab@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 66 EP 67 PG 2 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500152 ER PT J AU Ferrer, RA Portnoy, DB Klein, WM AF Ferrer, Rebecca A. Portnoy, David B. Klein, William M. TI INCREASED COGNITIVE AND AFFECTIVE RISK PERCEPTIONS ARE RELATED TO LOWER FRUIT/VEGETABLE CONSUMPTION AND PHYSICAL ACTIVITY SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Ferrer, Rebecca A.; Portnoy, David B.; Klein, William M.] NCI, BRP DCCPS, Gaithersburg, MD 20878 USA. EM ferrerra@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 95 EP 95 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500221 ER PT J AU Cameron, LD Brown, P Sherman, K Marteau, T Klein, W AF Cameron, Linda D. Brown, Paul Sherman, Kerry Marteau, Theresa Klein, William TI PRESENTING COHERENT LINKS BETWEEN RISKS AND ACTION: IMPACT ON BELIEFS MOTIVATING BEHAVIOR AND EXPECTED VALUE OF GENETIC TESTS SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cameron, Linda D.; Brown, Paul] Univ Auckland, Auckland 1042, New Zealand. [Sherman, Kerry] Macquarie Univ, N Ryde, NSW 2109, Australia. [Marteau, Theresa] Kings Coll London, London WC2R 2LS, England. [Klein, William] NCI, NIH, Bethesda, MD 20892 USA. EM l.cameron@auckland.ac.nz NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 118 EP 119 PG 2 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500274 ER PT J AU Bates, B Hoyt, M Manne, S Kaufmann, PG AF Bates, Betsy Hoyt, Michael Manne, Sharon Kaufmann, Peter G. TI IMPACT OF MALE NORMS ON PROSTATE CANCER DIAGNOSIS AND RECOVERY SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bates, Betsy] Antioch Univ, Santa Barbara, CA USA. [Hoyt, Michael] Univ Calif Merced, Merced, CA USA. [Manne, Sharon] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Kaufmann, Peter G.] NHLBI, Clin Applicat & Prevent Branch Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 119 EP 120 PG 2 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500276 ER PT J AU Cameron, LD Humphris, G Hollands, G Persky, S Williams, B AF Cameron, Linda D. Humphris, Gerry Hollands, Gareth Persky, Susan Williams, Brian TI HARNESSING IMAGERY PROCESSES TO MOTIVATE HEALTH BEHAVIORS SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Cameron, Linda D.] Univ Auckland, Auckland 1042, New Zealand. [Humphris, Gerry] Univ St Andrews, St Andrews, Fife, Scotland. [Hollands, Gareth] Kings Coll London, London WC2R 2LS, England. [Persky, Susan] NHGRI, Bethesda, MD 20892 USA. [Williams, Brian] Univ Dundee, Dundee, Scotland. EM l.cameron@auckland.ac.nz RI Williams, Brian/G-5736-2012 OI Williams, Brian/0000-0003-0000-4354 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 203 EP 203 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500468 ER PT J AU Persky, S AF Persky, Susan TI HEIGHTENING THE IMPACT OF IMAGERY THROUGH USE OF IMMERSIVE VIRTUAL ENVIRONMENTS SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Persky, Susan] Natl Human Genome Res Inst, Social & Behav Res Branch, Bethesda, MD 20015 USA. EM perskys@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 205 EP 205 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500471 ER PT J AU Holstein, BE Soc, MS Hansen, EH Iannotti, R Andersen, A Tobi, H AF Holstein, Bjorn E. Soc, Mag Scient Hansen, Ebba H. Iannotti, Ron Andersen, Anette Tobi, Hilde TI ADOLESCENTS' MEDICINE USE: A RESPONSE TO STRAIN? SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Holstein, Bjorn E.; Soc, Mag Scient; Andersen, Anette] Univ So Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark. [Hansen, Ebba H.] Univ Copenhagen, Dept Pharmacol & Pharmacotherapy, Copenhagen, Denmark. [Iannotti, Ron] NICHHD, Washington, DC USA. [Tobi, Hilde] Univ Wageningen & Res Ctr, Wageningen, Netherlands. EM bho@niph.dk RI Tobi, Hilde/A-1512-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 209 EP 209 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500483 ER PT J AU Iannotti, RJ Levin, K AF Iannotti, Ronald J. Levin, Kate TI ADOLESCENT MENTAL HEALTH AND MEDICINE USE IN SEVEN COUNTRIES SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Levin, Kate] Univ Edinburgh, Edinburgh, Midlothian, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 209 EP 210 PG 2 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500484 ER PT J AU Fikkan, JL Baime, M Sanders, L Greeson, J Jennifer, W Wakefield, J Ladden, L Gresko, J Wai, M Stoney, C Wolever, R AF Fikkan, Janna L. Baime, Michael Sanders, Linda Greeson, Jeffrey Jennifer, Webb Wakefield, Jessica Ladden, Lawrence Gresko, Jeanne Wai, Mara Stoney, Catherine Wolever, Ruth TI MINDFULNESS IN THE MAINTENANCE OF WEIGHT LOSS: A RANDOMIZED CONTROLLED TRIAL OF THE EMPOWER PROGRAM SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Fikkan, Janna L.; Sanders, Linda; Greeson, Jeffrey; Wakefield, Jessica; Gresko, Jeanne; Wolever, Ruth] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Baime, Michael; Ladden, Lawrence; Wai, Mara] Univ Penn, Penn Program Mindfulness, Philadelphia, PA 19104 USA. [Stoney, Catherine] Natl Ctr Complementary & Alternat Med, NIH, Washington, DC USA. [Jennifer, Webb] Univ N Carolina, Dept Psychol, Charlotte, NC 28223 USA. EM Janna.Fikkan@duke.edu RI Greeson, Jeffrey/A-9272-2009 OI Greeson, Jeffrey/0000-0003-4871-1197 NR 0 TC 0 Z9 0 U1 5 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 215 EP 215 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500497 ER PT J AU Stoney, CM Davidson, KW AF Stoney, Catherine M. Davidson, Karina W. TI COMPARATIVE EFFECTIVENESS RESEARCH IN CARDIOVASCULAR BEHAVIORAL MEDICINE SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stoney, Catherine M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Davidson, Karina W.] Columbia Univ, New York, NY USA. EM stoneyc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 270 EP 270 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500616 ER PT J AU de Heer, H Morera, O Pederson, R AF de Heer, Hendrik Morera, Osvaldo Pederson, Rockie TI PROJECT LEAN: AN AFTER-SCHOOL HEALTH EDUCATION AND PHYSICAL ACTIVITY PROGRAM FOR ELEMENTARY SCHOOL CHILDREN IN EL PASO, TEXAS SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [de Heer, Hendrik] Natl Human Genome Res Inst, Social & Behav Res Branch, Silver Spring, MD 20910 USA. [Pederson, Rockie] Univ Texas El Paso, Coll Hlth Sci, El Paso, TX 79968 USA. EM dirk.deheer@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 274 EP 274 PG 1 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500625 ER PT J AU Ma, Y Zhang, FJ Zhao, Y Zang, CP Zhao, DC Dou, ZH Yu, L Fang, H Zhu, TY Chen, RY AF Ma, Ye Zhang, Fujie Zhao, Yan Zang, Chunpeng Zhao, Decai Dou, Zhihui Yu, Lan Fang, Hua Zhu, Timothy Y. Chen, Ray Y. TI Cohort Profile: The Chinese national free antiretroviral treatment cohort SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID CHALLENGES; PROGRAM; THERAPY C1 [Ma, Ye; Zhang, Fujie; Zhao, Yan; Zang, Chunpeng; Zhao, Decai; Dou, Zhihui; Yu, Lan; Fang, Hua; Zhu, Timothy Y.] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Beijing 100050, Peoples R China. [Zhang, Fujie] Beijing Ditan Hosp, Beijing, Peoples R China. [Chen, Ray Y.] US Embassy, Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Beijing, Peoples R China. RP Zhang, FJ (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, 27 Nanwei Rd, Beijing 100050, Peoples R China. EM treatment@chinaaids.cn OI Chen, Ray/0000-0001-6344-1442 FU FIC NIH HHS [U2R TW006918, U2R TW006918-04S1] NR 11 TC 32 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2010 VL 39 IS 4 BP 973 EP 979 DI 10.1093/ije/dyp233 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 646IH UT WOS:000281532300011 PM 19556327 ER PT J AU Gaudet, MM Olshan, AF Chuang, SC Berthiller, J Zhang, ZF Lissowska, J Zaridze, D Winn, DM Wei, QY Talamini, R Szeszenia-Dabrowska, N Sturgis, EM Schwartz, SM Rudnai, P Eluf-Neto, J Muscat, J Morgenstern, H Menezes, A Matos, E Bucur, A Levi, F Lazarus, P La Vecchia, C Koifman, S Kelsey, K Herrero, R Hayes, RB Franceschi, S Wunsch, V Fernandez, L Fabianova, E Daudt, AW Dal Maso, L Curado, MP Chen, C Castellsague, X Benhamou, S Boffetta, P Brennan, P Hashibe, M AF Gaudet, Mia M. Olshan, Andrew F. Chuang, Shu-Chun Berthiller, Julien Zhang, Zuo-Feng Lissowska, Jolanta Zaridze, David Winn, Deborah M. Wei, Qingyi Talamini, Renato Szeszenia-Dabrowska, Neolilia Sturgis, Erich M. Schwartz, Stephen M. Rudnai, Peter Eluf-Neto, Jose Muscat, Joshua Morgenstern, Hal Menezes, Ana Matos, Elena Bucur, Alexandru Levi, Fabio Lazarus, Philip La Vecchia, Carlo Koifman, Sergio Kelsey, Karl Herrero, Rolando Hayes, Richard B. Franceschi, Silva Wunsch-Filho, Victor Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W. Dal Maso, Luigino Curado, Maria Paula Chen, Chu Castellsague, Xavier Benhamou, Simone Boffetta, Paolo Brennan, Paul Hashibe, Mia TI Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BMI; head and neck cancer; smoking ID OXIDATIVE DNA-DAMAGE; UPPER AERODIGESTIVE TRACT; SQUAMOUS-CELL CARCINOMAS; LUNG-CANCER; PHARYNGEAL CANCER; ORAL-CANCER; CIGARETTE-SMOKING; ALCOHOL-DRINKING; TOBACCO USE; LEANNESS AB Methods We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < 18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI > 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >= 30 kg/m(2) (0.43, 0.33-0.57), compared with BMI > 18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < 18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies. C1 [Hashibe, Mia] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84108 USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. [Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Chuang, Shu-Chun; Franceschi, Silva; Curado, Maria Paula; Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Chuang, Shu-Chun] Univ London Imperial Coll Sci Technol & Med, London, England. [Berthiller, Julien] Hosp Civils Lyon, Lyon, France. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. [Winn, Deborah M.; Sturgis, Erich M.; Hayes, Richard B.] NCI, Bethesda, MD 20892 USA. [Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Talamini, Renato; Dal Maso, Luigino] Aviano Canc Ctr, I-33081 Aviano, Italy. [Szeszenia-Dabrowska, Neolilia] Inst Occupat Med, Lodz, Poland. [Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary. [Eluf-Neto, Jose] Univ Sao Paulo, Sao Paulo, Brazil. [Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI USA. [Menezes, Ana; Wunsch-Filho, Victor] Univ Fed Pelotas, Pelotas, Brazil. [Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, RA-1053 Buenos Aires, DF, Argentina. [Bucur, Alexandru] Univ Med & Pharm Carol Davila, Bucharest, Romania. [Levi, Fabio] Inst Univ Med Sociale & Prevent, CH-1005 Lausanne, Switzerland. [La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy. [Koifman, Sergio] Escola Nacl Saude Publica, Rio De Janeiro, Brazil. [Kelsey, Karl] Brown Univ, Bio Med Ctr Environm & Technol, Providence, RI 02912 USA. [Herrero, Rolando] Inst Invest Epidemiol, San Jose, Costa Rica. [Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba. [Fabianova, Eleonora] Specialized State Hlth Inst, Banska Bystrica, Slovakia. [Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Curado, Maria Paula] Hosp Araujo Jorge, Goiania, Go, Brazil. [Castellsague, Xavier] CIBER ESP, IDIBELL, Inst Catala Oncol, Lhospitalet De Llobregat, Spain. [Benhamou, Simone] INSERM, U794, Paris, France. [Benhamou, Simone] CNRS, FRE2939, Villejuif, France. RP Hashibe, M (reprint author), Univ Utah, Sch Med, Dept Family & Prevent Med, 375 Chipeta Way,Suite A, Salt Lake City, UT 84108 USA. EM mia.hashibe@utah.edu RI Menezes, Ana/G-7266-2012; Wunsch Filho, Victor/C-4475-2012; Inca, Inct/K-2204-2013; Zaridze, David/K-5605-2013; Szeszenia-Dabrowska, Neonila/F-7190-2010; Castellsague Pique, Xavier/N-5795-2014; Benhamou, Simone/K-6554-2015; Curado, Maria Paula/M-6200-2013; Epidemiologicas, Centro de pesquisas /D-4561-2013; Chuang, Shu-Chun/N-3358-2013; Eluf-Neto, Jose/B-2522-2009 OI Lissowska, Jolanta/0000-0003-2695-5799; dal maso, luigino/0000-0001-6163-200X; La Vecchia, Carlo/0000-0003-1441-897X; Hayes, Richard/0000-0002-0918-661X; Castellsague Pique, Xavier/0000-0002-0802-3595; Curado, Maria Paula/0000-0001-8172-2483; Eluf-Neto, Jose/0000-0001-7504-2115 FU US National Institutes of Health (NIH); National Cancer Institute (NCI) [R03CA113157]; Italian Association for Research on Cancer (AIRC); Swiss League against Cancer [KFS1069-09-2000]; Fribourg League against Cancer [FOR381.88]; Swiss Cancer Research [AKT 617]; Gustave-Roussy Institute [88D28]; Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]; World Cancer Research Fund; European Commission [IC15-CT98-0332, IC18-CT97-0222]; National Institutes of Health (NIH) US [P01CA068384, K07CA104231, R01CA048896, R01DE012609, R01CA078609, R01CA100679, NIDCR R01DE11979, NIDCR R01DE13110, NIH FIRCA TW01500, R01CA61188, R01DE13158, P50CA90388, R01DA11386, R03CA77954, T32CA09142, U01CA96134, R21ES011667, R01ES11740, R01CA100264]; National Institute of Environmental Health Sciences [P30ES010126]; National Institutes of Health (NCI) US; Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina; IMIM (Barcelona); Fundacao de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP) [01/01768-2]; Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013]; International Union Against Cancer (UICC); YamagiwaYoshida Memorial International Cancer Study Grant; Italian League Against Cancer; Italian Ministry of Research; UCLA Jonsson Comprehensive Cancer Centre; NIDCR FX Grant from the US National Institutes of Health (NIH), National Cancer Institute (NCI) [R03CA113157]. The individual studies were funded by the following grants: Milan study: Italian Association for Research on Cancer (AIRC); Aviano and Italy multicentre studies: Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research; France study: Swiss League against Cancer [KFS1069-09-2000], Fribourg League against Cancer [FOR381.88], Swiss Cancer Research [AKT 617] and Gustave-Roussy Institute [88D28]; Swiss study: Swiss League against Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]; Central Europe study: World Cancer Research Fund and the European Commission's INCO- COPERNICUS Programme [Contract No. IC15-CT98-0332]; New York study: National Institutes of Health (NIH) US [P01CA068384 K07CA104231]; Seattle study: National Institutes of Health (NIH) US [R01CA048896, R01DE012609]; Boston study: National Institutes of Health (NIH) US [R01CA078609, R01CA100679]; Iowa study: National Institutes of Health (NIH) US [NIDCR R01DE11979, NIDCR R01DE13110, NIH FIRCA TW01500] and Veterans Affairs Merit Review Funds; North Carolina study: National Institutes of Health (NIH) US [R01CA61188], and in part by a grant from the National Institute of Environmental Health Sciences [P30ES010126]; Tampa study: National Institutes of Health (NIH) US [P01CA068384, K07CA104231, R01DE13158]; Los Angeles study: National Institute of Health (NIH) US [P50CA90388, R01DA11386, R03CA77954, T32CA09142, U01CA96134, R21ES011667] and the Alper Research Programme for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Centre; Houston study: National Institutes of Health (NIH) US [R01ES11740, R01CA100264]; Puerto Rico study: jointly funded by National Institutes of Health (NCI) US and NIDCR intramural programmes; Latin America study: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundacao de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2], and European Commission [IC18-CT97-0222]; IARC Multicentre study: Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013], International Union Against Cancer (UICC), and YamagiwaYoshida Memorial International Cancer Study Grant. NR 56 TC 38 Z9 40 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2010 VL 39 IS 4 BP 1091 EP 1102 DI 10.1093/ije/dyp380 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 646IH UT WOS:000281532300028 PM 20123951 ER PT J AU Kumar, M Kumar, A Nagpal, R Mohania, D Behare, P Verma, V Kumar, P Poddar, D Aggarwal, PK Henry, CJK Jain, S Yadav, H AF Kumar, Manoj Kumar, Ashok Nagpal, Ravinder Mohania, Dheeraj Behare, Pradip Verma, Vinod Kumar, Pramod Poddar, Dev Aggarwal, P. K. Henry, C. J. K. Jain, Shalini Yadav, Hariom TI Cancer-preventing attributes of probiotics: an update SO INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION LA English DT Article DE Probiotics; cancer; prebiotics; synbiotics; functional food ID LACTIC-ACID BACTERIA; ABERRANT CRYPT FOCI; CONJUGATED LINOLEIC-ACID; LACTOBACILLUS-CASEI PREPARATION; SUPERFICIAL BLADDER-CANCER; ANTI-TUMOR ACTIVITY; COLON-CANCER; BIFIDOBACTERIUM-LONGUM; LIPID-PEROXIDATION; COLORECTAL-CANCER AB Cancer is a serious global public health problem. Cancer incidence and mortality have been steadily rising throughout the past century in most places of the world. There are several epidemiological evidences that support a protective role of probiotics against cancer. Lactic acid bacteria and their probioactive cellular substances exert many beneficial effects in the gastrointestinal tract, and also release various enzymes into the intestinal lumen and exert potential synergistic (LAB) effects on digestion and alleviate symptoms of intestinal malabsorption. Consumption of fermented dairy products with LAB may elicit anti-tumor effects. These effects are attributed to the inhibition of mutagenic activity, the decrease in several enzymes implicated in the generation of carcinogens, mutagens, or tumor-promoting agents, suppression of tumors, and epidemiology correlating dietary regimes and cancer. Specific cellular components in lactic acid bacteria seem to induce strong adjuvant effects including modulation of cell-mediated immune responses, activation of the reticulo-endothelial system, augmentation of cytokine pathways, and regulation of interleukins and tumor necrosis factors. Studies on the effect of probiotic consumption on cancer appear promising, since recent in vitro and in vivo studies have indicated that probiotic bacteria might reduce the risk, incidence and number of tumors of the colon, liver and bladder. The protective effect against cancer development may be ascribed to binding of mutagens by intestinal bacteria, may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine, reduction of the enzymes beta-glucuronidase and beta-glucosidase and deconjugation of bile acids, or merely by enhancing the immune system of the host. There are isolated reports citing that administration of LAB results in increased activity of anti-oxidative enzymes or by modulating circulatory oxidative stress that protects cells against carcinogen-induced damage. These include glutathione-S-transferase, glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. However, there is no direct experimental evidence for cancer suppression in human subjects as a result of the consumption of probiotic cultures in fermented or unfermented dairy products, but there is a wealth of indirect evidence based largely on laboratory studies. C1 [Yadav, Hariom] NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Kumar, Manoj; Behare, Pradip; Kumar, Pramod; Poddar, Dev; Aggarwal, P. K.] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal 132001, Haryana, India. [Kumar, Ashok] MLK PG Coll, Dept Zool, Balrampur, UP, India. [Nagpal, Ravinder] Lovely Profess Univ, Dept Biotechnol, Phagwara, Punjab, India. [Mohania, Dheeraj] Natl Dairy Res Inst, Anim Biochem Div, Karnal 132001, Haryana, India. [Verma, Vinod] AgResearch Ltd, Ruakura Res Ctr, Reprod Technol, Hamilton, New Zealand. [Henry, C. J. K.] Oxford Brookes Univ, Sch Biol & Mol Sci, Oxford OX3 0BP, England. RP Yadav, H (reprint author), NIDDKD, Diabet Branch, NIH, 5W5872,CRC,Bld 10, Bethesda, MD 20892 USA. EM yadavhariom@gmail.com OI Yadav, Hariom/0000-0003-4504-1597 NR 157 TC 62 Z9 63 U1 4 U2 46 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0963-7486 J9 INT J FOOD SCI NUTR JI Int. J. Food Sci. Nutr. PD AUG PY 2010 VL 61 IS 5 BP 473 EP 496 DI 10.3109/09637480903455971 PG 24 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 634OB UT WOS:000280591300004 PM 20187714 ER PT J AU Kitchener, HC Hoskins, W Small, W Thomas, GM Trimble, EL AF Kitchener, Henry Charles Hoskins, William Small, William, Jr. Thomas, Gillian M. Trimble, Edward Lloyd CA Cervical Cancer Consensus Grp TI The Development of Priority Cervical Cancer Trials A Gynecologic Cancer InterGroup Report SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Review DE Cancer of the cervix; Trials ID VAGINAL RADICAL TRACHELECTOMY; NEOADJUVANT CHEMOTHERAPY; INTRAEPITHELIAL NEOPLASIA; PELVIC EXENTERATION; RANDOMIZED-TRIAL; PHASE-II; SURGERY; CARCINOMA; CISPLATIN; RADIOTHERAPY AB Since the late 1990s, when a spate of US studies reported the benefit of chemoradiation for cervical cancer, there has been a dearth of clinical trials in cervical cancer. This requires to be addressed with urgency because this disease is responsible for a quarter of a million deaths globally each year, mostly in developing countries, but therapeutic advances are required in all health care settings. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaborative of leading national groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representations from most of the GCIG groups and selected large centers in low- and middle-income countries. The focus was to identify consensus on several concepts for clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps most needing new evidence. The second half of the meeting was concerned with achieving consensus on the way forward. There were 2 principal outcomes. The first was a proposal to establish, under the umbrella of GCIG, a cervical cancer trials network of centers from countries currently outside GCIG (Eastern Europe, India, Thailand, Southern Africa, and South and Central America), which could increase international participation in trials, conducted within the principles of good clinical practice. The second was to identify the priorities for clinical trials. These included additional systemic therapy before or after chemoradiation; less radical surgery for small, early-stage tumors; the use of fewer fractions to improve cost-effectiveness of treatment in centers with limited resources; and chemotherapy to improve resectability of bulky tumors. C1 [Kitchener, Henry Charles] Univ Manchester, Acad Hlth Sci Ctr, St Marys Hosp, Cent Manchester Univ Hosp,NHS Fdn Trust, Manchester M13 9WL, Lancs, England. [Hoskins, William] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Small, William, Jr.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Thomas, Gillian M.] Univ Toronto, Odette Canc Ctr, Toronto, ON, Canada. [Trimble, Edward Lloyd] NCI, NIH, Bethesda, MD 20892 USA. RP Kitchener, HC (reprint author), Univ Manchester, Acad Hlth Sci Ctr, St Marys Hosp, Cent Manchester Univ Hosp,NHS Fdn Trust, 5th Floor Res,Oxford Rd, Manchester M13 9WL, Lancs, England. EM henry.kitchener@manchester.ac.uk FU National Cancer Research Institute; UK GlaxoSmithKline, United Kingdom FX The meeting was funded with unrestricted grants from National Cancer Research Institute, UK GlaxoSmithKline, United Kingdom. NR 33 TC 16 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD AUG PY 2010 VL 20 IS 6 BP 1092 EP 1100 DI 10.1111/IGC.0b013e3181e730aa PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 634HR UT WOS:000280572000030 PM 20683424 ER PT J AU Brown, RJ de Banate, MA Rother, KI AF Brown, Rebecca J. de Banate, Mary Ann Rother, Kristina I. TI Artificial Sweeteners: A systematic review of metabolic effects in youth SO INTERNATIONAL JOURNAL OF PEDIATRIC OBESITY LA English DT Review DE Acesulfame-K; artificial sweetener; aspartame; neotame; obesity; saccharine; sucralose; weight gain ID SOFT DRINK CONSUMPTION; FOOD-INTAKE; BODY-WEIGHT; BEVERAGE CONSUMPTION; INTENSE SWEETENERS; TASTE RECEPTORS; CALORIC COMPENSATION; PHYSICAL-ACTIVITY; DIETARY PATTERNS; SELF-REGULATION AB Epidemiological data have demonstrated an association between artificial sweetener use and weight gain. Evidence of a causal relationship linking artificial sweetener use to weight gain and other metabolic health effects is limited. However, recent animal studies provide intriguing information that supports an active metabolic role of artificial sweeteners. This systematic review examines the current literature on artificial sweetener consumption in children and its health effects. Eighteen studies were identified. Data from large, epidemiologic studies support the existence of an association between artificially-sweetened beverage consumption and weight gain in children. Randomized controlled trials in children are very limited, and do not clearly demonstrate either beneficial or adverse metabolic effects of artificial sweeteners. Presently, there is no strong clinical evidence for causality regarding artificial sweetener use and metabolic health effects, but it is important to examine possible contributions of these common food additives to the global rise in pediatric obesity and diabetes. C1 [Brown, Rebecca J.; de Banate, Mary Ann; Rother, Kristina I.] Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD USA. RP Brown, RJ (reprint author), Bldg 10,Room 7C-432A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM brownrebecca@mail.nih.gov FU National Institute of Diabetes, Digestive and Kidney Diseases FX This work was supported by the intramural research program of the National Institute of Diabetes, Digestive and Kidney Diseases. NR 60 TC 50 Z9 50 U1 20 U2 107 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1747-7166 J9 INT J PEDIATR OBES JI Int. J. Pediatr. Obes. PD AUG PY 2010 VL 5 IS 4 BP 305 EP 312 DI 10.3109/17477160903497027 PG 8 WC Pediatrics SC Pediatrics GA 636MW UT WOS:000280741600002 PM 20078374 ER PT J AU Ocama, P Castelnuovo, B Kamya, MR Kirk, GD Reynolds, SJ Kiragga, A Colebunders, R Thomas, DL AF Ocama, P. Castelnuovo, B. Kamya, M. R. Kirk, G. D. Reynolds, S. J. Kiragga, A. Colebunders, R. Thomas, D. L. TI Low frequency of liver enzyme elevation in HIV-infected patients attending a large urban treatment centre in Uganda SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE liver toxicity; AST; antiretroviral therapy; nevirapine ID HEPATITIS-B-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; IMMUNE RECONSTITUTION; RISK-FACTORS; C-VIRUS; COHORT; COINFECTION; MORTALITY; DISEASE AB Liver enzyme elevations among patients on antiretroviral therapy (ART) were determined by prospectively evaluating aspartate aminotransferase (AST) data in a cohort of patients in Kampala over 36 months. A proportion of patients had hepatitis B virus (HBV) status determined. Hepatotoxicity was graded I to IV according to the AIDS Clinical Trial Group criteria. Of 546 patients, 377 (69%) were women; overall median baseline CD4+ T-cell was 97/mu L (interquartile range [IQR] 20-164). Hepatitis B surface antigen (HBsAg) was detected in 42 (9%) of 470 persons. ART included lamivudine, with either nevirapine and d4T (74%) or efavirenz and AZT (26%). Median (IQR) AST level at baseline was 35 (27,53 IU/L). Over 36 months, only eight patients had grade III AST elevation. Neither HBsAg nor ART regimen influenced AST levels. Male gender and CD4+ change from baseline were correlated with AST elevation. Patients with HIV/HBV co-infection were not at an increased risk of AST elevation, which occurred uncommonly in this setting. C1 [Ocama, P.; Castelnuovo, B.; Kiragga, A.] Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda. [Ocama, P.; Kamya, M. R.] Makerere Univ, Coll Hlth Sci, Dept Med, Kampala, Uganda. [Kirk, G. D.; Reynolds, S. J.; Thomas, D. L.] Johns Hopkins Univ, Baltimore, MD USA. [Reynolds, S. J.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Colebunders, R.] Inst Trop Med, B-2000 Antwerp, Belgium. RP Ocama, P (reprint author), Makerere Univ, Coll Hlth Sci, Infect Dis Inst, POB 22418, Kampala, Uganda. EM pocama@idi.co.ug FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; [R01DA16078] FX We would like to acknowledge Kenneth Opio and Joseph Sempa for performing some of the statistical analysis, Yuka Manabe who supported the program as Head of Research at Infectious Diseases Institute and Gilead for sponsoring the fellowship. This study was funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. DT was supported for this work by R01DA16078. NR 27 TC 10 Z9 11 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD AUG PY 2010 VL 21 IS 8 BP 553 EP 557 DI 10.1258/ijsa.2010.010027 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 683AX UT WOS:000284445200005 PM 20975087 ER PT J AU Hachinski, V Donnan, GA Gorelick, PB Hacke, W Cramer, SC Kaste, M Fisher, M Brainin, M Buchan, AM Lo, EH Skolnick, BE Furie, KL Hankey, GJ Kivipelto, M Morris, J Rothwell, PM Sacco, RL Smith, SC Wang, YL Bryer, A Ford, GA Iadecola, C Martins, SCO Saver, J Skvortsova, V Bayley, M Bednar, MM Duncan, P Enney, L Finklestein, S Jones, TA Kalra, L Kleim, J Nitkin, R Teasell, R Weiller, C Desai, B Goldberg, MP Heiss, WD Saarelma, O Schwamm, LH Shinohara, Y Trivedi, B Wahlgren, N Wong, LK Hakim, A Norrving, B Prudhomme, S Bornstein, NM Davis, SM Goldstein, LB Leys, D Tuomilehto, J AF Hachinski, Vladimir Donnan, Geoffrey A. Gorelick, Philip B. Hacke, Werner Cramer, Steven C. Kaste, Markku Fisher, Marc Brainin, Michael Buchan, Alastair M. Lo, Eng H. Skolnick, Brett E. Furie, Karen L. Hankey, Graeme J. Kivipelto, Miia Morris, John Rothwell, Peter M. Sacco, Ralph L. Smith, Sidney C., Jr. Wang, Yulun Bryer, Alan Ford, Gary A. Iadecola, Costantino Martins, Sheila C. O. Saver, Jeff Skvortsova, Veronika Bayley, Mark Bednar, Martin M. Duncan, Pamela Enney, Lori Finklestein, Seth Jones, Theresa A. Kalra, Lalit Kleim, Jeff Nitkin, Ralph Teasell, Robert Weiller, Cornelius Desai, Bhupat Goldberg, Mark P. Heiss, Wolf-Dieter Saarelma, Osmo Schwamm, Lee H. Shinohara, Yukito Trivedi, Bhargava Wahlgren, Nils Wong, Lawrence K. Hakim, Antoine Norrving, Bo Prudhomme, Stephen Bornstein, Natan M. Davis, Stephen M. Goldstein, Larry B. Leys, Didier Tuomilehto, Jaakko TI Stroke: working toward a prioritized world agenda SO INTERNATIONAL JOURNAL OF STROKE LA English DT Editorial Material DE prevention; rehabilitation; stroke; translational; treatment ID VASCULAR COGNITIVE IMPAIRMENT; TISSUE-PLASMINOGEN ACTIVATOR; TRANSIENT ISCHEMIC ATTACK; HEALTHY LIFE-STYLE; PRIMARY PREVENTION; POLICY STATEMENT; CARE; RECOMMENDATIONS; PROGRESS; BRAIN AB Background and Purpose The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. Conclusions To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress. C1 [Hachinski, Vladimir] Univ Western Ontario, London Hlth Sci Ctr, Dept Clin Neurol Sci, London, ON N6A 5A5, Canada. [Donnan, Geoffrey A.] Florey Neurosci Inst, Carlton S Victoria, Australia. [Gorelick, Philip B.] Univ Illinois, Chicago, IL USA. [Hacke, Werner] Univ Heidelberg, Heidelberg, Germany. [Cramer, Steven C.] Univ Calif Irvine, Orange, CA 92668 USA. [Kaste, Markku] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA USA. [Brainin, Michael] Univ Krems, Univ Donau, Krems, Austria. [Buchan, Alastair M.] Univ Oxford, Oxford, England. [Lo, Eng H.; Furie, Karen L.; Schwamm, Lee H.] Massachusetts Gen Hosp, Charlestown, MA USA. [Skolnick, Brett E.] Novo Nordisk AS, Princeton, NJ USA. [Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia. [Kivipelto, Miia] Karolinska Inst, Stockholm, Sweden. [Morris, John; Goldberg, Mark P.] Washington Univ, Sch Med, St Louis, MO USA. [Rothwell, Peter M.] John Radcliffe Hosp, Oxford OX3 9DU, England. [Sacco, Ralph L.] Univ Miami, AHA, Miami, FL USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. World Heart Federat, Geneva, Switzerland. [Wang, Yulun] InTouch Hlth, Goleta, CA USA. [Bryer, Alan] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Bryer, Alan] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Ford, Gary A.] Univ Newcastle, Newcastle Upon Tyne, Tyne & Wear, England. [Iadecola, Costantino] Weill Cornell Med Coll, New York, NY USA. [Martins, Sheila C. O.] Hosp Clin, Porto Alegre, RS, Brazil. [Saver, Jeff] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Skvortsova, Veronika] Russian State Res Stroke Inst, Moscow, Russia. [Bayley, Mark] Toronto Rehabil Inst, Toronto, ON, Canada. [Bednar, Martin M.] Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA. [Duncan, Pamela] Duke Univ, Durham, NC USA. [Enney, Lori] GlaxoSmithKline Inc, Durham, NC USA. [Finklestein, Seth] Biotrofix Inc, Waltham, MA USA. [Jones, Theresa A.] Univ Texas Austin, Austin, TX 78712 USA. [Kalra, Lalit] Kings Coll London, London WC2R 2LS, England. [Kleim, Jeff] Univ Florida, Gainesville, FL USA. [Nitkin, Ralph] NICHHD, Natl Ctr Med Rehabil, NIH, Rockville, MD USA. [Teasell, Robert] St Josephs Healthcare London, London, ON, Canada. [Weiller, Cornelius] Univ Freiburg, Freiburg, Germany. [Desai, Bhupat] Pomona Valley Hosp Med Ctr, Pomona, CA USA. [Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, Cologne, Germany. [Saarelma, Osmo] Terveystalo Med Ctr, Helsinki, Finland. [Shinohara, Yukito] Tachikawa Hosp, Tokyo, Japan. [Trivedi, Bhargava] So Illinois Healthcare, Carbondale, IL USA. [Wahlgren, Nils] Karolinska Inst, Stockholm, Sweden. [Wong, Lawrence K.] Chinese Univ Hong Kong, Sha Tin, Hong Kong, Peoples R China. Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Hakim, Antoine] Univ Ottawa, Canadian Stroke Network, Ottawa, ON, Canada. [Norrving, Bo] Univ Lund Hosp, S-22185 Lund, Sweden. [Prudhomme, Stephen] Amer Heart Assoc, Dallas, TX USA. [Bornstein, Natan M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Univ Melbourne, Melbourne, Vic, Australia. [Davis, Stephen M.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Goldstein, Larry B.] Duke Univ, Durham, NC USA. [Goldstein, Larry B.] Durham VA Med Ctr, Durham, NC USA. [Leys, Didier] Univ Lille Nord France, Lille, France. [Tuomilehto, Jaakko] Univ Helsinki, Helsinki, Finland. RP Hachinski, V (reprint author), Univ Western Ontario, Univ Hosp, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM Vladimir.Hachinski@lhsc.on.ca RI Jones, Theresa/F-1182-2010; Skolnick, Brett/B-5140-2009; Ford, Gary/A-6353-2012; Buchan, Alastair/B-9095-2009; Hankey, Graeme /H-4968-2014; OI Kaste, Markku/0000-0001-6557-6412; Jones, Theresa/0000-0003-0906-6439; Buchan, Alastair/0000-0002-2918-5200; Hankey, Graeme /0000-0002-6044-7328; Norrving, Bo/0000-0002-8024-5096; Schwamm, Lee/0000-0003-0592-9145; Kivipelto, Miia/0000-0003-0992-3875; Donnan, Geoffrey/0000-0001-6324-3403; Saver, Jeffrey/0000-0001-9141-2251 FU Medical Research Council [G0500495]; NINDS NIH HHS [P01 NS055104, RC2 NS069335] NR 87 TC 17 Z9 18 U1 0 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD AUG PY 2010 VL 5 IS 4 BP 238 EP 256 DI 10.1111/j.1747-4949.2010.00442.x PG 19 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 619RC UT WOS:000279446600002 PM 20636706 ER PT J AU Johansson, A Celli, J Conlan, W Elkins, KL Forsman, M Keim, PS Larsson, P Manoil, C Nano, FE Petersen, JM Sjostedt, A AF Johansson, Anders Celli, Jean Conlan, Wayne Elkins, Karen L. Forsman, Mats Keim, Paul S. Larsson, Par Manoil, Colin Nano, Francis E. Petersen, Jeannine M. Sjostedt, Anders TI Objections to the transfer of Francisella novicida to the subspecies rank of Francisella tularensis SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Letter ID DIVERSITY; NAMES C1 [Johansson, Anders; Sjostedt, Anders] Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden. [Celli, Jean] NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Conlan, Wayne] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1C 2M7, Canada. [Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Forsman, Mats; Larsson, Par] Swedish Def Res Agcy, Div CBRN Def & Secur, SE-90182 Umea, Sweden. [Keim, Paul S.] No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 86011 USA. [Manoil, Colin] Univ Washington, Seattle, WA 98195 USA. [Nano, Francis E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. [Petersen, Jeannine M.] Ctr Dis Control, Div Vector Borne Infect Dis, Bacterial Dis Branch, Ft Collins, CO 80521 USA. [Petersen, Jeannine M.] Ctr Dis Prevent, Div Vector Borne Infect Dis, Bacterial Dis Branch, Ft Collins, CO 80521 USA. RP Johansson, A (reprint author), Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden. EM anders.johansson@climi.umu.se RI Keim, Paul/A-2269-2010; Forsman, Mats/A-1426-2016; Johansson, Anders/D-2928-2012; OI Forsman, Mats/0000-0002-4466-5325; Johansson, Anders/0000-0003-0548-5943; Sjostedt, Anders/0000-0002-0768-8405 NR 11 TC 31 Z9 31 U1 1 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD AUG PY 2010 VL 60 BP 1717 EP 1718 DI 10.1099/ijs.0.022830-0 PN 8 PG 2 WC Microbiology SC Microbiology GA 642AS UT WOS:000281175700001 PM 20688748 ER PT J AU Kirby, AC Nager, CW Litman, HJ FitzGerald, MP Kraus, S Norton, P Sirls, L Rickey, L Wilson, T Dandreo, KJ Zimmern, P AF Kirby, A. C. Nager, C. W. Litman, H. J. FitzGerald, M. P. Kraus, S. Norton, P. Sirls, L. Rickey, L. Wilson, T. Dandreo, K. J. Zimmern, P. CA UIT N TI PREOPERATIVE VOIDING DETRUSOR PRESSURES AND STRESS INCONTINENCE SURGERY OUTCOMES SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Meeting Abstract C1 [Kirby, A. C.; Nager, C. W.] Univ Calif San Diego, San Diego, CA 92103 USA. [FitzGerald, M. P.] Loyola Univ Med Ctr, Maywood, IL USA. [Kraus, S.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Norton, P.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Sirls, L.] Beaumont Hosp, Med Ctr, Dublin, Ireland. [Rickey, L.] Univ Maryland, College Pk, MD 20742 USA. [Wilson, T.] Univ Alabama, Birmingham, AL USA. [Zimmern, P.] Univ Texas SW, Dallas, TX USA. [UIT N] NIDDK, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD AUG PY 2010 VL 21 SU 1 MA 38 BP S56 EP S58 PG 3 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 640OV UT WOS:000281061800039 ER PT J AU Sezgin, E Hendrickson, SL Jabs, DA Van Natta, ML Lewis, RA Troyer, JL O'Brien, SJ AF Sezgin, Efe Hendrickson, Sher L. Jabs, Douglas A. Van Natta, Mark L. Lewis, Richard A. Troyer, Jennifer L. O'Brien, Stephen J. CA SOCA Res Grp TI Effect of Host Genetics on Incidence of HIV Neuroretinal Disorder in Patients With AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; HIV-1; host genetics; HIV-neuroretinal disorder ID ACTIVE ANTIRETROVIRAL THERAPY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; DISEASE PROGRESSION; OCULAR COMPLICATIONS; TNF-ALPHA; INFECTED INDIVIDUALS; NEURONAL APOPTOSIS; IL10 HAPLOTYPES; OPTIC NERVES; PROMOTER AB Approximately 10%-15% of patients with AIDS but without ocular opportunistic infections will have a presumed neuroretinal disorder (HIV-NRD), manifested by reduced contrast sensitivity and abnormal visual fields. The loss of contrast sensitivity often is sufficient to impair reading speed. To evaluate the effect of host genetics on HIV-NRD, we explored validated AIDS restriction gene variants CCR5 Delta 32, CCR2-64I, CCR5 P1, SDF-3'A, IL-10-5'A, RANTES -403A, RANTES -28G, RANTES-In1.1C, CX3CR1-249I, CX3CR1-280M, IFNG-179T, MDR1-3435T, and MCP-1364G, each of which has been implicated previously to influence HIV-1 infection, AIDS progression, therapy response, and antiviral drug metabolism, and an IL-10 receptor gene, IL-10R1, in the Longitudinal Study of the Ocular Complications of AIDS cohort. In European Americans (cases = 55, controls = 290), IL-10-5' A variant and its promoter haplotype (hazard ratio = 2.09, confidence interval. 1.19 to 3.67, P = 0.01), in African Americans (cases = 54, controls = 180), RANTES-In1.1C and the associated haplotype (hazard ratio = 2.72, confidence interval.: 1.48 to 5.00, P = 0.001), showed increased HIV-NRD susceptibility. Although sample sizes are small and P values do not pass a strict Bonferroni correction, our results suggest that, in European Americans, an IL-10-related pathway, and, in African Americans, chemokine receptor ligand polymorphisms in RANTES are risk factors for HIV-NRD development. Clearly, further studies are warrented. C1 [Sezgin, Efe; Troyer, Jennifer L.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Jabs, Douglas A.; Van Natta, Mark L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Ctr Clin Trials, Baltimore, MD USA. [Lewis, Richard A.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. [Lewis, Richard A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Lewis, Richard A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lewis, Richard A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Sezgin, E (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. EM sezginef@mail.nih.gov RI Sezgin, Efe/B-8418-2012; Troyer, Jennifer/B-8415-2012 OI Sezgin, Efe/0000-0002-8000-7485; FU National Cancer Institute [N01-CO-12400]; National Cancer Institute, National Institutes of Health [HHSN26120080001E]; National Eye Institute, National Institutes of Health [U10-EY-08052]; Mount Sinai School of Medicine, New York, NY [U10-EY-08057, U10-EY-08067] FX Supported in part by contract N01-CO-12400 from the National Cancer Institute to the Laboratory of Genomic Diversity, Frederick, MD, with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E and cooperative agreements from the National Eye Institute, National Institutes of Health, U10-EY-08052 to the Mount Sinai School of Medicine, New York, NY, U10-EY-08057 to the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, and U10-EY-08067 to the University of Wisconsin, Madison, Madison, WI. NR 57 TC 9 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2010 VL 54 IS 4 BP 343 EP 351 DI 10.1097/QAI.0b013e3181deaf4d PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 627BR UT WOS:000280013600002 PM 20531015 ER PT J AU Best, BM Stek, AM Mirochnick, M Hu, CC Li, H Burchett, SK Rossi, SS Smith, E Read, JS Capparelli, EV AF Best, Brookie M. Stek, Alice M. Mirochnick, Mark Hu, Chengcheng Li, Hong Burchett, Sandra K. Rossi, Steven S. Smith, Elizabeth Read, Jennifer S. Capparelli, Edmund V. CA Int Maternal Pediat Adolescent AID TI Lopinavir Tablet Pharmacokinetics With an Increased Dose During Pregnancy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; lopinavir; mother-to-child transmission; pharmacokinetics; pregnancy ID INHIBITOR-EXPERIENCED PATIENTS; RITONAVIR; WOMEN; ANTIRETROVIRALS; EXPOSURE; CAPSULE AB Objective: Reduced lopinavir concentrations have been demonstrated with use of the capsule formulation during the third trimester of pregnancy. This study determined lopinavir exposure with an increased dose of the new tablet formulation during the third trimester. Design: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is a prospective nonblinded pharmacokinetic study in HIV-infected pregnant women, including a cohort receiving 2 lopinavir/ritonavir tablets (400 mg/100 mg) twice daily during the second trimester, 3 tablets (600 mg/150 mg) twice daily during the third trimester, and 2 tablets (400 mg/100 mg) twice daily postdelivery through 2 weeks postpartum. Methods: Steady-state 12-hour pharmacokinetic profiles were performed during pregnancy and at 2 weeks postpartum. Lopinavir and ritonavir were measured by reverse-phase high-performance liquid chromatography (detection limit, 0.09 mcg/mL). Results: Thirty-three women were studied. Median lopinavir AUC for the second trimester (n = 11), third trimester (n = 33), and postpartum (n = 27) were 72, 96, and 133 mcg.hr/mL, respectively. Median minimum lopinavir concentrations were 3.4, 4.9, and 6.9 mcg/mL. Conclusions: The higher lopinavir/ritonavir tablet dose (600 mg/150 mg) provided exposure during the third trimester similar to the average AUC (98 mcg.hr.mL(-1)) in nonpregnant adults taking 400 mg/100 mg twice daily. The higher dose should be used during the second and third trimesters of pregnancy. Postpartum dosing can be reduced to standard dosing before 2 weeks postpartum. C1 [Best, Brookie M.; Capparelli, Edmund V.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Best, Brookie M.; Rossi, Steven S.; Capparelli, Edmund V.] Univ Calif San Diego, Dept Pediat, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA. [Stek, Alice M.] Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Mirochnick, Mark] Boston Univ, Sch Med, Dept Pediat Neonatol, Boston, MA 02118 USA. [Hu, Chengcheng; Li, Hong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Burchett, Sandra K.] Childrens Hosp Boston, Dept Med, Boston, MA USA. [Smith, Elizabeth] NIAID, Bethesda, MD 20892 USA. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, DHHS, Bethesda, MD USA. RP Best, BM (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr,MC 0719, La Jolla, CA 92093 USA. EM brookie@ucsd.edu RI Hu, Chengcheng/A-8391-2017 FU National Institute of Allergy and Infectious Diseases [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200800001C, N01-DK-8-0001]; National Institute of Mental Health [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110, 1 U01 AI068616]; National Institute of Allergy and Infectious Diseases FX Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group was provided by the National Institute of Allergy and Infectious Diseases [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health [AI068632]. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group and #1 U01 AI068616 with the International Maternal Pediatric Adolescent AIDS Clinical Trials Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number HHSN267200800001C, control number N01-DK-8-0001). NR 24 TC 43 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2010 VL 54 IS 4 BP 381 EP 388 DI 10.1097/QAI.0b013e3181d6c9ed PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 627BR UT WOS:000280013600007 PM 20632458 ER PT J AU Wang, J Iannotti, RJ AF Wang, Jing Iannotti, Ronald J. TI Cyberbullying, Let the Computer Help Reply SO JOURNAL OF ADOLESCENT HEALTH LA English DT Letter C1 [Wang, Jing; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. RP Wang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD AUG PY 2010 VL 47 IS 2 BP 209 EP 210 DI 10.1016/j.jadohealth.2010.05.014 PG 3 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 627SR UT WOS:000280063400015 ER PT J AU Carter, MC AF Carter, Melody C. TI Successful treatment of idiopathic anaphylaxis in an adolescent Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID SYSTEMIC MASTOCYTOSIS; OMALIZUMAB; DISORDERS C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Carter, MC (reprint author), NIAID, NIH, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mcarter@niaid.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 2010 VL 126 IS 2 BP 416 EP 416 DI 10.1016/j.jaci.2010.05.044 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 642IL UT WOS:000281203800044 ER PT J AU Scichilone, N Morici, G Zangla, D Chimenti, L Davi, E Reitano, S Paterno, A Santagata, R Togias, A Bellia, V Bonsignore, MR AF Scichilone, Nicola Morici, Giuseppe Zangla, Daniele Chimenti, Laura Davi, Eva Reitano, Simona Paterno, Alessandra Santagata, Roberta Togias, Alkis Bellia, Vincenzo Bonsignore, Maria Rosaria TI Effects of exercise training on airway responsiveness and airway cells in healthy subjects SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE rowing; methacholine; neutrophils ID SMOOTH-MUSCLE; DEEP INSPIRATION; BRONCHIAL HYPERRESPONSIVENESS; PHYSICAL-ACTIVITY; ELITE SWIMMERS; INDUCED ASTHMA; LUNG-FUNCTION; MILD ASTHMA; FOLLOW-UP; METHACHOLINE AB Scichilone N, Morici G, Zangla D, Chimenti L, Davi E, Reitano S, Paterno A, Santagata R, Togias A, Bellia V, Bonsignore MR. Effects of exercise training on airway responsiveness and airway cells in healthy subjects. J Appl Physiol 109: 288-294, 2010. First published June 10, 2010; doi:10.1152/japplphysiol.01200.2009.-Airway responsiveness to methacholine (Mch) in the absence of deep inspirations (DIs) is lower in athletes compared with sedentary individuals. In this prospective study, we tested the hypothesis that a training exercise program reduces the bronchoconstrictive effect of Mch. Ten healthy sedentary subjects (M/F: 3/7; mean +/- SD age: 22 +/- 3 yr) entered a 10-wk indoor rowing exercise program on rowing ergometer and underwent Mch bronchoprovocation in the absence of DIs at baseline, at weeks 5 and 10, as well as 4-6 wk after the training program was completed. Exercise-induced changes on airway cells and markers of airway inflammation were also assessed by sputum induction and venous blood samples. Mean power output during the 1,000 m test was 169 +/- 49 W/stroke at baseline, 174 +/- 49 W/stroke at 5 wk, and 200 +/- 60 W/stroke at 10 wk of training (P < 0.05). The median Mch dose used at baseline was 50 mg/ml (range 25-75 mg/ml) and remained constant per study design. At the pretraining evaluation, the percent reduction in the primary outcome, the inspiratory vital capacity (IVC) after inhalation of Mch in the absence of DIs was 31 +/- 13%; at week 5, the Mch-induced reduction in IVC was 22 +/- 19%, P = 0.01, and it further decreased to 15 +/- 11% at week 10 (P = 0.0008). The percent fall in IVC 4-6 wk after the end of training was 15 +/- 11% (P = 0.87 vs. end of training). Changes in airway cells were not associated with changes in airway responsiveness. Our data show that a course of exercise training can attenuate airway responsiveness against Mch inhaled in the absence of DIs in healthy subjects and suggest that a sedentary lifestyle may favor development of airways hyperresponsiveness. C1 [Scichilone, Nicola; Chimenti, Laura; Davi, Eva; Reitano, Simona; Paterno, Alessandra; Santagata, Roberta; Bonsignore, Maria Rosaria] Univ Palermo, Dept Internal Med, Div Pulmonol DIBIMIS, Villa Sofia Cervello Hosp, I-90146 Palermo, Italy. [Morici, Giuseppe] Univ Palermo, DIMES, Dept Expt Med, I-90146 Palermo, Italy. [Zangla, Daniele] Univ Palermo, DISMOT, Dept Motor Sci, I-90146 Palermo, Italy. [Morici, Giuseppe; Chimenti, Laura; Bonsignore, Maria Rosaria] CNR, Natl Res Council Italy, IBIM, Palermo, Italy. [Togias, Alkis; Bellia, Vincenzo] NIAID, NIH, Bethesda, MD 20892 USA. RP Scichilone, N (reprint author), Univ Palermo, Dept Internal Med, Div Pulmonol DIBIMIS, Villa Sofia Cervello Hosp, Via Trabucco 180, I-90146 Palermo, Italy. EM n.scichilone@libero.it OI Bonsignore, Maria R/0000-0002-4875-7796; Scichilone, Nicola/0000-0001-6400-6573 NR 47 TC 9 Z9 9 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2010 VL 109 IS 2 BP 288 EP 294 DI 10.1152/japplphysiol.01200.2009 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 636RY UT WOS:000280758800007 PM 20538849 ER PT J AU Williamson, DA Anton, SD Han, HM Champagne, CM Allen, R LeBlanc, E Ryan, DH Rood, J McManus, K Laranjo, N Carey, VJ Loria, CM Bray, GA Sacks, FM AF Williamson, Donald A. Anton, Stephen D. Han, Hongmei Champagne, Catherine M. Allen, Ray LeBlanc, Eric Ryan, Donna H. Rood, Jennifer McManus, Katherine Laranjo, Nancy Carey, Vincent J. Loria, Catherine M. Bray, George A. Sacks, Frank M. TI Early behavioral adherence predicts short and long-term weight loss in the POUNDS LOST study SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Obesity; Weight management; Adherence; Computer tracking; Waist circumference; Insulin ID LIFE-STYLE INTERVENTION; DIETARY ADHERENCE; PHYSICAL-ACTIVITY AB The primary aim of this study was to test the association of early (first 6 months) adherence related to diet, self-monitoring, and attendance with changes in adiposity and cardiovascular risk factors. This study used data from the 24-month POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for short-and long-term weight loss. A computer tracking system was used to record data on eight indicator variables related to adherence. Using canonical correlations at the 6 and 24 month measurement periods, early behavioral adherence was associated with changes in percent weight loss and waist circumference at 6 months (R = 0.52) and 24 months (R = 0.37), but was not associated with cardiovascular disease risk factor levels. Early dietary adherence was associated with changes in insulin at 6 months (R = 0.19), but not at 24 months (R = 0.08, ns). Early dietary adherence was not associated with changes in adiposity. C1 [Williamson, Donald A.; Anton, Stephen D.; Han, Hongmei; Champagne, Catherine M.; Allen, Ray; LeBlanc, Eric; Ryan, Donna H.; Rood, Jennifer; Bray, George A.] LSU Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [McManus, Katherine; Laranjo, Nancy; Carey, Vincent J.; Sacks, Frank M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA. RP Williamson, DA (reprint author), LSU Syst, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA USA. EM williada@pbrc.edu FU NCRR NIH HHS [M01 RR002635, RR-02635]; NHLBI NIH HHS [HL073286, U01 HL073286, U01 HL073286-05]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-15] NR 15 TC 19 Z9 19 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD AUG PY 2010 VL 33 IS 4 BP 305 EP 314 DI 10.1007/s10865-010-9253-0 PG 10 WC Psychology, Clinical SC Psychology GA 628OE UT WOS:000280129000006 PM 20195742 ER PT J AU Demner-Fushman, D Mork, JG Shooshan, SE Aronson, AR AF Demner-Fushman, Dina Mork, James G. Shooshan, Sonya E. Aronson, Alan R. TI UMLS content views appropriate for NLP processing of the biomedical literature vs. clinical text SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE UMLS; Metathesaurus; Content views; Natural Language Processing; Indexing; Clinical text ID WORD SENSE DISAMBIGUATION; SEMANTIC LEXICON; RESOURCES; KNOWLEDGE; DOMAIN AB Identification of medical terms in free text is a first step in such Natural Language Processing (NLP) tasks as automatic indexing of biomedical literature and extraction of patients' problem lists from the text of clinical notes. Many tools developed to perform these tasks use biomedical knowledge encoded in the Unified Medical Language System (UMLS) Metathesaurus. We continue our exploration of automatic approaches to creation of subsets (UMLS content views) which can support NLP processing of either the biomedical literature or clinical text. We found that suppression of highly ambiguous terms in the conservative AutoFilter content view can partially replace manual filtering for literature applications, and suppression of two character mappings in the same content view achieves 89.5% precision at 78.6% recall for clinical applications. Published by Elsevier Inc. C1 [Demner-Fushman, Dina; Mork, James G.; Shooshan, Sonya E.; Aronson, Alan R.] NIH, LHNCBC, US Natl Lib Med, Bethesda, MD 20894 USA. RP Demner-Fushman, D (reprint author), NIH, LHNCBC, US Natl Lib Med, Bldg 38A,Room 10S-1020,8600 Rockville Pike,MSC 38, Bethesda, MD 20894 USA. EM ddemner@mail.nih.gov FU NIH, National Library of Medicine FX This work was supported by the Intramural Research Program of the NIH, National Library of Medicine. The authors thank Dr. Roger Mark for permission to make the clinical dataset publicly available. NR 25 TC 7 Z9 7 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD AUG PY 2010 VL 43 IS 4 BP 587 EP 594 DI 10.1016/j.jbi.2010.02.005 PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 627FQ UT WOS:000280025300011 PM 20152935 ER PT J AU Patel, CO Cimino, JJ AF Patel, Chintan O. Cimino, James J. TI A network-theoretic approach for decompositional translation across Open Biological Ontologies SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Network theory; Biomedical ontologies; Ontology translation; Open biomedical ontologies ID TERMS AB Biological ontologies are now being widely used for annotation, sharing and retrieval of the biological data. Many of these ontologies are hosted under the umbrella of the Open Biological Ontologies Foundry. In order to support interterminology mapping, composite terms in these ontologies need to be translated into atomic or primitive terms in other, orthogonal ontologies, for example, gluconeogenesis (biological process term) to glucose (chemical ontology term). Identifying such decompositional ontology translations is a challenging problem. In this paper, we propose a network-theoretic approach based on the structure of the integrated OBO relationship graph. We use a network-theoretic measure, called the clustering coefficient, to find relevant atomic terms in the neighborhood of a composite term. By eliminating the existing GO to ChEBI Ontology mappings from OBO, we evaluate whether the proposed approach can re-identify the corresponding relationships. The results indicate that the network structure provides strong cues for decompositional ontology translation and the existing relationships can be used to identify new translations. (C) 2010 Elsevier Inc. All rights reserved. C1 [Patel, Chintan O.] Columbia Univ, Dept Biomed Informat, Vanderbilt Clin, New York, NY 10032 USA. [Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Patel, CO (reprint author), Columbia Univ, Dept Biomed Informat, Vanderbilt Clin, 5th Floor,622 West,168th St, New York, NY 10032 USA. EM chintan.patel@dbmi.columbia.edu RI Patel, Chintan/H-3580-2011; OI Cimino, James/0000-0003-4101-1622 FU National Library of Medicine [R21LM009638]; NIH Clinical Center FX We thank the anonymous reviewers of AMIA 2009 Annual Symposium for their insightful comments and the National Library of Medicine for their grant support (R21LM009638) that funded this research. Dr. Cimino is supported by funds from the intramural research program at the NIH Clinical Center and the National Library of Medicine. NR 17 TC 3 Z9 3 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD AUG PY 2010 VL 43 IS 4 BP 608 EP 612 DI 10.1016/j.jbi.2010.01.007 PG 5 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 627FQ UT WOS:000280025300014 PM 20144734 ER PT J AU Aman, MJ Karauzum, H Bowden, MG Nguyen, TL AF Aman, M. Javad Karauzum, Hatice Bowden, M. Gabriela Nguyen, Tam Luong TI Structural Model of the Pre-pore Ring-like Structure of Panton-Valentine Leukocidin: Providing Dimensionality to Biophysical and Mutational Data SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article DE Pore-forming toxin; Pre-pore structure; Binary cytolysin; Methicillin-resistant; Staphylococcus aureus; Octamerization; Protein modeling; Channel; Protein interface; Mutation ID STAPHYLOCOCCAL ALPHA-HEMOLYSIN; TRANSMEMBRANE PORE; FORMING TOXINS; N-TERMINUS; PROTEIN; AUREUS; DOCKING; HINT; ORGANIZATION; INHIBITORS AB Panton-Valentine leukocidin (PVL) is a bipartite toxin that plays an important role in the pathogenesis of methicillin-resistant Staphylococcus Queens. Recent clinical data suggest a correlation between PVL and severe cases of S. omens pneumonia. A clear understanding of the structure and function of PVL is critical to the development of novel. effective treatments. Here, we report an all-atom model or the macromolecular structure of Panton-Valentine leukocidin in its octamerie, pre-pore conformation that confirms and extends our understanding or the toxin's mechanism of action. C1 [Nguyen, Tam Luong] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. [Aman, M. Javad; Karauzum, Hatice] Integrated BioTherapeut Inc, Germantown, MD 20876 USA. [Bowden, M. Gabriela] Texas A&M Univ, Ctr Infect & Inflammatory Dis, Inst Biosci & Technol, Syst Hlth Sci Ctr, Houston, TX 77030 USA. RP Nguyen, TL (reprint author), NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. EM nguyent5@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; Division of Cancer Treatment and Diagnosis of the National Cancer Institute 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 N01-CO-12400. The content of this publication does not necessarily Felled 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. NR 34 TC 60 Z9 62 U1 0 U2 6 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD AUG PY 2010 VL 28 IS 1 BP 1 EP 12 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 607OW UT WOS:000278516000001 PM 20476791 ER PT J AU Yang, L Edwards, CM Mundy, GR AF Yang, Li Edwards, Claire M. Mundy, Gregory R. TI Gr-1(+)CD11b(+) Myeloid-Derived Suppressor Cells: Formidable Partners in Tumor Metastasis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE MYELOID-DERIVED SUPPRESSOR CELLS; GR-1; CD11B; MYELOMA; METASTASIS; OSTEOCLASTS ID GROWTH-FACTOR-BETA; NF-KAPPA-B; BONE-MARROW NICHE; TGF-BETA; LUNG METASTASIS; COLON-CANCER; INFLAMMATION; ANGIOGENESIS; OSTEOCLASTS; RECRUITMENT AB The growth and metastasis of solid tumors not only depends on their ability to escape from immune surveillance but also hinges on their ability to invade the vasculature system as well as to induce the formation of new blood vessels. Gr-1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs), overproduced in tumor-bearing hosts, contribute significantly to all these aspects. They also have a potential role in the osteolysis associated with bone metastases. They are formidable partners in tumor metastasis. (c) 2010 American Society for Bone and Mineral Research. C1 [Edwards, Claire M.] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Vanderbilt Ctr Bone Biol, Nashville, TN 37232 USA. [Yang, Li] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mundy, Gregory R.] Vanderbilt Univ, Med Ctr, Dept Med Clin Pharmacol, Vanderbilt Ctr Bone Biol, Nashville, TN 37232 USA. RP Edwards, CM (reprint author), Vanderbilt Univ, Med Ctr, Dept Canc Biol, Vanderbilt Ctr Bone Biol, 2215 Garland Ave,1235 Med Res Bldg 4, Nashville, TN 37232 USA. EM claire.edwards@vanderbilt.edu RI Edwards, Claire/D-7114-2011 OI Edwards, Claire/0000-0002-1257-5659 FU National Cancer Institute [P01 CA40035]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the National Cancer Institute through P01 CA40035 (GRM). Li Yang is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 43 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2010 VL 25 IS 8 BP 1701 EP 1706 DI 10.1002/jbmr.154 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643UO UT WOS:000281325000001 ER PT J AU Kozloff, KM Volakis, LI Marini, JC Caird, MS AF Kozloff, Kenneth M. Volakis, Leo I. Marini, Joan C. Caird, Michelle S. TI Near-Infrared Fluorescent Probe Traces Bisphosphonate Delivery and Retention In Vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BISPHOSPHONATES; MOLECULAR IMAGING; FLUORESCENCE; OSTEOGENESIS IMPERFECTA; OSTEONECROSIS OF THE JAW ID PEDIATRIC OSTEOGENESIS IMPERFECTA; NONINVASIVE OPTICAL-DETECTION; BONE-RESORPTION; TRAUMATIC OSTEONECROSIS; POSTMENOPAUSAL WOMEN; ZOLEDRONIC ACID; BREAST-CANCER; FEMORAL-HEAD; MOUSE MODEL; CHILDREN AB Bisphosphonate use has expanded beyond traditional applications to include treatment of a variety of low-bone-mass conditions. Complications associated with long-term bisphosphonate treatment have been noted, generating a critical need for information describing the local bisphosphonate-cell interactions responsible for these observations. This study demonstrates that a fluorescent bisphosphonate analogue, far-red fluorescent pamidronate (FRFP), is an accurate biomarker of bisphosphonate deposition and retention in vivo and can be used to monitor site-specific local drug concentration. In vitro, FRFP is competitively inhibited from the surface of homogenized rat cortical bone by traditional bisphosphonates. In vivo, FRFP delivery to the skeleton is rapid, with fluorescence linearly correlated with bone surface area. Limb fluorescence increases linearly with injected dose of FRFP; injected FRFP does not interfere with binding of standard bisphosphonates at the doses used in this study. Long-term FRFP retention studies demonstrated that FRFP fluorescence decreases in conditions of normal bone turnover, whereas fluorescence was retained in conditions of reduced bone turnover, demonstrating preservation of local FRFP concentration. In the mandible, FRFP localized to the alveolar bone and bone surrounding the periodontal ligament and molar roots, consistent with findings of osteonecrosis of the jaw. These findings support a role for FRFP as an effective in vivo marker for bisphosphonate site-specific deposition, turnover, and long-term retention in the skeleton. (C) 2010 American Society for Bone and Mineral Research. C1 [Kozloff, Kenneth M.; Volakis, Leo I.; Caird, Michelle S.] Univ Michigan, Dept Orthopaed Surg, Orthopaed Res Labs, Ann Arbor, MI 48109 USA. [Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Kozloff, Kenneth M.; Volakis, Leo I.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. RP Kozloff, KM (reprint author), 2015 Biomed Sci Res Bldg,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM kenkoz@umich.edu NR 74 TC 35 Z9 35 U1 2 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2010 VL 25 IS 8 BP 1748 EP 1758 DI 10.1002/jbmr.66 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643UO UT WOS:000281325000006 PM 20200982 ER PT J AU Bhatti, S Tripodi, DJ Waclawiw, MA Rosing, DR Shizukuda, Y AF Bhatti, Sabha Tripodi, Dorothy J. Waclawiw, Myron A. Rosing, Douglas R. Shizukuda, Yukitaka TI Characteristics of Left Atrial Function of Transplanted Hearts SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Bhatti, Sabha; Shizukuda, Yukitaka] Univ Cincinnati, Div Cardiovasc Dis, Cincinnati, OH USA. [Tripodi, Dorothy J.; Waclawiw, Myron A.; Rosing, Douglas R.] Natl Heart Lung Blood Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 079 BP S27 EP S27 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800080 ER PT J AU Thomas, MK Weaver, C LaCroix, B Prokunina-Olsson, M Hall, JL AF Thomas, Melissa K. Weaver, Cyprian LaCroix, Bonnie Prokunina-Olsson, Mila Hall, Jennifer L. TI Defining the Role of the Transcription Factor TCF7L2 in Type 2 Diabetes SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 Mass Gen Hosp, Boston, MA USA. Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 113 BP S37 EP S37 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800114 ER PT J AU Kuehn, HS Radinger, M Brown, JM Ali, K Vanhaesebroeck, B Beaven, MA Metcalfe, DD Gilfillan, AM AF Kuehn, Hye Sun Radinger, Madeleine Brown, Jared M. Ali, Khaled Vanhaesebroeck, Bart Beaven, Michael A. Metcalfe, Dean D. Gilfillan, Alasdair M. TI Btk-dependent Rac activation and actin rearrangement following Fc epsilon RI aggregation promotes enhanced chemotactic responses of mast cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE Mast cells; Fc epsilon RI; Btk; Rac activation; Actin rearrangement; Chemotaxis; SCF; PGE(2) ID BRUTONS TYROSINE KINASE; BONE-MARROW; KIT; DEGRANULATION; MIGRATION; ADENOSINE; RECEPTOR; INVOLVEMENT; MECHANISM; MEMBRANE AB Mast cells infiltrate the sites of inflammation associated with chronic atopic disease and during helminth and bacterial infection. This process requires receptor-mediated cell chemotaxis across a concentration gradient of their chemotactic ligands. In vivo, mast cells are likely to be exposed to several such agents, which can cooperate in a synergistic manner to regulate mast cell homing. Here, we report that chemotaxis of mouse bone-marrow-derived mast cells (BMMCs) in response to the chemoattractants stem-cell factor (SCF) and prostaglandin (PG)E(2), is substantially enhanced following antigen-dependent ligation of the high-affinity receptor for IgE (Fc epsilon RI). These responses were associated with enhanced activation of phosphoinositide 3-kinase (PI3K), and downstream activation of the tyrosine protein kinase Btk, with subsequent enhanced phospholipase (PL)C gamma-mediated Ca(2+) mobilization, Rac activation and F-actin rearrangement. Antigen-induced chemotaxis, and the ability of antigen to amplify responses mediated by SCF(2) adenosine and PGE(2) were suppressed following inhibition of PI3K, and were impaired in BMMCs derived from Btk(/) mice. There were corresponding decreases in the PLC gamma-mediated Ca(2+) signal, Rac activation and F-actin rearrangement, which, as they are essential for BMMC chemotaxis, accounts for the impaired migration of Btk-deficient cells. Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses. C1 [Kuehn, Hye Sun; Radinger, Madeleine; Brown, Jared M.; Metcalfe, Dean D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Ali, Khaled; Vanhaesebroeck, Bart] Inst Canc Barts, Ctr Cell Signalling, London EC1M 6BQ, England. [Ali, Khaled; Vanhaesebroeck, Bart] London Sch Med & Dent, John Vane Sci Ctr, London EC1M 6BQ, England. [Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov FU National Institutes of Health FX This work was supported by the Division of Intramural Research of NIAID and NHLBI within the National Institutes of Health. We thank Anne B. Satterthwaite, University of Texas Southwestern Medical Center, for kindly providing Btk-/- mice. Deposited in PMC for release after 12 months. NR 41 TC 31 Z9 33 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2010 VL 123 IS 15 BP 2576 EP 2585 DI 10.1242/jcs.071043 PG 10 WC Cell Biology SC Cell Biology GA 629CN UT WOS:000280172000006 PM 20587594 ER PT J AU Hyde, RK Liu, PP AF Hyde, R. Katherine Liu, P. Paul TI RUNX1 Repression-Independent Mechanisms of Leukemogenesis by Fusion Genes CBFB-MYH11 and AML1-ETO (RUNX1-RUNX1T1) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE CBFB; RUNX1; AML1-ETO; CBFB-MYH11; AML ID ACUTE MYELOID-LEUKEMIA; CORE-BINDING-FACTOR; ACUTE MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; CBF-BETA-SMMHC; FETAL LIVER HEMATOPOIESIS; MYOSIN HEAVY-CHAIN; TRANSCRIPTION FACTOR; DEFINITIVE HEMATOPOIESIS; PROTEIN AML1-ETO AB The core binding factor (CBF) acute myeloid leukemias (AMLs) are a prognostically distinct subgroup that includes patients with the inv(16) and t(8 21) chromosomal rearrangements. Both of these rearrangements result in the formation of fusion proteins, CBFB-MYH11 and AML1-ETO, respectively, that involve members of the CBF family of transcription factors. It has been proposed that both of these fusion proteins function primarily by dominantly repressing normal CBF transcription However, recent reports have indicted that additional. CBF-repression independent activities may be equally important during leukemogenesis This article will focus on these recent advances. J. Cell. Biochem. 110. 1039-1045, 2010 Published 2010 Wiley-Liss, Inc. C1 [Hyde, R. Katherine; Liu, P. Paul] NHGRI, Oncogenesis & Dev Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Liu, PP (reprint author), 49 Convent Dr,3A26,Bldg 49, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012; OI Liu, Paul/0000-0002-6779-025X; Hyde, R. Katherine/0000-0003-2808-1749 FU National Human Genome Research Institute, National Institutes of Health FX Grant sponsor Intramural Research Program of National Human Genome Research Institute, National Institutes of Health; This work was supported by the Intramural Research Program of National Human Genome Research Institute, National Institutes of Health NR 57 TC 7 Z9 7 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG 1 PY 2010 VL 110 IS 5 BP 1039 EP 1045 DI 10.1002/jcb.22596 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 632PE UT WOS:000280435900001 PM 20589720 ER PT J AU Veronese, M Bertoldo, A Bishu, S Unterman, A Tomasi, G Smith, CB Schmidt, KC AF Veronese, Mattia Bertoldo, Alessandra Bishu, Shrinivas Unterman, Aaron Tomasi, Giampaolo Smith, Carolyn Beebe Schmidt, Kathleen C. TI A spectral analysis approach for determination of regional rates of cerebral protein synthesis with the L-[1-C-11]leucine PET method SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain; kinetic analysis; leucine; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; AMINO-ACIDS; BRAIN; TISSUE; MOUSE; MODEL; VALIDATION; RECEPTORS; BINDING AB A spectral analysis approach was used to estimate kinetic model parameters of the L-[1-C-11] leucine positron emission tomography (PET) method and regional rates of cerebral protein synthesis (rCPS) in predefined regions of interest (ROIs). Unlike analyses based on the assumption that tissue ROIs are kinetically homogeneous, spectral analysis allows for heterogeneity within a region. To improve estimation performance, a new approach was developed-spectral analysis with iterative filter (SAIF). In simulation SAIF produced low bias, low variance estimates of the influx rate constant for leucine (K-1), blood volume fraction (V-b), fraction of unlabeled leucine in the tissue precursor pool for protein synthesis derived from arterial plasma (lambda), and rCPS. Simulation of normal count rate studies showed that SAIF applied to ROI time-activity curves (TACs) performed comparably to the basis function method (BFM) applied to voxel TACs when voxelwise estimates were averaged over all voxels in the ROI. At low count rates, however, SAIF performed better. In measured L-[1-C-11] leucine PET data, there was good agreement between ROI-based SAIF estimates and average voxelwise BFM estimates of K-1, V-b, lambda, and rCPS. We conclude that SAIF sufficiently addresses the problem of tissue heterogeneity in ROI data and provides a valid tool for estimation of rCPS, even in low count rate studies. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1460-1476; doi: 10.1038/jcbfm.2010.26; published online 3 March 2010 C1 [Veronese, Mattia; Bishu, Shrinivas; Unterman, Aaron; Smith, Carolyn Beebe; Schmidt, Kathleen C.] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA. [Veronese, Mattia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, Padua, Italy. [Tomasi, Giampaolo] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA. RP Schmidt, KC (reprint author), NIMH, Sect Neuroadaptat & Prot Metab, Bldg 10,Rm 2D54,10 Ctr Dr, Bethesda, MD 20892 USA. EM SchmidtK@intra.nimh.nih.gov RI Veronese, Mattia/A-6012-2013; OI Veronese, Mattia/0000-0003-3562-0683; Bertoldo, Alessandra/0000-0002-6262-6354 FU Intramural Research Program, National Institute of Mental Health FX This research was supported by the Intramural Research Program, National Institute of Mental Health. NR 35 TC 10 Z9 10 U1 1 U2 4 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 AUG PY 2010 VL 30 IS 8 BP 1460 EP 1476 DI 10.1038/jcbfm.2010.26 PG 17 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 634EH UT WOS:000280561900006 PM 20197782 ER PT J AU Coffey, BJ Rapoport, J AF Coffey, Barbara J. Rapoport, Judith TI Obsessive-Compulsive Disorder and Tourette's Disorder: Where Are We Now? SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 [Coffey, Barbara J.] NYU, Ctr Child Study, New York, NY 10016 USA. [Coffey, Barbara J.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Rapoport, Judith] NIMH, Bethesda, MD 20892 USA. RP Coffey, BJ (reprint author), NYU, Ctr Child Study, New York, NY 10016 USA. NR 4 TC 2 Z9 2 U1 4 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2010 VL 20 IS 4 SI SI BP 235 EP 236 DI 10.1089/cap.2010.2041 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 645FG UT WOS:000281435700001 PM 20807061 ER PT J AU Grant, P Song, JY Swedo, SE AF Grant, Paul Song, Jane Y. Swedo, Susan E. TI Review of the Use of the Glutamate Antagonist Riluzole in Psychiatric Disorders and a Description of Recent Use in Childhood Obsessive-Compulsive Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; OPEN-LABEL TRIAL; ANTIGLUTAMATERGIC AGENT RILUZOLE; SERUM CONCENTRATIONS; INDUCED PANCREATITIS; BIPOLAR DEPRESSION; IN-VITRO; PHARMACOKINETICS; THERAPY; ALS AB The antiglutamatergic drug riluzole (Rilutek (R)) is presently being used off label in the treatment of psychiatric conditions in adult patients and, increasingly, in children. This article briefly reviews the pharmacology of this drug and its current investigative and clinical uses and adverse effects. It also reports on our experience to date in the study of the drug in children, with emphasis on adverse effects noted so far in these younger patients. C1 [Grant, Paul; Song, Jane Y.; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci PDN Branch, Bethesda, MD 20892 USA. RP Grant, P (reprint author), NIMH, Pediat & Dev Neurosci PDN Branch, Bldg 10,Rm 4N208,MSC 1255, Bethesda, MD 20892 USA. EM paul.grant@mail.nih.gov NR 60 TC 25 Z9 27 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2010 VL 20 IS 4 SI SI BP 309 EP 315 DI 10.1089/cap.2010.0009 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 645FG UT WOS:000281435700009 PM 20807069 ER PT J AU Malek, R Chong, AY Lupsa, BC Lungu, AO Cochran, EK Soos, MA Semple, RK Balow, JE Gorden, P AF Malek, R. Chong, A. Y. Lupsa, B. C. Lungu, A. O. Cochran, E. K. Soos, M. A. Semple, R. K. Balow, J. E. Gorden, P. TI Treatment of Type B Insulin Resistance: A Novel Approach to Reduce Insulin Receptor Autoantibodies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HODGKINS-DISEASE; ANTIBODIES; PATIENT; THERAPY; HYPOGLYCEMIA; ADIPONECTIN; BINDING; CYCLOPHOSPHAMIDE; CYCLOSPORINE AB Background: Type B insulin resistance belongs to a class of diseases caused by an autoantibody to a cell surface receptor. Blockade of insulin action results in hyperglycemia, hypercatabolism, severe acanthosis nigricans, and hyperandrogenism in women. This rare autoimmune disorder has been treated with various forms of immunosuppression with mixed success. Methods: We describe 14 patients with type B insulin resistance referred to the National Institutes of Health, adding to an existing cohort of 24 patients. This report focuses on seven patients who were treated with an intensive combination protocol of rituximab, cyclophosphamide, and pulse corticosteroids aimed at control of pathogenic autoantibody production. Hematological, metabolic, and endocrine parameters, including fasting glucose, glycated hemoglobin, insulin dose, lipids, and testosterone, were monitored before and after treatment. Results: All seven treated patients achieved remission, defined as amelioration of hyperglycemia, discontinuation of insulin therapy, and resolution of hyperandrogenism. Glycated hemoglobin has normalized in all seven treated patients. Remission was achieved on average in 8 months from initiation of treatment. The medication regimen was well tolerated, with no serious adverse events. Conclusions: In seven patients with type B insulin resistance, standardized treatment with rituximab, cyclophosphamide, and pulse steroids results in remission of the disease. Future studies will determine whether this treatment protocol can be applied to other autoantibody/cell surface receptor disease states. (J Clin Endocrinol Metab 95: 3641-3647, 2010) C1 [Malek, R.; Chong, A. Y.; Lupsa, B. C.; Lungu, A. O.; Cochran, E. K.; Gorden, P.] NIDDKD, Clin Endocrine Branch, NIH, Bethesda, MD 20892 USA. [Balow, J. E.] NIDDKD, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. [Soos, M. A.; Semple, R. K.] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 0QQ, England. RP Malek, R (reprint author), Bldg 10 CRC,Room 5-5940,10 Ctr Dr,MSC 1453, Bethesda, MD 20892 USA. EM malekr@niddk.nih.gov OI Semple, Robert/0000-0001-6539-3069 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Wellcome Trust [080952/Z/06/Z]; U.K. National Institute for Health Research Cambridge Biomedical Research Centre FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; the Wellcome Trust (Intermediate Clinical Fellowship 080952/Z/06/Z, to R.K.S.); and the U.K. National Institute for Health Research Cambridge Biomedical Research Centre. NR 25 TC 19 Z9 25 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2010 VL 95 IS 8 BP 3641 EP 3647 DI 10.1210/jc.2010-0167 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400014 PM 20484479 ER PT J AU Preis, SR Massaro, JM Hoffmann, U D'Agostino, RB Levy, D Robins, SJ Meigs, JB Vasan, RS O'Donnell, CJ Fox, CS AF Preis, Sarah Rosner Massaro, Joseph M. Hoffmann, Udo D'Agostino, Ralph B., Sr. Levy, Daniel Robins, Sander J. Meigs, James B. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Neck Circumference as a Novel Measure of Cardiometabolic Risk: The Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VISCERAL ADIPOSE-TISSUE; FATTY-ACID-METABOLISM; INSULIN-RESISTANCE; SLEEP-APNEA; ASSOCIATION; OBESITY; HYPERTENSION; CHOLESTEROL; POPULATION; COMMUNITY AB Background: Neck circumference, a proxy for upper-body sc fat, may be a unique fat depot that confers additional cardiovascular risk above and beyond central body fat. Methods and Results: Participants with neck circumference measures who underwent multidetector computed tomography to assess visceral adipose tissue (VAT) were included [n = 3307, 48% women; mean age = 51 yr; mean body mass index (BMI) = 27.8 kg/m(2); mean neck circumference = 40.5 cm (men) and 34.2 cm (women)]. Sex-specific linear regression models were used to assess the association between SD increase in neck circumference and cardiovascular disease (CVD) risk factors (systolic and diastolic blood pressure; total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglycerides; and fasting plasma glucose, insulin, proinsulin, and homeostasis model assessment of insulin resistance). Neck circumference was correlated with VAT [r = 0.63 (men); r = 0.74 (women); P < 0.001] and BMI [r = 0.79 (men); r = 0.80 (women); P < 0.001]. After further adjustment for VAT, neck circumference was positively associated with systolic blood pressure, diastolic blood pressure in men only, triglycerides, fasting plasma glucose in women only, insulin, proinsulin, and homeostasis model assessment of insulin resistance and was inversely associated with high-density lipoprotein (all P values < 0.01). Similar results were observed in models that adjusted for both VAT and BMI. In a secondary analysis of incident CVD as an outcome, there was no statistically significant association observed for neck circumference in multivariable-adjusted models. Conclusions: Neck circumference is associated with CVD risk factors even after adjustment for VAT and BMI. These findings suggest that upper-body sc fat may be a unique, pathogenic fat depot. (J Clin Endocrinol Metab 95: 3701-3710, 2010) C1 [Preis, Sarah Rosner; D'Agostino, Ralph B., Sr.; Levy, Daniel; Robins, Sander J.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham, MA 01702 USA. [Preis, Sarah Rosner; D'Agostino, Ralph B., Sr.; Levy, Daniel; Robins, Sander J.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA. [Preis, Sarah Rosner; Levy, Daniel; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20824 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Massachusetts Gen Hosp, Sect Prevent Med, Boston, MA 02114 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Massachusetts Gen Hosp, Serv Cardiol, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Preis, Sarah/0000-0002-9360-4166; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; American Diabetes Association FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195) and by an American Diabetes Association Career Development Award (to J.B.M.). NR 31 TC 94 Z9 108 U1 0 U2 6 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 AUG PY 2010 VL 95 IS 8 BP 3701 EP 3710 DI 10.1210/jc.2009-1779 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400021 PM 20484490 ER PT J AU Beydoun, MA Boueiz, A Shroff, MR Beydoun, HA Wang, Y Zonderman, AB AF Beydoun, M. A. Boueiz, A. Shroff, M. R. Beydoun, H. A. Wang, Y. Zonderman, A. B. TI Associations among 25-Hydroxyvitamin D, Diet Quality, and Metabolic Disturbance Differ by Adiposity in Adults in the United States SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR RISK-FACTORS; VITAMIN-D-RECEPTOR; 3RD NATIONAL-HEALTH; C-REACTIVE PROTEIN; LOW SERUM 25-HYDROXYVITAMIN-D; TYPE-2 DIABETES-MELLITUS; MAJOR CHRONIC DISEASE; BODY-MASS INDEX; INSULIN-RESISTANCE AB Context: Recent evidence indicates that a higher plasma level of 25-hydroxyvitamin D [25(OH) D] is associated with lower adiposity and a reduced number of metabolic disturbances (MetD). Objectives: We examined associations among dietary quality, 25(OH) D, percent body fat (% BF), and MetD, and a pathway linking them, across central obesity. Design: This cross-sectional nationally representative study used extensive data from the National Health and Nutrition Examination Surveys of 2001-2004. Participants: U. S. adults aged at least 20 yr were stratified by central obesity (CO) status. Sample sizes ranged from 1943 (all MetD combined) to 7796 (each component). Main Outcome Measures: % BF was measured using dual-energy x-ray absorptiometry, and MetD was measured with individual continuous nonadiposity outcomes (e. g. fasting plasma glucose) and with a composite count index of binary MetD with prespecified cutoff points (Index I). Results: A higher 25(OH) D was associated with better dietary quality, lower % BF, and lower number of MetD. These inverse 25(OH) D-% BF and 25(OH) D-MetD associations (i.e. fasting blood glucose, homeostatic model assessment of insulin resistance, C-reactive protein, and Index I) were significantly stronger among the CO(+) group. Finally, the pathway linking the dairy component of the Healthy Eating Index (HEI(dairy)) to Index I through 25(OH) D and % BF indicated complete mediation among the CO(-) group, but HEIdairy and 25(OH) D had direct inverse associations with Index I among the CO(+) group. Conclusions: Due to potential genetic differences between CO(-) and CO(+) groups, empowering U. S. adults with central obesity to make related behavioral changes may be especially effective in improving their vitamin D status and metabolic profile. (J Clin Endocrinol Metab 95: 3814-3827, 2010) C1 [Beydoun, M. A.] NIA, NIH, Biomed Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. [Boueiz, A.] Johns Hopkins Univ, Sch Med, Dept Internal Med, Baltimore, MD 21205 USA. [Wang, Y.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD 21205 USA. [Shroff, M. R.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Beydoun, H. A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA. RP Beydoun, MA (reprint author), NIA, NIH, Biomed Res Ctr, Intramural Res Program, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA. EM baydounm@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging, (NIA/NIH) FX This study was supported by the National Institute on Aging, Intramural Research Program (NIA/NIH/IRP). NR 85 TC 32 Z9 32 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 AUG PY 2010 VL 95 IS 8 BP 3814 EP 3827 DI 10.1210/jc.2010-0410 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400037 PM 20463091 ER PT J AU Laferrere, B Swerdlow, N Bawa, B Arias, S Bose, M Olivan, B Teixeira, J McGinty, J Rother, KI AF Laferrere, Blandine Swerdlow, Nicholas Bawa, Baani Arias, Sara Bose, Mousumi Olivan, Blanca Teixeira, Julio McGinty, James Rother, Kristina I. TI Rise of Oxyntomodulin in Response to Oral Glucose after Gastric Bypass Surgery in Patients with Type 2 Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; WEIGHT-LOSS; FOOD-INTAKE; INCRETIN LEVELS; OBESE SUBJECTS; DIET; ENTEROGLUCAGON; PANCREAS; RECEPTOR; PLASMA AB Context: The mechanisms by which Roux-en-Y gastric bypass surgery (GBP) results in sustained weight loss and remission of type 2 diabetes are not fully understood. Objective: We hypothesized that the anorexic hormone oxyntomodulin (OXM) might contribute to the marked weight reduction and the rapid improvement in glucose metabolism observed in morbidly obese diabetic patients after GBP. Methods: Twenty obese women with type 2 diabetes were studied before and 1 month after GBP (n = 10) or after a diet-induced equivalent weight loss (n = 10). Patients from both groups were matched for age, body weight, body mass index, and diabetes duration and control. OXM concentrations were measured during a 50-g oral glucose challenge before and after weight loss. Results: At baseline, OXM levels (fasting and stimulated values) were indistinguishable between the GBP and the diet group. However, OXM levels rose remarkably in response to an oral glucose load more than 2-fold (peak, 5.25 +/- 1.31 to 13.8 +/- 16.2 pmol/liter; P = 0.025) after GBP but not after diet. The peak of OXM after glucose was significantly correlated with glucagon-like peptide-1 and peptide YY3-36. Conclusions: Our data suggest that the observed changes in OXM primarily occur in response to GBP and not as a consequence of weight loss. These changes were observed early after surgery and occurred in parallel with previously reported increases in incretins and peptide YY. We speculate that the combination of gut hormone changes is essential for the improved glucose homeostasis and may partially explain the success of this surgery on diabetes resolution and weight loss. (J Clin Endocrinol Metab 95: 4072-4076, 2010) C1 [Laferrere, Blandine; Swerdlow, Nicholas; Bawa, Baani; Arias, Sara; Bose, Mousumi; Olivan, Blanca] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Obes Res Ctr, New York, NY 10025 USA. [Teixeira, Julio; McGinty, James] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Bariatr Div, New York, NY 10025 USA. [Rother, Kristina I.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Laferrere, B (reprint author), St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10025 USA. EM BBL14@columbia.edu FU American Diabetes Association [CR-7-05, CR-18]; National Institutes of Health (NIH) [R01-DK67561, NYONRCDK-26687, DERC DK-63068-05]; National Center for Research Resources, NIH [UL1 RR024156]; NIH Roadmap for Medical Research; NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by grants from the American Diabetes Association CR-7-05 and CR-18, and National Institutes of Health (NIH), R01-DK67561, NYONRCDK-26687, DERC DK-63068-05, and UL1 RR024156 from the National Center for Research Resources, a component of the NIH and NIH Roadmap for Medical Research, and in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. NR 20 TC 49 Z9 53 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2010 VL 95 IS 8 BP 4072 EP 4076 DI 10.1210/jc.2009-2767 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400071 PM 20501690 ER PT J AU Berger, VW AF Berger, Vance W. TI Testing for baseline balance: Can we finally get it right? SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA. EM vb78c@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 4 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 2010 VL 63 IS 8 BP 939 EP 940 DI 10.1016/j.jclinepi.2010.02.014 PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 619OQ UT WOS:000279439900023 PM 20456920 ER PT J AU Tam, J Vemuri, VK Liu, J Batkai, S Mukhopadhyay, B Godlewski, G Osei-Hyiaman, D Ohnuma, S Ambudkar, SV Pickel, J Makriyannis, A Kunos, G AF Tam, Joseph Vemuri, V. Kiran Liu, Jie Batkai, Sandor Mukhopadhyay, Bani Godlewski, Grzegorz Osei-Hyiaman, Douglas Ohnuma, Shinobu Ambudkar, Suresh V. Pickel, James Makriyannis, Alexandros Kunos, George TI Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DIET-INDUCED OBESITY; ENDOCANNABINOID SYSTEM; ENERGY-BALANCE; FOOD-INTAKE; ADIPOSE-TISSUE; OVERWEIGHT PATIENTS; LEPTIN RESISTANCE; SUBCUTANEOUS FAT; WEIGHT-LOSS; FA/FA RATS AB Obesity and its metabolic consequences are a major public health concern worldwide. Obesity is associated with overactivity of the endocannabinoicl system, which is involved in the regulation of appetite, lipogenesis, and insulin resistance. Cannabinoid-1 receptor (CB(1)R) antagonists reduce body weight and improve cardiometabolic abnormalities in experimental and human obesity, but their therapeutic potential is limited by neuropsychiatric side effects. Here we have demonstrated that a CB(1)R neutral antagonist largely restricted to the periphery does not affect behavioral responses mediated by CB(1)R in the brains of mice with genetic or diet-induced obesity, but it does cause weight-independent improvements in glucose homeostasis, fatty liver, and plasma lipid profile. These effects were due to blockade of CB(1)R in peripheral tissues, including the liver, as verified through the use of CB(1)R-deficient mice with or without transgenic expression of CB(1)R in the liver. These results suggest that targeting peripheral CB(1)R has therapeutic potential for alleviating cardiometabolic risk in obese patients. C1 [Tam, Joseph; Liu, Jie; Batkai, Sandor; Mukhopadhyay, Bani; Godlewski, Grzegorz; Osei-Hyiaman, Douglas; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Vemuri, V. Kiran; Makriyannis, Alexandros] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. [Ohnuma, Shinobu; Ambudkar, Suresh V.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Pickel, James] NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM a.makriyannis@neu.edu; gkunos@mail.nih.gov RI Batkai, Sandor/H-7983-2014 FU NIH [2R01 DA007215] FX This work was supported by the NIH (intramural funds from the NIAAA to G. Kunos and from the NCI to S.V. Ambudkar, and 2R01 DA007215 to A. Makriyannis). We thank Christoph Buettner for helpful discussions. NR 63 TC 191 Z9 194 U1 2 U2 8 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 AUG PY 2010 VL 120 IS 8 BP 2953 EP 2966 DI 10.1172/JCI42551 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 633HI UT WOS:000280492100030 PM 20664173 ER PT J AU Mendoza, A Hong, SH Osborne, T Khan, MA Campbell, K Briggs, J Eleswarapu, A Buquo, L Ren, L Hewitt, SM Dakir, E Garfield, S Walker, R Merlino, G Green, JE Hunter, KW Wakefield, LM Khanna, C AF Mendoza, Arnulfo Hong, Sung-Hyeok Osborne, Tanasa Khan, Mohammed A. Campbell, Kirk Briggs, Joseph Eleswarapu, Ananth Buquo, Lauren Ren, Ling Hewitt, Stephen M. Dakir, El-H. Garfield, Susan Walker, Renard Merlino, Glenn Green, Jeffrey E. Hunter, Kent W. Wakefield, Lalage M. Khanna, Chand TI Modeling metastasis biology and therapy in real time in the mouse lung SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INTRAVITAL VIDEOMICROSCOPY; MAMMARY-TUMOR; MURINE MODEL; IN-VIVO; OSTEOSARCOMA; CELLS; PROGRESSION; BEHAVIOR; CYTOSKELETON; SYSTEMS AB Pulmonary metastasis remains the leading ca use of death for cancer patients. Opportunities to improve treatment outcomes for patients require new methods to study and view the biology of metastatic progression. Here, we describe an ex vivo pulmonary metastasis assay (PuMA) in which the metastatic progression of GFP-expressing cancer cells, from a single cell to the formation of multicellular colonies, in the mouse lung microenvironment was assessed in real time for up to 21 days. The biological validity of this assay was confirmed by its prediction of the in vivo behavior of a variety of high- and low-metastatic human and mouse cancer cell lines and the discrimination of tumor microenvironments in the lung that were most permissive to metastasis. Using this approach, we provide what we believe to be new insights into the importance of tumor cell interactions with the stromal components of the lung microenvironment. Finally, the translational utility of this assay was demonstrated through its use in the evaluation of therapeutics at discrete time points during metastatic progression. We believe that this assay system is uniquely capable of advancing our understanding of both metastasis biology and therapeutic strategies. C1 [Mendoza, Arnulfo; Hong, Sung-Hyeok; Osborne, Tanasa; Khan, Mohammed A.; Campbell, Kirk; Briggs, Joseph; Eleswarapu, Ananth; Buquo, Lauren; Ren, Ling; Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Khan, Mohammed A.; Campbell, Kirk; Eleswarapu, Ananth] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Dakir, El-H.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Garfield, Susan] NCI, Ctr Canc Res, Confocal Microscopy Core Facil, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. [Walker, Renard; Merlino, Glenn; Green, Jeffrey E.; Hunter, Kent W.; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 37 Convent Dr,Km 2144, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov RI DAKIR, EL HABIB/O-1383-2015; OI Khan, Mohammed/0000-0002-6985-2418; Hewitt, Stephen/0000-0001-8283-1788 FU Howard Hughes Medical Institute NR 25 TC 33 Z9 34 U1 1 U2 3 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 AUG PY 2010 VL 120 IS 8 BP 2979 EP 2988 DI 10.1172/JCI40252 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 633HI UT WOS:000280492100032 PM 20644255 ER PT J AU Conville, PS Murray, PR Zelazny, AM AF Conville, Patricia S. Murray, Patrick R. Zelazny, Adrian M. TI Evaluation of the Integrated Database Network System (IDNS) SmartGene Software for Analysis of 16S rRNA Gene Sequences for Identification of Nocardia Species SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PATHOGEN; COMPLEX AB 16S rRNA gene sequences of 102 Nocardia isolates were analyzed using the Integrated Database Network System (IDNS) SmartGene centroid database. A total of 76% of the isolates were correctly identified. Discordant identifications were due to inadequate centroid length (3 species), inaccurate or insufficient entries in the public databases (5 species), and heterogeneous sequences among members of a species (1 species). C1 [Conville, Patricia S.; Murray, Patrick R.; Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr,US Dept Hlth & Hum, Bethesda, MD 20892 USA. RP Conville, PS (reprint author), NIH, Microbiol Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr,US Dept Hlth & Hum, 10 Ctr Dr,MSC 1508,Bldg 10,Room 2C-385, Bethesda, MD 20892 USA. EM pconville@mail.nih.gov NR 10 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2010 VL 48 IS 8 BP 2995 EP 2998 DI 10.1128/JCM.00681-10 PG 4 WC Microbiology SC Microbiology GA 634AQ UT WOS:000280550500059 PM 20573863 ER PT J AU Hallett, M AF Hallett, Mark TI Physiology of psychogenic movement disorders SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Review DE Clinical neurophysiology; Conversion disorder; Dystonia; Gait; Myoclonus; Parkinsonism; Psychogenic movement disorders; Somatization; Tremor ID REGIONAL PAIN SYNDROME; WRITERS CRAMP; PROPRIOSPINAL MYOCLONUS; ASSOCIATIVE PLASTICITY; CLINICAL-FEATURES; FUNCTIONAL MRI; LIE DETECTION; DYSTONIA; TREMOR; CORTEX AB Psychogenic movement disorders (PMDs) are common, but their physiology is largely unknown. In most situations, the movement is involuntary, but in a minority, when the disorder is malingering or factitious, the patient is lying and the movement is voluntary. Physiologically, we cannot tell the difference between voluntary and involuntary. The Bereitschaftspotential (BP) is indicative of certain brain mechanisms for generating movement, and is seen with ordinarily voluntary movements, but by itself does not indicate that a movement is voluntary. There are good clinical neurophysiological methods available to determine whether myoclonus or tremor is a PMD. For example, psychogenic myoclonus generally has a BP, and psychogenic stimulus-sensitive myoclonus has a variable latency with times similar to normal reaction times. Psychogenic tremor will have variable frequency over time, be synchronous in the two arms, and might well be entrained with voluntary rhythmic movements. These facts suggest that PMDs share voluntary mechanisms for movement production. There are no definitive tests to differentiate psychogenic dystonia from organic dystonia, although one has been recently reported. Similar physiological abnormalities are seen in both groups. The question arises as to how a movement can be produced with voluntary mechanisms, but not be considered voluntary. Published by Elsevier Ltd. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU NINDS Intramural Research Program FX This work was supported by the NINDS Intramural Research Program. NR 53 TC 38 Z9 39 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD AUG PY 2010 VL 17 IS 8 BP 959 EP 965 DI 10.1016/j.jocn.2009.11.021 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 623GK UT WOS:000279726700001 PM 20493708 ER PT J AU Fouladi, M Park, JR Stewart, CF Gilbertson, RJ Schaiquevich, P Sun, JF Reid, JM Ames, MM Speights, R Ingle, AM Zwiebel, J Blaney, SM Adamson, PC AF Fouladi, Maryam Park, Julie R. Stewart, Clinton F. Gilbertson, Richard J. Schaiquevich, Paula Sun, Junfeng Reid, Joel M. Ames, Matthew M. Speights, Roseanne Ingle, Ashish M. Zwiebel, James Blaney, Susan M. Adamson, Peter C. TI Pediatric Phase I Trial and Pharmacokinetic Study of Vorinostat: A Children's Oncology Group Phase I Consortium Report SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE-DEACETYLASE INHIBITORS; T-CELL LYMPHOMA; MOLECULAR-MECHANISMS; ADVANCED CANCER; SOLID TUMORS; SAHA; NEUROBLASTOMA; COMBINATION; THERAPY AB Purpose The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of vorinostat administered as a single agent and in combination 13-cis retinoic acid (13cRA) in children with refractory solid tumors; to evaluate the tolerability of the solid tumor MTD in children with refractory leukemias; and to characterize the pharmacokinetics of a vorinostat suspension in children. Patients and Methods Vorinostat was administered orally daily starting at 180 mg/m(2)/d with escalations planned in 30% increments. Pharmacokinetic studies were performed with the initial dose. Acetyl-histone (H3) accumulation was assessed by Western blotting of peripheral blood mononuclear cells (PBMC). Results Sixty-four patients were enrolled on this multipart trial. In patients with solid tumors, the MTD was 230 mg/m(2)/d with dose-limiting neutropenia, thrombocytopenia, and hypokalemia at 300 mg/m(2)/d. DLTs observed with the combination of 13cRA and vorinostat included thrombocytopenia, neutropenia, anorexia, and hypertriglyceridemia, resulting in a MTD of vorinostat 180 mg/m(2)/d 4 times per week and 13cRA 80 mg/m(2)/dose twice per day, days 1 through 14 every 28 days. Wide interpatient variability was noted in vorinostat disposition, with area under the concentration-time curves at 230 mg/m(2)/d for the capsule (range, 1,415 to 9,291 ng/mL x hr) and oral suspension (range, 1,186 to 4,780 ng/mL x hr). Significant accumulation of acetylated H3 histone in PBMC was observed after administration of vorinostat, particularly at higher doses. One patient with neuroblastoma experienced a complete response to the combination. Conclusion In children with recurrent solid tumors, vorinostat is well-tolerated at 230 mg/m(2)/d, with a modest dose reduction being required when combining vorinostat with 13cRA. Drug disposition is similar to that observed in adults. C1 St Jude Childrens Hosp, Memphis, TN 38105 USA. Seattle Childrens Hosp, Seattle, WA USA. Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. Mayo Clin, Coll Med, Rochester, MN USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Fouladi, M (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Hematol Oncol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM maryam.fouladi@cchmc.org FU National Cancer Institute [U01 CA97452, NCRR M01 RR00188] FX Supported by Grants No. U01 CA97452 and NCRR M01 RR00188 from the National Cancer Institute. NR 30 TC 74 Z9 77 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2010 VL 28 IS 22 BP 3623 EP 3629 DI 10.1200/JCO.2009.25.9119 PG 7 WC Oncology SC Oncology GA 633GA UT WOS:000280486700014 PM 20606092 ER PT J AU Figg, WD Smith, EK Price, DK English, BC Thurman, PW Steinberg, SM Emanuel, E AF Figg, William D. Smith, Erika K. Price, Douglas K. English, Bevin C. Thurman, Paul W. Steinberg, Seth M. Emanuel, Ezekiel TI Disclosing a Diagnosis of Cancer: Where and How Does It Occur? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BAD-NEWS; COMMUNICATION; PATIENT; PREFERENCES; ATTITUDES AB Purpose While disclosing a cancer diagnosis to a patient is common practice, how it is disclosed and the impact it has on the patient are poorly understood. We examined how cancer diagnoses were first given to patients and the impact of different aspects of disclosure on patient satisfaction. Patients and Methods We provided a self-administered questionnaire to a total of 460 oncology patients of the National Cancer Institute (NCI) being treated at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD. Results Of the 437 patients who completed the survey, 54% were told their diagnosis in-person in the physician's office, 18% by phone, and 28% in the hospital. Forty-four percent of patients reported discussions of 10 minutes or fewer, 53% reported discussions lasting longer than 10 minutes, and 5% could not remember. Treatment options were not discussed for 31% of those who could clearly remember. Higher mean satisfaction scores were associated with diagnoses revealed in person rather than over the phone (68.2 +/- 1.6 v 47.2 +/- 3.7), diagnoses revealed in a personal setting rather than an impersonal setting (68.9 +/- 1.6 v 55.7 +/- 2.8), discussions lasting longer than 10 minutes rather than fewer than 10 minutes (73.5 +/- 1.9 v 54.1 +/- 2.4), and inclusion of treatment options rather than exclusion (72.0 +/- 1.9 v 50.7 +/- 3.2; P < .001 for each aspect). Conclusion Physicians should disclose a cancer diagnosis in a personal setting, discussing the diagnosis and treatment options for a substantial period of time whenever possible. C1 NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Figg, William D.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10 Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 21 TC 16 Z9 16 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2010 VL 28 IS 22 BP 3630 EP 3635 DI 10.1200/JCO.2009.24.6389 PG 6 WC Oncology SC Oncology GA 633GA UT WOS:000280486700015 PM 20606078 ER PT J AU Kelly, RJ Browne, SK Rajan, A Giaccone, G AF Kelly, Ronan J. Browne, Sarah K. Rajan, Arun Giaccone, Giuseppe TI Thymoma-Associated Paraneoplastic Polymyositis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID AIRE; CELLS C1 [Kelly, Ronan J.; Rajan, Arun; Giaccone, Giuseppe] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Browne, Sarah K.] NIAID, NIH, Bethesda, MD 20892 USA. RP Kelly, RJ (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 7 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2010 VL 28 IS 22 BP E378 EP E378 DI 10.1200/JCO.2010.28.7946 PG 1 WC Oncology SC Oncology GA 633GA UT WOS:000280486700027 PM 20458028 ER PT J AU Cizza, G Nguyen, VT Eskandari, F Duan, ZG Wright, EC Reynolds, JC Ahima, RS Blackman, MR AF Cizza, Giovanni Nguyen, Vi T. Eskandari, Farideh Duan, Zhigang Wright, Elizabeth C. Reynolds, James C. Ahima, Rexford S. Blackman, Marc R. CA POWER Study Grp TI Low 24-Hour Adiponectin and High Nocturnal Leptin Concentrations in a Case-Control Study of Community-Dwelling Premenopausal Women With Major Depressive Disorder: The Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression (POWER) Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLASMA ADIPONECTIN; WEIGHT-LOSS; MARKERS; RISK; ASSOCIATION; PULSATILITY; PREVALENCE; ADIPOKINES; BIOMARKERS; DYNAMICS AB Objective: Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipo-cytokine with anti-inflammatory and antiatherogenic effects: Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were (1) to establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; (2) to assess whether there is a relationship between adiponectin and MDD; and (3) to explore the temporal relationships among adiponectin, leptin, corticotropin, and cortisol secretion. Method: We conducted a case-control study of community-dwelling premenopausal women with DSM-IV MDD (n=23) and age- and body mass index (BMI)-matched control subjects (n=23). Main outcome measures were circulating concentrations of adiponectin, leptin, corticotropin, and cortisol measured hourly for 24 hours. Subjects were recruited from July 1, 2001, to February 28, 2003. Results: Women with MDD had approximately 30% lower mean 24-hour concentration of adiponectin than did control subjects. Adiponectin concentration was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, mean nocturnal leptin concentration was higher in the MDD versus control groups. Mean leptin concentration was inversely related to cortisol and adiponectin concentrations, both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between corticotropin and cortisol concentrations was stronger in women with MDD than in control subjects, a finding consistent with hypothalamic-pituitary-adrenal (HPA) axis activation in MDD. Conclusions: In premenopausal women with MDD, reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis. J Clin Psychiatry 2010;71(8):1079-1087 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Cizza, Giovanni] NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. [Nguyen, Vi T.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Eskandari, Farideh] NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Duan, Zhigang; Wright, Elizabeth C.] NIDDK, Off Director, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Ahima, Rexford S.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Blackman, Marc R.] NIH, Endocrine Sect, NCCAM, Bethesda, MD 20892 USA. [Blackman, Marc R.] Vet Affairs Med Ctr, Res Serv, Washington, DC 20422 USA. RP Cizza, G (reprint author), NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH,CRC, Bldg 10,Rm 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov FU NIMH; NIDDK; NCCAM, NIH, Bethesda, Maryland FX The study was fully supported by the Intramural Research Programs of the NIMH; NIDDK; and NCCAM, NIH, Bethesda, Maryland. NR 45 TC 36 Z9 40 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2010 VL 71 IS 8 BP 1079 EP 1087 DI 10.4088/JCP.09m05314blu PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 643KY UT WOS:000281296500016 PM 20492842 ER PT J AU Findling, RL Landersdorfer, CB Kafantaris, V Pavuluri, M McNamara, NK McClellan, J Frazier, JA Sikich, L Kowatch, R Lingler, J Faber, J Taylor-Zapata, P Jusko, WJ AF Findling, Robert L. Landersdorfer, Cornelia B. Kafantaris, Vivian Pavuluri, Mani McNamara, Nora K. McClellan, Jon Frazier, Jean A. Sikich, Linmarie Kowatch, Robert Lingler, Jacqui Faber, Jon Taylor-Zapata, Perdita Jusko, William J. TI First-Dose Pharmacokinetics of Lithium Carbonate in Children and Adolescents SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE lithium; pharmacokinetics; adolescents; children; bipolar ID STEADY-STATE PHARMACOKINETICS; GLOMERULAR-FILTRATION-RATE; QUANTIFICATION; DOSAGE; SCHIZOPHRENIA; RELIABILITY; PARAMETERS; CLEARANCE; DISORDER; VALIDITY AB This study examines the pharmacokinetics of oral doses of lithium carbonate immediate-release capsules after administration of 600 or 900 mg in children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar I disorder. Lithium plasma concentrations were followed over 48 to 72 hours in 39 subjects (20 male and 19 female subjects; ages, 7-17 years) with mixed or manic episodes enrolled at 7 clinical sites participating in the Collaborative Lithium Trials. Population pharmacokinetic modeling was performed using NONMEM, and influences of patient covariates on pharmacokinetics parameters were examined. The pharmacokinetics of lithium was best described using a 2-compartment model with a lag time and first-order absorption. There was considerable variability in lithium exposures. Lithium clearance related best to fat-free mass. Inclusion of fat-free mass as a covariate reduced the between-subject variability from 52% to 42%. Lithium clearances did not vary systematically with age group, dose, sex, or creatinine clearances. Allometrically scaled clearance and volume of distribution from the population analysis were within the range reported in adults. Single-dose profiles of lithium in young patients with BP-1 show marked variability. Therefore, ongoing serum monitoring is needed during continued therapy. The developed population pharmacokinetic model may be used to predict other dosage regimens, support scaling from adult to pediatric pharmacokinetics, and support the design of future clinical trials. C1 [Findling, Robert L.] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Landersdorfer, Cornelia B.; Jusko, William J.] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. [Kafantaris, Vivian] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. [Pavuluri, Mani] Univ Illinois, Chicago, IL USA. [McClellan, Jon] Univ Washington, Seattle, WA 98195 USA. [Frazier, Jean A.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Sikich, Linmarie] Univ N Carolina, Chapel Hill, NC USA. [Kowatch, Robert] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Taylor-Zapata, Perdita] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Findling, RL (reprint author), Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, 10524 Euclid Ave,Suite 1155, Cleveland, OH 44106 USA. EM robert.findling@uhhospitals.org RI Jusko, William/G-4885-2015 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Department of Health and Human Services [HHSN275200503406C]; National Institutes of Health [GCRC M01 RR000080, RR025014] FX This project has been funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275200503406C. Additional support for clinical research centers used in this project has been funded by the National Institutes of Health, Grant Nos. GCRC M01 RR000080 and RR025014. NR 34 TC 9 Z9 9 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2010 VL 30 IS 4 BP 404 EP 410 DI 10.1097/JCP.0b013e3181e66a62 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 625MY UT WOS:000279900700010 PM 20531219 ER PT J AU Mannelli, P Peindl, K Patkar, AA Wu, T Pae, CU Gorelick, DA AF Mannelli, Paolo Peindl, Kathi Patkar, Ashwin A. Wu, Li-Tzy Pae, Chi-Un Gorelick, David A. TI Reduced Cannabis Use After Low-Dose Naltrexone Addition to Opioid Detoxification SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID MARIJUANA SMOKERS; HEROIN; THC C1 [Mannelli, Paolo; Peindl, Kathi; Patkar, Ashwin A.; Wu, Li-Tzy] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Pae, Chi-Un] Catholic Univ Korea, Coll Med, Seoul, South Korea. [Gorelick, David A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. RP Mannelli, P (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. EM paolo.mannelli@duke.edu FU Intramural NIH HHS; NIDA NIH HHS [01DA019901, DA15469, R01 DA019901, R21 DA015469, R21 DA015469-04, U10 DA013727] NR 16 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2010 VL 30 IS 4 BP 476 EP 478 DI 10.1097/JCP.0b013e3181e5c168 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 625MY UT WOS:000279900700030 PM 20631574 ER PT J AU McMullen, DC Hallenbeck, JM AF McMullen, David C. Hallenbeck, John M. TI Regulation of Akt during torpor in the hibernating ground squirrel, Ictidomys tridecemlineatus SO JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY LA English DT Article DE Ictidomys tridecemlineatus; Hibernation; Metabolic rate depression; Akt; PRAS40; mTOR ID TRANSCRIPTION FACTOR FOXO3A; METABOLIC-RATE DEPRESSION; AKT/PROTEIN-KINASE-B; SPERMOPHILUS-TRIDECEMLINEATUS; MAMMALIAN HIBERNATION; PROTEIN-KINASE; UP-REGULATION; TRANSLATIONAL CONTROLS; CEREBRAL-ISCHEMIA; GLYCOGEN-SYNTHASE AB The 13-lined ground squirrel (Ictidomys tridecemlineatus) is capable of entering into extended periods of torpor during winter hibernation. The state of torpor represents a hypometabolic shift wherein the rate of oxygen consuming processes are strongly repressed in an effort to maintain cellular homeostasis as the availability of food energy becomes limited. We are interested in studying hibernation/torpor because of the robust state of tolerance to constrained oxygen delivery, oligemia, and hypothermia achieved by the tissues of hibernating mammals. The role of the serine/threonine kinase Akt (also known as PKB) has been examined in torpor in previous studies. However, this is the first study that examines the level of Akt phosphorylation in the liver during the two transition phases of the hibernation cycle: entrance into torpor, and the subsequent arousal from torpor. Our results indicate that Akt is activated in the squirrel liver by phosphorylation of two key residues (Thr(308) and Ser(473)) during entrance into torpor and arousal from torpor. Moreover, we observed increased phosphorylation of key substrates of Akt during the two transition stages of torpor. Finally, this study reports the novel finding that PRAS40, a component of the TORC1 multi-protein complex and a potentially important modulator of metabolism, is regulated during torpor. C1 [McMullen, David C.; Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, 10 Ctr Dr,MSC 1401,Bldg 10,Room 5B02, Bethesda, MD 20892 USA. EM HallenbJ@ninds.nih.gov FU NIH, NINDS FX The authors would like to thank Jan Storey and Dr. Maria Spatz for critical review of this manuscript. This research was supported (in part) by the Intramural Research Program of the NIH, NINDS. NR 52 TC 33 Z9 39 U1 0 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0174-1578 J9 J COMP PHYSIOL B JI J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol. PD AUG PY 2010 VL 180 IS 6 BP 927 EP 934 DI 10.1007/s00360-010-0468-8 PG 8 WC Physiology; Zoology SC Physiology; Zoology GA 627YO UT WOS:000280081000014 PM 20352231 ER PT J AU Leopold, DA Rhodes, G AF Leopold, David A. Rhodes, Gillian TI A Comparative View of Face Perception SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article DE face; perception; comparative; vision; recognition ID CHIMPANZEES PAN-TROGLODYTES; MONKEYS MACACA-MULATTA; BUDGERIGARS MELOPSITTACUS-UNDULATUS; DOLPHINS TURSIOPS-TRUNCATUS; RIGHT-HEMISPHERE ADVANTAGE; SUPERIOR TEMPORAL SULCUS; FOLLOW GAZE DIRECTION; BOTTLE-NOSED-DOLPHIN; HUMANS HOMO-SAPIENS; HUMAN NEURAL SYSTEM AB Face perception serves as the basis for much of human social exchange. Diverse information can be extracted about an individual from a single glance at their face, including their identity, emotional state, and direction of attention. Neuropsychological and functional magnetic resonance imaging (fMRI) experiments reveal a complex network of specialized areas in the human brain supporting these face-reading skills. Here we consider the evolutionary roots of human face perception by exploring the manner in which different animal species view and respond to faces. We focus on behavioral experiments collected from both primates and nonprimates, assessing the types of information that animals are able to extract from the faces of their conspecifics, human experimenters, and natural predators. These experiments reveal that faces are an important category of visual stimuli for animals in all major vertebrate taxa, possibly reflecting the early emergence of neural specialization for faces in vertebrate evolution. At the same time, some aspects of facial perception are only evident in primates and a few other social mammals, and may therefore have evolved to suit the needs of complex social communication. Because the human brain likely utilizes both primitive and recently evolved neural specializations for the processing of faces, comparative studies may hold the key to understanding how these parallel circuits emerged during human evolution. C1 [Leopold, David A.] NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, NINDS,NEI,NIH, Bethesda, MD 20892 USA. [Rhodes, Gillian] Univ Western Australia, Sch Psychol, Nedlands, WA 6009, Australia. RP Leopold, DA (reprint author), NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, NINDS,NEI,NIH, 49 Convent Dr,1BE-21,MSC 4400, Bethesda, MD 20892 USA. EM leopoldd@mail.nih.gov OI Leopold, David/0000-0002-1345-6360 FU National Institute of Mental Health, National Eye Institute, and National Institute of Nervous Disorders and Stroke; Australian Research Council FX This work was supported by the Intramural Research Programs of the National Institute of Mental Health, National Eye Institute, and National Institute of Nervous Disorders and Stroke and an Australian Research Council Discovery Grant and Professorial Fellowship to G. Rhodes. We thank Drs. Keith Kendrick, Sarah Brosnan, Chris Baker, and Asif Ghazanfar for comments on an earlier version of the manuscript, Drs. Evan Balaban and William Hodos for discussion, and two anonymous reviewers for many helpful suggestions. NR 304 TC 62 Z9 63 U1 10 U2 60 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7036 J9 J COMP PSYCHOL JI J. Comp. Psychol. PD AUG PY 2010 VL 124 IS 3 BP 233 EP 251 DI 10.1037/a0019460 PG 19 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA 635PO UT WOS:000280668700001 PM 20695655 ER PT J AU Pennington, JAT Fisher, RA AF Pennington, Jean A. T. Fisher, Rachel A. TI Food component profiles for fruit and vegetable subgroups SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE Botanical family; Food component profiles; Food composition; Food analysis; Food groups; Fruit subgroups; Nutrient profiles; Phytochemicals; Total antioxidant capacity (TAC); Vegetable subgroups; USDA MyPyramid food guide AB To be of practical use to nutrition professionals and consumers, subgroup classifications for fruits and vegetables should be based on similarity in food composition and on easily identifiable classification characteristics. The means and standard deviations (SDs) for 24 food components (including total antioxidant capacity) in previously identified subgroups for fruits and vegetables were determined. The subgroups (dark green leafy vegetables; cabbage family vegetables; lettuces; legumes; Allium family bulbs; deep orange/yellow fruits, roots, and tubers; tomatoes and other red vegetables and fruits; citrus family fruits; red/purple/blue berries; and other fruits and vegetables) highest in food component concentrations were identified. In addition, proposed vegetable subgroups for the 2010 version of the USDA MyPyramid food guide were identified as dark green leafy vegetables and broccoli, other leafy vegetables, legumes, unique vegetables (deep orange, tomatoes, Allium vegetables, etc.), and additional vegetables. Means and SDs for 24 food components in the 5 proposed MyPyramid vegetable subgroups were determined to assess which groups had the highest concentrations of the food components. Published by Elsevier Inc. C1 [Pennington, Jean A. T.; Fisher, Rachel A.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. RP Fisher, RA (reprint author), NIH, Div Nutr Res Coordinat, 6707 Democracy Blvd,Room 629, Bethesda, MD 20892 USA. EM fisherrachel@mail.nih.gov NR 6 TC 25 Z9 26 U1 3 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD AUG PY 2010 VL 23 IS 5 BP 411 EP 418 DI 10.1016/j.jfca.2010.01.008 PG 8 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 664AJ UT WOS:000282931000005 ER PT J AU Nadel, MR Berkowitz, Z Klabunde, CN Smith, RA Coughlin, SS White, MC AF Nadel, Marion R. Berkowitz, Zahava Klabunde, Carrie N. Smith, Robert A. Coughlin, Steven S. White, Mary C. TI Fecal Occult Blood Testing Beliefs and Practices of US Primary Care Physicians: Serious Deviations from Evidence-Based Recommendations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE colorectal cancer; cancer screening; primary care; quality of care; fecal occult blood test ID AMERICAN-CANCER-SOCIETY; SERVICES TASK-FORCE; COLORECTAL-CANCER; CLINICAL GUIDELINES; NATIONAL-SURVEY; COLONOSCOPY; SURVEILLANCE; UPDATE; RATIONALE; TECHNOLOGIES AB Fecal occult blood testing (FOBT) is an important option for colorectal cancer screening that should be available in order to achieve high population screening coverage. However, results from a national survey of clinical practice in 1999-2000 indicated that many primary care physicians used inadequate methods to implement FOBT screening and follow-up. To determine whether methods to screen for fecal occult blood have improved, including the use of newer more sensitive stool tests. Cross-sectional national survey of primary care physicians. Participants consisted of 1,134 primary care physicians who reported ordering or performing FOBT in the 2006-2007 National Survey of Primary Care Physicians' Recommendations and Practices for Cancer Screening. Self-reported data on details of FOBT implementation and follow-up of positive results. Most physicians report using standard guaiac tests; higher sensitivity guaiac tests and immunochemical tests were reported by only 22.0% and 8.9%, respectively. In-office testing, that is, testing of a single specimen collected during a digital rectal examination in the office, is still widely used although inappropriate for screening: 24.9% of physicians report using only in-office tests and another 52.9% report using both in-office and home tests. Recommendations improved for follow-up after a positive test: fewer physicians recommend repeating the FOBT (17.8%) or using tests other than colonoscopy for the diagnostic work-up (6.6%). Only 44.3% of physicians who use home tests have reminder systems to ensure test completion and return. Many physicians continue to use inappropriate methods to screen for fecal occult blood. Intensified efforts to inform physicians of recommended technique and promote the use of tracking systems are needed. C1 [Nadel, Marion R.; Berkowitz, Zahava; Coughlin, Steven S.; White, Mary C.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA. [Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Smith, Robert A.] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. [Coughlin, Steven S.] Dept Vet Affairs, Environm Epidemiol Serv, Washington, DC USA. RP Nadel, MR (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Highway,MS K55, Atlanta, GA 30341 USA. EM mrn1@cdc.gov RI White, Mary /C-9242-2012 OI White, Mary /0000-0002-9826-3962 FU NCI [N02-PC-51308]; CDC [Y3-PC-6017-01]; AHRQ [Y3-PC-5019-01, Y3-PC-5019-02] FX This study was funded by NCI contract N02-PC-51308, CDC inter-agency agreement Y3-PC-6017-01 and AHRQ inter-agency agreement Y3-PC-5019-01 and Y3-PC-5019-02. NR 41 TC 31 Z9 31 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2010 VL 25 IS 8 BP 833 EP 839 DI 10.1007/s11606-010-1328-7 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 620MZ UT WOS:000279505300020 PM 20383599 ER PT J AU Johnson, TV Fan, S Zhan, GL Camras, CB Toris, CB AF Johnson, Thomas V. Fan, Shan Zhan, Guilin Camras, Carl B. Toris, Carol B. TI Efficacy and Mechanisms of Intraocular Pressure Reduction With Latanoprost and Timolol in Participants With Ocular Hypertension: A Comparison of 1 and 6 Weeks of Treatment SO JOURNAL OF GLAUCOMA LA English DT Article DE aqueous humor dynamics; intraocular pressure; outflow facility; aqueous flow; latanoprost; timolol ID AQUEOUS-HUMOR DYNAMICS; UVEOSCLERAL OUTFLOW PATHWAY; CILIARY MUSCLE-CELLS; POOLED-DATA ANALYSIS; OPEN-ANGLE GLAUCOMA; LONG-TERM DRIFT; HUMAN EYES; FLOW; DORZOLAMIDE; 6-MONTH AB Purpose: To investigate whether the intraocular pressure (IOP) reduction and mechanism of action of timolol and latanoprost change between 1 and 6 weeks of treatment. Patients and Methods: Thirty participants on no ocular medications completed this double-masked, 6-visit, crossover study. At each visit IOP was determined by pneumatonometry, aqueous flow by fluorophotometry, and outflow facility by fluorophotometry and tonography. Separate values of uveoscleral outflow were calculated using the Goldmann equation, an episcleral venous pressure of 11 mm Hg, and each of the 2 outflow facility values. In a randomized fashion, both eyes were treated for 6 weeks with latanoprost 0.005% once daily or timolol 0.5% twice daily. Measurements were repeated at 1 and 6 weeks of dosing. After 6 weeks of washout, the second drug was administered in a crossover manner. One and 6 weeks of treatment were compared with appropriate baselines using 1-way analyses of variance (ANOVA). Results: Timolol reduced aqueous flow by 27% at week 1 (P < 0.001) and 16% at week 6 (P = 0.03). Latanoprost increased uveoscleral outflow several fold at each visit (P < 0.05). Neither drug altered outflow facility. Neither drug showed a detectable change in aqueous humor dynamics at week 6 compared with week 1. Both drugs significantly (P < 0.001) reduced IOP at 1 and 6 weeks of treatment. Conclusions: Timolol and latanoprost significantly reduce IOP by different mechanisms. Timolol reduces aqueous flow whereas latanoprost increases uveoscleral outflow. Continued treatment with timolol or latanoprost for 6 weeks did not alter effects on aqueous humor dynamics. Outflow facility changes sometimes reported with prostaglandin analogues were not detected in this study. C1 [Johnson, Thomas V.; Fan, Shan; Zhan, Guilin; Camras, Carl B.; Toris, Carol B.] Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA. [Johnson, Thomas V.] NEI, Mol Mech Glaucoma Sect, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Toris, CB (reprint author), Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, 985840 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ctoris@unmc.edu RI Johnson, Thomas/C-9351-2011 OI Johnson, Thomas/0000-0002-5372-5457 FU Pfizer, New York, NY FX Supported by Pfizer and Research to Prevent Blindness, New York, NY NR 48 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD AUG PY 2010 VL 19 IS 6 BP 356 EP 364 DI 10.1097/IJG.0b013e3181d12dd8 PG 9 WC Ophthalmology SC Ophthalmology GA 639YM UT WOS:000281013100002 PM 20179619 ER PT J AU Prograis, LJ AF Prograis, Lawrence J., Jr. TI Tuskegee Bioethics Center 10th Anniversary Presentation: "Commemorating 10 Years: Ethical Perspectives on Origin and Destiny" SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Editorial Material DE Tuskegee; bioethics; African American; culture AB More than 70 years have passed since the beginning of the Public Health Service syphilis study in Tuskegee, Alabama, and it has been over a decade since President Bill Clinton formally apologized for it and held a ceremony for the Tuskegee study participants. The official launching of the Tuskegee University National Center for Bioethics in Research and Health Care took place two years after President Clinton's apology. How might we fittingly discuss the Center's 10th Anniversary and the topic Commemorating 10 Years: Ethical Perspectives on Origin and Destiny? Over a decade ago, a series of writers, many of them African Americans, wrote a text entitled African-American Perspectives on Biomedical Ethics; their text was partly responsible for a prolonged reflection by others to produce a subsequent work, African American Bioethics: Culture, Race and Identity. What is the relationship between the discipline of bioethics and African American culture? This and related questions are explored in this commentary. C1 [Prograis, Lawrence J., Jr.] Georgetown Univ, Ctr Clin Bioeth, Sch Med, Washington, DC 20057 USA. [Prograis, Lawrence J., Jr.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. RP Prograis, LJ (reprint author), Georgetown Univ, Ctr Clin Bioeth, Sch Med, Box 571409,236 Bldg D, Washington, DC 20057 USA. NR 12 TC 1 Z9 1 U1 3 U2 5 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 2010 VL 21 IS 3 SU S BP 21 EP 25 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 632PK UT WOS:000280436500004 PM 20675942 ER PT J AU Yang, YY Liu, HQ Nam, SW Kunos, G Lee, SS AF Yang, Ying-Ying Liu, Hongqun Nam, Soon Woo Kunos, George Lee, Samuel S. TI Mechanisms of TNF alpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: Interaction between TNF alpha and endocannabinoids SO JOURNAL OF HEPATOLOGY LA English DT Article DE Cardiac dysfunction; Endocannabinoids; Tumor necrosis factor-alpha (TNF alpha); Nuclear factor-B (NF kappa B); Inducible nitric oxide synthase (iNOS) 3 ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; CIRRHOTIC CARDIOMYOPATHY; NITRIC-OXIDE; CONTRACTILE DYSFUNCTION; IN-VITRO; RATS; RECEPTORS; PATHOGENESIS; INHIBITION AB Background & Aims: Chronic liver disease is associated with endotoxemia, oxidative stress, increased endocannabinoids and decreased cardiac responsiveness. Endocannabinoids activate the tumor necrosis factor-alpha (TNF alpha)-nuclear factor kappa B (NF kappa B) pathway. However, how they interact with each other remains obscure. We therefore aimed to clarify the relationship between the TNF alpha-NF kappa B pathway and endocannabinoids in the pathogenesis of cardiodepression of cholestatic bile duct ligated (BDL) mice. Methods: BDL mice with TNF alpha knockout (TNF alpha-/-) and infusion of anti-TNF alpha antibody were used. Cardiac mRNA and protein expression of NF kappa Bp65, c-Jun-N-terminal kinases (INK), p38 mitogen-activated protein kinase (p38MAPK), extracelullar-signal-regulated kinase (ERK), inducible nitric oxide synthase (iNOS), Copper/Zinc and Magnesium-superoxide dismutase (Cu/Zn- and Mn-SOD), cardiac anandamide, 2-arachidonoylglycerol (2-AG), nitric oxide (NOx) and glutathione, and plasma TNF alpha were measured. The effects of TNF alpha, cannabinoid receptor (CB1) antagonist AM251 and the endocannabinoid reuptake inhibitor UCM707, on the contractility of isolated cardiomyocytes, were assessed. Results: In BDL mice, cardiac mRNA and protein expression of NF kappa Bp65, p38MAPK, iNOS, NOx, anandamide, and plasma TNF alpha were increased, whereas glutathione, Cu/Zn-SOD, and Mn-SOD were decreased. Cardiac contractility was blunted in BDL mice. Anti-TNF alpha treatment in BDL mice decreased cardiac anandamide and NOx, reduced expression of NF kappa Bp65, p38MAPK, and iNOS, enhanced expression of Cu/Zn-SOD and Mn-SOD, increased reductive glutathione and restored cardiomyocyte contractility. TNF alpha-depressed contractility was worsened by UCM707, whereas AM251 improved contractility. Conclusions: Increased TNF alpha, acting via NF kappa B-iNOS and p38MAPK signaling pathways, plays an important role in the pathogenesis of cardiodepression in BDL mice. TNFa also suppressed contractility by increasing oxidative stress and endocannabinoid activity. (C) 2010 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Lee, Samuel S.] Univ Calgary, Hlth Sci Ctr, Liver Unit, Fac Med, Calgary, AB T2N 4N1, Canada. [Yang, Ying-Ying] Natl Yang Ming Univ, Sch Med, Taipei Vet Gen Hosp, Dept Med,Div Gen Med, Taipei 112, Taiwan. [Yang, Ying-Ying] Natl Yang Ming Univ, Sch Med, Inst Publ Hlth, Dept Prevent Med, Taipei 112, Taiwan. [Kunos, George] NIAAA, NIH, Lab Physiol Studies, Bethesda, MD USA. RP Lee, SS (reprint author), Univ Calgary, Hlth Sci Ctr, Liver Unit, Fac Med, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM samlee@ucalgary.ca FU Intramural NIH HHS [ZIA AA000351-09] NR 32 TC 17 Z9 17 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD AUG PY 2010 VL 53 IS 2 BP 298 EP 306 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 633AE UT WOS:000280470900014 PM 20626112 ER PT J AU Memarzadeh, F AF Memarzadeh, F. TI Active warming systems to maintain perioperative normothermia in hip replacement surgery SO JOURNAL OF HOSPITAL INFECTION LA English DT Letter C1 NIH, DTR, ORF, Bethesda, MD 20892 USA. RP Memarzadeh, F (reprint author), NIH, DTR, ORF, Bldg 10, Bethesda, MD 20892 USA. EM fm30c@nih.gov NR 3 TC 3 Z9 3 U1 0 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-6701 J9 J HOSP INFECT JI J. Hosp. Infect. PD AUG PY 2010 VL 75 IS 4 BP 332 EP 333 DI 10.1016/j.jhin.2010.02.006 PG 3 WC Infectious Diseases SC Infectious Diseases GA 634IZ UT WOS:000280575600023 PM 20542595 ER PT J AU Chapman, DJ Morel, K Anderson, AK Damio, G Perez-Escamilla, R AF Chapman, Donna J. Morel, Katherine Anderson, Alex Kojo Damio, Grace Perez-Escamilla, Rafael TI Breastfeeding Peer Counseling: From Efficacy Through Scale-Up SO JOURNAL OF HUMAN LACTATION LA English DT Review DE breastfeeding; peer counseling; lay support; community health worker; scale-up ID RANDOMIZED CONTROLLED-TRIAL; LOW-INCOME; SUPPORT; COMMUNITY; PROMOTION; DURATION; PROGRAM; INITIATION; WOMEN; MOTHERS AB An increasing number of publications have evaluated various breastfeeding peer counseling models. This article describes a systematic review of (a) the randomized trials assessing the effectiveness of breastfeeding peer counseling in improving rates of breastfeeding initiation, duration, exclusivity, and maternal and child health outcomes and (b) scientific literature describing the scale-up of breastfeeding peer counseling programs. Twenty-six peer-reviewed publications were included in this review. The overwhelming majority of evidence from randomized controlled trials evaluating breastfeeding peer counseling indicates that peer counselors effectively improve rates of breastfeeding initiation, duration, and exclusivity. Peer counseling interventions were also shown to significantly decrease the incidence of infant diarrhea and significantly increase the duration of lactational amenorrhea. Breastfeeding peer counseling initiatives are effective and can be scaled up in both developed and developing countries as part of well-coordinated national breastfeeding promotion or maternal-child health programs. J Hum Lact. 26(3):314-326. C1 [Chapman, Donna J.] Univ Connecticut, Dept Nutr Sci, Ctr Eliminating Hlth Dispar Latinos, Storrs, CT 06269 USA. [Chapman, Donna J.] Univ Connecticut, Connecticut NIH EXPORT Ctr Eliminating Hlth Dispa, Storrs, CT 06269 USA. [Anderson, Alex Kojo] Univ Georgia, Dept Food & Nutr, Athens, GA 30602 USA. [Perez-Escamilla, Rafael] Yale Univ, Off Community Hlth, Sch Publ Hlth, New Haven, CT 06520 USA. [Perez-Escamilla, Rafael] Yale Univ, Connecticut NIH EXPORT Ctr Eliminating Hlth Dispa, New Haven, CT 06520 USA. RP Chapman, DJ (reprint author), Univ Connecticut, Dept Nutr Sci, Ctr Eliminating Hlth Dispar Latinos, 3624 Horsebarn Rd Extens, Storrs, CT 06269 USA. FU National Center on Minority Health and Health Disparities, NIH [P20 MD001765] FX This project was supported by the National Center on Minority Health and Health Disparities, NIH EXPORT Grant P20 MD001765. NR 44 TC 39 Z9 40 U1 2 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-3344 J9 J HUM LACT JI J. Hum. Lact. PD AUG PY 2010 VL 26 IS 3 BP 314 EP 326 DI 10.1177/0890334410369481 PG 13 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 635GS UT WOS:000280644200013 PM 20715336 ER PT J AU Messerli, FH Levy, D AF Messerli, Franz H. Levy, Daniel TI Inappropriate priority claim SO JOURNAL OF HYPERTENSION LA English DT Letter ID OBESITY C1 [Messerli, Franz H.] Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp, Hypertens Program,Div Cardiol, New York, NY 10019 USA. [Levy, Daniel] Boston Univ, Sch Med, NHLBI, Boston, MA 02118 USA. RP Messerli, FH (reprint author), Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp, Hypertens Program,Div Cardiol, 1000 10th Ave,Suite 3B-30, New York, NY 10019 USA. EM fmesserl@chpnet.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD AUG PY 2010 VL 28 IS 8 BP 1778 EP 1778 DI 10.1097/HJH.0b013e32833cd074 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 628JJ UT WOS:000280115300025 PM 20647862 ER PT J AU Breen, N Rao, SR Meissner, HI AF Breen, Nancy Rao, Sowmya R. Meissner, Helen I. TI Immigration, Health Care Access, and Recent Cancer Tests Among Mexican-Americans in California SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Mexican-American; Mammography; Pap; FOBT; Colorectal endoscopy; Access to care; Immigration; Language; Cancer testing; CHIS ID UNITED-STATES; SCREENING PRACTICES; HISPANIC WOMEN; INTERVIEW SURVEY; BEHAVIORAL-MODEL; ASIAN-AMERICAN; BREAST; ACCULTURATION; INSURANCE; LANGUAGE AB Immigrants' lower rates of cancer testing may be due to lack of fluency in English and other skills and knowledge about navigating US health care markets, lack of access to health services, or both. We analyzed 9,079 Mexican-American respondents to the 2001 California Health Interview Survey (CHIS) grouped as born in the US, living in the US 10 or more years, or living in the US less than 10 years. The CHIS provides the largest Mexican-American sample in a US survey. Access to care meant having health insurance coverage and a usual source of care. English proficiency meant the respondent took the interview in English. Multivariate logistic regression was used to predict outcomes. Respondents reporting more time in the US were more likely to report access to medical care and to report getting a cancer screening exam. Regardless of time in the US, respondents reporting access had similar test rates. Regression results indicate that time in the US and primary language were not significant relative to use of cancer screening tests, but access to care was. Cancer screening tests that are covered by Every Woman Counts, California's breast and cervical cancer early detection program, had smaller gaps among groups than colorectal cancer screening which is not covered by a program. California is the only state with a survey able to monitor changes in small population groups. Understanding barriers specific to subgroups is key to developing appropriate policy and interventions to increase use of cancer screening exams. C1 [Breen, Nancy] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Inst Hlth Policy, Ctr Biostat, Boston, MA 02114 USA. [Meissner, Helen I.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Breen, N (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, Rockville, MD 20892 USA. EM Breenn@mail.nih.gov NR 47 TC 14 Z9 14 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD AUG PY 2010 VL 12 IS 4 BP 433 EP 444 DI 10.1007/s10903-008-9198-3 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 645ZY UT WOS:000281505900002 PM 19052868 ER PT J AU Hasenkrug, KJ Dittmer, U AF Hasenkrug, Kim J. Dittmer, Ulf TI Comment on "Premature Terminal Exhaustion of Friend Virus-Specific Effector CD8(+) T Cells by Rapid Induction of Multiple Inhibitory Receptors" SO JOURNAL OF IMMUNOLOGY LA English DT Letter ID RETROVIRAL INFECTION; DYSFUNCTION; RESPONSES C1 [Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Dittmer, Ulf] Univ Duisburg Essen, Inst Virol, Univ Clin Essen, Duisburg, North Rhine Wes, Germany. [Dittmer, Ulf] Univ Duisburg Essen, Inst Virol, Univ Clin Essen, Essen, North Rhine Wes, Germany. RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. FU Intramural NIH HHS [ZIA AI000753-16] NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1349 EP 1349 DI 10.4049/jimmunol.1090058 PG 1 WC Immunology SC Immunology GA 629EI UT WOS:000280177400001 PM 20660355 ER PT J AU Orr, SJ Roessler, S Quigley, L Chan, T Ford, JW O'Connor, GM McVicar, DW AF Orr, Selinda J. Roessler, Stephen Quigley, Laura Chan, Tim Ford, Jill W. O'Connor, Geraldine M. McVicar, Daniel W. TI Implications for Gene Therapy-Limiting Expression of IL-2R gamma(c) Delineate Differences in Signaling Thresholds Required for Lymphocyte Development and Maintenance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; NATURAL-KILLER-CELLS; INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN; IN-VIVO; CYTOMEGALOVIRUS-INFECTION; KINASE-ACTIVITY; T-CELLS; MICE; PROLIFERATION; CYTOKINE AB X-linked SCID patients are deficient in functional IL-2R gamma(c) leading to the loss of IL-2/IL-4/IL-7/IL-9/IL-15/IL-21 signaling and a lack of NK and mature T cells. Patients treated with IL-2R gamma(c) gene therapy have T cells develop; however, their NK cell numbers remain low, suggesting antiviral responses may be compromised. Similarly, IL-2R gamma(-/-)(c) mice reconstituted with IL-2R gamma(c) developed few NK cells, and reconstituted T cells exhibited defective proliferative responses suggesting incomplete recovery of IL-2R gamma(c) signaling. Given the shift toward self-inactivating long terminal repeats with weaker promoters to control the risk of leukemia, we assessed NK and T cell numbers and function in IL-2R gamma(-/-)(c) mice reconstituted with limiting amounts of IL-2R gamma(c). Reconstitution resulted in lower IL-2/-15-mediated STAT5 phosphorylation and proliferation in NK and T cells. However, TCR costimulation restored cytokine-driven T cell proliferation to wild-type levels. Vector modifications that improved IL-2R gamma(c) levels increased cytokine-induced STAT5 phosphorylation in both populations and increased NK cell proliferation demonstrating that IL-2R gamma(c) levels are limiting. In addition, although the half-lives of both NK and T cells expressing intermediate levels of IL-2R gamma(c) are reduced compared with wild-type cells, the reduction in NK cell half-live is much more severe than in T cells. Collectively, these data indicate different IL-2R gamma(c) signaling thresholds for lymphocyte development and proliferation making functional monitoring imperative during gene therapy. Further, our findings suggest that IL-2R gamma(c) reconstituted T cells may persist more efficiently than NK cells due to compensation for suboptimal IL-2R gamma(c) signaling by the TCR. The Journal of Immunology, 2010, 185: 1393-1403. C1 [Orr, Selinda J.; Roessler, Stephen; Quigley, Laura; Chan, Tim; Ford, Jill W.; O'Connor, Geraldine M.; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. RP McVicar, DW (reprint author), NCI, Canc & Inflammat Program, Bldg 560,Room 31-46, Frederick, MD 21702 USA. EM mcvicard@mail.nih.gov RI McVicar, Daniel/G-1970-2015; OI Orr, Selinda/0000-0001-8539-7825 FU National Institutes of Health-National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health-National Cancer Institute. NR 40 TC 6 Z9 6 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1393 EP 1403 DI 10.4049/jimmunol.0903528 PG 11 WC Immunology SC Immunology GA 629EI UT WOS:000280177400014 PM 20592278 ER PT J AU Lindsay, RWB Darrah, PA Quinn, KM Wille-Reece, U Mattei, LM Iwasaki, A Kasturi, SP Pulendran, B Gall, JGD Spies, AG Seder, RA AF Lindsay, Ross W. B. Darrah, Patricia A. Quinn, Kylie M. Wille-Reece, Ulrike Mattei, Lisa M. Iwasaki, Akiko Kasturi, Sudhir P. Pulendran, Bali Gall, Jason G. D. Spies, A. Gregory Seder, Robert A. TI CD8(+) T Cell Responses following Replication-Defective Adenovirus Serotype 5 Immunization Are Dependent on CD11c(+) Dendritic Cells but Show Redundancy in Their Requirement of TLR and Nucleotide-Binding Oligomerization Domain-Like Receptor Signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE IMMUNE-RESPONSE; PRIME-BOOST REGIMENS; RECOMBINANT ADENOVIRUS; IN-VIVO; VACCINE VECTORS; INFECTED HEPATOCYTES; ANTI-AD5 IMMUNITY; ADAPTIVE IMMUNITY; LANGERHANS CELLS; RHESUS-MONKEYS AB Replication-defective adenovirus serotype 5 (rAd5) is the most potent recombinant vector for eliciting CD8 T cell responses in humans. In this study, the innate mechanisms that influence T cell responses following rAd5 immunization were assessed in mice. Using rAd5 expressing enhanced GFP (eGFP-rAd5), we show that rAd5 transfects CD11c(+) dendritic cells (DCs) in draining lymph nodes in vivo following s.c. or i.m. immunization. Among distinct DC subsets, eGFP expression was highest in CD11c(+) CD8(-)B220(-) with a lower frequency detected in CD11c(+)CD8(+)B220(-) and CD11c(+)B220(+) plasmacytoid DCs. CD11c(+) DCs but not CD11c(-) cells from mice immunized with rAd5 encoding the SIINFEKL peptide induced proliferation of naive OT-I CD8 T cells. Furthermore, CD11c(+)CD8(+)B220(-) was the most potent DC subset for eliciting naive OT-I CD8 T cell proliferation. Of note, mice with preexisting immunity to rAd5 had a substantial decrease in eGFP expression in DCs, which was associated with similar to 2-fold decrease in Th1 and complete inhibition of CD8 responses. Thus, pre-existing rAd5 immunity has a greater influence on CD8 compared with CD4 T cell responses. In terms of how innate cytokines and signaling pathways influenced T cell immunity following rAd5 immunization, we show that the magnitude and quality of CD8 T cell responses are partially dependent on MyD88 but independent of IL-12, type I IFN, apoptosis-associated speck-like protein, nucleotide-binding oligomerization domain-like receptor protein 3, and IL-1. Taken together, these data demonstrate a critical role for CD11c(+) DCs for CD8 responses but striking redundancy for innate cytokines and signaling by TLR and nucleotide-binding oligomerization domain-like receptor pathways. The Journal of Immunology, 2010, 185: 1513-1521. C1 [Lindsay, Ross W. B.; Darrah, Patricia A.; Quinn, Kylie M.; Wille-Reece, Ulrike; Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Mattei, Lisa M.; Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. [Kasturi, Sudhir P.; Pulendran, Bali] Emory Vaccine Ctr, Atlanta, GA 30329 USA. [Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA. [Spies, A. Gregory] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98109 USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr MSC 3025,Bldg 40,Room 3512, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov NR 44 TC 43 Z9 43 U1 2 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1513 EP 1521 DI 10.4049/jimmunol.1000338 PG 9 WC Immunology SC Immunology GA 629EI UT WOS:000280177400027 PM 20610651 ER PT J AU Leone, A Rohankhedkar, M Okoye, A Legasse, A Axthelm, MK Villinger, F Piatak, M Lifson, JD Assouline, B Morre, M Picker, LJ Sodora, DL AF Leone, Amanda Rohankhedkar, Mukta Okoye, Afam Legasse, Alfred Axthelm, Michael K. Villinger, Francois Piatak, Michael, Jr. Lifson, Jeffrey D. Assouline, Brigitte Morre, Michel Picker, Louis J. Sodora, Donald L. TI Increased CD4(+) T Cell Levels during IL-7 Administration of Antiretroviral Therapy-Treated Simian Immunodeficiency Virus-Positive Macaques Are Not Dependent on Strong Proliferative Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EFFECTOR MEMORY CD4(+); HIV-INFECTED PATIENTS; RHESUS MACAQUES; DISEASE PROGRESSION; INTERLEUKIN-7 RECEPTOR; IMMUNE ACTIVATION; SIV INFECTION; SUBCUTANEOUS INTERLEUKIN-2; NONHUMAN-PRIMATES AB CD4(+) T cell depletion is a fundamental component of HIV infection and AIDS pathogenesis and is not always reversed following antiretroviral therapy (ART). In this study, the SIV-infected rhesus macaque model was used to assess recombinant simian IL-7 in its glycosylated form (rsIL-7gly) to enhance regeneration of CD4(+) T cells, particularly the crucial central memory compartment, after ART. We assessed the impact of rsIL-7gly administration as single injections and as a cluster of three doses. Irrespective of the dosing strategy used, the rsIL-7gly administration transiently increased proliferation of both central memory and naive cells, in both CD4(+) and CD8(+) subsets, without increasing SIV levels in the blood. Administration of rsIL-7gly at intervals of 4-6 wk maximized the proliferative response to therapy but resulted in only transient increases in peripheral blood T cell counts. Although more frequent rsIL-7gly "clustered" dosing (three times weekly with 2 wk of rest and then repeat) induced only an initial proliferative burst by CD4(+) T cells, this dosing strategy resulted in sustained increases in peripheral blood CD4(+) T cell counts. The clustered rsIL-7gly treatment regimen was shown to increase the half-life of a BrdU label among memory T cells in the blood when compared with that of macaques treated with ART alone, which is consistent with enhanced cell survival. These results indicate that dosing intervals have a major impact on the response to rsIL-7gly in SIV-positive ART-treated rhesus macaques and that optimum dosing strategies may be ones that induce CD4(+) T cell proliferation initially and provide increased CD4(+) T cell survival. The Journal of Immunology, 2010, 185: 1650-1659. C1 [Leone, Amanda; Sodora, Donald L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Rohankhedkar, Mukta; Okoye, Afam; Legasse, Alfred; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. [Villinger, Francois] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30329 USA. [Villinger, Francois] Emory Univ, Sch Med, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Assouline, Brigitte; Morre, Michel] Cytheris SA, Issy Les Moulineaux, France. RP Sodora, DL (reprint author), Seattle Biomed Res Inst, 307 Westlake Ave N,Suite 500, Seattle, WA 98109 USA. EM don.sodora@sbri.org FU National Institutes of Health [R01-AI035522, R01-DE017541, R37-AI054292, P51-RR00163] FX This work was supported by National Institutes of Health Grants R01-AI035522 (to D. L. S.), R01-DE017541 (to D. L. S.), R37-AI054292 (to L.J.P.), and P51-RR00163 (Oregon National Primate Research Center Core Grant) as well as the Pendleton Trust (to D. L. S.). NR 80 TC 23 Z9 24 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1650 EP 1659 DI 10.4049/jimmunol.0902626 PG 10 WC Immunology SC Immunology GA 629EI UT WOS:000280177400042 PM 20622118 ER PT J AU Madenspacher, JH Draper, DW Smoak, KA Li, HT Griffiths, GL Suratt, BT Wilson, MD Rudel, LL Fessler, MB AF Madenspacher, Jennifer H. Draper, David W. Smoak, Kathleen A. Li, Haitao Griffiths, Gary L. Suratt, Benjamin T. Wilson, Martha D. Rudel, Lawrence L. Fessler, Michael B. TI Dyslipidemia Induces Opposing Effects on Intrapulmonary and Extrapulmonary Host Defense through Divergent TLR Response Phenotypes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; KLEBSIELLA-PNEUMONIAE INFECTION; FREE-CHOLESTEROL ACCUMULATION; TOLL-LIKE RECEPTORS; E-DEFICIENT MICE; APOLIPOPROTEIN-E; NEUTROPHIL RECRUITMENT; IN-VIVO; PULMONARY INFLAMMATION; INSULIN-RESISTANCE AB Dyslipidemia influences innate immune responses in the bloodstream, but whether and how pulmonary innate immunity is sensitive to circulating lipoproteins is largely unknown. To define whether dyslipidemia impacts responses to bacteria in the airspace and, if so, whether differently from its effects in other tissues, airspace, bloodstream, and i.p. responses to LPS and Klebsiella pneumoniae were investigated using murine models of dyslipidemia. Dyslipidemia reduced neutrophil (PMN) recruitment to the airspace in response to LPS and K. pneumoniae by impairing both chemokine induction in the airspace and PMN chemotaxis, thereby compromising pulmonary bacterial clearance. Paradoxically, bacteria were cleared more effectively from the bloodstream during dyslipidemia. This enhanced systemic response was due, at least in part, to basal circulating neutrophilia and basal TLR4/MyD88-dependent serum cytokine induction and enhanced serum cytokine responses to systemically administered TLR ligands. Dyslipidemia did not globally impair PMN transvascular trafficking to, and host defense within all loci, because neutrophilia, cytokine induction, and bacterial clearance were enhanced within the infected peritoneum. Peritoneal macrophages from dyslipidemic animals were primed for more robust TLR responses, reflecting increased lipid rafts and increased TLR4 expression, whereas macrophages from the airspace, in which cholesterol was maintained constant during dyslipidemia, had normal responses and rafts. Dyslipidemia thus imparts opposing effects upon intra-and extrapulmonary host defense by inducing tissue-divergent TLR response phenotypes and dysregulating airspace/blood compartmental levels of PMNs and cytokines. We propose that the airspace is a "privileged" site, thereby uniquely sensitive to dyslipidemia. The Journal of Immunology, 2010, 185: 1660-1669. C1 [Madenspacher, Jennifer H.; Draper, David W.; Smoak, Kathleen A.; Fessler, Michael B.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Li, Haitao; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. [Suratt, Benjamin T.] Univ Vermont, Coll Med, Vermont Lung Ctr, Burlington, VT 05405 USA. [Wilson, Martha D.; Rudel, Lawrence L.] Wake Forest Univ Hlth Sci, Dept Pathol, Sect Lipid Sci, Winston Salem, NC 27157 USA. RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, 111 TW Alexander Dr,POB 12233,MD D2 01, Res Triangle Pk, NC 27709 USA. EM fesslerm@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences; National Institutes of Health [R01 HL84200, HL-49373]; Amgen; GlaxoSmithKline FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences and by National Institutes of Health Grants R01 HL84200 and HL-49373.; L. L. R. has received research funding from Amgen and GlaxoSmithKline in excess of $5000 within the past 5 years. NR 49 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1660 EP 1669 DI 10.4049/jimmunol.0903501 PG 10 WC Immunology SC Immunology GA 629EI UT WOS:000280177400043 PM 20581153 ER PT J AU Oh, I Ozaki, K Meguro, A Hatanaka, K Kadowaki, M Matsu, H Tatara, R Sato, K Iwakura, Y Nakae, S Sudo, K Teshima, T Leonard, WJ Ozawa, K AF Oh, Iekuni Ozaki, Katsutoshi Meguro, Akiko Hatanaka, Keiko Kadowaki, Masanori Matsu, Haruko Tatara, Raine Sato, Kazuya Iwakura, Yoichiro Nakae, Susumu Sudo, Katsuko Teshima, Takanori Leonard, Warren J. Ozawa, Keiya TI Altered Effector CD4(+) T Cell Function in IL-21R(-/-) CD4(+) T Cell-Mediated Graft-Versus-Host Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; INTERFERON-GAMMA; IN-VIVO; TH17 CELLS; IL-21; RECEPTOR; DIFFERENTIATION; INTERLEUKIN-21; MICE; AUTOIMMUNITY AB We previously showed that transplantation with IL-21R gene-deficient splenocytes resulted in less severe graft-versus-host disease (GVHD) than was observed with wild type splenocytes. In this study, we sought to find mechanism(s) explaining this observation. Recipients of donor CD4(+) T cells lacking IL-21R exhibited diminished GVHD symptoms, with reduced inflammatory cell infiltration into the liver and intestine, leading to prolonged survival. After transplantation, CD4(+) T cell numbers in the spleen were reduced, and MLR and cytokine production by CD4(+) T cells were impaired. These results suggest that IL-21 might promote GVHD through enhanced production of effector CD4(+) T cells. Moreover, we found that CD25 depletion altered neither the impaired MLR in vitro nor the ameliorated GVHD symptoms in vivo. Thus, the attenuated GVHD might be caused by an impairment of effector T cell differentiation itself, rather than by an increase in regulatory T cells and suppression of effector T cells. The Journal of Immunology, 2010, 185: 1920-1926. C1 [Oh, Iekuni; Ozaki, Katsutoshi; Meguro, Akiko; Hatanaka, Keiko; Matsu, Haruko; Tatara, Raine; Sato, Kazuya; Ozawa, Keiya] Jichi Med Univ, Dept Med, Div Hematol, Shimotsuke, Tochigi 3290498, Japan. [Kadowaki, Masanori; Teshima, Takanori] Kyushu Univ, Grad Sch Med, Dept Med & Biosyst Sci, Fukuoka 812, Japan. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1138654, Japan. [Nakae, Susumu] Univ Tokyo, Inst Med Sci, Frontier Res Initiat, Tokyo 1138654, Japan. [Sudo, Katsuko] Tokyo Med Univ, Anim Res Ctr, Tokyo, Japan. [Leonard, Warren J.] Natl Heart Lung & Blood Inst, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Ozaki, K (reprint author), Jichi Med Univ, Dept Med, Div Hematol, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan. EM ozakikat@jichi.ac.jp RI teshima, takanori/G-1671-2012; Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 FU Ministry of Health, Labor and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD FX This work was supported in part by grants from the Ministry of Health, Labor and Welfare of Japan; by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and by the Intramural Research Program of the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD. NR 42 TC 11 Z9 12 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1920 EP 1926 DI 10.4049/jimmunol.0902217 PG 7 WC Immunology SC Immunology GA 629EI UT WOS:000280177400070 PM 20574002 ER PT J AU Yoshimura, T AF Yoshimura, Teizo TI Activation of Discoidin Domain Receptor 1 Facilitates the Maturation of Human Monocyte-Derived Dendritic Cells Through the TNF Receptor Associated Factor 6/TGF-beta-Activated Protein Kinase 1 Binding Protein 1 beta/p38 alpha Mitogen-Activated Protein Kinase Signaling Cascade (Retraction of vol 171, pg 3520, 2003) SO JOURNAL OF IMMUNOLOGY LA English DT Correction C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. RP Yoshimura, T (reprint author), NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. NR 1 TC 0 Z9 0 U1 5 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1984 EP 1984 DI 10.4049/jimmunol.1090057 PG 1 WC Immunology SC Immunology GA 629EI UT WOS:000280177400077 PM 20660362 ER PT J AU Carrillo-Carrasco, N Venditti, CP AF Carrillo-Carrasco, Nuria Venditti, Charles P. TI Response to: Hydroxocobalamin for cobalamin C: which dosage? by V. Wiwanitkit SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Letter ID HEALTHY-VOLUNTEERS C1 [Carrillo-Carrasco, Nuria; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, Natl Inst Hlth Bldg 49,Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov RI Carrillo-Carrasco, Nuria/B-9034-2009 OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808 NR 4 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2010 VL 33 IS 4 BP 455 EP 455 DI 10.1007/s10545-010-9092-8 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 627YN UT WOS:000280080900020 ER PT J AU Blasco, AJ Serrano, J Navas, VM Lopez, SJP Ortiz, PP Carazo, B Sierra, C Cochran, EK Gorden, P AF Blasco, Alonso J. Serrano, J. Navas, V. M. Lopez, Siguero J. P. Ortiz, Perez P. Carazo, B. Sierra, C. Cochran, E. K. Gorden, P. TI METABOLIC CORRECTION INDUCED BY LEPTIN SUBSTITUTION THERAPY IN CONGENITAL GENERALIZED LYPODISTROPHY SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 [Lopez, Siguero J. P.] Hosp Materno Infantil, Endocrinol Unit, Malaga, Spain. [Cochran, E. K.; Gorden, P.] NIH Bethesda, Clin Endocrin Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2010 VL 33 SU 1 BP S124 EP S124 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 648ZT UT WOS:000281735000388 ER PT J AU Chandler, RJ Phillips, D Boja, ES Carrillo-Carrasco, N Caldovic, L Morizono, H Balaban, RS Venditti, CP AF Chandler, R. J. Phillips, D. Boja, E. S. Carrillo-Carrasco, N. Caldovic, L. Morizono, H. Balaban, R. S. Venditti, C. P. TI PROTEOMICS REVEALS NEW INSIGHTS INTO THE CAUSES OF HYPERAMMONEMIA IN METHYLMALONIC ACIDEMIA SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 [Chandler, R. J.; Phillips, D.; Boja, E. S.; Carrillo-Carrasco, N.; Balaban, R. S.; Venditti, C. P.] NIH, Bethesda, MD 20892 USA. [Caldovic, L.; Morizono, H.] Childrens Natl Med Ctr, Washington, DC 20010 USA. RI Carrillo-Carrasco, Nuria/B-9034-2009 OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2010 VL 33 SU 1 BP S174 EP S174 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 648ZT UT WOS:000281735000569 ER PT J AU Manoli, I Sysol, JR Chandler, RJ Sloan, J Cusmano-Ozog, K Zerfas, P Hoffmann, V Abu-Asab, M Tsokos, M Enns, GM Venditti, CP AF Manoli, I Sysol, J. R. Chandler, R. J. Sloan, J. Cusmano-Ozog, K. Zerfas, P. Hoffmann, V Abu-Asab, M. Tsokos, M. Enns, G. M. Venditti, C. P. TI INSIGHTS INTO THE PATHOPHYSIOLOGY OF METHYLMALONIC ACIDEMIA (MMA) FROM TISSUE-SPECIFIC TRANSGENIC MOUSE MODELS SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 [Manoli, I; Sysol, J. R.; Chandler, R. J.; Sloan, J.; Venditti, C. P.] NHGRI, Gen Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Cusmano-Ozog, K.; Enns, G. M.] Stanford Univ, Div Gen Med, Stanford, CA 94305 USA. [Zerfas, P.; Hoffmann, V] NIH, Div Veterin Res, ORS, Bethesda, MD 20892 USA. [Abu-Asab, M.; Tsokos, M.] NIH, Ultrastr Path Sec, CCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2010 VL 33 SU 1 BP S53 EP S53 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 648ZT UT WOS:000281735000127 ER PT J AU Tuysuz, B Goldin, E Metin, B Korkmaz, B Yalcinkaya, C AF Tuysuz, B. Goldin, E. Metin, B. Korkmaz, B. Yalcinkaya, C. TI MUCOLIPIDOSIS TYPE IV IN A TURKISH CHILD ASSOCIATED WITH A NOVEL MCOLNI MUTATION SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 [Tuysuz, B.] 1st Uni Cerrahpasa Med, Dep Ped Genet, Istanbul, Turkey. [Goldin, E.] NIH Med Genet, Bethesda, MD USA. [Metin, B.; Korkmaz, B.; Yalcinkaya, C.] 1st Uni Cerrahpasa Med, Dep Ped Neurol, Istanbul, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2010 VL 33 SU 1 BP S134 EP S134 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 648ZT UT WOS:000281735000422 ER PT J AU Ong, DS Anzinger, JJ Leyva, FJ Rubin, N Addadi, L Kruth, HS AF Ong, Daniel S. Anzinger, Joshua J. Leyva, Francisco J. Rubin, Noa Addadi, Lia Kruth, Howard S. TI Extracellular cholesterol-rich microdomains generated by human macrophages and their potential function in reverse cholesterol transport SO JOURNAL OF LIPID RESEARCH LA English DT Article DE atherosclerosis; unesterified; macrophage-colony stimulating factor; Src family kinase; actin; apolipoprotein A-I; high-density lipoprotein ID MONOCYTE-DERIVED MACROPHAGES; REGULATES ACTIN DYNAMICS; APOLIPOPROTEIN-A-I; ATHEROSCLEROTIC LESIONS; FOAM CELLS; UNESTERIFIED CHOLESTEROL; LIPID PARTICLES; PLASMA-MEMBRANE; EFFLUX; MECHANISM AB Previous studies have shown that cholesterol in atherosclerotic plaques is present in both intracellular and extracellular forms. In the current study, we investigated a mechanism for extracellular cholesterol accumulation and examined the capacity of this pool of cholesterol to be removed by cholesterol acceptors, a step in reverse cholesterol transport. Human monocyte-derived macrophages differentiated with macrophage-colony stimulating factor were incubated with acetylated LDL to allow cholesterol enrichment and processing. These macrophages were subsequently labeled with a monoclonal antibody that specifically detects ordered cholesterol arrays, revealing the presence of unesterified cholesterol-rich microdomains on the cell surfaces and in the extracellular matrix. Similar unesterified cholesterol-rich microdomains were present in human atherosclerotic plaques. Actin microfilaments functioned in microdomain deposition or maintenance, and Src family kinases regulated transfer of these microdomains from the cell surface onto the extracellular matrix. Mediators of reverse cholesterol transport, apolipoprotein A-I (apoA-I), and HDL were capable of removing these extracellular unesterified cholesterol-rich microdomains. However, apoA-I removed the microdomains only when macrophages were present. ApoA-I removal of microdomains was blocked by glyburide and inhibitor of ATP-binding cassette transporter A1 (ABCA1) function. In summary, cultures of cholesterol-enriched human monocyte-derived macrophages generate extracellular unesterified cholesterol-rich microdomains, which can subsequently be removed by cholesterol acceptors and therefore potentially function in reverse cholesterol transport.-Ong, D. S., J. J. Anzinger, F. J. Leyva, N. Rubin, L. Addadi, and H. S. Kruth. Extracellular cholesterol-rich microdomains generated by human macrophages and their potential function in reverse cholesterol transport. J. Lipid Res. 2010. 51: 2303-2313 C1 [Ong, Daniel S.; Anzinger, Joshua J.; Leyva, Francisco J.; Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. NIH, Clin Res Training Program, Bethesda, MD 20892 USA. [Rubin, Noa; Addadi, Lia] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU National Institutes of Health; Pfizer Inc FX This research was made possible through the Clinical Research Training Program, a public-private partnership supported jointly by the National Institutes of Health and Pfizer Inc (via a grant to the Foundation for the National Institutes of Health from Pfizer Inc). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies. NR 40 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2010 VL 51 IS 8 BP 2303 EP 2313 DI 10.1194/jlr.M005660 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 625LM UT WOS:000279896800026 PM 20421591 ER PT J AU Ramadan, E Rosa, AO Chang, L Chen, M Rapoport, SI Basselin, M AF Ramadan, Epolia Rosa, Angelo O. Chang, Lisa Chen, Mei Rapoport, Stanley I. Basselin, Mireille TI Extracellular-derived calcium does not initiate in vivo neurotransmission involving docosahexaenoic acid SO JOURNAL OF LIPID RESEARCH LA English DT Article DE arachidonic; calcium; cPLA(2); iPLA(2); NMDA; MK-801; imaging ID INDEPENDENT PHOSPHOLIPASE A(2); POLYUNSATURATED FATTY-ACIDS; CEREBELLAR GRANULE CELLS; RAT-BRAIN ASTROCYTES; ARACHIDONIC-ACID; UNANESTHETIZED RATS; FRONTAL-CORTEX; ADMINISTRATION INCREASES; SIGNAL-TRANSDUCTION; ADULT RATS AB In vitro studies show that docosahexaenoic acid (DHA) can be released from membrane phospholipid by Ca(2+)-independent phospholipase A(2) (iPLA(2)), Ca(2+)-independent plasmalogen PLA(2) or secretory PLA(2) (sPLA(2)), but not by Ca(2+)-dependent cytosolic PLA(2) (cPLA(2)), which selectively releases arachidonic acid (AA). Since glutamatergic NMDA (N-methyl-D-aspartate) receptor activation allows extracellular Ca(2+) into cells, we hypothesized that brain DHA signaling would not be altered in rats given NMDA, to the extent that in vivo signaling was mediated by Ca(2+)-independent mechanisms. Isotonic saline, a subconvulsive dose of NMDA (25 mg/kg), MK-801, or MK-801 followed by NMDA was administered i.p. to unanesthetized rats. Radiolabeled DHA or AA was infused intravenously and their brain incorporation coefficients k*, measures of signaling, were imaged with quantitative autoradiography. NMDA or MK-801 compared with saline did not alter k* for DHA in any of 81 brain regions examined, whereas NMDA produced widespread and significant increments in k* for AA. In conclusion, in vivo brain DHA but not AA signaling via NMDA receptors is independent of extracellular Ca(2+) and of cPLA(2). DHA signaling may be mediated by iPLA 2, plasmalogen PLA(2), or other enzymes insensitive to low concentrations of Ca(2+). Greater AA than DHA release during glutamate-induced excitotoxicity could cause brain cell damage.-Ramadan, E., A. O. Rosa, L. Chang, M. Chen, S. I. Rapoport, and M. Basselin. Extracellular- derived calcium does not initiate in vivo neurotransmission involving docosahexaenoic acid. J. Lipid Res. 2010. 51: 2334-2340. C1 [Ramadan, Epolia; Rosa, Angelo O.; Chang, Lisa; Chen, Mei; Rapoport, Stanley I.; Basselin, Mireille] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Ramadan, E (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM ramadanir@mail.nih.gov OI da Rosa, Angelo/0000-0003-3715-4751 FU National Institutes of Health; National Institute on Aging FX This work was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. None of the authors has a financial or other conflict of interest related to this work. NR 58 TC 23 Z9 23 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2010 VL 51 IS 8 BP 2334 EP 2340 DI 10.1194/jlr.M006262 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 625LM UT WOS:000279896800029 PM 20388940 ER PT J AU Tycko, R Hu, KN AF Tycko, Robert Hu, Kan-Nian TI A Monte Carlo/simulated annealing algorithm for sequential resonance assignment in solid state NMR of uniformly labeled proteins with magic-angle spinning SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Automated assignment; Chemical shifts; Amyloid; Prion; HET-s; Stochastic recoupling ID NUCLEAR-MAGNETIC-RESONANCE; HET-S PRION; CHEMICAL-SHIFT ASSIGNMENTS; AMYLOID FIBRILS; SECONDARY-STRUCTURE; SIDE-CHAIN; ROTATING SOLIDS; 3D NMR; SPECTROSCOPY; BACKBONE AB We describe a computational approach to sequential resonance assignment in solid state NMR studies of uniformly (15)N,(13)C-labeled proteins with magic-angle spinning. As input, the algorithm uses only the protein sequence and lists of (15)N/(13)C(alpha), crosspeaks from 2D NCACX and NCOCX spectra that include possible residue-type assignments of each crosspeak. Assignment of crosspeaks to specific residues is carried out by a Monte Carlo/simulated annealing algorithm, implemented in the program MC_ASSIGN1. The algorithm tolerates substantial ambiguity in residue-type assignments and coexistence of visible and invisible segments in the protein sequence. We use MC_ASSIGN1 and our own 2D spectra to replicate and extend the sequential assignments for uniformly-labeled HET-s(218-289) fibrils previously determined manually by Siemer et al. (J. Biomol. NMR, 34 (2006) 75-87) from a more extensive set of 2D and 3D spectra. Accurate assignments by MC_ASSIGN1 do not require data that are of exceptionally high quality. Use of MC_ASSIGN1 (and its extensions to other types of 2D and 3D data) is likely to alleviate many of the difficulties and uncertainties associated with manual resonance assignments in solid state NMR studies of uniformly labeled proteins, where spectral resolution and signal-to-noise are often sub-optimal. Published by Elsevier Inc. C1 [Tycko, Robert; Hu, Kan-Nian] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU National Insitute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; National Institutes of Health FX We thank Reed B. Wickner for his assistance with the production of HET-s(218-289) fibrils. This work was supported by the Intramural Research Program of the National Insitute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health. Additional support was provided by the Intramural AIDS Targeted Antiviral Program of the National Institutes of Health. NR 47 TC 25 Z9 26 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD AUG PY 2010 VL 205 IS 2 BP 304 EP 314 DI 10.1016/j.jmr.2010.05.013 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 627SZ UT WOS:000280064500016 PM 20547467 ER PT J AU Chaiworapongsa, T Romero, R Kusanovic, JP Savasan, ZA Kim, SK Mazaki-Tovi, S Vaisbuch, E Ogge, G Madan, I Dong, Z Yeo, L Mittal, P Hassan, SS AF Chaiworapongsa, Tinnakorn Romero, Roberto Kusanovic, Juan P. Savasan, Zeynep A. Kim, Sun Kwon Mazaki-Tovi, Shali Vaisbuch, Edi Ogge, Giovanna Madan, Ichchha Dong, Zhong Yeo, Lami Mittal, Pooja Hassan, Sonia S. TI Unexplained fetal death is associated with increased concentrations of anti-angiogenic factors in amniotic fluid SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Angiogenic factor; soluble vascular endothelial growth factor receptor-1; sFlt-1; soluble endoglin; stillbirth; fetal demise; preeclampsia; congenital anomalies ID ENDOTHELIAL-GROWTH-FACTOR; FOR-GESTATIONAL-AGE; FACTOR RECEPTOR-1 CONCENTRATION; LATE-ONSET PREECLAMPSIA; SOLUBLE ENDOGLIN; TYROSINE KINASE-1; MATERNAL PLASMA; HUMAN PLACENTA; BIRTH-WEIGHT; SERUM CONCENTRATIONS AB Objective. Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors. Study design. This cross-sectional study included patients with fetal death (n = 35) and controls (n = 129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained (n = 25); (2) preeclampsia and/or placental abruption (n - 5); and (3) chromosomal/congenital anomalies (n - 5). The control group consisted of patients with preterm labor (PTL) who delivered at term (n = 92) and women at term not in labor (n = 37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group (p < 0.001 for each); (2) these results remained significant among different subgroups of stillbirth (p < 0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR = 10.8; 95% CI 1.3-89.2 and adjusted OR 87; 95% CI 2.3-3323, respectively). Conclusion. Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations. C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Romero, Roberto; Kusanovic, Juan P.; Savasan, Zeynep A.; Mazaki-Tovi, Shali; Vaisbuch, Edi; Madan, Ichchha; Yeo, Lami; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Ogge, Giovanna/G-6109-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 77 TC 9 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD AUG PY 2010 VL 23 IS 8 BP 794 EP 805 DI 10.3109/14767050903443467 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 634OI UT WOS:000280592200007 PM 20199197 ER PT J AU Ogge, G Romero, R Kusanovic, JP Chaiworapongsa, T Dong, Z Mittal, P Vaisbuch, E Mazaki-Tovi, S Gonzalez, JM Yeo, L Hassan, SS AF Ogge, Giovanna Romero, Roberto Kusanovic, Juan Pedro Chaiworapongsa, Tinnakorn Dong, Zhong Mittal, Pooja Vaisbuch, Edi Mazaki-Tovi, Shali Gonzalez, Juan M. Yeo, Lami Hassan, Sonia S. TI Serum and plasma determination of angiogenic and anti-angiogenic factors yield different results: The need for standardization in clinical practice SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Preeclampsia; anti-angiogenic state; sFlt-1; sVEGFR-1; sVEGFR-2; PlGF; placental growth factor; sEng; soluble endoglin; vascular endothelial growth factor; prediction; pregnancy ID ENDOTHELIAL GROWTH-FACTOR; UTERINE ARTERY DOPPLER; FOR-GESTATIONAL-AGE; MATERNAL SERUM; FACTOR RECEPTOR-1; SEVERE PREECLAMPSIA; TYROSINE KINASE-1; SOLUBLE ENDOGLIN; NORMAL-PREGNANCY; FACTOR VEGF AB Objective. The importance of an anti-angiogenic state as a mechanism of disease in preeclampsia is now recognized. Assays for the determination of concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF) and soluble endoglin (sEng) have been developed for research and clinical laboratories. A key question is whether these factors should be measured in plasma or serum. The purpose of this study was to determine if there are differences in the concentrations of these analytes between plasma and serum in normal pregnancy and in preeclampsia. Methods. Samples of maternal blood were obtained by venipuncture and collected in EDTA (lavender top) and serum collection tubes (red top). A standard laboratory procedure was implemented for the centrifugation, aliquoting and storage of samples. Plasma and serum from 70 women with normal pregnancies and 34 patients with preeclampsia were assayed for sVEGFR-1, sVEGFR-2, PlGF and sEng by ELISA. Nonparametric paired tests were used for analyses. Results. A significant difference between plasma and serum concentration was observed for sVEGFR-1 and sVEGFR-2 in normal pregnancy, and for sVEGFR-1, sVEGFR-2, PlGF and sEng in women with preeclampsia. Conclusion. The concentrations of sVEGFR-1, sVEGFR-2, PlGF and sEng when measured in maternal plasma and in serum are different. Therefore, the matrix used for the assay (serum versus plasma) needs to be considered when selecting thresholds for predictive studies and interpreting the growing body of literature on this subject. C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Vaisbuch, Edi; Mazaki-Tovi, Shali; Gonzalez, Juan M.; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Hosp, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Ogge, Giovanna/G-6109-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 84 TC 11 Z9 11 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD AUG PY 2010 VL 23 IS 8 BP 820 EP 827 DI 10.3109/14767050903366119 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 634OI UT WOS:000280592200010 PM 20158394 ER PT J AU Savasan, ZA Romero, R Chaiworapongsa, T Kusanovic, JP Kim, SK Mazaki-Tovi, S Vaisbuch, E Mittal, P Ogge, G Madan, I Dong, Z Yeo, L Hassan, SS AF Savasan, Zeynep Alpay Romero, Roberto Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Kim, Sun Kwon Mazaki-Tovi, Shali Vaisbuch, Edi Mittal, Pooja Ogge, Giovanna Madan, Ichchha Dong, Zhong Yeo, Lami Hassan, Sonia S. TI Evidence in support of a role for anti-angiogenic factors in preterm prelabor rupture of membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE sVEGFR-1; sflt-1; sKDR; sVEGFR-2; intraamniotic infection; intraamniotic inflammation; parturition; microbial invasion of the amniotic cavity; MIAC; chorioamnionitis; prematurity; parturition; preterm labor; term labor; preterm PROM; angiogenesis; amniotic fluid ID ENDOTHELIAL-GROWTH-FACTOR; FACTOR RECEPTOR-1 CONCENTRATION; LATE-ONSET PREECLAMPSIA; FOR-GESTATIONAL-AGE; PREMATURE RUPTURE; FETAL MEMBRANES; AMNIOTIC-FLUID; HUMAN PLACENTA; INTRAAMNIOTIC INFECTION; INTRAUTERINE INFECTION AB Objective. Vaginal bleeding, placental abruption, and defective placentation are frequently observed in patients with preterm prelabor rupture of membranes (PROM). Recently, a role of vascular endothelial growth factor (VEGF) and its receptor, VEGF receptor (VEGFR)-1 has been implicated in the mechanisms of membrane rupture. The purpose of this study was to determine whether the soluble form of VEGFR-1 and -2 concentrations in amniotic fluid (AF) change with preterm PROM, intra-amniotic infection/inflammation (IAI), or parturition. Study design. This cross-sectional study included 544 patients in the following groups: (1) midtrimester (MT) (n = 48); (2) preterm labor (PTL) leading to term delivery (n - 143); (3) PTL resulting in preterm delivery with (n - 72) and without IAI (n = 100); (4) preterm PROM with (n = 46) and without IAI (n = 42); (5) term in labor (n = 48); and (6) term not in labor (n = 45). The concentrations of sVEGFR-1 and sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Preterm PROM (with and without IAI) had a lower median AF concentration of sVEGFR-1 than patients with PTL who delivered at term (p < 0.001 for each comparison); (2) A decrease in AFsVEGFR-1 concentrations per each quartile was associated with PROM after adjusting for confounders (OR 1.8; 95% CI 1.4-2.3); (3) IAI, regardless of the membrane status, was not associated with a change in the median AF concentrations of sVEGFR-1 and sVEGFR-2 (p > 0.05 for each comparison); and (4) Spontaneous term and PTL did not change the median sVEGFR-1 and sVEGFR-2 concentrations (p > 0.05 for each comparison). Conclusion. (1) This is the first evidence that preterm PROM is associated with a lower AF concentration of sVEGFR-1 than patients with PTL intact membranes. These findings cannot be attributed to gestational age, labor, or IAI; and (2) AF concentrations of sVEGFR-2 did not change with preterm PROM, IAI, or labor at term and preterm. C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Savasan, Zeynep Alpay; Romero, Roberto; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Vaisbuch, Edi; Mittal, Pooja; Madan, Ichchha; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Ogge, Giovanna/G-6109-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 105 TC 12 Z9 12 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD AUG PY 2010 VL 23 IS 8 BP 828 EP 841 DI 10.3109/14767050903440471 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 634OI UT WOS:000280592200011 PM 20158393 ER PT J AU Mazaki-Tovi, S Romero, R Kim, SK Vaisbuch, E Kusanovic, JP Erez, O Chaiworapongsa, T Gotsch, F Mittal, P Nhan-Chang, CL Than, NG Gomez, R Nien, JK Edwin, SS Pacora, P Yeo, L Hassan, SS AF Mazaki-Tovi, Shali Romero, Roberto Kim, Sun Kwon Vaisbuch, Edi Kusanovic, Juan Pedro Erez, Offer Chaiworapongsa, Tinnakorn Gotsch, Francesca Mittal, Pooja Nhan-Chang, Chia-Ling Than, Nandor Gabor Gomez, Ricardo Nien, Jyh Kae Edwin, Samuel S. Pacora, Percy Yeo, Lami Hassan, Sonia S. TI Could alterations in maternal plasma visfatin concentration participate in the phenotype definition of preeclampsia and SGA? SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Adipokine; pregnancy; fetal growth; metabolism; obesity ID COLONY-ENHANCING FACTOR; FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH RESTRICTION; HEALTHY NULLIPAROUS WOMEN; HUMAN FETAL MEMBRANES; FACTOR RECEPTOR-1 CONCENTRATION; CIRCULATING ANGIOGENIC FACTORS; UTERINE ARTERY DOPPLER; NECROSIS-FACTOR-ALPHA; NORMAL-PREGNANCY AB Objective. Women with preeclampsia and those who delivered a small-for-gestational-age (SGA) neonate share several mechanisms of disease, including chronic uteroplacental ischemia and failure of physiologic transformation of the spiral arteries. However, the clinical manifestation of these obstetrical syndromes is remarkably different. It has been proposed that an altered maternal metabolic state, as well as a unique circulating cytokines milieu, predispose women to develop either preeclampsia or SGA. Compelling evidence suggests that adipose tissue orchestrates both metabolic pathways and immunological responses via the production of adipokines. Visfatin is a novel adipocytokine with metabolic and immunomodulating properties. The objective of this study was to determine whether preeclampsia and SGA are associated with alterations in maternal circulating visfatin concentrations. Methods. This cross-sectional study included pregnant women in the following groups: (1) normal pregnancy (n = 158); (2) patients with preeclampsia (n = 43) of which 32 had an AGA and 11 had an SGA neonate; (3) patients without preeclampsia who delivered an SGA neonate (n = 55). Maternal plasma visfatin concentrations were measured by ELISA. Nonparametric tests and multiple linear regression analysis were used. Results. (1) Women who delivered an SGA neonate had a higher median maternal plasma visfatin concentration than those with a normal pregnancy (20.0 ng/ml, interquartile range: 17.2-24.6 vs. 15.2 ng/ml, 12.1-19.2, respectively; P < 0.001) and than those with preeclampsia (14.5 ng/ml, 12.5-18.7; P < 0.001); (2) the median maternal plasma visfatin concentration did not differ significantly between patients with preeclampsia and those with a normal pregnancy (P = 0.8); (3) among patients with preeclampsia, there was no significant difference in the median maternal plasma visfatin concentration between those with or without an SGA neonate (P = 0.5); (4) in a linear regression model, delivery of an SGA neonate and pregestational body mass index were independently associated with increased visfatin concentration after adjustment for confounding factors (maternal age, smoking, gestational age at blood collection and the presence of preeclampsia or SGA). Conclusion. (1) Patients with SGA, but not those with preeclampsia, had a higher maternal plasma visfatin concentration than those with a normal pregnancy; (2) this finding suggests differential involvement of visfatin in SGA and preeclampsia; (3) we propose that changes in circulating maternal visfatin concentration may be implicated in the phenotypic definitions and distinction of preeclampsia and SGA. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Kim, Sun Kwon; Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Chaiworapongsa, Tinnakorn; Gotsch, Francesca; Mittal, Pooja; Nhan-Chang, Chia-Ling; Than, Nandor Gabor; Edwin, Samuel S.; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA. [Mazaki-Tovi, Shali; Romero, Roberto; Kim, Sun Kwon; Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Chaiworapongsa, Tinnakorn; Gotsch, Francesca; Mittal, Pooja; Nhan-Chang, Chia-Ling; Than, Nandor Gabor; Edwin, Samuel S.; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Nhan-Chang, Chia-Ling; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo; Nien, Jyh Kae] Pontificia Univ Catolica Chile, Sotero Rio Hosp, Dept Obstet & Gynecol, CEDIP Ctr Perinatal Diag & Res, Santiago, Chile. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This study was supported by the Perinatology Research Branch, Division of Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 175 TC 19 Z9 19 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD AUG PY 2010 VL 23 IS 8 BP 857 EP 868 DI 10.3109/14767050903301017 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 634OI UT WOS:000280592200015 PM 19900033 ER PT J AU Solomon, BD Lacbawan, F Mercier, S Clegg, NJ Delgado, MR Rosenbaum, K Dubourg, C David, V Olney, AH Wehner, LE Hehr, U Bale, S Paulussen, A Smeets, HJ Hardisty, E Tylki-Szymanska, A Pronicka, E Clemens, M McPherson, E Hennekam, RCM Hahn, J Stashinko, E Levey, E Wieczorek, D Roeder, E Schell-Apacik, CC Booth, CW Thomas, RL Kenwrick, S Cummings, DAT Bous, SM Keaton, A Balog, JZ Hadley, D Zhou, N Long, R Velez, JI Pineda-Alvarez, DE Odent, S Roessler, E Muenke, M AF Solomon, Benjamin D. Lacbawan, Felicitas Mercier, Sandra Clegg, Nancy J. Delgado, Mauricio R. Rosenbaum, Kenneth Dubourg, Christele David, Veronique Olney, Ann Haskins Wehner, Lars-Erik Hehr, Ute Bale, Sherri Paulussen, Aimee Smeets, Hubert J. Hardisty, Emily Tylki-Szymanska, Anna Pronicka, Ewa Clemens, Michelle McPherson, Elizabeth Hennekam, Raoul C. M. Hahn, Jin Stashinko, Elaine Levey, Eric Wieczorek, Dagmar Roeder, Elizabeth Schell-Apacik, Chayim Can Booth, Carol W. Thomas, Ronald L. Kenwrick, Sue Cummings, Derek A. T. Bous, Sophia M. Keaton, Amelia Balog, Joan Z. Hadley, Donald Zhou, Nan Long, Robert Velez, Jorge I. Pineda-Alvarez, Daniel E. Odent, Sylvie Roessler, Erich Muenke, Maximilian TI Mutations in ZIC2 in human holoprosencephaly: description of a Novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID LOSS-OF-FUNCTION; PRENATAL-DIAGNOSIS; UNUSUAL VARIANT; SPECTRUM; POPULATION; REGION; GENE; SHH; 13Q; PERSPECTIVES AB Background Holoprosencephaly (HPE), the most common malformation of the human forebrain, may be due to mutations in genes associated with non-syndromic HPE. Mutations in ZIC2, located on chromosome 13q32, are a common cause of non-syndromic, non-chromosomal HPE. Objective To characterise genetic and clinical findings in patients with ZIC2 mutations. Methods Through the National Institutes of Health and collaborating centres, DNA from approximately 1200 individuals with HPE spectrum disorders was analysed for sequence variations in ZIC2. Clinical details were examined and all other known cases of mutations in ZIC2 were included through a literature search. Results By direct sequencing of DNA samples of an unselected group of unrelated patients with HPE in our NIH laboratory, ZIC2 mutations were found in 8.4% (49/582) of probands. A total of 157 individuals from 119 unrelated kindreds are described, including 141 patients with intragenic sequence determined mutations in ZIC2. Only 39/157 patients have previously been clinically described. Unlike HPE due to mutations in other genes, most mutations occur de novo and the distribution of HPE types differs significantly from that of non-ZIC2 related HPE. Evidence is presented for the presence of a novel facial phenotype which includes bitemporal narrowing, upslanting palpebral fissures, a short nose with anteverted nares, a broad and well demarcated philtrum, and large ears. Conclusions HPE due to ZIC2 mutations is distinct from that due to mutations in other genes. This may shed light on the mechanisms involved in formation of the forebrain and face and will help direct genetic counselling and diagnostic strategies. C1 [Solomon, Benjamin D.; Lacbawan, Felicitas; Bous, Sophia M.; Keaton, Amelia; Balog, Joan Z.; Hadley, Donald; Zhou, Nan; Long, Robert; Velez, Jorge I.; Pineda-Alvarez, Daniel E.; Roessler, Erich; Muenke, Maximilian] NHGRI, NIH, Bethesda, MD 20892 USA. [Lacbawan, Felicitas] SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Mercier, Sandra; Dubourg, Christele; David, Veronique; Odent, Sylvie] Univ Rennes, CNRS Genet & Dev, F-35043 Rennes, France. [Mercier, Sandra; Odent, Sylvie] CHU Hop Sud, Serv Genet Clin, F-35043 Rennes, France. [Clegg, Nancy J.; Delgado, Mauricio R.] Univ Texas SW Med Ctr Dallas, Texas Scottish Rite Hosp Children, Dept Neurol, Dallas, TX 75390 USA. [Rosenbaum, Kenneth] Childrens Natl Med Ctr, Dept Genet, Washington, DC 20010 USA. [Olney, Ann Haskins] Univ Nebraska, Med Ctr, Munroe Meyer Inst Genet & Rehabil, Dept Med Genet, Omaha, NE USA. [Hehr, Ute] Univ Regensburg, Ctr & Dept Human Genet, Regensburg, Germany. [Bale, Sherri] GeneDx, Gaithersburg, MD USA. [Paulussen, Aimee; Smeets, Hubert J.] MUMC, Dept Clin Genet, Maastricht, Netherlands. [Smeets, Hubert J.] MUMC, Sch Oncol & Dev Biol, GROW, Maastricht, Netherlands. [Hardisty, Emily] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Tylki-Szymanska, Anna; Pronicka, Ewa] Childrens Mem Hlth Inst, Clin Metab Dis Endocrinol & Diabetol, Warsaw, Poland. [Clemens, Michelle] Univ Pittsburgh, Med Ctr, Dept Genet, Pittsburgh, PA USA. [McPherson, Elizabeth] Marshfield Clin Fdn Med Res & Educ, Dept Genet, Marshfield, WI USA. [Hennekam, Raoul C. M.] UCL, Great Ormond St Hosp Children, Inst Child Hlth, Clin & Mol Genet Unit, London, England. [Hahn, Jin] Stanford Univ, Sch Med, Dept Neurol, Palo Alto, CA 94304 USA. [Hennekam, Raoul C. M.] Univ Amsterdam, Acad Med Ctr, Dept Pediat, NL-1105 AZ Amsterdam, Netherlands. [Stashinko, Elaine; Levey, Eric] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD USA. [Wieczorek, Dagmar] Univ Duisburg Essen, Inst Human Genet, Essen, Germany. [Roeder, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Div Genet & Metab Disorders, Dept Pediat, San Antonio, TX 78229 USA. [Schell-Apacik, Chayim Can] Univ Munich, Inst Social Pediat & Adolescent Med, Munich, Germany. [Booth, Carol W.] Lutheran Gen Hosp, Dept Genet, Park Ridge, IL 60068 USA. [Thomas, Ronald L.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Kenwrick, Sue] Addenbrookes Hosp, Addenbrookes Treatment Ctr, Cambridge, England. [Cummings, Derek A. T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Muenke, M (reprint author), NHGRI, NIH, Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov FU Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, United States of America; GIS Maladies Rares, France [GISMR0701/DHOS]; NIH; Howard Hughes Medical Institute FX This research was supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, United States of America and GIS Maladies Rares GISMR0701/DHOS, France. Other Funders: NIH; Howard Hughes Medical Institute. NR 36 TC 29 Z9 30 U1 1 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2010 VL 47 IS 8 BP 513 EP 524 DI 10.1136/jmg.2009.073049 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 630LI UT WOS:000280274200002 PM 19955556 ER PT J AU Stewart, DR Sloan, JL Yao, L Mannes, AJ Moshyedi, A Lee, CCR Sciot, R De Smet, L Mautner, VF Legius, E AF Stewart, Douglas R. Sloan, Jennifer L. Yao, Lawrence Mannes, Andrew J. Moshyedi, Armin Lee, Chyi-Chia Richard Sciot, Raf De Smet, Luc Mautner, Victor-Felix Legius, Eric TI Diagnosis, management, and complications of glomus tumours of the digits in neurofibromatosis type 1 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID HAND AB Background Glomus tumours are benign painful tumours of the glomus body, a thermoregulatory shunt in the digits. Glomus tumours of the fingers and toes are associated with the monogenic disorder neurofibromatosis type 1 (NF1) and are recently recognised as part of the NF1 phenotype. Methods and Results A multi-institutional experience with 15 individuals with NF1 and glomus tumours of the fingers or toes is reported. The majority of individuals presented with at least two of the symptoms in the classic triad of localised tenderness, severe paroxysmal pain, and sensitivity to cold. Appearance of the nail and finger or toe is often normal. Women are affected more often than men. Multifocal tumours are common. There is often a delay in diagnosis of many years and clinical suspicion is key to diagnosis, although magnetic resonance imaging may be useful in some scenarios. Surgical extirpation can be curative; however, local tumour recurrence and metachronous tumours are common. Three of our patients developed signs and symptoms of the complex regional pain syndrome. Conclusions Glomus tumours in NF1 are more common than previously recognised and NF1 patients should be specifically queried about fingertip or toe pain. C1 [Stewart, Douglas R.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Sloan, Jennifer L.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Yao, Lawrence] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Mannes, Andrew J.] NIH, Dept Anaesthesia & Surg Serv, Ctr Clin, Bethesda, MD 20892 USA. [Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Sciot, Raf] Catholic Univ Louvain, Dept Pathol, B-3000 Leuven, Belgium. [De Smet, Luc] Univ Hosp Pellenberg, Dept Orthopaed Surg, Lubbeek, Belgium. [Mautner, Victor-Felix] Univ Hosp Eppendorf, Dept Maxillofacial Surg, Lab Tumour Biol & Dev Disorders, Hamburg, Germany. [Legius, Eric] Catholic Univ Louvain, Dept Human Genet, B-3000 Leuven, Belgium. RP Stewart, DR (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM drstewart@mail.nih.gov RI Lee, Chyi-Chia/I-1938-2013 OI Lee, Chyi-Chia/0000-0002-5306-7781 FU Division of Intramural Research of the National Human Genome Research Institute (DRS); Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0096.02]; Federal Office for Scientific, Technical and Cultural Affairs, Belgium [2007-2011, P5/25] FX The work was supported in part by the Division of Intramural Research of the National Human Genome Research Institute (DRS), research grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (G.0096.02, EL), the Interuniversity Attraction Poles granted by the Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2007-2011; P5/25, EL), and by a Concerted Action Grant from the K.U. Leuven (EL, RS). 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 organisations imply endorsement by the US Government. NR 30 TC 16 Z9 17 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2010 VL 47 IS 8 BP 525 EP 532 DI 10.1136/jmg.2009.073965 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 630LI UT WOS:000280274200003 PM 20530151 ER PT J AU Hirsch, V AF Hirsch, Vanessa TI In Memory of Jonathan Sawyer Allan, MSc, DVM SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Biographical-Item C1 NIAID, Dept Mol Microbiol, Bethesda, MD 20851 USA. RP Hirsch, V (reprint author), NIAID, Dept Mol Microbiol, NIH 4 Ctr Dr,Rm B1-41, Bethesda, MD 20851 USA. EM vhirsch@nih.gov 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 BP 192 EP 193 DI 10.1111/j.1600-0684.2010.00436.x PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900002 ER PT J AU Keele, BF Li, H Desrosiers, RC Hahn, BH Shaw, GM Lifson, JD AF Keele, Brandon F. Li, Hui Desrosiers, Ronald C. Hahn, Beatrice H. Shaw, George M. Lifson, Jeffrey D. TI PREFERENTIAL TRANSMISSION OF SIVMAC251 VARIANTS FOLLOWING INTRARECTAL INOCULATION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Keele, Brandon F.; Lifson, Jeffrey D.] NCI, SAIC Frederick, AIDS & Canc Virus Program, Frederick, MD 21702 USA. [Li, Hui; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35223 USA. [Desrosiers, Ronald C.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 6 BP 268 EP 268 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900015 ER PT J AU Zahn, RC Rett, M Hagan, E Carville, A Okoye, A Hirsch, V Kunkel, D Mueller-Trutwin, M Hasselschwert, DL Brenchley, J Picker, L Villinger, F Schmitz, J AF Zahn, Roland Christian Rett, Melisa Hagan, Emily Carville, Angela Okoye, Afam Hirsch, Vanessa Kunkel, Desiree Mueller-Trutwin, Michaela Hasselschwert, Dana L. Brenchley, Jason Picker, Louis Villinger, Francois Schmitz, Joern TI UNUSUAL MATURATION OF CD4+T CELLS IN AFRICAN GREEN MONKEYS, A NATURAL HOST OF SIV INFECTION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Zahn, Roland Christian; Rett, Melisa; Hagan, Emily; Schmitz, Joern] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Sch Med, Boston, MA 02115 USA. [Carville, Angela] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Okoye, Afam; Picker, Louis] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. [Hirsch, Vanessa] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Kunkel, Desiree; Mueller-Trutwin, Michaela] Inst Pasteur, Unite Regulat Infect Retrovirales, F-75724 Paris, France. [Hasselschwert, Dana L.] UL Lafayette New Iberia Res Ctr, New Iberia, LA 70562 USA. [Villinger, Francois] Emory Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 10 BP 269 EP 270 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900019 ER PT J AU Reeves, RK Gillis, J Wong, FE Yu, Y Li, YA Piatak, M Lifson, J Johnson, RP AF Reeves, R. Keith Gillis, Jacqueline Wong, Fay E. Yu, Yi Li, Yuan Piatak, Michael Lifson, Jeff Johnson, R. Paul TI EVOLUTION OF SIVMAC239 NEF-INDUCED PROTECTION AGAINST VAGINAL CHALLENGE IS ASSOCIATED WITH MATURATION OF CD8+T CELL RESPONSES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Reeves, R. Keith; Gillis, Jacqueline; Wong, Fay E.; Yu, Yi; Johnson, R. Paul] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. [Li, Yuan; Piatak, Michael; Lifson, Jeff] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 13 BP 270 EP 271 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900022 ER PT J AU Rahmberg, A Neidermyer, W Ng, SK Carville, A Mansfield, KG Piatak, M Lifson, JD Johnson, RP Evans, DT AF Rahmberg, Andrew Neidermyer, William, Jr. Ng, Sharon K. Carville, Angela Mansfield, Keith G. Piatak, Michael, Jr. Lifson, Jeffrey D. Johnson, R. Paul Evans, David T. TI PHENOTYPIC DIFFERENCES IN HOMING RECEPTOR EXPRESSION ON CD8+T CELLS ELICITED BY INTRAVENOUS VERSUS SUBCUTANEOUS INOCULATION DO NOT AFFECT PROTECTION AGAINST AN INTRARECTAL SIV CHALLENGE SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Rahmberg, Andrew; Neidermyer, William, Jr.; Ng, Sharon K.; Evans, David T.] Harvard Univ, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Sch Med, Southborough, MA 01772 USA. [Carville, Angela; Mansfield, Keith G.] Harvard Univ, New England Primate Res Ctr, Dept Pathol, Sch Med, Southborough, MA 01772 USA. [Piatak, Michael, Jr.] NCI, SAIC Frederick Inc, Frederick, MD USA. [Lifson, Jeffrey D.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. [Johnson, R. Paul] Harvard Univ, New England Primate Res Ctr, Sch Med, Dept Med, Southborough, MA 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 15 BP 271 EP 271 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900024 ER PT J AU Strbo, N Vaccari, M Pahwa, S Kolber, MA Fisher, E Gonzalez, L Felber, BK Pavlakis, GN Franchini, G Podack, ER AF Strbo, Natasa Vaccari, Monica Pahwa, Savita Kolber, Michael A. Fisher, Eva Gonzalez, Louis Felber, Barbara K. Pavlakis, George N. Franchini, Genoveffa Podack, Eckhard R. TI SIV-GP96-IG VACCINE INDUCES HIGH LEVELS OF ADAPTIVE MUCOSAL CD8 EFFECTOR CELLS IN RHESUS MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Strbo, Natasa; Pahwa, Savita; Kolber, Michael A.; Fisher, Eva; Gonzalez, Louis; Podack, Eckhard R.] Univ Miami, Miller Sch Med, D CFAR, Miami, FL 33136 USA. [Vaccari, Monica; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. [Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. [Pavlakis, George N.] NCI, Human Retrovirus Sect, Frederick, MD 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 19 BP 272 EP 272 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900028 ER PT J AU Apetrei, C Gaufin, T Gautam, R Hirsch, V Lewis, M Brenchley, J Pandrea, I AF Apetrei, Cristian Gaufin, Thaidra Gautam, Rajeev Hirsch, Vanessa Lewis, Mark Brenchley, Jason Pandrea, Ivona TI SIVAGM INFECTION IN PATAS MONKEYS ERYTHROCEBUS PATAS. HOST ADAPTATION TO SIV INFECTION MAY RESULT IN VIRUS EXTINCTION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA. [Gaufin, Thaidra; Gautam, Rajeev] Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. [Hirsch, Vanessa; Brenchley, Jason] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Lewis, Mark] Bioqual Inc, Rockville, MD 20850 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 20 BP 273 EP 273 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900029 ER PT J AU Sundaravaradan, V Milush, JM Brenchley, JM Sodora, D AF Sundaravaradan, Vasudha Milush, Jeffrey M. Brenchley, Jason M. Sodora, Donald TI POTENTIAL TH1 AND TH2 FUNCTIONALITY IN DOUBLE NEGATIVE (CD3+/CD4-/CD8-) T CELLS DURING NATURAL SIV INFECTION OF SOOTY MANGABEYS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Sundaravaradan, Vasudha; Sodora, Donald] Seattle Biomed Res Inst, Viral Vaccine Program, Seattle, WA 98109 USA. [Milush, Jeffrey M.] Univ Calif San Francisco, San Francisco Gen Hosp Expt Med, San Francisco, CA 94110 USA. [Brenchley, Jason M.] NIAID, 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 21 BP 273 EP 273 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900030 ER PT J AU Barratt-Boyes, SM Brown, KN Wijewardana, V Liu, XD AF Barratt-Boyes, Simon M. Brown, Kevin N. Wijewardana, Viskam Liu, Xiangdong TI PATHOGENIC SIV INFECTION LEADS TO RAPID MOBILIZATION AND DEATH OF PLASMACYTOID DENDRITIC CELLS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Barratt-Boyes, Simon M.; Wijewardana, Viskam; Liu, Xiangdong] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA. [Brown, Kevin N.] NCI, Expt Immunol Branch, 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 25 BP 274 EP 274 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900034 ER PT J AU Harris, LD Pitaluga, S Silvestri, G Douek, DC Miller, CJ Haase, AT Lifson, J Brenchley, JM Estes, JD AF Harris, Levelle D. Pitaluga, Stefania Silvestri, Guido Douek, Daniel C. Miller, Christopher J. Haase, Ashley T. Lifson, Jeffrey Brenchley, Jason M. Estes, Jacob D. TI DAMAGED INTESTINAL EPITHELIAL INTEGRITY AND MICROBIAL TRANSLOCATION IN SIMIAN IMMUNODEFICIENCY VIRUS INFECTIONS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Harris, Levelle D.; Brenchley, Jason M.] NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Pitaluga, Stefania] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Silvestri, Guido] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Miller, Christopher J.] Univ Calif Davis, Ctr Comparat Med, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Haase, Ashley T.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. [Lifson, Jeffrey; Estes, Jacob D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 27 BP 275 EP 275 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900036 ER PT J AU Mori, K Sugimoto, C Shiino, T Kimura, A Miyazawa, M Hirsch, V Yamamoto, N Nagai, Y AF Mori, Kazuyasu Sugimoto, Chie Shiino, Teiichiro Kimura, Akinori Miyazawa, Masaaki Hirsch, Vanessa Yamamoto, Naoki Nagai, Yoshiyuki TI LONG-TERM CONTROL OF HETEROLOGOUS CHALLENGE INFECTION IN RHESUS MACAQUES VACCINATED WITH LIVE ATTENUATED DEGLYSOYLATED SIV BY CD8+CELLS MEDIATED RESPONSE SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Mori, Kazuyasu; Shiino, Teiichiro; Yamamoto, Naoki] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo 1628640, Japan. [Sugimoto, Chie] Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. [Kimura, Akinori] Tokyo Med & Dent Univ, Med Res Inst, Tokyo 1138510, Japan. [Miyazawa, Masaaki] Kinki Univ, Sch Med, Osaka 5898511, Japan. [Hirsch, Vanessa] NIAID, NIH, Bethesda, MD 20892 USA. [Nagai, Yoshiyuki] RIKEN, Ctr Res Network Infect Dis, Tokyo 1000006, Japan. 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 31 BP 276 EP 276 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900040 ER PT J AU Patel, V Rosati, M von Gegerfelt, A Valentin, A Bergamaschi, C Kulkarni, V Jalah, R Ohlen, C Khan, AS Draghia-Akli, R Venzon, DM Robert-Guroff, M Van Rompay, KKA Felber, BK Pavlakis, GN AF Patel, Vainav Rosati, Margherita von Gegerfelt, Agneta Valentin, Antonio Bergamaschi, Cristina Kulkarni, Viraj Jalah, Rashmi Ohlen, Claes Khan, Amir S. Draghia-Akli, Ruxandra Venzon, David M. Robert-Guroff, Marjorie Van Rompay, Koen K. A. Felber, Barbara K. Pavlakis, George N. TI INTRAMUSCULAR DNA DELIVERY BY ELECTROPORATION LEADS TO GREATLY ENHANCED SYSTEMIC AND MUCOSAL IMMUNE RESPONSES AND CONTROL OF SIVMAC251 CHALLENGE SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Patel, Vainav; Rosati, Margherita; von Gegerfelt, Agneta; Valentin, Antonio; Bergamaschi, Cristina; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. [Kulkarni, Viraj; Jalah, Rashmi; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. [Ohlen, Claes] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Khan, Amir S.; Draghia-Akli, Ruxandra] Inovio VGX Pharmaceut Inc, The Woodlands, TX 77381 USA. [Venzon, David M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Robert-Guroff, Marjorie] NCI, Immune Biol Retroviral Infect Sect, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Van Rompay, Koen K. A.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 33 BP 277 EP 277 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900042 ER PT J AU Rout, N Pozzi, LA Chan, K Pryputniewicz, S Kasheta, M Rosati, M Lifson, J Piatak, M Pavlakis, G Felber, B Desrosiers, R Knipe, D Kaur, A AF Rout, Namita Pozzi, Lu-Ann Chan, Kenneth Pryputniewicz, Sarah Kasheta, Melissa Rosati, Margherita Lifson, Jeffrey Piatak, Michael Pavlakis, George Felber, Barbara Desrosiers, Ronald Knipe, David Kaur, Amitinder TI IMMUNOGENICITY AND PROTECTIVE EFFICACY OF RECOMBINANT REPLICATION-DEFECTIVE HERPES SIMPLEX VIRUS AND DNA VECTOR-BASED AIDS VACCINES AGAINST SIV CHALLENGE IN RHESUS MACAQUES DEPENDS ON THE PRIME-BOOST SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Rout, Namita; Pozzi, Lu-Ann; Chan, Kenneth; Pryputniewicz, Sarah; Kasheta, Melissa; Kaur, Amitinder] Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA. [Rosati, Margherita; Pavlakis, George] NCI, Human Retrovirus Sect, Vaccine Branch, Frederick, MD 21702 USA. [Lifson, Jeffrey; Piatak, Michael] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. [Felber, Barbara] NCI, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. [Knipe, David] Harvard Univ, Sch Med, Boston, MA 02115 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 36 BP 278 EP 278 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900045 ER PT J AU O'Connor, SL Lhost, JJ Detmer, AM Johnson, RC Wiseman, RW MacNair, CE Karl, JA Greene, JM Burwitz, BJ Bimber, BN Lank, SM Friedrich, TC Carrington, M O'Connor, DH AF O'Connor, Shelby L. Lhost, Jennifer J. Detmer, Ann M. Johnson, Randall C. Wiseman, Roger W. MacNair, Caitlin E. Karl, Julie A. Greene, Justin M. Burwitz, Benjamin J. Bimber, Benjamin N. Lank, Simon M. Friedrich, Thomas C. Carrington, Mary O'Connor, David H. TI IDENTIFICATION OF MHC HETEROZYGOTE ADVANTAGE IN SIV-INFECTED MAURITIAN CYNOMOLGUS MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [O'Connor, Shelby L.; Lhost, Jennifer J.; Greene, Justin M.; Burwitz, Benjamin J.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Detmer, Ann M.; Wiseman, Roger W.; MacNair, Caitlin E.; Karl, Julie A.; Bimber, Benjamin N.; Lank, Simon M.; Friedrich, Thomas C.] Univ Wisconsin, Wisconsin Primate Res Ctr, Madison, WI 53706 USA. [Johnson, Randall C.] NCI, Lab Genom Div, Frederick, MD 21702 USA. [Carrington, Mary] NCI, SAIC Frederick, Frederick, MD 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 44 BP 281 EP 281 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900053 ER PT J AU Lopker, MJ Li, H Decker, J Bibollet-Ruche, F Kraus, MH Mascola, JR Nabel, GJ Letvin, NL Piatak, M Lifson, RD Keele, BF Hahn, BH Shaw, GM AF Lopker, Michael J. Li, Hui Decker, Julie Bibollet-Ruche, Frederic Kraus, Matthias H. Mascola, John R. Nabel, Gary J. Letvin, Norman L. Piatak, Michael, Jr. Lifson, Rey D. Keele, Brandon F. Hahn, Beatrice H. Shaw, George M. TI IDENTIFICATION, MOLECULAR CLONING AND CHARACTERIZATION OF MUCOSALLY TRANSMITTED SIVSME660 SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Lopker, Michael J.; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama Birmingaham, Dept Med, Birmingham, AL USA. [Mascola, John R.; Nabel, Gary J.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Keele, Brandon F.; Hahn, Beatrice H.; Shaw, George M.] NCI, SAIC Frederick Inc, 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA LB4 BP 282 EP 283 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900058 ER PT J AU Li, YA Schmitz, J de la Rosa, M Letvin, N Johnson, RP Salisch, N Reeves, RK Desrosiers, RC Lifson, JD Piatak, M AF Li, Yuan Schmitz, Joern de la Rosa, Maurus Letvin, Norman Johnson, R. Paul Salisch, Nadine Reeves, R. Keith Desrosiers, Ronald C. Lifson, Jeffrey D. Piatak, Michael, Jr. TI INDEPENDENT QUANTIFICATION OF SIVMAC239 NEF AND UNMODIFIED CHALLENGE VIRUSES IN DUAL-INFECTED MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Li, Yuan; Lifson, Jeffrey D.; Piatak, Michael, Jr.] NCI, SAIC Frederick, AIDS & Canc Virus Program, Frederick, MD 21702 USA. [Schmitz, Joern; de la Rosa, Maurus; Letvin, Norman] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Johnson, R. Paul; Salisch, Nadine; Reeves, R. Keith; Desrosiers, Ronald C.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 48 BP 284 EP 284 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900061 ER PT J AU Liu, XW Yu, R Liu, Y Lagenaur, LA Cheng, A Jia, LT Xia, Q Hamer, DH Li, J Sanders-Beer, BE Lee, PP Xu, Q AF Liu, Xiaowen Yu, Rosa Liu, Yang Lagenaur, Laurel A. Cheng, Andrew Jia, Letong Xia, Qing Hamer, Dean H. Li, Jeffery Sanders-Beer, Brigitte E. Lee, Peter P. Xu, Qiang TI MUCOSAL DELIVERY OF AN ANTI-HIV MOLECULE CYANOVIRIN-N BY LACTOBACILLUS IN A MACAQUE MODEL SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Liu, Xiaowen; Yu, Rosa; Liu, Yang; Lagenaur, Laurel A.; Cheng, Andrew; Jia, Letong; Xia, Qing; Lee, Peter P.; Xu, Qiang] Osel Inc, Santa Clara, CA 95054 USA. [Hamer, Dean H.] NCI, NIH, Bethesda, MD 20892 USA. [Li, Jeffery; Sanders-Beer, Brigitte E.] BIOQUAL Inc, Rockville, MD 20850 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 49 BP 285 EP 285 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900062 ER PT J AU Minang, JT Trivett, MT Barsov, EV Thomas, JA Gorelick, RJ Ott, DE Ohlen, CR AF Minang, Jacob T. Trivett, Matthew T. Barsov, Eugene V. Thomas, James A. Gorelick, Robert J. Ott, David E. Ohlen, Claes R. TI SIVMAC239 INFECTION OF PRIMARY RHESUS MACAQUE CD4+T-CELL CLONES IN VITRO IS INDEPENDENT OF ACTIVATION STATUS AND SURFACE CCR5 EXPRESSION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Minang, Jacob T.; Trivett, Matthew T.; Barsov, Eugene V.; Thomas, James A.; Gorelick, Robert J.; Ott, David E.; Ohlen, Claes R.] NCI, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 50 BP 285 EP 285 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900063 ER PT J AU Mandell, D Gaufin, T Gautam, R Sandler, N Douek, D Apetrei, C Pandrea, I AF Mandell, Daniel Gaufin, Thaidra Gautam, Rajeev Sandler, Netanya Douek, Daniel Apetrei, Cristian Pandrea, Ivona TI A SINGLE SERIAL PASSAGE OF SIVAGM.SAB IN PIGTAILED MACAQUES RESULTS IN A DRAMATIC INCREASE IN PATHOGENICITY OF INFECTION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Mandell, Daniel; Gaufin, Thaidra; Gautam, Rajeev] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA 70433 USA. [Sandler, Netanya; Douek, Daniel] NIAID, Human Immunol Sect, Vaccine Res Ctr, Natl Inst, Bethesda, MD 20892 USA. [Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 64 BP 289 EP 289 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900076 ER PT J AU von Gegerfelt, A Valentin, A Alicea, C Patel, V Pavlakis, GN Felber, BK AF von Gegerfelt, Agneta Valentin, Antonio Alicea, Candido Patel, Vainav Pavlakis, George N. Felber, Barbara K. TI ALTERED MUCOSAL DISTRIBUTION OF SIV-SPECIFIC T CELLS IN RHESUS MACAQUES INFECTED WITH THE LIVE-ATTENUATED REV-INDEPENDENT SIV SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [von Gegerfelt, Agneta; Valentin, Antonio; Patel, Vainav; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. [Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 63 BP 289 EP 289 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900075 ER PT J AU Hidajat, R Kuate, S Venzon, D Kalyanaraman, V Kalisz, I Treece, J Lian, Y Barnett, SW Robert-Guroff, M AF Hidajat, Rachmat Kuate, Seraphin Venzon, David Kalyanaraman, Vaniambadi Kalisz, Irene Treece, James Lian, Ying Barnett, Susan W. Robert-Guroff, Marjorie TI IMMUNOGENICITY EVALUATION OF HIV-1 GP160 OF SF162 AND TV1 STRAINS EXPRESSED BY REPLICATION COMPETENT ADENOVIRUS 5 HOST RANGE RECOMBINANTS IN BALB/C MICE SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Hidajat, Rachmat; Kuate, Seraphin; Venzon, David; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Bethesda, MD 20892 USA. [Kalyanaraman, Vaniambadi; Kalisz, Irene; Treece, James] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Lian, Ying] Adv BioSci Labs Inc, Kensington, MD USA. [Barnett, Susan W.] Chiron Corp, Emeryville, CA 94608 USA. Novartis Vaccines & Diagnost, Cambridge, MA 02139 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 88 BP 296 EP 296 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900100 ER PT J AU Sui, YJ Zhu, Q Gagnon, S Dzutsev, A Terabe, M Vaccari, M Venzon, D Klinman, D Strober, W Kelsall, B Franchini, G Belyakov, IM Berzofsky, JA AF Sui, Yongjun Zhu, Qing Gagnon, Susan Dzutsev, Amiran Terabe, Masaki Vaccari, Monica Venzon, David Klinman, Dennis Strober, Warren Kelsall, Brian Franchini, Genoveffa Belyakov, Igor M. Berzofsky, Jay A. TI ROLE OF VACCINE-INDUCED INNATE AND ADAPTIVE IMMUNITY IN CONTROLLING MUCOSAL TRANSMISSION OF SIV IN MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Sui, Yongjun; Gagnon, Susan; Dzutsev, Amiran; Terabe, Masaki; Vaccari, Monica; Venzon, David; Klinman, Dennis; Strober, Warren; Franchini, Genoveffa; Berzofsky, Jay A.] NCI, NIH, Bethesda, MD 20892 USA. [Zhu, Qing; Kelsall, Brian] NIAID, NIH, Bethesda, MD 20892 USA. [Belyakov, Igor M.] Midwest Res Inst, Frederick, MD 21702 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 91 BP 297 EP 297 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900102 ER PT J AU O'Neill, RR Harding, JD Watson, HL von Kollmar, DE Grieder, FB AF O'Neill, Raymond R. Harding, John D. Watson, Harold L. von Kollmar, Desiree E. Grieder, Franziska B. TI NONHUMAN PRIMATE RESEARCH IN AIDS: NCRR-SUPPORTED RESOURCES AND FUNDING OPPORTUNITIES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [O'Neill, Raymond R.; Harding, John D.; Watson, Harold L.; von Kollmar, Desiree E.; Grieder, Franziska B.] NIH, DCM, NCRR, 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 97 BP 299 EP 299 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900108 ER PT J AU Liu, JY Keele, B Carville, A Mansfield, KG Shaw, G Barouch, DH AF Liu, Jinyan Keele, Brandon Carville, Angela Mansfield, Keith G. Shaw, George Barouch, Dan H. TI IMPACT OF VIRUS INOCULUM DOSE ON REPLICATION KINETICS AND TRANSMITTED/FOUNDER VARIANTS FOLLOWING MUCOSAL SIV INFECTION OF RHESUS MONKEYS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Liu, Jinyan; Barouch, Dan H.] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA. [Keele, Brandon] NIH, Bethesda, MD 20892 USA. [Carville, Angela; Mansfield, Keith G.] New England Primate Res Ctr, Southborough, MA USA. [Shaw, George] Univ Alabama, Birmingham, AL 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 101 BP 300 EP 300 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900112 ER PT J AU Whitney, JB Hraber, PT Ludemann, C Rao, SS Mascola, JR Korber, B Nabel, GJ Letvin, NL AF Whitney, James B. Hraber, Peter T. Ludemann, Corinne Rao, Srinivas S. Mascola, John R. Korber, Bette Nabel, Gary J. Letvin, Norman L. TI EARLY GENITAL TRACT SEQUESTRATION DURING ACUTE SIV INFECTION SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Whitney, James B.; Ludemann, Corinne; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Hraber, Peter T.; Korber, Bette] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Rao, Srinivas S.; Mascola, John R.] NIAID, Vaccine Res Ctr, 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2010 VL 39 IS 4 MA 102 BP 301 EP 301 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 619RV UT WOS:000279448900113 ER PT J AU Qian, L Flood, PM Hong, JS AF Qian, Li Flood, Patrick M. Hong, Jau-Shyong TI Neuroinflammation is a key player in Parkinson's disease and a prime target for therapy SO JOURNAL OF NEURAL TRANSMISSION LA English DT Review DE Inflammation; Oxidative stress; Neurodegeneration ID NF-KAPPA-B; LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; NIGROSTRIATAL DOPAMINERGIC NEURODEGENERATION; MICROGLIA-MEDIATED NEUROTOXICITY; AMYOTROPHIC-LATERAL-SCLEROSIS; MUTANT ALPHA-SYNUCLEIN; REGULATORY T-CELLS; NADPH OXIDASE; MOUSE MODEL; INNATE IMMUNITY AB Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Increasing evidence has demonstrated that inflammation is the fundamental process contributing to neuron death in PD. Neuroinflammation, which is characterized by activated microglia and infiltrating T cells at sites of neuronal injury, is a prominent contributor to the pathogenesis of progressive PD. Microglia play a critical role in forming a self-propelling cycle leading to sustained chronic neuroinflammation and driving the progressive neurodegeneration in PD. This activation depends heavily on the respiratory burst within the microglia, which in turn regulates a number of downstream pro-inflammatory activities. On the other hand, the adaptive immune responses, most notably T cells, are now emerging as important components of the inflammatory response that contribute to the pathogenesis of PD. This review paper focus on the understanding of the inflammatory etiology of PD, as well as the molecular signaling involved in this inflammatory response, with the aim to provide more effective treatments to slow down or halt the progression of chronic inflammation-induced CNS disorders, such as PD. C1 [Qian, Li; Flood, Patrick M.] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. [Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Qian, L (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. EM qianl@email.unc.edu FU Intramural NIH HHS [ZIA ES090082-14] NR 87 TC 129 Z9 140 U1 6 U2 26 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD AUG PY 2010 VL 117 IS 8 SI SI BP 971 EP 979 DI 10.1007/s00702-010-0428-1 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 636AX UT WOS:000280701200007 PM 20571837 ER PT J AU Lou, H Park, JJ Cawley, NX Sarcon, A Sun, L Adams, T Peng Loh, Y AF Lou, Hong Park, Joshua J. Cawley, Niamh X. Sarcon, Annahita Sun, Lei Adams, Tiffany Peng Loh, Yoke TI Carboxypeptidase E cytoplasmic tail mediates localization of synaptic vesicles to the pre-active zone in hypothalamic pre-synaptic terminals SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE actin cortex; carboxypeptidase E; glutamate secretion; hypothalamic neuron; PC12 cells; gamma-adducin ID REGULATED SECRETORY PATHWAY; ACTIVITY-DEPENDENT SECRETION; PROHORMONE SORTING RECEPTOR; SYNAPSIN; EXOCYTOSIS; TRANSPORT; GRANULES; TRANSMISSION; CONVERTASE; DOCKING AB P>How synaptic vesicles (SVs) are localized to the pre-active zone (5-200 nm beneath the active zone) in the nerve terminal, which may represent the slow response SV pool, is not fully understood. Electron microscopy revealed the number of SVs located in the pre-active zone, was significantly decreased in hypothalamic neurons of carboxypeptidase E knockout (CPE-KO) mice compared with wild-type mice. Additionally, we found K+-stimulated glutamate secretion from hypothalamic embryonic neurons was impaired in CPE-KO mice. Biochemical studies indicate that SVs from the hypothalamus of wild-type mice and synaptic-like microvesicles from PC12 cells contain a transmembrane form of CPE, with a cytoplasmic tail (CPE(C10)), maybe involved in synaptic function. Yeast two-hybrid and pull-down experiments showed that the CPE cytoplasmic tail interacted with gamma-adducin, which binds actin enriched at the nerve terminal. Total internal reflective fluorescence (TIRF) microscopy using PC12 cells as a model showed that expression of GFP-CPE(C15) reduced the steady-state level of synaptophysin-mRFP containing synaptic-like microvesicles accumulated in the area within 200 nm from the sub-plasma membrane (TIRF zone). Our findings identify the CPE cytoplasmic tail, as a new mediator for the localization of SVs in the actin-rich pre-active zone in hypothalamic neurons and the TIRF zone of PC12 cells. C1 [Lou, Hong; Park, Joshua J.; Cawley, Niamh X.; Sarcon, Annahita; Adams, Tiffany; Peng Loh, Yoke] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Park, Joshua J.] Univ Toledo, Dept Neurosci, Sch Med, Toledo, OH 43606 USA. [Sun, Lei] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP Peng Loh, Y (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bldg 49,Rm 5A22,49 Convent Dr, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov FU NIH [RO1 DK050127]; Intramural Research Program of the NICHD; NIH; NICHD [K22]; ARRA FX We thank to laboratory members in SCN, NICHD for technical assistance and helpful discussions. We thank Dr Ronald W. Holz (U. Michgan) for his scientific advice about TIRF microscopy, Dr Leon Lagnado (Cambridge, UK) for Syn-mRFP. We thank Dr Vincent Schram in the NICHD Microscopy Imaging Core for their technical support. Lei Sun was supported by NIH grant RO1 DK050127 to Ronald W. Holz. This research was supported by the Intramural Research Program of the NICHD, NIH. Joshua J. Park has been supported by NICHD K22 and ARRA grants. NR 35 TC 9 Z9 10 U1 0 U2 0 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 AUG PY 2010 VL 114 IS 3 BP 886 EP 896 DI 10.1111/j.1471-4159.2010.06820.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 620ZI UT WOS:000279541900024 PM 20492353 ER PT J AU Oz, M Libby, T Kivell, B Jaligam, V Ramamoorthy, S Shippenberg, TS AF Oz, Murat Libby, Therissa Kivell, Bronwyn Jaligam, Vanaja Ramamoorthy, Sammanda Shippenberg, Toni S. TI Real-time, spatially resolved analysis of serotonin transporter activity and regulation using the fluorescent substrate, ASP(+) SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 4-(4-(dimethylamino)-styryl)-N-methylpyridinium; live-cell imaging; monoamine transporter; p38 mitogen-activated protein kinase; protein kinase C. ID PROTEIN-KINASE-C; CELL-SURFACE EXPRESSION; DOPAMINE TRANSPORTER; TOURETTE-SYNDROME; BIPOLAR DISORDER; ACTIVATION; PHOSPHORYLATION; RECEPTORS; BINDING; GENE AB The serotonin transporter (SEAT) mediates clearance of serotonin from the synapse, thereby, regulating extracellular serotonin concentrations. Radioligand uptake techniques are typically used to assess SEAT function in tissue and heterologous expression systems. The need for sufficient protein in samples, however, requires use of homogenate preparations, potentially masking effects limited to specific cell populations. 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP(+)) is a fluorescent monoamine transporter substrate that has been used for real-time monitoring of dopamine and norepinephrine transporter function in single cells. The present live cell imaging studies examine the utility of ASP for quantifying human SEAT function in HEK293 and neuroblastoma cells. We show rapid membrane binding and intracellular ASP(+) accumulation in human SERT-expressing cells. Accumulation is saturable; dependent on temperature and the presence of sodium and chloride in the media, and attenuated by serotonin. Acute or prolonged exposure of cells to serotonin re-uptake inhibitors produces a concentration-dependent decrease in accumulation. Similar effects are produced by protein kinase C activation whereas p38 MAPK activation increases ASP(+) accumulation. These data demonstrate the validity of ASP(+) as a probe for monitoring SEAT function in living cells. Alterations in SEAT binding and uptake can be quantified in the same cell and use of a within-cell design permits analysis of time-related alterations in SEAT function. C1 [Oz, Murat; Libby, Therissa; Kivell, Bronwyn; Jaligam, Vanaja; Shippenberg, Toni S.] NIDA, Integrat Neurosci Sect, IRP, NIH,US Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Ramamoorthy, Sammanda] Med Coll S Carolina, Dept Neurosci, Charleston, SC USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Sect, IRP, NIH,US Dept Hlth & Human Serv, 333 Cassell Dr, Baltimore, MD 21224 USA. EM tshippen@intra.nida.nih.gov RI Oz, Murat/E-2148-2012; Kivell, Bronwyn/P-3140-2014 OI Kivell, Bronwyn/0000-0001-9699-553X FU DHHS NIH/NIDA IRP; NIH [MH062612] FX We gratefully acknowledge the gift of pEGFP-hSERT from Dr Harold Sitte. This research was supported by DHHS NIH/NIDA IRP and NIH grant (MH062612: S.R). NR 35 TC 15 Z9 16 U1 0 U2 3 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 AUG PY 2010 VL 114 IS 4 BP 1019 EP 1029 DI 10.1111/j.1471-4159.2010.06828.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 636EC UT WOS:000280710100008 PM 20524964 ER PT J AU Vidal, JS Vidailhet, M Derkinderen, P Tzourio, C Alperovitch, A AF Vidal, Jean-Sebastien Vidailhet, Marie Derkinderen, Pascal Tzourio, Christophe Alperovitch, Annick TI Familial aggregation in atypical Parkinson's disease: a case control study in multiple system atrophy and progressive supranuclear palsy SO JOURNAL OF NEUROLOGY LA English DT Article DE Progressive supranuclear palsy; Multiple system atrophy; Parkinsonism; Dementia; Genetics; Case control study ID RISK-FACTORS; TAU; PREVALENCE AB Familial aggregation has been consistently found in PD, but it is unclear whether there is a familial aggregation in families of patients with multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). MSA and PSP cases were recruited from a two-arm case control study. One control was matched to each case for age, gender and living area. Medical history of first-degree relatives was obtained through a face-to-face questionnaire. Age-specific cumulative incidence of Parkinsonism and dementia in first-degree relatives of cases and controls was compared for MSA and PSP separately. Seventy-one pairs for MSA and their controls and 79 pairs for PSP and their controls were included. No significant familial aggregation was found in PSP. MSA cases reported Parkinsonism more often, but not dementia in their first-degree relatives than controls. MSA patients, but not those with PSP, have Parkinsonism more often in their first-degree relatives than controls. C1 [Vidal, Jean-Sebastien] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Vidal, Jean-Sebastien; Tzourio, Christophe; Alperovitch, Annick] INSERM, U708, Paris, France. [Vidal, Jean-Sebastien; Vidailhet, Marie; Tzourio, Christophe; Alperovitch, Annick] Univ Paris 06, UPMC, Paris, France. [Vidailhet, Marie] Grp Hosp Pitie Salpetriere, INSERM, U679, F-75634 Paris, France. [Vidailhet, Marie] Grp Hosp Pitie Salpetriere, Dept Neurol, F-75634 Paris, France. [Derkinderen, Pascal] Hop Laennec, Dept Neurol, Nantes, France. [Derkinderen, Pascal] Hop Laennec, Ctr Clin Invest, Nantes, France. RP Vidal, JS (reprint author), NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM vidaljs@mail.nih.gov RI Tzourio, christophe/B-4015-2009; Derkinderen, Pascal/K-2393-2015; Vidal, Jean-Sebastien/D-1941-2016 OI Tzourio, christophe/0000-0002-6517-2984; Vidal, Jean-Sebastien/0000-0001-6770-0720 NR 25 TC 12 Z9 14 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD AUG PY 2010 VL 257 IS 8 BP 1388 EP 1393 DI 10.1007/s00415-010-5638-9 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 632AW UT WOS:000280393400025 PM 20625759 ER PT J AU Lamy, JC Russmann, H Shamim, EA Meunier, S Hallett, M AF Lamy, Jean-Charles Russmann, Heike Shamim, Ejaz A. Meunier, Sabine Hallett, Mark TI Paired Associative Stimulation Induces Change in Presynaptic Inhibition of Ia Terminals in Wrist Flexors in Humans SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; MOTOR CORTEX EXCITABILITY; POST-ACTIVATION DEPRESSION; SPINAL-CORD; MUSCLE AFFERENTS; HUMAN FOREARM; H-REFLEX; RECIPROCAL INHIBITION; PREMOTOR CORTEX; PLASTICITY AB Lamy J-C, Russmann H, Shamim EA, Meunier S, Hallett M. Paired associative stimulation induces change in presynaptic inhibition of Ia terminals in wrist flexors in humans. J Neurophysiol 104: 755-764, 2010. First published June 10, 2010; doi:10.1152/jn.00761.2009. Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments (experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1 and D2 inhibitions methods; experiment 2) and postactivation depression (experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals. C1 [Lamy, Jean-Charles; Russmann, Heike; Shamim, Ejaz A.; Meunier, Sabine; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Natl Inst Hlth, Bethesda, MD USA. [Russmann, Heike] Univ Vaudois, Dept Neurol, Ctr Hosp, Lausanne, Switzerland. [Shamim, Ejaz A.] Kaiser Permanente, Dept Neurol, Suitland, MD USA. [Meunier, Sabine] Inst Natl Sante & Rech Med, Ctr Rech Inst Cerveau & Moelle Epiniere, Unite Mixte Rech Sante, Paris, France. [Meunier, Sabine] 975 Ctr Natl Rech Sci, Unite Mixte Rech 7225, Paris, France. RP Lamy, JC (reprint author), Stanford Univ, Stanford Neural Plast Lab, Med Ctr, Vet Affairs Palo Alto Hlth Care Syst, 3801 Miranda Ave,Bldg 4,Rm A-101-C, Palo Alto, CA 94304 USA. EM jeancharles.lamy@gmail.com RI meunier, sabine/G-7622-2014 OI meunier, sabine/0000-0002-6167-4602 FU National Institutes of Health, National Institute of Neurological Disorders and Stroke; Fondation pour la Recherche Medicale; Intramural National Institutes of Health; Swiss National Funds [PBSKB-104264]; Swiss Parkinson Society FX This research was funded by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. J.-C. Lamy was funded by Fondation pour la Recherche Medicale and Intramural National Institutes of Health. H. Russmann was funded by Swiss National Funds Grant PBSKB-104264, the Swiss Parkinson Society, and Intramural National Institutes of Health. NR 58 TC 14 Z9 15 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2010 VL 104 IS 2 BP 755 EP 764 DI 10.1152/jn.00761.2009 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 638XN UT WOS:000280932400019 PM 20538768 ER PT J AU Bromberg-Martin, ES Matsumoto, M Hong, S Hikosaka, O AF Bromberg-Martin, Ethan S. Matsumoto, Masayuki Hong, Simon Hikosaka, Okihide TI A Pallidus-Habenula-Dopamine Pathway Signals Inferred Stimulus Values SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PREFRONTAL CORTEX; LATERAL HABENULA; PREDICTION ERROR; CAUDATE-NUCLEUS; NEURONS; REWARD; MODEL; RAT; REPRESENTATION; STIMULATION AB Bromberg-Martin ES, Matsumoto M, Hong S, Hikosaka O. A pallidus-habenula-dopamine pathway signals inferred stimulus values. J Neurophysiol 104: 1068-1076, 2010. First published June 10, 2010; doi: 10.1152/jn.00158.2010. The reward value of a stimulus can be learned through two distinct mechanisms: reinforcement learning through repeated stimulus-reward pairings and abstract inference based on knowledge of the task at hand. The reinforcement mechanism is often identified with midbrain dopamine neurons. Here we show that a neural pathway controlling the dopamine system does not rely exclusively on either stimulus-reward pairings or abstract inference but instead uses a combination of the two. We trained monkeys to perform a reward-biased saccade task in which the reward values of two saccade targets were related in a systematic manner. Animals used each trial's reward outcome to learn the values of both targets: the target that had been presented and whose reward outcome had been experienced (experienced value) and the target that had not been presented but whose value could be inferred from the reward statistics of the task (inferred value). We then recorded from three populations of reward-coding neurons: substantia nigra dopamine neurons; a major input to dopamine neurons, the lateral habenula; and neurons that project to the lateral habenula, located in the globus pallidus. All three populations encoded both experienced values and inferred values. In some animals, neurons encoded experienced values more strongly than inferred values, and the animals showed behavioral evidence of learning faster from experience than from inference. Our data indicate that the pallidus-habenula-dopamine pathway signals reward values estimated through both experience and inference. C1 [Bromberg-Martin, Ethan S.; Matsumoto, Masayuki; Hong, Simon; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Matsumoto, Masayuki] Kyoto Univ, Primate Res Inst, Aichi, Japan. RP Bromberg-Martin, ES (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr,Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM bromberge@mail.nih.gov FU National Eye Institute FX This research was supported by the Intramural Research Program at the National Eye Institute. NR 36 TC 64 Z9 66 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2010 VL 104 IS 2 BP 1068 EP 1076 DI 10.1152/jn.00158.2010 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 638XN UT WOS:000280932400047 PM 20538770 ER PT J AU Palazzolo, I Nedelsky, NB Askew, CE Harmison, GG Kasantsev, AG Taylor, JP Fischbeck, KH Pennuto, M AF Palazzolo, Isabella Nedelsky, Natalia B. Askew, Caitlin E. Harmison, George G. Kasantsev, Aleksey G. Taylor, J. Paul Fischbeck, Kenneth H. Pennuto, Maria TI B2 Attenuates Polyglutamine-Expanded Androgen Receptor Toxicity in Cell and Fly Models of Spinal and Bulbar Muscular Atrophy SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE polyglutamine disease; SBMA; androgen receptor; B2; inclusions ID TRANSGENIC MOUSE MODEL; INTRANUCLEAR INCLUSIONS; TRANSCRIPTIONAL REGULATION; KENNEDY-DISEASE; PROTEIN-KINASE; NEURODEGENERATION; HUNTINGTIN; NUCLEAR; BINDING; ACETYLATION AB Expanded polyglutamine tracts cause neurodegeneration through a toxic gain-of-function mechanism. Generation of inclusions is a common feature of polyglutamine diseases and other protein misfolding disorders. Inclusion formation is likely to be a defensive response of the cell to the presence of unfolded protein. Recently, the compound B2 has been shown to increase inclusion formation and decrease toxicity of polyglutamine-expanded huntingtin in cultured cells. We explored the effect of B2 on spinal and bulbar muscular atrophy (SBMA). SBMA is caused by expansion of polyglutamine in the androgen receptor (AR) and is characterized by the loss of motor neurons in the brain-stem and spinal cord. We found that B2 increases the deposition of mutant AR into nuclear inclusions, without altering the ligand-induced aggregation, expression, or subcellular distribution of the mutant protein. The effect of B2 on inclusions was associated with a decrease in AR transactivation function. We show that B2 reduces mutant AR toxicity in cell and fly models of SBMA, further supporting the idea that accumulation of polyglutamine-expanded protein into inclusions is protective. Our findings suggest B2 as a novel approach to therapy for SBMA. (C) 2010 Wiley-Liss, inc. C1 [Pennuto, Maria] Italian Inst Technol, Dept Neurosci, I-16163 Genoa, Italy. [Palazzolo, Isabella; Askew, Caitlin E.; Harmison, George G.; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Palazzolo, Isabella] Univ Milan, Inst Endocrinol, Milan, Italy. [Nedelsky, Natalia B.; Taylor, J. Paul] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Nedelsky, Natalia B.] Univ Penn, Neurosci Grad Grp, Philadelphia, PA 19104 USA. [Kasantsev, Aleksey G.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pennuto, M (reprint author), Italian Inst Technol, Dept Neurosci & Brain Technol, Via Morego 30, I-16163 Genoa, Italy. EM maria.pennuto@iit.it OI Pennuto, Maria/0000-0001-8634-0767 FU NINDS-NIH; Kennedy's Disease Association; Muscular Dystrophy Association; NIH [NS053825] FX Contract grant sponsor: NINDS-NIH; Contract grant sponsor: Kennedy's Disease Association (to M.P.); Contract grant sponsor: Muscular Dystrophy Association (to M.P., J.P.T.); Contract grant sponsor: NIH; Contract grant number: NS053825 (to J.P.T.). NR 48 TC 17 Z9 17 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 2010 VL 88 IS 10 BP 2207 EP 2216 DI 10.1002/jnr.22389 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 622ZM UT WOS:000279706200013 PM 20336775 ER PT J AU Lu, J Zhuang, ZP Song, DK Mehta, GU Ikejiri, B Mushlin, H Park, DM Lonser, RR AF Lu, Jie Zhuang, Zhengping Song, Debbie K. Mehta, Gautam U. Ikejiri, Barbara Mushlin, Harry Park, Deric M. Lonser, Russell R. TI The effect of a PP2A inhibitor on the nuclear receptor corepressor pathway in glioma Laboratory investigation SO JOURNAL OF NEUROSURGERY LA English DT Article DE nuclear receptor corepressor; glioma; xenograft; protein phosphatase 2A; phosphorylation ID SUBEROYLANILIDE HYDROXAMIC ACID; PROTEIN PHOSPHATASE 2A; CANCER STEM-CELL; GLIOBLASTOMA; GROWTH; DIFFERENTIATION; RADIOTHERAPY; DEATH; MTOR AB Object. Nuclear receptor corepressor (N-CoR) forms a complex that maintains neural stem cells in an undifferentiated state through transcriptional repression. Recently, it has been shown that N-CoR is overexpressed in glioblastoma multiforme (GBM) tumor stem cells and has a putative role in maintaining these cells in an undifferentiated immortal state. To determine the effects of disruption of N-CoR complex function by serine/threonine protein phosphatase 2A (PP2A) inhibition on GBM tumor cell differentiation and proliferation, the authors developed and investigated a competitive small molecule inhibitor (LB1) of PP2A in GBM. Methods. The authors investigated the effects of LB1 on GBM proliferation and molecular differentiation pathways using in vitro and in vivo studies. Results. The LB1 inhibited PP2A, leading to increased levels of phosphorylated Akt kinase and decreased NCoR expression, as well as dose-dependent antiproliferative activity in cultured U87 and U251 malignant glioma cells (dose range 1-10 mu M). Systemic LB1 treatment (1.5 mg/kg/day for 21 (lays) had significant tumor antiproliferative effects in mice harboring U87 glioma xenografts (73% mean reduction in tumor volume compared with controls; p < 0.001). Moreover, a reduction in PP2A expression and activity after LB1 treatment in vivo correlated with increased Akt phosphorylation, reduced nuclear N-CoR expression and N-CoR cytoplasmic translocation, and increased accumulation of acetylated core histones, which coincided with the appearance of glial fibrillary acidic protein expressing tumor cells. Conclusions. These findings indicate that PP2A inhibition effectively disrupts N-CoR complex function/expression and leads to cytoplasmic translocation of N-CoR with subsequent tumor cell differentiation and/or death. Therapeutic paradigms that target N-CoR function in the cancer stem cell component of malignant gliomas may have treatment utility. (DO!: 10.3171/2009.11.JNS091272) C1 [Lu, Jie; Zhuang, Zhengping; Song, Debbie K.; Mehta, Gautam U.; Ikejiri, Barbara; Mushlin, Harry; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Park, Deric M.] Univ Pittsburgh, Med Ctr, Dept Neurol Surg, Pittsburgh, PA USA. RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Park, Deric/C-5675-2013; OI Mehta, Gautam/0000-0002-8009-6430 FU National Institute of Neurological Disorders and Stroke at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and a cooperative research and development agreement between the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and Lixte Biotechnology Holdings, Inc. NR 18 TC 14 Z9 15 U1 1 U2 5 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2010 VL 113 IS 2 BP 225 EP 233 DI 10.3171/2009.11.JNS091272 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 632FH UT WOS:000280405900018 PM 20001590 ER PT J AU DeGrado, TR Bhattacharyya, F Pandey, MK Belanger, AP Wang, SY AF DeGrado, Timothy R. Bhattacharyya, Falguni Pandey, Mukesh K. Belanger, Anthony P. Wang, Shuyan TI Synthesis and Preliminary Evaluation of 18-F-18-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE fatty acid oxidation; PET; myocardial metabolism ID POSITRON-EMISSION-TOMOGRAPHY; MYOCARDIAL-METABOLISM; MOLECULAR-MECHANISMS; RAT-HEART; HUMANS; TRACERS; LIVER; CARDIOMYOPATHY; DYSFUNCTION; PALMITATE AB Fatty acid oxidation (FAO) is a major energy-providing process with important implications in cardiovascular, oncologic, neurologic, and metabolic diseases. A novel 4-thia oleate analog, 18-F-18-fluoro-4-thia-oleate (F-18-FTO), was evaluated in relationship to the previously developed palmitate analog 16-F-18-fluoro-4-thia-palmitate (F-18-FTP) as an FAO probe. Methods: F-18-FTO was synthesized from a corresponding bromoester. Biodistribution and metabolite analysis studies were performed in rats. Preliminary small-animal PET studies were performed with F-18-FTO and F-18-FTP in rats. Results: A practical synthesis of F-18-FTO was developed, providing a radiotracer of high radiochemical purity (>99%). In fasted rats, myocardial uptake of F-18-FTO (0.70 +/- 0.30% dose kg [body mass]/g [tissue mass]) was similar to that of F-18-FTP at 30 min after injection. At 2 h, myocardial uptake of F-18-FTO was maintained, whereas F-18-FTP uptake in the heart was 82% reduced. Similar to F-18-FTP, F-18-FTO uptake by the heart was approximately 80% reduced at 30 min by pretreatment of rats with the CPT-I inhibitor etomoxir. Folch-type extraction analyses showed 70-90% protein-bound fractions in the heart, liver, and skeletal muscle, consistent with efficient trafficking of F-18-FTO to the mitochondrion with subsequent metabolism to protein-bound species. Preliminary small-animal PET studies showed rapid blood clearance and avid extraction of F-18-FTO and of F-18-FTP into the heart and liver. Images of F-18-FTO accumulation in the rat myocardium were clearly superior to those of F-18-FTP. Conclusion: F-18-FTO is shown to be a promising metabolically trapped FAO probe that warrants further evaluation. C1 [DeGrado, Timothy R.; Pandey, Mukesh K.; Belanger, Anthony P.; Wang, Shuyan] Harvard Univ, Dept Radiol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Bhattacharyya, Falguni] NIH, Imaging Probe Dev Ctr, Bethesda, MD 20892 USA. RP DeGrado, TR (reprint author), Harvard Univ, Dept Radiol, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM tdegrado@partners.org FU NIH [R01 HL-63371, R01 CA108620] FX We thank Aditya Bansal for his assistance. We acknowledge the support of the NIH (grants R01 HL-63371 and R01 CA108620). Dr. Timothy DeGrado is a shareholder of Tracera, LLC. NR 38 TC 14 Z9 14 U1 2 U2 3 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 AUG 1 PY 2010 VL 51 IS 8 BP 1310 EP 1317 DI 10.2967/jnumed.109.074245 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 635HG UT WOS:000280645600030 PM 20660391 ER PT J AU Freedman, LS Guenther, PM Krebs-Smith, SM Dodd, KW Midthune, D AF Freedman, Laurence S. Guenther, Patricia M. Krebs-Smith, Susan M. Dodd, Kevin W. Midthune, Douglas TI A Population's Distribution of Healthy Eating Index-2005 Component Scores Can Be Estimated When More Than One 24-Hour Recall Is Available SO JOURNAL OF NUTRITION LA English DT Article ID EPISODICALLY CONSUMED FOODS AB The USDA's Healthy Eating Index-2005 (HEI-2005) is a tool to quantify the quality of diet consumed by individuals in the U.S. It comprises 12 components expressed as ratios of a food group or nutrient intake to energy intake. Components are scored on a scale from 0 to M, where M is 5, 10, or 20. Ideally, the HEI-2005 is calculated on the basis of the usual, or long-term average, dietary intake of an individual. In recent cycles of the NHANES, intake data have been collected via 24-h recalls for more than 1 d on most participants. We present here a statistical method to estimate a population's distribution of usual HEI-2005 component scores when >= 2 d of dietary information is available for a sample of individuals from the population. Distributions for the total population and for age-gender subgroups may be estimated. The method also yields an estimate of the population's mean total HEI-2005 score. Application of the method to NHANES data for 2001-2004 yielded estimated distributions for all 12 components; those of total vegetables (range 0-5), whole grains (range 0-5), and energy from solid fats, alcoholic beverages, and added sugars (range 0-20) are presented. The total population mean scores for these components were 3.21, 1.00, and 8.41, respectively. An estimated 30% of the total population had a score of <2.5 for total vegetables. This is the first time, to our knowledge, that estimated distributions of usual HEI-2005 component scores have been published. J. Nutr. 140: 1529-1534, 2010. C1 [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. [Guenther, Patricia M.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA. [Krebs-Smith, Susan M.; Dodd, Kevin W.; Midthune, Douglas] NCI, Bethesda, MD 20892 USA. RP Freedman, LS (reprint author), Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. EM lsf@actcom.co.il FU Information Management Services Inc with the US National Cancer Institute; USDA; National Cancer Institute FX Supported by a contract held by Information Management Services Inc with the US National Cancer Institute (to L.S.F.); the remaining authors were supported by their respective institutions, the USDA, and the National Cancer Institute. NR 10 TC 22 Z9 23 U1 2 U2 4 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD AUG PY 2010 VL 140 IS 8 BP 1529 EP 1534 DI 10.3945/jn.110.124594 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 629PE UT WOS:000280211300022 PM 20573940 ER PT J AU Yan, H Sun, LG Wang, YH Liu, XD Qiu, SC Cheng, WH AF Yan, Hong Sun, Liguang Wang, Yuhong Liu, Xiaodong Qiu, Shican Cheng, Wenhan TI A 2000-year record of copper pollution in South China Sea derived from seabird excrements: a potential indicator for copper production and civilization of China SO JOURNAL OF PALEOLIMNOLOGY LA English DT Article DE South China Sea; Sediment core; Seabird excrements; Copper content; Civilization; Copper production ID RED-FOOTED BOOBY; METAL LEVELS; TEMPORAL TRENDS; LAKE-SEDIMENTS; PACIFIC-OCEAN; PEAT BOG; ANTARCTICA; HISTORY; ATOLL; LEAD AB In the Chinese feudal era, copper was widely used in coinage and weapons, and its production was coupled with political stability and economic prosperity. In the smelting process, copper was released into the environment and accumulated in the food web, and it became enriched in animal tissues and in seabird droppings. Here we report a 2000-year record of copper in red-footed booby excrement from Dongdao Island, South China Sea. There exists a striking correlation between the copper content in the seabird excrements and the ancient copper production of China for past two millennia. The increased Cu content corresponds to the flourishing times of dynasties, such as the Tang and Sung Dynasties, and declines in Cu content correspond with dynastic declines. Even some brief (decadal) wars and calamities, such as the Anshi Rebellion in AD 755-763 and the Taiping Heavenly Kingdom in AD 1851-1864, were recorded in the copper content profile. We established an approximate function to model the quantitative relationship between the copper content in the seabird excrement and the ancient copper production. We estimate that a total of similar to 14 million tons of copper was produced during the past two millennia in China. Among the 14 million tons of copper, about 0.65 million tons was released into the atmosphere. C1 [Yan, Hong; Sun, Liguang; Liu, Xiaodong; Qiu, Shican; Cheng, Wenhan] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. [Wang, Yuhong] NIH, Bethesda, MD 20892 USA. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM slg@ustc.edu.cn RI Yan, Hong/I-8970-2014 FU Natural Science Foundation of China (NSFC) [40730107] FX This work was supported by the Natural Science Foundation of China (NSFC) (40730107). We wish to thank Nan Jia, Sanping Zhao, Xuebin Yin, Honghao Luo and Jie Fei for their help in sampling and analyzing. We especially appreciate Editor in Chief Dr. Thomas J Whitmore, Associate Editor Dr. Neil Rose and two anonymous reviewers for their constructive reviews, comments and suggestions to improve this manuscript. NR 48 TC 8 Z9 9 U1 6 U2 37 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0921-2728 J9 J PALEOLIMNOL JI J. Paleolimn. PD AUG PY 2010 VL 44 IS 2 BP 431 EP 442 DI 10.1007/s10933-010-9413-9 PG 12 WC Environmental Sciences; Geosciences, Multidisciplinary; Limnology SC Environmental Sciences & Ecology; Geology; Marine & Freshwater Biology GA 627VB UT WOS:000280070500006 ER PT J AU Sobin, LH Compton, CA Gospodarowicz, M Greene, FL Gunderson, LL Jessup, JM Wittekind, C AF Sobin, Leslie H. Compton, Carolyn A. Gospodarowicz, Mary Greene, Frederick L. Gunderson, Leonard L. Jessup, J. Milburn Wittekind, Christian TI 'Evidence-based medicine: the time has come to set standards for staging'. Is a radical overhaul really needed? SO JOURNAL OF PATHOLOGY LA English DT Article DE TNM staging; evidence-based medicine; colorectal cancer; lymph nodes; tumour deposits; staging ID FORTHCOMING 7TH EDITION; IASLC LUNG-CANCER; ADJUVANT RECTAL-CANCER; TNM CLASSIFICATION; POOLED ANALYSIS; INTERNATIONAL-ASSOCIATION; MALIGNANT-TUMORS; STAGE GROUPINGS; COLON-CANCER; PROJECT AB This Invited Response addresses concerns and opinions expressed in an Invited Commentary, 'Evidence-based medicine: the time has come to set standards for staging', by Quirke et al., published in this issue of The Journal of Pathology. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Sobin, Leslie H.] Int Union Canc, CH-1207 Geneva, Switzerland. [Compton, Carolyn A.; Jessup, J. Milburn] NCI, Bethesda, MD 20892 USA. [Gospodarowicz, Mary] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Greene, Frederick L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Gunderson, Leonard L.] Mayo Clin, Ctr Canc, Scottsdale, AZ USA. [Wittekind, Christian] Univ Hosp, Inst Pathol, Leipzig, Germany. RP Sobin, LH (reprint author), Int Union Canc, 62 Route Frontenex, CH-1207 Geneva, Switzerland. EM sobin@uicc.org NR 23 TC 9 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD AUG PY 2010 VL 221 IS 4 BP 361 EP 362 DI 10.1002/path.2729 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 627AN UT WOS:000280010300002 PM 20593484 ER PT J AU Lester, BM LaGasse, LL Shankaran, S Bada, HS Bauer, CR Lin, R Das, A Higgins, R AF Lester, Barry M. LaGasse, Linda L. Shankaran, Seetha Bada, Henrietta S. Bauer, Charles R. Lin, Richard Das, Abhik Higgins, Rosemary TI Prenatal Cocaine Exposure Related to Cortisol Stress Reactivity in 11-Year-Old Children SO JOURNAL OF PEDIATRICS LA English DT Article ID PITUITARY-ADRENAL AXIS; MATERNAL LIFE-STYLE; COMMUNITY VIOLENCE PROJECT; LOW-INCOME WOMEN; SALIVARY CORTISOL; MALTREATED CHILDREN; NEUROENDOCRINE ACTIVITY; BEHAVIOR PROBLEMS; CONDUCT DISORDER; PSYCHOLOGICAL STRESS AB Objective Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school-aged children. Study design Subjects included 743 11-year-old children (n = 320 cocaine-exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse, and quality of the home. Results With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Children exposed to cocaine and who experienced domestic violence showed the strongest effects. Conclusions The combination of prenatal cocaine exposure and an adverse postnatal environment could downregulate the hypothalamic-pituitary-adrenal axis resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease. (J Pediatr 2010;157:288-95). C1 [Lester, Barry M.; LaGasse, Linda L.; Lin, Richard] Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp Rhode Isl,Dept Pediat, Brown Ctr Study Children Risk, Providence, RI 02905 USA. [Lester, Barry M.; LaGasse, Linda L.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02905 USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Bada, Henrietta S.] Univ Kentucky Hosp, Dept Pediat, Lexington, KY USA. [Bauer, Charles R.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Das, Abhik] RTI Int, Rockville, MD USA. [Higgins, Rosemary] NICHHD, Bethesda, MD 20892 USA. RP Lester, BM (reprint author), Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp Rhode Isl,Dept Pediat, Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA. EM Barry_Lester@Brown.edu FU National Institute of Child Health and Human Development (NICHD) Neonatal Research Network; National Institute on Drug Abuse (NIDA) [U10-DA-024117-01, U10-HD-21385, U10-DA-024128-06, U10-HD-2786, U10-DA-024119-01, U10-HD-27904, U10-DA-024118-01, U10-HD-21397]; NICHD [N01-HD2-3159]; NIMH FX Supported by the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network and an interinstitute agreement with the National Institute on Drug Abuse (NIDA) through cooperative agreements: U10-DA-024117-01, U10-HD-21385 (S.S.), U10-DA-024128-06, U10-HD-2786 (H.B.), U10-DA-024119-01, U10-HD-27904 (B.L.), and U10-DA-024118-01, U10-HD-21397 (C.B.); and NICHD contract N01-HD2-3159 (B.L.). The authors declare no conflicts of interest.; Participating institutions, investigators, and key research personnel include Warren Alpert Medical School of Brown University, (Barry M. Lester, PhD, Cynthia Miller-Loncar, PhD, Linda LaGasse, PhD, and Jean Twomey, PhD); Wayne State University, (Seetha Shankaran, MD, Eunice Woldt, MSN, and Jay Ann Nelson, BSN); University of Tennessee, (Henrietta S. Bada, MD, Toni Whitaker, MD, Charlotte Bursi, MSSW, Leann Pollard, BA, and Jonathan Rowland, BS), University of Miami, (Charles R. Bauer, MD, Ann L. Graziotti, ARNP, and Susan Gautier, MS); RTI International, (W. Kenneth Poole, PhD, Abhik Das, PhD, Jane Hammond, PhD, and Debra Fleischmann BS); National Institute on Drug Abuse (Nicolette Borek, PhD, and Vincent L. Smeriglio, PhD); Eunice Kennedy Shriver National Institute of Child Health and Human Development (Rosemary D. Higgins, MD). The MLS is funded as a cooperative agreement and as such the funding sponsors (NIDA, NICHD, and NIMH) have input into the design and conduct of the study. NR 96 TC 32 Z9 32 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 2010 VL 157 IS 2 BP 288 EP U150 DI 10.1016/j.jpeds.2010.02.039 PG 9 WC Pediatrics SC Pediatrics GA 625DA UT WOS:000279871700026 PM 20400094 ER PT J AU Nguyen, D Smith, LM LaGasse, LL Derauf, C Grant, P Shah, R Arria, A Huestis, MA Haning, W Strauss, A Della Grotta, S Liu, J Lester, BM AF Nguyen, Diana Smith, Lynne M. LaGasse, Linda L. Derauf, Chris Grant, Penny Shah, Rizwan Arria, Amelia Huestis, Marilyn A. Haning, William Strauss, Arthur Della Grotta, Sheri Liu, Jing Lester, Barry M. TI Intrauterine Growth of Infants Exposed to Prenatal Methamphetamine: Results from the Infant Development, Environment, and Lifestyle Study SO JOURNAL OF PEDIATRICS LA English DT Article ID PREGNANCY; SHEEP AB Previous studies suggest that prenatal methamphetamine exposure inhibits fetal growth. We examined neonatal growth effects of prenatal methamphetamine exposure in a prospective cohort study. After adjusting for covariates, exposed neonates had a higher incidence of being small for gestational age than unexposed neonates. (J Pediatr 2010;157:337-9) C1 [Smith, Lynne M.] Harbor UCLA Med Ctr, Martin Res Ctr, Los Angeles Biomed Inst, Torrance, CA 90502 USA. [Nguyen, Diana; Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Strauss, Arthur] Long Beach Mem Med Ctr, Long Beach, CA USA. [LaGasse, Linda L.; Della Grotta, Sheri; Liu, Jing; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Brown Med Sch, Providence, RI USA. [Derauf, Chris; Haning, William] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Grant, Penny] Univ Oklahoma, Norman, OK 73019 USA. [Shah, Rizwan] Blank Childrens Hosp Iowa Hlth, Des Moines, IA USA. [Arria, Amelia] Univ Maryland, College Pk, MD 20742 USA. [Huestis, Marilyn A.] NIDA, Intramural Res Program, Bethesda, MD 20892 USA. RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Martin Res Ctr, Los Angeles Biomed Inst, 1124 W Carson St, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU NIDA [1RO1DA014918]; National Center on Research Resources [3 M01 RR00425, P20 RR11091] FX This study was supported by NIDA Grant# 1RO1DA014918 and in part by the National Center on Research Resources, Grant # 3 M01 RR00425 and P20 RR11091. The authors declare no conflicts of interest. NR 10 TC 37 Z9 37 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 2010 VL 157 IS 2 BP 337 EP 339 DI 10.1016/j.jpeds.2010.04.024 PG 3 WC Pediatrics SC Pediatrics GA 625DA UT WOS:000279871700035 PM 20570284 ER PT J AU Cwik, MJ Wu, HP Muzzio, M McCormick, DL Kapetanovic, I AF Cwik, Michael J. Wu, Huaping Muzzio, Miguel McCormick, David L. Kapetanovic, Izet TI Direct quantitation of glucoraphanin in dog and rat plasma by LC-MS/MS SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Glucoraphanin; Glucosinolate; LC-MS/MS; Rat plasma; Dog plasma ID BROCCOLI SPROUTS; CRUCIFEROUS VEGETABLES; LIQUID-CHROMATOGRAPHY; ISOTHIOCYANATES; METABOLISM; HUMANS; MECHANISMS; EXCRETION; SEEDS AB A rapid method to quantify levels of the beta-thioglycoside N-hydroxyl sulfate, glucoraphanin, in dog and rat plasma to support pre-clinical toxicological and pharmacological studies has been developed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Glucoraphanin was extracted from plasma by protein precipitation with acetonitrile and separated via hydrophilic interaction liquid chromatography (HILIC) using a Luna 5 mu m Silica (2) 100 angstrom column (50 mm x 2.0 mm) at a flow rate of 0.3 mL/min. Solvent A consisted of 200 mM ammonium acetate and formic acid (99:1, v/v) and Solvent B was acetonitrile. Initial conditions (90% Solvent B) were held for 0.01 min after injection, decreased to 40% in 0.5 min and held constant for 2.5 min, returning to initial conditions for 3 min (reequilibration time). Glucoraphanin was detected by MS/MS using a turbo ion spray interface as the ion source operating in negative ion mode. Acquisition was performed in multiple reaction monitoring mode at m/z 435.8 -> 96.7. The method was validated for the calibration range 10-2000 ng/mL. Within- and between-run precision for the low, mid and high QC levels was 8% R.S.D. or less and accuracy ranged from 100 to 113%. The lower limit of quantification was 10 ng/mL; calibration curves encompassed the range of plasma concentrations expected to be found in bioavailability and pharmacokinetics studies with glucoraphanin. The method has successfully been applied to the determination of glucoraphanin in dog and rat plasma and should be extendable to other species as well. (C) 2010 Elsevier B.V. All rights reserved. C1 [Cwik, Michael J.; Wu, Huaping; Muzzio, Miguel; McCormick, David L.] IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. [Kapetanovic, Izet] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Muzzio, M (reprint author), IIT, Res Inst, Life Sci Grp, 10 W 35th St, Chicago, IL 60616 USA. EM mmuzzio@iitri.org FU Division of Cancer Prevention, National Cancer Institute [N01-CN-43304 (HHSN261200433004C)] FX This research was supported by contract N01-CN-43304 (HHSN261200433004C) from the Division of Cancer Prevention, National Cancer Institute. The authors thank Leigh Ann Senoussi for assistance with the manuscript. NR 16 TC 15 Z9 15 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD AUG 1 PY 2010 VL 52 IS 4 BP 544 EP 549 DI 10.1016/j.jpba.2010.01.020 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 575HE UT WOS:000276057300015 PM 20144518 ER PT J AU Li, QQ Wang, GD Huang, FR Banda, M Reed, E AF Li, Qingdi Quentin Wang, Gangduo Huang, Furong Banda, Malathi Reed, Eddie TI Antineoplastic effect of beta-elemene on prostate cancer cells and other types of solid tumour cells SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article DE apoptosis; beta-elemene; caspases; Chinese medicine; natural product; prostate cancer ID POMEGRANATE FRUIT; INDUCED APOPTOSIS; CARCINOMA-CELLS; GENE-THERAPY; ANDROGEN; BCL-2; EXPRESSION; GROWTH; DEATH; PATHWAY AB Objectives beta-Elemene, a natural compound extracted from over 50 different Chinese medicinal herbs and plants, has been effective in the treatment of hyperplastic and proliferative disorders such as prostatic hypertrophy, hysteromyoma and neoplasms. Our previous studies have demonstrated that beta-elemene exhibits strong inhibitory activity in ovarian cancer cells. The aim of the present study was to assess the effect of beta-elemene on prostate cancer cells as well as other types of tumour cells and to determine whether the effect of beta-elemene on prostate cancer cell death was mediated through the induction of apoptosis. Methods The MTT assay was used to evaluate the ability of beta-elemene to inhibit cellular proliferation in cancer cells. Cellular apoptosis was assessed by annexin V binding, TUNEL and ELISA-based assays. Caspase activity was measured using a caspases assay kit. The protein levels of Bcl-2, caspases, cytochrome c and poly(ADP-ribose) polymerase (PARP) were analysed by Western blotting. Key findings Here, we showed that beta-elemene had an antiproliferative effect on androgen-insensitive prostate carcinoma DU145 and PC-3 cells. Treatment with beta-elemene also inhibited the growth of brain, breast, cervical, colon and lung carcinoma cells. The effect of beta-elemene on cancer cells was dose dependent, with IC50 values ranging from 47 to 95 mu g/ml (230-465 mu m). TUNEL assay and flow cytometric analysis using annxin V/propidium iodide staining revealed that the percentage of apoptotic prostate cancer cells was increased by beta-elemene in a dose- and time-dependent manner. Moreover, beta-elemene exposure resulted in a decreased Bcl-2 protein level, increased cytochrome c release, and activated PARP and caspase-3, -7, -9, and -10 in prostate cancer cells. Conclusions Overall, these findings suggest that beta-elemene exerts broad-spectrum antitumour activity against many types of solid carcinoma and supports a proposal of beta-elemene as a new potentially therapeutic drug for castration-resistant prostate cancer and other solid tumours. C1 [Li, Qingdi Quentin] NIAID, NIH, Bethesda, MD 20892 USA. [Li, Qingdi Quentin; Wang, Gangduo; Huang, Furong; Banda, Malathi; Reed, Eddie] W Virginia Univ, Hlth Sci Ctr, Sch Med, Morgantown, WV 26506 USA. RP Li, QQ (reprint author), NIAID, NIH, Bldg 10,Room 11N234, Bethesda, MD 20892 USA. EM liquenti@niaid.nih.gov FU National Institutes of Health [P20RR016440-010003, P20RR016440-020003, P20RR016440-040003]; West Virginia University School of Medicine; BRIN/INBRE FX This work was supported by grants from the National Institutes of Health (Nos P20RR016440-010003, P20RR016440-020003 and P20RR016440-040003 to QQ Li) and West Virginia University School of Medicine (to QQ Li). Malathi Banda was supported by a BRIN/INBRE grant.; We thank Dr. Christopher F. Cuff of the Flow Cytometry Facility (grant No. RR020866) for technical contribution during the FACS measurements. NR 65 TC 50 Z9 62 U1 5 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD AUG PY 2010 VL 62 IS 8 BP 1018 EP 1027 DI 10.1111/j.2042-7158.2010.01135.x PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 629ME UT WOS:000280202300008 PM 20663036 ER PT J AU Wang, HL Viatchenko-Karpinski, S Sun, JH Gyorke, I Benkusky, NA Kohr, MJ Valdivia, HH Murphy, E Gyorke, S Ziolo, MT AF Wang, Honglan Viatchenko-Karpinski, Serge Sun, Junhui Gyorke, Inna Benkusky, Nancy A. Kohr, Mark J. Valdivia, Hector H. Murphy, Elizabeth Gyorke, Sandor Ziolo, Mark T. TI Regulation of myocyte contraction via neuronal nitric oxide synthase: role of ryanodine receptor S-nitrosylation SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID RAT VENTRICULAR MYOCYTES; BETA-ADRENERGIC STIMULATION; SARCOPLASMIC-RETICULUM; CALCIUM-RELEASE; SKELETAL-MUSCLE; CA2+ RELEASE; HEART-FAILURE; LEAK; PHOSPHOLAMBAN; MODULATION AB The sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor, RyR2) has been proposed to be an end target of neuronal nitric oxide synthase (NOS1) signalling. The purpose of this study is to investigate the mechanism of NOS1 modulation of RyR2 activity and the corresponding effect on myocyte function. Myocytes were isolated from NOS1 knockout (NOS1-/-) and wild-type mice. NOS1-/- myocytes displayed a decreased fractional SR Ca2+ release, NOS1 knockout also led to reduced RyR2 S-nitrosylation levels. RyR2 channels from NOS1-/- hearts had decreased RyR2 open probability. Additionally, knockout of NOS1 led to a decrease in [3H]ryanodine binding, Ca2+ spark frequency (CaSpF) and a rightward shift in the SR Ca2+ leak/load relationship. Similar effects were observed with acute inhibition of NOS1. These data are indicative of decreased RyR2 activity in myocytes with NOS1 knockout or acute inhibition. Interestingly, the NO donor and nitrosylating agent SNAP reversed the depressed RyR2 open probability, the reduced CaSpF, and caused a leftward shift in the leak/load relationship in NOS1-/- myocytes. SNAP also normalized Ca2+ transient and cell shortening amplitudes and SR fractional release in myocytes with NOS1 knockout or acute inhibition. Furthermore, SNAP was able to normalize the RyR2 S-nitrosylation levels. These data suggest that NOS1 signalling increases RyR2 activity via S-nitrosylation, which contributes to the NOS1-induced positive inotropic effect. Thus, RyR2 is an important end target of NOS1. C1 [Wang, Honglan; Viatchenko-Karpinski, Serge; Gyorke, Inna; Kohr, Mark J.; Gyorke, Sandor; Ziolo, Mark T.] Ohio State Univ, Dept Physiol & Cell Biol, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [Sun, Junhui; Murphy, Elizabeth] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Benkusky, Nancy A.; Valdivia, Hector H.] Univ Wisconsin, Dept Physiol Satellite Labs, Madison, WI 53711 USA. RP Ziolo, MT (reprint author), Ohio State Univ, Dept Physiol & Cell Biol, Davis Heart & Lung Res Inst, 304 Hamilton Hall,1645 Neil Ave, Columbus, OH 43210 USA. EM ziolo.1@osu.edu RI Sun, Junhui/C-3499-2011; Ziolo, Mark/E-4371-2011; OI Kohr, Mark/0000-0002-6034-5962 FU American Heart Association [0725560B, SDG 0435033N, 0715159B]; National Institutes of Health [HL 055438, HL 074045, HL 063043, HL 079283, HL 094692] FX This work was supported by the American Heart Association (Post-doctoral Fellowship 0725560B, H. W.; SDG 0435033N, S.V.-K.; Pre-doctoral Fellowship 0715159B, M.J.K.) and the National Institutes of Health (HL 055438, H. H. V.; HL 074045 and HL 063043, S. G.; HL 079283 and HL 094692, M.T.Z.). We thank Sean Little and Dr Jonathan Davis for their technical assistance. NR 44 TC 41 Z9 47 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 1 PY 2010 VL 588 IS 15 BP 2905 EP 2917 DI 10.1113/jphysiol.2010.192617 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 635EL UT WOS:000280638300017 PM 20530114 ER PT J AU Simons-Morton, BG Farhat, T AF Simons-Morton, Bruce G. Farhat, Tilda TI Recent Findings on Peer Group Influences on Adolescent Smoking SO JOURNAL OF PRIMARY PREVENTION LA English DT Article DE Adolescents; Smoking; Peer influence; Literature review ID INNER-CITY ADOLESCENTS; GROWTH CURVE ANALYSES; SUBSTANCE USE; CIGARETTE-SMOKING; DRUG-USE; PARENT INFLUENCES; RISK BEHAVIORS; PSYCHOSOCIAL PREDICTORS; LONGITUDINAL ANALYSIS; HEALTH BEHAVIOR AB This review addresses peer group influences on adolescent smoking with a particular focus on recently published longitudinal studies that have investigated the topic. Specifically, we examine the theoretical explanations for how social influence works with respect to adolescent smoking; discuss the association between peer and adolescent smoking; consider socialization and selection processes with respect to smoking; investigate the relative influence of best friends, close friends, and crowd affiliations; and examine parenting behaviors that could buffer the effects of peer influence. Our review indicates the following with respect to adolescent smoking: (a) substantial peer group homogeneity of smoking behavior; (b) support for both socialization and selection effects, although evidence is somewhat stronger for selection; (c) an interactive influence of best friends, peer groups, and crowd affiliation; and (d) an indirect protective effect of positive parenting practices against the uptake of adolescent smoking. We conclude with implications for research and prevention programs. C1 [Simons-Morton, Bruce G.; Farhat, Tilda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Farhat, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd Room 7B13C, Bethesda, MD 20892 USA. EM farhatti@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [ZIA HD002525-17] NR 113 TC 105 Z9 106 U1 8 U2 37 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0278-095X J9 J PRIM PREV JI J. Prim. Prev. PD AUG PY 2010 VL 31 IS 4 BP 191 EP 208 DI 10.1007/s10935-010-0220-x PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 646AK UT WOS:000281507100002 PM 20614184 ER PT J AU Francischetti, IMB Calvo, E Andersen, JF Pham, VM Favreau, AJ Barbian, KD Romero, A Valenzuela, JG Ribeiro, JMC AF Francischetti, Ivo M. B. Calvo, Eric Andersen, John F. Pham, Van M. Favreau, Amanda J. Barbian, Kent D. Romero, Alvaro Valenzuela, Jesus G. Ribeiro, Jose M. C. TI Insight into the Sialome of the Bed Bug, Cimex lectularius SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE bedbug; saliva; salivary transcriptome; salivary proteome ID ADULT FEMALE MOSQUITO; SALIVARY-GLAND TRANSCRIPTS; RICH SECRETORY PROTEINS; AMINE-BINDING PROTEIN; BLOOD-FEEDING INSECT; RHODNIUS-PROLIXUS; BLOODSUCKING BUG; NITRIC-OXIDE; ANOPHELES-GAMBIAE; CODON VOLATILITY AB The evolution of insects to a blood diet leads to the development of a saliva that antagonizes their hosts' hemostasis and inflammation. Hemostasis and inflammation are redundant processes, and thus a complex salivary potion composed of dozens or near 100 different polypeptides is commonly found by transcriptome or proteome analysis of these organisms. Several insect orders or families evolved independently to hematophagy, creating unique salivary potions in the form of novel pharmacological use of endogenous substances and in the form of unique proteins not matching other known proteins, these probably arriving by fast evolution of salivary proteins as they evade their hosts' immune response. In this work we present a preliminary description of the sialome (from the Greek Sialo = saliva) of the common bed bug Cimex lectularius, the first such work from a member of the Cimicidae family. This manuscript is a guide for the supplemental database files http://exon.niaid.nih.gov/transcriptome/C_lectularius/S1/Cimex-S1.zip and http://exon.niaid.nih.gov/transcriptome/C_lectularius/S2/Cimex-S2.xls C1 [Francischetti, Ivo M. B.; Calvo, Eric; Andersen, John F.; Pham, Van M.; Valenzuela, Jesus G.; Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Favreau, Amanda J.; Barbian, Kent D.] NIAID, Rocky Mt Labs, Genom Unit, Res Technol Sect, Hamilton, MT 59840 USA. [Romero, Alvaro] Univ Kentucky, Dept Entomol, Agr Sci Ctr S 225, Lexington, KY 40546 USA. RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jribeiro@niaid.nih.gov OI Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [NO1-CO-12400] FX We are grateful for the expert assistance of Dr. Carl Hammer from the NIAID Research Technology Branch. This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract NO1-CO-12400. 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 organization imply endorsement by the government of the United States of America. NR 101 TC 28 Z9 29 U1 1 U2 15 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 AUG PY 2010 VL 9 IS 8 BP 3820 EP 3831 DI 10.1021/pr1000169 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 634LT UT WOS:000280583700006 PM 20441151 ER PT J AU Han, BN Stockwin, LH Hancock, C Yu, SX Hollingshead, MG Newton, DL AF Han, Bingnan Stockwin, Luke H. Hancock, Chad Yu, Sherry X. Hollingshead, Melinda G. Newton, Dianne L. TI Proteomic Analysis of Nuclei Isolated from Cancer Cell Lines Treated with Indenoisoquinoline NSC 724998, a Novel Topoisomerase I Inhibitor SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE topoisomerase I; indenoisoquinoline; DNA damage; KAP1; proteasome; gamma H2AX; nuclear proteome ID UBIQUITIN-PROTEASOME SYSTEM; DNA-DAMAGE; MJ-III-65 NSC-706744; CLEAVAGE COMPLEXES; MAJOR PLAYER; CAMPTOTHECIN; STRESS; INDUCTION; PROTEIN; PHOSPHORYLATION AB The indenoisoquinoline NSC724998 is a novel topoisomerase I (Top1) inhibitor entering Phase I clinical trials at the National Cancer Institute, USA. In this study, 2-D PAGE analysis was performed on nuclear lysates prepared from HCT-116 and A375 cells treated with 1 mu M NSC724998 for 24 h and the differentially regulated spots identified by LC-MS/MS. One-hundred fourteen protein spot differentials were identified, 66 from A375 cells and 48 from HCT-116 cells. Proteins related to apoptosis changed specifically in A375 cells, whereas proteins involved in the ubiquitin-proteasome system were highly enriched in treated HCT-116 cells. Importantly, 12 differentially expressed proteins (ETFA, HCC1, HNRCL, KAP1, NPM, NUCL, PRDX1, PRP19, PSB6, RAE1L, RU2A, and SFRS9) were common to both cell lines. Western blotting and immunocytochemistry confirmed significant nuclear upregulation of both the proteasome subunit PSB6 and the transcriptional repressor KAP1. Interestingly, increased KAP1 polypeptide was accompanied by enhanced phosphorylation at Ser824. Similar to gamma H2AX, KAP1 phosphorylation was consistently enhanced in a panel of 12 cell lines and in A375 xenografts following NSC 724998 treatment. In summary, these data enhance our understanding of protein dynamics in the nucleus following DNA damage and provide an alternate marker (pKAP1) with potential for monitoring clinical responses to Top1 poisons. C1 [Han, Bingnan; Stockwin, Luke H.; Hancock, Chad; Yu, Sherry X.; Newton, Dianne L.] NCI, Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Hollingshead, Melinda G.] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Newton, DL (reprint author), NCI, Dev Therapeut Program, SAIC Frederick Inc, Bldg 320,Room 9, Frederick, MD 21702 USA. EM newtondianne@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 No. 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. NCI-Frederick is accredited by AAALACi and follows the Public Health Service Policy on the Care and Use of Laboratory Animals. All animals used in this research project were cared for and used humanely according to the following policies: The U.S. Public Health Service Policy on Humane Care and Use of Animals (1996); the Guide for the Care and Use of Laboratory Animals (1996); and the U.S. Government Principles for Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training (1985). NR 52 TC 9 Z9 11 U1 0 U2 1 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 AUG PY 2010 VL 9 IS 8 BP 4016 EP 4027 DI 10.1021/pr100194d PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 634LT UT WOS:000280583700023 PM 20515076 ER PT J AU Kim, HK Reyzer, ML Choi, IJ Kim, CG Kim, HS Oshima, A Chertov, O Colantonio, S Fisher, RJ Allen, JL Caprioli, RM Green, JE AF Kim, Hark Kyun Reyzer, Michelle L. Choi, Il Ju Kim, Chan Gyoo Kim, Hee Sung Oshima, Akira Chertov, Oleg Colantonio, Simona Fisher, Robert J. Allen, Jamie L. Caprioli, Richard M. Green, Jeffrey E. TI Gastric Cancer-Specific Protein Profile Identified Using Endoscopic Biopsy Samples via MALDI Mass Spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE direct tissue MALDI; gastric cancer; diagnosis ID DIRECT TISSUE-ANALYSIS; CEA; BIOMARKERS; CARCINOMA; PEPTIDES; CA19-9; MS AB To date, proteomic analyses on gastrointestinal cancer tissue samples have been performed using surgical specimens only, which are obtained after a diagnosis is made. To determine if a proteomic signature obtained from endoscopic biopsy samples could be found to assist with diagnosis, frozen endoscopic biopsy samples collected from 63 gastric cancer patients and 43 healthy volunteers were analyzed using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. A statistical classification model was developed to distinguish tumor from normal tissues using half the samples and validated with the other half. A protein profile was discovered consisting of 73 signals that could classify 32 cancer and 22 normal samples in the validation set with high predictive values (positive and negative predictive values for cancer, 96.8% and 91.3%; sensitivity, 93.8%; specificity, 95.5%). Signals overexpressed in tumors were identified as alpha-defensin-1, alpha-defensin-2, calgranulin A, and calgranulin B. A protein profile was also found to distinguish pathologic stage la (pT1N0M0) samples In = 10) from more advanced stage (Ib or higher) tumors (n = 48). Thus, protein profiles obtained from endoscopic biopsy samples may be useful in assisting with the diagnosis of gastric cancer and, possibly, in identifying early stage disease. C1 [Kim, Hark Kyun; Oshima, Akira; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Kim, Hark Kyun; Choi, Il Ju; Kim, Chan Gyoo; Kim, Hee Sung] Natl Canc Ctr, Goyang 410769, Gyeonggi, South Korea. [Reyzer, Michelle L.; Allen, Jamie L.; Caprioli, Richard M.] Vanderbilt Univ, Mass Spectrometry Res Ctr, Nashville, TN 37232 USA. [Chertov, Oleg; Colantonio, Simona; Fisher, Robert J.] NCI, Prot Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov OI Kim, Chan Gyoo/0000-0002-1651-2559 FU Center for Cancer Research, National Cancer Institute; Korean Ministry of Education, Science, and Technology [0931480]; Korean National Cancer Center [0910570]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported in part by National Institute of Health Intramural Program, Center for Cancer Research, National Cancer Institute; by Korean Ministry of Education, Science, and Technology Grant 0931480; and by Korean National Cancer Center Grant 0910570. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. NR 28 TC 50 Z9 53 U1 0 U2 11 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 AUG PY 2010 VL 9 IS 8 BP 4123 EP 4130 DI 10.1021/pr100302b PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 634LT UT WOS:000280583700034 PM 20557134 ER PT J AU Manna, SK Patterson, AD Yang, QA Krausz, KW Li, HH Idle, JR Fornace, AJ Gonzalez, FJ AF Manna, Soumen K. Patterson, Andrew D. Yang, Qian Krausz, Kristopher W. Li, Henghong Idle, Jeffrey R. Fornace, Albert J., Jr. Gonzalez, Frank J. TI Identification of Noninvasive Biomarkers for Alcohol-Induced Liver Disease Using Urinary Metabolomics and the Ppara-null Mouse SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE alcohol-induced liver disease; PPAR alpha; Ppara-null mouse; steatosis; metabolomics; UPLC-ESI-QTOF-MS; multivariate data analysis; biomarker; indole-3-lactic acid ID PROLIFERATOR-ACTIVATED-RECEPTOR; RAT-LIVER; FATTY LIVER; ALPHA; GENE; METABOLISM; DATABASE; EXPRESSION; OXIDATION; DRINKING AB Alcohol-induced liver disease (ALD) is a leading cause of nonaccident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively nonspecific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study, the metabolic changes associated with ALD were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-beta-D-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of a metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model. C1 [Manna, Soumen K.; Patterson, Andrew D.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Yang, Qian; Li, Henghong; Fornace, Albert J., Jr.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Idle, Jeffrey R.] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague 12800, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov RI Patterson, Andrew/G-3852-2012; OI Patterson, Andrew/0000-0003-2073-0070; Fornace, Albert/0000-0001-9695-085X; Idle, Jeff/0000-0002-6143-1520 FU National Cancer Institute; National Institute of Environmental Health Sciences [U01ES016013]; United States Smokeless Tobacco Company FX This work was supported by the National Cancer Institute Intramural Research Program, the National Institute of Environmental Health Sciences (grant number U01ES016013), and a grant for collaborative research from United States Smokeless Tobacco Company (J.R.I.) NR 39 TC 37 Z9 39 U1 0 U2 13 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 AUG PY 2010 VL 9 IS 8 BP 4176 EP 4188 DI 10.1021/pr100452b PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 634LT UT WOS:000280583700040 PM 20540569 ER PT J AU Hamazaki, K Choi, KH Kim, HY AF Hamazaki, Kei Choi, Kwang H. Kim, Hee-Yong TI Phospholipid profile in the postmortem hippocampus of patients with schizophrenia and bipolar disorder: No changes in docosahexaenoic acid species SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Bipolar disorder; Schizophrenia; Hippocampus; Phospholipids; Polyunsaturated fatty acids; Postmortem brain ID MAGNETIC-RESONANCE-SPECTROSCOPY; MONOZYGOTIC TWINS DISCORDANT; NEVER-MEDICATED 1ST-EPISODE; POLYUNSATURATED FATTY-ACID; BRAIN PHOSPHOLIPIDS; ARACHIDONIC-ACID; NEUROPSYCHOLOGICAL PERFORMANCE; GLUTAMATE CONCENTRATION; ORBITOFRONTAL CORTEX; MASS-SPECTROMETRY AB Previous studies with postmortem brain tissues showed abnormalities not only in n-3 long-chain polyunsaturated fatty acids (PUFA) but also in phospholipid metabolism in the cortex of individuals with schizophrenia and mood disorder. In this study we investigated whether there is similar abnormality in n-3 long-chain PUFAs and/or in phospholipid profile in the hippocampus of schizophrenia and bipolar disorder patients compared to unaffected controls. Using high-performance liquid chromatography/electrospray ionization-mass spectrometry (LC/MS), the phospholipid contents in the postmortem hippocampus from 35 individuals with schizophrenia, 34 individuals with bipolar disorder and 35 controls were evaluated. Unlike the previous findings form orbitofrontal cortex, we found no significant differences in either n-3 long-chain PUFA or total phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC). However, docosapentaenoic acid (n-6, 22:5n-6)-PS and 22:5n-6-PC were significantly lower in individuals with schizophrenia or bipolar disorder than the controls. When fatty acid contents were estimated from PS, PE and PC, 22:5n-6 was significantly lower in both patient groups compared to the controls. From these results we concluded that DHA loss associated with these psychiatric disorders may be specific to certain regions of the brain. The selective decrease in 22:5n-6 without affecting DHA contents suggests altered lipid metabolism, particularly n-6 PUFA rather than n-3 PUFA, in the hippocampus of individuals with schizophrenia or bipolar disorder. Published by Elsevier Ltd. C1 [Hamazaki, Kei; Choi, Kwang H.; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Choi, Kwang H.] Stanley Lab Brain Res, Rockville, MD 20850 USA. RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, 5625 Fishers Lane,Room 3N07,MSC9410, Bethesda, MD 20892 USA. EM keihama@med.u-toyama.ac.jp; hykim@nih.gov FU NIAAA FX This work was supported by the Intramural Program of NIAAA. The NIAAA 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 60 TC 26 Z9 26 U1 2 U2 5 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 AUG PY 2010 VL 44 IS 11 BP 688 EP 693 DI 10.1016/j.jpsychires.2009.11.017 PG 6 WC Psychiatry SC Psychiatry GA 635MZ UT WOS:000280661100002 PM 20056243 ER PT J AU Dveksler, GS Lisboa, FA Warren, J Aparicio, M Zudaire, E AF Dveksler, G. S. Lisboa, F. A. Warren, J. Aparicio, M. Zudaire, E. TI Receptor characterization of human pregnancy specific glycoprotein 1 SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Meeting Abstract CT 11th International Congress of Reproductive Immunology CY AUG 15-19, 2010 CL Palm Grove, AUSTRALIA C1 [Dveksler, G. S.; Lisboa, F. A.; Warren, J.] USUHS, Bethesda, MD USA. [Aparicio, M.; Zudaire, E.] NIH, Angiogenesis Core Facil, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD AUG PY 2010 VL 86 IS 1 SI SI BP 44 EP 44 DI 10.1016/j.jri.2010.06.087 PG 1 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 635MG UT WOS:000280659200083 ER PT J AU Fay, MP Shaw, PA AF Fay, Michael P. Shaw, Pamela A. TI Exact and Asymptotic Weighted Logrank Tests for Interval Censored Data: The interval R Package SO JOURNAL OF STATISTICAL SOFTWARE LA English DT Article DE logrank test; Wilcoxon test; exact tests; network algorithm; R ID FAILURE TIME DATA; PROPORTIONAL HAZARDS MODEL; NONPARAMETRIC-ESTIMATION; SURVIVAL-DATA; RANK-TESTS; INFERENCE; IMPUTATION AB For right-censored data perhaps the most commonly used tests are weighted logrank tests, such as the logrank and Wilcoxon-type tests. In this paper we review several generalizations of those weighted logrank tests to interval-censored data and present an R package, interval, to implement many of them. The interval package depends on the perm package, also presented here, which performs exact and asymptotic linear permutation tests. The perm package performs many of the tests included in the already available coin package, and provides an independent validation of coin. We review analysis methods for interval-censored data, and we describe and show how to use the interval and perm packages. C1 [Fay, Michael P.; Shaw, Pamela A.] NIAID, Bethesda, MD 20892 USA. RP Fay, MP (reprint author), NIAID, 6700B Rockledge Dr,MSC 7630, Bethesda, MD 20892 USA. EM mfay@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 NR 44 TC 84 Z9 84 U1 2 U2 12 PU JOURNAL STATISTICAL SOFTWARE PI LOS ANGELES PA UCLA DEPT STATISTICS, 8130 MATH SCIENCES BLDG, BOX 951554, LOS ANGELES, CA 90095-1554 USA SN 1548-7660 J9 J STAT SOFTW JI J. Stat. Softw. PD AUG PY 2010 VL 36 IS 2 BP 1 EP 34 PG 34 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 647CJ UT WOS:000281593100001 ER PT J AU Ziegler, RG Faupel-Badger, JM Sue, LY Fuhrman, BJ Falk, RT Boyd-Morin, J Henderson, MK Hoover, RN Veenstra, TD Keefer, LK Xu, X AF Ziegler, R. G. Faupel-Badger, J. M. Sue, L. Y. Fuhrman, B. J. Falk, R. T. Boyd-Morin, J. Henderson, M. K. Hoover, R. N. Veenstra, T. D. Keefer, L. K. Xu, X. TI A new approach to measuring estrogen exposure and metabolism in epidemiologic studies SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Estradiol; Estrogen metabolism; Estrone; Liquid chromatography-tandem mass spectrometry ID BREAST-CANCER RISK; CHROMATOGRAPHY-MASS SPECTROMETRY; ASIAN-AMERICAN WOMEN; 15 URINARY ESTROGENS; POSTMENOPAUSAL WOMEN; ENDOGENOUS ESTROGENS; PREMENOPAUSAL WOMEN; HORMONE-LEVELS; SEX-HORMONES; REPRODUCIBILITY AB Endogenous estrogen plays an integral role in the etiology of breast and endometrial cancer, and conceivably ovarian cancer. However, the underlying mechanisms and the importance of patterns of estrogen metabolism and specific estrogen metabolites have not been adequately explored. Long-standing hypotheses, derived from laboratory experiments, have not been tested in epidemiologic research because of the lack of robust, rapid, accurate measurement techniques appropriate for large-scale studies. We have developed a stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS(2)) method that can measure concurrently all 15 estrogens and estrogen metabolites (EM) in urine and serum with high sensitivity (level of detection = 2.5-3.0 fmol EM/mL serum), specificity, accuracy, and precision [laboratory coefficients of variation (CV's) <= 5% for nearly all EM]. The assay requires only extraction, a single chemical derivatization, and less than 0.5 mL of serum or urine. By incorporating enzymatic hydrolysis, the assay measures total (glucuronidated + sulfated + unconjugated) EM. If the hydrolysis step is omitted, the assay measures unconjugated EM. Interindividual differences in urinary EM concentrations (pg/mL creatinine), which reflect total EM production, were consistently large, with a range of 10-100-fold for nearly all EM in premenopausal and postmenopausal women and men. Correlational analyses indicated that urinary estrone and estradiol, the most commonly measured EM, do not accurately represent levels of total urinary EM or of the other EM. In serum, all 15 EM were detected as conjugates, but only 5 were detected in unconjugated form. When we compared our assay methods with indirect radioimmunoassays for estrone, estradiol, and estriol and enzyme-linked immunosorbent assays for 2-hydroxyestrone and 16 alpha-hydroxyestrone, ranking of individuals agreed well for premenopausal women [Spearman r(r(s)) = 0.8-0.9], but only moderately for postmenopausal women (r(s) = 0.4-0.8). Our absolute readings were consistently lower, especially at the low concentrations characteristic of postmenopausal women, possibly because of improved specificity. We are currently applying our EM measurement techniques in several epidemiologic studies of premenopausal and postmenopausal breast cancer. Published by Elsevier Ltd. C1 [Ziegler, R. G.; Faupel-Badger, J. M.; Sue, L. Y.; Fuhrman, B. J.; Falk, R. T.; Henderson, M. K.; Hoover, R. N.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Faupel-Badger, J. M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Bethesda, MD 20892 USA. [Boyd-Morin, J.] Informat Management Serv Inc, Silver Spring, MD 20904 USA. [Veenstra, T. D.; Xu, X.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA. [Keefer, L. K.] Natl Canc Inst Frederick, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Ziegler, RG (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Execut Plaza S,Room 8098, Bethesda, MD 20892 USA. EM zieglerr@mail.nih.gov RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Fuhrman, Barbara/0000-0002-1777-9888 FU Center for Cancer Research and Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; National Cancer Institute [N01-CO-12400] FX This project has been funded by the Intramural Research Programs of the Center for Cancer Research and Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, and with federal funds from the National Cancer Institute under Contract N01-CO-12400 to SAIC-Frederick, Inc. 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 United States Government. NR 33 TC 33 Z9 34 U1 1 U2 12 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 AUG PY 2010 VL 121 IS 3-5 SI SI BP 538 EP 545 DI 10.1016/j.jsbmb.2010.03.068 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 642AC UT WOS:000281174000009 PM 20382222 ER PT J AU Murphy, GE Lowekamp, BC Zerfas, PM Chandler, RJ Narasimha, R Venditti, CP Subramaniam, S AF Murphy, Gavin E. Lowekamp, Bradley C. Zerfas, Patricia M. Chandler, Randy J. Narasimha, Rajesh Venditti, Charles P. Subramaniam, Sriram TI Ion-abrasion scanning electron microscopy reveals distorted liver mitochondrial morphology in murine methylmalonic acidemia SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Scanning electron microscopy; Focused ion beam; Ion-abrasion; Mitochondria; Methylmalonic acidemia; Diagnostic imaging ID TOMOGRAPHY; CELLS AB Methylmalonic acidemia is a lethal inborn error of metabolism that causes mitochondrial impairment, multi-organ dysfunction and a shortened lifespan. Previous transmission electron microscope studies of thin sections from normal (Mut(+/+)) and diseased (Mut(-/-)) tissue found that the mitochondria appear to occupy a progressively larger volume of mutant cells with age, becoming megamitochondria. To assess changes in shape and volume of mitochondria resulting from the mutation, we carried out ion-abrasion scanning electron microscopy (IA-SEM), a method for 3D imaging that involves the iterative use of a focused gallium ion beam to abrade the surface of the specimen, and a scanning electron beam to image the newly exposed surface. Using IA-SEM, we show that mitochondria are more convoluted and have a broader distribution of sizes in the mutant tissue. Compared to normal cells, mitochondria from mutant cells have a larger surface-area-to-volume ratio, which can be attributed to their convoluted shape and not to their elongation or reduced volume. The 3D imaging approach and image analysis described here could therefore be useful as a diagnostic tool for the evaluation of disease progression in aberrant cells at resolutions higher than that currently achieved using confocal light microscopy. Published by Elsevier Inc. C1 [Murphy, Gavin E.; Narasimha, Rajesh; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lowekamp, Bradley C.] NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20892 USA. [Zerfas, Patricia M.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Chandler, Randy J.] George Washington Univ, Inst Biomed Sci, Washington, DC 20037 USA. [Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM ss1@nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Center for Cancer Research, which is the Intramural Research Program of the National Cancer Institute, NIH. NR 21 TC 16 Z9 16 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD AUG PY 2010 VL 171 IS 2 BP 125 EP 132 DI 10.1016/j.jsb.2010.04.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 615QX UT WOS:000279151900002 PM 20399866 ER PT J AU Ashikaga, T Krag, DN Land, SR Julian, TB Anderson, SJ Brown, AM Skelly, JM Harlow, SP Weaver, DL Mamounas, EP Costantino, JP Wolmark, N AF Ashikaga, Takamaru Krag, David N. Land, Stephanie R. Julian, Thomas B. Anderson, Stewart J. Brown, Ann M. Skelly, Joan M. Harlow, Seth P. Weaver, Donald L. Mamounas, Eleftherios P. Costantino, Joseph P. Wolmark, Norman CA NSABP TI Morbidity Results From the NSABP B-32 Trial Comparing Sentinel Lymph Node Dissection Versus Axillary Dissection SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE shoulder abduction; arm swelling; numbness; tingling ID BREAST-CANCER; BIOPSY; RESECTION AB Background and Objectives: Three year post-surgical morbidity levels were compared between patients with negative sentinel lymph node dissection alone (SLND) and those with negative sentinel node dissection and negative axillary lymph node dissection (ALND) in the NSABP B-32 trial. Methods: A total of 1,975 ALND and 2,008 SLND node negative breast cancer patients had shoulder range of motion and arm volumes assessed along with self reports of arm tingling and numbness. Relative shoulder abduction deficits and relative arm volume differences between ipsilateral and contralateral arms were calculated. Results: Shoulder abduction deficits >= 10% peaked at 1 week for the ALND (75%) and SLND (41%) groups. Arm volume differences >= 10% at 36 months were evident for the ALND (14%) and SLND (8%) groups. Numbness and tingling peaked at 6 months for the ALND (49%, 23%) and SLND (15%, 10%) groups. Logistic regression correlates of residual morbidity included treatment group, age, handedness, tumor size, systemic chemotherapy, and radiation to the axilla. Conclusions: Although residual morbidity for both treatment groups was evident, the results of the NSABP B-32 study indicate the superiority of the SLND compared to the ALND treatment approach relative to post-surgical morbidity outcomes over a 3-year follow-up period. J. Surg. Oncol. 2010;102:111-118. (c) 2010 Wiley-Liss, Inc. C1 [Ashikaga, Takamaru] Univ Vermont, Coll Med, Dept Med Biostat, Burlington, VT 05405 USA. [Land, Stephanie R.; Julian, Thomas B.; Wolmark, Norman] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Land, Stephanie R.; Julian, Thomas B.; Anderson, Stewart J.; Brown, Ann M.; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Mamounas, Eleftherios P.] Aultman Hlth Fdn, Canton, OH USA. [Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA USA. RP Ashikaga, T (reprint author), Univ Vermont, Coll Med, Dept Med Biostat, Burlington, VT 05405 USA. EM takamaru.ashikaga@uvm.edu OI Anderson, Stewart/0000-0001-8948-0650 FU National Cancer Institute, Department of Health and Human Services, Public Health Service [P30-CA-22435, 5RO1-CA-74137-9, U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974] FX Grant sponsor: National Cancer Institute, Department of Health and Human Services, Public Health Service; Grant numbers: P30-CA-22435, 5RO1-CA-74137-9, U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974. NR 14 TC 138 Z9 145 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD AUG 1 PY 2010 VL 102 IS 2 BP 111 EP 118 DI 10.1002/jso.21535 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 638GX UT WOS:000280882700003 PM 20648579 ER PT J AU Pine, DS Ernst, M Leibenluft, E AF Pine, Daniel S. Ernst, Monique Leibenluft, Ellen TI Imaging Genetics Applications in Child Psychiatry SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE imaging; genetics; anxiety; children and adolescents ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN-TRANSPORTER; BIPOLAR DISORDER; ENVIRONMENT INTERACTIONS; ENDOPHENOTYPE CONCEPT; AMYGDALA-FUNCTION; RISK; METAANALYSIS; NEUROSCIENCE AB Objective: To place imaging-genetics research in the context of child psychiatry Method: A conceptual overview is provided, followed by discussion of specific research examples Results: Imaging-genetics research is described linking brain function to two specific genes, for the serotonin-reuptake-transporter protein and a monoamine oxidase enzyme Work is then described on phenotype selection in imaging genetics Conclusions: Child psychiatry applications of imaging genetics are only beginning to emerge The approach holds promise for advancing understandings of pathophysiology and therapeutics J Am Acad Child Adolesc Psychiatry, 2010,49(8) 772-782 C1 [Pine, Daniel S.; Ernst, Monique; Leibenluft, Ellen] NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 MH002778-09] NR 54 TC 13 Z9 13 U1 3 U2 8 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 AUG PY 2010 VL 49 IS 8 BP 772 EP 782 DI 10.1016/j.jaac.2009.12.022 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 632PM UT WOS:000280436700004 PM 20643311 ER PT J AU Aldrich, SL Hong, CH Groves, L Olsen, C Moss, J Darling, TN AF Aldrich, Shelley L. Hong, Chien-Hui Groves, Leslie Olsen, Cara Moss, Joel Darling, Thomas N. TI Acral lesions in tuberous sclerosis complex: Insights into pathogenesis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE fingernails; periungual fibroma; subungual fibroma; toenails; tuberous sclerosis complex ID SPLINTER HEMORRHAGES; DIAGNOSTIC-SIGNIFICANCE; FIBROKERATOMA; MANAGEMENT; HAMARTOMAS; FEATURES; DISEASE; TUMOR AB Background: Patients with tuberous sclerosis complex (TSC) are predisposed to developing ungual fibromas and other acral lesions. Objective: We sought to determine the numbers, types, and locations of acral skin lesions in TSC. Methods: We examined and photographed 76 adult women with TSC. Results: The age of the patients ranged from 20 to 69 years, with a mean age of 39 +/- 11 years. Ungual fibromas were observed in 61 of 76 patients (80%). Periungual fibromas were more common than subungual fibromas, were more common on the feet than the hands, and showed the greatest frequency on the fifth toe. Longitudinal grooves in the nails occurred with or without a visible fibroma. Longitudinal short red streaks-lesions that we term "red comets"-were observed in 22 patients (29%). Longitudinal leukonychia was observed in 14 patients (18%). One patient had isolated digital overgrowth and one patient had pachydermodactyly. Limitations: No men or children were included in this study. Conclusions: Examination of patients for skin lesions of TSC could be improved by including inspection for longitudinal nail grooves, red comets, longitudinal leukonychia, and splinter hemorrhages in addition to Lingual fibromas. The anatomic distribution of TSC ungual fibromas is not random and appears consistent with trauma-promoted tumor formation. (J Am Acad Dermatol 2010;63:244-51.) C1 [Aldrich, Shelley L.; Hong, Chien-Hui; Groves, Leslie; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. [Olsen, Cara] Uniformed Serv Univ Hlth Sci, Biostat Consulting Ctr, Bethesda, MD 20814 USA. [Hong, Chien-Hui] Kaohsiung Vet Gen Hosp, Dept Dermatol, Kaohsiung, Taiwan. [Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM tdarling@usuhs.mil OI Darling, Thomas/0000-0002-5161-1974 FU Doris Duke Charitable Foundation [R01 CA100907]; National Institutes of Health, National Heart, Lung, and Blood Institute FX Supported by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation, R01 CA100907, and the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. NR 34 TC 11 Z9 13 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2010 VL 63 IS 2 BP 244 EP 251 DI 10.1016/j.jaad.2009.08.042 PG 8 WC Dermatology SC Dermatology GA 630DJ UT WOS:000280252100007 PM 20462663 ER PT J AU Zhou, XL Khan, SG Tamura, D Patronas, NJ Zein, WM Brooks, BP Kraemer, KH DiGiovanna, JJ AF Zhou, Xiaolong Khan, Sikandar G. Tamura, Deborah Patronas, Nicholas J. Zein, Wadih M. Brooks, Brian P. Kraemer, Kenneth H. DiGiovanna, John J. TI Brittle hair, developmental delay, neurologic abnormalities, and photosensitivity in a 4-year-old girl SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE collodion membrane; congenital ichthyosis; DNA repair; erythroderma; genetic diseases; hair abnormalities; recurrent infections; trichothiodystrophy ID XERODERMA-PIGMENTOSUM; SHAFT ABNORMALITIES; COCKAYNE-SYNDROME; DNA-REPAIR; TRICHOTHIODYSTROPHY; MUTATIONS; BIDS; COMPLEX; CANCER; GENE C1 [Zhou, Xiaolong; Khan, Sikandar G.; Tamura, Deborah; Kraemer, Kenneth H.; DiGiovanna, John J.] NCI, Dermatol Branch, DNA Repair Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Zhou, Xiaolong] NIH, Clin Res Training Program, Bethesda, MD 20892 USA. [Patronas, Nicholas J.] NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. [Zein, Wadih M.; Brooks, Brian P.] NEI, NIH, Bethesda, MD 20892 USA. [DiGiovanna, John J.] Brown Univ, Div Dermatopharmacol, Dept Dermatol, Warren Alpert Sch Med, Providence, RI 02912 USA. RP Kraemer, KH (reprint author), NCI, Dermatol Branch, DNA Repair Sect, Ctr Canc Res, Bldg 37,Room 4002, Bethesda, MD 20892 USA. EM kraemerk@nih.gov OI Zhou, Alan/0000-0002-6177-2472 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH); NIH; Pfizer Inc FX Supported by the Intramural Research Programs of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH). Support for Mr Zhou was made possible through the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). NR 18 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2010 VL 63 IS 2 BP 323 EP 328 DI 10.1016/j.jaad.2010.03.041 PG 6 WC Dermatology SC Dermatology GA 630DJ UT WOS:000280252100015 PM 20633800 ER PT J AU Kopp, JB AF Kopp, Jeffrey B. TI TGF-beta Signaling and the Renal Tubular Epithelial Cell: Too Much, Too Little, and Just Right SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID MESENCHYMAL TRANSITION; POLARITY; HOMEOSTASIS; RHOA C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS NR 12 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2010 VL 21 IS 8 BP 1241 EP 1243 DI 10.1681/ASN.2010060676 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 636OE UT WOS:000280746200005 PM 20651160 ER PT J AU Ramalingam, SS Belani, CP Mack, PC Vokes, EE Longmate, J Govindan, R Koczywas, M Ivy, SP Gandara, DR AF Ramalingam, Suresh S. Belani, Chandra P. Mack, Philip C. Vokes, Everett E. Longmate, Jeffrey Govindan, Ramaswamy Koczywas, Marianna Ivy, S. Percy Gandara, David R. TI Phase II Study of Cediranib (AZD 2171), an Inhibitor of the Vascular Endothelial Growth Factor Receptor, for Second-Line Therapy of Small Cell Lung Cancer (National Cancer Institute #7097) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Angiogenesis; Small cell lung cancer; Cediranib; Biomarkers ID CHEMOTHERAPY; TOPOTECAN; CARCINOMA; AZD2171; DISEASE; TRIAL; VEGF AB Background: Inhibition of angiogenesis is a novel strategy for the treatment of cancer. We evaluated the safety and efficacy of cediranib, a potent small molecule inhibitor of the vascular endothelial growth factor receptor, in patients with refractory or recurrent small cell lung cancer (SCLC). Methods: Patients with SCLC with progression after prior platinum-based chemotherapy only; performance status (PS) of 0 to 2; and adequate bone marrow, renal, and hepatic function were included. The dose of cediranib was 45 mg PO once a day for the first 12 patients and was reduced to 30 mg PO once a day for the subsequent patients because of intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary end point was determination of the response rate. Results: Twenty-five patients were enrolled. Patient characteristics were as follows: 13 men; median age 61 years; PS 0 (12 pts), PS 1 (12 pts). A median of two cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria, and elevated liver enzymes. Tolerability was better with the 30 mg dose once a day. Nine patients had stable disease, but none had a confirmed partial response. The median progression-free survival and overall survival were 2 and 6 months, respectively. Response criteria to proceed to full accrual were not met. Increase in circulating endothelial cell count was noted at the time of progression in several patients. Conclusions: Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients. C1 [Ramalingam, Suresh S.] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Belani, Chandra P.] Penn State Hershey Canc Inst, Dept Med, Hershey, PA USA. [Mack, Philip C.; Gandara, David R.] Univ Calif Davis, Ctr Canc, Dept Med, Sacramento, CA 95817 USA. [Vokes, Everett E.] Univ Chicago, Dept Med, Ctr Canc, Chicago, IL 60637 USA. [Longmate, Jeffrey] City Hope Canc Ctr, Dept Biostat, Duarte, CA USA. [Koczywas, Marianna] City Hope Canc Ctr, Dept Med, Duarte, CA USA. [Govindan, Ramaswamy] Washington Univ, Dept Med, St Louis, MO USA. [Ivy, S. Percy] NCI, Bethesda, MD 20892 USA. RP Ramalingam, SS (reprint author), Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, 1365 Clifton Rd NE,Rm C-3090, Atlanta, GA 30322 USA. EM suresh.ramalingam@emory.edu OI Belani, Chandra/0000-0001-5049-5329; Longmate, Jeffrey/0000-0002-0869-7928 FU NCI [N01-CM-62209, N01-CM-62201, N01-CM-62205]; American Society of Clinical Oncology Foundation FX Supported by NCI N01-CM-62209, N01-CM-62201, and N01-CM-62205 and an American Society of Clinical Oncology Foundation Career Development Award (to S.S.R.). NR 23 TC 48 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD AUG PY 2010 VL 5 IS 8 BP 1279 EP 1284 DI 10.1097/JTO.0b013e3181e2fcb0 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 631RY UT WOS:000280366700026 PM 20559150 ER PT J AU Szabo, R Rasmussen, AL Moyer, AB Schafer, JM Molinolo, AA Gutkind, JS Bugge, TH AF Szabo, R. Rasmussen, A. L. Moyer, A. B. Schafer, J. M. Molinolo, A. A. Gutkind, J. S. Bugge, T. H. TI Matriptase induces formation of skin carcinoma through activation of hepatocyte growth factor-dependent signaling pathway SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Szabo, R.; Rasmussen, A. L.; Moyer, A. B.; Schafer, J. M.; Molinolo, A. A.; Gutkind, J. S.; Bugge, T. H.] NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2010 VL 8 SU 1 SI SI BP 14 EP 14 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 642LY UT WOS:000281216700036 ER PT J AU Bugge, TH Szabo, R Kosa, P List, K AF Bugge, T. H. Szabo, R. Kosa, P. List, K. TI Epithelial development and homeostasis require complex interactions between matriptase and the Kunitz-type transmembrane serine protease inhibitors, HAI-1 and HAI-2 SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Bugge, T. H.; Szabo, R.; Kosa, P.] NIH, Bethesda, MD 20892 USA. [List, K.] Wayne State Univ, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2010 VL 8 SU 1 SI SI BP 43 EP 43 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 642LY UT WOS:000281216700112 ER PT J AU Maynard, DM Heijnen, HFG Gahl, WA Gunay-Aygun, M AF Maynard, D. M. Heijnen, H. F. G. Gahl, W. A. Gunay-Aygun, M. TI The alpha-granule proteome: novel proteins in normal and ghost granules in gray platelet syndrome SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE alpha-granule; gray platelet syndrome; LTBP1; mass spectrometry; platelet ID GROWTH-FACTOR-BETA; ACTIVATED PLATELETS; MASS-SPECTROMETRY; TGF-BETA; CELLS; MEGAKARYOCYTES; LOCALIZATION; FIBRINOGEN; RELEASE; SURFACE AB Background: Deficiencies in granule-bound substances in platelets cause congenital bleeding disorders known as storage pool deficiencies. For disorders such as gray platelet syndrome (GPS), in which thrombocytopenia, enlarged platelets and a paucity of alpha-granules are observed, only the clinical and histologic states have been defined. Objectives: In order to understand the molecular defect in GPS, the alpha-granule fraction protein composition from a normal individual was compared with that of a GPS patient by mass spectrometry (MS). Methods: Platelet organelles were separated by sucrose gradient ultracentrifugation. Proteins from sedimented fractions were separated by sodium dodecylsulfate polyacrylamide gel electrophoresis, reduced, alkylated, and digested with trypsin. Peptides were analyzed by liquid chromatography-tandem MS. Mascot was used for peptide/protein identification and to determine peptide false-positive rates. MassSieve was used to generate and compare parsimonious lists of proteins. Results: As compared with control, the normalized peptide hits (NPHs) from soluble, biosynthetic alpha-granule proteins were markedly decreased or undetected in GPS platelets, whereas the NPHs from soluble, endocytosed alpha-granule proteins were only moderately affected. The NPHs from membrane-bound alpha-granule proteins were similar in normal platelets and GPS platelets, although P-selectin and Glut3 were slightly decreased, consistent with immunoelectron microscopy findings in resting platelets. We also identified proteins not previously known to be decreased in GPS, including latent transforming growth factor-beta-binding protein 1(LTBP1), a component of the transforming growth factor-beta (TGF-beta) complex. Conclusions: Our results support the existence of 'ghost granules' in GPS, point to the basic defect in GPS as failure to incorporate endogenously synthesized megakaryocytic proteins into alpha-granules, and identify specific new proteins as alpha-granule inhabitants. C1 [Maynard, D. M.; Gahl, W. A.; Gunay-Aygun, M.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, Bethesda, MD 20892 USA. [Heijnen, H. F. G.] Univ Med Ctr Utrecht, Lab Clin Chem & Haematol, Utrecht, Netherlands. [Heijnen, H. F. G.] Univ Med Ctr Utrecht, Cell Microscopy Ctr, Utrecht, Netherlands. [Gunay-Aygun, M.] NIH, Intramural Off Rare Dis Res, Bethesda, MD 20892 USA. RP Maynard, DM (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, 10 Ctr Dr,10-10C103,MSC 1851, Bethesda, MD 20892 USA. EM maynardd@mail.nih.gov FU National Human Genome Research Institute; NIH Clinical Center [NCT00369421]; [NCT00001846] FX We thank S. F. Leitman, Department of Transfusion Medicine, NIH Clinical Center, for control blood samples (Clinical trials identifier NCT00001846), H. Dorward for assistance in obtaining light microscope images, S. van Dijk for the immuno-EM work, and S. Markey and M. McFarland for helpful discussions regarding proteomic data normalization. This research was supported by the Intramural Research Programs of the National Human Genome Research Institute and the NIH Clinical Center (Clinical trials identifier NCT00369421). NR 33 TC 30 Z9 31 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD AUG PY 2010 VL 8 IS 8 BP 1786 EP 1796 DI 10.1111/j.1538-7836.2010.03932.x PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 635HN UT WOS:000280646300018 PM 20524979 ER PT J AU Wood, BJ Kruecker, J Abi-Jaoudeh, N Locklin, JK Levy, E Xu, S Solbiati, L Kapoor, A Amalou, H Venkatesan, AM AF Wood, Bradford J. Kruecker, Jochen Abi-Jaoudeh, Nadine Locklin, Julia K. Levy, Elliot Xu, Sheng Solbiati, Luigi Kapoor, Ankur Amalou, Hayet Venkatesan, Aradhana M. TI Navigation Systems for Ablation SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID ELECTROMAGNETIC TRACKING; RADIOFREQUENCY ABLATION; GUIDANCE AB Navigation systems, devices, and intraprocedural software are changing the way interventional oncology is practiced. Before the development of precision navigation tools integrated with imaging systems, thermal ablation of hard-to-image lesions was highly dependent on operator experience, spatial skills, and estimation of positron emission tomography avid or arterial-phase targets. Numerous navigation systems for ablation bring the opportunity for standardization and accuracy that extends the operator's ability to use imaging feedback during procedures. In this report, existing systems and techniques are reviewed and specific clinical applications for ablation are discussed to better define how these novel technologies address specific clinical needs and fit into clinical practice. C1 [Wood, Bradford J.; Abi-Jaoudeh, Nadine; Locklin, Julia K.; Levy, Elliot; Kapoor, Ankur; Amalou, Hayet; Venkatesan, Aradhana M.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Kruecker, Jochen; Xu, Sheng] Philips Res N Amer, Briarcliff Manor, NY USA. [Solbiati, Luigi] Gen Hosp Busto Arsizio, Dept Diagnost Imaging, Busto Arsizio, Italy. RP Wood, BJ (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 9000 Rockville Pike,Bldg 10,Room 1C341 MSC 1182, Bethesda, MD 20892 USA. EM bwood@cc.nih.gov OI Solbiati, Luigi/0000-0002-3109-1449 FU National Institutes of Health (NIH) [01864] FX This work was partially supported by the National Institutes of Health (NIH) Intramural Research Program and NIH Cooperative Research and Development Agreement 01864 with Philips Healthcare (Eindhoven, The Netherlands). B.J.W., J.K., S.X., and NIH have intellectual property in the field. B.J.W. is negotiating a Cooperative Research and Development Agreement with Biosound/Esaote (Indianapolis, Indiana and Genoa, Italy). None of the other authors have identified a conflict of interest. NR 12 TC 30 Z9 30 U1 0 U2 4 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 AUG PY 2010 VL 21 IS 8 SU S BP S257 EP S263 DI 10.1016/j.jvir.2010.05.003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 640IT UT WOS:000281045600011 PM 20656236 ER PT J AU Howard, AR Weisberg, AS Moss, B AF Howard, Amanda R. Weisberg, Andrea S. Moss, Bernard TI Congregation of Orthopoxvirus Virions in Cytoplasmic A-Type Inclusions Is Mediated by Interactions of a Bridging Protein (A26p) with a Matrix Protein (ATIp) and a Virion Membrane-Associated Protein (A27p) SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR MATURE VIRUS; VACCINIA VIRUS; COWPOX VIRUS; STABLE COMPLEX; MAJOR PROTEIN; FUSION; GENE; INFECTION; POXVIRUS; BODY AB Some orthopoxviruses, e.g., the cowpox, ectromelia, and raccoonpox viruses, form large, discrete cytoplasmic inclusions within which mature virions (MVs) are embedded by a process called occlusion. These inclusions, which may protect occluded MVs in the environment, are composed of aggregates of the A-type inclusion protein (ATIp), which is truncated in orthopoxviruses such as vaccinia virus (VACV) and variola virus that fail to form inclusions. In addition to an intact ATIp, occlusion requires the A26 protein (A26p). Although VACV contains a functional A26p, determined by complementation of a cowpox virus occlusion-defective mutant, its role in occlusion was unknown. We found that restoration of the full-length ATI gene was sufficient for VACV inclusion formation and the ensuing occlusion of MVs. A26p was present in inclusions even when virion assembly was inhibited, suggesting a direct interaction of A26p with ATIp. Analysis of a panel of ATIp mutants indicated that the C-terminal repeat region was required for inclusion formation and the N-terminal domain for interaction with A26p and occlusion. A26p is tethered to MVs via interaction with the A27 protein (A27p); A27p was not required for association of A26p with ATIp but was necessary for occlusion. In addition, the C-terminal domain of A26p, which mediates A26p-A27p interactions, was necessary but insufficient for occlusion. Taken together, the data suggest a model for occlusion in which A26p has a bridging role between ATIp and A27p, and A27p provides a link to the MV membrane. C1 [Howard, Amanda R.; Weisberg, Andrea S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 N Dr,MSC 3210, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research, NIAID, NIH FX This research was supported by the Division of Intramural Research, NIAID, NIH. NR 25 TC 12 Z9 14 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 AUG PY 2010 VL 84 IS 15 BP 7592 EP 7602 DI 10.1128/JVI.00704-10 PG 11 WC Virology SC Virology GA 626TK UT WOS:000279989800016 PM 20484506 ER PT J AU Galli, A Kearney, M Nikolaitchik, OA Yu, S Chin, MPS Maldarelli, F Coffin, JM Pathak, VK Hu, WS AF Galli, Andrea Kearney, Mary Nikolaitchik, Olga A. Yu, Sloane Chin, Mario P. S. Maldarelli, Frank Coffin, John M. Pathak, Vinay K. Hu, Wei-Shau TI Patterns of Human Immunodeficiency Virus Type 1 Recombination Ex Vivo Provide Evidence for Coadaptation of Distant Sites, Resulting in Purifying Selection for Intersubtype Recombinants during Replication SO JOURNAL OF VIROLOGY LA English DT Article ID DRUG-RESISTANCE MUTATIONS; GENETIC-RECOMBINATION; MOLECULAR EPIDEMIOLOGY; REVERSE-TRANSCRIPTASE; HIV-1 RECOMBINATION; TARGET-CELLS; POL GENE; SUBTYPE; IDENTIFICATION; SUPERINFECTION AB High-frequency recombination is a hallmark of HIV-1 replication. Recombination can occur between two members of the same subtype or between viruses from two different subtypes, generating intra-or intersubtype recombinants, respectively. Many intersubtype recombinants have been shown to circulate in human populations. We hypothesize that sequence diversity affects the emergence of viable recombinants by decreasing recombination events and reducing the ability of the recombinants to replicate. To test our hypothesis, we compared recombination between two viruses containing subtype B pol genes (B/B) and between viruses with pol genes from subtype B or F (B/F). Recombination events generated during a single cycle of infection without selection pressure on pol gene function were analyzed by single-genome sequencing. We found that recombination occurred slightly (similar to 30%) less frequently in B/F than in B/B viruses, and the overall distribution of crossover junctions in pol was similar for the two classes of recombinants. We then examined the emergence of recombinants in a multiple cycle assay, so that functional pol gene products were selected. We found that the emerging B/B recombinants had complex patterns, and the crossover junctions were distributed throughout the pol gene. In contrast, selected B/F recombinants had limited recombination patterns and restricted crossover junction distribution. These results provide evidence for the evolved coadapted sites in variants from different subtypes; these sites may be segregated by recombination events, causing the newly generated intersubtype recombinants to undergo purifying selection. Therefore, the ability of the recombinants to replicate is the major barrier for many of these viruses. C1 [Galli, Andrea; Kearney, Mary; Nikolaitchik, Olga A.; Yu, Sloane; Chin, Mario P. S.; Maldarelli, Frank; Pathak, Vinay K.; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 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 OI Galli, Andrea/0000-0002-4404-430X FU NIH, National Cancer Institute, Center for Cancer Research; University of Milan; F.M. Kirby Foundation FX This work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. A.G. was supported in part by a predoctoral fellowship from University of Milan. J.M.C. was a Research Professor of the American Cancer Society, with support from the F.M. Kirby Foundation. NR 51 TC 25 Z9 25 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 AUG PY 2010 VL 84 IS 15 BP 7651 EP 7661 DI 10.1128/JVI.00276-10 PG 11 WC Virology SC Virology GA 626TK UT WOS:000279989800022 PM 20504919 ER PT J AU Umehara, D Watanabe, S Ochi, H Anai, Y Ahmed, N Kannagi, M Hanson, C Ruscetti, S Nishigaki, K AF Umehara, Daigo Watanabe, Shinya Ochi, Haruyo Anai, Yukari Ahmed, Nursarat Kannagi, Mari Hanson, Charlotte Ruscetti, Sandra Nishigaki, Kazuo TI Role of Phosphatidylinositol 3-Kinase in Friend Spleen Focus-Forming Virus-Induced Erythroid Disease SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; PHOSPHOINOSITIDE 3-KINASE; ERYTHROPOIETIN RECEPTOR; SIGNAL-TRANSDUCTION; TRUNCATED FORM; SF-STK; CONSTITUTIVE ACTIVATION; INDUCED ERYTHROLEUKEMIA; STRESS ERYTHROPOIESIS; ENVELOPE GLYCOPROTEIN AB Infection of erythroid cells by Friend spleen focus-forming virus (SFFV) leads to acute erythroid hyperplasia in mice due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator, erythropoietin (Epo), because of interaction of the viral envelope protein with the erythropoietin receptor and a short form of the receptor tyrosine kinase Stk (sf-Stk), leading to constitutive activation of several signal transduction pathways. Our previous in vitro studies showed that phosphatidylinositol 3-kinase (PI3-kinase) is activated in SFFV-infected cells and is important in mediating the biological effects of the virus. To determine the role of PI3-kinase in SFFV-induced disease, mice deficient in the p85 alpha regulatory subunit of class IA PI3-kinase were inoculated with different strains of SFFV. We observed that p85 alpha status determined the extent of erythroid hyperplasia induced by the sf-Stk-dependent viruses SFFV-P (polycythemia-inducing strain of SFFV) and SFFV-A (anemia-inducing strain of SFFV) but not by the sf-Stk-independent SFFV variant BB6. Our data also indicate that p85 alpha status determines the response of mice to stress erythropoiesis, consistent with a previous report showing that SFFV uses a stress erythropoiesis pathway to induce erythroleukemia. We further showed that sf-Stk interacts with p85 alpha and that this interaction depends upon sf-Stk kinase activity and tyrosine 436 in the multifunctional docking site. Pharmacological inhibition of PI3-kinase blocked proliferation of primary erythroleukemia cells from SFFV-infected mice and the erythroleukemia cell lines derived from them. These results indicate that p85 alpha may regulate sf-Stk-dependent erythroid proliferation induced by SFFV as well as stress-induced erythroid hyperplasia. C1 [Umehara, Daigo; Watanabe, Shinya; Ochi, Haruyo; Anai, Yukari; Nishigaki, Kazuo] Yamaguchi Univ, Lab Mol Immunol & Infect Dis, Dept Vet Med, Yamaguchi 7538515, Japan. [Ahmed, Nursarat; Kannagi, Mari] Tokyo Med & Dent Univ, Dept Immunotherapeut, Grad Sch, Tokyo 1138519, Japan. [Hanson, Charlotte; Ruscetti, Sandra] NCI, Lab Canc Prevent, Frederick, MD 21702 USA. RP Nishigaki, K (reprint author), Yamaguchi Univ, Lab Mol Immunol & Infect Dis, Dept Vet Med, 1677-1 Yoshida, Yamaguchi 7538515, Japan. EM kaz@yamaguchi-u.ac.jp FU Ministry of Education, Science, Sports, and Culture of Japan FX This study was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan. NR 52 TC 4 Z9 4 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 AUG PY 2010 VL 84 IS 15 BP 7675 EP 7682 DI 10.1128/JVI.00488-10 PG 8 WC Virology SC Virology GA 626TK UT WOS:000279989800025 PM 20504929 ER PT J AU Chen, GL Lamirande, EW Yang, CF Jin, H Kemble, G Subbarao, K AF Chen, Grace L. Lamirande, Elaine W. Yang, Chin-Fen Jin, Hong Kemble, George Subbarao, Kanta TI Evaluation of Replication and Cross-Reactive Antibody Responses of H2 Subtype Influenza Viruses in Mice and Ferrets SO JOURNAL OF VIROLOGY LA English DT Article ID A VIRUSES; NORTH-AMERICA; MOUSE MODEL; LIVE; VACCINE; TRANSMISSION; PROTECTION; EFFICACY; ORIGIN; DUCKS AB H2 influenza viruses have not circulated in humans since 1968, and therefore a large segment of the population would likely be susceptible to infection should H2 influenza viruses reemerge. The development of an H2 pandemic influenza virus vaccine candidate should therefore be considered a priority in pandemic influenza preparedness planning. We selected a group of geographically and temporally diverse wild-type H2 influenza viruses and evaluated the kinetics of replication and compared the ability of these viruses to induce a broadly cross-reactive antibody response in mice and ferrets. In both mice and ferrets, A/Japan/305/1957 (H2N2), A/mallard/NY/1978 (H2N2), and A/swine/MO/2006 (H2N3) elicited the broadest cross-reactive antibody responses against heterologous H2 influenza viruses as measured by hemagglutination inhibition and microneutralization assays. These data suggested that these three viruses may be suitable candidates for development as live attenuated H2 pandemic influenza virus vaccines. C1 [Subbarao, Kanta] NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Yang, Chin-Fen; Jin, Hong; Kemble, George] MedImmune, Mountain View, CA 94043 USA. RP Subbarao, K (reprint author), NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bldg 33,Room 3E13C1,33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM KSUBBARAO@niaid.nih.gov FU NIH; National Institute of Allergy and Infectious Diseases (NIAID) FX This work was supported by the Intramural Research Program of the NIH and the National Institute of Allergy and Infectious Diseases (NIAID). This research was performed as part of a cooperative research and development agreement between the Laboratory of Infectious Diseases, NIAID, and MedImmune. NR 36 TC 23 Z9 23 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 AUG PY 2010 VL 84 IS 15 BP 7695 EP 7702 DI 10.1128/JVI.00511-10 PG 8 WC Virology SC Virology GA 626TK UT WOS:000279989800027 PM 20504935 ER PT J AU Kwilas, AR Yednak, MA Zhang, LQ Liesman, R Collins, PL Pickles, RJ Peeples, ME AF Kwilas, Anna R. Yednak, Mark A. Zhang, Liqun Liesman, Rachael Collins, Peter L. Pickles, Raymond J. Peeples, Mark E. TI Respiratory Syncytial Virus Engineered To Express the Cystic Fibrosis Transmembrane Conductance Regulator Corrects the Bioelectric Phenotype of Human Cystic Fibrosis Airway Epithelium In Vitro SO JOURNAL OF VIROLOGY LA English DT Article ID INTEGRATING LENTIVIRAL VECTORS; MEDIATED GENE-TRANSFER; OF-THE-ART; ADENOASSOCIATED VIRUS; SENDAI-VIRUS; CFTR GENE; NASAL EPITHELIA; DIRECTED EVOLUTION; ADENOVIRUS VECTORS; CILIATED CELLS AB Cystic fibrosis (CF) is the most common lethal recessive genetic disease in the Caucasian population. It is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that is normally expressed in ciliated airway epithelial cells and the submucosal glands of the lung. Since the CFTR gene was first characterized in 1989, a major goal has been to develop an effective gene therapy for CF lung disease, which has the potential to ameliorate morbidity and mortality. Respiratory syncytial virus (RSV) naturally infects the ciliated cells in the human airway epithelium. In addition, the immune response mounted against an RSV infection does not prevent subsequent infections, suggesting that an RSV-based vector might be effectively readministered. To test whether the large 4.5-kb CFTR gene could be expressed by a recombinant RSV and whether infectious virus could be used to deliver CFTR to ciliated airway epithelium derived from CF patients, we inserted the CFTR gene into four sites in a recombinant green fluorescent protein-expressing RSV (rgRSV) genome to generate virus expressing four different levels of CFTR protein. Two of these four rgRSV-CFTR vectors were capable of expressing CFTR with little effect on viral replication. rgRSV-CFTR infection of primary human airway epithelial cultures derived from CF patients resulted in expression of CFTR protein that was properly localized at the luminal surface and corrected the chloride ion channel defect in these cells. C1 [Peeples, Mark E.] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH 43205 USA. [Kwilas, Anna R.] Ohio State Univ, Coll Med, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA. [Peeples, Mark E.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Zhang, Liqun; Pickles, Raymond J.] Univ N Carolina, CF Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. [Liesman, Rachael; Pickles, Raymond J.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Peeples, ME (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, 700 Childrens Dr, Columbus, OH 43205 USA. EM Mark.Peeples@nationwidechildrens.org FU National Institutes of Health [PO1 HL051818]; NIH Molecular Therapy Core Center [P30 DK065988-01]; Research Institute at Nationwide Children's Hospital; NIAID, NIH FX This work was funded by National Institutes of Health PO1 HL051818 (M. E. P. and R.J.P.) and NIH Molecular Therapy Core Center P30 DK065988-01 (R.J.P.). A. R. K. was supported by a graduate fellowship from the General Mason Scholarship Fund of The Research Institute at Nationwide Children's Hospital. P. L. C. was supported by the Intramural Program of NIAID, NIH. NR 90 TC 15 Z9 15 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD AUG PY 2010 VL 84 IS 15 BP 7770 EP 7781 DI 10.1128/JVI.00346-10 PG 12 WC Virology SC Virology GA 626TK UT WOS:000279989800035 PM 20504917 ER PT J AU Harris, LD Tabb, B Sodora, DL Paiardini, M Klatt, NR Douek, DC Silvestri, G Muller-Trutwin, M Vasile-Pandrea, I Apetrei, C Hirsch, V Lifson, J Brenchley, JM Estes, JD AF Harris, Levelle D. Tabb, Brian Sodora, Donald L. Paiardini, Mirko Klatt, Nichole R. Douek, Daniel C. Silvestri, Guido Mueller-Trutwin, Michaela Vasile-Pandrea, Ivona Apetrei, Cristian Hirsch, Vanessa Lifson, Jeffrey Brenchley, Jason M. Estes, Jacob D. TI Downregulation of Robust Acute Type I Interferon Responses Distinguishes Nonpathogenic Simian Immunodeficiency Virus (SIV) Infection of Natural Hosts from Pathogenic SIV Infection of Rhesus Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; DENDRITIC CELL PRECURSORS; INFLAMED LYMPH-NODES; CD4(+) T-CELLS; SOOTY MANGABEYS; AIDS PATHOGENESIS; IMMUNE ACTIVATION; INDUCTION; REPLICATION; DEPLETION AB The mechanisms underlying the AIDS resistance of natural hosts for simian immunodeficiency virus (SIV) remain unknown. Recently, it was proposed that natural SIV hosts avoid disease because their plasmacytoid dendritic cells (pDCs) are intrinsically unable to produce alpha interferon (IFN-alpha) in response to SIV RNA stimulation. However, here we show that (i) acute SIV infections of natural hosts are associated with a rapid and robust type I IFN response in vivo, (ii) pDCs are the principal in vivo producers of IFN-alpha/beta at peak acute infection in lymphatic tissues, and (iii) natural SIV hosts downregulate these responses in early chronic infection. In contrast, persistently high type I IFN responses are observed during pathogenic SIV infection of rhesus macaques. C1 [Lifson, Jeffrey; Estes, Jacob D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 20892 USA. [Harris, Levelle D.; Klatt, Nichole R.; Hirsch, Vanessa; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Tabb, Brian] NCI, Lab Anim Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Sodora, Donald L.] Seattle BioMed, Seattle, WA USA. [Paiardini, Mirko; Silvestri, Guido] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. [Paiardini, Mirko; Silvestri, Guido] Univ Penn, Lab Med, Philadelphia, PA 19104 USA. [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Mueller-Trutwin, Michaela] Inst Pasteur, Paris, France. [Vasile-Pandrea, Ivona; Apetrei, Cristian] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA. RP Estes, JD (reprint author), NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 20892 USA. EM estesj@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. NR 29 TC 88 Z9 88 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 AUG PY 2010 VL 84 IS 15 BP 7886 EP 7891 DI 10.1128/JVI.02612-09 PG 6 WC Virology SC Virology GA 626TK UT WOS:000279989800046 PM 20484518 ER PT J AU Blair-Handon, R Mueller, K Hoogstraten-Miller, S AF Blair-Handon, Robin Mueller, Kristen Hoogstraten-Miller, Shelley TI An alternative method for intrathymic injections in mice SO LAB ANIMAL LA English DT Article AB The thymus is a bi-lobed lymphatic organ located in the anterior portion of the ventral thoracic cavity, just behind the sternum. Because the thymus is the site of development of T lymphocytes (T cells), it is frequently targeted in research studies that involve the immune system. Furthermore, the rapid expansion of transgenic and gene-targeted mouse models of immune disorders has enabled a concomitant increase in the number of studies of T-cell development. Such studies may require the administration of intrathymic injections, which have traditionally been done using a surgical approach. Surgical manipulation can result in pain or distress to the animal, which may affect the immune system, potentially confounding experimental results. Here, the authors describe a nonsurgical, ultrasound-guided approach for intrathymic injection in the mouse that results in negligible distress to the animal. C1 [Hoogstraten-Miller, Shelley] NHGRI, Off Lab Anim Med, NIH, Bethesda, MD 20892 USA. [Blair-Handon, Robin; Mueller, Kristen] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Hoogstraten-Miller, S (reprint author), NHGRI, Off Lab Anim Med, NIH, Bethesda, MD 20892 USA. EM shoogstr@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX We thank Daryl Despres from the National Institutes of Health Mouse Imaging Facility for his assistance with this project. This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 8 TC 7 Z9 7 U1 0 U2 2 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 AUG PY 2010 VL 39 IS 8 BP 248 EP 252 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 636CG UT WOS:000280704900012 PM 20664574 ER PT J AU Landi, MT Chatterjee, N Caporaso, NE Rotunno, M Albanes, D Thun, M Wheeler, W Rosenberger, A Bickeboller, H Risch, A Wang, YF Gaborieau, V Thorgeirsson, T Gudbjartsson, D Sulem, P Spitz, MR Wichmann, HE Rafnar, T Stefansson, K Houlston, RS Brennan, P AF Landi, Maria Teresa Chatterjee, Nilanjan Caporaso, Neil E. Rotunno, Melissa Albanes, Demetrius Thun, Michael Wheeler, William Rosenberger, Albert Bickeboller, Heike Risch, Angela Wang, Yufei Gaborieau, Valerie Thorgeirsson, Thorgeir Gudbjartsson, Daniel Sulem, Patrick Spitz, Margaret R. Wichmann, H. Erich Rafnar, Thorunn Stefansson, Kari Houlston, Richard S. Brennan, Paul TI GPC5 rs2352028 variant and risk of lung cancer in never smokers SO LANCET ONCOLOGY LA English DT Editorial Material C1 [Landi, Maria Teresa; Chatterjee, Nilanjan; Caporaso, Neil E.; Rotunno, Melissa; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA. [Wheeler, William] Informat Management Serv Inc, Rockville, MD USA. [Rosenberger, Albert; Bickeboller, Heike] Univ Gottingen, Sch Med, Dept Genet Epidemiol, Gottingen, Germany. [Risch, Angela] German Canc Res Ctr, Div Epigenet & Canc Risk Factors, D-6900 Heidelberg, Germany. [Wang, Yufei; Houlston, Richard S.] Inst Canc Res, Sect Canc Genet, Surrey, England. [Gaborieau, Valerie; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Thorgeirsson, Thorgeir; Gudbjartsson, Daniel; Sulem, Patrick; Rafnar, Thorunn; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Wichmann, H. Erich] Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany. [Wichmann, H. Erich] Res Ctr Environm Hlth, Neuherberg, Germany. [Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany. RP Landi, MT (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7114, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015; Risch, Angela/H-2669-2013; OI Risch, Angela/0000-0002-8026-5505; Houlston, Richard/0000-0002-5268-0242 FU Intramural NIH HHS [ZIA CP010200-03]; NIDA NIH HHS [R01 DA017932] NR 6 TC 13 Z9 13 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 AUG PY 2010 VL 11 IS 8 BP 714 EP 716 DI 10.1016/S1470-2045(10)70096-6 PG 3 WC Oncology SC Oncology GA 639XD UT WOS:000281009500011 PM 20688270 ER PT J AU Romagnoli, R Baraldi, PG Carrion, MD Cara, CL Casolari, A Hamel, E Fabbri, E Gambari, R AF Romagnoli, Romeo Baraldi, Pier Giovanni Carrion, Maria Dora Cara, Carlota Lopez Casolari, Alberto Hamel, Ernest Fabbri, Enrica Gambari, Roberto TI Synthesis and Evaluation of Haloacetyl, alpha-Bromoacryloyl and Nitrooxyacetyl Benzo[b]furan and Benzo[b]thiophene Derivatives as Potent Antiproliferative Agents Against Leukemia L1210 and K562 Cells SO LETTERS IN DRUG DESIGN & DISCOVERY LA English DT Article DE Benzo[b]thiophene; Benzo[b]furan; Tumor cell growth; Antiproliferative agents ID GLOBIN MESSENGER-RNA; ANTIMITOTIC AGENTS; TUBULIN POLYMERIZATION; BIOLOGICAL EVALUATION; ANTITUMOR AGENTS; GENE-EXPRESSION; DIFFERENTIATION; APOPTOSIS; INHIBITORS; DISCOVERY AB Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. In search of new compounds with strong antiproliferative activity and simple molecular structure, we have synthesized three different series of compounds in which different substituents were linked to the 3-amino position of the 2-(3', 4', 5'-trimethoxybenzoyl)-benzo[b]furan or benzo[b]thiophene ring system. These substituents, corresponding to acetyl/haloacetyl, alpha-bromoacryloyl and nitrooxyacetyl moieties had different electrophilic properties. The benzoheterocycle parent structures were selected because of their reported bioactivities. Compounds bearing a methoxy group at the 6-position of the benzo[b]furan skeleton, were identified as potent antiproliferative agents against the human chronic myelogenous K562 and murine L1210 leukemia cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 6- to the 5- or 7-position yielded inactive compounds. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. The analysis of structure-activity relationships observed in the series of compounds described here may represent a platform for the design of more active molecules. C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Carrion, Maria Dora; Cara, Carlota Lopez; Casolari, Alberto] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. [Fabbri, Enrica; Gambari, Roberto] Univ Ferrara, Dipartimento Biochim & Biol Mol, I-44100 Ferrara, Italy. [Hamel, Ernest] NCI, Screening Tecnol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, Via Fossato Mortara 17-19, I-44100 Ferrara, Italy. EM rmr@unife.it RI LOPEZ-CARA, LUISA CARLOTA/F-9686-2014; Gambari, Roberto/F-9555-2015; Carrion, M. Dora/G-8638-2015; Romagnoli, Romeo/G-9887-2015; Fabbri, Enrica/O-8059-2015; Baraldi, Pier Giovanni/B-7933-2017 OI LOPEZ-CARA, LUISA CARLOTA/0000-0003-1142-6448; Gambari, Roberto/0000-0001-9205-6033; Carrion, M. Dora/0000-0002-6794-3949; Fabbri, Enrica/0000-0002-9836-8262; FU AIRC; Fondazione Cassa di Risparmio di Padova e Rovigo FX RG is supported by grants from the AIRC and the "Fondazione Cassa di Risparmio di Padova e Rovigo". NR 28 TC 7 Z9 7 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-1808 J9 LETT DRUG DES DISCOV JI Lett. Drug Des. Discov. PD AUG PY 2010 VL 7 IS 7 BP 476 EP 486 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 633BI UT WOS:000280474100001 PM 20676361 ER PT J AU Pratz, KW Cho, E Levis, MJ Karp, JE Gore, SD McDevitt, M Stine, A Zhao, M Baker, SD Carducci, MA Wright, JJ Rudek, MA Smith, BD AF Pratz, K. W. Cho, E. Levis, M. J. Karp, J. E. Gore, S. D. McDevitt, M. Stine, A. Zhao, M. Baker, S. D. Carducci, M. A. Wright, J. J. Rudek, M. A. Smith, B. D. TI A pharmacodynamic study of sorafenib in patients with relapsed and refractory acute leukemias SO LEUKEMIA LA English DT Article DE acute myeloid leukemia; FLT3 targeted therapy; signal transduction inhibitors; clinical trial ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; FACTOR RECEPTOR INHIBITOR; DAYS ON/7 DAYS; SOLID TUMORS; PHASE-I; RAF KINASE; ANTITUMOR-ACTIVITY; FLT3 INHIBITORS AB We report the results of a phase I dose escalation trial of the multikinase inhibitor sorafenib in relapsed and refractory acute leukemia patients using an intermittent dosing regimen. Fifteen patients with advanced leukemia (12 with acute myeloid leukemia, 2 with acute lymphoblastic leukemia, 1 with biphenotypic) and a median age of 63 (range 37-85) years were enrolled and treated on a dose escalation trial. Toxicities >= grade 3 were present in 55% of cycles and the maximum tolerated dose (MTD) was determined to be 400 mg b.i.d. x 21 days in a 28-day cycle. Plasma inhibitory assays of kinase targets extracellular signal-regulated kinase (ERK) and FLT3-internal tandem duplication (ITD) showed excellent target inhibition, with FLT3-ITD silencing occurring below the MTD. The N-oxide metabolite of sorafenib seemed to be a more potent inhibitor of FLT3-ITD than the parent compound. Despite marked ex vivo FLT-3 ITD inhibition, no patients met the criteria for complete or partial response in this monotherapy study. Out of 15 patients, 11 experienced stable disease as best response. Although sorafenib showed only modest clinical activity as a single agent in this heavily treated population, robust inhibition of FLT3 and ERK suggests that there may be a potential important role in combination therapies. Leukemia (2010) 24, 1437-1444; doi:10.1038/leu.2010.132; published online 10 June 2010 C1 [Pratz, K. W.; Cho, E.; Levis, M. J.; Karp, J. E.; Gore, S. D.; McDevitt, M.; Stine, A.; Zhao, M.; Carducci, M. A.; Rudek, M. A.; Smith, B. D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Div Hematol Malignancies, Baltimore, MD 21231 USA. [Baker, S. D.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Wright, J. J.] NCI, Invest Drug Branch, Bethesda, MD 20892 USA. RP Pratz, KW (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Div Hematol Malignancies, 1650 Orleans St,CRB1 Room 2M45, Baltimore, MD 21231 USA. EM Kpratz1@jhmi.edu FU National Institutes of Health [P30CA006973, U01CA70095, UL1 RR025005]; NCI [P50 CA100632-06, R01 CA128864]; American Society of Clinical Oncology FX We thank Carol Hartke, Ping He, Aleksandr Mnatsakanyan, Yelena Zabelina and Linping Xu for their technical assistance; and Susan Davidson for quality assurance of the pharmacokinetic data. This work was supported by National Institutes of Health grants P30CA006973, U01CA70095, UL1 RR025005, NCI Leukemia SPORE P50 CA100632-06, R01 CA128864 and the by American Society of Clinical Oncology (MJL). MJL is a Clinical Scholar of the Leukemia and Lymphoma Society. NR 35 TC 50 Z9 51 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 2010 VL 24 IS 8 BP 1437 EP 1444 DI 10.1038/leu.2010.132 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 637PP UT WOS:000280830900006 PM 20535150 ER PT J AU Wilson, WH Hernandez-Ilizaliturri, FJ Dunleavy, K Little, RF O'Connor, OA AF Wilson, Wyndham H. Hernandez-Ilizaliturri, Francisco J. Dunleavy, Kieron Little, Richard F. O'Connor, Owen A. TI Novel disease targets and management approaches for diffuse large B-cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 7th International Workshop on Non-Hodgkin's Lymphoma CY OCT 02-03, 2009 CL Barcelona, SPAIN DE Diffuse large B-cell lymphoma; Bcl-2; novel agents; gene expression profiling ID PROTEASOME INHIBITOR BORTEZOMIB; CHRONIC LYMPHOCYTIC-LEUKEMIA; SINGLE-AGENT TEMSIROLIMUS; NON-HODGKINS-LYMPHOMA; GENE-EXPRESSION; ANTITUMOR-ACTIVITY; MOLECULAR SUBTYPES; CANCER-PATIENTS; PHASE-II; IN-VITRO AB Diffuse large B-cell lymphoma (DLBCL) responds well to treatment with CHOP and the R-CHOP regimen, but a subset of patients still fail to achieve complete or durable responses. Recent advances in gene expression profiling have led to the identification of three different subtypes of DLBCL, and confirmed that patients with the activated B-cell (ABC) disease subtype are less likely to respond well to CHOP-based regimens than those with germinal centre B-cell-type (GCB) disease. This discovery could herald the use of gene expression profiling to aid treatment decisions in DLBCL, and help identify the most effective management strategies for patients. Treatment options for patients with relapsed or refractory DLBCL are limited and several novel agents are being developed to address this unmet clinical need. Novel agents developed to treat plasma cell disorders such as multiple myeloma have shown promising activity in patients with NHL. Indeed, the immunomodulatory agent lenalidomide and the proteasome inhibitors bortezomib and carfilzomib, as single agents or in combination with chemotherapy, have already demonstrated promising activity in patients with the ABC subtype of DLBCL. One should not be complacent however when applying these agents to new disease types, because dose and drug scheduling can have marked effects on the responses achieved with investigational agents. As more targeted agents are developed, the timing of administration with other agents in clinical trials will become increasingly important to ensure maximal efficacy while minimizing side effects. C1 [Hernandez-Ilizaliturri, Francisco J.] Roswell Pk Canc Inst, Dept Med Oncol, Buffalo, NY 14263 USA. [Little, Richard F.] NCI, Clin Invest Branch, Div Canc Therapy & Diag, Bethesda, MD 20892 USA. [O'Connor, Owen A.] NYU, Div Hematol & Med Oncol, NYU Langone Med Ctr, Inst Canc, New York, NY USA. [Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, Lymphoma Therapeut Sect, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Metab Branch, Ctr Canc Res, Lymphoma Therapeut Sect, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 58 TC 16 Z9 18 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 2010 VL 51 SU 1 BP 1 EP 10 DI 10.3109/10428194.2010.500045 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 655FN UT WOS:000282233100001 PM 20658952 ER PT J AU Dunleavy, K Mikhaeel, G Sehn, LH Hicks, RJ Wilson, WH AF Dunleavy, Kieron Mikhaeel, George Sehn, Laurie H. Hicks, Rodney J. Wilson, Wyndham H. TI The value of positron emission tomography in prognosis and response assessment in non-Hodgkin lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 7th International Workshop on Non-Hodgkins Lymphoma CY OCT 02-03, 2009 CL Barcelona, SPAIN DE Lymphoma; positron emission tomography; prognosis; response ID B-CELL LYMPHOMA; SUV-BASED ASSESSMENT; FOLLOW-UP; MALIGNANT-LYMPHOMA; F-18-FDG PET; 4 CYCLES; FDG-PET; CHEMOTHERAPY; PROGRESSION; DISEASE AB Positron emission tomography (PET) is widely used for post-treatment response assessment in lymphoma. However, the role of PET in prognosis and early response assessment is still being defined. Studies have shown that PET can identify response early during chemotherapy and that interim PET can predict outcome in diffuse large B-cell lymphoma (DLBCL). Whether the results of early or post-treatment response assessment can be used to determine prognosis and/or guide therapeutic decisions, known as response-adapted therapy, is currently being investigated, with considerable promise in certain lymphomas such as Hodgkin lymphoma (HL) and DLBCL. The use of interim PET is currently limited by a lack of standardized imaging protocols and reporting criteria, and unproven reproducibility of interpretation. As a result, until further data are generated and a consensus reached, interim PET should be considered investigational and applied only within the confines of clinical studies. This review provides an overview of the use of PET for prognosis and response assessment, and in response-adapted therapy. Current limitations of the technique will be summarized, and innovative uses of PET in grading, staging, and surveying lymphomas will be briefly explored. C1 [Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, Bethesda, MD 20892 USA. [Mikhaeel, George] St Thomas Hosp, London, England. [Sehn, Laurie H.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Hicks, Rodney J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Hicks, Rodney J.] Univ Melbourne, Melbourne, Vic, Australia. RP Wilson, WH (reprint author), NCI, Lymphoma Therapeut Sect, Metab Branch, 9000 Rockville Pike,Bldg 10,Room 4N-115, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 24 TC 12 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 2010 VL 51 SU 1 BP 28 EP 33 DI 10.3109/10428194.2010.500051 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 655FN UT WOS:000282233100004 PM 20658958 ER PT J AU Harauma, A Salem, N Moriguchi, T AF Harauma, Akiko Salem, Norman, Jr. Moriguchi, Toru TI Repletion of n-3 Fatty Acid Deficient Dams with alpha-Linolenic Acid: Effects on Fetal Brain and Liver Fatty Acid Composition SO LIPIDS LA English DT Article DE Docosahexaenoic acid; Docosapentaenoic acid; Fetal brain; Infant nutrition; n-3 fatty acid deficiency ID RAT-BRAIN; DOCOSAHEXAENOIC ACID; LIPIDS; ACCUMULATION; TRANSPORT; DIETS AB Docosahexaenoic acid (DHA) supply to the fetal brain depends upon the dam's dietary intake of n-3 fats. In this study, we measured the incorporation of DHA into the fetal brain and liver in n-3 fatty acid deficient (0.1% alpha-linolenate) mice upon switching to an n-3 fatty acid adequate (2.1% alpha-linolenate) diet. Second generation mice raised and maintained on an n-3 deficient diet during mating were switched to an n-3 adequate diet on embryonic day 1 (ED 1) or ED 13. Fatty acid analysis was performed on fetal brains and livers and on maternal serum on ED 13, 15, 17, and 19. Although fetal brain and liver DHA began at a very low level (both exhibited an 85% decline), recovery was nearly complete by ED 15 in the group switched near conception but thereafter diverged. The maternal serum and fetal liver were very similar in their DHA and docosapentaenoic acid time courses. However, when repletion began on ED 13, brain DHA recovery was only about 44%. These results suggest that a nutritional intervention with alpha-linolenic acid can nearly but incompletely rescue the mouse fetal DHA deficiency if began at the time of conception but that the third trimester is too late, thus leaving a large DHA gap. C1 [Harauma, Akiko; Moriguchi, Toru] Wakunaga Pharmaceut Co Ltd, Inst Healthcare Res, Hiroshima, Japan. [Salem, Norman, Jr.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Salem, N (reprint author), 6480 Dobbin Rd, Columbia, MD 21045 USA. EM nsalem@martek.com NR 19 TC 9 Z9 9 U1 1 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PD AUG PY 2010 VL 45 IS 8 BP 659 EP 668 DI 10.1007/s11745-010-3443-y PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 640DJ UT WOS:000281027800001 PM 20625936 ER PT J AU Sharif, B Derbyshire, JA Faranesh, AZ Bresler, Y AF Sharif, Behzad Derbyshire, J. Andrew Faranesh, Anthony Z. Bresler, Yoram TI Patient-Adaptive Reconstruction and Acquisition in Dynamic Imaging with Sensitivity Encoding (PARADISE) SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cardiac MRI; nongated; model-based; patient adaptive; k-t sampling; sensitivity encoding ID STATE FREE PRECESSION; K-T SENSE; FIELD-OF-VIEW; REAL-TIME; VENTRICULAR-FUNCTION; MRI; UNFOLD; HEART; IMAGES; MOTION AB MRI of the human heart without explicit cardiac synchronization promises to extend the applicability of cardiac MR to a larger patient population and potentially expand its diagnostic capabilities. However, conventional nongated imaging techniques typically suffer from low image quality or inadequate spatio-temporal resolution and fidelity. Patient-Adaptive Reconstruction and Acquisition in Dynamic Imaging with Sensitivity Encoding (PARADISE) is a highly accelerated nongated dynamic imaging method that enables artifact-free imaging with high spatio-temporal resolutions by utilizing novel computational techniques to optimize the imaging process. In addition to using parallel imaging, the method gains acceleration from a physiologically driven spatio-temporal support model; hence, it is doubly accelerated. The support model is patient adaptive, i.e., its geometry depends on dynamics of the imaged slice, e.g., subject's heart rate and heart location within the slice. The proposed method is also doubly adaptive as it adapts both the acquisition and reconstruction schemes. Based on the theory of time-sequential sampling, the proposed framework explicitly accounts for speed limitations of gradient encoding and provides performance guarantees on achievable image quality. The presented in-vivo results demonstrate the effectiveness and feasibility of the PARADISE method for high-resolution nongated cardiac MRI during short breath-hold. Magn Reson Med 64:501-513, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Sharif, Behzad; Bresler, Yoram] Univ Illinois, Coordinated Sci Lab, Urbana, IL 61801 USA. [Sharif, Behzad; Bresler, Yoram] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Sharif, Behzad; Bresler, Yoram] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Derbyshire, J. Andrew; Faranesh, Anthony Z.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Sharif, B (reprint author), Univ Illinois, Coordinated Sci Lab, Room 339MC-228,1308 W Main St, Urbana, IL 61801 USA. EM sharif@illinois.edu FU Translational Medicine Branch (TMB); NHLBI; National Institutes of Health (NIH); Beckman Institute; University of Illinois; TMB FX We acknowledge Dr. Robert J. Lederman and Ms. Annette M. Stine of the Translational Medicine Branch (TMB), NHLBI, National Institutes of Health (NIH), for supporting the imaging experiments. We thank Dr. Ashvin K. George (TMB, NHLBI, NIH) for assisting with the experiments and Dr. Peter Kellman (Laboratory of Cardiac Energetics, NHLBI, NIH) for helping with the coil profile estimation technique. We also acknowledge Mr. Nitin Aggarwal (University of Illinois) for insightful discussions. This work was partially supported by Ph.D. fellowships from the Beckman Institute and the Computational Science and Engineering Program, University of Illinois. The imaging experiments were partially supported by the TMB, NHLBI, National Institutes of Health. NR 52 TC 24 Z9 24 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2010 VL 64 IS 2 BP 501 EP 513 DI 10.1002/mrm.22444 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 632KG UT WOS:000280422000021 PM 20665794 ER PT J AU Agarwal, HK Prince, JL Abd-Emoniem, KZ AF Agarwal, Harsh K. Prince, Jerry L. Abd-Emoniem, Khaled Z. TI Total Removal of Unwanted Harmonic Peaks (TruHARP) MRI for Single Breath-Hold High-Resolution Myocardial Motion and Strain Quantification SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; HARP; tagging; cardiac motion; strain quantification ID ARTIFACT-GENERATING ECHOES; ENCODED CARDIAC MRI; HUMAN-HEART; STIMULATED ECHOES; PHASE; DENSE; TRACKING; HARP; ECHOCARDIOGRAPHY; ATHEROSCLEROSIS AB Current MRI methods for myocardial motion and strain quantification have limited resolution because of Fourier space spectral peak interference. Methods have been proposed to remove this interference in order to improve resolution; however, these methods are clinically impractical due to the prolonged imaging times. In this paper, we propose total removal of unwanted harmonic peaks (TruHARP); a myocardial motion and strain quantification methodology that uses a novel single breath-hold MR image acquisition protocol. In post-processing, TruHARP separates the spectral peaks in the acquired images, enabling high-resolution motion and strain quantification. The impact of high resolution on calculated circumferential and radial strains is studied using realistic Monte Carlo simulations, and the improvement in strain maps is demonstrated in six human subjects. Magn Reson Med 64:574-585, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Abd-Emoniem, Khaled Z.] NIDDK, NIH, Bethesda, MD 20892 USA. [Agarwal, Harsh K.; Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Prince, Jerry L.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Abd-Emoniem, KZ (reprint author), NIDDK, NIH, Bldg 10,CRC Room 3-5340, Bethesda, MD 20892 USA. EM abdelmoniemkz@niddk.nih.gov RI Prince, Jerry/A-3281-2010; Abd-Elmoniem, Khaled/B-9289-2008 OI Prince, Jerry/0000-0002-6553-0876; Abd-Elmoniem, Khaled/0000-0002-1001-1702 FU NIH/NHLBI [R01HL47405] FX Grant sponsor: NIH/NHLBI; Grant number: R01HL47405. NR 38 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2010 VL 64 IS 2 BP 574 EP 585 DI 10.1002/mrm.22403 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 632KG UT WOS:000280422000028 PM 20665800 ER PT J AU Usharauli, D AF Usharauli, David TI Chronic infection and the origin of adaptive immune system SO MEDICAL HYPOTHESES LA English DT Article ID NATURAL-KILLER-CELLS; SELF; RECOGNITION; RESPONSES; RECEPTORS; NONSELF; DANGER AB It has been speculated that the rise of the adaptive immune system in jawed vertebrates some 400 million years ago gave them a superior protection to detect and defend against pathogens that became more elusive and/or virulent to the host that had only innate immune system. First, this line of thought implies that adaptive immune system was a new, more sophisticated layer of host defense that operated independently of the innate immune system. Second, the natural consequence of this scenario would be that pathogens would have exercised so strong an evolutionary pressure that eventually no host could have afforded not to have an adaptive immune system. Neither of these arguments is supported by the facts. First, new experimental evidence has firmly established that operation of adaptive immune system is critically dependent on the ability of the innate immune system to detect invader-pathogens and second, the absolute majority of animal kingdom survives just fine with only an innate immune system. Thus, these data raise the dilemma: If innate immune system was sufficient to detect and protect against pathogens, why then did adaptive immune system develop in the first place? In contrast to the innate immune system, the adaptive immune system has one important advantage, precision. By precision I mean the ability of the defense system to detect and remove the target, for example, infected cells, without causing unwanted bystander damage of surrounding tissue. While the target precision per se is not important for short-term immune response, it becomes a critical factor when the immune response is long-lasting, as during chronic infection. In this paper I would like to propose new, "toxic index" hypothesis where I argue that the need to reduce the collateral damage to the tissue during chronic infection(s) was the evolutionary pressure that led to the development of the adaptive immune system. (C) 2010 Elsevier Ltd. All rights reserved. C1 NIAID, Cell Tolerance & Memory Sect T, Ghost Lab, LCMI,NIH, Bethesda, MD 20892 USA. RP Usharauli, D (reprint author), NIAID, Cell Tolerance & Memory Sect T, Ghost Lab, LCMI,NIH, Bldg 4,Room 111,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dusharauli@gmail.com FU Division of intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX I would like to thank Tirumalai Kamala for expert editorial assistance. This work was supported by the Division of intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 21 TC 5 Z9 5 U1 0 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD AUG PY 2010 VL 75 IS 2 BP 241 EP 243 DI 10.1016/j.mehy.2010.02.031 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 638ZM UT WOS:000280940600022 PM 20299160 ER PT J AU Simitsopoulou, M Georgiadou, E Walsh, TJ Roilides, E AF Simitsopoulou, Maria Georgiadou, Elpiniki Walsh, Thomas J. Roilides, Emmanuel TI Cunninghamella bertholletiae exhibits increased resistance to human neutrophils with or without antifungal agents as compared to Rhizopus spp. SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy/46th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25, 2008 CL Washington, DC SP Infect Dis Soc Amer DE Zygomycetes; antifungal agents; human neutrophils; cytokines ID ASPERGILLUS-FUMIGATUS; ZYGOMYCOSIS; POLYMORPHONUCLEAR; EPIDEMIOLOGY AB Among Zygomycetes, Cunninghamella bertholletiae occurs less frequently as the etiologic agent of human disease but causes more aggressive, refractory, and fatal infections despite antifungal therapy. Little is known about the differential innate host response against Cunninghamella and other Zygomycetes in the presence of antifungal agents. We therefore studied the activity of human neutrophils (PMNs) alone or in combination with caspofungin, posaconazole (PSC), and voriconazole (VRC) against hyphae of Rhizopus oryzae, Rhizopus microsporus and C. bertholletiae. Hyphal damage was measured by XTT metabolic assay and release of IL-6, IL-8 and TNF-alpha from PMNs by ELISA. Cunninghamella bertholletiae was more resistant to PMN-induced hyphal damage than either Rhizopus spp. at effector: target (E:T) ratios of 1:1, 5:1 and 10:1 (P < 0.05). The hyphal damage caused by caspofungin at 0.1 mu g/ml or PSC and VRC at 0.5 mu g/ml with C. bertholletiae and R. oryzae and by caspofungin against R. microsporus ranged from 18-29%. The PMN-induced hyphal damage was not modulated by combination with antifungal agents. Cunninghamella bertholletiae induced significantly decreased IL-8 (P < 0.05), but increased TNF-alpha release from PMNs compared to both Rhizopus spp. (P < 0.01). No IL-6 was released from PMNs exposed to the three Zygomycetes. In comparison to R. oryzae and R. microsporus, C. bertholletiae is more resistant to PMN-induced hyphal damage with or without antifungal therapy and is more capable of suppressing release of IL-8. C1 [Simitsopoulou, Maria; Georgiadou, Elpiniki; Roilides, Emmanuel] Aristotle Univ Thessaloniki, Hippokrat Hosp, Infect Dis Lab, Dept Pediat 3, GR-54642 Thessaloniki, Greece. [Walsh, Thomas J.; Roilides, Emmanuel] Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD USA. RP Roilides, E (reprint author), Aristotle Univ Thessaloniki, Hippokrat Hosp, Infect Dis Lab, Dept Pediat 3, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece. EM roilides@med.auth.gr NR 15 TC 11 Z9 11 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD AUG PY 2010 VL 48 IS 5 BP 720 EP 724 DI 10.3109/13693780903476635 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 636AU UT WOS:000280700800006 PM 20100138 ER PT J AU Davis, JL Ripley, RT Frankel, TL Maric, I Lozier, JN Rosenberg, SA AF Davis, Jeremy L. Ripley, R. Taylor Frankel, Timothy L. Maric, Irina Lozier, Jay N. Rosenberg, Steven A. TI Paraneoplastic granulocytosis in metastatic melanoma SO MELANOMA RESEARCH LA English DT Article DE granulocyte colony-stimulating factor; melanoma; paraneoplastic syndromes ID COLONY-STIMULATING FACTOR; MALIGNANT-MELANOMA; LEUKEMOID REACTION; SYSTEMIC CHEMOTHERAPY; COMPLETE RESPONSES; PROGNOSTIC FACTORS; CELL-LINE; CANCER; CARCINOMA; MECHANISM AB Paraneoplastic syndromes are an uncommon, yet well-described, phenomenon in cancer patients. The syndrome of granulocytosis caused by granulocyte colony-stimulating factor (G-CSF) production by tumors is rare and is difficult to diagnose in patients receiving treatment for metastatic disease. From January 2005 to May 2009, 626 patients were evaluated for treatment of metastatic melanoma. At initial evaluation or during the course of treatment, six patients had an elevated white blood cell count and no evidence of infection. All six had significantly elevated serum G-CSF. The level of serum G-CSF was directly correlated with the absolute neutrophil count. In-vitro assay of melanoma tumor from two patients showed elevated G-CSF in cell culture supernatant. The paraneoplastic syndrome of granulocytosis resulting from ectopic G-CSF production in patients with metastatic melanoma is rare. This diagnosis should be considered when common causes of granulocytosis have been ruled out. Melanoma Res 20: 326-329 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Maric, Irina; Lozier, Jay N.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr,3W-3940,MSC 1201, Bethesda, MD 20892 USA. EM sar@nih.gov FU Intramural NIH HHS [Z01 SC003811-33] NR 27 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD AUG PY 2010 VL 20 IS 4 BP 326 EP 329 DI 10.1097/CMR.0b013e328339da1e PG 4 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 622IT UT WOS:000279656300009 PM 20440226 ER PT J AU Eichhoff, OM Zipser, MC Xu, M Weeraratna, AT Mihic, D Dummer, R Hoek, KS AF Eichhoff, Ossia M. Zipser, Marie C. Xu, Mai Weeraratna, Ashani T. Mihic, Daniela Dummer, Reinhard Hoek, Keith S. TI The immunohistochemistry of invasive and proliferative phenotype switching in melanoma: a case report SO MELANOMA RESEARCH LA English DT Article DE immunohistochemistry; melanoma; phenotype switching ID MAST-CELLS; EXPRESSION; MITF; GALLBLADDER; MELANOCYTES; PROTEINS; DISEASE; TARGETS; WNT5A AB To date there is no effective therapy for metastatic melanoma and at the molecular level the disease progression is poorly understood. A recent study by our group led to the development of a novel phenotype switching model for melanoma progression, wherein cells transition back-and-forth between states of proliferation and invasion to drive disease progression. To explore the model's clinical relevance we interrogated phenotype-specific expression patterns in human melanoma patient material. A matched primary/metastasis pair from a human melanoma patient was obtained and immunohistochemically stained for proliferative and invasive phenotype markers. These were also stained for hypoxia and blood vessel markers. Proliferative phenotype markers Melan-A and Mitf showed consistent anti-correlation with invasive phenotype marker Wnt5A and hypoxia marker Glut-1. These also correlated with observed intra-tumoural vascularization patterns. Similar pattern distributions were present in both primary and metastasis samples. Strikingly, we observed that late phase metastatic melanoma cells adopt morphologies and behaviours identical to very early phase cells. The expression patterns observed closely matched expectations derived from previous in vitro and xenografting experiments. These results highlight the likelihood that disease progression involves melanoma cells retaining the capacity to regulate the expression of metastatic potential critical factors according to changing microenvironmental conditions. Melanoma Res 20: 349-355 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Eichhoff, Ossia M.; Zipser, Marie C.; Dummer, Reinhard; Hoek, Keith S.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Mihic, Daniela] Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. [Xu, Mai; Weeraratna, Ashani T.] NIA, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Hoek, KS (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. EM keith.hoek@usz.ch FU Krebsliga-Oncosuisse; Julia Bangerter Rhyner Stiftung; National Institute on Aging, Baltimore, MD FX This study was supported by grants from Krebsliga-Oncosuisse (Keith Sean Hoek), the Julia Bangerter Rhyner Stiftung (Reinhard Dummer) and the Intramural Research Program of the National Institute on Aging, Baltimore, MD (Ashani T. Weeraratna). NR 22 TC 19 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD AUG PY 2010 VL 20 IS 4 BP 349 EP 355 DI 10.1097/CMR.0b013e32833bd89e PG 7 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 622IT UT WOS:000279656300013 PM 20526217 ER PT J AU Peterson, MJ Morey, MC Giuliani, C Pieper, CF Evenson, KR Mercer, V Visser, M Brach, JS Kritchevsky, SB Goodpaster, BH Rubin, S Satterfield, S Simonsick, EM AF Peterson, Matthew J. Morey, Miriam C. Giuliani, Carol Pieper, Carl F. Evenson, Kelly R. Mercer, Vicki Visser, Marjolein Brach, Jennifer S. Kritchevsky, Stephen B. Goodpaster, Bret H. Rubin, Susan Satterfield, Suzanne Simonsick, Eleanor M. CA Hlth ABC Study TI Walking in Old Age and Development of Metabolic Syndrome: The Health, Aging, and Body Composition Study SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article ID OF-SPORTS-MEDICINE; LIFE-STYLE FACTORS; PHYSICAL-ACTIVITY; PUBLIC-HEALTH; ADULTS; RECOMMENDATION; DISEASE; OBESE AB Background: The specific health benefits of meeting physical activity guidelines are unclear in older adults. We examined the association between meeting, not meeting, or change in status of meeting physical activity guidelines through walking and the 5-year incidence of metabolic syndrome in older adults. Methods: A total of 1,863 Health, Aging, and Body Composition (Health ABC) Study participants aged 70-79 were followed for 5 years (1997-1998 to 2002-2003). Four walking groups were created based on self-report during years 1 and 6: Sustained low (Year 1, <150 min/week, and year 6, <150 min/week), decreased (year 1, >150 min/week, and year 6, <150 min/week), increased (year 1, <150 min/week, and year 6, >150 min/week), and sustained high (year 1, >150 min/week, and year 6, >150 min/week). Based on the Adult Treatment Panel III (ATP III) panel guidelines, the metabolic syndrome criterion was having three of five factors: Large waist circumference, elevated blood pressure, triglycerides, blood glucose, and low high-density lipoprotein (HDL) levels. Results: Compared to the sustained low group, the sustained high group had a 39% reduction in odds of incident metabolic syndrome [adjusted odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.40-0.93], and a significantly lower likelihood of developing the number of metabolic syndrome risk factors that the sustained low group developed over 5 years (beta = -0.16, P = 0.04). Conclusions: Meeting or exceeding the physical activity guidelines via walking significantly reduced the odds of incident metabolic syndrome and onset of new metabolic syndrome components in older adults. This protective association was found only in individuals who sustained high levels of walking for physical activity. C1 [Peterson, Matthew J.; Morey, Miriam C.; Pieper, Carl F.] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. [Peterson, Matthew J.; Giuliani, Carol; Mercer, Vicki] Univ N Carolina, Curriculum Human Movement Sci, Sch Publ Hlth, Chapel Hill, NC USA. [Evenson, Kelly R.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Peterson, Matthew J.; Morey, Miriam C.; Pieper, Carl F.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA. [Peterson, Matthew J.; Morey, Miriam C.; Pieper, Carl F.] Duke Univ, Older Amer Independence Ctr, Durham, NC USA. [Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. [Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Goodpaster, Bret H.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Rubin, Susan] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Simonsick, Eleanor M.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. RP Peterson, MJ (reprint author), Durham VA Med Ctr, GRECC 182,508 Fulton St, Durham, NC 27705 USA. EM peter076@mc.duke.edu OI Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institutes of Health (NIH), National Institute of Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, AG-028716] FX This research was supported in part by the Intramural Research program of the National Institutes of Health (NIH), National Institute of Aging, contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, and AG-028716. NR 19 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD AUG PY 2010 VL 8 IS 4 BP 317 EP 322 DI 10.1089/met.2009.0090 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 637GA UT WOS:000280803500004 PM 20367219 ER PT J AU Fornage, M Papanicolaou, G Lewis, CE Boerwinkle, E Siscovick, DS AF Fornage, Myriam Papanicolaou, George Lewis, Cora E. Boerwinkle, Eric Siscovick, David S. TI Common INSIG2 polymorphisms are associated with age-related changes in body size and high-density lipoprotein cholesterol from young adulthood to middle age SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID GENETIC VARIANT; HAPLOTYPE MAP; OBESITY; BINDING; GENOME; DEGRADATION; EXPRESSION; PROTEIN; COHORTS; TRAITS AB Insulin-induced gene 2 (INSIG2) plays an important role in the regulation of cholesterol and fatty acids synthesis. A polymorphism, rs7566605, located 10 kilobases upstream of the INSIG2 gene, was identified in a genomewide association study of obesity. We conducted an association study of 12 INSIG2 tag single nucleotide polymorphisms with longitudinal measures of body size (body mass index and waist circumference) and lipid metabolism (plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides levels). We investigated their interaction with age in 4304 Coronary Artery Risk Development in Young Adults participants (49.5% blacks, 50.5% whites) followed prospectively for 20 years. rs7566605 was not associated with variation in body size or lipid metabolism at any age in either racial group. However, rs1352083 and rs10185316 were associated with age-related decline in high-density lipoprotein cholesterol in whites (P = .0005 and .04, respectively). A similar trend was observed in blacks who consistently maintained a body mass index less than 25 kg/m(2) over the study period. These data support a role of INSIG2 sequence variation in the regulation of cholesterol metabolism. (C) 2010 Elsevier Inc. All rights reserved. C1 [Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77225 USA. [Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Sch Publ Hlth, Houston, TX USA. [Papanicolaou, George] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lewis, Cora E.] Univ Alabama, Div Prevent Med, Dept Med, Birmingham, AL USA. [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. RP Fornage, M (reprint author), Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77225 USA. EM myriam.fornage@uth.tmc.edu FU National Heart, Lung, and Blood Institute [R01-HL69126, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095] FX This study is supported by grant R01-HL69126 to MF and by contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC-95095 from the National Heart, Lung, and Blood Institute to the CARDIA investigators. The authors thank the staff and participants of the CARDIA study for their important contributions. NR 29 TC 10 Z9 12 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2010 VL 59 IS 8 BP 1084 EP 1091 DI 10.1016/j.metabol.2009.11.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635PZ UT WOS:000280669900004 PM 20045156 ER PT J AU Matthews, CE Sui, XM LaMonte, MJ Adams, SA Hebert, JR Blair, SN AF Matthews, Charles E. Sui, Xuemei LaMonte, Michael J. Adams, Swann A. Hebert, James R. Blair, Steven N. TI Metabolic syndrome and risk of death from cancers of the digestive system SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CARDIOVASCULAR-DISEASE MORTALITY; INSULIN-RESISTANCE SYNDROME; ALL-CAUSE MORTALITY; BODY-MASS INDEX; CARDIORESPIRATORY FITNESS; PHYSICAL-ACTIVITY; COLORECTAL-CANCER; BARRETTS-ESOPHAGUS; PANCREATIC-CANCER; UNITED-STATES AB We tested the hypothesis that risk of early mortality from cancers of the digestive system will be greater in men with, compared with men without, the metabolic syndrome (MetS). Participants were 33 230 men who were seen at the Cooper Clinic in Dallas, TX, and followed for 14.4 (SD = 7.0) years. Metabolic syndrome was defined as having at least 3 of the following risk factors: abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, or high fasting glucose level or diabetes. Metabolic syndrome was associated with higher mortality (hazard ratio [HR] = 1.90 [95% confidence interval = 1.42-2.55]), and there was a graded positive association for the addition of more syndrome components (P < .01). Adjustment for cardiorespiratory fitness attenuated the risk estimates by 20% to 30%, but they remained significant after this adjustment. Evaluation of the independent contribution of each of the syndrome components revealed that both abdominal obesity (HR = 1.89 [1.36-2.62]) and high glucose (HR = 1.38 [1.02-1.87]) were independently associated with cancer mortality. Our results support the hypothesis that metabolic syndrome is positively associated with mortality from cancers of the digestive system. Interventions that reduce abnormalities associated with the syndrome could reduce risk of premature death from these cancers. Published by Elsevier Inc. C1 [Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD 20892 USA. [Sui, Xuemei; Blair, Steven N.] Univ S Carolina, Dept Exercise Sci, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [LaMonte, Michael J.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY USA. [Adams, Swann A.; Hebert, James R.; Blair, Steven N.] Univ S Carolina, Dept Epidemiol & Biostat, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Adams, Swann A.; Hebert, James R.] Univ S Carolina, Canc Prevent & Control Program, Columbia, SC 29208 USA. RP Matthews, CE (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD 20892 USA. EM charles.matthews2@nih.gov RI Arp Adams, Swann/C-7337-2015; matthews, Charles/E-8073-2015 OI Arp Adams, Swann/0000-0001-5779-6802; matthews, Charles/0000-0001-8037-3103 FU National Institute of Health [AG06945, HL62508]; Coca-Cola company FX Supported by National Institute of Health grants AG06945 and HL62508 and supported in part by an unrestricted research grant from The Coca-Cola company. NR 53 TC 22 Z9 24 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2010 VL 59 IS 8 BP 1231 EP 1239 DI 10.1016/j.metabol.2009.11.019 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635PZ UT WOS:000280669900019 PM 20045534 ER PT J AU Copeland, WC AF Copeland, William C. TI Understanding heterogeneous diseases in mtDNA maintenance Introduction SO METHODS LA English DT Editorial Material C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD AUG PY 2010 VL 51 IS 4 BP 363 EP 363 DI 10.1016/j.ymeth.2010.07.008 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 640KK UT WOS:000281049900001 PM 20682411 ER PT J AU Kasiviswanathan, R Longley, MJ Young, MJ Copeland, WC AF Kasiviswanathan, Rajesh Longley, Matthew J. Young, Matthew J. Copeland, William C. TI Purification and functional characterization of human mitochondrial DNA polymerase gamma harboring disease mutations SO METHODS LA English DT Article DE Mitochondrial DNA; DNA polymerase gamma; p55 accessory subunit; Alpers syndrome; Progressive external ophthalmoplegia ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; ACCESSORY SUBUNIT; W748S MUTATION; REPLICATION; DEFECTS AB More than 150 different point mutations in POLG, the gene encoding the human mitochondrial DNA polymerase gamma (pol gamma), cause a broad spectrum of childhood and adult onset diseases like Alpers syndrome, ataxia-neuropathy syndrome and progressive external ophthalmoplegia. These disease mutations can affect the pot gamma enzyme's properties in numerous ways, thus potentially influencing the severity of the disease. Hence, a detailed characterization of disease mutants will greatly assist researchers and clinicians to develop a clear understanding of the functional defects caused by these mutant enzymes. Experimental approaches for characterizing the wild-type (WT) and mutant pot gamma enzymes are extensively described in this manuscript. The methods start with construction and purification of the recombinant wild-type and mutant forms of pot gamma protein, followed by assays to determine its structural integrity and thermal stability. Next, the biochemical characterization of these enzymes is described in detail, which includes measuring the purified enzyme's catalytic activity, its steady-state kinetic parameters and DNA binding activity, and determining the physical and functional interaction of these pot gamma proteins with the p55 accessory subunit. Published by Elsevier Inc. C1 [Kasiviswanathan, Rajesh; Longley, Matthew J.; Young, Matthew J.; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr,Bldg 101,Rm E316, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov RI Kasiviswanathan, Rajesh/D-2744-2012 FU NIEHS FX The authors would like to thank Drs. Deepti Dwivedi and Rajendra Prasad for critical reading of this manuscript. This work was supported by the NIEHS Intramural Research Program. NR 19 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD AUG PY 2010 VL 51 IS 4 BP 379 EP 384 DI 10.1016/j.ymeth.2010.02.015 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 640KK UT WOS:000281049900004 PM 20176107 ER PT J AU Maynard, S de Souza-Pinto, NC Scheibye-Knudsen, M Bohr, VA AF Maynard, Scott de Souza-Pinto, Nadja C. Scheibye-Knudsen, Morten Bohr, Vilhelm A. TI Mitochondrial base excision repair assays SO METHODS LA English DT Review DE Mitochondria; Base excision repair; Incision activity; Reactive oxygen species ID OXIDATIVE DNA-DAMAGE; MAMMALIAN-CELLS; SKELETAL-MUSCLE; INNER MEMBRANE; LYASE ACTIVITY; ANIMAL-CELLS; RAT-LIVER; NUCLEAR; GENE; 8-OXOGUANINE AB The main source of mitochondrial DNA (mtDNA) damage is reactive oxygen species (ROS) generated during normal cellular metabolism. The main mtDNA lesions generated by ROS are base modifications, such as the ubiquitous 8-oxoguanine (8-oxoG) lesion; however, base loss and strand breaks may also occur. Many human diseases are associated with mtDNA mutations and thus maintaining mtDNA integrity is critical. All of these lesions are repaired primarily by the base excision repair (BER) pathway. It is now known that mammalian mitochondria have BER, which, similarly to nuclear BER, is catalyzed by DNA glycosylases, AP endonuclease, DNA polymerase (POL gamma in mitochondria) and DNA ligase. This article outlines procedures for measuring oxidative damage formation and BER in mitochondria, including isolation of mitochondria from tissues and cells, protocols for measuring BER enzyme activities, gene-specific repair assays, chromatographic techniques as well as current optimizations for detecting 8-oxoG lesions in cells by immunofluorescence. Throughout the assay descriptions we will include methodological considerations that may help optimize the assays in terms of resolution and repeatability. Published by Elsevier Inc. C1 [Maynard, Scott; Scheibye-Knudsen, Morten; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21236 USA. [de Souza-Pinto, Nadja C.] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, Brazil. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21236 USA. EM BohrV@grc.nia.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; Maynard, Scott/0000-0001-5625-936X; Scheibye-Knudsen, Morten/0000-0002-6637-1280 FU National Institute of Health, National Institute on Aging FX We thank Drs. Chandrika Canugovi and Mahesh Ramamoorthy for editing the paper. Support was provided by funds from the National Institute of Health, National Institute on Aging Intramural Research Program. NR 101 TC 23 Z9 23 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 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD AUG PY 2010 VL 51 IS 4 BP 416 EP 425 DI 10.1016/j.ymeth.2010.02.020 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 640KK UT WOS:000281049900010 PM 20188838 ER PT J AU Roffe, E Oliveira, F Souza, ALS Pinho, V Souza, DG Souza, PRS Russo, RC Santiago, HC Romanha, AJ Tanowitz, HB Valenzuela, JG Teixeira, MM AF Roffe, Ester Oliveira, Fabiano Souza, Adriano L. S. Pinho, Vanessa Souza, Danielle G. Souza, Patricia R. S. Russo, Remo C. Santiago, Helton C. Romanha, Alvaro J. Tanowitz, Herbert B. Valenzuela, Jesus G. Teixeira, Mauro M. TI Role of CCL3/MIP-1 alpha and CCL5/RANTES during acute Trypanosoma cruzi infection in rats SO MICROBES AND INFECTION LA English DT Article DE Chemokines; CCR5; Trypanosoma cruzi; Myocarditis ID INFLAMMATION FOLLOWING INFECTION; CARDIAC INFLAMMATION; CHEMOKINE RECEPTORS; CHAGAS-DISEASE; T-CELLS; MYOCARDITIS; MICE; CONTRIBUTE; PROMOTE; LESIONS AB Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-gamma production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T cruzi infection. These data reinforce the important role of chemolcines during T cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection. (c) 2010 Elsevier Masson SAS. All rights reserved. C1 [Roffe, Ester; Souza, Adriano L. S.; Pinho, Vanessa; Souza, Danielle G.; Souza, Patricia R. S.; Russo, Remo C.; Santiago, Helton C.; Teixeira, Mauro M.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil. [Oliveira, Fabiano; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD USA. [Romanha, Alvaro J.] Fiocruz MS, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. [Tanowitz, Herbert B.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. RP Roffe, E (reprint author), 9000 Rockville Pike,MSC-1886,Bldg 10,Room 11N07, Bethesda, MD 20892 USA. EM roffeest@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; Santiago, Helton/F-8704-2012; Roffe, Ester/H-4688-2012; Vacinas, Inct/J-9431-2013; souza, danielle/D-3378-2014; Russo, Remo/F-9048-2010 OI Oliveira, Fabiano/0000-0002-7924-8038; Santiago, Helton/0000-0002-5695-8256; Russo, Remo/0000-0002-1715-3834 FU Conselho Nacional de Pesquisa (CNPq, Brazil); Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil); NIH/FIRCA, USA [1 R03-TW006857-01A1]; NIH, USA [AI-076248] FX This work was supported by Conselho Nacional de Pesquisa (CNPq, Brazil), Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil), Fogarty International Research Collaboration Award (NIH/FIRCA, 1 R03-TW006857-01A1, USA), and NIH (AI-076248, USA). NR 28 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD AUG PY 2010 VL 12 IS 8-9 BP 669 EP 676 DI 10.1016/j.micinf.2010.04.011 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 636YG UT WOS:000280780100010 PM 20452453 ER PT J AU Panepinto, JC Misener, AL Oliver, BG Hu, GW Park, YD Shin, S White, TC Williamson, PR AF Panepinto, John C. Misener, Amanda L. Oliver, Brian G. Hu, Guowu Park, Yoon Dong Shin, Soowan White, Theodore C. Williamson, Peter R. TI Overexpression of TUF1 restores respiratory growth and fluconazole sensitivity to a Cryptococcus neoformans vad1 Delta mutant SO MICROBIOLOGY-SGM LA English DT Article ID ELONGATION-FACTOR TU; CRYPTOCOCCUS-NEOFORMANS; MITOCHONDRIAL TRANSLATION; TRANSPLANT RECIPIENTS; IMMUNE RECONSTITUTION; CANDIDA-ALBICANS; FISSION YEAST; SUSCEPTIBILITY; VIRULENCE; MENINGITIS AB The yeast-like fungus Cryptococcus neoformans favours respiration as a mechanism of energy production, and thus depends heavily on mitochondria! function. Previous studies of a C neoformans vad1 Delta mutant revealed reduced expression of the mitochondrial elongation factor TUF1 and defects in glycerol utilization, consistent with mitochondrial dysfunction In this study, we found that in trans expression of TUF1 in the vad1 Delta mutant suppressed the mitochondrial defects, including growth on respiration-dependent carbon sources and fluconazole resistance, associated with VAD1 deletion Tetracycline, an inhibitor of mitochondrial translation, was found to confer resistance to fluconazole in the wild-type and vad1 Delta mutant, whereas the fluconazole susceptibility of the TUF1-overexpressing strain was unaffected by tetracycline treatment In the presence of fluconazole, the vad1 Delta mutant exhibited increased activation of the global transcriptional regulator Sre1 TUF1 overexpression failed to alter cleavage of Sre1 in response to fluconazole in the vad1 Delta mutant, suggesting that TUF1 repression in the vad1 Delta mutant is distal to Sre1, or that it occurs through an independent pathway. C1 [Panepinto, John C.; Misener, Amanda L.] SUNY Buffalo, Dept Microbiol & Immunol, Witebsky Ctr Microbial Pathogenesis & Immunol, Buffalo, NY 14260 USA. [Oliver, Brian G.; White, Theodore C.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Hu, Guowu; Park, Yoon Dong; Shin, Soowan; Williamson, Peter R.] Univ Illinois, Infect Dis Sect, Chicago, IL USA. [Williamson, Peter R.] NIAID, Sect Translat Mycol, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Panepinto, JC (reprint author), SUNY Buffalo, Dept Microbiol & Immunol, Witebsky Ctr Microbial Pathogenesis & Immunol, Buffalo, NY 14260 USA. FU Public Health Service [AI45995] FX This work was supported by Public Health Service Grant AI45995 to P R w NR 21 TC 1 Z9 1 U1 1 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 AUG PY 2010 VL 156 BP 2558 EP 2565 DI 10.1099/mic.0.035923-0 PN 8 PG 8 WC Microbiology SC Microbiology GA 642TA UT WOS:000281239600028 PM 20430817 ER PT J AU Li, M Mazilu, D Horvath, KA AF Li, M. Mazilu, D. Horvath, K. A. TI Computer aided minimally invasive cardiac procedures SO MINERVA CHIRURGICA LA English DT Article DE Cardiac surgical procedures; Surgical procedures, minimally invasive; Thoracic surgery ID MITRAL-VALVE REPAIR; BEATING-HEART-SURGERY; ATRIAL-FIBRILLATION ABLATION; CORONARY-ARTERY-BYPASS; X-RAY FLUOROSCOPY; CARDIOPULMONARY BYPASS; ROBOTIC ASSISTANCE; CATHETER ABLATION; MULTICENTER TRIAL; PORT PLACEMENT AB Minimally invasive cardiac procedures have been investigated to reduce the risks associated with open heart surgery. With the assistance of improvements in engineering technologies such as medical imaging, surgical navigation, and robotic devices, more cardiac surgeries can be performed in a minimally invasive fashion. We have surveyed these state-of-the-art engineering technologies and the minimally invasive cardiac procedures that are benefited from these technologies. C1 [Li, M.; Mazilu, D.; Horvath, K. A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RP Horvath, KA (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, 10 Ctr Dr MSC 1550 10-131047, Bethesda, MD 20892 USA. EM khorvath@nih.gov NR 75 TC 0 Z9 0 U1 0 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0026-4733 EI 1827-1626 J9 MINERVA CHIR JI Minerva Chir. PD AUG PY 2010 VL 65 IS 4 BP 439 EP 450 PG 12 WC Surgery SC Surgery GA 658BX UT WOS:000282465000004 PM 20802432 ER PT J AU Kotarsky, H Karikoski, R Morgelin, M Marjavaara, S Bergman, P Zhang, DL Smet, J van Coster, R Fellman, V AF Kotarsky, Heike Karikoski, Riitta Morgelin, Matthias Marjavaara, Sanna Bergman, Petra Zhang, De-Liang Smet, Joel van Coster, Rudy Fellman, Vineta TI Characterization of complex III deficiency and liver dysfunction in GRACILE syndrome caused by a BCS1L mutation SO MITOCHONDRION LA English DT Article DE Mitochondria; Rieske FeS protein; Core I; Hemochromatosis; Ceruloplasmin; Fellman syndrome ID MITOCHONDRIAL RESPIRATORY-CHAIN; FETAL-GROWTH-RETARDATION; HYPOXIA-INDUCIBLE FACTOR; POLYACRYLAMIDE-GEL ELECTROPHORESIS; BLUE-NATIVE-ELECTROPHORESIS; LETHAL METABOLIC-DISORDER; CYTOCHROME BC(1) COMPLEX; OXIDATIVE-PHOSPHORYLATION; LACTIC-ACIDOSIS; IRON-OVERLOAD AB A homozygous mutation in the complex III chaperone BCS1L causes GRACILE syndrome (intrauterine growth restriction, aminoaciduria, cholestasis, hepatic iron overload, lactacidosis). In control and patient fibroblasts we localized BCS1L in inner mitochondria' membranes. In patient liver, kidney, and heart BCS1L and Rieske protein levels, as well as the amount and activity of complex Ill, were decreased. Major histopathology was found in kidney and liver with cirrhosis and iron deposition, but of iron-related proteins only ferritin levels were high. In placenta from a GRACILE fetus, the ferrooxidases ceruloplasmin and hephaestin were upregulated suggesting association between iron overload and placental dysfunction. (C) 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Kotarsky, Heike] Lund Univ, Dept Pediat, BMC, S-22184 Lund, Sweden. [Karikoski, Riitta] Helsinki Univ Hosp, Diagnost Lab, Cent Pathol Lab, Helsinki, Finland. [Morgelin, Matthias] Lund Univ, Div Infect Med, Lund, Sweden. [Marjavaara, Sanna] Univ Helsinki, Helsinki, Finland. [Zhang, De-Liang] NICHHD, Program Mol Med, NIH, Bethesda, MD 20892 USA. [Smet, Joel; van Coster, Rudy] Ghent Univ Hosp, Dept Pediat, Div Pediat Neurol & Metabolism, Ghent, Belgium. [Fellman, Vineta] Univ Helsinki, Dept Pediat, Helsinki, Finland. RP Kotarsky, H (reprint author), Lund Univ, Dept Pediat, BMC, C14,Tornavagen 10, S-22184 Lund, Sweden. EM Heike.Kotarsky@med.lu.se; Riitta.Karikoski@hus.fi; Matthias.Morgelin@med.lu.se; Sanna.Marjavaara@helsinki.fi; Petra.Bergman@gmail.com; zhangdel@mail.nih.gov; Joel.Smet@ugent.be; Rudy.vanCoster@ugent.be; Vineta.Fellman@med.lu.se RI Smet, Joel/B-7428-2013; Zhang, Deliang/F-7848-2013; OI Smet, Joel/0000-0002-9551-6282; Zhang, Deliang/0000-0001-9478-5344 FU Royal Physiographic Society in Lund; Medical Society of Finland; Swedish Research Council; Lund University FX This study was supported by grants from the Royal Physiographic Society in Lund, the Medical Society of Finland (Finska Lakaresallskapet), the Swedish Research Council, and Lund University. We are most grateful to the patient families for their participation in this study. We thank Theresa Powel and Stefan Hansson for their gift of placental control RNA extracts and Pierre Rustin for the measurement of liver CIII activity. Leena Peltonen is acknowledged for the kind gift of reagent. Eskil Elmer is acknowledged for introduction into the OROBOROS equipment and Alexandra Utz for help with BNP. Eva Hanson, Maria Baumgarten and Rita Wallen are gratefully acknowledged for expert technical assistance. Furthermore, we thank Tracy Rouault, and Anu Wartiovaara for fruitful discussions of the project. NR 68 TC 18 Z9 21 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD AUG PY 2010 VL 10 IS 5 BP 497 EP 509 DI 10.1016/j.mito.2010.05.009 PG 13 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 640LA UT WOS:000281051500012 PM 20580947 ER PT J AU Shaughnessy, DT Worth, L Lawler, CP McAllister, KA Longley, MJ Copeland, WC AF Shaughnessy, Daniel T. Worth, Leroy, Jr. Lawler, Cindy P. McAllister, Kimberly A. Longley, Matthew J. Copeland, William C. TI Meeting report: Identification of biomarkers for early detection of mitochondrial dysfunction SO MITOCHONDRION LA English DT Letter C1 [Shaughnessy, Daniel T.; Worth, Leroy, Jr.; Lawler, Cindy P.; McAllister, Kimberly A.] NIEHS, Div Extramural Res & Training, NIH, Res Triangle Pk, NC 27709 USA. [Longley, Matthew J.; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Shaughnessy, DT (reprint author), NIEHS, Div Extramural Res & Training, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM shaughn1@niehs.nih.gov NR 0 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD AUG PY 2010 VL 10 IS 5 BP 579 EP 581 DI 10.1016/j.mito.2010.02.001 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 640LA UT WOS:000281051500023 PM 20197119 ER PT J AU Shakarian, AM McGugan, GC Joshi, MB Stromberg, M Bowers, L Ganim, C Barowski, J Dwyer, DM AF Shakarian, Alison M. McGugan, Glen C. Joshi, Manju B. Stromberg, Mary Bowers, Lauren Ganim, Christine Barowski, Jessica Dwyer, Dennis M. TI Identification, characterization, and expression of a unique secretory lipase from the human pathogen Leishmania donovani SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Leishmania; Human parasite; Gene structure; Trypanosomatid; Kinetoplastid protozoan; Lipase ID SURFACE-MEMBRANE; FUNCTIONAL DOMAINS; GENE; AMASTIGOTES; MEXICANA; METABOLISM; MACROPHAGE; PROMASTIGOTES; TRANSCRIPTION; TRYPANOSOMA AB Lipases have been implicated to be of importance in the life cycle development, virulence, and transmission of a variety of parasitic organisms. Potential functions include the acquisition of host resources for energy metabolism and as simple building blocks for the synthesis of complex parasite lipids important for membrane remodeling and structural purposes. Using a molecular approach, we identified and characterized the structure of an LdLip3-lipase gene from the primitive trypanosomatid pathogen of humans, Leishmania donovani. The LdLip3 encodes a similar to 33 kDa protein, with a well-conserved substrate-binding and catalytic domains characteristic of members of the serine lipase-protein family. Further, we showed that LdLip3 mRNA is constitutively expressed by both the insect vector (i.e., promastigote) and mammalian (i.e., amastigote) life cycle developmental forms of this protozoan parasite. Moreover, a homologous episomal expression system was used to express an HA epitope-tagged LdLip3 chimeric construct (LdLip3::HA) in these parasites. Expression of the LdLip3 chimera was verified in these transfectants by Western blots and indirect immuno-fluorescence analyses. Results of coupled immuno-affinity purification and enzyme activity experiments demonstrated that the LdLip3::HA chimeric protein was secreted/released by transfected L. donovani parasites and that it possessed functional lipase enzyme activity. Taken together these observations suggest that this novel secretory lipase might play essential role(s) in the survival, growth, and development of this important group of human pathogens. C1 [Shakarian, Alison M.; Stromberg, Mary; Bowers, Lauren; Ganim, Christine; Barowski, Jessica] Salve Regina Univ, Dept Biol & Biomed Sci, Newport, RI 02840 USA. [McGugan, Glen C.; Joshi, Manju B.; Dwyer, Dennis M.] NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Shakarian, AM (reprint author), Salve Regina Univ, Dept Biol & Biomed Sci, Newport, RI 02840 USA. EM shakaria@salve.edu FU NCRR, NIH [P20RR016457]; Division of Intramural Research, NIAID, NIH; Intramural Research Training Award at LPD/NIAID/NIH FX Dr. Alison Shakarian was supported in part by RI-INBRE Grant # P20RR016457 from the NCRR, NIH. This study was supported in part by the Intramural Research Program of the Division of Intramural Research, NIAID, NIH. Dr. Glen McGugan was supported by an Intramural Research Training Award at LPD/NIAID/NIH. We thank Dr. Greg Matlashewski (McGill University) for providing the pKSNEO leishmanial expression vector. The contents of this document are solely the responsibility of the authors and do not necessarily represent the official views of NCRR, or NIH. NR 49 TC 3 Z9 4 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD AUG PY 2010 VL 341 IS 1-2 BP 17 EP 31 DI 10.1007/s11010-010-0433-6 PG 15 WC Cell Biology SC Cell Biology GA 630KE UT WOS:000280271100003 PM 20349119 ER PT J AU Chang, N Yi, J Guo, GE Liu, XW Shang, YF Tong, TJ Cui, QH Zhan, M Gorospe, M Wang, WG AF Chang, Na Yi, Jie Guo, Gaier Liu, Xinwen Shang, Yongfeng Tong, Tanjun Cui, Qinghua Zhan, Ming Gorospe, Myriam Wang, Wengong TI HuR Uses AUF1 as a Cofactor To Promote p16(INK4) mRNA Decay SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING PROTEIN HUR; ENDOTHELIAL GROWTH-FACTOR; ELAV-LIKE PROTEIN; 3'-UNTRANSLATED REGION; REPLICATIVE SENESCENCE; STABILITY FACTOR; TRANSLATION; EXPRESSION; STABILIZATION; ELEMENT AB In this study, we show that HuR destabilizes p16(INK4) mRNA. Although the knockdown of HuR or AUF1 increased p16 expression, concomitant AUF1 and HuR knockdown had a much weaker effect. The knockdown of Ago2, a component of the RNA-induced silencing complex (RISC), stabilized p16 mRNA. The knockdown of HuR diminished the association of the p16 3' untranslated region (3'UTR) with AUF1 and vice versa. While the knockdown of HuR or AUF1 reduced the association of Ago2 with the p16 3'UTR, Ago2 knockdown had no influence on HuR or AUF1 binding to the p16 3'UTR. The use of EGFP-p16 chimeric reporter transcripts revealed that p16 mRNA decay depended on a stem-loop structure present in the p16 3'UTR, as HuR and AUF1 destabilized EGFP-derived chimeric transcripts bearing wild-type sequences but not transcripts with mutations in the stem-loop structure. In senescent and HuR-silenced IDH4 human diploid fibroblasts, the EGFP-p16 3'UTR transcript was more stable. Our results suggest that HuR destabilizes p16 mRNA by recruiting the RISC, an effect that depends on the secondary structure of the p16 3'UTR and requires AUF1 as a cofactor. C1 [Chang, Na; Yi, Jie; Liu, Xinwen; Shang, Yongfeng; Tong, Tanjun; Wang, Wengong] Peking Univ, Res Ctr Aging, Dept Biochem & Mol Biol, Hlth Sci Ctr, Beijing 100191, Peoples R China. [Guo, Gaier] Changzhi Med Coll, Dept Biochem, Changzhi 046000, Shanxi, Peoples R China. [Cui, Qinghua] Peking Univ, Hlth Sci Ctr, Dept Med Bioinformat, Beijing 100191, Peoples R China. [Zhan, Ming] NIA, Bioinformat Unit, NIH, Baltimore, MD 21224 USA. [Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Wang, WG (reprint author), Peking Univ, Res Ctr Aging, Dept Biochem & Mol Biol, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China. EM wwg@bjmu.edu.cn FU Major State Basic Research Development Program of China [2007CB507400]; National Science Foundation of China [30672202, 30621002, 30921062, 30973147]; Ministry of Education of the People's Republic of China [B07001]; National Institute on Aging-IRP, National Institutes of Health FX This work was supported by grant 2007CB507400 from the Major State Basic Research Development Program of China; grants 30672202, 30621002, 30921062, and 30973147 from the National Science Foundation of China; and grant B07001 (111 project) from the Ministry of Education of the People's Republic of China. M.G. was supported by the National Institute on Aging-IRP, National Institutes of Health. NR 39 TC 59 Z9 62 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2010 VL 30 IS 15 BP 3875 EP 3886 DI 10.1128/MCB.00169-10 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 623CF UT WOS:000279714500014 PM 20498276 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, AN Novichkov, PS Spiridonov, NA Koonin, EV AF Shabalina, Svetlana A. Ogurtsov, Aleksey Y. Spiridonov, Alexey N. Novichkov, Pavel S. Spiridonov, Nikolay A. Koonin, Eugene V. TI Distinct Patterns of Expression and Evolution of Intronless and Intron-Containing Mammalian Genes SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE alternative splicing; intronless genes; monomorphic genes; polymorphic genes; mammalian gene evolution ID NETWORK; GENOME; EXPORT; CELLS; RATES AB Comparison of expression levels and breadth and evolutionary rates of intronless and intron-containing mammalian genes shows that intronless genes are expressed at lower levels, tend to be tissue specific, and evolve significantly faster than spliced genes. By contrast, monomorphic spliced genes that are not subject to detectable alternative splicing and polymorphic alternatively spliced genes show similar statistically indistinguishable patterns of expression and evolution. Alternative splicing is most common in ancient genes, whereas intronless genes appear to have relatively recent origins. These results imply tight coupling between different stages of gene expression, in particular, transcription, splicing, and nucleocytosolic transport of transcripts, and suggest that formation of intronless genes is an important route of evolution of novel tissue-specific functions in animals. C1 [Shabalina, Svetlana A.; Ogurtsov, Aleksey Y.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Spiridonov, Alexey N.] MIT, Dept Math, Cambridge, MA 02139 USA. [Novichkov, Pavel S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. [Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM shabalin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; FU Department of Health and Human Services (National Library of Medicine, National Institutes of Health) FX The authors' research is supported by the intramural funds of the Department of Health and Human Services (National Library of Medicine, National Institutes of Health). NR 29 TC 34 Z9 36 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD AUG PY 2010 VL 27 IS 8 BP 1745 EP 1749 DI 10.1093/molbev/msq086 PG 5 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 630TI UT WOS:000280296700002 PM 20360214 ER PT J AU Lemey, P Rambaut, A Welch, JJ Suchard, MA AF Lemey, Philippe Rambaut, Andrew Welch, John J. Suchard, Marc A. TI Phylogeography Takes a Relaxed Random Walk in Continuous Space and Time SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE phylogeography; Bayesian inference; random walk; Brownian diffusion; rabies; BEAST; phylodynamics ID FLIGHT SEARCH PATTERNS; WANDERING ALBATROSSES; POPULATION-DYNAMICS; EVOLUTIONARY TREES; BAYESIAN-INFERENCE; SCALE MIXTURES; GIBBS SAMPLER; DNA-SEQUENCES; MODELS; LIKELIHOOD AB Research aimed at understanding the geographic context of evolutionary histories is burgeoning across biological disciplines. Recent endeavors attempt to interpret contemporaneous genetic variation in the light of increasingly detailed geographical and environmental observations. Such interest has promoted the development of phylogeographic inference techniques that explicitly aim to integrate such heterogeneous data. One promising development involves reconstructing phylogeographic history on a continuous landscape. Here, we present a Bayesian statistical approach to infer continuous phylogeographic diffusion using random walk models while simultaneously reconstructing the evolutionary history in time from molecular sequence data. Moreover, by accommodating branch-specific variation in dispersal rates, we relax the most restrictive assumption of the standard Brownian diffusion process and demonstrate increased statistical efficiency in spatial reconstructions of overdispersed random walks by analyzing both simulated and real viral genetic data. We further illustrate how drawing inference about summary statistics from a fully specified stochastic process over both sequence evolution and spatial movement reveals important characteristics of a rabies epidemic. Together with recent advances in discrete phylogeographic inference, the continuous model developments furnish a flexible statistical framework for biogeographical reconstructions that is easily expanded upon to accommodate various landscape genetic features. C1 [Lemey, Philippe] Katholieke Univ Leuven, Dept Microbiol & Immunol, Leuven, Belgium. [Rambaut, Andrew; Welch, John J.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland. [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. RP Lemey, P (reprint author), Katholieke Univ Leuven, Dept Microbiol & Immunol, Leuven, Belgium. EM philippe.lemey@uz.kuleuven.ac.be OI Rambaut, Andrew/0000-0003-4337-3707 FU Fund for Scientific Research (FWO) Flanders; FWO [G.0513.06]; Royal Society; Biotechnology and Biological Sciences Research Council [BB/D017750/1]; National Institute of Health [R01 GM086887]; National Science Foundation [0856099]; Marsden Fund FX We thank Roman Biek for providing the raccoon rabies data and Alexei Drummond for helpful discussions. P.L. was supported by a postdoctoral fellowship from the Fund for Scientific Research (FWO) Flanders and by FWO grant G.0513.06. A. R. was supported by the Royal Society. J.J.W. was supported by grant BB/D017750/1 from the Biotechnology and Biological Sciences Research Council. M.A.S. is supported by the National Institute of Health R01 GM086887, the National Science Foundation 0856099, and the Marsden Fund. NR 50 TC 171 Z9 171 U1 3 U2 49 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD AUG PY 2010 VL 27 IS 8 BP 1877 EP 1885 DI 10.1093/molbev/msq067 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 630TI UT WOS:000280296700015 PM 20203288 ER PT J AU Liu, ZF Liu, Y Jia, B Zhao, HY Jin, XN Li, F Chen, XY Wang, F AF Liu, Zhaofei Liu, Yan Jia, Bing Zhao, Huiyun Jin, Xiaona Li, Fang Chen, Xiaoyuan Wang, Fan TI Epidermal Growth Factor Receptor-Targeted Radioimmunotherapy of Human Head and Neck Cancer Xenografts Using Y-90-Labeled Fully Human Antibody Panitumumab SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; EGFR MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; BREAST-CANCER; INTEGRIN ALPHA(V)BETA(3); MDA-MB-435 CELLS; PHASE-II; IN-VITRO; CETUXIMAB; THERAPY AB Panitumumab (ABX-EGF or Vectibix), the first fully human monoclonal antibody targeting epidermal growth factor receptor (EGFR), was approved by the Food and Drug Administration for treatment of patients with metastatic colorectal cancer. Here, we report for the first time the radioimmunotherapy (RIT) of EGFR-positive human head and neck cancer in a nude mouse model using pure beta(-) emitter Y-90-labeled panitumumab. Biodistribution and planar gamma-imaging studies were carried out with In-111-DOTA-panitumumab. The RIT efficacy of Y-90-DOTA-panitumumab was evaluated in UM-SCC-22B tumor model. CD31, Ki67, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and H&E staining were done on UM-SCC-22B tumor sections after treatment. The tumor uptake of In-111-DOTA-panitumumab in UM-SCC-22B tumor-bearing nude mice was 26.10 +/- 4.93, 59.11 +/- 7.22, 44.57 +/- 9.80, 40.38 +/- 7.76, and 14.86 +/- 7.23 % injected dose per gram of tissue at 4, 24, 72, 120, and 168 hours after injection, respectively. Immunotherapy with cold panitumumab (four doses of 10 mg/kg) did not cause significant antitumor effect. RIT with a single dose of 100 mu Ci 90Y-DOTA-panitumumab caused significant tumor growth delay and improved the survival in UM-SCC-22B tumor model. A single dose of 200 mu Ci Y-90-DOTA-panitumumab led to almost complete tumor regression (tumor volumes were 34.83 +/- 11.11 mm(3) and 56.02 +/- 39.95 mm(3) on days 0 and 46 after treatment, respectively). Histopathologic analysis of tumors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of Y-90-DOTA-panitumumab. The high tumor uptake and prolonged tumor retention, as well as effective therapy, reveal that Y-90-DOTA-panitumumab may be a promising radioimmunotherapeutic agent to treat EGFR-positive solid tumors. Mol Cancer Ther; 9(8); 2297-308. (C) 2010 AACR. C1 [Liu, Zhaofei; Liu, Yan; Jia, Bing; Zhao, Huiyun; Wang, Fan] Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China. [Jin, Xiaona; Li, Fang] Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing, Peoples R China. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Wang, F (reprint author), Peking Univ, Med Isotopes Res Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China. EM wangfan@bjmu.edu.cn RI Jia, Bing/C-3796-2008 FU National Natural Science Foundation of China [30870728, 20820102035, 30930030, 30900373]; "863" project [2007AA02Z467]; Ministry of Science and Technology of China [2009ZX09103-733, 2009ZX09301-010, 2009ZX09103-746]; NIH, National Institute of Biomedical Imaging and Bioengineering FX National Natural Science Foundation of China grants 30870728, 20820102035, and 30930030 (F. Wang) and 30900373 (B. Jia); "863" project grant 2007AA02Z467 (F. Wang); Ministry of Science and Technology of China grants 2009ZX09103-733 and 2009ZX09301-010 (F. Wang) and 2009ZX09103-746 (B. Jia); and Intramural Research Program of the NIH, including the National Institute of Biomedical Imaging and Bioengineering (X. Chen). NR 43 TC 19 Z9 19 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2010 VL 9 IS 8 BP 2297 EP 2308 DI 10.1158/1535-7163.MCT-10-0444 PG 12 WC Oncology SC Oncology GA 636KU UT WOS:000280734200014 PM 20682654 ER PT J AU Gonzalez, JM Franzke, CV Romero, R Girardi, G AF Gonzalez, Juan M. Franzke, Claus V. Romero, Roberto Girardi, Guillermina TI Complement activation in preterm delivery in mice SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 23rd International National Complement Workshop CY AUG 01-05, 2010 CL New York, NY C1 [Gonzalez, Juan M.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Gonzalez, Juan M.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Franzke, Claus V.] Univ Freiburg, D-7800 Freiburg, Germany. [Girardi, Guillermina] CUNY York Coll, New York, NY 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 2010 VL 47 IS 13 SI SI MA 52 BP 2275 EP 2276 DI 10.1016/j.molimm.2010.05.231 PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 630JE UT WOS:000280268400224 ER PT J AU Putney, JW AF Putney, James W. TI Pharmacology of Store-operated Calcium Channels SO MOLECULAR INTERVENTIONS LA English DT Review ID ACTIVATED CA2+ CHANNELS; 2-AMINOETHOXYDIPHENYL BORATE 2-APB; SEVERE COMBINED IMMUNODEFICIENCY; INOSITOL TRISPHOSPHATE RECEPTOR; CRAC CHANNELS; PLASMA-MEMBRANE; CATION CHANNELS; TRPC CHANNELS; T-LYMPHOCYTES; CA2+-DEPENDENT INACTIVATION AB Store-operated calcium entry is a process by which the depletion of calcium from the endoplasmic reticulum activates calcium influx across the plasma membrane. In the past few years, the major players in this pathway have been identified. STIM1 and STIM2 function as calcium sensors in the endoplasmic reticulum and can interact with and activate plasma membrane channels comprised of Orai1, Orai2, or Orai3 subunits. This review discusses recent advances in our understanding of this widespread signaling mechanism as well as the mechanisms by which a number of interesting pharmacological agents modify it. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov FU National Institutes of Health FX I thank Stephen Shears, David Armstrong, and Juan Xing for reviewing the manuscript and providing helpful comments. Work from the author's laboratory described in this review was supported by the Intramural Research Program of the National Institutes of Health. NR 103 TC 52 Z9 54 U1 1 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD AUG PY 2010 VL 10 IS 4 BP 209 EP 218 DI 10.1124/mi.10.4.4 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 674FQ UT WOS:000283721300004 PM 20729487 ER PT J AU Yang, ZX Zhou, YN Yang, Y Jin, DJ AF Yang, Zhao Xu Zhou, Yan Ning Yang, Yi Jin, Ding Jun TI Polyphosphate binds to the principal sigma factor of RNA polymerase during starvation response in Helicobacter pylori SO MOLECULAR MICROBIOLOGY LA English DT Article ID INORGANIC POLYPHOSPHATE; ESCHERICHIA-COLI; STRINGENT RESPONSE; EXOPOLYPHOSPHATASE; SURVIVAL; TRANSCRIPTION; REVEALS; KINASE; GROWTH; ENZYME AB Helicobacter pylori persists deep in the human gastric mucus layer in a harsh, nutrient-poor environment. Survival under these conditions depends on the ability of this human pathogen to invoke starvation/stress responses when needed. Unlike many bacteria, H. pylori lacks starvation/stressresponding alternative sigma factors, suggesting an additional mechanism might have evolved in this bacterium. Helicobacter pylori produces polyphosphate; however, the role and target of polyphosphate during starvation/stress have not been identified. Here we show that polyphosphate accumulated during nutrient starvation directly targets transcriptional machinery by binding to the principal sigma factor in H. pylori, uncovering a novel mechanism in microbial stress response. A positively charged Lys-rich region at the N-terminal domain of the major sigma factor is identified as the binding region for polyphosphate (region P) in vivo and in vitro, revealing a new element in sigma 70 family proteins. This interaction is biologically significant because mutant strains defective in the interaction undergo premature cell death during starvation. We suggested that polyphosphate is a second messenger employed by H. pylori to mediate gene expression during starvation/stress. The putative 'region P' is present in sigma factors of other human pathogens, suggesting that the uncovered interaction might be a general strategy employed by other pathogens. C1 [Yang, Zhao Xu; Zhou, Yan Ning; Yang, Yi; Jin, Ding Jun] NCI, NIH, Frederick, MD 21701 USA. RP Jin, DJ (reprint author), NCI, NIH, Frederick, MD 21701 USA. EM djjin@helix.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX We thank D. E. Berg for strains, T. Durfee for the construction of pQE80-ppX (Ec), W. Xu for E. coli PPK, and B. Xiao and C. Cagliero for bioinformatics analysis of sigma factors. We are grateful for helpful comments for the manuscript from M. Kashlev, A. Klar, KX Jin, J. L. Caswell and M. Mills. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 10 Z9 13 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 2010 VL 77 IS 3 BP 618 EP 627 DI 10.1111/j.1365-2958.2010.07233.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 628NZ UT WOS:000280128500009 PM 20553390 ER PT J AU Mishra, A Wu, CG Yang, JH Cisar, JO Das, A Ton-That, H AF Mishra, Arunima Wu, Chenggang Yang, Jinghua Cisar, John O. Das, Asis Ton-That, Hung TI The Actinomyces oris type 2 fimbrial shaft FimA mediates co-aggregation with oral streptococci, adherence to red blood cells and biofilm development SO MOLECULAR MICROBIOLOGY LA English DT Article ID GRAM-POSITIVE BACTERIA; CORYNEBACTERIUM-DIPHTHERIAE; VISCOSUS T14V; RECEPTOR POLYSACCHARIDES; NAESLUNDII GENOSPECIES-1; PILI; WALL; IDENTIFICATION; RECOGNITION; PROTEINS AB Interbacterial interactions between oral streptococci and actinomyces and their adherence to tooth surface and the associated host cells are key early events that promote development of the complex oral biofilm referred to as dental plaque. These interactions depend largely on a lectin-like activity associated with the Actinomyces oris type 2 fimbria, a surface structure assembled by sortase (SrtC2)-dependent polymerization of the shaft and tip fimbrillins, FimA and FimB respectively. To dissect the function of specific fimbrillins in various adherence processes, we have developed a convenient new technology for generating unmarked deletion mutants of A. oris. Here, we show that the fimB mutant, which produced type 2 fimbriae composed only of FimA, like the wild type co-aggregated strongly with receptor-bearing streptococci, agglutinated with sialidase-treated red blood cells, and formed monospecies biofilm. In contrast, the fimA and srtC2 mutants lacked type 2 fimbriae and were non-adherent in each of these assays. Plasmid-based expression of the deleted gene in respective mutants restored adherence to wild-type levels. These findings uncover the importance of the lectin-like activity of the polymeric FimA shaft rather than the tip. The multivalent adhesive function of FimA makes it an ideal molecule for exploring novel intervention strategies to control plaque biofilm formation. C1 [Mishra, Arunima; Wu, Chenggang; Ton-That, Hung] Univ Texas Hlth Sci Ctr, Dept Microbiol & Mol Genet, Houston, TX 78229 USA. [Yang, Jinghua; Cisar, John O.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. [Das, Asis] Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT USA. RP Ton-That, H (reprint author), Univ Texas Hlth Sci Ctr, Dept Microbiol & Mol Genet, Houston, TX 78229 USA. EM ton-that.hung@uth.tmc.edu OI Ton-That, Hung/0000-0003-1611-0469 FU National Institute of Dental and Craniofacial Research (NIDCR), NIH [DE017382]; NIDCR FX We thank I-Hsiu Huang, Elizabeth Rogers and members of our laboratory for their critical inputs. This work was supported by the National Institute of Dental and Craniofacial Research (NIDCR), NIH Grant DE017382 to H. T-T. and by the Intramural Research Program of NIDCR to J.O.C. NR 54 TC 32 Z9 33 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 2010 VL 77 IS 4 BP 841 EP 854 DI 10.1111/j.1365-2958.2010.07252.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 635QY UT WOS:000280672400005 PM 20545853 ER PT J AU Morrow, MP Grant, A Mujawar, Z Dubrovsky, L Pushkarsky, T Kiselyeva, Y Jennelle, L Mukhamedova, N Remaley, AT Kashanchi, F Sviridov, D Bukrinsky, M AF Morrow, Matthew P. Grant, Angela Mujawar, Zahedi Dubrovsky, Larisa Pushkarsky, Tatiana Kiselyeva, Yana Jennelle, Lucas Mukhamedova, Nigora Remaley, Alan T. Kashanchi, Fatah Sviridov, Dmitri Bukrinsky, Michael TI Stimulation of the Liver X Receptor Pathway Inhibits HIV-1 Replication via Induction of ATP-Binding Cassette Transporter A1 SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRION-ASSOCIATED CHOLESTEROL; LIPID RAFTS; HDL CHOLESTEROL; PLASMA-MEMBRANE; T-LYMPHOCYTES; MACROPHAGES; INFECTION; EFFLUX; CELLS AB Cholesterol plays an important role in the HIV life cycle, and infectivity of cholesterol-depleted HIV virions is significantly impaired. Recently, we demonstrated that HIV-1, via its protein Nef, inhibits the activity of the major cellular cholesterol transporter ATP binding cassette transporter A1 (ABCA1), suggesting that the virus may use this mechanism to get access to cellular cholesterol. In this study, we investigated the effect on HIV infection of a synthetic liver X receptor (LXR) ligand, N-(2,2,2-trifluoro-ethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-benzenesulfonamide (TO-901317), which is a potent stimulator of ABCA1 expression. We demonstrate that TO-901317 restores cholesterol efflux from HIV-infected T lymphocytes and macrophages. TO-901317 potently suppressed HIV-1 replication in both cell types and inhibited HIV-1 replication in ex vivo cultured lymphoid tissue and in RAG-hu mice infected in vivo. This anti-HIV activity was dependent on ABCA1, because the effect of the drug was significantly reduced in ABCA1-defective T cells from a patient with Tangier disease, and RNA interference-mediated inhibition of ABCA1 expression eliminated the effect of TO-901317 on HIV-1 replication. TO-901317-mediated inhibition of HIV replication was due to reduced virus production and reduced infectivity of produced virions. The infectivity defect was in part due to reduced fusion activity of the virions, which was directly linked to reduced viral cholesterol. These results describe a novel approach to inhibiting HIV infection by stimulating ABCA1 expression. C1 [Bukrinsky, Michael] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Kiselyeva, Yana] NICHHD, NIH, Bethesda, MD 20892 USA. [Mukhamedova, Nigora; Sviridov, Dmitri] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Bukrinsky, M (reprint author), George Washington Univ, Med Ctr, 2300 Eye St NW,Ross Hall Suite 734, Washington, DC 20037 USA. EM mtmmib@gwumc.edu RI Sviridov, Dmitri/E-7943-2010; Bukrinsky, Jens/D-7151-2013 OI Bukrinsky, Jens/0000-0002-4993-6366 FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK072926]; National Institutes of Health National Institute of Allergy and Infectious Diseases [AI078743]; National Institutes of Health National Heart, Lung, and Blood Institute [HL093818]; American Heart Association; National Health and Medical Research Council of Australia FX This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK072926]; National Institutes of Health National Institute of Allergy and Infectious Diseases [Grant AI078743]; and National Institutes of Health National Heart, Lung, and Blood Institute [Grant HL093818]; the American Heart Association; and the National Health and Medical Research Council of Australia. NR 40 TC 34 Z9 36 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 2010 VL 78 IS 2 BP 215 EP 225 DI 10.1124/mol.110.065029 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 625IF UT WOS:000279888000007 PM 20479131 ER PT J AU Vogel, C Abreu, RD Ko, DJ Le, SY Shapiro, BA Burns, SC Sandhu, D Boutz, DR Marcotte, EM Penalva, LO AF Vogel, Christine Abreu, Raquel de Sousa Ko, Daijin Le, Shu-Yun Shapiro, Bruce A. Burns, Suzanne C. Sandhu, Devraj Boutz, Daniel R. Marcotte, Edward M. Penalva, Luiz O. TI Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE gene expression regulation; protein degradation; protein stability; translation ID GENOME-WIDE ANALYSIS; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; POSTTRANSCRIPTIONAL REGULATION; TRANSLATION EFFICIENCY; UNSTRUCTURED PROTEINS; STATISTICAL-MODEL; MASS-SPECTROMETRY; CODON BIAS; DEGRADATION AB Transcription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady-state protein concentrations in multi-cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA abundances in cellular lysate from the human Daoy medulloblastoma cell line, we quantitatively evaluate the impact of mRNA concentration and sequence features implicated in translation and protein degradation on protein expression. Sequence features related to translation and protein degradation have an impact similar to that of mRNA abundance, and their combined contribution explains two-thirds of protein abundance variation. mRNA sequence lengths, amino-acid properties, upstream open reading frames and secondary structures in the 50 untranslated region (UTR) were the strongest individual correlates of protein concentrations. In a combined model, characteristics of the coding region and the 3'UTR explained a larger proportion of protein abundance variation than characteristics of the 5'UTR. The absolute protein and mRNA concentration measurements for >1000 human genes described here represent one of the largest datasets currently available, and reveal both general trends and specific examples of post-transcriptional regulation. Molecular Systems Biology 6: 400; published online 24 August 2010; doi:10.1038/msb.2010.59 Subject Categories: bioinformatics; functional genomics C1 [Vogel, Christine; Boutz, Daniel R.; Marcotte, Edward M.] Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, Austin, TX 78229 USA. [Abreu, Raquel de Sousa; Burns, Suzanne C.; Sandhu, Devraj; Penalva, Luiz O.] Univ Texas Hlth Sci Ctr San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Ko, Daijin] Univ Texas San Antonio, Dept Management Sci & Stat, San Antonio, TX USA. [Le, Shu-Yun; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. RP Vogel, C (reprint author), Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, 2500 Speedway,MBB 3-210, Austin, TX 78229 USA. EM cvogel@mail.utexas.edu; penalva@uthscsa.edu RI Boutz, Daniel/M-4872-2013 OI Boutz, Daniel/0000-0001-7462-4105 FU Children's Cancer Research Institute; NIH [GM076536, GM67779, GM088624]; NIH/NINDS [NS60658]; NSF [0640923]; Welch Foundation [F-1515]; Tengg Foundation; Packard Foundation; International Human Frontier Science Program; NIH, National Cancer Institute, Center for Cancer Research FX We thank Jorg Gsponer for help with Disopred predictions, Barron Blackman for help with PEST predictions and Marcelo Bento Soares for ALU predictions. We thank Joshua Plotkin for helpful discussions. This work was supported by the Children's Cancer Research Institute (to RSA and LOP), the NIH (GM076536, GM67779, GM088624 to EMM), NIH/NINDS (NS60658 to DK) and NSF (0640923 to EMM); the Welch (F-1515, to EMM), Tengg (to LOP) and Packard (to EMM) Foundations and the International Human Frontier Science Program (to CV). This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 63 TC 219 Z9 221 U1 1 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD AUG PY 2010 VL 6 AR 400 DI 10.1038/msb.2010.59 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 684DL UT WOS:000284527700004 PM 20739923 ER PT J AU Shi, LM Campbell, G Jones, WD Campagne, F Wen, ZN Walker, SJ Su, ZQ Chu, TM Goodsaid, FM Pusztai, L Shaughnessy, JD Oberthuer, A Thomas, RS Paules, RS Fielden, M Barlogie, B Chen, WJ Du, P Fischer, M Furlanello, C Gallas, BD Ge, XJ Megherbi, DB Symmans, WF Wang, MD Zhang, J Bitter, H Brors, B Bushel, PR Bylesjo, M Chen, MJ Cheng, J Cheng, J Chou, J Davison, TS Delorenzi, M Deng, YP Devanarayan, V Dix, DJ Dopazo, J Dorff, KC Elloumi, F Fan, JQ Fan, SC Fan, XH Fang, H Gonzaludo, N Hess, KR Hong, H Huan, J Irizarry, RA Judson, R Juraeva, D Lababidi, S Lambert, CG Li, L Li, Y Li, Z Lin, SM Liu, GZ Lobenhofer, EK Luo, J Luo, W McCall, MN Nikolsky, Y Pennello, GA Perkins, RG Philip, R Popovici, V Price, ND Qian, F Scherer, A Shi, TL Shi, WW Sung, JY Thierry-Mieg, D Thierry-Mieg, J Thodima, V Trygg, J Vishnuvajjala, L Wang, SJ Wu, JP Wu, YC Xie, Q Yousef, WA Zhang, L Zhang, XG Zhong, S Zhou, YM Zhu, S Arasappan, D Bao, WJ Lucas, AB Berthold, F Brennan, RJ Buness, A Catalano, JG Chang, C Chen, R Cheng, YY Cui, J Czika, W Demichelis, F Deng, XT Dosymbekov, D Eils, R Feng, Y Fostel, J Fulmer-Smentek, S Fuscoe, JC Gatto, L Ge, WG Goldstein, DR Guo, L Halbert, DN Han, J Harris, SC Hatzis, C Herman, D Huang, JP Jensen, RV Jiang, R Johnson, CD Jurman, G Kahlert, Y Khuder, SA Kohl, M Li, JY Li, L Li, ML Li, QZ Li, S Li, ZG Liu, J Liu, Y Liu, ZC Meng, L Madera, M Martinez-Murillo, F Medina, I Meehan, J Miclaus, K Moffitt, RA Montaner, D Mukherjee, P Mulligan, GJ Neville, P Nikolskaya, T Ning, BT Page, GP Parker, J Parry, RM Peng, XJ Peterson, RL Phan, JH Quanz, B Ren, Y Riccadonna, S Roter, AH Samuelson, FW Schumacher, MM Shambaugh, JD Shi, QA Shippy, R Si, SZ Smalter, A Sotiriou, C Soukup, M Staedtler, F Steiner, G Stokes, TH Sun, QL Tan, PY Tang, R Tezak, Z Thorn, B Tsyganova, M Turpaz, Y Vega, SC Visintainer, R von Frese, J Wang, C Wang, E Wang, JW Wang, W Westermann, F Willey, JC Woods, M Wu, SJ Xiao, NQ Xu, J Xu, L Yang, L Zeng, X Zhang, JL Zhang, L Zhang, M Zhao, C Puri, RK Scherf, U Tong, W Wolfinger, RD AF Shi, Leming Campbell, Gregory Jones, Wendell D. Campagne, Fabien Wen, Zhining Walker, Stephen J. Su, Zhenqiang Chu, Tzu-Ming Goodsaid, Federico M. Pusztai, Lajos Shaughnessy, John D., Jr. Oberthuer, Andre Thomas, Russell S. Paules, Richard S. Fielden, Mark Barlogie, Bart Chen, Weijie Du, Pan Fischer, Matthias Furlanello, Cesare Gallas, Brandon D. Ge, Xijin Megherbi, Dalila B. Symmans, W. Fraser Wang, May D. Zhang, John Bitter, Hans Brors, Benedikt Bushel, Pierre R. Bylesjo, Max Chen, Minjun Cheng, Jie Cheng, Jing Chou, Jeff Davison, Timothy S. Delorenzi, Mauro Deng, Youping Devanarayan, Viswanath Dix, David J. Dopazo, Joaquin Dorff, Kevin C. Elloumi, Fathi Fan, Jianqing Fan, Shicai Fan, Xiaohui Fang, Hong Gonzaludo, Nina Hess, Kenneth R. Hong, Huixiao Huan, Jun Irizarry, Rafael A. Judson, Richard Juraeva, Dilafruz Lababidi, Samir Lambert, Christophe G. Li, Li Li, Yanen Li, Zhen Lin, Simon M. Liu, Guozhen Lobenhofer, Edward K. Luo, Jun Luo, Wen McCall, Matthew N. Nikolsky, Yuri Pennello, Gene A. Perkins, Roger G. Philip, Reena Popovici, Vlad Price, Nathan D. Qian, Feng Scherer, Andreas Shi, Tieliu Shi, Weiwei Sung, Jaeyun Thierry-Mieg, Danielle Thierry-Mieg, Jean Thodima, Venkata Trygg, Johan Vishnuvajjala, Lakshmi Wang, Sue Jane Wu, Jianping Wu, Yichao Xie, Qian Yousef, Waleed A. Zhang, Liang Zhang, Xuegong Zhong, Sheng Zhou, Yiming Zhu, Sheng Arasappan, Dhivya Bao, Wenjun Lucas, Anne Bergstrom Berthold, Frank Brennan, Richard J. Buness, Andreas Catalano, Jennifer G. Chang, Chang Chen, Rong Cheng, Yiyu Cui, Jian Czika, Wendy Demichelis, Francesca Deng, Xutao Dosymbekov, Damir Eils, Roland Feng, Yang Fostel, Jennifer Fulmer-Smentek, Stephanie Fuscoe, James C. Gatto, Laurent Ge, Weigong Goldstein, Darlene R. Guo, Li Halbert, Donald N. Han, Jing Harris, Stephen C. Hatzis, Christos Herman, Damir Huang, Jianping Jensen, Roderick V. Jiang, Rui Johnson, Charles D. Jurman, Giuseppe Kahlert, Yvonne Khuder, Sadik A. Kohl, Matthias Li, Jianying Li, Li Li, Menglong Li, Quan-Zhen Li, Shao Li, Zhiguang Liu, Jie Liu, Ying Liu, Zhichao Meng, Lu Madera, Manuel Martinez-Murillo, Francisco Medina, Ignacio Meehan, Joseph Miclaus, Kelci Moffitt, Richard A. Montaner, David Mukherjee, Piali Mulligan, George J. Neville, Padraic Nikolskaya, Tatiana Ning, Baitang Page, Grier P. Parker, Joel Parry, R. Mitchell Peng, Xuejun Peterson, Ron L. Phan, John H. Quanz, Brian Ren, Yi Riccadonna, Samantha Roter, Alan H. Samuelson, Frank W. Schumacher, Martin M. Shambaugh, Joseph D. Shi, Qiang Shippy, Richard Si, Shengzhu Smalter, Aaron Sotiriou, Christos Soukup, Mat Staedtler, Frank Steiner, Guido Stokes, Todd H. Sun, Qinglan Tan, Pei-Yi Tang, Rong Tezak, Zivana Thorn, Brett Tsyganova, Marina Turpaz, Yaron Vega, Silvia C. Visintainer, Roberto von Frese, Juergen Wang, Charles Wang, Eric Wang, Junwei Wang, Wei Westermann, Frank Willey, James C. Woods, Matthew Wu, Shujian Xiao, Nianqing Xu, Joshua Xu, Lei Yang, Lun Zeng, Xiao Zhang, Jialu Zhang, Li Zhang, Min Zhao, Chen Puri, Raj K. Scherf, Uwe Tong, Weida Wolfinger, Russell D. CA MAQC Consortium TI The MicroArray Quality Control (MAQC)-IIII study of common practices for the development and validation of microarray-based predictive models SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION DATA; CONTROL MAQC PROJECT; MULTIPLE-MYELOMA; BREAST-CANCER; PUBLISHED MICROARRAY; FOLLICULAR LYMPHOMA; RISK-STRATIFICATION; DNA MICROARRAYS; CLASSIFICATION; PERFORMANCE AB Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis. C1 [Shi, Leming; Wen, Zhining; Chen, Minjun; Hong, Huixiao; Perkins, Roger G.; Fuscoe, James C.; Ge, Weigong; Harris, Stephen C.; Li, Zhiguang; Liu, Jie; Liu, Zhichao; Ning, Baitang; Shi, Qiang; Thorn, Brett; Xu, Lei; Yang, Lun; Zhang, Min; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Campbell, Gregory; Chen, Weijie; Gallas, Brandon D.; Pennello, Gene A.; Philip, Reena; Vishnuvajjala, Lakshmi; Martinez-Murillo, Francisco; Samuelson, Frank W.; Tang, Rong; Tezak, Zivana; Scherf, Uwe] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Jones, Wendell D.; Parker, Joel] Express Anal Inc, Durham, NC USA. [Campagne, Fabien] Cornell Univ, Dept Physiol & Biophys, Weill Med Coll, New York, NY 10021 USA. [Walker, Stephen J.] Wake Forest Univ, Wake Forest Inst Regenerat Med, Winston Salem, NC 27109 USA. [Su, Zhenqiang; Fang, Hong; Qian, Feng; Arasappan, Dhivya; Meehan, Joseph; Xu, Joshua] Z Tech, Jefferson, AR USA. [Chu, Tzu-Ming; Li, Li; Bao, Wenjun; Czika, Wendy; Miclaus, Kelci; Neville, Padraic; Tan, Pei-Yi; Wolfinger, Russell D.] SAS Inst Inc, Cary, NC USA. [Goodsaid, Federico M.; Wang, Sue Jane; Soukup, Mat; Zhang, Jialu; Zhang, Li] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Pusztai, Lajos] Univ Texas MD Anderson Canc Ctr, Breast Med Oncol Dept, Houston, TX 77030 USA. [Shaughnessy, John D., Jr.; Barlogie, Bart; Zhou, Yiming] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Oberthuer, Andre; Fischer, Matthias; Berthold, Frank; Kahlert, Yvonne] Univ Cologne, Dept Pediat Oncol & Hematol, Cologne, Germany. [Oberthuer, Andre; Fischer, Matthias; Berthold, Frank; Kahlert, Yvonne] Univ Cologne, Ctr Mol Med CMMC, Cologne, Germany. [Thomas, Russell S.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Paules, Richard S.; Bushel, Pierre R.; Chou, Jeff; Fostel, Jennifer] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. [Fielden, Mark] Roche Palo Alto LLC, San Francisco, CA USA. [Du, Pan; Lin, Simon M.] Northwestern Univ, Biomed Informat Ctr, Chicago, IL 60611 USA. [Furlanello, Cesare; Jurman, Giuseppe; Riccadonna, Samantha; Visintainer, Roberto] Fdn Bruno Kessler, Povo, Italy. [Ge, Xijin] S Dakota State Univ, Dept Math & Stat, Brookings, SD 57007 USA. [Megherbi, Dalila B.; Madera, Manuel] Univ Massachusetts Lowell, CMINDS Res Ctr, Dept Elect & Comp Engn, Lowell, MA USA. [Symmans, W. Fraser] UI MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Wang, May D.; Moffitt, Richard A.; Parry, R. Mitchell; Phan, John H.; Stokes, Todd H.] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. [Wang, May D.; Moffitt, Richard A.; Parry, R. Mitchell; Phan, John H.; Stokes, Todd H.] Emory Univ, Atlanta, GA 30322 USA. [Zhang, John; Luo, Jun; Wang, Eric; Woods, Matthew] Syst Analyt Inc, Waltham, MA USA. [Bitter, Hans] Hoffmann LaRoche, Nutley, NJ USA. [Brors, Benedikt; Juraeva, Dilafruz; Eils, Roland; Westermann, Frank] German Canc Res Ctr, Dept Theoret Bioinformat, Heidelberg, Germany. [Bylesjo, Max; Trygg, Johan] Umea Univ, Computat Life Sci Cluster CLiC, Chem Biol Ctr KBC, Umea, Sweden. [Cheng, Jie] GlaxoSmithKline Inc, Collegeville, PA USA. [Cheng, Jing] Tsinghua Univ, Sch Med, Med Syst Biol Res Ctr, Beijing 100084, Peoples R China. [Davison, Timothy S.] Almac Diagnost Ltd, Craigavon, North Ireland. [Delorenzi, Mauro; Popovici, Vlad] Swiss Inst Bioinformat, Lausanne, Switzerland. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Devanarayan, Viswanath] Global Pharmaceut R&D, Abbott Labs, Souderton, PA USA. [Dix, David J.; Elloumi, Fathi; Judson, Richard; Li, Zhen] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. [Dopazo, Joaquin] CIPF, Dept Bioinformat & Genom, Valencia, Spain. [Fan, Jianqing; Feng, Yang] Princeton Univ, Dept Operat Res & Financial Engn, Princeton, NJ 08544 USA. [Fan, Shicai; Zhang, Xuegong; Jiang, Rui; Liu, Ying; Meng, Lu] Tsinghua Univ, MOE Key Lab Bioinformat, TNLIST, Dept Automat, Beijing 100084, Peoples R China. [Fan, Xiaohui; Cheng, Yiyu; Huang, Jianping; Li, Shao] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut Informat, Hangzhou 310003, Zhejiang, Peoples R China. [Gonzaludo, Nina] Roche Palo Alto LLC, Palo Alto, CA USA. [Hess, Kenneth R.] UT MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA. [Huan, Jun; Quanz, Brian; Smalter, Aaron] Univ Kansas, Dept Elect Engn & Comp Sci, Lawrence, KS 66045 USA. [Irizarry, Rafael A.; McCall, Matthew N.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Lababidi, Samir; Catalano, Jennifer G.; Han, Jing; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Lambert, Christophe G.] Golden Helix Inc, Bozeman, MT USA. [Li, Yanen] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA. [Liu, Guozhen; Zeng, Xiao] SABiosciences Corp, Frederick, MD USA. [Lobenhofer, Edward K.] Cogenics, Morrisville, NC USA. [Luo, Wen] Ligand Pharmaceut Inc, La Jolla, CA 92037 USA. [Nikolsky, Yuri; Shi, Weiwei; Brennan, Richard J.; Nikolskaya, Tatiana] GeneGo Inc, Encinitas, CA USA. [Price, Nathan D.; Sung, Jaeyun] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Scherer, Andreas] Spheromics, Kontiolahti, Finland. [Shi, Tieliu; Chang, Chang; Cui, Jian; Wang, Junwei; Zhao, Chen] E China Normal Univ, Ctr Bioinformat, Shanghai 200062, Peoples R China. [Shi, Tieliu; Chang, Chang; Cui, Jian; Wang, Junwei; Zhao, Chen] E China Normal Univ, Inst Biomed Sci, Sch Life Sci, Shanghai 200062, Peoples R China. [Thierry-Mieg, Danielle; Thierry-Mieg, Jean] Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. [Thodima, Venkata] Mem Sloan Kettering Canc Ctr, Rockefeller Res Labs, New York, NY 10021 USA. [Wu, Jianping; Zhang, Liang; Zhu, Sheng; Sun, Qinglan] CapitalBio Corp, Beijing, Peoples R China. [Wu, Yichao] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Xie, Qian] SRA Int FMMFS, Rockville, MD USA. [Yousef, Waleed A.] Helwan Univ, Helwan, Egypt. [Zhong, Sheng] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Lucas, Anne Bergstrom; Fulmer-Smentek, Stephanie] Agilent Technol, Santa Clara, CA USA. [Buness, Andreas] F Hoffmann La Roche Ltd, Basel, Switzerland. [Chen, Rong] Stanford Univ, Stanford Ctr Biomed Informat Res, Stanford, CA 94305 USA. [Demichelis, Francesca] Cornell Univ, Weill Med Coll, Dept Pathol, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA. [Demichelis, Francesca] Cornell Univ, Weill Med Coll, Lab Med, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA. [Deng, Xutao; Wang, Charles] Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. [Dosymbekov, Damir; Tsyganova, Marina] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow, Russia. [Gatto, Laurent] DNAVision SA, Gosselies, Belgium. [Goldstein, Darlene R.] Ecole Polytech Fed Lausanne, Lausanne, Switzerland. [Guo, Li] Chinese Acad Sci, Inst Proc Engn, State Key Lab Multiphase Complex Syst, Beijing, Peoples R China. [Halbert, Donald N.] Abbott Labs, Abbott Pk, IL 60064 USA. [Hatzis, Christos] Nuvera Biosci Inc, Woburn, MA USA. [Herman, Damir] Univ Arkansas Med Sci, Winthrop P Rockefeller Canc Inst, Little Rock, AR 72205 USA. [Jensen, Roderick V.] VirginiaTech, Blacksburg, VA USA. [Johnson, Charles D.] BioMath Solut LLC, Austin, TX USA. [Khuder, Sadik A.] Univ Toledo, Bioinformat Program, Toledo, OH 43606 USA. [Kohl, Matthias] Univ Bayreuth, Dept Math, Bayreuth, Germany. [Li, Jianying] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Li, Li] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Li, Menglong] Sichuan Univ, Coll Chem, Chengdu 610064, Sichuan, Peoples R China. [Li, Quan-Zhen] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Medina, Ignacio; Montaner, David] CIPF, Valencia, Spain. [Mulligan, George J.] Millennium Pharmaceut Inc, Cambridge, MA USA. [Page, Grier P.] RTI Int, Atlanta, GA USA. [Peng, Xuejun] Takeda Global R&D Ctr Inc, Deerfield, IL USA. [Peterson, Ron L.] Novartis Inst Biomed Res, Cambridge, MA USA. [Ren, Yi] Rutgers State Univ, WM Keck Ctr Collaborat Neurosci, Piscataway, NJ USA. [Roter, Alan H.] Entelos Inc, Foster City, CA USA. [Schumacher, Martin M.; Staedtler, Frank] Novartis Pharma AG, Biomarker Dev, Novartis Inst BioMed Res, Basel, Switzerland. [Shambaugh, Joseph D.] Genedata Inc, Lexington, MA USA. [Shippy, Richard] Affymetrix Inc, Santa Clara, CA USA. [Si, Shengzhu] Hefei Teachers Coll, Dept Chem & Chem Engn, Hefei, Anhui, Peoples R China. [Sotiriou, Christos] Inst Jules Bordet, B-1000 Brussels, Belgium. [Steiner, Guido] F Hoffmann La Roche Ltd, Biostat, Basel, Switzerland. [Turpaz, Yaron] Lilly Singapore, Ctr Drug Discovery, Immunos, Singapore, Singapore. [Vega, Silvia C.] Microsoft Corp, US Hlth Solut Grp, Redmond, WA 98052 USA. [von Frese, Juergen] Data Anal Solut DA SOL GmbH, Greifenberg, Germany. [Wang, Wei] Cornell Univ, Ithaca, NY USA. [Willey, James C.] Univ Toledo Hlth Sci Campus, Dept Med, Div Pulm & Crit Care Med, Toledo, OH USA. [Wu, Shujian] Bristol Myers Squibb, Pennington, NJ USA. [Xiao, Nianqing] OpGen Inc, Gaithersburg, MD USA. Tsinghua Univ, TNLIST, Dept Automat, Bioinformat Div, Beijing 100084, Peoples R China. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov RI Qiang, Shi/E-6266-2012; Nikolskaya, Tatiana/M-5008-2013; Dopazo, Joaquin/A-9270-2014; Liu, Zhichao/C-4035-2011; Huan, Jun/A-1007-2015; Popovici, Vlad/C-2039-2008; Campagne, Fabien/F-5158-2010; Yang, Lun/B-4859-2012; Zhang, Jinny/C-4794-2012; Chen, Weijie/A-3712-2012; Su, Zhenqiang/H-3914-2012; Su, Zhiguo/G-2422-2011; Jiang, Rui/B-1345-2012; Brors, Benedikt/E-5620-2013; Feng, Yang/D-3329-2015; Hatzis, Christos/M-3867-2015; Eils, Roland/B-6121-2009; THIERRY-MIEG, Jean/F-1975-2017 OI Dopazo, Joaquin/0000-0003-3318-120X; Huan, Jun/0000-0003-4929-2617; Popovici, Vlad/0000-0002-1311-9188; Jiang, Rui/0000-0002-7533-3753; Brors, Benedikt/0000-0001-5940-3101; Feng, Yang/0000-0001-7746-7598; Hatzis, Christos/0000-0002-8120-2290; Eils, Roland/0000-0002-0034-4036; THIERRY-MIEG, Jean/0000-0002-0396-6789 FU National Institutes of Health (NIH) [1R01GM083084-01, 1R01RR021967-01A2, T32GM074906]; National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina [HHSN273200700046U]; Biomedical Informatics Core of the Institutional Clinical and Translational Science [RFA-RM-07002] FX The MAQC-II project was funded in part by the FDA's Office of Critical Path Programs (to L. S.). Participants from the National Institutes of Health (NIH) were supported by the Intramural Research Program of NIH, Bethesda, Maryland or the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina. J.F. was supported by the Division of Intramural Research of the NIEHS under contract HHSN273200700046U. Participants from the Johns Hopkins University were supported by grants from the NIH (1R01GM083084-01 and 1R01RR021967-01A2 to R.A.I. and T32GM074906 to M.M.). Participants from the Weill Medical College of Cornell University were partially supported by the Biomedical Informatics Core of the Institutional Clinical and Translational Science Award RFA-RM-07002. F. C. acknowledges resources from The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine and from the David A. Cofrin Center for Biomedical Information at Weill Cornell. The data set from The Hamner Institutes for Health Sciences was supported by a grant from the American Chemistry Council's Long Range Research Initiative. The breast cancer data set was generated with support of grants from NIH (R-01 to L.P.), The Breast Cancer Research Foundation (to L.P. and W.F.S.) and the Faculty Incentive Funds of the University of Texas MD Anderson Cancer Center (to W.F.S.). The data set from the University of Arkansas for Medical Sciences was supported by National Cancer Institute (NCI) PO1 grant CA55819-01A1, NCI R33 Grant CA97513-01, Donna D. and Donald M. Lambert Lebow Fund to Cure Myeloma and Nancy and Steven Grand Foundation. We are grateful to the individuals whose gene expression data were used in this study. All MAQC-II participants freely donated their time and reagents for the completion and analyses of the MAQC-II project. The MAQC-II consortium also thanks R. O'Neill for his encouragement and coordination among FDA Centers on the formation of the RBWG. The MAQC-II consortium gratefully dedicates this work in memory of R.F. Wagner who enthusiastically worked on the MAQC-II project and inspired many of us until he unexpectedly passed away in June 2008. NR 65 TC 325 Z9 333 U1 11 U2 113 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2010 VL 28 IS 8 BP 827 EP U109 DI 10.1038/nbt.1665 PG 15 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 636RM UT WOS:000280757500023 PM 20676074 ER PT J AU Philpott, C AF Philpott, Caroline TI BIOINORGANIC CHEMISTRY Getting a grip on iron SO NATURE CHEMICAL BIOLOGY LA English DT News Item ID ISCHEMIA-REPERFUSION INJURY; LIPOCALIN; ENTEROBACTIN; ACQUISITION; INFECTION; DELIVERY; KIDNEY C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Philpott, C (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. EM CarolineP@intra.niddk.nih.gov NR 10 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD AUG PY 2010 VL 6 IS 8 BP 568 EP 570 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 628EG UT WOS:000280096600005 PM 20644542 ER PT J AU Albizu, L Cottet, M Kralikova, M Stoev, S Seyer, R Brabet, I Roux, T Bazin, H Bourrier, E Lamarque, L Breton, C Rives, ML Newman, A Javitch, J Trinquet, E Manning, M Pin, JP Mouillac, B Durroux, T AF Albizu, Laura Cottet, Martin Kralikova, Michaela Stoev, Stoytcho Seyer, Rene Brabet, Isabelle Roux, Thomas Bazin, Herve Bourrier, Emmanuel Lamarque, Laurent Breton, Christophe Rives, Marie-Laure Newman, Amy Javitch, Jonathan Trinquet, Eric Manning, Maurice Pin, Jean-Philippe Mouillac, Bernard Durroux, Thierry TI Time-resolved FRET between GPCR ligands reveals oligomers in native tissues SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PROTEIN-COUPLED-RECEPTORS; HUMAN OXYTOCIN RECEPTOR; FLUORESCENCE ENERGY-TRANSFER; VASOPRESSIN RECEPTOR; PEPTIDE ANTAGONIST; BINDING-PROPERTIES; HORMONE-RECEPTORS; DIMERIC GPCR; HUMAN V1A; IN-VIVO AB G protein-coupled receptor (GPCR) oligomers have been proposed to play critical roles in cell signaling, but confirmation of their existence in a native context remains elusive, as no direct interactions between receptors have been reported. To demonstrate their presence in native tissues, we developed a time-resolved FRET strategy that is based on receptor labeling with selective fluorescent ligands. Specific FRET signals were observed with four different receptors expressed in cell lines, consistent with their dimeric or oligomeric nature in these transfected cells. More notably, the comparison between FRET signals measured with sets of fluorescent agonists and antagonists was consistent with an asymmetric relationship of the two protomers in an activated GPCR dimer. Finally, we applied the strategy to native tissues and succeeded in demonstrating the presence of oxytocin receptor dimers and/or oligomers in mammary gland. C1 [Albizu, Laura; Cottet, Martin; Seyer, Rene; Brabet, Isabelle; Pin, Jean-Philippe; Mouillac, Bernard; Durroux, Thierry] CNRS, Inst Genom Fonct, Montpellier, France. [Albizu, Laura; Cottet, Martin; Seyer, Rene; Brabet, Isabelle; Pin, Jean-Philippe; Mouillac, Bernard; Durroux, Thierry] INSERM, Montpellier, France. [Albizu, Laura; Cottet, Martin; Seyer, Rene; Brabet, Isabelle; Pin, Jean-Philippe; Mouillac, Bernard; Durroux, Thierry] Univ Montpellier I, Montpellier, France. [Albizu, Laura; Cottet, Martin; Seyer, Rene; Brabet, Isabelle; Pin, Jean-Philippe; Mouillac, Bernard; Durroux, Thierry] Univ Montpellier 2, Montpellier, France. [Kralikova, Michaela; Rives, Marie-Laure; Javitch, Jonathan] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA. [Kralikova, Michaela; Rives, Marie-Laure; Javitch, Jonathan] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Kralikova, Michaela; Rives, Marie-Laure; Javitch, Jonathan] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA. [Stoev, Stoytcho; Manning, Maurice] Univ Toledo, Coll Med, Dept Biochem & Canc Biol, Toledo, OH 43606 USA. [Roux, Thomas; Bazin, Herve; Bourrier, Emmanuel; Lamarque, Laurent; Trinquet, Eric] Cisbio Bioassays, Bagnols Sur Ceze, France. [Breton, Christophe] Univ Sci & Technol Lille, Dept Physiol, Lab Neuroendocrinol Dev, Villeneuve Dascq, France. [Newman, Amy] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. [Javitch, Jonathan] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. [Albizu, Laura; Kralikova, Michaela] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Albizu, Laura; Kralikova, Michaela] Acad Sci Czech Republic, Dept Auditory Neurosci, Prague, Czech Republic. RP Pin, JP (reprint author), CNRS, Inst Genom Fonct, Montpellier, France. EM jppin@igf.cnrs.fr; bmouillac@igf.cnrs.fr; tdurroux@igf.cnrs.fr RI Kralikova, Michaela/H-2588-2014; MOUILLAC, Bernard/M-3896-2014 FU Centre National de la Recherche Scientifique; Institut National de la Sante et de la Recherche Medicale; Actions Concertees Incitatives "Molecules Cibles et Therapeutiques" [240, 355, ANR-06-BLAN-0087-03, ANR-09-BLAN-0272]; US National Institutes of Health [GM025280, DA022413, MH54137] FX Thanks are due to S. Granier, P. Rondard and L. Prezeau for their critical reading of the manuscript. This work was supported by research grants from the Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale, Actions Concertees Incitatives "Molecules Cibles et Therapeutiques" (no. 240 and 355), ANR-06-BLAN-0087-03 and ANR-09-BLAN-0272) and the US National Institutes of Health (grants GM025280, DA022413, MH54137). This work was also made possible by the Plateforme de Pharmacologie-Criblage of Montpellier and the Region Languedoc-Roussillon. NAPS and PPHT amines were synthesized by the National Institute of Mental Health Chemical Synthesis and Drug Supply Program and provided by A.N. and J.J. NR 50 TC 173 Z9 175 U1 3 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD AUG PY 2010 VL 6 IS 8 BP 587 EP 594 DI 10.1038/NCHEMBIO.396 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 628EG UT WOS:000280096600009 PM 20622858 ER PT J AU Conde, L Halperin, E Akers, NK Brown, KM Smedby, KE Rothman, N Nieters, A Slager, SL Brooks-Wilson, A Agana, L Riby, J Liu, JJ Adami, HO Darabi, H Hjalgrim, H Low, HQ Humphreys, K Melbye, M Chang, ET Glimelius, B Cozen, W Davis, S Hartge, P Morton, LM Schenk, M Wang, SS Armstrong, B Kricker, A Milliken, S Purdue, MP Vajdic, CM Boyle, P Lan, Q Zahm, SH Zhang, YW Zheng, TZ Becker, N Benavente, Y Boffetta, P Brennan, P Butterbach, K Cocco, P Foretova, L Maynadie, M de Sanjose, S Staines, A Spinelli, JJ Achenbach, SJ Call, TG Camp, NJ Glenn, M Caporaso, NE Cerhan, JR Cunningham, JM Goldin, LR Hanson, CA Kay, NE Lanasa, MC Leis, JF Marti, GE Rabe, KG Rassenti, LZ Spector, LG Strom, SS Vachon, CM Weinberg, JB Holly, EA Chanock, S Smith, MT Bracci, PM Skibola, CF AF Conde, Lucia Halperin, Eran Akers, Nicholas K. Brown, Kevin M. Smedby, Karin E. Rothman, Nathaniel Nieters, Alexandra Slager, Susan L. Brooks-Wilson, Angela Agana, Luz Riby, Jacques Liu, Jianjun Adami, Hans-Olov Darabi, Hatef Hjalgrim, Henrik Low, Hui-Qi Humphreys, Keith Melbye, Mads Chang, Ellen T. Glimelius, Bengt Cozen, Wendy Davis, Scott Hartge, Patricia Morton, Lindsay M. Schenk, Maryjean Wang, Sophia S. Armstrong, Bruce Kricker, Anne Milliken, Sam Purdue, Mark P. Vajdic, Claire M. Boyle, Peter Lan, Qing Zahm, Shelia H. Zhang, Yawei Zheng, Tongzhang Becker, Nikolaus Benavente, Yolanda Boffetta, Paolo Brennan, Paul Butterbach, Katja Cocco, Pierluigi Foretova, Lenka Maynadie, Marc de Sanjose, Silvia Staines, Anthony Spinelli, John J. Achenbach, Sara J. Call, Timothy G. Camp, Nicola J. Glenn, Martha Caporaso, Neil E. Cerhan, James R. Cunningham, Julie M. Goldin, Lynn R. Hanson, Curtis A. Kay, Neil E. Lanasa, Mark C. Leis, Jose F. Marti, Gerald E. Rabe, Kari G. Rassenti, Laura Z. Spector, Logan G. Strom, Sara S. Vachon, Celine M. Weinberg, J. Brice Holly, Elizabeth A. Chanock, Stephen Smith, Martyn T. Bracci, Paige M. Skibola, Christine F. TI Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32 SO NATURE GENETICS LA English DT Article ID NON-HODGKIN-LYMPHOMA; NECROSIS-FACTOR TNF; HIGH-RESOLUTION; HLA; SUSCEPTIBILITY; HAPLOTYPE; POLYMORPHISMS AB To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)). C1 [Conde, Lucia; Akers, Nicholas K.; Agana, Luz; Riby, Jacques; Smith, Martyn T.; Skibola, Christine F.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Halperin, Eran] Tel Aviv Univ, Mol Microbiol & Biotechnol Dept, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Brown, Kevin M.] Translat Genom Res Inst TGen, Integrat Canc Genom Div, Phoenix, AZ USA. [Smedby, Karin E.] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Rothman, Nathaniel; Hartge, Patricia; Morton, Lindsay M.; Wang, Sophia S.; Purdue, Mark P.; Lan, Qing; Zahm, Shelia H.; Caporaso, Neil E.; Goldin, Lynn R.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Nieters, Alexandra; Becker, Nikolaus; Butterbach, Katja] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Nieters, Alexandra] Univ Freiburg, Med Ctr, Ctr Chron Immunodeficiency, D-7800 Freiburg, Germany. [Slager, Susan L.; Achenbach, Sara J.; Call, Timothy G.; Cerhan, James R.; Cunningham, Julie M.; Hanson, Curtis A.; Kay, Neil E.; Leis, Jose F.; Rabe, Kari G.; Vachon, Celine M.] Mayo Clin, Coll Med, Rochester, MN USA. [Brooks-Wilson, Angela; Spinelli, John J.] British Columbia Canc Agcy, British Columbia Canc Res Ctr, Vancouver, BC V5Z 4E6, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Vancouver, BC, Canada. [Liu, Jianjun; Low, Hui-Qi] ASTAR, Genome Inst Singapore, Singapore, Singapore. [Adami, Hans-Olov; Darabi, Hatef; Humphreys, Keith] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hjalgrim, Henrik; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Chang, Ellen T.] Canc Prevent Inst Calif, Fremont, CA USA. [Chang, Ellen T.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Glimelius, Bengt] Karolinska Univ Hosp, Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden. [Glimelius, Bengt] Uppsala Univ, Akademiska Hosp, Dept Oncol Radiol & Clin Immunol, Uppsala, Sweden. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Davis, Scott] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Schenk, Maryjean] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Div Etiol, Duarte, CA 91010 USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Armstrong, Bruce; Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. [Milliken, Sam] St Vincents Hosp, Dept Haematol, Sydney, NSW 2010, Australia. [Vajdic, Claire M.] Univ New S Wales, Res Ctr, Prince Wales Clin Sch, Sydney, NSW, Australia. [Boyle, Peter; Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Zhang, Yawei; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Benavente, Yolanda; de Sanjose, Silvia] Catalan Inst Oncol, Unit Infect & Canc UNIC, Canc Epidemiol Res Programme, Barcelona, Spain. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic. [Maynadie, Marc] Univ Burgundy, Univ Hosp Dijon, Registry Hematol Malignancies, EA4184, Dijon, France. [Staines, Anthony] Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin 2, Ireland. [Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Camp, Nicola J.; Glenn, Martha] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA. [Lanasa, Mark C.; Weinberg, J. Brice] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Marti, Gerald E.] US Natl Inst Hlth, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapies, US FDA, Bethesda, MD USA. [Rassenti, Laura Z.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Spector, Logan G.] Univ Minnesota, Prevent & Etiol Res Program, Masonic Canc Ctr, Minneapolis, MN USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Holly, Elizabeth A.; Bracci, Paige M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Skibola, CF (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. EM chrisfs@berkeley.edu RI Armstrong, Bruce/K-9464-2015; Purdue, Mark/C-9228-2016; Benavente, Yolanda/H-9810-2014; Chang, Ellen/G-5700-2010; Conde, Lucia/D-9295-2011; Spinelli, John/B-6210-2013; Boyle, Peter/A-4380-2014; Tang, Macy/B-9798-2014; Brooks-Wilson, Angela/E-9399-2012; de Sanjose Llongueras, Silvia/H-6339-2014; Morton, Lindsay/B-5234-2015 OI Staines, Anthony/0000-0001-9161-1357; Spector, Logan/0000-0003-2516-0222; Armstrong, Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108; Vajdic, Claire/0000-0002-3612-8298; Cerhan, James/0000-0002-7482-178X; Boyle, Peter/0000-0001-6251-0610; Brooks-Wilson, Angela/0000-0003-1009-6408; Morton, Lindsay/0000-0001-9767-2310 FU National Cancer Institute (NCI), US National Institutes of Health (NIH) [CA122663, CA104682, CA45614, CA89745]; American Cancer Society [IRG-07-06401]; Agency for Science and Technology and Research of Singapore (A*STAR); NCI [R01 CA91253, R01 CA118444, CA62006]; Swedish Cancer Society; Swedish Research Council; Danish Medical Research Council; Information Management Services, Inc.; NIH (NCI); US Public Health Service (PHS) [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105]; National Health and Medical Research Council of Australia; Cancer Council NSW; University of Sydney Medical Foundation; Canadian Cancer Society; Canadian Institutes of Health Research; German Jose Carreras Leukemia Foundation [DJCLS_R04/08, R07/26f]; EC [QLK4-CT-2000-00422]; Federal Office for Radiation Protection (Germany) [StSch4261, StSch4420]; Spanish Ministry of Health [06/02/0073]; FIS [08-1555]; Marato TV3 (Spain) [051210]; La Fondation de France [1999 0084 71]; Compagnia di San Paolo di Torino; Health Research Board, Ireland; Ministry of Health of the Czech Republic [MZ0 MOU 2005] FX This work was supported by grants CA122663 and CA104682 from the National Cancer Institute (NCI), US National Institutes of Health (NIH) (C. F. S.); grants CA45614 and CA89745 from the NCI, NIH (E. A. H.); the American Cancer Society (IRG-07-06401) and a charitable donation by S. Chase (K. B.). E. H. is a faculty fellow of the Edmond J. Safra Bioinformatics program at Tel-Aviv University. SCALE study: We thank X.Y. Chen, H. B. Toh, K. K. Heng and W.Y. Meah from Genome Institute of Singapore for their support in genotyping analyses. We are also grateful to L. Klareskog, Center for Molecular Medicine, and L. Alfredsson, Institute of Environmental Medicine at the Karolinska Institute, Stockholm, Sweden, for sharing DNA from their EIRA study control population and to E. Rehnberg for help with imputing genotypes in the SCALE study. The following agencies contributed funding to SCALE that facilitated the present project: Agency for Science and Technology and Research of Singapore (A*STAR), NCI, the Swedish Cancer Society, the Swedish Research Council and the Danish Medical Research Council. GEC-Mayo Study: This study is supported by grants R01 CA91253 and R01 CA118444 from the NCI. NCI-SEER study: We thank P. Hui of the Information Management Services, Inc. for programming support, and we acknowledge the contributions of the staff and scientists at the SEER centers of Iowa, Los Angeles, Detroit and Seattle for conducting the study's field effort. We especially acknowledge the contributions of study site principal investigator L. Bernstein (Los Angeles). The NCI-SEER study was supported by the Intramural Research Program of the NIH (NCI) and by US Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105. Yale study: This study is supported by grant CA62006 from the NCI and the Intramural Research Program of the NIH (NCI). NSW study: The NSW study was supported by a National Health and Medical Research Council of Australia project grant, Cancer Council NSW, a University of Sydney Medical Foundation Program Grant and the Intramural Research Program of the NIH (NCI). BC study: Funding for the British Columbia study was from the Canadian Cancer Society and the Canadian Institutes of Health Research. A.B.-W. is a Senior Scholar of the Michael Smith Foundation for Health Research. EpiLymph study: Funding was available from the German Jose Carreras Leukemia Foundation (DJCLS_R04/08 and R07/26f) (A.N.), the EC 5th Framework Program Quality of Life grant No. QLK4-CT-2000-00422 (P. Boffetta, P. Brennan), the Federal Office for Radiation Protection grants No. StSch4261 and StSch4420 (Germany), the Spanish Ministry of Health grants Centro de Investigacion Biomedica en Red de Epidemiologia y Salud Publica (CIBERESP) (06/02/0073), FIS 08-1555 and Marato TV3 (051210) (Spain), La Fondation de France, no. 1999 0084 71 (M. Maynadie), Compagnia di San Paolo di Torino, Programma Oncologia 2001 (P. C.), the Health Research Board, Ireland, and the Ministry of Health of the Czech Republic, MZ0 MOU 2005 (L. F.). NR 13 TC 86 Z9 88 U1 0 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 AUG PY 2010 VL 42 IS 8 BP 661 EP 664 DI 10.1038/ng.626 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 633RZ UT WOS:000280524000008 PM 20639881 ER PT J AU Sales, KU Masedunskas, A Bey, AL Rasmussen, AL Weigert, R List, K Szabo, R Overbeek, PA Bugge, TH AF Sales, Katiuchia Uzzun Masedunskas, Andrius Bey, Alexandra L. Rasmussen, Amber L. Weigert, Roberto List, Karin Szabo, Roman Overbeek, Paul A. Bugge, Thomas H. TI Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome SO NATURE GENETICS LA English DT Article ID SERINE-PROTEASE INHIBITOR; HUMAN STRATUM-CORNEUM; HEPATOCYTE GROWTH-FACTOR; BARRIER FUNCTION; TRYPSIN-LIKE; PROTEOLYTIC CASCADE; RECEPTORS PARS; EXPRESSION; DESQUAMATION; FILAGGRIN AB Deficiency in the serine protease inhibitor LEKTI is the etiological origin of Netherton syndrome, which causes detachment of the stratum corneum and chronic inflammation. Here we show that the membrane protease matriptase initiates Netherton syndrome in a LEKTI-deficient mouse model by premature activation of a pro-kallikrein cascade. Auto-activation of pro-inflammatory pro-kallikrein-related peptidases that are associated with stratum corneum detachment was either low or undetectable, but they were efficiently activated by matriptase. Ablation of matriptase from LEKTI-deficient mice dampened inflammation, eliminated aberrant protease activity, prevented detachment of the stratum corneum, and improved the barrier function of the epidermis. These results uncover a pathogenic matriptase-pro-kallikrein pathway that could operate in several human skin and inflammatory diseases. C1 [Sales, Katiuchia Uzzun; Bey, Alexandra L.; Rasmussen, Amber L.; List, Karin; Szabo, Roman; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Overbeek, Paul A.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov OI Masedunskas, Andrius/0000-0002-4533-5467 FU NIDCR FX We thank D. Martin, L. Fisher and L. Wahl for technical assistance, and J. Silvio Gutkind and M. J. Danton for reviewing this manuscript. Support for this study was provided by the NIDCR Intramural Research Program. NR 49 TC 56 Z9 58 U1 0 U2 1 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 AUG PY 2010 VL 42 IS 8 BP 676 EP U54 DI 10.1038/ng.629 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 633RZ UT WOS:000280524000011 PM 20657595 ER PT J AU Johansen, CT Wang, JA Lanktree, MB Cao, HN McIntyre, AD Ban, MR Martins, RA Kennedy, BA Hassell, RG Visser, ME Schwartz, SM Voight, BF Elosua, R Salomaa, V O'Donnell, CJ Dallinga-Thie, GM Anand, SS Yusuf, S Huff, MW Kathiresan, S Hegele, RA AF Johansen, Christopher T. Wang, Jian Lanktree, Matthew B. Cao, Henian McIntyre, Adam D. Ban, Matthew R. Martins, Rebecca A. Kennedy, Brooke A. Hassell, Reina G. Visser, Maartje E. Schwartz, Stephen M. Voight, Benjamin F. Elosua, Roberto Salomaa, Veikko O'Donnell, Christopher J. Dallinga-Thie, Geesje M. Anand, Sonia S. Yusuf, Salim Huff, Murray W. Kathiresan, Sekar Hegele, Robert A. TI Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia SO NATURE GENETICS LA English DT Article ID HYPERLIPOPROTEINEMIA PHENOTYPES; POPULATION; DISEASE; LOCI; RISK; TRIGLYCERIDES; CHOLESTEROL; CONTRIBUTE; MUTATIONS; ALLELES AB Genome-wide association studies (GWAS) have identified multiple loci associated with plasma lipid concentrations(1-5). Common variants at these loci together explain <10% of variation in each lipid trait(4,5). Rare variants with large individual effects may also contribute to the heritability of lipid traits(6,7); however, the extent to which rare variants affect lipid phenotypes remains to be determined. Here we show an accumulation of rare variants, or a mutation skew, in GWAS-identified genes in individuals with hypertriglyceridemia (HTG). Through GWAS, we identified common variants in APOA5, GCKR, LPL and APOB associated with HTG. Resequencing of these genes revealed a significant burden of 154 rare missense or nonsense variants in 438 individuals with HTG, compared to 53 variants in 327 controls (P = 6.2 x 10(-8)), corresponding to a carrier frequency of 28.1% of affected individuals and 15.3% of controls (P = 2.6 x 10(-5)). Considering rare variants in these genes incrementally increased the proportion of genetic variation contributing to HTG. C1 [Johansen, Christopher T.; Wang, Jian; Lanktree, Matthew B.; Cao, Henian; McIntyre, Adam D.; Ban, Matthew R.; Martins, Rebecca A.; Kennedy, Brooke A.; Hassell, Reina G.; Huff, Murray W.; Hegele, Robert A.] Univ Western Ontario, Dept Biochem, Robarts Res Inst, London, ON, Canada. [Visser, Maartje E.; Dallinga-Thie, Geesje M.] Univ Amsterdam, Acad Med Ctr, Dept Expt Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Visser, Maartje E.; Dallinga-Thie, Geesje M.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Schwartz, Stephen M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Voight, Benjamin F.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Voight, Benjamin F.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Voight, Benjamin F.; Kathiresan, Sekar] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Elosua, Roberto] Inst Municipal Invest Med, E-08003 Barcelona, Spain. [Salomaa, Veikko] Natl Inst Hlth & Welf, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Anand, Sonia S.; Yusuf, Salim] McMaster Univ, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada. [Huff, Murray W.; Hegele, Robert A.] Univ Western Ontario, Dept Med, Schulich Sch Med & Dent, London, ON, Canada. RP Hegele, RA (reprint author), Univ Western Ontario, Dept Biochem, Robarts Res Inst, London, ON, Canada. EM hegele@robarts.ca RI Voight, Benjamin/F-1775-2011; Hegele, Robert/G-3301-2011; OI Lanktree, Matthew/0000-0002-5750-6286; ELOSUA, ROBERTO/0000-0001-8235-0095 FU US National Institutes of Health through the National Heart, Lung, and Blood Institute [R01 HL087676]; National Center for Research Resources [U54 RR020278]; Canadian Institutes of Health Research (CIHR) [MOP-13430, MOP-79523, CTP-79853]; Heart and Stroke Foundation of Ontario; Sigrid Juselius Foundation; Finnish Academy [129494]; Michael G. DeGroote Heart and Stroke Foundation of Ontario Chair; Eli Lilly May Cohen Chair in Women's Health Research at McMaster University; Jacob J. Wolfe Distinguished Medical Research Chair; Edith Schulich Vinet Canada Research Chair in Human Genetics (Tier I); Heart and Stroke Foundation of Ontario [NA-6059, T-6018, PRG-4854]; Pfizer Jean Davignon Distinguished Cardiovascular and Metabolic; Genome Canada through the Ontario Genomics Institute FX We thank the London Regional Genomics Centre (D. Carter, G. Barbe and K. Kang) for their dedication to this project, and the Myocardial Infarction Genetics Consortium (MIGen) study for the use of their genotype data as control data in our study. The MIGen study was funded by the US National Institutes of Health through the National Heart, Lung, and Blood Institute's STAMPEED genomics research program (R01 HL087676) and the National Center for Research Resources (U54 RR020278). This work was made possible by the facilities of the Shared Hierarchical Academic Research Computing Network (SHARCNET). C.T.J. is supported by a Canadian Institutes of Health Research (CIHR) Banting and Best Canada Graduate Scholarship, a Heart and Stroke Foundation of Ontario Program Grant and a CIHR Vascular Research Fellowship. V. S. was supported by the Sigrid Juselius Foundation and by the Finnish Academy (grant 129494). S. S. A. is supported by the Michael G. DeGroote Heart and Stroke Foundation of Ontario Chair and the Eli Lilly May Cohen Chair in Women's Health Research at McMaster University. R. A. H. is supported by the Jacob J. Wolfe Distinguished Medical Research Chair, the Edith Schulich Vinet Canada Research Chair in Human Genetics (Tier I), the Martha G. Blackburn Chair in Cardiovascular Research and operating grants from the CIHR (MOP-13430, MOP-79523, CTP-79853), the Heart and Stroke Foundation of Ontario (NA-6059, T-6018, PRG-4854), the Pfizer Jean Davignon Distinguished Cardiovascular and Metabolic Research Award and Genome Canada through the Ontario Genomics Institute. NR 27 TC 255 Z9 263 U1 0 U2 15 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 AUG PY 2010 VL 42 IS 8 BP 684 EP U59 DI 10.1038/ng.628 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 633RZ UT WOS:000280524000012 PM 20657596 ER PT J AU Remmers, EF Cosan, F Kirino, Y Ombrello, MJ Abaci, N Satorius, C Le, JM Yang, B Korman, BD Cakiris, A Aglar, O Emrence, Z Azakli, H Ustek, D Tugal-Tutkun, I Akman-Demir, G Chen, W Amos, CI Dizon, MB Kose, AA Azizlerli, G Erer, B Brand, OJ Kaklamani, VG Kaklamanis, P Ben-Chetrit, E Stanford, M Fortune, F Ghabra, M Ollier, WER Cho, YH Bang, D O'Shea, J Wallace, GR Gadina, M Kastner, DL Gul, A AF Remmers, Elaine F. Cosan, Fulya Kirino, Yohei Ombrello, Michael J. Abaci, Neslihan Satorius, Colleen Le, Julie M. Yang, Barbara Korman, Benjamin D. Cakiris, Aris Aglar, Oznur Emrence, Zeliha Azakli, Hulya Ustek, Duran Tugal-Tutkun, Ilknur Akman-Demir, Gulsen Chen, Wei Amos, Christopher I. Dizon, Michael B. Kose, Afet Akdag Azizlerli, Gulsevim Erer, Burak Brand, Oliver J. Kaklamani, Virginia G. Kaklamanis, Phaedon Ben-Chetrit, Eldad Stanford, Miles Fortune, Farida Ghabra, Marwen Ollier, William E. R. Cho, Young-Hun Bang, Dongsik O'Shea, John Wallace, Graham R. Gadina, Massimo Kastner, Daniel L. Gul, Ahmet TI Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease SO NATURE GENETICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTERLEUKIN-10 RECEPTOR; LOCI; RISK; GENE; SUSCEPTIBILITY; TRANSCRIPTION; POLYMORPHISM; PROMOTER; COLITIS AB Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production. C1 [Remmers, Elaine F.; Kirino, Yohei; Ombrello, Michael J.; Satorius, Colleen; Le, Julie M.; Korman, Benjamin D.; Kastner, Daniel L.] NIAMSD, Clin Invest Lab, Bethesda, MD 20892 USA. [Cosan, Fulya; Erer, Burak; Gul, Ahmet] Istanbul Univ, Dept Internal Med, Istanbul Fac Med, Div Rheumatol, Istanbul, Turkey. [Abaci, Neslihan; Cakiris, Aris; Aglar, Oznur; Emrence, Zeliha; Azakli, Hulya; Ustek, Duran; Gul, Ahmet] Istanbul Univ, Dept Genet, Inst Expt Med, Istanbul, Turkey. [Yang, Barbara; Dizon, Michael B.; Gadina, Massimo] NIAMSD, Translat Immunol Sect, Off Sci & Technol, Bethesda, MD 20892 USA. [Tugal-Tutkun, Ilknur] Istanbul Univ, Istanbul Fac Med, Dept Ophthalmol, Istanbul, Turkey. [Akman-Demir, Gulsen] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Istanbul, Turkey. [Chen, Wei; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kose, Afet Akdag; Azizlerli, Gulsevim] Istanbul Univ, Dept Dermatol, Istanbul Fac Med, Istanbul, Turkey. [Brand, Oliver J.] Univ Birmingham, Sch Clin & Expt Med, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Kaklamani, Virginia G.] Northwestern Univ, Translat Breast Canc Res Div Hematol & Oncol, Chicago, IL 60611 USA. [Kaklamanis, Phaedon] Athens Med Ctr, Dept Rheumatol, Athens, Greece. [Ben-Chetrit, Eldad] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Stanford, Miles] Kings Coll London, London WC2R 2LS, England. [Fortune, Farida] Queen Marys Coll, London, England. [Ghabra, Marwen] Univ Hosp, Damascus, Syria. [Ollier, William E. R.] Univ Manchester, Ctr Integrated Genom Med Res, Sch Immun & Infect, Manchester, Lancs, England. [Cho, Young-Hun] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Bang, Dongsik] Yonsei Univ, Coll Med, Dept Dermatol, Seoul, South Korea. [O'Shea, John] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. [Wallace, Graham R.] Univ Birmingham, Acad Unit Ophthalmol, Birmingham, W Midlands, England. RP Remmers, EF (reprint author), NIAMSD, Clin Invest Lab, Bethesda, MD 20892 USA. EM remmerse@mail.nih.gov RI 桐野, 洋平/B-3701-2009; Ustek, Duran/C-3484-2009 OI 桐野, 洋平/0000-0002-9488-661X; Ustek, Duran/0000-0002-0060-2859 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the US National Institutes of Health; Istanbul University; UK Behcet's Syndrome Society; US NIH [AR44422, PC30CA016772] FX This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the US National Institutes of Health, by the Istanbul University Research Fund and by the UK Behcet's Syndrome Society. This work was also supported in the part by US NIH grants to C. I. A. (AR44422 and PC30CA016772). We thank all of our subjects for their enthusiastic support of our studies aiming to understand and find better treatments for Behcet's disease, and we thank O. Aksakalli and H. Ustek for their help in blood collection. NR 24 TC 279 Z9 288 U1 2 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 AUG PY 2010 VL 42 IS 8 BP 698 EP U78 DI 10.1038/ng.625 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 633RZ UT WOS:000280524000015 PM 20622878 ER PT J AU Carpenter, AC Bosselut, R AF Carpenter, Andrea C. Bosselut, Remy TI Decision checkpoints in the thymus SO NATURE IMMUNOLOGY LA English DT Review ID T-CELL-RECEPTOR; THYMOCYTE POSITIVE SELECTION; DELTA LINEAGE FATE; GAMMA-DELTA; ALPHA-BETA; ZINC-FINGER; TRANSCRIPTION FACTORS; CD8 LINEAGE; PHOSPHATIDYLINOSITOL 3-KINASE; INTERLEUKIN-7 RECEPTOR AB The development of T cells in the thymus involves several differentiation and proliferation events, during which hematopoietic precursors give rise to T cells ready to respond to antigen stimulation and undergo effector differentiation. This review addresses signaling and transcriptional checkpoints that control the intrathymic journey of T cell precursors. We focus on the divergence of alpha beta and gamma delta lineage cells and the elaboration of the alpha beta T cell repertoire, with special emphasis on the emergence of transcriptional programs that direct lineage decisions. C1 [Carpenter, Andrea C.; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM remy@helix.nih.gov FU National Cancer Institute, Center for Cancer Research, US National Institutes of Health FX We thank J. Ashwell, A. Bhandoola, A. Gegonne, P. Love and A. Singer for their comments on the manuscript. We apologize to colleagues whose work was not directly referenced because of space constraints. Research work in the authors' laboratory is supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, US National Institutes of Health. NR 130 TC 106 Z9 107 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2010 VL 11 IS 8 BP 666 EP 673 DI 10.1038/ni.1887 PG 8 WC Immunology SC Immunology GA 628UX UT WOS:000280149400004 PM 20644572 ER PT J AU Hansen, AM Caspi, RR AF Hansen, Anna M. Caspi, Rachel R. TI Glutamate joins the ranks of immunomodulators SO NATURE MEDICINE LA English DT Editorial Material ID NITRIC-OXIDE; DISEASE; HEALTH; CELLS AB Elevated amounts of glutamate, which acts as a neurotransmitter but is also a neurotoxin, are a hallmark of the autoimmune neurological disease multiple sclerosis and may contribute to its pathology. The discovery that a receptor for glutamate can inhibit the development of autoimmunity and protect from neuroinflammation in a mouse model of multiple sclerosis suggests that glutamate may also have a protective role and that its receptor may represent a therapeutic target (pages 897-902). C1 [Hansen, Anna M.; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Hansen, AM (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 Intramural NIH HHS [ZIA EY000184-28] NR 10 TC 10 Z9 10 U1 0 U2 5 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 AUG PY 2010 VL 16 IS 8 BP 856 EP 858 DI 10.1038/nm0810-856 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 635IQ UT WOS:000280649200020 PM 20689547 ER PT J AU Gavara, N Chadwick, RS AF Gavara, Nuria Chadwick, Richard S. TI Noncontact microrheology at acoustic frequencies using frequency-modulated atomic force microscopy SO NATURE METHODS LA English DT Article ID TECTORIAL MEMBRANE; HUMAN PLATELETS; LIQUIDS; CELLS; SUBSTRATE; STIFFNESS; SURFACES; ADHESION; SPHERE AB We report an atomic force microscopy (AFM) method for assessing elastic and viscous properties of soft samples at acoustic frequencies under non-contact conditions. The method can be used to measure material properties via frequency modulation and is based on hydrodynamics theory of thin gaps we developed here. A cantilever with an attached microsphere is forced to oscillate tens of nanometers above a sample. The elastic modulus and viscosity of the sample are estimated by measuring the frequency-dependence of the phase lag between the oscillating microsphere and the driving piezo at various heights above the sample. This method features an effective area of pyramidal tips used in contact AFM but with only piconewton applied forces. Using this method, we analyzed polyacrylamide gels of different stiffness and assessed graded mechanical properties of guinea pig tectorial membrane. The technique enables the study of microrheology of biological tissues that produce or detect sound. C1 [Gavara, Nuria; Chadwick, Richard S.] Natl Inst Deafness & Other Commun Disorders, Auditory Mech Sect, NIH, Bethesda, MD USA. RP Chadwick, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, Auditory Mech Sect, NIH, Bethesda, MD USA. EM chadwick@helix.nih.gov FU US National Institute of Deafness and Other Communication Disorders FX We thank T. B. Friedman and K. H. Iwasa for critical input. This work was supported by the Intramural Program of the US National Institute of Deafness and Other Communication Disorders. NR 28 TC 27 Z9 27 U1 5 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD AUG PY 2010 VL 7 IS 8 BP 650 EP U70 DI 10.1038/NMETH.1474 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 633KD UT WOS:000280500000011 PM 20562866 ER PT J AU Tessarollo, L AF Tessarollo, Lino TI Brain disorders: getting 'Down' to the gene SO NATURE NEUROSCIENCE LA English DT Editorial Material ID TS65DN MOUSE MODEL; DOWN-SYNDROME AB Narrowing down the genetic basis of Down syndrome, in which hundreds of genes are triplicated, has been difficult. A new study finds that the expression of two affected genes, Olig1 and Olig2, is critical for maintaining the balance of inhibitory and excitatory signaling in a mouse model of Down syndrome. C1 NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Tessarollo, L (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. EM tessarol@mail.nih.gov NR 13 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2010 VL 13 IS 8 BP 909 EP 910 DI 10.1038/nn0810-909 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 632DK UT WOS:000280400600002 PM 20661264 ER PT J AU Tost, H Braus, DF Hakimi, S Ruf, M Vollmert, C Hohn, F Meyer-Lindenberg, A AF Tost, Heike Braus, Dieter F. Hakimi, Shabnam Ruf, Matthias Vollmert, Christian Hohn, Fabian Meyer-Lindenberg, Andreas TI Acute D-2 receptor blockade induces rapid, reversible remodeling in human cortical-striatal circuits SO NATURE NEUROSCIENCE LA English DT Article ID HALOPERIDOL; NEURONS; BRAIN; SIZE; GENE AB Structural remodeling has been observed in the human brain over periods of weeks to months, but the molecular mechanisms governing this process remain incompletely characterized. Using multimodal pharmaco-neuroimaging, we found that acute D-2 receptor blockade induced reversible striatal volume changes and structural-functional decoupling in motor circuits within hours; these alterations predicted acute extrapyramidal motor symptoms with high precision. Our findings suggest a role for D-2 receptors in short-term neural plasticity and identify a potential biomarker for neuroleptic side effects in humans. C1 [Tost, Heike; Braus, Dieter F.; Ruf, Matthias; Vollmert, Christian; Hohn, Fabian; Meyer-Lindenberg, Andreas] Univ Heidelberg, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. [Tost, Heike; Hakimi, Shabnam] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Braus, Dieter F.] Clin Psychiat & Psychotherapy, Dr Horst Schmidt Clin, Wiesbaden, Germany. [Ruf, Matthias] Univ Heidelberg, Med Fac Mannheim, Dept Neuroimaging, Cent Inst Mental Hlth, D-6800 Mannheim, Germany. [Vollmert, Christian] Univ Heidelberg, Med Fac Mannheim, Dept Addict Behav & Addict Med, Cent Inst Mental Hlth, D-6800 Mannheim, Germany. RP Tost, H (reprint author), Univ Heidelberg, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. EM tosth@mail.nih.gov RI Meyer-Lindenberg, Andreas/H-1076-2011; OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Hakimi, Shabnam/0000-0003-4122-6041 FU National Institute of Mental Health; US National Institutes of Health; Deutsche Forschungsgemeinschaft-National Institutes of Health [To 539/1-1] FX We thank A. Tenckhoff, J. Rauschenberg, A. Schmitt, M. Hoerst and I. Wolf for research assistance. This research was supported in part by the Intramural Research Program of the National Institute of Mental Health, the US National Institutes of Health and a Deutsche Forschungsgemeinschaft-National Institutes of Health scholarship grant to H. T. (To 539/1-1). NR 15 TC 70 Z9 70 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2010 VL 13 IS 8 BP 920 EP 922 DI 10.1038/nn.2572 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 632DK UT WOS:000280400600008 PM 20526332 ER PT J AU Chakrabarti, L Best, TK Cramer, NP Carney, RSE Isaac, JTR Galdzicki, Z Haydar, TF AF Chakrabarti, Lina Best, Tyler K. Cramer, Nathan P. Carney, Rosalind S. E. Isaac, John T. R. Galdzicki, Zygmunt Haydar, Tarik F. TI Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome SO NATURE NEUROSCIENCE LA English DT Article ID TS65DN MOUSE MODEL; LONG-TERM POTENTIATION; CORTICAL INTERNEURONS; FRONTAL-CORTEX; SPECIFICATION; EXPRESSION; HIPPOCAMPUS; FOREBRAIN; PHENOTYPE; DEFICITS AB Over-inhibition is thought to be one of the underlying causes of the cognitive deficits in Ts65Dn mice, the most widely used model of Down syndrome. We found a direct link between gene triplication and defects in neuron production during embryonic development. These neurogenesis defects led to an imbalance between excitatory and inhibitory neurons and to increased inhibitory drive in the Ts65Dn forebrain. We discovered that Olig1 and Olig2, two genes that are triplicated in Down syndrome and in Ts65Dn mice, were overexpressed in the Ts65Dn forebrain. To test the hypothesis that Olig triplication causes the neurological phenotype, we used a genetic approach to normalize the dosage of these two genes and thereby rescued the inhibitory neuron phenotype in the Ts65Dn brain. These data identify seminal alterations during brain development and suggest a mechanistic relationship between triplicated genes and these brain abnormalities in the Ts65Dn mouse. C1 [Chakrabarti, Lina; Carney, Rosalind S. E.; Haydar, Tarik F.] Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA. [Best, Tyler K.; Cramer, Nathan P.; Galdzicki, Zygmunt] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Isaac, John T. R.] NINDS, Dev Synapt Plast Sect, Bethesda, MD 20892 USA. RP Haydar, TF (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. EM thaydar@bu.edu OI Haydar, Tarik/0000-0001-6772-3076 FU Dana Foundation; National Down Syndrome Society; Jerome Lejeune Foundation; Uniformed Services University of the Health Sciences; Intellectual and Developmental Disabilities Research Center [P30 HD40677]; [RO1 HD05780] FX We wish to thank V. Gallo, J. Corbin, and members of Corbin and Haydar laboratories for discussions and critical reading of the manuscript. This work was supported by a Dana Foundation Neuro-Immuno Imaging grant (T. F. H.), RO1 HD05780 (T. F. H. and Z.G.), the National Down Syndrome Society (L. C.), the Jerome Lejeune Foundation (Z.G.), Uniformed Services University of the Health Sciences (Z.G.) and a gift from Robin and Rob Wilder. Imaging was supported by the Intellectual and Developmental Disabilities Research Center (P30 HD40677). NR 50 TC 79 Z9 79 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2010 VL 13 IS 8 BP 927 EP U39 DI 10.1038/nn.2600 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 632DK UT WOS:000280400600010 PM 20639873 ER PT J AU Trepel, J Mollapour, M Giaccone, G Neckers, L AF Trepel, Jane Mollapour, Mehdi Giaccone, Giuseppe Neckers, Len TI Targeting the dynamic HSP90 complex in cancer SO NATURE REVIEWS CANCER LA English DT Review ID HEAT-SHOCK-PROTEIN; MOLECULAR CHAPERONE HSP90; SQUAMOUS-CELL CARCINOMA; PHASE-II TRIAL; BREAST-CANCER; PROSTATE-CANCER; TYROSINE KINASE; ATPASE CYCLE; SOLID TUMORS; BCR-ABL AB The molecular chaperone heat shock protein 90 (HSP90) has been used by cancer cells to facilitate the function of numerous oncoproteins, and it can be argued that cancer cells are 'addicted' to HSP90. However, although recent reports of the early clinical efficacy of HSP90 inhibitors are encouraging, the optimal use of HSP90-targeted therapeutics will depend on understanding the complexity of HSP90 regulation and the degree to which HSP90 participates in both neoplastic and normal cellular physiology. C1 [Mollapour, Mehdi; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Trepel, Jane; Neckers, Len] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bldg 10,Room 1-5940,9000 Rockville Pike, Bethesda, MD 20892 USA. EM len@helix.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 174 TC 627 Z9 644 U1 16 U2 100 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2010 VL 10 IS 8 BP 537 EP 549 DI 10.1038/nrc2887 PG 13 WC Oncology SC Oncology GA 629LJ UT WOS:000280199600013 PM 20651736 ER PT J AU Litman, GW Rast, JP Fugmann, SD AF Litman, Gary W. Rast, Jonathan P. Fugmann, Sebastian D. TI The origins of vertebrate adaptive immunity SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID VARIABLE LYMPHOCYTE RECEPTORS; ANCIENT EVOLUTIONARY ORIGIN; CLASS-SWITCH RECOMBINATION; B-CELL; SOMATIC HYPERMUTATION; V(D)J RECOMBINATION; SEA-URCHIN; IMMUNOGLOBULIN SECRETION; ANTIBODY REPERTOIRE; ANTIGEN RECEPTORS AB Adaptive immunity is mediated through numerous genetic and cellular processes that generate favourable somatic variants of antigen-binding receptors under evolutionary selection pressure by pathogens and other factors. Advances in our understanding of immunity in mammals and other model organisms are revealing the underlying basis and complexity of this remarkable system. Although the evolution of adaptive immunity has been thought to occur by the acquisition of novel molecular capabilities, an increasing amount of information from new model systems suggest that co-option and redirection of pre-existing systems are the main source of innovation. We combine evidence from a wide range of organisms to obtain an integrated view of the origins and patterns of divergence in adaptive immunity. C1 [Litman, Gary W.] All Childrens Hosp, Dept Mol Genet, St Petersburg, FL 33701 USA. [Litman, Gary W.] Univ S Florida, Dept Pediat, Coll Med, St Petersburg, FL 33701 USA. [Litman, Gary W.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Rast, Jonathan P.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Biophys, Toronto, ON M4N 3M5, Canada. [Rast, Jonathan P.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Immunol, Toronto, ON M4N 3M5, Canada. [Fugmann, Sebastian D.] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Litman, GW (reprint author), All Childrens Hosp, Dept Mol Genet, St Petersburg, FL 33701 USA. EM litmang@allkids.org FU US National Institutes of Health [AI23338, AI57559]; Canadian Institutes for Health Research [MOP74667]; National Science and Engineering Research Council of Canada [NSERC 458115/211598]; US National Institutes of Health, National Institute on Aging FX The work in the laboratory of G.W.L. is supported by US National Institutes of Health grants AI23338 and AI57559. The work in the laboratory of J.P.R. is supported by Canadian Institutes for Health Research grant MOP74667 and National Science and Engineering Research Council of Canada grant NSERC 458115/211598. The work in the laboratory of S. D. F. is supported by the Intramural Research Program of the US National Institutes of Health, National Institute on Aging. NR 95 TC 106 Z9 111 U1 5 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD AUG PY 2010 VL 10 IS 8 BP 543 EP 553 DI 10.1038/nri2807 PG 11 WC Immunology SC Immunology GA 629KX UT WOS:000280198400009 PM 20651744 ER PT J AU Hurley, JH Hanson, PI AF Hurley, James H. Hanson, Phyllis I. TI Membrane budding and scission by the ESCRT machinery: it's all in the neck SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID MULTIVESICULAR BODY PATHWAY; ENDOSOME-ASSOCIATED COMPLEX; AAA ATPASE VPS4; STRUCTURAL BASIS; UBIQUITIN RECOGNITION; SORTING COMPLEX; TRAFFICKING COMPLEX; EAP45-GLUE DOMAIN; VESICLE FORMATION; III RECOGNITION AB The endosomal sorting complexes required for transport (ESCRTs) catalyse one of the most unusual membrane remodelling events in cell biology. ESCRT-I and ESCRT-II direct membrane budding away from the cytosol by stabilizing bud necks without coating the buds and without being consumed in the buds. ESCRT-III cleaves the bud necks from their cytosolic faces. ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis and, probably, autophagy. Recent studies of ultrastructures induced by ESCRT-III overexpression in cells and the in vitro reconstitution of the budding and scission reactions have led to breakthroughs in understanding these remarkable membrane reactions. C1 [Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Hanson, Phyllis I.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov; phanson22@wustl.edu RI Hanson, Phyllis/E-9420-2012 FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; Intramural AIDS Targeted Antiretroviral Program; American Heart Association FX Research in the Hurley laboratory is supported by the intramural program of the National Institutes of Health, The National Institute of Diabetes and Digestive and Kidney Diseases and the Intramural AIDS Targeted Antiretroviral Program. Research in the Hanson laboratory is supported by grants from the National Institutes of Health and the American Heart Association. Both authors thank the members of their laboratories and other colleagues for helpful discussions. NR 103 TC 299 Z9 304 U1 5 U2 64 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD AUG PY 2010 VL 11 IS 8 BP 556 EP 566 DI 10.1038/nrm2937 PG 11 WC Cell Biology SC Cell Biology GA 629LU UT WOS:000280201100012 PM 20588296 ER PT J AU Skinner, M AF Skinner, Mhairi TI CELL CYCLE ARPC1B-a regulator of regulators SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Editorial Material C1 [Skinner, Mhairi] NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. RP Skinner, M (reprint author), NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. NR 1 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD AUG PY 2010 VL 11 IS 8 DI 10.1038/nrm2946 PG 1 WC Cell Biology SC Cell Biology GA 629LU UT WOS:000280201100008 PM 20651704 ER PT J AU Swaroop, A Kim, D Forrest, D AF Swaroop, Anand Kim, Douglas Forrest, Douglas TI Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID NUCLEAR RECEPTOR NR2E3; DEVELOPING MOUSE RETINA; MUTUALLY EXCLUSIVE EXPRESSION; THYROID-HORMONE RECEPTOR; CELL-FATE DETERMINATION; CONE OPSIN EXPRESSION; LOCUS-CONTROL REGION; HUMAN COLOR-VISION; CRX-DEFICIENT MICE; ROD PHOTORECEPTORS AB In the developing vertebrate retina, diverse neuronal subtypes originate from multipotent progenitors in a conserved order and are integrated into an intricate laminated architecture. Recent progress in mammalian photoreceptor development has identified a complex relationship between six key transcription-regulatory factors (ROR beta, OTX2, NRL, CRX, NR2E3 and TR beta 2) that determine rod versus M cone or S cone cell fate. We propose a step-wise 'transcriptional dominance' model of photoreceptor cell fate determination, with the S cone representing the default state of a generic photoreceptor precursor. Elucidation of gene-regulatory networks that dictate photoreceptor genesis and homeostasis will have wider implications for understanding the development of nervous system function and for the treatment of neurodegenerative diseases. C1 [Swaroop, Anand; Kim, Douglas] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Forrest, Douglas] NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bldg 6-338,MSC 0610,6 Ctr Dr, Bethesda, MD 20892 USA. EM swaroopa@nei.nih.gov OI Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute and National Institute of Diabetes, Digestive and Kidney Diseases FX This Review is dedicated to the memory of R. Adler, an outstanding scientist and a generous mentor and colleague. We are grateful to P. Raymond for constructive suggestions, T. Cogliati for productive discussions, and L. Ng, D. Sharlin, Alok Swaroop, S. Veleri and L. Kibiuk for help with the figures. We apologize to colleagues whose papers have not been cited because of page limitations. Our research is supported by intramural programmes of the National Eye Institute and National Institute of Diabetes, Digestive and Kidney Diseases. NR 155 TC 185 Z9 189 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD AUG PY 2010 VL 11 IS 8 BP 563 EP 576 DI 10.1038/nrn2880 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 628UY UT WOS:000280149600010 PM 20648062 ER PT J AU Colbert, RA AF Colbert, Robert A. TI Classification of juvenile spondyloarthritis: enthesitis-related arthritis and beyond SO NATURE REVIEWS RHEUMATOLOGY LA English DT Review ID ONSET ANKYLOSING-SPONDYLITIS; GENOME-WIDE ASSOCIATION; IDIOPATHIC ARTHRITIS; PSORIATIC-ARTHRITIS; CHILDHOOD ARTHRITIS; RHEUMATOLOGY CLASSIFICATION; SERONEGATIVE ENTHESOPATHY; RADIOGRAPHIC PROGRESSION; INTERNATIONAL LEAGUE; DURBAN CRITERIA AB Spondyloarthritis (SpA) refers to a spectrum of immune-mediated inflammatory diseases with overlapping features, which differ from other types of inflammatory arthritis in genetic predisposition, pathogenesis and outcome. SpA frequently involves the axial skeleton, and can result in abnormal bone formation with eventual ankylosis of the spine, resulting in substantial disability. SpA often begins as an 'undifferentiated' disease, the presentation of which differs in children and adults; most notably, spinal involvement is uncommon, while hip arthritis and enthesitis are frequently seen in juvenile-onset disease. Currently, the classification of SpA in adults and children is approached differently. Using the International League of Associations for Rheumatology (ILAR) system for juvenile idiopathic arthritis, most childhood SpA is classified as enthesitis-related arthritis. However, in contrast to adult SpA classification, the presence of, or a family history of, psoriasis dictates a separate category of juvenile idiopathic arthritis. More importantly, the ILAR system does not specifically recognize the presence of axial disease in juvenile SpA. Resolution of these issues will improve communication and the transitioning of patients from pediatric to adult clinics, will facilitate research in genetics and pathogenesis, and will be particularly important in the evaluation of tumor necrosis factor inhibitors and other biologic agents for early, axial SpA. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Colbert, RA (reprint author), NIAMSD, NIH, Bldg 10-CRC,Room 1-5142,10 Ctr Dr,MSC 1102, Bethesda, MD 20892 USA. EM colbertr@mail.nih.gov FU Intramural NIH HHS [ZIA AR041184-01] NR 70 TC 40 Z9 42 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4790 J9 NAT REV RHEUMATOL JI Nat. Rev. Rheumatol. PD AUG PY 2010 VL 6 IS 8 BP 477 EP 485 DI 10.1038/nrrheum.2010.103 PG 9 WC Rheumatology SC Rheumatology GA 634EE UT WOS:000280561500008 PM 20606622 ER PT J AU Iwamoto, FM Lamborn, KR Robins, HI Mehta, MP Chang, SM Butowski, NA DeAngelis, LM Abrey, LE Zhang, WT Prados, MD Fine, HA AF Iwamoto, Fabio M. Lamborn, Kathleen R. Robins, H. Ian Mehta, Minesh P. Chang, Susan M. Butowski, Nicholas A. DeAngelis, Lisa M. Abrey, Lauren E. Zhang, Wei-Ting Prados, Michael D. Fine, Howard A. TI Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma SO NEURO-ONCOLOGY LA English DT Article DE cintredekin besudotox; convection-enhanced delivery; Gliadel wafers; glioblastoma multiforme; IL13-PE38QQR ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; TUMOR VASCULATURE; ANTIANGIOGENIC THERAPY; EUROPEAN ORGANIZATION; PROLONGS SURVIVAL; MALIGNANT GLIOMAS; MESSENGER-RNA; BRAIN-TUMORS; ANGIOGENESIS AB Convection-enhanced delivery (CED) of cintredekin besudotox (CB) was compared with Gliadel wafers (GW) in adult patients with glioblastoma multiforme (GBM) at first recurrence. Patients were randomized 2:1 to receive CB or GW. CB (0.5 mu g/mL; total flow rate 0.75 mL/h) was administered over 96 hours via 2-4 intraparenchymal catheters placed after tumor resection. GW (3.85%/7.7 mg carmustine per wafer; maximum 8 wafers) were placed immediately after tumor resection. The primary endpoint was overall survival from the time of randomization. Prestated interim analyses were built into the study design. Secondary and tertiary endpoints were safety and health-related quality-of-life assessments. From March 2004 to December 2005, 296 patients were enrolled at 52 centers. Demographic and baseline characteristics were balanced between the 2 treatment arms. Median survival was 36.4 weeks (9.1 months) for CB and 35.3 weeks (8.8 months) for GW (P = .476). For the efficacy evaluable population, the median survival was 45.3 weeks (11.3 months) for CB and 39.8 weeks (10 months) for GW (P = .310). The adverse-events profile was similar in both arms, except that pulmonary embolism was higher in the CB arm (8% vs 1%, P = .014). This is the first randomized phase III evaluation of an agent administered via CED and the first with an active comparator in GBM patients. There was no survival difference between CB administered via CED and GW. Drug distribution was not assessed and may be crucial for evaluating future CED-based therapeutics. C1 [Iwamoto, Fabio M.; Zhang, Wei-Ting; Fine, Howard A.] NCI, NIH, Neuro Oncol Branch, Bethesda, MD 20892 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Butowski, Nicholas A.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Robins, H. Ian; Mehta, Minesh P.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [DeAngelis, Lisa M.; Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Fine, HA (reprint author), NCI, NIH, Neuro Oncol Branch, 9030 Old Georgetown Rd,Bloch Bldg 82,Room 225, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov FU National Institutes of Health [CA62399, CA62422, M01-RR00079, U01CA62421-08, M01 RR03186, 5-U01CA62399-09] FX This study was funded by the National Institutes of Health: NABTC # CA62399 and Member # CA62422, GCRC Grant # M01-RR00079 (S.M.C., K.R.L., and M.D.P.); U01CA62421-08, GCRC Grant # M01 RR03186 (M.P.M.); 5-U01CA62399-09 (L.M.D.). NR 33 TC 90 Z9 90 U1 0 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2010 VL 12 IS 8 BP 855 EP 861 DI 10.1093/neuonc/nop025 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 636CM UT WOS:000280705800011 PM 20200024 ER PT J AU Parkman, HP Hasler, W Koch, K Pasricha, PJ Farrugia, G Snape, W Mccallum, R Calles, J Abell, T Nguyen, L Lee, L Unalp, A Tonascia, J Hamilton, F AF Parkman, H. P. Hasler, W. Koch, K. Pasricha, P. J. Farrugia, G. Snape, W. Mccallum, R. Calles, J. Abell, T. Nguyen, L. Lee, L. Unalp, A. Tonascia, J. Hamilton, F. CA NIH Gastroparesis Clin Res TI Inflammatory and autoimmune markers in diabetic and idiopathic gastroparesis SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract CT Joint International Meeting for Neurogastroenterology and Motility CY AUG 26-29, 2010 CL Boston, MA C1 [Parkman, H. P.] Temple Univ, Philadelphia, PA 19122 USA. [Hasler, W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Koch, K.; Calles, J.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Pasricha, P. J.; Nguyen, L.] Stanford Sch Med, Stanford, CA USA. [Farrugia, G.] Mayo Clin, Rochester, MN USA. [Snape, W.] Calif Pacific Med Ctr, San Francisco, CA USA. [Mccallum, R.] Texas Tech Univ, El Paso, TX USA. [Abell, T.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Lee, L.; Unalp, A.; Tonascia, J.] Johns Hopkins Univ, Baltimore, MD USA. [Hamilton, F.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD AUG PY 2010 VL 22 SU 1 SI SI MA 225 BP 65 EP 65 PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA V45OJ UT WOS:000209825600225 ER PT J AU Cai, LS Liow, JS Houlihan, B Morse, C Innis, RB Pike, VW AF Cai, Lisheng Liow, Jeih-San Houlihan, Brenna Morse, Cheryl Innis, Robert B. Pike, Victor W. TI Synthesis of [C-11]astemizole as a lead candidate radioligand for imaging brain neurofibrillary tangles SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING ID ALZHEIMERS-DISEASE C1 [Cai, Lisheng; Liow, Jeih-San; Houlihan, Brenna; Morse, Cheryl; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S152 EP S153 DI 10.1016/j.neuroimage.2010.04.125 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900127 ER PT J AU Fujita, M Mallinger, AG Zarate, CA Dickstein, LP Zoghbi, SS Pike, VW Zhang, Y Innis, RB Drevets, WC AF Fujita, Masahiro Mallinger, Alan G. Zarate, Carlos A. Dickstein, Leah P. Zoghbi, Sami S. Pike, Victor W. Zhang, Yi Innis, Robert B. Drevets, Wayne C. TI Changes of brain phosphodiesterase 4 in major depression SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Fujita, Masahiro; Mallinger, Alan G.; Zarate, Carlos A.; Dickstein, Leah P.; Zoghbi, Sami S.; Pike, Victor W.; Zhang, Yi; Innis, Robert B.; Drevets, Wayne C.] NIMH, Bethesda, MD 20892 USA. OI Dickstein, Leah/0000-0002-4779-4122 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S51 EP S51 DI 10.1016/j.neuroimage.2010.04.232 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900040 ER PT J AU Hirvonen, J Goodwin, RS Li, CT Morse, C Zoghbi, SS Pike, VW Volkow, ND Huestis, M Innis, RB AF Hirvonen, Jussi Goodwin, Robert S. Li, Cheng-Ta Morse, Cheryl Zoghbi, Sami S. Pike, Victor W. Volkow, Nora D. Huestis, Marilyn Innis, Robert B. TI Chronic heavy cannabis use downregulates brain cannabinoid CB1 receptors in humans SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Hirvonen, Jussi; Li, Cheng-Ta; Morse, Cheryl; Zoghbi, Sami S.; Pike, Victor W.; Innis, Robert B.] NIMH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S14 EP S14 DI 10.1016/j.neuroimage.2010.04.199 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900007 ER PT J AU Kannan, P Brimacombe, KR Zoghbi, SS Liow, JS Morse, C Taku, A Telu, S Pike, VW Halldin, C Gottesman, MM Hall, MD Innis, RB AF Kannan, P. Brimacombe, K. R. Zoghbi, S. S. Liow, J. -S. Morse, C. Taku, A. Telu, S. Pike, V. W. Halldin, C. Gottesman, M. M. Hall, M. D. Innis, R. B. TI [11C]N-desmethyl-loperamide, a substrate that selectively images P-glycoprotein function, is trapped in lysosomes SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Kannan, P.; Zoghbi, S. S.; Liow, J. -S.; Morse, C.; Taku, A.; Telu, S.; Pike, V. W.; Innis, R. B.] NIMH, Bethesda, MD 20892 USA. [Brimacombe, K. R.; Gottesman, M. M.; Hall, M. D.] NCI, Bethesda, MD 20892 USA. [Halldin, C.] Karolinska Inst, Stockholm, Sweden. NR 3 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S72 EP S72 DI 10.1016/j.neuroimage.2010.04.057 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900059 ER PT J AU Kreisl, WC Liow, JS Kimura, N Seneca, N Zoghbi, SS Morse, CL Herscovitch, P Pike, VW Innis, RB AF Kreisl, William C. Liow, Jeih-San Kimura, Nobuyo Seneca, Nicholas Zoghbi, Sami S. Morse, Cheryl L. Herscovitch, Peter Pike, Victor W. Innis, Robert B. TI P-glycoprotein function at the blood-brain barrier in humans can be quantified with the substrate radiotracer [11C]-N-desmethyl-loperamide SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Kreisl, William C.; Liow, Jeih-San; Kimura, Nobuyo; Seneca, Nicholas; Zoghbi, Sami S.; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S36 EP S36 DI 10.1016/j.neuroimage.2010.04.218 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900026 ER PT J AU Liow, JS Lu, SY Zoghbi, SS Gladding, RL Morse, C Hirvonen, J Parsey, RV Innis, RB Pike, VW AF Liow, Jeih-San Lu, Shuiyu Zoghbi, Sami S. Gladding, Robert L. Morse, Cheryl Hirvonen, Jussi Parsey, Ramin V. Innis, Robert B. Pike, Victor W. TI [C-11]CUMI-101, an agonist radioligand for serotonin 5-HT1A receptors, also binds to brain alpha(1)-adrenoceptors in rodents and monkeys SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Liow, Jeih-San; Lu, Shuiyu; Zoghbi, Sami S.; Gladding, Robert L.; Morse, Cheryl; Hirvonen, Jussi; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Parsey, Ramin V.] Columbia Univ, Dept Psychiat, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S56 EP S57 DI 10.1016/j.neuroimage.2010.04.043 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900045 ER PT J AU Logan, J Biegon, A Kim, SW Alexoff, D Fowler, J AF Logan, Jean Biegon, Anat Kim, Sung Won Alexoff, David Fowler, Joanna TI Quantitating aromatase in the human brain with PET and [N-methyl-11C]vorozole([11C]VOR) SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Logan, Jean; Biegon, Anat; Alexoff, David; Fowler, Joanna] Brookhaven Natl Lab, Upton, NY 11973 USA. [Kim, Sung Won] NIAAA, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S114 EP S114 DI 10.1016/j.neuroimage.2010.04.093 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900095 ER PT J AU Pike, VW Zoghbi, SS Shetty, HU Hirvonen, J Anderson, KB Jenko, KJ Morse, C Innis, RB AF Pike, Victor W. Zoghbi, Sami S. Shetty, H. Umesha Hirvonen, Jussi Anderson, Kacey B. Jenko, Kimberly J. Morse, Cheryl Innis, Robert B. TI Comparison of human plasma arterial input function for [C-11]MePPEP determined with LC-MS/MS and radiometric methods SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Pike, Victor W.; Zoghbi, Sami S.; Shetty, H. Umesha; Hirvonen, Jussi; Anderson, Kacey B.; Jenko, Kimberly J.; Morse, Cheryl; Innis, Robert B.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S162 EP S162 DI 10.1016/j.neuroimage.2010.04.132 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900134 ER PT J AU Tuominen, L Salo, J Hirvonen, J Nagren, K Laine, P Melartin, T Isometsa, E Viikari, J Raitakari, O Keltikangas-Jarvinen, L Hietala, J AF Tuominen, Lauri Salo, Johanna Hirvonen, Jussi Nagren, Kjell Laine, Pauliina Melartin, Tarja Isometsa, Erkki Viikari, Jorma Raitakari, Olli Keltikangas-Jarvinen, Liisa Hietala, Jarmo TI Serotonin and harm avoidance revisited SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Tuominen, Lauri; Laine, Pauliina; Hietala, Jarmo] Univ Turku, Dept Psychiat, SF-20500 Turku, Finland. [Tuominen, Lauri; Hirvonen, Jussi; Hietala, Jarmo] Univ Turku, Turku PET Ctr, SF-20500 Turku, Finland. [Salo, Johanna; Keltikangas-Jarvinen, Liisa] Univ Helsinki, Dept Psychol, FIN-00014 Helsinki, Finland. [Hirvonen, Jussi] NIMH, Mol Imaging Branch, NIH, Bethesda, MD USA. [Nagren, Kjell] Odense Univ Hosp, Dept Nucl Med, PET & Cyclotron Unit, Odense, Denmark. [Hirvonen, Jussi; Melartin, Tarja; Isometsa, Erkki] Univ Helsinki, Dept Psychiat, FIN-00014 Helsinki, Finland. [Nagren, Kjell; Viikari, Jorma] Univ Turku, Dept Internal Med, SF-20500 Turku, Finland. [Raitakari, Olli] Univ Turku, Dept Clin Physiol, SF-20500 Turku, Finland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S92 EP S92 DI 10.1016/j.neuroimage.2010.04.074 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900076 ER PT J AU Veronese, M Bertoldo, A Schmidt, KC AF Veronese, Mattia Bertoldo, Alessandra Schmidt, Kathleen C. TI A spectral analysis approach for voxelwise determination of regional rates of cerebral protein synthesis with the L-[1-11C]leucine PET method SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Veronese, Mattia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, Padua, Italy. [Schmidt, Kathleen C.] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA. OI Veronese, Mattia/0000-0003-3562-0683 NR 3 TC 0 Z9 0 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S212 EP S212 DI 10.1016/j.neuroimage.2010.04.173 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900175 ER PT J AU Zanotti-Fregonara, P Liow, JS Fujita, M Zoghbi, SS Comtat, C Elise, L Boellaard, R Pike, VW Innis, RB AF Zanotti-Fregonara, Paolo Liow, Jeih-San Fujita, Masahiro Zoghbi, Sami S. Comtat, Claude Elise, Luong Boellaard, Ronald Pike, Victor W. Innis, Robert B. TI Image-derived input function for brain imaging using the high-resolution research tomograph SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING ID INDEPENDENT COMPONENT ANALYSIS; POSITRON-EMISSION-TOMOGRAPHY; PET; QUANTIFICATION C1 [Zanotti-Fregonara, Paolo; Liow, Jeih-San; Fujita, Masahiro; Zoghbi, Sami S.; Elise, Luong; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Comtat, Claude] CEA SHFJ, Orsay, France. [Boellaard, Ronald] Vrije Univ Amsterdam, Med Ctr, Dept Nucl Med, Amsterdam, Netherlands. NR 6 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S222 EP S222 DI 10.1016/j.neuroimage.2010.04.181 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900183 ER PT J AU Zanotti-Fregonara, P Zoghbi, SS Liow, JS Hong, J Boellaard, R Pike, VW Innis, RB Fujita, M AF Zanotti-Fregonara, Paolo Zoghbi, Sami S. Liow, Jeih-San Hong, Jinsoo Boellaard, Ronald Pike, Victor W. Innis, Robert B. Fujita, Masahiro TI Category: Methodology: Quantification and test-retest study of C-11-(R)-rolipram, a PET tracer of the cAMP cascade, using an arterial input function and an image-derived input function SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Zanotti-Fregonara, Paolo; Zoghbi, Sami S.; Liow, Jeih-San; Hong, Jinsoo; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Boellaard, Ronald] Vrije Univ Amsterdam Med Ctr, Dept Nucl Med, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S161 EP S161 DI 10.1016/j.neuroimage.2010.04.131 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900133 ER PT J AU Zoghbi, SS Anderson, KB Jenko, KJ Innis, RB Pike, VW AF Zoghbi, Sami S. Anderson, Kacey B. Jenko, Kimberley J. Innis, Robert B. Pike, Victor W. TI On the quantitative relationship between radiotracer lipophilicity and plasma free fraction SO NEUROIMAGE LA English DT Meeting Abstract CT 8th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 22-24, 2010 CL Glasgow, SCOTLAND SP GE, GlaxoSmithKline, Map Med Technologies, Nexxus, Pfizer, PMOD Technologies, PsyRING C1 [Zoghbi, Sami S.; Anderson, Kacey B.; Jenko, Kimberley J.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2010 VL 52 SU 1 BP S221 EP S221 DI 10.1016/j.neuroimage.2010.04.180 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 629FZ UT WOS:000280181900182 ER PT J AU Mueller, SC Maheu, FS Dozier, M Peloso, E Mandell, D Leibenluft, E Pine, DS Ernst, M AF Mueller, Sven C. Maheu, Francoise S. Dozier, Mary Peloso, Elizabeth Mandell, Darcy Leibenluft, Ellen Pine, Daniel S. Ernst, Monique TI Early-life stress is associated with impairment in cognitive control in adolescence: An fMRI study SO NEUROPSYCHOLOGIA LA English DT Article DE Stress; Development; Inhibition; Task switching; Maltreatment; Change task ID DEFICIT HYPERACTIVITY DISORDER; EVENT-RELATED FMRI; PEDIATRIC BIPOLAR DISORDER; ANTERIOR CINGULATE CORTEX; RESPONSE-INHIBITION TASK; BRAIN ACTIVATION; FOSTER-CHILDREN; NEURAL-NETWORKS; WORKING-MEMORY; FRONTAL-CORTEX AB Early-life stress (ES) has been associated with diverse forms of psychopathology. Some investigators suggest that these associations reflect the effects of stress on the neural circuits that support cognitive control. However, very few prior studies have examined the associations between ES, cognitive control, and underlying neural architecture. The present study compares adolescents with a documented history of ES to typical adolescents on a cognitive control task using functional magnetic resonance imaging (fMRI). Twelve ES adolescents who were adopted because of early caregiver deprivation (9 females, age = 13 years +/- 2.58) and 21 healthy control adolescents without a history of ES (10 females, age =13 years +/- 1.96) who resided with their biological parents performed the change task (Nelson, Vinton et al., 2007)- a variant of the stop task - during fMRI. Behaviourally, ES adolescents took longer to switch from a prepotent response ("go") to an alternative response ("change") than control adolescents. During correct "change" responses vs. correct "go" responses, this behavioural group difference was accompanied by higher activation in ES subjects than controls. These differences were noted in regions involved in primary sensorimotor processes (pre- and postcentral gyri), conflict monitoring (dorsal anterior cingulate gyrus), inhibitory and response control (inferior prefrontal cortex and striatum), and somatic representations (posterior insula). Furthermore, correct "change" responses vs. incorrect "change" responses recruited the inferior prefrontal cortex (BA 44/46) more strongly in ES subjects than controls. These data suggest impaired cognitive control in youth who experienced ES. Published by Elsevier Ltd. C1 [Mueller, Sven C.; Maheu, Francoise S.; Mandell, Darcy; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Maheu, Francoise S.] Univ Montreal, Res Ctr, CHU Ste Justine, Montreal, PQ H3C 3J7, Canada. [Maheu, Francoise S.] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Dozier, Mary; Peloso, Elizabeth] Univ Delaware, Dept Psychol, Newark, DE USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Mueller, SC (reprint author), NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM msven@mail.nih.gov FU National Alliance for Research on Schizophrenia and Depression (NARSAD); Fonds de la Recherche en Sante du Quebec (FRSQ); NIMH FX This study was supported by a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award and a postdoctoral fellowship from the Fonds de la Recherche en Sante du Quebec (FRSQ) to FSM, and by the NIMH Intramural Research Program. loline Henter provided invaluable editorial assistance. We would also like to thank the three anonymous reviewers for their very helpful and constructive comments in improving earlier versions of this manuscript. NR 74 TC 70 Z9 71 U1 9 U2 34 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 AUG PY 2010 VL 48 IS 10 BP 3037 EP 3044 DI 10.1016/j.neuropsychologia.2010.06.013 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 642AU UT WOS:000281175900025 PM 20561537 ER PT J AU Scheidweiler, KB Ladenheim, B Cadet, JL Huestis, MA AF Scheidweiler, Karl B. Ladenheim, Bruce Cadet, Jean Lud Huestis, Marilyn A. TI Mice Lacking Multidrug Resistance Protein 1a Show Altered Dopaminergic Responses to Methylenedioxymethamphetamine (MDMA) in Striatum SO NEUROTOXICITY RESEARCH LA English DT Article DE Multidrug resistance protein 1a (MDR1a); Methylenedioxymethamphetamine (MDMA); Ecstasy; Dopamine; Striatum; Transgenic mouse ID VESICULAR MONOAMINE TRANSPORTER; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; P-GLYCOPROTEIN; NONLINEAR PHARMACOKINETICS; CELLULAR MECHANISMS; DRUG DISPOSITION; ECSTASY MDMA; NEUROTOXICITY; METHAMPHETAMINE; BRAIN AB Multidrug resistance protein 1a (MDR1a) potentiated methylenedioxymethamphetamine (MDMA)-induced decreases of dopamine (DA) and dopamine transport protein in mouse brain one week after MDMA administration. In the present study, we examined if mdr1a wild-type (mdr1a +/+) and knock-out (mdr1a -/-) mice differentially handle the acute effects of MDMA on the nigrostriatal DA system 0-24 h following a single drug injection. 3-way ANOVA revealed significant 2-way interactions of strain x time (F (5,152) = 32.4, P < 0.001) and strain x dose (F (3,152) = 25.8, P < 0.001) on 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratios in mdr1a +/+ and -/- mice. 0.3-3 h after 10 mg/kg MDMA, DOPAC/DA ratios were increased in mdr1a +/+ mice, but decreased 0.3-1 h after MDMA in mdr1a -/- mice. Twenty-four hours after 10 mg/kg MDMA, DOPAC/DA ratios were increased 600% in mdr1a +/+ mice compared to saline-treated control mice, while in mdr1a -/- mice DOPAC/DA ratios were unchanged. Striatal MDMA and its metabolite, methylenedioxyamphetamine, concentrations by gas chromatography-mass spectrometry were similar in both strains 0.3-4 h after MDMA, discounting the role of MDR1a-facilitated MDMA transport in observed inter-strain differences. Increased DOPAC/DA turnover in mdr1a +/+ mice following MDMA is consistent with the previous report that MDMA neurotoxicity is increased in mdr1a +/+ mice. Increased DA turnover via monoamine oxidase in mdr1a +/+ vs -/- mice might increase exposure to neurotoxic reactive oxygen species. C1 [Ladenheim, Bruce; Cadet, Jean Lud; Huestis, Marilyn A.] NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,Biomed Res Ctr, 251 Bayview Blvd Suite 200,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX We would like to thank David Epstein and Jennifer Bossert from the National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD for assistance with statistical analysis. This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 54 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD AUG PY 2010 VL 18 IS 2 BP 200 EP 209 DI 10.1007/s12640-009-9124-z PG 10 WC Neurosciences SC Neurosciences & Neurology GA 607AR UT WOS:000278471100010 PM 19851718 ER PT J AU Nevo, U Ozarslan, E Komlosh, ME Koay, CG Sarlls, JE Basser, PJ AF Nevo, Uri Oezarslan, Evren Komlosh, Michal E. Koay, Cheng Guan Sarlls, Joelle E. Basser, Peter J. TI A system and mathematical framework to model shear flow effects in biomedical DW-imaging and spectroscopy SO NMR IN BIOMEDICINE LA English DT Article DE DWI, pseudo-diffusion; transport; multiple-scales; IVIM; Rheo-NMR; shear flow; in vivo ID GRADIENT SPIN-ECHO; ANISOTROPIC WATER DIFFUSION; ACUTE ISCHEMIC-STROKE; MAGNETIC-RESONANCE; RESTRICTED DIFFUSION; BRAIN TEMPERATURE; SELF-DIFFUSION; NERVOUS-SYSTEM; TENSOR; NMR AB The pulsed-field gradient (PFG) MR experiment enables one to measure particle displacements, velocities, and even higher moments of complex fluid motions. In diffusion-weighted MRI (DWI) in living tissue, where the PFG MRI experiment is used to measure diffusion, Brownian motion is assumed to dominate the displacements causing the observed signal loss. However, motions of water molecules caused by various active biological processes occurring at different length and time scales may also cause additional dephasing of magnetization and signal loss. To help understand their relative effects on the DWI signal attenuation, we used an integrated experimental and theoretical framework: a Rheo-NMR, which served as an experimental model system to precisely prescribe a microscopic velocity distribution; and a mathematical model that relates the DW signal intensity in the Rheo-NMR to experimental parameters that characterize the impressed velocity field. A technical innovation reported here is our use of 'natural' (in this case, polar) coordinates both to simplify the description the fluid motion within the Couette cell of the Rheo-NMR, as well as to acquire and reconstruct magnitude and phase MR images obtained within it. We use this integrated model system to demonstrate how shear flows appears as pseudo-diffusion in magnitude DW MR signals obtained using PFG spin-echo (PGSE) NMR and MRI sequences. Our results lead us to reinterpret the possible causes of signal loss in DWI in vivo, in particular to revise and generalize the previous notion of intra-voxel incoherent motion (IVIM) in order to describe activity driven flows that appear as pseudo-diffusion over multiple length and time scales in living tissues. Published (C) 2010 John Wiley & Sons, Ltd. C1 [Nevo, Uri; Oezarslan, Evren; Komlosh, Michal E.; Koay, Cheng Guan; Sarlls, Joelle E.; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, STBB, NIH, Bethesda, MD 20892 USA. [Nevo, Uri] Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. RP Basser, PJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, STBB, NIH, 13 South Dr,MSC 5772,Bldg 13,Room 3W16, Bethesda, MD 20892 USA. EM pjbasser@helix.nih.gov RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011 OI Ozarslan, Evren/0000-0003-0859-1311; FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; EU FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. Uri Nevo is a Colton Foundation Fellow, and is supported by the IRG grant of the EU. We wish to thank Liz Salak for editing this manuscript. NR 48 TC 11 Z9 11 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD AUG PY 2010 VL 23 IS 7 SI SI BP 734 EP 744 DI 10.1002/nbm.1591 PG 11 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 665DB UT WOS:000283014300007 PM 20886564 ER PT J AU Shemesh, N Ozarslan, E Komlosh, ME Basser, PJ Cohen, Y AF Shemesh, Noam Oezarslan, Evren Komlosh, Michal E. Basser, Peter J. Cohen, Yoram TI From single-pulsed field gradient to double-pulsed field gradient MR: gleaning new microstructural information and developing new forms of contrast in MRI SO NMR IN BIOMEDICINE LA English DT Review DE double-PFG; microstructure; MRI; diffusion-diffraction; restricted diffusion; pore size; compartment shape; anisotropy ID Q-SPACE DIFFUSION; SPIN-ECHO NMR; ANISOTROPIC WATER DIFFUSION; NUCLEAR-MAGNETIC-RESONANCE; AXON DIAMETER DISTRIBUTION; DOUBLE-PGSE NMR; STRUCTURAL INFORMATION; RESTRICTED DIFFUSION; POROUS-MEDIA; EXPERIMENTAL PARAMETERS AB One of the hallmarks of diffusion NMR and MRI is its ability to utilize restricted diffusion to probe compartments much smaller than the excited volume or the MRI voxel, respectively, and to extract microstructural information from them. Single-pulsed field gradient (s-PFG) MR methodologies have been employed with great success to probe microstructures in various disciplines, ranging from chemistry to neuroscience. However, s-PFG MR also suffers from inherent shortcomings, especially when specimens are characterized by orientation or size distributions: in such cases, the microstructural information available from s-PFG experiments is limited or lost. Double-pulsed field gradient (d-PFG) MR methodology, an extension of s-PFG MR, has attracted attention owing to recent theoretical studies predicting that it can overcome certain inherent limitations of s-PFG MR. In this review, we survey the microstructural features that can be obtained from conventional s-PFG methods in the different q regimes, and highlight its limitations. The experimental aspects of d-PFG methodology are then presented, together with an overview of its theoretical underpinnings and a general framework for relating the MR signal decay and material microstructure, affording new microstructural parameters. We then discuss recent studies that have validated the theory using phantoms in which the ground truth is well known a priori, a crucial step prior to the application of d-PFG methodology in neuronal tissue. The experimental findings are in excellent agreement with the theoretical predictions and reveal, inter alia, zero-crossings of the signal decay, robustness towards size distributions and angular dependences of the signal decay from which accurate microstructural parameters, such as compartment size and even shape, can be extracted. Finally, we show some initial findings in d-PFG MR imaging. This review lays the foundation for future studies, in which accurate and novel microstructural information could be extracted from complex biological specimens, eventually leading to new forms of contrast in MRI. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Shemesh, Noam; Cohen, Yoram] Tel Aviv Univ, Sch Chem, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. [Oezarslan, Evren; Komlosh, Michal E.; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA. RP Cohen, Y (reprint author), Tel Aviv Univ, Sch Chem, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011; OI Ozarslan, Evren/0000-0003-0859-1311; Shemesh, Noam/0000-0001-6681-5876 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX P.J.B, M.E.K. and E.O. were all supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. We thank Ms Liz Salak for editing the manuscript. NR 116 TC 41 Z9 41 U1 3 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD AUG PY 2010 VL 23 IS 7 SI SI BP 757 EP 780 DI 10.1002/nbm.1550 PG 24 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 665DB UT WOS:000283014300009 PM 20690130 ER PT J AU Zambre, A Shukla, R Chanda, N Kan, P Watkinson, LD Carmack, TL Engelbrecht, H Lever, JR Katti, K Fent, GM Casteel, SW Smith, CJ Miller, WH Jurisson, S Boote, E Robertson, JD Cutler, C Dobrovolskaia, M Kannan, R Kotti, KV AF Zambre, Ajit Shukla, Ravi Chanda, Nripen Kan, Para Watkinson, Lisa D. Carmack, Terry L. Engelbrecht, Hendrik Lever, John R. Katti, Kavita Fent, Genevieve M. Casteel, Stan W. Smith, C. Jeffrey Miller, William H. Jurisson, Silvia Boote, Evan Robertson, J. David Cutler, Cathy Dobrovolskaia, Marina Kannan, Raghuraman Kotti, Kattesh V. TI Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy of a biocompatible (AuNP)-Au-198-GA nanotherapeutic agent SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Meeting Abstract C1 [Zambre, Ajit; Shukla, Ravi; Chanda, Nripen; Katti, Kavita; Smith, C. Jeffrey; Boote, Evan; Kannan, Raghuraman; Kotti, Kattesh V.] Univ Missouri, Dept Radiol, Columbia, MO USA. [Kan, Para; Jurisson, Silvia; Robertson, J. David; Cutler, Cathy] Univ Missouri, Dept Chem, Columbia, MO USA. [Watkinson, Lisa D.; Carmack, Terry L.; Lever, John R.; Fent, Genevieve M.; Casteel, Stan W.; Smith, C. Jeffrey] Univ Missouri, Dept Vet Pathobiol, Columbia, MO USA. [Engelbrecht, Hendrik; Smith, C. Jeffrey; Miller, William H.; Robertson, J. David; Cutler, Cathy; Kotti, Kattesh V.] Univ Missouri, Missouri Univ Res Reactor, Columbia, MO USA. [Jurisson, Silvia; Robertson, J. David; Cutler, Cathy] Univ Missouri, Nucl Sci & Engn Inst, Columbia, MO USA. [Dobrovolskaia, Marina] NCI, Nanotechnol Characterizat Lab, SAIC Frederick, Frederick, MD 21701 USA. [Kannan, Raghuraman; Kotti, Kattesh V.] Nanoparticle Biochem Inc, Columbia, MO USA. OI Robertson, John/0000-0002-6675-8469 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 2010 VL 37 IS 6 BP 720 EP 720 DI 10.1016/j.nucmedbio.2010.04.172 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 640TK UT WOS:000281075100167 ER PT J AU Berquist, BR Singh, DK Fan, JS Kim, D Gillenwater, E Kulkarni, A Bohr, VA Ackerman, EJ Tomkinson, AE Wilson, DM AF Berquist, Brian R. Singh, Dharmendra Kumar Fan, Jinshui Kim, Daemyung Gillenwater, Elizabeth Kulkarni, Avanti Bohr, Vilhelm A. Ackerman, Eric J. Tomkinson, Alan E. Wilson, David M., III TI Functional capacity of XRCC1 protein variants identified in DNA repair-deficient Chinese hamster ovary cell lines and the human population SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; STRAND-BREAK REPAIR; POLYMERASE-BETA INTERACTION; SITE-DIRECTED MUTAGENESIS; LIGASE-III; CANCER-RISK; DAMAGE; BINDING; POLYMORPHISMS; DISEASE AB XRCC1 operates as a scaffold protein in base excision repair, a pathway that copes with base and sugar damage in DNA. Studies using recombinant XRCC1 proteins revealed that: a C389Y substitution, responsible for the repair defects of the EM-C11 CHO cell line, caused protein instability; a V86R mutation abolished the interaction with POL beta, but did not disrupt the interactions with PARP-1, LIG3 alpha and PCNA; and an E98K substitution, identified in EM-C12, reduced protein integrity, marginally destabilized the POL beta interaction, and slightly enhanced DNA binding. Two rare (P161L and Y576S) and two frequent (R194W and R399Q) amino acid population variants had little or no effect on XRCC1 protein stability or the interactions with POL beta, PARP-1, LIG3 alpha, PCNA or DNA. One common population variant (R280H) had no pronounced effect on the interactions with POL beta, PARP-1, LIG3 alpha and PCNA, but did reduce DNA-binding ability. When expressed in HeLa cells, the XRCC1 variants-excluding E98K, which was largely nucleolar, and C389Y, which exhibited reduced expression-exhibited normal nuclear distribution. Most of the protein variants, including the V86R POL beta-interaction mutant, displayed normal relocalization kinetics to/from sites of laser-induced DNA damage: except for E98K and C389Y, and the polymorphic variant R280H, which exhibited a slightly shorter retention time at DNA breaks. C1 [Berquist, Brian R.; Singh, Dharmendra Kumar; Bohr, Vilhelm A.; Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Fan, Jinshui; Tomkinson, Alan E.] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Kim, Daemyung] Cheongju Univ, Dept Genet Engn, Cheongju 360764, South Korea. [Gillenwater, Elizabeth] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Kulkarni, Avanti] UCSF Sch Med, Dept Radiat Oncol, San Francisco, CA 94103 USA. [Ackerman, Eric J.] Sandia Natl Labs, Dept Nanobiol, Albuquerque, NM 87123 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM wilsonda@mail.nih.gov FU National Institute on Aging, National Institutes of Health; National Institute on Aging [ES12512, CA92584] FX Funding for open access charge: Intramural Research Program, National Institute on Aging, National Institutes of Health; National Institute on Aging; (ES12512 and CA92584 to A. E. T.). NR 56 TC 28 Z9 28 U1 0 U2 5 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 AUG PY 2010 VL 38 IS 15 BP 5023 EP 5035 DI 10.1093/nar/gkq193 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 644BR UT WOS:000281345900019 PM 20385586 ER PT J AU Yeung, EH Appel, LJ Miller, ER Kao, WHL AF Yeung, Edwina H. Appel, Lawrence J. Miller, Edgar R., III Kao, W. H. Linda TI The Effects of Macronutrient Intake on Total and High-molecular Weight Adiponectin: Results From the OMNI-Heart Trial SO OBESITY LA English DT Article ID MODERATE ALCOHOL-CONSUMPTION; INSULIN-RESISTANCE; INFLAMMATORY MARKERS; PLASMA ADIPONECTIN; FATTY-ACIDS; MONOUNSATURATED FAT; METABOLIC SYNDROME; RANDOMIZED-TRIAL; RISK; DIET AB Higher levels of the adipocyte-specific hormone adiponectin have been linked to increased high-density lipoprotein (HDL) and lower insulin resistance. This study was conducted to determine the influence of macronutrient intake on adiponectin levels. One hundred and sixty-four pre- and stage-1 hypertensive adults participated in the Optimal Macro-Nutrient Intake Heart (OMNI-Heart) trial, a crossover feeding study originally testing the effects of macronutrients on blood pressure. Participants underwent three 6-week feeding periods: one rich in carbohydrates (CARB), one rich in monounsaturated fat (MUFA), and one rich in protein (PROT), while maintaining body weight. Their median plasma high molecular weight (HMW) and total adiponectin levels were 2.3 and 8.2 mu g/ml, respectively, resulting in an average of 27% HMW adiponectin. Both HMW and total adiponectin levels decreased after baseline while the percent HMW adiponectin remained unchanged. Between diets, the MUFA diet maintained a higher level of both HMW and total adiponectin levels than either the CARB (HMW: +6.8%, P = 0.02; total: +4.5%, P = 0.001) or PROT (HMW: +8.4%, P = 0.003; total: +5.6%, P < 0.001) diets. Changes in total adiponectin levels were positively correlated to changes in HDL cholesterol irrespective of diets (Spearman r = 0.22-0.40). No correlation was found between changes in lipids, blood pressure, or insulin resistance by the homeostasis model assessment (HOMAIR). Macronutrient intake has effects on HMW and total adiponectin levels independent of weight loss. A diet rich in MUFA was associated with higher levels of total and HMW adiponectin in comparison to a carbohydrate- or protein-rich diet. Effects seen in adiponectin paralleled those found with HDL cholesterol. C1 [Yeung, Edwina H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Appel, Lawrence J.; Miller, Edgar R., III; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Appel, Lawrence J.; Miller, Edgar R., III; Kao, W. H. Linda] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Appel, Lawrence J.; Miller, Edgar R., III; Kao, W. H. Linda] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. RP Yeung, EH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. EM yeungedw@mail.nih.gov RI Yeung, Edwina/F-5992-2015 OI Yeung, Edwina/0000-0002-3851-2613 FU National Institutes of Health at National Institute of Child Health and Human Development; National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK62707-03]; Merck; NIH [HL67098, D63214, HL68712, RR02635] FX This article was previously presented at the American Diabetes Association 68th Annual Scientific sessions 9 June 2008. E.H.Y. was supported in part by the intramural research program of the National Institutes of Health at National Institute of Child Health and Human Development and by a National Institute of Diabetes and Digestive and Kidney Diseases training grant (T32 DK62707-03). Measurements of adiponectin were made with funding from an educational grant from Merck to W. H. L. K. The OMNI-Heart study was funded through grants HL67098, D63214, HL68712, and RR02635 from the NIH. Food was donated from The Almond Board, International Tree Nut Council, Olivio Premium Products Inc., and The Peanut Institute. NR 29 TC 14 Z9 14 U1 0 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 AUG PY 2010 VL 18 IS 8 BP 1632 EP 1637 DI 10.1038/oby.2009.402 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 632AN UT WOS:000280392400023 PM 19876001 ER PT J AU Taylor, HA Coady, SA Levy, D Walker, ER Vasan, RS Liu, JK Akylbekova, EL Garrison, RJ Fox, C AF Taylor, Herman A., Jr. Coady, Sean A. Levy, Daniel Walker, Evelyn R. Vasan, Ramachandran S. Liu, Jiankang Akylbekova, Ermeg L. Garrison, Robert J. Fox, Caroline TI Relationships of BMI to Cardiovascular Risk Factors Differ by Ethnicity SO OBESITY LA English DT Article ID BODY-MASS INDEX; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; AFRICAN-AMERICANS; FAT DISTRIBUTION; NATIONAL-HEART; UNITED-STATES; WHITE WOMEN; US ADULTS; PREVALENCE AB The burden of cardiovascular risk associated with obesity disproportionately affects African Americans and little is known about ethnic/racial differences in the relationship of obesity to cardiometabolic risk. This report assesses whether obesity is similarly associated with cardiometabolic risk factors in African Americans and whites of European ancestry. Cross-sectional observational data from the Jackson Heart Study (JHS) and the Framingham Heart Study (FHS) were compared. This analysis uses participants aged 35-74 years with BMI > 18.5 kg/m(2), and free of prevalent cardiovascular disease (CVD), from the initial JHS clinical examination (2000-2004) and the FHS Offspring (1998-2001) and Third Generation (2002-2005) cohorts. Participants were evaluated for the presence of lipid abnormalities, hypertension, and diabetes. Overall, 4,030 JHS (mean age 54 years, 64% women) and 5,245 FHS (mean age 51 years, 54% women) participants were available for analysis. The prevalence of all risk factors except high triglycerides and low high-density lipoprotein (HDL) was substantially higher in JHS (all P < 0.001) and BMI was associated with increasing prevalence of most CVD risk factors within each race. For diabetes mellitus, hypertension, and low HDL, steeper relationships to BMI were observed in FHS than in JHS (P values < 0.001-0.016). There were larger proportional increases in risk factor prevalence with increasing BMI in whites than in African Americans. The higher prevalence rates of cardiometabolic risk factors at nearly all levels of BMI in African Americans, however, suggest that additional factors contribute to the burden of CVD risk in African Americans. C1 [Taylor, Herman A., Jr.; Liu, Jiankang; Garrison, Robert J.] Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA. [Taylor, Herman A., Jr.; Akylbekova, Ermeg L.] Jackson State Univ, Jackson, MS USA. [Taylor, Herman A., Jr.] Tougaloo Coll, Tougaloo, MS USA. [Levy, Daniel; Fox, Caroline] NHLBI, Framingham Heart Study, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Walker, Evelyn R.] NHLBI, Jackson Heart Study, NIH, Bethesda, MD 20892 USA. RP Taylor, HA (reprint author), Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA. EM htaylor@medicine.umsmed.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute, National Institutes of Health [N01-HC-95170, N01-HC-95171, N01-HC-95172, N01-HC-25195]; National Center on Minority Health and Health Disparities, National Institutes of Health [N01-HC-95170, N01-HC-95171, N01-HC-95172] FX The Jackson Heart Study is supported by the National Institutes of Health contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172 that are provided by the National Heart, Lung, and Blood Institute and the National Center on Minority Health and Health Disparities. The Framingham Heart Study is supported by the National Heart, Lung, and Blood Institute contract N01-HC-25195. The National, Heart, Lung, and Blood Institute participates in the governance of the Framingham Heart Study and the Jackson Heart Study and reviewed this manuscript. Some of the findings in this report were presented at the American Heart Association's 48th Cardiovascular Disease Epidemiology and Prevention Conference, March 2008, Colorado Springs, CO. NR 27 TC 26 Z9 27 U1 0 U2 2 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 AUG PY 2010 VL 18 IS 8 BP 1638 EP 1645 DI 10.1038/oby.2009.407 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 632AN UT WOS:000280392400024 PM 19927137 ER PT J AU Ghoussaini, M Stutzmann, F Couturier, C Vatin, V Durand, E Lecoeur, C Degraeve, F Heude, B Tauber, M Hercberg, S Levy-Marchal, C Tounian, P Weill, J Traurig, M Bogardus, C Baier, LJ Michaud, JL Froguel, P Meyre, D AF Ghoussaini, Maya Stutzmann, Fanny Couturier, Cyril Vatin, Vincent Durand, Emmanuelle Lecoeur, Cecile Degraeve, Franck Heude, Barbara Tauber, Maithe Hercberg, Serge Levy-Marchal, Claire Tounian, Patrick Weill, Jacques Traurig, Michael Bogardus, Clifton Baier, Leslie J. Michaud, Jacques L. Froguel, Philippe Meyre, David TI Analysis of the SIM1 Contribution to Polygenic Obesity in the French Population SO OBESITY LA English DT Article ID GENOME-WIDE ASSOCIATION; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; CHILDHOOD OBESITY; EARLY-ONSET; GENE; MASS; HYPOTHALAMUS; VARIANTS; TRAITS AB SIM1 (single-minded 1) haploinsufficiency is responsible for obesity in both humans and mice, but the contribution of frequent DNA variation to polygenic obesity is unknown. Sequencing of all exons, exon/intron boundaries, 870 base pairs (bp) of the putative promoter, and 1,095 bp of the 3'UTR of SIM1 gene in 143 obese children and 24 control adults identified 13 common variants. After analysis of the linkage disequilibrium (LD) structure, association study of eight variants was performed in 1,275 obese children and severely obese adults, in 1,395 control subjects, and in 578 obesity-selected pedigrees. A nominal evidence of association was found for the nonsynonymous variant P352T C/A (rs3734354) (P = 0.01, OR = 0.81 (0.70-0.95)), the +2,004 TGA -/insT SNP (rs35180395) (P = 0.02, OR = 1.21 (1.02-1.43)), the +2,215A/G TGA SNP (rs9386126) (P = 0.002, OR = 0.81 (0.71-0.93)), and pooled childhood/adult obesity. Even though transmission disequilibrium test (TDT) further supported the association of P352T and +2,004-/inst T with obesity, none of these nominal associations remained significant after a multiple testing Bonferroni correction. Therefore, our study excludes a major contribution of SIM1 common variants in exons, 5' and 3'UTR regions in polygenic obesity susceptibility in French Europeans. C1 [Ghoussaini, Maya; Stutzmann, Fanny; Couturier, Cyril; Vatin, Vincent; Durand, Emmanuelle; Lecoeur, Cecile; Degraeve, Franck; Froguel, Philippe; Meyre, David] Inst Pasteur, CNRS 8090, Inst Biol, F-59019 Lille, France. [Heude, Barbara] INSERM, U780, Villejuif, France. [Heude, Barbara] Univ Paris 11, Orsay, France. [Tauber, Maithe] CHU, Childrens Hosp, INSERM, Ctr Physiopathol Toulouse Purpan,U563, Toulouse, France. [Hercberg, Serge] Univ Paris 13, CRNH IdF, CNAM, U1125,INRA,INSERM,UMR U557,Ctr Res Nutr, Bobigny, France. [Levy-Marchal, Claire] INSERM, U690, Dept Pediat Endocrinol & Diabetol, Paris, France. [Levy-Marchal, Claire] Univ Paris Diderot, Paris, France. [Tounian, Patrick] Armand Trousseau Hosp, AP HP, Dept Pediat Gastroenterol & Nutr, Paris, France. [Weill, Jacques] Jeanne Flandre Hosp, Pediat Endocrine Unit, Lille, France. [Traurig, Michael; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. [Michaud, Jacques L.] Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Genom Med, London, England. RP Froguel, P (reprint author), Inst Pasteur, CNRS 8090, Inst Biol, F-59019 Lille, France. EM p.froguel@imperial.ac.uk RI Meyre, David/D-7315-2011; TAUBER, Maithe/K-7386-2014; Couturier, Cyril/I-3020-2016; Heude, Barbara/G-3095-2016 OI Heude, Barbara/0000-0002-1565-1629 FU ALFEDIAM (Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques); 200 Familles pour Vaincre le Diabete et l'Obesite; Association Francaise des Diabetiques; le Conseil National de la Recherche Scientifique Libanais (CNRS-L); le Conseil Regional Nord Pas de Calais/FEDER FX We are indebted to all families who participated in this study. We also thank the ALFEDIAM (Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques), "200 Familles pour Vaincre le Diabete et l'Obesite," and "Association Francaise des Diabetiques" charities; and " le Conseil National de la Recherche Scientifique Libanais (CNRS-L)" and " le Conseil Regional Nord Pas de Calais/FEDER" institutions for their financial support. NR 27 TC 10 Z9 11 U1 0 U2 1 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 AUG PY 2010 VL 18 IS 8 BP 1670 EP 1675 DI 10.1038/oby.2009.468 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 632AN UT WOS:000280392400029 PM 20075856 ER PT J AU Dudley, DJ Goldenberg, R Conway, D Silver, RM Saade, GR Varner, MW Pinar, H Coustan, D Bukowski, R Stoll, B Koch, MA Parker, CB Reddy, UM AF Dudley, Donald J. Goldenberg, Robert Conway, Deborah Silver, Robert M. Saade, George R. Varner, Michael W. Pinar, Halit Coustan, Donald Bukowski, Radek Stoll, Barbara Koch, Matthew A. Parker, Corette B. Reddy, Uma M. CA Stillbirth Res Collaborative Netwo TI A New System for Determining the Causes of Stillbirth SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PERINATAL-MORTALITY; FETAL-GROWTH; CLASSIFICATION AB OBJECTIVE: To describe the methods for assigning the cause of death for stillbirths enrolled in the Stillbirth Collaborative Research Network (SCRN). METHODS: A complete evaluation, including postmortem examination, placental pathology, medical record abstraction, and maternal interview was available on 512 stillbirths among 500 women. These 512 stillbirths were evaluated for cause of death using the definitions outlined in this report. Using the best available evidence, SCRN investigators developed a new methodology to assign the cause of death of stillbirths using clinical, postmortem, and placental pathology data. This new tool, designated the Initial Causes of Fetal Death, incorporates known causes of death and assigns them as possible or probable based on strict diagnostic criteria, derived from published references and pathophysiologic sequences that lead to stillbirth. RESULTS: Six broad categories of causes of death are accounted for, including maternal medical conditions; obstetric complications; maternal or fetal hematologic conditions; fetal genetic, structural, and karyotypic abnormalities; placental infection, fetal infection, or both; and placental pathologic findings. Isolated histologic chorioamnionitis and small for gestational age were not considered causes of death. CONCLUSION: A new system, Initial Causes of Fetal Death, to assign cause of death in stillbirths was developed by the SCRN investigators for use in this study but has broader applicability. Initial Causes of Fetal Death is a standardized method to assign probable and possible causes of death of stillbirths based on information routinely collected during prenatal care and the clinical evaluation of fetal death. C1 [Dudley, Donald J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. Drexel Univ, Sch Med, Philadelphia, PA 19104 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Univ Texas Med Branch, Galveston, TX USA. Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RTI Int, Res Triangle Pk, NC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Rockville, MD USA. RP Dudley, DJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM dudleyd@uthscsa.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Brown University, Rhode Island [U10-HD045953]; Emory University, Georgia [U10-HD045925]; University of Texas Medical Branch at Galveston, Texas [U10-HD045952]; University of Texas Health Science Center at San Antonio, Texas [U10-HD045955]; University of Utah Health Sciences Center, Utah [U10-HD045944]; RTI International, North Carolina [U01-HD-45954]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NICHD FX Supported in part by grant funding from the Stillbirth Collaborative Research Network sites: U10-HD045953 (Brown University, Rhode Island); U10-HD045925 (Emory University, Georgia); U10-HD045952 (University of Texas Medical Branch at Galveston, Texas); U10-HD045955 (University of Texas Health Science Center at San Antonio, Texas); U10-HD045944 (University of Utah Health Sciences Center, Utah); and U01-HD-45954 (RTI International, North Carolina); and by funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.; Robert L. Goldenberg is a consultant to United Healthcare, Research Triangle Institute; is employed by Drexel University College of Medicine; and has received grants or has grants pending from the Global Network funded by the NICHD. The other authors did not report any potential conflicts of interest. NR 13 TC 43 Z9 43 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2010 VL 116 IS 2 BP 254 EP 260 DI 10.1097/AOG.0b013e3181e7d975 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 629HI UT WOS:000280186300003 PM 20664383 ER PT J AU Wing, RR Creasman, JM West, DS Richter, HE Myers, D Burgio, KL Franklin, F Gorin, AA Vittinghoff, E Macer, J Kusek, JW Subak, LL AF Wing, Rena R. Creasman, Jennifer M. West, Delia Smith Richter, Holly E. Myers, Deborah Burgio, Kathryn L. Franklin, Frank Gorin, Amy A. Vittinghoff, Eric Macer, Judith Kusek, John W. Subak, Leslee L. CA PRIDE TI Improving Urinary Incontinence in Overweight and Obese Women Through Modest Weight Loss SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LIFE-STYLE INTERVENTION; RISK-FACTORS; CARDIOVASCULAR-DISEASE; STRESS-INCONTINENCE; BEHAVIORAL-THERAPY; TRIAL; PREVENTION; REDUCTION; EXERCISE; HEALTH AB OBJECTIVE: To examine the relationship between magnitude of weight loss and changes in urinary incontinence frequency. METHODS: Overweight and obese women (N = 338) with 10 or more urinary incontinence episodes per week were assigned randomly to an intensive 6-month behavioral weight loss program followed immediately by a 12-month weight maintenance program (intervention; n = 226) or to a structured education program (control; n = 112). The intervention and control groups were combined to examine the effects of the magnitude of weight loss on changes in urinary incontinence assessed by 7-day voiding diary, pad test, and self-reported satisfaction with change in urinary incontinence. RESULTS: Compared with participants who gained weight (reference), those who lost 5% to less than 10% or 10% or more of their body weight had significantly greater percent reductions in urinary incontinence episodes and were more likely to achieve at least a 70% reduction in the frequency of total and urge urinary incontinence episodes at 6, 12, and 18 months. Satisfaction was also related to magnitude of weight loss; approximately 75% of women who lost 5% to less than 10% of their body weight reported being moderately or very satisfied with their changes in urine leakage. CONCLUSION: Weight losses between 5% and 10% of body weight were sufficient for significant urinary incontinence benefits. Thus, weight loss should be considered as initial treatment for incontinence in overweight and obese women. C1 [Wing, Rena R.] Brown Univ, Miriam Hosp, Providence, RI 02903 USA. Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02903 USA. Brown Univ, Warren Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02903 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Obstet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Maternal & Child Hlth, Birmingham, AL USA. Dept Vet Affairs, Birmingham, AL USA. Univ Connecticut, Dept Psychol, Storrs, CT USA. NIDDK, Bethesda, MD USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Wing, RR (reprint author), Brown Univ, Miriam Hosp, 196 Richmond St, Providence, RI 02903 USA. EM rwing@lifespan.org FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK067860, U01 DK067861, U01 DK067862]; Office of Research on Women's Health; Pfizer; Astellas; University of California-San Francisco/Pfizer; American Geriatrics Society FX Supported by grant nos. U01DK067860, U01 DK067861, and U01 DK067862 from the National Institute of Diabetes and Digestive and Kidney Diseases. Funding also was provided by the Office of Research on Women's Health.; Dr. Richter is a consultant for IDEO and Xanodyne Pharmaceuticals, Inc and has received grants on behalf of her institution from Pfizer, Astellas, the University of California-San Francisco/Pfizer, and the American Geriatrics Society. Dr. Burgio is a consultant with Pfizer, Astellas, and Johnson & Johnson and has received grant support from Pfizer. Dr. Subak has received grants on behalf of her institution from Pfizer. The other authors did not report any potential conflicts of interest. NR 34 TC 32 Z9 36 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2010 VL 116 IS 2 BP 284 EP 292 DI 10.1097/AOG.0b013e3181e8fb60 PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 629HI UT WOS:000280186300007 PM 20664387 ER PT J AU Livingston, EG Huo, YL Patel, K Brogly, SB Tuomala, R Scott, GB Bardeguez, A Stek, A Read, JS AF Livingston, Elizabeth G. Huo, Yanling Patel, Kunjal Brogly, Susan B. Tuomala, Ruth Scott, Gwendolyn B. Bardeguez, Arlene Stek, Alice Read, Jennifer S. CA Protocol 1025 Study Team TI Mode of Delivery and Infant Respiratory Morbidity Among Infants Born to HIV-1-Infected Women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INFECTED PREGNANT-WOMEN; ELECTIVE CESAREAN DELIVERY; ANTIRETROVIRAL THERAPY; NEONATAL-MORTALITY; UNITED-STATES; TERM; SECTION; RISK; HEPATOTOXICITY; CONTAMINATION AB OBJECTIVE: To estimate risk of infant respiratory morbidity associated with cesarean delivery before labor and ruptured membranes among HIV-1-infected women. METHODS: In a prospective cohort study of HIV-1-infected women and their infants, mode of delivery was determined by clinicians at the participating sites. For this analysis, "elective cesarean delivery" was defined as any cesarean delivery, regardless of gestational age, without labor and with duration of ruptured membranes of less than 5 minutes. Nonelective cesarean deliveries were those performed after the onset of labor, rupture of membranes, or both. Vaginal delivery included normal spontaneous and instrument deliveries. Associations between mode of delivery and infant respiratory morbidity were assessed using chi(2) or Fisher's exact test. Adjusted odds of respiratory distress syndrome by delivery mode were assessed using multivariable logistic regression. RESULTS: Among 1,194 mother-infant pairs, there were significant differences according to mode of delivery in median gestational age (weeks) at delivery (vaginal, n = 566, median = 38.8; nonelective cesarean, n = 216, median = 38.0; and elective cesarean, n = 412, median 38.1; P < .001) and incidence of respiratory distress syndrome (vaginal, n = 9, 1.6%, reference; nonelective cesarean, n = 16, 7.4%; elective cesarean, n = 18; 4.4%; (P < .001). In analyses adjusted for gestational age and birth weight, mode of delivery was not statistically significantly associated with infant respiratory distress syndrome (P = .10), although a trend toward an increased risk of respiratory distress syndrome among infants delivered by cesarean was suggested (nonelective cesarean adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.95-5.67; elective cesarean OR 2.56, 95% CI 1.01-6.48). CONCLUSION: Respiratory distress syndrome rates associated with elective cesarean delivery among HIV-1-infected women are low, comparable with published rates among uninfected women. There is minimal neonatal respiratory morbidity risk in near-term infants born by elective cesarean delivery to HIV-1-infected women. C1 [Livingston, Elizabeth G.] Duke Univ, Med Ctr, Durham, NC 27710 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat Acquired Immunodeficiency Syndrome AI, Boston, MA 02115 USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Univ So Calif, Los Angeles, CA USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Livingston, EG (reprint author), Duke Univ, Med Ctr, Box 3967, Durham, NC 27710 USA. EM livin001@mc.duke.edu FU National Institute of Allergy and Infectious Diseases [U01AI068632, U01 AI068616, HHSN272200800014C]; International and Domestic Pediatric and Maternal HIV Clinical Trials Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-3-3365, HHSN267200800001C, N01-DK-8-0001] FX Supported by National Institute of Allergy and Infectious Diseases grants U01AI068632 and U01 AI068616 and contract number HHSN272200800014C and the International and Domestic Pediatric and Maternal HIV Clinical Trials Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development under contracts N01-HD-3-3365 and HHSN267200800001C (control # N01-DK-8-0001). NR 35 TC 6 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2010 VL 116 IS 2 BP 335 EP 343 DI 10.1097/AOG.0b013e3181e8f38a PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 629HI UT WOS:000280186300014 PM 20664394 ER PT J AU Abbassi-Ghanavati, M Casey, BM Spong, CY McIntire, DD Halvorson, LM Cunningham, FG AF Abbassi-Ghanavati, Mina Casey, Brian M. Spong, Catherine Y. McIntire, Donald D. Halvorson, Lisa M. Cunningham, F. Gary TI Pregnancy Outcomes in Women With Thyroid Peroxidase Antibodies SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SUBCLINICAL HYPOTHYROIDISM; MATERNAL HYPOTHYROXINEMIA; RISK; DYSFUNCTION; DISEASE; AUTOANTIBODIES; AUTOIMMUNITY; MISCARRIAGE; CHILD; AGE AB OBJECTIVE: To estimate the prevalence of antithyroid peroxidase antibodies in the general obstetric population and to compare pregnancy outcomes in women who are antithyroid peroxidase-antibody positive with those who are antithyroid peroxidase-antibody negative. METHODS: Between November 2000 and April 2003, all women who presented for prenatal care underwent thyroid screening. Serum samples from women without clinical hypothyroidism who had been screened in the first 20 weeks of gestation and delivered a singleton newborn weighing 500 g or more were analyzed for concentrations of antithyroid peroxidase antibodies. Serum thyroid peroxidase antibody levels were determined using a chemiluminescent immunoassay. Pregnancy outcomes in women with positive antithyroid peroxidase antibodies (more than 50 international units/mL) were compared with those with negative levels. RESULTS: Serum samples from 17,298 women were tested. Of these, 1,012 (6%) women were identified with positive antithyroid peroxidase antibodies. Women who were antithyroid peroxidase-antibody positive were older, heavier, and more often parous than women with negative antithyroid peroxidase antibodies. Rate of placental abruption was threefold higher in women with antithyroid peroxidase antibodies (1.0% compared with 0.3%, odds ratio 3.4, 95% confidence interval 1.7-6.7) after adjustment for differences in maternal demographics. Seven of the 10 abruptions associated with antithyroid peroxidase antibody occurred in women with normal thyroid-stimulating hormone and free thyroxine levels. CONCLUSION: Antithyroid peroxidase antibodies are present in 6% of the general obstetric population and are associated with a threefold increase in the rate of placental abruption. However, this increase in placental abruption does not currently warrant routine antithyroid antibody screening during pregnancy. C1 [Casey, Brian M.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Casey, BM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM brian.casey@utsouthwestern.edu FU NIH [HD-04-023] FX Supported by NIH grant no. HD-04-023 to University of Texas Southwestern Medical Center. NR 22 TC 44 Z9 48 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2010 VL 116 IS 2 BP 381 EP 386 DI 10.1097/AOG.0b013e3181e904e5 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 629HI UT WOS:000280186300019 PM 20664399 ER PT J AU Wagner, M Browne, HN Linehan, WM Merino, M Babar, N Stratton, P AF Wagner, Marnie Browne, Hyacinth N. Linehan, W. Marston Merino, Maria Babar, Nabeel Stratton, Pamela TI Lipid Cell Tumors in Two Women With von Hippel-Lindau Syndrome SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PAPILLARY CYSTADENOMA; OVARIAN; CARCINOMA; DISEASE AB BACKGROUND: Lipid-cell tumors are rare, functioning ovarian neoplasms. They have not been reported in women with von Hippel-Lindau syndrome, an autosomal-dominant tumor-suppressor gene mutation that is associated with renal cell carcinoma, and other vascular tumors. CASES: Two women with von Hippel-Lindau syndrome and kidney tumors were evaluated for secondary amenorrhea, hirsutism, and complex adnexal masses seen on computed tomography. The first patient had known renal cancer and bilateral adnexal masses, one with central necrosis. Because metastatic renal cell cancer could not be excluded on frozen section, bilateral salpingo-oophorectomy was performed. The second patient underwent right salpingo-oophorectomy after human chorionic gonadotropin testing confirmed that the ovarian tumor produced testosterone. Final pathology in both cases revealed testosterone-secreting lipid cell tumors. CONCLUSION: Lipid cell ovarian tumors should be considered in women with von Hippel-Lindau presenting with adnexal mass, amenorrhea, and hirsuitism. (Obstet Gynecol 2010;116:535-9) C1 [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Surg Pathol Branch, Bethesda, MD 20892 USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. Univ Toledo, Coll Med, Toledo, OH 43606 USA. RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Urol Oncol Branch, CRC 1 E Rm 1-E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM strattop@mail.nih.gov FU Urologic Oncology Branch, NCI; Surgical Pathology Branch, NCI; Clinical Endocrinology Branch, NIDDK; Eunice Kennedy Shriver NICHD; Clinical Center, NIH FX Supported in part by the Urologic Oncology Branch, NCI, Surgical Pathology Branch, NCI, Clinical Endocrinology Branch, NIDDK, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver NICHD, and the Clinical Center, NIH. NR 11 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 2010 VL 116 IS 2 BP 535 EP 539 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 630SU UT WOS:000280295200025 PM 20664446 ER PT J AU Mahdi, N Faia, LJ Goodwin, J Nussenblatt, RB Sen, HN AF Mahdi, Nicole Faia, Lisa J. Goodwin, James Nussenblatt, Robert B. Sen, H. Nida TI A Case of Autoimmune Retinopathy Associated with Thyroid Carcinoma SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE autoantibodies; autoimmune retinopathy; electroretinogram (ERG); thyroid carcinoma; rituxumab AB Purpose: To report a case of autoimmune retinopathy (AIR) associated with a thyroid carcinoma. Design: Case report. Method: A 51-year-old Caucasian woman presented with a rapid decline in vision. Initial visual field and immunohistochemical testing revealed autoimmune retinopathy without an apparent underlying malignancy. Conventional local and systemic immunosuppressive therapies failed to halt the progression. Results: Rituximab treatments were initiated and a slowing of visual loss was seen. Continued surveillance for malignancy revealed a thyroid adenoma, and later a thyroidectomy revealed a thyroid carcinoma. Conclusions: This report highlights the unique presentation of AIR associated with a thyroid carcinoma, the need for continued surveillance for malignancy in cases of AIR, and the possible new use of rituximab for the treatment of AIR. C1 [Mahdi, Nicole; Nussenblatt, Robert B.; Sen, H. Nida] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Faia, Lisa J.] William Beaumont Hosp, Associated Retinal Consultants PC, Royal Oak, MI 48072 USA. [Goodwin, James] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. RP Sen, HN (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10 N 112, Bethesda, MD 20892 USA. EM senh@nei.nih.gov NR 5 TC 11 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD AUG PY 2010 VL 18 IS 4 BP 322 EP 323 DI 10.3109/09273941003802379 PG 2 WC Ophthalmology SC Ophthalmology GA 638ZD UT WOS:000280939000014 PM 20662664 ER PT J AU Wang, Y Ngo, VN Marani, M Yang, Y Wright, G Staudt, LM Downward, J AF Wang, Y. Ngo, V. N. Marani, M. Yang, Y. Wright, G. Staudt, L. M. Downward, J. TI Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells SO ONCOGENE LA English DT Article DE KRAS; synthetic lethal; oncogene addiction; epithelial-mesenchymal transition ID EPITHELIAL-MESENCHYMAL TRANSITIONS; E-CADHERIN EXPRESSION; RNA INTERFERENCE; P53-MEDIATED APOPTOSIS; TUMOR PROGRESSION; CANCER-CELLS; FACTOR SLUG; LINES; GROWTH; GENE AB Activating mutations in the KRAS gene are among the most prevalent genetic changes in human cancers. To identify synthetic lethal interactions in cancer cells harbouring mutant KRAS, we performed a large-scale screen in isogenic paired colon cancer cell lines that differ by a single allele of mutant KRAS using an inducible short hairpin RNA interference library. Snail2, a zinc finger transcriptional repressor encoded by the SNAI2 gene, was found to be selectively required for the long-term survival of cancer cells with mutant KRAS that have undergone epithelial-mesenchymal transition (EMT), a transdifferentiation event that is frequently seen in advanced tumours and is promoted by RAS activation. Snail2 expression is regulated by the RAS pathway and is required for EMT. Our findings support Snail2 as a possible target for the treatment of the broad spectrum of human cancers of epithelial origin with mutant RAS that have undergone EMT and are characterized by a high degree of chemoresistance and radioresistance. Oncogene (2010) 29, 4658-4670; doi:10.1038/onc.2010.218; published online 21 June 2010 C1 [Wang, Y.; Marani, M.; Downward, J.] Canc Res UK London Res Inst, Signal Transduct Lab, London WC2A 3PX, England. [Ngo, V. N.; Yang, Y.; Staudt, L. M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wright, G.] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA. RP Downward, J (reprint author), Canc Res UK London Res Inst, Signal Transduct Lab, 44 Lincolns Inn Fields, London WC2A 3PX, England. EM julian.downward@cancer.org.uk OI Downward, Julian/0000-0002-2331-4729 FU Cancer Research UK; NIH, National Cancer Institute, Center for Cancer Research FX We thank Alberto Bardelli for providing SW48 and SW48 KRAS G13D cells and Senji Shirasawa for providing HCT-116, HKe-3 and HKh-2 cells. This work was supported by funding from Cancer Research UK and from the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 50 TC 52 Z9 54 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 2010 VL 29 IS 33 BP 4658 EP 4670 DI 10.1038/onc.2010.218 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 641LK UT WOS:000281127400005 PM 20562906 ER PT J AU Taylor, SK Chia, S Dent, S Clemons, M Agulnik, M Grenci, P Wang, LS Oza, AM Ivy, P Pritchard, KI Leighl, NB AF Taylor, Sara K. Chia, Stephen Dent, Susan Clemons, Mark Agulnik, Mark Grenci, Pamela Wang, Lisa Oza, Amit M. Ivy, Percy Pritchard, Kathleen I. Leighl, Natasha B. TI A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium SO ONCOLOGIST LA English DT Article DE Breast neoplasms; Pazopanib; Targeted therapy; Phase II ID ENDOTHELIAL GROWTH-FACTOR; PACLITAXEL PLUS BEVACIZUMAB; CELL LUNG-CANCER; CLINICAL-TRIALS; END-POINTS; ANGIOGENIC FACTORS; TUMOR VASCULATURE; SYSTEMIC THERAPY; FACTOR PDGF; EXPRESSION AB Purpose. Angiogenesis is an important hallmark of breast cancer growth and progression. Pazopanib, an oral small molecule inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and KIT, has activity across a range of solid tumors. We evaluated the activity of single-agent pazopanib in recurrent or metastatic breast cancer (MBC). Patients and Methods. Patients with recurrent breast cancer or MBC, treated with up to two prior lines of chemotherapy, were eligible to receive pazopanib, 800 mg daily until progression. The primary endpoint was the objective response rate as measured by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included time to progression, the stable disease rate, and toxicity. Using a two-stage design, confirmed response in three of 18 patients was required to proceed to stage 2. Results. Twenty evaluable patients were treated, with a median age of 56 years; 70% were estrogen receptor positive, all were human epidermal growth factor receptor 2 negative. The majority had one or two prior lines of chemotherapy. One patient (5%) had a partial response, 11 (55%) had stable disease (SD) [four (20%) with SD >= 6 months], and seven (35%) had progressive disease as their best response. One (5%) was not evaluable. The median time to progression was 5.3 months. Pazopanib did not cause significant severe toxicity aside from grade 3-4 transaminitis, hypertension, and neutropenia in three patients each (14% each) and grade 3 gastrointestinal hemorrhage in one patient (5%). Conclusion. Pazopanib provides disease stability in advanced breast cancer. The activity seen is comparable with that of other antiangiogenic agents in this setting. Pazopanib may be of interest for future studies in breast cancer, including in combination with other systemic agents. The Oncologist 2010;15:810-818 C1 [Taylor, Sara K.; Chia, Stephen; Dent, Susan; Clemons, Mark; Agulnik, Mark; Grenci, Pamela; Wang, Lisa; Oza, Amit M.; Pritchard, Kathleen I.; Leighl, Natasha B.] Princess Margaret Hosp Phase II Consortium, Toronto, ON, Canada. [Taylor, Sara K.; Clemons, Mark; Agulnik, Mark; Grenci, Pamela; Wang, Lisa; Oza, Amit M.; Leighl, Natasha B.] Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. [Taylor, Sara K.; Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Chia, Stephen] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Dent, Susan; Clemons, Mark] Ottawa Hosp Canc Ctr, Ottawa, ON, Canada. [Agulnik, Mark] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Pritchard, Kathleen I.] Univ Toronto, Dept Med, Toronto, ON, Canada. RP Leighl, NB (reprint author), 5-105 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM Natasha.Leighl@uhn.on.ca FU NCI [N01-CM-62203] FX This work was supported by NCI contract number N01-CM-62203. NR 46 TC 37 Z9 38 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD AUG PY 2010 VL 15 IS 8 BP 810 EP 818 DI 10.1634/theoncologist.2010-0081 PG 9 WC Oncology SC Oncology GA 647FN UT WOS:000281603300004 PM 20682606 ER PT J AU Van Houtven, CH Ramsey, SD Hornbrook, MC Atienza, AA van Ryn, M AF Van Houtven, Courtney Harold Ramsey, Scott D. Hornbrook, Mark C. Atienza, Audie A. van Ryn, Michelle TI Economic Burden for Informal Caregivers of Lung and Colorectal Cancer Patients SO ONCOLOGIST LA English DT Article DE Informal care; Opportunity costs; Out-of-pocket costs; Cancer caregiving; Stage of disease; Phase of disease; Lung cancer; Colorectal cancer ID OPPORTUNITY COSTS; HEALTH; CARE; PARENT; TESTS AB Background. Informal care provides many benefits to cancer patients, but can be costly to caregivers. This study quantified the economic burden for informal caregivers of lung cancer (LC) and colorectal cancer (CRC) patients, examining differences by cancer type, phase of disease, stage at diagnosis, patient age, and relationship. Methods. A cross-sectional survey of caregivers of LC and CRC patients participating in the Share Thoughts on Care survey was conducted. Economic burden was calculated using the opportunity cost of caregiver time, the value of work hours lost, and out-of-pocket expenditures. Factors associated with economic burden to caregivers were modeled using fixed-effects generalized least squares estimation. Results. Informal caregivers (1,629) completed mailed surveys. Of these, 663, 822, and 144 were surveyed during the patient's initial phase (first year after diagnosis, not within 6 months of death), continuing phase (after 1 year, not within 6 months of death), and terminal phase (within 6 months of death) of disease, respectively. The accumulated economic burdens for caregivers were $7,028, $19,701, and $14,234 for those evaluated during the patient's initial phase, continuing phase, and terminal phase of disease, respectively. Economic burden was higher for caregivers of LC patients than CRC patients (p = .044) and for caregivers of patients diagnosed at stage 4 versus stage 1 (p = .001). Spouses faced higher economic burden than other relatives (p = .000) or friends (p = .000). Conclusions. Economic burden for informal caregivers of LC and CRC patients is substantial and should be included in estimates of the societal cost of cancer care. The Oncologist 2010;15:883-893 C1 [Van Houtven, Courtney Harold; van Ryn, Michelle] Duke Univ, Med Ctr, Ctr Hlth Serv Res Primary Care, Durham VAMC, Durham, NC USA. [Van Houtven, Courtney Harold; van Ryn, Michelle] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hornbrook, Mark C.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Atienza, Audie A.] NCI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. RP Van Houtven, CH (reprint author), Bldg 16 HSRD,VAMC,508 Fulton St 558-152, Durham, NC 27705 USA. EM courtney.vanhoutven@duke.edu FU National Cancer Institute; National Cancer Institute [U01 CA93324, U01 CA93326, U01 CA93329, U01 CA93332, U01 CA93339, U01 CA93344, U01 CA93348]; Department of Veterans Affairs [CRS 02-164]; VA Health Services [MRP 05-311] FX Disclosures: Courtney Harold Van Houtven: None; Scott D. Ramsey: None; Mark C. Hornbrook: Employment/leadership position: Kaiser Permanente Hospitals, Inc.; Research funding/contracted research: National Cancer Institute; Audie A. Atienza: None; Michelle van Ryn: None.; This work was funded by the National Cancer Institute (U01 CA93324, U01 CA93326, U01 CA93329, U01 CA93332, U01 CA93339, U01 CA93344, and U01 CA93348) and the Department of Veterans Affairs (CRS 02-164). Courtney Van Houtven was supported by the VA Health Services Research and Development Merit Review Program (MRP 05-311). NR 28 TC 39 Z9 40 U1 0 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD AUG PY 2010 VL 15 IS 8 BP 883 EP 893 DI 10.1634/theoncologist.2010-0005 PG 11 WC Oncology SC Oncology GA 647FN UT WOS:000281603300013 PM 20667966 ER PT J AU Hendrix, A Braems, G Bracke, M Seabra, MC Gahl, WA De Wever, O Westbroek, W AF Hendrix, An Braems, Geert Bracke, Marc Seabra, Miguel C. Gahl, William A. De Wever, Olivier Westbroek, Wendy TI The secretory small GTPase Rab27B as a marker for breast cancer progression SO ONCOTARGET LA English DT Article ID GRISCELLI-SYNDROME; MELANOCYTES; EXPRESSION; METASTASIS; PROTEINS; GROWTH; CELLS; GENE AB In contemporary oncology practice, an urgent need remains to refine the prognostic assessment of breast cancer. It is still difficult to identify patients with early breast cancer who are likely to benefit from adjuvant chemotherapy. Although invasion of cancer cells is the main prognostic denominator in tumor malignancy, our molecular understanding and diagnosis are often inadequate to cope with this activity. Therefore, deciphering molecular pathways of how tumors invade and metastasize may help in the identification of a useful prognostic marker. We recently discovered that the secretory small GTPase Rab27B, a regulator of vesicle exocytosis, delivers proinvasive signals for increased invasiveness, tumor size, and metastasis of various estrogen receptor (ER)-positive breast cancer cell lines, both in vitro and in vivo. In human breast cancer specimens, the presence of Rab27B protein proved to be associated with a low degree of differentiation and the presence of lymph node metastasis in ER-positive breast cancer. C1 [Gahl, William A.; Westbroek, Wendy] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Hendrix, An] Ghent Univ Hosp, Dept Med Oncol, B-9000 Ghent, Belgium. [Braems, Geert] Ghent Univ Hosp, Dept Gynecol, B-9000 Ghent, Belgium. [Bracke, Marc; De Wever, Olivier] Ghent Univ Hosp, Lab Expt Canc Res, Dept Radiat Oncol & Expt Canc Res, B-9000 Ghent, Belgium. [Seabra, Miguel C.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England. [Seabra, Miguel C.] Univ Nova Lisboa, Fac Ciencias Med, CEDOC, P-1200 Lisbon, Portugal. [Seabra, Miguel C.] Inst Gulbenkian Ciencias, Oeiras, Portugal. RP Westbroek, W (reprint author), NHGRI, Med Genet Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM an.hendrix@ugent.be; wwestbro@mail.nih.gov RI de wever, olivier/J-3094-2013; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013; OI de wever, olivier/0000-0002-5453-760X; Seabra, Miguel/0000-0002-6404-4892 FU National Human Genome Research Institute; Centrum voor gezwelziekten; European Association for Cancer Research; Fund for Scientific Research-Flanders FX We thank Ben Pederson and Riko Klootwijk for assistance with Q-PCR analysis. This work was supported by the Intramural Research Program of the National Human Genome Research Institute, 'Centrum voor gezwelziekten', European Association for Cancer Research (to AH and ODW) travel fellowships and a travel grant (AH and ODW) and postdoctoral grant (ODW) from Fund for Scientific Research-Flanders. NR 20 TC 23 Z9 25 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG PY 2010 VL 1 IS 4 BP 304 EP 308 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 801YT UT WOS:000293477200010 PM 21304180 ER PT J AU Li, XR Kumar, A Zhang, F Lee, C Li, Y Tang, ZS Arjunan, P AF Li, Xuri Kumar, Anil Zhang, Fan Lee, Chunsik Li, Yang Tang, Zhongshu Arjunan, Pachiappan TI VEGF-independent angiogenic pathways induced by PDGF-C SO ONCOTARGET LA English DT Article DE PDGF-C; angiogenesis; VEGF; choroidal neovascularization ID GROWTH-FACTOR-C; TISSUE-PLASMINOGEN ACTIVATOR; ENDOTHELIAL-CELLS; ALPHA-RECEPTOR; BETA-RECEPTOR; FIBROBLASTS; EXPRESSION; FAMILY; BRAIN; SURVIVAL AB VEGF is believed to be a master regulator in both developmental and pathological angiogenesis. The role of PDGF-C in angiogenesis, however, is only at the beginning of being revealed. We and others have shown that PDGF-C is a critical player in pathological angiogenesis because of its pleiotropic effects on multiple cellular targets. The angiogenic pathways induced by PDGF-C are, to a large extent, VEGF-independent. These pathways may include, but not limited to, the direct effect of PDGF-C on vascular cells, the effect of PDGF-C on tissue stroma fibroblasts, and its effect on macrophages. Taken together, the pleiotropic, versatile and VEGF-independent angiogenic nature of PDGF-C has placed it among the most important target genes for antiangiogenic therapy. C1 [Li, Xuri; Kumar, Anil; Zhang, Fan; Lee, Chunsik; Li, Yang; Tang, Zhongshu; Arjunan, Pachiappan] NEI, NIH, Rockville, MD 20852 USA. RP Li, XR (reprint author), NEI, NIH, Rockville, MD 20852 USA. EM lixur@nei.nih.gov RI Kumar, Anil/K-8504-2012 FU NIH, National Eye Institute FX Our research is supported by the Intramural Research Program of the NIH, National Eye Institute. NR 46 TC 29 Z9 33 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG PY 2010 VL 1 IS 4 BP 309 EP 314 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 801YT UT WOS:000293477200011 PM 20871734 ER PT J AU Murthy, GVS Vashist, P John, N Pokharel, G Ellwein, LB AF Murthy, Gudlavalleti V. S. Vashist, Praveen John, Neena Pokharel, Gopal Ellwein, Leon B. TI Prevelence and Causes of Visual Impairment and Blindness in Older Adults in an Area of India with a High Cataract Surgical Rate SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE Blindness; Cataract; India; Refractive error; Visual impairment ID ARAVIND COMPREHENSIVE EYE; VISION IMPAIRMENT; RURAL-POPULATION; LENS OPACITIES; SOUTH-INDIA; SURGERY; PREVALENCE; DISTRICT; COUNTY; SIGHT AB Background: The cataract surgical rate (CSR) in Gujarat, India is reported to be above 10,000 per million population. This study was conducted to investigate the prevalence and causes of vision impairment/blindness among older adults in a high CSR area. Methods: Geographically defined cluster sampling was used in randomly selecting persons >= 50 years of age in Navsari district. Subjects in 35 study clusters were enumerated and invited for measurement of presenting and best-corrected visual acuity and an ocular examination. The principal cause was identified for eyes with presenting visual acuity < 20/32. Results: A total of 5158 eligible persons were enumerated and 4738 (91.9%) examined. Prevalence of presenting visual impairment < 20/63 to 20/200 in the better eye was 29.3% (95% confidence interval [CI]: 27.5-31.2) and 13.5% (95% CI: 12.0-14.9) with best correction. The prevalence of presenting bilateral blindness (< 20/200) was 6.9% (95% CI: 5.7-8.1), and 3.1% (95% CI: 2.5-3.7) with best correction. Presenting and best-corrected blindness were both associated with older age and illiteracy; gender and rural/urban residence were not significant. Cataract in one or both eyes was the main cause of bilateral blindness (82.6%), followed by retinal disorders (8.9%). Cataract (50.3%) and refractive error (35.4%) were the main causes in eyes with vision acuity < 20/63 to 20/200, and refractive error (86.6%) in eyes with acuity < 20/ 32 to 20/63. Conclusions: Visual impairment and blindness is a significant problem among the elderly in Gujarat. Despite a reportedly high CSR, cataract remains the predominant cause of blindness. C1 [Murthy, Gudlavalleti V. S.] Univ London London Sch Hyg & Trop Med, Int Ctr Eye Hlth, London WC1E 7HT, England. [Vashist, Praveen; John, Neena] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Community Ophthalmol Unit, New Delhi 110029, India. [Ellwein, Leon B.] NEI, NIH, Bethesda, MD 20892 USA. RP Murthy, GVS (reprint author), Univ London London Sch Hyg & Trop Med, Int Ctr Eye Hlth, Keppel St, London WC1E 7HT, England. EM GVS.Murthy@ishtm.ac.uk FU World Health Organization, Geneva, Switzerland under National Institutes of Health [Bethesda, Maryland] [N01-EY-2103] FX Supported by the World Health Organization, Geneva, Switzerland (under National Institutes of Health [Bethesda, Maryland] contract no. N01-EY-2103). NR 31 TC 23 Z9 23 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD AUG PY 2010 VL 17 IS 4 BP 185 EP 195 DI 10.3109/09286586.2010.483751 PG 11 WC Ophthalmology SC Ophthalmology GA 628UO UT WOS:000280148400002 PM 20642340 ER PT J AU Saligan, LN Levy-Clarke, G Wu, TT Faia, LJ Wroblewski, K Yeh, S Nussenblatt, RB Sen, HN AF Saligan, Leorey N. Levy-Clarke, Grace Wu, Tongtong Faia, Lisa J. Wroblewski, Keith Yeh, Steven Nussenblatt, Robert B. Sen, H. Nida TI Quality of Life in Sarcoidosis: Comparing the Impact of Ocular and Non-ocular Involvement of the Disease SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE Health-related quality of life; Vision-related quality of life; Ocular sarcoidosis; Pulmonary sarcoidosis; Burden of disease ID VISUAL FUNCTION QUESTIONNAIRE; HEALTH-STATUS; PULMONARY; EYE; SEVERITY; UVEITIS; IMPAIRMENT; NEI-VFQ-25; DEPRESSION; EXPERIENCE AB Purpose: To compare the differences in vision and health-related quality of life (HRQOL) of individuals with ocular and non-ocular sarcoidosis; and to examine the impact of specific demographic and clinical factors on the noted differences. Methods: A cross-sectional study using non-randomized prospective cohort was conducted at the National Eye Institute (protocol number: 06-EI-0239, NCT00379275) from August 31, 2006 until November 15, 2007. Each participant completed vision and HRQOL questionnaires, the Sarcoidosis Health Questionnaire (SHQ) and the National Eye Institute Visual Function Questionnaire (NEI-VFQ), along with a demographic/environmental exposure survey. Clinical data were collected through an ophthalmic exam as part of the research protocol. Results: The study enrolled 75 biopsy-proven and 20 clinically presumed sarcoidosis participants which were divided into two cohorts, ocular (N = 60) and non-ocular groups (N = 35). The ocular group had significantly lower (P < 0.01) total NEI-VFQ scores compared to the non-ocular group. Multiple linear regression analysis showed that participants with ocular sarcoidosis who had an annual household income of < $50,000 (P < 0.01) had significantly lower total SHQ scores while participants with ocular sarcoidosis whose visual acuity was 20/100 or worse had significantly lower total NEI-VFQ scores (P = 0.03). Conclusions: Ocular involvement impacts both overall and vision-related quality of life among sarcoidosis patients. Lower economic status appears to have a significant impact on the quality of life of sarcoidosis patients. Assessment of visual function and general health status provide pertinent information for individuals with sarcoidosis and should be included in their care to assess burden of their disease on their quality of life. C1 [Saligan, Leorey N.; Levy-Clarke, Grace; Faia, Lisa J.; Wroblewski, Keith; Yeh, Steven; Nussenblatt, Robert B.; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA. [Saligan, Leorey N.] NINR, NIH, Bethesda, MD 20892 USA. [Levy-Clarke, Grace] St Lukes Laser & Eye Ctr, St Petersburg, FL USA. [Wu, Tongtong] Univ Maryland, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N112, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU Intramural NIH HHS [Z99 NR999999] NR 37 TC 5 Z9 5 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD AUG PY 2010 VL 17 IS 4 BP 217 EP 224 DI 10.3109/09286586.2010.483754 PG 8 WC Ophthalmology SC Ophthalmology GA 628UO UT WOS:000280148400006 PM 20642344 ER PT J AU Ferris, FL Miller, KM Glassman, AR Beck, RW AF Ferris, Frederick L. Miller, Kellee M. Glassman, Adam R. Beck, Roy W. CA Diabetic Retinopathy Clinical Res TI A Proposed Method of Logarithmic Transformation of Optical Coherence Tomography Data for Use in Clinical Research SO OPHTHALMOLOGY LA English DT Article ID DIABETIC MACULAR EDEMA; RETINAL THICKNESS; VISUAL-ACUITY; RETINOPATHY AB Purpose: To evaluate a logarithmic transformation of retinal thickness measurements from optical coherence tomography as a new approach to assess clinically meaningful changes in retinal thickness. Design: Methodologic, evidence-based review. Methods: Standard published approaches for assessing change in retinal thickness over time, as measured by optical coherence tomography (OCT), were compared with a new approach based on a logarithmic transformation of the retinal thickness data. Comparative examples were derived using published data from a clinical trial comparing intravitreal corticosteroid injections for diabetic macular edema with standard laser treatment. Main Outcome Measures: Comparative examples using Diabetic Retinopathy Clinical Research Network data. Results: Logarithmic transformation of retinal thickness data results in a more normalized distribution of OCT data and allows for data analyses assessing proportionate changes in retinal thickness during follow-up. Conclusions: For analysis of grouped data, a logarithmic transformation of the OCT retinal thickness measurements (logOCT) provides several analytic advantages. Distributions of retinal thickness in groups of eyes with diabetic macular edema, and many other causes of macular thickening, tend to be skewed to the right; the logOCT transformation tends to normalize these distributions, which has value for statistical comparisons. For assessing whether the observed OCT change in a patient is real (and not due to testing variability), a 1-step log scale change exceeds the measurement error for all degrees of retinal thickness in current instruments. In addition, this log scale is similar to the logarithm of the minimum angle of resolution (logMAR) scale used for visual acuity. Steps on the log scale for change in thickness seem to be better related to clinical importance than the actual change in microns because each step on the log scale is the same proportionate change in thickness, with a 3-step change equaling a halving or doubling of thickness, regardless of the baseline value. Transformation of OCT retinal thickness data to logOCT may assist in the assessment of clinically meaningful changes in retinal thickness just as use of the logMAR scale has helped to assess clinically meaningful changes in visual acuity. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2010; 117: 1512-1516 (C) 2010 by the American Academy of Ophthalmology. C1 [Miller, Kellee M.; Glassman, Adam R.; Beck, Roy W.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Ferris, Frederick L.] NEI, NIH, Bethesda, MD 20892 USA. RP Miller, KM (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat4@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services [EY14231, EY14269, EY14229] FX Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services EY14231, EY14269, EY14229. NR 8 TC 17 Z9 18 U1 0 U2 0 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 AUG PY 2010 VL 117 IS 8 BP 1512 EP 1516 DI 10.1016/j.ophtha.2009.12.014 PG 5 WC Ophthalmology SC Ophthalmology GA 634QU UT WOS:000280598900009 PM 20363505 ER PT J AU Klein, ML Ferris, FL Francis, PJ Lindblad, AS Chew, EY Hamon, SC Ott, J AF Klein, Michael L. Ferris, Frederick L., III Francis, Peter J. Lindblad, Anne S. Chew, Emily Y. Hamon, Sara C. Ott, Jurg TI Progression of Geographic Atrophy and Genotype in Age-Related Macular Degeneration SO OPHTHALMOLOGY LA English DT Article ID COMPLEMENT FACTOR-H; RISK-FACTORS; EYE DISEASE; FAMILIAL AGGREGATION; VISUAL IMPAIRMENT; POOLED FINDINGS; GENETIC RISK; 3 CONTINENTS; VARIANT; HTRA1 AB Purpose: We sought to determine whether genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD). Design: Prospective analysis of participants in a randomized controlled clinical trial. Participants: We included 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS). Methods: Fundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed. Main Outcome Measures: Genotype frequencies and change in cumulative area of GA. Results: The mean growth rate of GA for the 114 eyes was 1.79 mm(2)/year (range, 0.17-4.76). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3 genes. For the single nucleotide polymorphism rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared with the homozygous nonrisk genotype (unadjusted P = 0.002; Bonferroni-corrected P = 0.014) and for allelic association (Bonferroni-corrected P value = 0.011). Analyses of other measures of GA progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype. Conclusions: Growth rates of GA calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, or TLR3 genes. There was a nominally significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations is needed to establish the existence of an association. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2010; 117: 1554-1559 (C) 2010 by the American Academy of Ophthalmology. C1 [Klein, Michael L.; Francis, Peter J.] Oregon Hlth & Sci Univ, Macular Degenerat Ctr, Casey Eye Inst, Portland, OR 97239 USA. [Klein, Michael L.; Francis, Peter J.] Devers Eye Inst, Portland, OR USA. [Ferris, Frederick L., III; Chew, Emily Y.] NEI, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Lindblad, Anne S.] EMMES Corp, Rockville, MD USA. [Hamon, Sara C.; Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. [Ott, Jurg] Chinese Acad Sci, Beijing Inst Gen, Beijing, Peoples R China. RP Klein, ML (reprint author), Oregon Hlth & Sci Univ, Macular Degenerat Ctr, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM kleinm@ohsu.edu FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [R01-EY12203]; China NSFC [30730057]; Casey Eye Institute; Research to Prevent Blindness, New York, New York; Foundation Fighting Blindness, Owings Mills, Maryland FX Supported by contracts and grants from the National Eye Institute, National Institutes of Health, Bethesda, Maryland, R01-EY12203 (MLK), China NSFC grant 30730057 (JO), grants to the Casey Eye Institute, Oregon Health & Science University from Research to Prevent Blindness, New York, New York (PJF, MLK), the Foundation Fighting Blindness, Owings Mills, Maryland (PJF), and the Casey Eye Institute Macular Degeneration Fund (MLK and PJF). The authors have no proprietary interest in any materials or products discussed herein. No authors have any financial/conflicting interests to disclose. NR 45 TC 33 Z9 33 U1 0 U2 1 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 AUG PY 2010 VL 117 IS 8 BP 1554 EP U117 DI 10.1016/j.ophtha.2009.12.012 PG 7 WC Ophthalmology SC Ophthalmology GA 634QU UT WOS:000280598900015 PM 20381870 ER PT J AU Kulke, MH Anthony, LB Bushnell, DL de Herder, WW Goldsmith, SJ Klimstra, DS Marx, SJ Pasieka, JL Pommier, RF Yao, JC Jensen, RT AF Kulke, Matthew H. Anthony, Lowell B. Bushnell, David L. de Herder, Wouter W. Goldsmith, Stanley J. Klimstra, David S. Marx, Stephen J. Pasieka, Janice L. Pommier, Rodney F. Yao, James C. Jensen, Robert T. TI NANETS Treatment Guidelines Well-Differentiated Neuroendocrine Tumors of the Stomach and Pancreas SO PANCREAS LA English DT Article DE islet cell; gastric; carcinoid; guidelines; review ID ZOLLINGER-ELLISON-SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; GASTRIC CARCINOID-TUMORS; PROTON-PUMP INHIBITORS; ISLET-CELL-CARCINOMA; DUODX AFFECT RATE; PHASE-II TRIAL; LONG-TERM; LIVER METASTASES AB Well-differentiated neuroendocrine tumors (NETs) of the stomach and pancreas represent 2 major subtypes of gastrointestinal NETs. Historically, there has been little consensus on the classification and management of patients with these tumor subtypes. We provide an overview of well-differentiated NETs of the stomach and pancreas and describe consensus guidelines for the treatment of patients with these malignancies. C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Anthony, Lowell B.] Louisiana State Univ, Div Hematol Oncol, Hlth Sci Ctr, New Orleans, LA USA. [Bushnell, David L.] Univ Iowa Hosp & Clin, Dept Radiol, Iowa City, IA 52242 USA. [de Herder, Wouter W.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Goldsmith, Stanley J.] Cornell Univ, Div Nucl Med, Dept Radiol, New York Presbyterian Hosp,Weill Med Coll, Ithaca, NY 14853 USA. [Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Marx, Stephen J.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Pasieka, Janice L.] Univ Calgary, Dept Surg, Calgary, AB, Canada. [Pommier, Rodney F.] Oregon Hlth & Sci Univ, Div Surg Oncol, Dept Gen Surg, Portland, OR 97201 USA. [Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Jensen, Robert T.] NIH, Digest Dis Branch, Bethesda, MD 20892 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Matthew_kulke@dfci.harvard.edu FU Intramural NIH HHS [Z01 DK053200-17, Z01 DK053215-02, Z99 DK999999, ZIA DK053200-19]; NCI NIH HHS [K23 CA093401-01A2, K23 CA093401, K23 CA093401-02, K23 CA093401-03, K23 CA093401-04, K23 CA093401-05] NR 192 TC 183 Z9 198 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD AUG PY 2010 VL 39 IS 6 BP 735 EP 752 DI 10.1097/MPA.0b013e3181ebb168 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 629JA UT WOS:000280190900004 PM 20664472 ER PT J AU Boudreaux, JP Klimstra, DS Hassan, MM Woltering, EA Jensen, RT Goldsmith, SJ Nutting, C Bushnell, DL Caplin, ME Yao, JC AF Boudreaux, J. Philip Klimstra, David S. Hassan, Manal M. Woltering, Eugene A. Jensen, Robert T. Goldsmith, Stanley J. Nutting, Charles Bushnell, David L. Caplin, Martyn E. Yao, James C. TI The NANETS Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors Well-Differentiated Neuroendocrine Tumors of the Jejunum, Ileum, Appendix, and Cecum SO PANCREAS LA English DT Article DE neuroendocrine tumors; jejunum; ileum; appendix; cecum ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; RECOMBINANT INTERFERON-ALPHA; METASTATIC CARCINOID-TUMORS; SMALL-INTESTINAL CANCER; ENDOCRINE TUMORS; CHROMOGRANIN-A; RISK-FACTORS; PHASE-II; 5-HYDROXYINDOLEACETIC ACID; ANESTHETIC MANAGEMENT AB Well-differentiated neuroendocrine tumors (NETs) of the jejunum, ileum, and appendix are also collectively known as midgut carcinoids. Similar to NETs in general, the diagnosed incidence of the midgut NETs is on the rise. Their presenting symptoms vary depending on stage and primary site. Local-regional NETs often present with vague and nonspecific symptoms. Classic carcinoid syndrome is more likely to appear in patients with advanced disease. Local-regional NETs of the small bowel should be resected whenever possible. With the exception of small well-differentiated NETs of the appendix, NETs of the midgut have substantial risk of relapse after resection and need to be followed for at least 7 years. Metastatic/advanced NETs of the midgut are incurable. Optimal management requires a multidisciplinary approach. Somatostatin analogs are effective in the management of carcinoid syndrome. Octreotide long-acting release has also recently been shown to delay disease progression. Liver-directed therapy and surgical debulking can improve quality of life in selected patients. Pivotal phase 3 studies with bevacizumab targeting vascular endothelial growth factor and everolimus targeting mTOR (mammalian target of rapamycin) are ongoing and may lead to improved outcome. Further studies of novel approaches such as peptide receptor radiotherapy are also warranted. C1 [Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, Houston, TX 77030 USA. [Boudreaux, J. Philip; Woltering, Eugene A.] Louisiana State Univ, Dept Surg, Hlth Sci Ctr, New Orleans, LA USA. [Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Jensen, Robert T.] NIH, Digest Dis Branch, Bethesda, MD 20892 USA. [Goldsmith, Stanley J.] Cornell Univ, Div Nucl Med, Dept Radiol, New York Presbyterian Hosp,Weill Med Coll, New York, NY 10021 USA. [Nutting, Charles] Swedish Med Ctr, Dept Intervent Radiol, Englewood, CO 80110 USA. [Bushnell, David L.] Univ Iowa Hosp & Clin, Dept Radiol, Iowa City, IA 52242 USA. [Caplin, Martyn E.] Royal Free Hosp, Ctr Gastroenterol, London NW3 2QG, England. RP Yao, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jyao@mdanderson.org NR 62 TC 135 Z9 150 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD AUG PY 2010 VL 39 IS 6 BP 753 EP 766 DI 10.1097/MPA.0b013e3181ebb2a5 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 629JA UT WOS:000280190900005 PM 20664473 ER PT J AU Chen, H Sippel, RS O'Dorisio, MS Vinik, AI Lloyd, RV Pacak, K AF Chen, Herbert Sippel, Rebecca S. O'Dorisio, M. Sue Vinik, Aaron I. Lloyd, Ricardo V. Pacak, Karel TI The North American Neuroendocrine Tumor Society Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors Pheochromocytoma, Paraganglioma, and Medullary Thyroid Cancer SO PANCREAS LA English DT Article DE neuroendocrine tumors; pheochromocytoma; paraganglioma; medullary thyroid cancer ID POSITRON-EMISSION-TOMOGRAPHY; GENOTYPE-PHENOTYPE CORRELATIONS; ENDOCRINE NEOPLASIA TYPE-2; LYMPH-NODE DISSECTION; BIOCHEMICAL-DIAGNOSIS; I-123 METAIODOBENZYLGUANIDINE; LOCALIZING PHEOCHROMOCYTOMAS; MALIGNANT PHEOCHROMOCYTOMAS; METASTATIC PHEOCHROMOCYTOMA; FUNCTIONAL PARAGANGLIOMA AB Pheochromocytomas, intra-adrenal paraganglioma, and extra-adrenal sympathetic and parasympathetic paragangliomas are neuroendocrine tumors derived from adrenal chromaffin cells or similar cells in extra-adrenal sympathetic and parasympathetic paraganglia, respectively. Serious morbidity and mortality rates associated with these tumors are related to the potent effects of catecholamines on various organs, especially those of the cardiovascular system. Before any surgical procedure is done, preoperative blockade is necessary to protect the patient against significant release of catecholamines due to anesthesia and surgical manipulation of the tumor. Treatment options vary with the extent of the disease, with laparoscopic surgery being the preferred treatment for removal of primary tumors. Medullary thyroid cancer (MTC) is a malignancy of the thyroid C cells or parafollicular cells. Thyroid C cells elaborate a number of peptides and hormones, such as calcitonin, carcinoembryonic antigen, and chromogranin A. Some or all of these markers are elevated in patients with MTC and can be used to confirm the diagnosis as well as to follow patients longitudinally for recurrence. Medullary thyroid cancer consists of a spectrum of diseases that ranges from extremely indolent tumors that are stable for many years to aggressive types associated with a high mortality rate. Genetic testing for RET mutations has allowed identification of familial cases and prophylactic thyroidectomy for cure. The only curative treatment is complete surgical resection. C1 [Chen, Herbert; Sippel, Rebecca S.] Univ Wisconsin, Dept Surg, Madison, WI 53792 USA. [O'Dorisio, M. Sue] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Strelitz Diabet Res Ctr, Norfolk, VA 23501 USA. [Lloyd, Ricardo V.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Pacak, Karel] NICHHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chen, H (reprint author), Univ Wisconsin, Dept Surg, H4-722 CSC,600 Highland Ave, Madison, WI 53792 USA. EM chen@surgery.wisc.edu; karel@mail.nih.gov FU Intramural NIH HHS [ZIA HD008735-11]; NCI NIH HHS [R01 CA167632] NR 78 TC 142 Z9 153 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD AUG PY 2010 VL 39 IS 6 BP 775 EP 783 DI 10.1097/MPA.0b013e3181ebb4f0 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 629JA UT WOS:000280190900007 PM 20664475 ER PT J AU Huang, A Li, JA Summers, RM Petrick, N Hara, AK AF Huang, Adam Li, Jiang Summers, Ronald M. Petrick, Nicholas Hara, Amy K. TI Improving polyp detection algorithms for CT colonography: Pareto front approach SO PATTERN RECOGNITION LETTERS LA English DT Article DE Pareto front; Computer-aided detection; Polyp detection; CT colonography; Virtual colonoscopy ID COMPUTER-AIDED DIAGNOSIS; TOMOGRAPHIC VIRTUAL COLONOSCOPY; SUPPORT VECTOR MACHINES; FINITE-SAMPLE SIZE; COLONIC POLYPS; COLORECTAL NEOPLASIA; FEATURE-SELECTION; NEURAL-NETWORKS; CLASSIFICATION; SEGMENTATION AB We investigated a Pareto front approach to improve polyp detection algorithms for CT colonography (CTC). A dataset of 56 CTC colon surfaces with 87 proven positive detections of 53 polyps sized 4-60 mm was used to evaluate the performance of a one-step and a two-step curvature-based region growing algorithm. The algorithmic performance was statistically evaluated and compared based on the Pareto optimal solutions from 20 experiments by evolutionary algorithms. The false positive rate was lower (p < 0.05) by the two-step algorithm than by the one-step for 63% of all possible operating points. While operating at a suitable sensitivity level such as 90.8% (79/87) or 88.5% (77/87), the false positive rate was reduced by 24.4% (95% confidence intervals 17.9-31.0%) or 45.8% (95% confidence intervals 40.1-51.0%), respectively. We demonstrated that, with a proper experimental design, the Pareto optimization process can effectively help in fine-tuning and redesigning polyp detection algorithms. (C) 2010 Elsevier B.V. All rights reserved. C1 [Huang, Adam; Li, Jiang; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Huang, Adam] Natl Cent Univ, Res Ctr Adapt Data Anal, Jhongli, Taiwan. [Li, Jiang] Old Dominion Univ, Dept Elect & Comp Engn, Virginia Modeling Anal & Simulat Ctr, Norfolk, VA 23529 USA. [Petrick, Nicholas] US FDA, NIBIB, Ctr Devices & Radiol Hlth Lab Assessment, Silver Spring, MD 20993 USA. [Hara, Amy K.] Mayo Clin, Scottsdale, AZ 85259 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C368X MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU iCAD; National Institutes of Health (NIH) Clinical Center; National Institute of Biomedical Imaging and Bioengineering at NIH (NP); National Science Council of Republic of China (Taiwan) [NSC 98-2314-B-008-001, 97-2627-B-008-007] FX Authors A. Huang, J. Li, and R.M. Summers have pending and/or awarded patents for the subject matter described in the manuscript. Authors A. Huang and R.M. Summers receive patent royalties from iCAD. Author Summers' lab is supported in part by a Cooperative Research and Development Agreement with iCAD and received free research software from Viatronix.; We thank the anonymous reviewer who suggests adding the FN example in Fig. 8. This additional figure adds clarity to our discussion and leads us to correct an error in the operating parameter NB value given in (Huang et al., 2007). This research was conducted while the first and second authors were post-doctoral fellows supported by the intramural programs of the National Institutes of Health (NIH) Clinical Center. Support was also provided by the intramural program of the National Institute of Biomedical Imaging and Bioengineering at NIH (NP). This study utilized the high-performance computational capabilities of the NIH Biowulf PC/Linux cluster. The first author was partially supported by the National Science Council of Republic of China (Taiwan), NSC 98-2314-B-008-001 and 97-2627-B-008-007. NR 50 TC 0 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 EI 1872-7344 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD AUG 1 PY 2010 VL 31 IS 11 BP 1461 EP 1469 DI 10.1016/j.patrec.2010.03.013 PG 9 WC Computer Science, Artificial Intelligence SC Computer Science GA 624QO UT WOS:000279834800028 PM 20548966 ER PT J AU Morton, CL Houghton, PJ Kolb, EA Gorlick, R Reynolds, CP Kang, MH Maris, JM Keir, ST Wu, JR Smith, MA AF Morton, Christopher L. Houghton, Peter J. Kolb, E. Anders Gorlick, Richard Reynolds, C. Patrick Kang, Min H. Maris, John M. Keir, Stephen T. Wu, Jianrong Smith, Malcolm A. TI Initial Testing of the Replication Competent Seneca Valley Virus (NTX-010) by the Pediatric Preclinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; preclinical testing; Seneca Valley virus (NTX-010) ID NEWCASTLE-DISEASE VIRUS; ONCOLYTIC PICORNAVIRUS; REOVIRUS THERAPY; IMMUNE-RESPONSES; CANCER MODELS; IN-VIVO; TUMOR; XENOGRAFTS; ADENOVIRUSES; VIROTHERAPY AB Background. Seneca Valley virus (NTX-010) is a nonrecombinant, replication competent RNA virus that is undergoing phase 1 clinical trials in adults for tumors with neuroendocrine characteristics. Here we have evaluated the antitumor activity of NTX-010 administered systemically. Procedures. In vitro NTX-010 was tested against 23 cell lines exposed for 96 hr at 1 x 10(-4) to 10(4) viral particles (vp)/cell. In vivo NTX-010 was administered intravenously once at 3 x 10(12) vp/kg. Three measures of antitumor activity were used: (1) an objective response measure modeled after the clinical setting; (2) a treated to control (TIC) tumor volume measure; and (3) a time to event (fourfold increase in tumor volume for solid tumor models), measure based on the median event-free survival (EFS) of treated and control animals for each xenograft. Results. In vitro NTX-010 demonstrated a marked cytotoxic effect in a subset of the cell lines from the neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma panels. In vivo the most consistent activity was observed for the rhabdomyosarcoma and the neuroblastoma panels, with all four of the alveolar rhabdomyosarcoma xenografts and four of five neuroblastoma xenografts achieving CR or maintained CR. Objective responses were also observed in the rhabdoid tumor, Wilms tumor, and glioblastoma panels. Conclusions. NTX-010 demonstrated a high level of activity both in vitro and in vivo. Further analysis of existing testing and molecular characterization data may help define the biological characteristics of cancer cells that are associated with response to NTX-010. Pediatr Blood Cancer. 2010;55:295-303. (C) 2010 Wiley-Liss, Inc. C1 [Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, Columbus, OH 43205 USA. [Morton, Christopher L.; Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, 700 Childrens Dr, Columbus, OH 43205 USA. EM peter.houghton@nationwidechildrens.org RI Houghton, Peter/E-3265-2011 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216, CA21765, CA108786. NR 33 TC 28 Z9 29 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD AUG PY 2010 VL 55 IS 2 BP 295 EP 303 DI 10.1002/pbc.22535 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 621EY UT WOS:000279559200018 PM 20582972 ER PT J AU Brogly, SB Abzug, MJ Watts, DH Cunningham, CK Williams, PL Oleske, J Conway, D Sperling, RS Spiegel, H Van Dyke, RB AF Brogly, Susan B. Abzug, Mark J. Watts, D. Heather Cunningham, Coleen K. Williams, Paige L. Oleske, James Conway, Daniel Sperling, Rhoda S. Spiegel, Hans Van Dyke, Russell B. TI Birth Defects Among Children Born to Human Immunodeficiency Virus-Infected Women Pediatric AIDS Clinical Trials Protocols 219 and 219C SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE in utero exposure; antiretroviral therapy; congenital abnormalities/anomalies; HIV ID ANTIRETROVIRAL THERAPY; CONGENITAL-ABNORMALITIES; EXPOSURE; TRANSMISSION; PREVALENCE; EFAVIRENZ; INFANTS; DISEASE; TRIAL; RISK AB Background: Some studies have detected associations between in utero antiretroviral therapy (ARV) exposure and birth defects but evidence is inconclusive. Methods: A total of 2202 human immunodeficiency virus (HIV)-exposed children enrolled in the Pediatric AIDS Clinical Trials Group 219 and 219 C protocols before 1 year of age were included. Birth defects were classified using the Metropolitan Atlanta Congenital Defects Program coding. Logistic regression models were used to evaluate associations between first trimester in utero ARV exposure and birth defects. Results: A total of 117 live-born children had birth defects for a prevalence of 5.3% (95% confidence interval [CI] : 4.4, 6.3). Prevalence did not differ by HIV infection status or overall ARV exposure; rates were 4.8% (95% CI: 3.7, 6.1) and 5.8% (95% CI: 4.2, 7.8) in children without and with first trimester ARV exposure, respectively. The defect rate was higher among children with first trimester efavirenz exposure (5/32, 15.6%) versus children without first trimester efavirenz exposure (adjusted odds ratio [aOR] = 4.31 [95% CI: 1.56, 11.86]). Protective effects of first trimester zidovudine exposure on musculoskeletal defects were detected (aOR = 0.24 [95% CI: 0.08, 0.69]), while a higher risk of heart defects was found (aOR = 2.04 [95% CI: 1.03, 4.05]). Conclusions: The prevalence of birth defects was higher in this cohort of HIV-exposed children than in other pediatric cohorts. There was no association with overall ARV exposure, but there were some associations with specific agents, including efavirenz. Additional studies are needed to rule out confounding and to evaluate newer ARV agents. C1 [Brogly, Susan B.; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Brogly, Susan B.; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Abzug, Mark J.] Univ Colorado, Dept Pediat Infect Dis, Denver Sch Med, Aurora, CO USA. [Abzug, Mark J.] Childrens Hosp, Aurora, CO USA. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA. [Cunningham, Coleen K.] Duke Univ, Med Ctr, Dept Pediat, Div Infect Dis, Durham, NC 27710 USA. [Oleske, James] Univ Med & Dent New Jersey, Dept Pediat, Newark, NJ 07103 USA. [Conway, Daniel] Drexel Univ, Dept Pediat, Coll Med, Philadelphia, PA 19104 USA. [Sperling, Rhoda S.] Mt Sinai Sch Med, Dept Obstet Gynecol & Reprod Sci, New York, NY USA. [Spiegel, Hans] Montefiore Med Ctr, Adolescent AIDS Program, Bronx, NY 10467 USA. [Van Dyke, Russell B.] Tulane Univ, Dept Pediat, Hlth Sci Ctr, New Orleans, LA 70118 USA. RP Brogly, SB (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, 715 Albany St,Talbot 419E, Boston, MA 02115 USA. EM sbrogly@bu.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the NIAID [5 U01 AI41110, 1 U01 AI068616]; NICHD [N01-DK-9-001/HHSN267200800001C] FX Supported by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632) (to the International Maternal Pediatric Adolescent AIDS Clinical Trials Group [IMPAACT]). This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the NIAID cooperative agreement 5 U01 AI41110 with the PACTG and 1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the NIAID (NIAID) the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). NR 21 TC 38 Z9 39 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD AUG PY 2010 VL 29 IS 8 BP 721 EP 727 DI 10.1097/INF.0b013e3181e74a2f PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 630ZF UT WOS:000280314900009 PM 20539252 ER PT J AU Bell, EF Hansen, NI Morriss, FH Stoll, BJ Ambalavanan, N Gould, JB Laptook, AR Walsh, MC Carlo, WA Shankaran, S Das, A Higgins, RD AF Bell, Edward F. Hansen, Nellie I. Morriss, Frank H., Jr. Stoll, Barbara J. Ambalavanan, Namasivayam Gould, Jeffrey B. Laptook, Abbot R. Walsh, Michele C. Carlo, Waldemar A. Shankaran, Seetha Das, Abhik Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst Human Dev Neonatal Res Network TI Impact of Timing of Birth and Resident Duty-Hour Restrictions on Outcomes for Small Preterm Infants SO PEDIATRICS LA English DT Article DE neonatal; preterm infants; morbidity; death; resident education/training; workforce ID EARLY NEONATAL-MORTALITY; INTENSIVE-CARE UNITS; WORK-HOURS; PATIENT SAFETY; PERINATAL-MORTALITY; DANGEROUS TIME; DEATH; RISK; WEIGHT; WEEKEND AB OBJECTIVE: The goal was to examine the impact of birth at night, on the weekend, and during July or August (the first months of the academic year) and the impact of resident duty-hour restrictions on mortality and morbidity rates for very low birth weight infants. METHODS: Outcomes were analyzed for 11 137 infants with birth weights of 501 to 1250 g who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network registry in 2001-2005. Approximately one-half were born before the introduction of resident duty-hour restrictions in 2003. Follow-up assessments at 18 to 22 months were completed for 4508 infants. Mortality rate, short-term morbidities, and neurodevelopmental outcome were examined with respect to the timing of birth. RESULTS: There was no effect of the timing of birth on mortality rate and no impact on the risks of short-term morbidities except that the risk of retinopathy of prematurity (stage >= 2) was higher after the introduction of duty-hour restrictions and the risk of retinopathy of prematurity requiring operative treatment was lower for infants born during the late night than during the day. There was no impact of the timing of birth on neurodevelopmental outcome except that the risk of hearing impairment or death was slightly lower among infants born in July or August. CONCLUSION: In this network, the timing of birth had little effect on the risks of death and morbidity for very low birth weight infants, which suggests that staffing patterns were adequate to provide consistent care. Pediatrics 2010;126:222-231 C1 [Bell, Edward F.; Morriss, Frank H., Jr.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Hansen, Nellie I.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Stoll, Barbara J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Ambalavanan, Namasivayam; Carlo, Waldemar A.] Univ Alabama Birmingham, Sch Med, Dept Pediat, Birmingham, AL USA. [Gould, Jeffrey B.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA. [Laptook, Abbot R.] Brown Univ, Dept Pediat, Providence, RI 02912 USA. [Walsh, Michele C.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Bell, EF (reprint author), Univ Iowa, Dept Pediat, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM edward-bell@uiowa.edu RI Myers , Gary /I-4901-2013; OI Myers , Gary /0000-0003-4317-015X; Ambalavanan, Namasivayam/0000-0003-0731-9092 FU Case Western Reserve University: Rainbow Babies and Children's Hospital, National Institutes of Health [GCRC M01 RR80, U10 HD21364]; Children's Memorial Hermann Hospital and Lyndon Baines Johnson General Hospital/Harris County Hospital District [U10 HD21373]; Wayne State University: Hutzel Women's Hospital and Children's Hospital of Michigan [U10 HD21385]; University of Miami: Holtz Children's Hospital [GCRC M01 RR16587, U10 HD21397]; Emory University: Children's Healthcare of Atlanta, Grady Memorial Hospital; Emory Crawford Long Hospital [GCRC M01 RR39, U10 HD27851]; University of Cincinnati: University Hospital, Cincinnati Children's Hospital Medical Center; Good Samaritan Hospital [GCRC M01 RR8084, U10 HD27853]; Indiana University: Indiana University Hospital, Methodist Hospital, Riley Hospital for Children; Wishard Health Services [GCRC M01 RR750, U10 HD27856]; Yale University: Yale-New Haven Children's Hospital [GCRC M01 RR125, U10 HD27871]; Stanford University: Lucile Packard Children's Hospital; El Camino Hospital [GCRC M01 RR70, U10 HD27880]; Brown University: Women and Infants Hospital of Rhode Island [U10 HD27904]; CAS; University of Alabama at Birmingham: Health System and Children's Hospital of Alabama [GCRC M01 RR32, U10 HD34216]; University of California, San Diego: Medical Center and Sharp Mary Birch Hospital for Women [U10 HD40461]; Duke University School of Medicine University Hospital, Alamance Regional Medical Center; Durham Regional Hospital [GCRC M01 RR30, U10 HD40492]; Wake Forest University: Baptist Medical Center, Forsyth Medical Center; Brenner Children's Hospital [GCRC M01 RR7122, U10 HD40498]; University of Rochester School of Medicine and Dentistry: Golisano Children's Hospital at Strong [GCRC M01 RR44, U10 HD40521]; University of Texas Southwestern Medical Center at Dallas: Parkland Health and Hospital System and Children's Medical Center Dallas [GCRC M01 RR633, U10 HD40689]; RTI International (Data Coordinating Centre) [U01 HD36790] FX The following investigators, in addition to those listed as authors, participated in this study: NRN Steering Committee chair: Alan H. Jobe, MD, PhD; Eunice Kennedy Shriver National Institute of Child Health and Human Development: Linda L. Wright, MD; University of Iowa: Carver College of Medicine (National Institutes of Health grants U10 HD53109, CTSA UL1 RR24979, and GCRC M01 RR59): Karen J. Johnson, RN; Case Western Reserve University: Rainbow Babies and Children's Hospital (National Institutes of Health grants GCRC M01 RR80 and U10 HD21364): Avroy A. Fanaroff, MD; Nancy S. Newman, RN; Harriet G. Friedman, MA; Bonnie S. Siner, RN; Deanne E. Wilson-Costello, MD; University of Texas Health Science Center at Houston: Children's Memorial Hermann Hospital and Lyndon Baines Johnson General Hospital/Harris County Hospital District (National Institutes of Health grant U10 HD21373): Jon E. Tyson, MD, MPH; Kathleen A. Kennedy, MD, MPH; Patricia W. Evans, MD; Esther G. Akpa, RN, BSN; Nora Alaniz, BS; Patty A. Cluff, RN; Claudia I. Franco, RNC, MSN; Anna E. Lis, RN, BSN; Sarah Martin, RN, BSN; Maegan C. Simmons, RN; Georgia E. McDavid, RN; Patti L. Tate, RCP; Pamela J. Bradt, MD, MPH; Susan Dieterich, PhD; Terri Major-Kincade, MD, MPH; Brenda H. Morris, MD; Stacey Reddoch, BA; Laura L. Whitely, MD; Wayne State University: Hutzel Women's Hospital and Children's Hospital of Michigan (National Institutes of Health grant U10 HD21385): Rebecca Bara, RN, BSN; Geraldine Muran, RN, BSN; Laura Goldston, MA; Yvette R. Johnson, MD, MPH; Athina Pappas, MD; Deborah Kennedy, RN, BSN; Rebecca Wheeler; University of Miami: Holtz Children's Hospital (National Institutes of Health grants GCRC M01 RR16587 and U10 HD21397): Charles R. Bauer, MD; Shahnaz Duara, MD; Ruth EverettThomas, RN, MSN; Maria Calejo, MS; Alexis N. Diaz, BA; Silvia M. Frade Eguaras, MA; Yamiley C. Gideon, BA; Sylvia HiriartFajardo, MD; Ann Londono; Elaine O. Mathews, RN; Emory University: Children's Healthcare of Atlanta, Grady Memorial Hospital, and Emory Crawford Long Hospital (National Institutes of Health grants GCRC M01 RR39 and U10 HD27851): Susie Buchter, MD; Marcia Berry Bishop, MS, NNP-BC; Irma Seabrook, RRT; Ellen C. Hale, RN, BS, CCRC; Ira Adams-Chapman, MD; Sheena Carter, PhD; Elisabeth Dinkins, PNP; Judson Miller, MD; Maureen Mulligan LaRossa, RN; Gloria Smikle, PNP; University of Cincinnati: University Hospital, Cincinnati Children's Hospital Medical Center, and Good Samaritan Hospital (National Institutes of Health grants GCRC M01 RR8084 and U10 HD27853): Edward F. Donovan, MD; Barbara Alexander, RN; Kate Bridges, MD; Cathy Grisby, BSN, CCRC; Marcia Worley Mersmann, RN, CCRC; Holly L. Mincey, RN, BSN; Jody Hessling, RN; Teresa L. Gratton, PA; Jean J. Steichen, MD; Indiana University: Indiana University Hospital, Methodist Hospital, Riley Hospital for Children, and Wishard Health Services (National Institutes of Health grants GCRC M01 RR750 and U10 HD27856): Brenda B. Poindexter, MD, MS; James A. Lemons, MD; Diana D. Appel, RN, BSN; Dianne E. Herron, RN; Lucy C. Miller, RN, BSN, CCRC; Richard Hooper, RRT; Lon G. Bohnke, MS; Marilyn Bull, MD; Ann B. Cook, MS; Anna M. Dusick, MD, FAAP; Greg Eaken, PhD; Darlene Kardatzke, MD; Carolyn Lytle, MD, MPH; Heike M. Minnich, PsyD, HSPP; Leslie Richard, RN; Yale University: Yale-New Haven Children's Hospital (National Institutes of Health grants GCRC M01 RR125 and U10 HD27871): Richard A.; Ehrenkranz, MD; Patricia Gettner, RN; Monica Konstantino, RN, BSN; JoAnn Poulsen, RN; Janet Taft, RN, BSN; Nancy Close, PhD; Elaine Romano, MSN; Joanne Wlliams, RN, BSN; Stanford University: Lucile Packard Children's Hospital and El Camino Hospital (National Institutes of Health grants GCRC M01 RR70 and U10 HD27880): David K. Stevenson, MD; Krisa P. Van Meurs, MD; Susan R. Hintz, MD, MS; M. Bethany Ball, BS, CCRC; Anne M. DeBattista, RN, PNP; Joan M. Baran, PhD; Lori E. Bond, PhD; Ginger K. Brudos, PhD; Julie C. Lee-Ancajas, PhD; Renee P. Pyle, PhD; Nicholas H. St John, PhD; Marian M. Adams, MD; Jean G. Kohn, MD, MPH; Dharshi Sivakumar, MD; Brown University: Women and Infants Hospital of Rhode Island (National Institutes of Health grant U10 HD27904): William Oh, MD; Angelita M. Hensman, RN, BSN; Barbara Alksninis, PNP; William J. Cashore, MD; Regina A. Gargus, MD; Shabnam Lainwala, MD; Theresa M. Leach, MEd, CAES; Martha R. Leonard, BA, BS; Kalida Mehta, MD; James R. Moore, MD; Lucy Noel; Bonnie E. Stephens, MD; Rachel V. Walden, MD; Betty R. Vohr, MD; Victoria E. Watson, MS, CAS; University of Alabama at Birmingham: Health System and Children's Hospital of Alabama (National Institutes of Health grants GCRC M01 RR32 and U10 HD34216): Monica V. Collins, RN, BSN, MaEd; Shirley S. Cosby, RN, BSN; Fred J. Biasini, PhD; Stephanie A. Chopko, PhD; MaryBeth Moses, PT, MS, PCS; Kathleen G. Nelson, MD; Myriam Peralta-Carcelen, MD, MPH; Vivien A. Phillips, RN, BSN; Richard V. Rector, PhD; Sally Whitley, MA, OTR-L, FAOTA; University of California, San Diego: Medical Center and Sharp Mary Birch Hospital for Women (National Institutes of Health grant U10 HD40461): Neil N. Finer, MD; Maynard R. Rasmussen, MD; Paul R. Wozniak, MD; Kathy Arnell, RNC; Renee Bridge, RN; Clarence Demetrio, RN; Jim Goodmar, RRT; Chris Henderson, RCP, CRTT; Wade Rich, BSHS, RRT, CCRC; Rene Barbieri-Welge; Ayala Ben-Tall; Martha G. Fuller, RN, MSN; Elaine Ito; Meghan Lukasik; Deborah Pontillo; Donna Posin, OTR/L, MPA; Cheryl Runyan; Yvonne E. Vaucher, MD, MPH; James Wilkes; Paul Zlotnik, MD; Duke University School of Medicine University Hospital, Alamance Regional Medical Center, and Durham Regional Hospital (National Institutes of Health grants GCRC M01 RR30 and U10 HD40492): Ronald N. Goldberg, MD; C. Michael Cotten, MD, MHS; Kathy J. Auten, MSHS; Ricki E. Goldstein, MD; Kathryn E. Gustafson, PhD; Melody B. Lohmeyer, RN; William F. Malcolm, MD; Wake Forest University: Baptist Medical Center, Forsyth Medical Center, and Brenner Children's Hospital (National Institutes of Health grants GCRC M01 RR7122 and U10 HD40498): T. Michael O'Shea, MD, MPH; Nancy J. Peters, RN, CCRP; Deborah Evans Allred, MA, LPA; Korinne Chiu, MA; Robert G. Dillard, MD; Donald J. Goldstein, PhD; Raquel Halfond, MA; Cherrie Heller, MD, MPH; Gail Wiley Hounshell, PhD; Barbara G. Jackson, RN, BSN; Melissa Whalen Morris, MA; Caroll Peterson, MA; Ellen L. Waldrep, MS; University of Rochester School of Medicine and Dentistry: Golisano Children's Hospital at Strong (National Institutes of Health grants GCRC M01 RR44 and U10 HD40521): Dale L. Phelps, MD; Linda J. Reubens, RN, CCRC; Mary Rowan, RN; Erica L. Burnell, RN; Julie Babish Johnson, MSW; Diane Hust, MS, RN, CS; Rosemary L. Jensen; Emily Kushner, MA; Joan Merzbach, LMSW; Gary J. Myers, MD; Kelley Yost, PhD; Lauren Zwetsch, RN, MS, PNP; University of Texas Southwestern Medical Center at Dallas: Parkland Health and Hospital System and Children's Medical Center Dallas (National Institutes of Health grants GCRC M01 RR633 and U10 HD40689): Charles R.; Roseneld, MD; Walid A. Salhab, MD; Gaynelle Hensley, RN; Susie Madison, RN; Nancy A. Miller, RN; Melissa Martin, RN; James Allen, RRT; Kerry Wilder, RN; Alicia Guzman; R. Sue Broyles, MD; Roy J. Heyne, MD; Sally S. Adams, MS, RN, CPNP; Catherine Twell Boatman, MS; Cristin Dooley, MS; Elizabeth Heyne, PA; Jackie F. Hickman, RN; Linda A. Madden, BSN, RN, CPNP; Janet S. Morgan, RN; RTI International (Data Coordinating Centre) (National Institutes of Health grant U01 HD36790): W. Kenneth Poole, PhD; Betty K. Hastings; Carolyn Petrie Huitema, MS; Elizabeth M. McClure, MEd; Jeanette O'Donnell Auman, BS; Kristin M. Zaterka-Baxter, RN, BSN; Jamie E. Newman, PhD, MPH. NR 45 TC 14 Z9 14 U1 1 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2010 VL 126 IS 2 BP 222 EP 231 DI 10.1542/peds.2010-0456 PG 10 WC Pediatrics SC Pediatrics GA 634FO UT WOS:000280565700005 PM 20643715 ER PT J AU Black, MM Hager, ER Le, K Anliker, J Arteaga, SS DiClemente, C Gittelsohn, J Magder, L Papas, M Snitker, S Treuth, MS Wang, Y AF Black, Maureen M. Hager, Erin R. Le, Katherine Anliker, Jean Arteaga, S. Sonia DiClemente, Carlo Gittelsohn, Joel Magder, Laurence Papas, Mia Snitker, Soren Treuth, Margarita S. Wang, Yan TI Challenge! Health Promotion/Obesity Prevention Mentorship Model Among Urban, Black Adolescents SO PEDIATRICS LA English DT Article DE adolescent obesity prevention; adolescence; overweight; intervention; randomized; controlled trial; mentor; black; physical activity; diet ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; BEVERAGE CONSUMPTION; CHILDHOOD OBESITY; WEIGHT STATUS; US CHILDREN; YOUNG ADULTHOOD; OVERWEIGHT; SCHOOL; GIRLS AB OBJECTIVES: The objective of this study was to evaluate a 12-session home/community-based health promotion/obesity prevention program (Challenge!) on changes in BMI status, body composition, physical activity, and diet. METHODS: A total of 235 black adolescents (aged 11-16 years; 38% overweight/obese) were recruited from low-income urban communities. Baseline measures included weight, height, body composition, physical activity (PA), and diet. PA was measured by 7-day play-equivalent physical activity (>= 1800 activity counts per minute). Participants were randomly assigned to health promotion/obesity prevention that is anchored in social cognitive theory and motivational interviewing and was delivered by college-aged black mentors or to control. Postintervention (11 months) and delayed follow-up (24 months) evaluations were conducted. Longitudinal analyses used multilevel models with random intercepts and generalized estimating equations, controlling for baseline age/gender. Stratified analyses examined baseline BMI category. RESULTS: Retention was 76% over 2 years; overweight/obese status declined 5% among intervention adolescents and increased 11% among control adolescents. Among overweight/obese youth, the intervention reduced total percentage of body fat and fat mass and increased fat-free mass at delayed follow-up and increased play-equivalent physical activity at postintervention but not at delayed follow-up. Intervention adolescents declined significantly more in snack/dessert consumption than control adolescents at both follow-up evaluations. CONCLUSIONS: At postintervention, there were intervention effects on diet and PA but not BMI category or body composition. At delayed follow-up, dietary changes were sustained and the intervention prevented an increase in BMI category. Body composition was improved for overweight/obese youth. Changes in body composition follow changes in diet and PA and may not be detected immediately after intervention. Pediatrics 2010;126:280-288 C1 [Black, Maureen M.; Hager, Erin R.; Le, Katherine; Papas, Mia; Wang, Yan] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. [Magder, Laurence] Univ Maryland, Sch Med, Dept Epidemiol, Baltimore, MD 21201 USA. [Snitker, Soren] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Anliker, Jean] Univ Massachusetts, Dept Nutr, Amherst, MA 01003 USA. [Arteaga, S. Sonia] NHLBI, NIH, Bethesda, MD 20892 USA. [DiClemente, Carlo] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. [Gittelsohn, Joel] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD USA. [Treuth, Margarita S.] Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD USA. RP Black, MM (reprint author), Univ Maryland, Sch Med, Dept Pediat, 737 W Lombard St,Room 161, Baltimore, MD 21201 USA. EM mblack@peds.umaryland.edu FU US Department of Health and Human Services [R40MC00241]; University of Maryland General Clinical Research Center [M01 RR16500]; National Center for Research Resources, National Institutes of Health FX This research was supported by grant R40MC00241 from the Maternal and Child Health Research Program, US Department of Health and Human Services, to Dr Black and the University of Maryland General Clinical Research Center grant M01 RR16500, General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health. NR 48 TC 49 Z9 50 U1 7 U2 30 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2010 VL 126 IS 2 BP 280 EP 288 DI 10.1542/peds.2009-1832 PG 9 WC Pediatrics SC Pediatrics GA 634FO UT WOS:000280565700015 PM 20660556 ER PT J AU Sancho, V Moody, TW Mantey, SA Di Florio, A Uehara, H Coy, DH Jensen, RT AF Sancho, Veronica Moody, Terry W. Mantey, Samuel A. Di Florio, Alessia Uehara, Hirotsugu Coy, David H. Jensen, Robert T. TI Pharmacology of putative selective hBRS-3 receptor agonists for human bombesin receptors (BnR): Affinities, potencies and selectivity in multiple native and BnR transfected cells SO PEPTIDES LA English DT Article DE Bombesin; Gastrin-releasing peptide; Neuromedin B; Agonist; Receptor ID HUMAN ORPHAN RECEPTOR; LUNG-CANCER CELLS; PROTEIN-KINASE-D; BRONCHIAL EPITHELIAL-CELLS; SUBTYPE-3-DEFICIENT MICE; PANCREATIC ACINI; SUBTYPE 3; PEPTIDE AGONIST; NERVOUS-SYSTEM; NEUROMEDIN-B AB The orphan receptor, bombesin receptor subtype-3(BRS-3) is a G-protein-coupled receptor classified in the bombesin (Bn) receptor family because of its high homology (47-51%) with other members of this family [gastrin-releasing peptide receptor [GRPR] and neuromedin B receptor [NIMBR]]. There is increasing interest in BRS-3, because primarily from receptor knockout studies, it seems important in energy metabolism, glucose control, insulin secretion, motility and tumor growth. Pharmacological tools to study the role of BRS-3 in physiology/pathophysiology are limited because the natural ligand is unknown and BRS-3 has low affinity for all naturally occurring Bn-related peptides. However, a few years ago a synthetic high-affinity agonist [DTyr(6),beta Ala(11),Phe(13),Nle(14)]Bn-(6-14) was described but was nonselective for BRS-3 over other Bn receptors. Based on this peptide, in various studies a number of putative selective, high-potency hBRS-3 agonists were described, however the results on their selectivity are conflicting in a number of cases. The purpose of the present study was to thoroughly study the pharmacology of four of the most select/potent putative hBRS-3 agonists (#2-4, 16a). Each was studied in multiple well-characterized Bn receptor-transfected cells and native Bn receptor bearing cells, using binding studies, alterations in cellular signaling (PLC, PKD) and changes in cellular function(growth). Two peptides (#2, #3) had nM affinities/potencies for hBRS-3, peptide #4 had low affinity/potency, and peptide #16a very low (>3000 nM). Peptide#3 had the highest selectivity for hBRS-3 (100-fold), whereas #2,4 had lower selectivity. Peptide #16a's selectivity could not be determined because of its low affinity/potencies for all hBn receptors. These results show that peptide #3 is the preferred hBRS-3 agonist for studies at present, although its selectivity of only 100-fold may limit its utility in some cases. This study underscores the importance of full pharmacological characterization of newly reported selective agonists. Published by Elsevier Inc. C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Sancho, Veronica; Moody, Terry W.; Mantey, Samuel A.; Di Florio, Alessia; Uehara, Hirotsugu; Jensen, Robert T.] NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Moody, Terry W.] NCI, CCR, Bethesda, MD 20892 USA. [Coy, David H.] Tulane Hlth Sci Ctr, Peptide Res Labs, Dept Med, New Orleans, LA 70112 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU NIDDK; NCI; NIH; Tulane University FX This work was partially supported by intramural funds of NIDDK and NCI, NIH, and Tulane University Peptide Research Fund. NR 65 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD AUG PY 2010 VL 31 IS 8 BP 1569 EP 1578 DI 10.1016/j.peptides.2010.04.023 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 635NY UT WOS:000280663600021 PM 20438784 ER PT J AU Zhang, FJ Yang, JY Mou, YH Sun, BS Wang, JM Wu, CF AF Zhang, Feng-Jiao Yang, Jing-Yu Mou, Yan-Hua Sun, Bao-Shan Wang, Ji-Ming Wu, Chun-Fu TI Oligomer procyanidins from grape seeds induce a paraptosis-like programmed cell death in human glioblastoma U-87 cells SO PHARMACEUTICAL BIOLOGY LA English DT Article DE Calcium mobilization; glioma; grape seed extract; MAPKs; oligomer procyanidins; paraptosis ID MECHANISMS; ACTIVATION; APOPTOSIS; FORM; NEURODEGENERATION; INHIBITION; FRACTIONS; CASPASES; TOXICITY; CALCIUM AB Context: We recently reported that F2, an oligomer procyanidin fraction isolated from grape seeds, triggered an original form of cell death in U-87 human glioblastoma cells with a phenotype resembling morphological characteristics of paraptosis. However, the specific death mode induced by F2 and the mechanism of its action have not been assessed so far. Objective: In the present work, we therefore further investigated the death mode of human glioblastma cells induced by F2 and gained insight into the nature of the signaling pathways activated by F2 in glioblastoma cells. Materials and methods: Cell viability assay using MTT, (AO/EB) double staining, Western blot analysis, and Ca(2+) assay using fura-2. Results: Morphology studies revealed extensive cytoplasmic vacuolization in dying cells and no apoptotic body formation, membrane bleb formation, or nuclear fragmentation, though some was accompanied by MAPK activation and new protein synthesis, and was independent of caspase activation. Moreover, we demonstrated the involvement of calcium mobilization in F2-induced U-87 cell signaling. Discussion and conclusion: Altogether we showed that F2 induced a kind of cell death resembling paraptosis in U-87 cells. The current report complements previous studies on the characterization of F2-induced U-87 cell death, enhances our understanding of the action mechanism of F2 on glioma, and helps in the development of novel antitumor therapeutics. C1 [Zhang, Feng-Jiao; Yang, Jing-Yu; Mou, Yan-Hua; Wu, Chun-Fu] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. [Sun, Bao-Shan] Quinta Almoinha, Inst Nacl Recursos Biol, Estacao Vitivinicola, Dois Portos, Portugal. [Wang, Ji-Ming] Natl Canc Inst, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD USA. RP Wu, CF (reprint author), Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. EM wucf@syphu.edu.cn FU Key Laboratory for New Drug Screening of Liaoning Province; national project for New Drug Discovery and Development FX This research is partially supported by the Project of Key Laboratory for New Drug Screening of Liaoning Province, and by a national project for New Drug Discovery and Development. NR 30 TC 7 Z9 11 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PD AUG PY 2010 VL 48 IS 8 BP 883 EP 890 DI 10.3109/13880200903311102 PG 8 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 643OA UT WOS:000281304800007 PM 20673175 ER PT J AU Tsai, HT Pfeiffer, R Landgren, CO AF Tsai, Huei-Ting Pfeiffer, Ruth Landgren, C. Ola TI Risk of Cardiovascular Events among 3,865 Elderly Diffuse Large B-Cell Lymphoma Patients Treated with Doxorubicin-Based Chemotherapy plus /-Rituximab: A Population-Based Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Tsai, Huei-Ting; Pfeiffer, Ruth; Landgren, C. Ola] NCI, NIH, Bethesda, MD 20892 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 445 BP S188 EP S189 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200427 ER PT J AU Walker, AM Patrick, AR Lauer, MS Laurencin, CT Marin, MG Platt, R Stang, P Schneeweiss, S AF Walker, A. M. Patrick, A. R. Lauer, M. S. Laurencin, C. T. Marin, M. G. Platt, R. Stang, P. Schneeweiss, S. TI Prioritizing Comparative Effectiveness Research SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract CT 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 19-22, 2010 CL Brighton, ENGLAND C1 [Walker, A. M.] WHISCON, Newton, MA USA. [Patrick, A. R.; Schneeweiss, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lauer, M. S.] NHLBI, Bethesda, MD 20892 USA. [Stang, P.] Johnson & Johnson PRD, Titusville, NJ USA. [Platt, R.] Harvard Med Sch, Boston, MA USA. [Marin, M. G.] AstraZeneca Pharmaceutcals, Wilmington, DE USA. [Laurencin, C. T.] Univ Connecticut, Storrs, CT 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 450 BP S190 EP S191 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200432 ER PT J AU Zee, AHMVD Freedman, A Daly, AK Holden, A AF Zee, Anke-Hilse Maitland-van der Freedman, Andrew Daly, Ann K. Holden, Arthur TI Identifying the Genetic Basis of Serious Adverse Events: Will High-Profile Genome-Wide Association (GWA) Studies Improve Drug Safety in the Next Decade? A Joint MEBPharmacogenomics-SIG & iSAEC Symposium SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zee, Anke-Hilse Maitland-van der] Univ Utrecht, Utrecht, Netherlands. [Freedman, Andrew] NCI, Bethesda, MD 20892 USA. [Daly, Ann K.] Newcastle Univ, Newcastle, NSW, Australia. [Holden, Arthur] iSAEC, Chicago, IL 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2010 VL 19 SU 1 MA 41 BP S18 EP S18 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA V45OP UT WOS:000209826200041 ER PT J AU Rusyn, I Gatti, DM Wilshire, T Kleeberger, SR Threadgill, DW AF Rusyn, Ivan Gatti, Daniel M. Wilshire, Timothy Kleeberger, Steven R. Threadgill, David W. TI Toxicogenetics: population-based testing of drug and chemical safety in mouse models SO PHARMACOGENOMICS LA English DT Review DE collaborative cross; expression quantitative trait locus mapping; mouse genetics; population screening; toxicity testing; toxicogenetics ID QUANTITATIVE TRAIT LOCI; GENOME-WIDE ASSOCIATION; ACUTE LUNG INJURY; COLLABORATIVE CROSS; B6C3F1 MICE; TRANSCRIPTION FACTORS; GENETIC DISSECTION; SYSTEMS GENETICS; INBRED STRAINS; HUMAN-DISEASES AB The rapid decline in the cost of dense genotyping is paving the way for new DNA sequence-based laboratory tests to move quickly into clinical practice, and to ultimately help realize the promise of 'personalized' therapies. These advances are based on the growing appreciation of genetics as an important dimension in science and the practice of investigative pharmacology and toxicology. On the clinical side, both the regulators and the pharmaceutical industry hope that the early identification of individuals prone to adverse drug effects will keep advantageous medicines on the market for the benefit of the vast majority of prospective patients. On the environmental health protection side, there is a clear need for better science to define the range and causes of susceptibility to adverse effects of chemicals in the population, so that the appropriate regulatory limits are established. In both cases, most of the research effort is focused on genome-wide association studies in humans where de novo genotyping of each subject is required. At the same time, the power of population-based preclinical safety testing in rodent models (e.g., mouse) remains to be fully exploited. Here, we highlight the approaches available to utilize the knowledge of DNA sequence and genetic diversity of the mouse as a species in mechanistic toxicology research. We posit that appropriate genetically defined mouse models may be combined with the limited data from human studies to not only discover the genetic determinants of susceptibility, but to also understand the molecular underpinnings of toxicity. C1 [Rusyn, Ivan; Gatti, Daniel M.] Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr, Chapel Hill, NC 27515 USA. [Rusyn, Ivan; Kleeberger, Steven R.; Threadgill, David W.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. [Wilshire, Timothy] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Natl Inst Hlth, Res Triangle Pk, NC USA. [Threadgill, David W.] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr, Chapel Hill, NC 27515 USA. EM jir@unc.edu RI Rusyn, Ivan/S-2426-2016; Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 FU National Institute of Environmental Health Sciences; [P42 ES005948]; [R01 ES015241] FX The authors were supported by research grants (P42 ES005948, R01 ES015241), and the Intramural Research Program of the National Institute of Environmental Health Sciences. 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 83 TC 18 Z9 18 U1 3 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD AUG PY 2010 VL 11 IS 8 BP 1127 EP 1136 DI 10.2217/PGS.10.100 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 645MV UT WOS:000281465500017 PM 20704464 ER PT J AU Fan, X Lobenhofer, EK Chen, M Shi, W Huang, J Luo, J Zhang, J Walker, SJ Chu, TM Li, L Wolfinger, R Bao, W Paules, RS Bushel, PR Li, J Shi, T Nikolskaya, T Nikolsky, Y Hong, H Deng, Y Cheng, Y Fang, H Shi, L Tong, W AF Fan, X. Lobenhofer, E. K. Chen, M. Shi, W. Huang, J. Luo, J. Zhang, J. Walker, S. J. Chu, T-M Li, L. Wolfinger, R. Bao, W. Paules, R. S. Bushel, P. R. Li, J. Shi, T. Nikolskaya, T. Nikolsky, Y. Hong, H. Deng, Y. Cheng, Y. Fang, H. Shi, L. Tong, W. TI Consistency of predictive signature genes and classifiers generated using different microarray platforms SO PHARMACOGENOMICS JOURNAL LA English DT Article DE microarray; cross-platform; gene signature; classifier; MAQC; hepatotoxicity ID CONTROL MAQC PROJECT; CROSS-PLATFORM; DNA MICROARRAY; EXPRESSION MEASUREMENTS; DECISION FOREST; PERFORMANCE; TECHNOLOGIES; REPRODUCIBILITY; NORMALIZATION; VISUALIZATION AB Microarray-based classifiers and associated signature genes generated from various platforms are abundantly reported in the literature; however, the utility of the classifiers and signature genes in cross-platform prediction applications remains largely uncertain. As part of the MicroArray Quality Control Phase II (MAQC-II) project, we show in this study 80-90% cross-platform prediction consistency using a large toxicogenomics data set by illustrating that: (1) the signature genes of a classifier generated from one platform can be directly applied to another platform to develop a predictive classifier; (2) a classifier developed using data generated from one platform can accurately predict samples that were profiled using a different platform. The results suggest the potential utility of using published signature genes in cross-platform applications and the possible adoption of the published classifiers for a variety of applications. The study reveals an opportunity for possible translation of biomarkers identified using microarrays to clinically validated non-array gene expression assays. The Pharmacogenomics Journal (2010) 10, 247-257; doi: 10.1038/tpj.2010.34 C1 [Fan, X.; Huang, J.; Cheng, Y.] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310003, Zhejiang, Peoples R China. [Lobenhofer, E. K.] Cogenics, Morrisville, NC USA. [Chen, M.; Huang, J.; Hong, H.; Shi, L.; Tong, W.] US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shi, W.; Nikolskaya, T.; Nikolsky, Y.] GeneGo Inc, St Joseph, MI USA. [Luo, J.; Zhang, J.] Syst Analyt Inc, Waltham, MA USA. [Walker, S. J.] Wake Forest Inst Regenerat Med, Winston Salem, NC USA. [Chu, T-M; Li, L.; Wolfinger, R.; Bao, W.] SAS Inst Inc, Cary, NC USA. [Paules, R. S.; Bushel, P. R.; Li, J.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Shi, T.] Chinese Acad Sci, Shanghai Informat Ctr Sci, Shanghai, Peoples R China. [Nikolskaya, T.] Russian Acad Sci, NI Vavilov Gen Genet Res Inst, Moscow, Russia. [Deng, Y.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Fang, H.] US FDA, Z Tech, NCTR, Tempe, AR USA. RP Tong, W (reprint author), US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov FU Chinese Key Technologies RD Program [2005CB23402]; National Science Foundation of China [30801556]; Research Fund for the Doctoral Program of Higher Education of China [20090101110126] FX Dr Xiaohui Fan thanks the support by Chinese Key Technologies R&D Program (No. 2005CB23402), the National Science Foundation of China (No. 30801556) and Research Fund for the Doctoral Program of Higher Education of China (No. 20090101110126) for participating in the MAQC project at National Center for Toxicological Research of the US Food and Drug Administration. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 32 TC 27 Z9 30 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 247 EP 257 DI 10.1038/tpj.2010.34 PG 11 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100002 PM 20676064 ER PT J AU Huang, J Shi, W Zhang, J Chou, JW Paules, RS Gerrish, K Li, J Luo, J Wolfinger, RD Bao, W Chu, TM Nikolsky, Y Nikolskaya, T Dosymbekov, D Tsyganova, MO Shi, L Fan, X Corton, JC Chen, M Cheng, Y Tong, W Fang, H Bushel, PR AF Huang, J. Shi, W. Zhang, J. Chou, J. W. Paules, R. S. Gerrish, K. Li, J. Luo, J. Wolfinger, R. D. Bao, W. Chu, T-M Nikolsky, Y. Nikolskaya, T. Dosymbekov, D. Tsyganova, M. O. Shi, L. Fan, X. Corton, J. C. Chen, M. Cheng, Y. Tong, W. Fang, H. Bushel, P. R. TI Genomic indicators in the blood predict drug-induced liver injury SO PHARMACOGENOMICS JOURNAL LA English DT Article DE prediction; acetaminophen; blood; cross-tissue; liver injury; microarray gene expression ID GENE-EXPRESSION PROFILES; COEXPRESSED GENES; SERUM BIOMARKERS; HEPATOTOXICITY; MICROARRAY; TOXICITY; MECHANISMS; RATS; NEUTROPHILS; PHENOTYPE AB Genomic biomarkers for the detection of drug-induced liver injury (DILI) from blood are urgently needed for monitoring drug safety. We used a unique data set as part of the Food and Drug Administration led MicroArray Quality Control Phase-II (MAQC-II) project consisting of gene expression data from the two tissues (blood and liver) to test cross-tissue predictability of genomic indicators to a form of chemically induced liver injury. We then use the genomic indicators from the blood as biomarkers for prediction of acetaminophen-induced liver injury and show that the cross-tissue predictability of a response to the pharmaceutical agent (accuracy as high as 92.1%) is better than, or at least comparable to, that of non-therapeutic compounds. We provide a database of gene expression for the highly informative predictors, which brings biological context to the possible mechanisms involved in DILI. Pathway-based predictors were associated with inflammation, angiogenesis, Toll-like receptor signaling, apoptosis, and mitochondrial damage. The results show for the first time and support the hypothesis that genomic indicators in the blood can serve as potential diagnostic biomarkers predictive of DILI. The Pharmacogenomics Journal (2010) 10, 267-277; doi: 10.1038/tpj.2010.33 C1 [Chou, J. W.; Li, J.; Bushel, P. R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Huang, J.; Fan, X.; Cheng, Y.] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310003, Zhejiang, Peoples R China. [Shi, W.; Nikolsky, Y.; Nikolskaya, T.] GeneGO, St Joseph, MI USA. [Zhang, J.; Luo, J.] Syst Analyt, Dept Bioinformat, Waltham, MA USA. [Paules, R. S.; Gerrish, K.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. [Wolfinger, R. D.; Bao, W.; Chu, T-M] SAS, Genom Div, Cary, NC USA. [Dosymbekov, D.; Tsyganova, M. O.] Russian Acad Sci, NI Vavilov Gen Genet Res Inst, Moscow, Russia. [Huang, J.; Shi, L.; Fan, X.; Chen, M.; Tong, W.] US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Corton, J. C.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Fang, H.] US FDA, Div Bioinformat, Z Tech Corp, NCTR, Jefferson, AR USA. [Nikolskaya, T.] Russian Acad Sci, Inst Gen Genet, Syst Biol Lab, Moscow V71, Russia. RP Bushel, PR (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM bushel@niehs.nih.gov FU Oak Ridge Institute for Science and Education (ORISE) at the National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA); China State; Chinese Key Technologies RD Program [2005CB23402]; National Science Foundation of China at the NCTR/FDA [30801556]; Intramural Research Program of the NIH; NIEHS [Z01 ES102345-03] FX We thank the National Center for Toxicogenomics at the National Institute of Environmental Health Sciences (NIEHS) for the hepatotoxicant compendium data. In addition, we thank the participants of MAQC-II for comments, feedback, and discussions on the topic of this paper during teleconferences and face-to-face project meetings. We also thank K Shockley, A Merrick, S Hester, B Ward, and D Mendrick for their critical review of the manuscript. JH acknowledge the support of the Oak Ridge Institute for Science and Education (ORISE) for the Post-graduate Research Program at the National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA). JH also acknowledges the support of the China State-funded Study Abroad Program that is organized by the China Scholarship Council (CSC). JH and XF both acknowledge the Chinese Key Technologies R&D Program (No. 2005CB23402) and the National Science Foundation of China (No. 30801556) for support to participate in the MAQC-II project at the NCTR/FDA. This research was supported, in part by, the Intramural Research Program of the NIH and NIEHS (Z01 ES102345-03). This document has been reviewed in accordance with the US FDA and Environmental Protection Agency (EPA) policies and is approved for publication. Approval does not signify that the contents necessarily reflect the position or opinions of the FDA or EPA nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The findings, views, and conclusions in this report are those of the authors and do not necessarily represent or reflect the views of the FDA or EPA. NR 42 TC 31 Z9 38 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 267 EP 277 DI 10.1038/tpj.2010.33 PG 11 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100004 PM 20676066 ER PT J AU Luo, J Schumacher, M Scherer, A Sanoudou, D Megherbi, D Davison, T Shi, T Tong, W Shi, L Hong, H Zhao, C Elloumi, F Shi, W Thomas, R Lin, S Tillinghast, G Liu, G Zhou, Y Herman, D Li, Y Deng, Y Fang, H Bushel, P Woods, M Zhang, J AF Luo, J. Schumacher, M. Scherer, A. Sanoudou, D. Megherbi, D. Davison, T. Shi, T. Tong, W. Shi, L. Hong, H. Zhao, C. Elloumi, F. Shi, W. Thomas, R. Lin, S. Tillinghast, G. Liu, G. Zhou, Y. Herman, D. Li, Y. Deng, Y. Fang, H. Bushel, P. Woods, M. Zhang, J. TI A comparison of batch effect removal methods for enhancement of prediction performance using MAQC-II microarray gene expression data SO PHARMACOGENOMICS JOURNAL LA English DT Article DE batch effect; batch effect removal; cross-batch prediction; microarray; gene expression; MAQC-II ID NORMALIZATION; CANCER; BLOOD AB Batch effects are the systematic non-biological differences between batches (groups) of samples in microarray experiments due to various causes such as differences in sample preparation and hybridization protocols. Previous work focused mainly on the development of methods for effective batch effects removal. However, their impact on cross-batch prediction performance, which is one of the most important goals in microarray-based applications, has not been addressed. This paper uses a broad selection of data sets from the Microarray Quality Control Phase II (MAQC-II) effort, generated on three microarray platforms with different causes of batch effects to assess the efficacy of their removal. Two data sets from cross-tissue and cross-platform experiments are also included. Of the 120 cases studied using Support vector machines (SVM) and K nearest neighbors (KNN) as classifiers and Matthews correlation coefficient (MCC) as performance metric, we find that Ratio-G, Ratio-A, EJLR, mean-centering and standardization methods perform better or equivalent to no batch effect removal in 89, 85, 83, 79 and 75% of the cases, respectively, suggesting that the application of these methods is generally advisable and ratio-based methods are preferred. The Pharmacogenomics Journal (2010) 10, 278-291; doi: 10.1038/tpj.2010.57 C1 [Zhang, J.] Syst Analyt Inc, Dept Bioinformat, Waltham, MA 02453 USA. [Schumacher, M.] Novartis Pharma AG, NIBR, Biomarker Dev Dept, Basel, Switzerland. [Scherer, A.] Spheromics, Kontiolahti, Finland. [Sanoudou, D.] Acad Athens, Biomed Res Fdn, Dept Mol Biol, Athens, Greece. [Sanoudou, D.] Univ Athens, Sch Med, Dept Pharmacol, Athens 11528, Greece. [Megherbi, D.] Univ Massachusetts, Dept Elect & Comp Engn, CMINDS Res Ctr, Lowell, MA USA. [Davison, T.] Almac Diagnost, Craigavon, North Ireland. [Shi, T.] Chinese Acad Sci, Shanghai Informat Ctr Life Sci, Shanghai, Peoples R China. [Tong, W.; Shi, L.; Hong, H.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Zhao, C.] NE Forestry Univ, Coll Life Sci, Harbin, Heilongjiang, Peoples R China. [Elloumi, F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Shi, W.] GeneGo Inc, St Joseph, MI USA. [Thomas, R.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA. [Lin, S.] Northwestern Univ, Clin & Translat Sci Inst, Chicago, IL 60611 USA. [Tillinghast, G.] Riverside Canc Care Ctr, Dept Clin Res, Newport News, VA USA. [Liu, G.] SABiosci Corp, R&D Div, Frederick, MD USA. [Zhou, Y.; Herman, D.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Li, Y.] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Deng, Y.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Fang, H.] US FDA, Z Tech, Natl Ctr Toxicol Res, Jefferson, AR USA. [Bushel, P.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Zhang, J (reprint author), Syst Analyt Inc, Dept Bioinformat, 55 Moody St,Suite 21, Waltham, MA 02453 USA. EM johnz@SystemsAnalytics.com OI Thomas, Russell/0000-0002-2340-0301; Sanoudou, Despina/0000-0003-3704-1941 NR 17 TC 71 Z9 75 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2010 VL 10 IS 4 BP 278 EP 291 DI 10.1038/tpj.2010.57 PG 14 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 636DT UT WOS:000280709100005 PM 20676067 ER PT J AU Penzak, SR Robertson, SM Hunt, JD Chairez, C Malati, CY Alfaro, RM Stevenson, JM Kovacs, JA AF Penzak, Scott R. Robertson, Sarah M. Hunt, Jennifer D. Chairez, Cheryl Malati, Christine Y. Alfaro, Raul M. Stevenson, James M. Kovacs, Joseph A. TI Echinacea purpurea Significantly Induces Cytochrome P450 3A Activity but Does Not Alter Lopinavir-Ritonavir Exposure in Healthy Subjects SO PHARMACOTHERAPY LA English DT Article DE human immunodeficiency virus; HIV; protease inhibitors; lopinavir; ritonavir; Echinacea purpurea; herb; cytochrome P450; CYP; P-glycoprotein; P-gp; drug interaction ID HIV-INFECTED PATIENTS; ST-JOHNS WORT; DRUG-INTERACTIONS; GINKGO-BILOBA; IN-VIVO; PHARMACOKINETICS; COMPLEMENTARY; LOPINAVIR/RITONAVIR; SAQUINAVIR; INDINAVIR AB Study Objective. To determine the influence of Echinacea purpurea on the pharmacokinetics of lopinavir-ritonavir and on cytochrome P450 (CYP) 3A and P-glycoprotein activity by using the probe substrates midazolam and fexofenadine, respectively. Design. Open-label, single-sequence pharmacokinetic study. Setting. Outpatient clinic in a federal government research center. Subjects. Thirteen healthy volunteers (eight men, five women). Intervention. Subjects received lopinavir 400 mg-ritonavir 100 mg twice/day with meals for 29.5 days. On day 16, subjects received E. purpurea 500 mg 3 times/day for 28 days: 14 days in combination with lopinavir-ritonavir and 14 days of E. purpurea alone. In order to assess CYP3A and P-glycoprotein activity subjects received single oral doses of midazolam 8 mg and fexofenadine 120 mg, respectively, before and after the 28 days of E. purpurea. Measurements and Main Results. On days 15 and 30 of lopinavir-ritonavir administration (before and after E. puipurea administration, respectively), serial blood samples were collected over 12 hours to determine lopinavir and ritonavir concentrations and subsequent pharmacokinetic parameters by using noncompartmental methods. Neither lopinavir nor ritonavir pharmacokinetics were significantly altered by 14 days of E. purpurea coadministration. The post-echinacea:pre-echinacea geometric mean ratios (GMRs) for lopinavir area under the concentration-time curve (AUC) from 0-12 hours and for maximum concentration were 0.96 (90% confidence interval [CI] 0.83-1.10, p=0.82) and 1.00 (90% CI 0.88-1.12, p=0.72), respectively. Conversely, GMRs for midazolam AUC from time zero extrapolated to infinity and oral clearance were 0.73 (90% CI 0.61-0.85, p=0.008) and 1.37 (90% CI 1.10-1.63, p=0.02), respectively. Fexofenadine pharmacokinetics did not significantly differ before and after E. purpurea administration (p>0.05). Conclusion. Echinacea purpurea induced CYP3A activity but did not alter lopinavir concentrations, most likely due to the presence of the potent CYP3A inhibitor, ritonavir. Echinacea purpurea is unlikely to alter the pharmacokinetics of ritonavir-boosted protease inhibitors but may cause modest decreases in plasma concentrations of other CYP3A substrates. C1 [Penzak, Scott R.; Malati, Christine Y.; Alfaro, Raul M.] NIH, Clin Res Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. [Hunt, Jennifer D.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Clin Res Ctr, Bethesda, MD 20892 USA. [Chairez, Cheryl] NIAID, NIH, Bethesda, MD 20892 USA. [Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Dept Hlth & Human Serv, Silver Spring, MD USA. [Stevenson, James M.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. RP Penzak, SR (reprint author), NIH, Clin Res Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,1N 257, Bethesda, MD 20892 USA. EM spenzak@mail.cc.nih.gov FU National Institutes of Health Clinical Center; National Institute of Allergy and Infectious Diseases FX Supported by the Intramural Research Programs of the National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases. NR 28 TC 28 Z9 29 U1 0 U2 3 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2010 VL 30 IS 8 BP 797 EP 805 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 632QA UT WOS:000280439300007 PM 20653355 ER PT J AU Alter, KE AF Alter, Katharine E. TI High-Frequency Ultrasound Guidance for Neurotoxin Injections SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Ultrasound; Botulinum toxin; Spasticity; Dystonia; Pain; Spastic bladder ID BOTULINUM-TOXIN-A; AMYOTROPHIC-LATERAL-SCLEROSIS; BENIGN PROSTATIC HYPERPLASIA; SONOGRAPHY-GUIDED INJECTION; PLACEBO-CONTROLLED TRIAL; MANUAL NEEDLE PLACEMENT; CEREBRAL-PALSY; PIRIFORMIS SYNDROME; DOUBLE-BLIND; BLOOD-FLOW AB In the last decade, advances in ultrasound technology, specifically the development of high-frequency linear transducers, have made ultrasound an indispensable tool for imaging the musculoskeletal system. Using ultrasound to identify target structures for botulinum neurotoxin injection is a natural extension of the applications of musculoskeletal ultrasound. The goals of incorporating ultrasound with neurotoxin injections are to improve the accuracy of needle placement, avoid undesired structures, minimize volume overload during injection, and reduce the risk of the procedure. This article provides an update on the neurotoxins and their expanded use in clinical practice, and a detailed review of the use of ultrasound for the varied indications and applications for neurotoxin injection. C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NICHHD, NIH, Bethesda, MD 20892 USA. [Alter, Katharine E.] Ctr Clin, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, 1708 W Rogers Ave, Baltimore, MD 21209 USA. EM KAlter@MWPH.ORG NR 67 TC 18 Z9 19 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD AUG PY 2010 VL 21 IS 3 BP 607 EP + DI 10.1016/j.pmr.2010.05.001 PG 25 WC Rehabilitation SC Rehabilitation GA 654EN UT WOS:000282151400010 PM 20797552 ER PT J AU Harris, ML Baxter, LL Loftus, SK Pavan, WJ AF Harris, Melissa L. Baxter, Laura L. Loftus, Stacie K. Pavan, William J. TI Sox proteins in melanocyte development and melanoma SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Review DE sox; transcription factor; regulation; melanocyte; melanoma; development; adult ID TRANSCRIPTION FACTOR SOX10; NEURAL CREST DEVELOPMENT; CHRONIC INTESTINAL PSEUDOOBSTRUCTION; WAARDENBURG-HIRSCHSPRUNG-DISEASE; PERIPHERAL NERVOUS SYSTEMS; MOBILITY-GROUP DOMAIN; OF-THE-LITERATURE; MOUSE MODEL; DOPACHROME-TAUTOMERASE; OVERLAPPING FUNCTIONS AB Over 10 years have passed since the first Sox gene was implicated in melanocyte development. Since then, we have discovered that SOX5, SOX9, SOX10 and SOX18 all participate as transcription factors that affect key melanocytic genes in both regulatory and modulatory fashions. Both SOX9 and SOX10 play major roles in the establishment and normal function of the melanocyte; SOX10 has been shown to heavily influence melanocyte development and SOX9 has been implicated in melanogenesis in the adult. Despite these advances, the precise cellular and molecular details of how these SOX proteins are regulated and interact during all stages of the melanocyte life cycle remain unknown. Improper regulation of SOX9 or SOX10 is also associated with cancerous transformation, and thus understanding the normal function of SOX proteins in the melanocyte will be key to revealing how these proteins contribute to melanoma. C1 [Harris, Melissa L.; Baxter, Laura L.; Loftus, Stacie K.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Pavan, WJ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM bpavan@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX This review was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 145 TC 60 Z9 63 U1 2 U2 8 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 AUG PY 2010 VL 23 IS 4 BP 496 EP 513 DI 10.1111/j.1755-148X.2010.00711.x PG 18 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 636EL UT WOS:000280711100006 PM 20444197 ER PT J AU Boyko, AR Quignon, P Li, L Schoenebeck, JJ Degenhardt, JD Lohmueller, KE Zhao, KY Brisbin, A Parker, HG vonHoldt, BM Cargill, M Auton, A Reynolds, A Elkahloun, AG Castelhano, M Mosher, DS Sutter, NB Johnson, GS Novembre, J Hubisz, MJ Siepel, A Wayne, RK Bustamante, CD Ostrander, EA AF Boyko, Adam R. Quignon, Pascale Li, Lin Schoenebeck, Jeffrey J. Degenhardt, Jeremiah D. Lohmueller, Kirk E. Zhao, Keyan Brisbin, Abra Parker, Heidi G. vonHoldt, Bridgett M. Cargill, Michele Auton, Adam Reynolds, Andy Elkahloun, Abdel G. Castelhano, Marta Mosher, Dana S. Sutter, Nathan B. Johnson, Gary S. Novembre, John Hubisz, Melissa J. Siepel, Adam Wayne, Robert K. Bustamante, Carlos D. Ostrander, Elaine A. TI A Simple Genetic Architecture Underlies Morphological Variation in Dogs SO PLOS BIOLOGY LA English DT Article ID MULTILOCUS GENOTYPE DATA; GENOME-WIDE ASSOCIATION; POPULATION-STRUCTURE; LINKAGE DISEQUILIBRIUM; DOMESTIC DOGS; HISTORY; INFERENCE; MUTATION; MODEL; PATTERNS AB Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms ( SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (<= 3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species. C1 [Boyko, Adam R.; Zhao, Keyan; Bustamante, Carlos D.] Stanford Sch Med, Dept Genet, Stanford, CA USA. [Boyko, Adam R.; Li, Lin; Degenhardt, Jeremiah D.; Lohmueller, Kirk E.; Zhao, Keyan; Brisbin, Abra; Auton, Adam; Reynolds, Andy; Sutter, Nathan B.; Hubisz, Melissa J.; Siepel, Adam; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA. [Quignon, Pascale; Schoenebeck, Jeffrey J.; Parker, Heidi G.; Elkahloun, Abdel G.; Mosher, Dana S.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [vonHoldt, Bridgett M.; Novembre, John; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Environm Biol, Los Angeles, CA USA. [Cargill, Michele] Affymetrix Corp, Santa Clara, CA USA. [Castelhano, Marta; Sutter, Nathan B.] Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. [Johnson, Gary S.] Univ Missouri, Dept Vet Pathobiol, Columbia, MO USA. RP Boyko, AR (reprint author), Stanford Sch Med, Dept Genet, Stanford, CA USA. EM cdbustam@stanford.edu; eostrand@mail.nih.gov RI Novembre, John/G-1339-2011; OI Siepel, Adam/0000-0002-3557-7219; Ostrander, Elaine/0000-0001-6075-9738 FU NIH/NHLBI [1U01HL084706]; NSF (DBI) [0516310, 0701382]; NSF (DEB) [0948510]; Cornell Center for Vertebrate Genomics; National Human Genome Research Institute FX We acknowledge grants NIH/NHLBI 1U01HL084706, NSF (DBI) 0516310, NSF (DBI) 0701382, NSF (DEB) 0948510, the Cornell Center for Vertebrate Genomics, and the Intramural Program of the National Human Genome Research Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 156 Z9 161 U1 29 U2 137 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 AUG PY 2010 VL 8 IS 8 AR e1000451 DI 10.1371/journal.pbio.1000451 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 645MQ UT WOS:000281464500009 PM 20711490 ER PT J AU Kirmaier, A Wu, F Newman, RM Hall, LR Morgan, JS O'Connor, S Marx, PA Meythaler, M Goldstein, S Buckler-White, A Kaur, A Hirsch, VM Johnson, WE AF Kirmaier, Andrea Wu, Fan Newman, Ruchi M. Hall, Laura R. Morgan, Jennifer S. O'Connor, Shelby Marx, Preston A. Meythaler, Mareike Goldstein, Simoy Buckler-White, Alicia Kaur, Amitinder Hirsch, Vanessa M. Johnson, Welkin E. TI TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species SO PLOS BIOLOGY LA English DT Article ID RESTRICTION FACTOR TRIM5-ALPHA; HIV-1 INFECTION; RETROVIRAL RESTRICTION; RHESUS MACAQUES; CYCLOPHILIN-A; SIV; REPLICATION; AIDS; DOMAIN; SUSCEPTIBILITY AB Simian immunodeficiency viruses of sooty mangabeys (SIVsm) are the source of multiple, successful cross-species transmissions, having given rise to HIV-2 in humans, SIVmac in rhesus macaques, and SIVstm in stump-tailed macaques. Cellular assays and phylogenetic comparisons indirectly support a role for TRIM5 alpha, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature. Here, we investigate the in vivo role of TRIM5 directly, focusing on transmission of primate immunodeficiency viruses between outbred primate hosts. Specifically, we retrospectively analyzed experimental cross-species transmission of SIVsm in two cohorts of rhesus macaques and found a significant effect of TRIM5 genotype on viral replication levels. The effect was especially pronounced in a cohort of animals infected with SIVsmE543-3, where TRIM5 genotype correlated with approximately 100-fold to 1,000-fold differences in viral replication levels. Surprisingly, transmission occurred even in individuals bearing restrictive TRIM5 genotypes, resulting in attenuation of replication rather than an outright block to infection. In cell-culture assays, the same TRIM5 alleles associated with viral suppression in vivo blocked infectivity of two SIVsm strains, but not the macaque-adapted strain SIVmac239. Adaptations appeared in the viral capsid in animals with restrictive TRIM5 genotypes, and similar adaptations coincide with emergence of SIVmac in captive macaques in the 1970s. Thus, host TRIM5 can suppress viral replication in vivo, exerting selective pressure during the initial stages of cross-species transmission. C1 [Kirmaier, Andrea; Hall, Laura R.; Morgan, Jennifer S.; Johnson, Welkin E.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. [Kirmaier, Andrea; Meythaler, Mareike] Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-8520 Erlangen, Germany. [Wu, Fan; Goldstein, Simoy; Buckler-White, Alicia; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Newman, Ruchi M.] Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, Cambridge, MA USA. [O'Connor, Shelby] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. [Marx, Preston A.] Tulane Reg Primate Res Ctr, Covington, LA USA. [Meythaler, Mareike; Kaur, Amitinder] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. RP Kirmaier, A (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. EM wjohnson@hms.harvard.edu OI Kirmaier, Andrea/0000-0001-7206-7640 FU National Institutes of Health (NIH) [AI057039, AI083118, AI077423, AI049809, AI084810]; NIH/NCRR [RR00168 (NEPRC)] FX This work was supported by grants from the National Institutes of Health (NIH), including grants AI057039 and AI083118 (WEJ), NIH ARRA award AI077423 (WEJ), AI049809 and AI084810 (A Kaur), and by NIH/NCRR grant RR00168 (NEPRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 107 Z9 107 U1 0 U2 12 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 AUG PY 2010 VL 8 IS 8 AR e1000462 DI 10.1371/journal.pbio.1000462 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 645MQ UT WOS:000281464500016 ER PT J AU Pan, YP Nussinov, R AF Pan, Yongping Nussinov, Ruth TI Lysine120 Interactions with p53 Response Elements can Allosterically Direct p53 Organization SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR P53; DNA-BINDING SITE; STRUCTURAL BASIS; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; TRANSCRIPTIONAL ACTIVITY; ARGININE METHYLATION; HELICOIDAL ANALYSIS; SIGNALING PROTEIN; RECOGNITION AB p53 can serve as a paradigm in studies aiming to figure out how allosteric perturbations in transcription factors (TFs) triggered by small changes in DNA response element (RE) sequences, can spell selectivity in co-factor recruitment. p53-REs are 20-base pair (bp) DNA segments specifying diverse functions. They may be located near the transcription start sites or thousands of bps away in the genome. Their number has been estimated to be in the thousands, and they all share a common motif. A key question is then how does the p53 protein recognize a particular p53-RE sequence among all the similar ones? Here, representative p53-REs regulating diverse functions including cell cycle arrest, DNA repair, and apoptosis were simulated in explicit solvent. Among the major interactions between p53 and its REs involving Lys120, Arg280 and Arg248, the bps interacting with Lys120 vary while the interacting partners of other residues are less so. We observe that each p53-RE quarter site sequence has a unique pattern of interactions with p53 Lys120. The allosteric, DNA sequence-induced conformational and dynamic changes of the altered Lys120 interactions are amplified by the perturbation of other p53-DNA interactions. The combined subtle RE sequence-specific allosteric effects propagate in the p53 and in the DNA. The resulting amplified allosteric effects far away are reflected in changes in the overall p53 organization and in the p53 surface topology and residue fluctuations which play key roles in selective co-factor recruitment. As such, these observations suggest how similar p53-RE sequences can spell the preferred co-factor binding, which is the key to the selective gene transactivation and consequently different functional effects. C1 [Pan, Yongping; Nussinov, Ruth] NCI, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Pan, YP (reprint author), NCI, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. EM ruthnu@helix.nih.gov 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 number HHSN261200800001E. 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. 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. NR 77 TC 6 Z9 6 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD AUG PY 2010 VL 6 IS 8 AR e1000878 DI 10.1371/journal.pcbi.1000878 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 644OU UT WOS:000281389500010 ER PT J AU Tozluoglu, M Karaca, E Nussinov, R Halilogiu, T AF Tozluoglu, Melda Karaca, Ezgi Nussinov, Ruth Halilogiu, Tuerkan TI A Mechanistic View of the Role of E3 in Sumoylation SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID UBIQUITIN-LIKE PROTEIN; NUCLEAR-PORE COMPLEX; SACCHAROMYCES-CEREVISIAE; SUBSTRATE PROTEINS; LIGASE ACTIVITY; SUMO; UBC9; RANGAP1; RANBP2; CONJUGATION AB Sumoylation, the covalent attachment of SUMO (Small Ubiquitin-Like Modifier) to proteins, differs from other Ubl (Ubiquitin-like) pathways. In sumoylation, E2 ligase Ubc9 can function without E3 enzymes, albeit with lower reaction efficiency. Here, we study the mechanism through which E3 ligase RanBP2 triggers target recognition and catalysis by E2 Ubc9. Two mechanisms were proposed for sumoylation. While in both the first step involves Ubc9 conjugation to SUMO, the subsequent sequence of events differs: in the first E2-SUMO forms a complex with the target and E3, followed by SUMO transfer to the target. In the second, Ubc9-SUMO binds to the target and facilitates SUMO transfer without E3. Using dynamic correlations obtained from explicit solvent molecular dynamic simulations we illustrate the key roles played by allostery in both mechanisms. Pre-existence of conformational states explains the experimental observations that sumoylation can occur without E3, even though at a reduced rate. Furthermore, we propose a mechanism for enhancement of sumoylation by E3. Analysis of the conformational ensembles of the complex of E2 conjugated to SUMO illustrates that the E2 enzyme is already largely pre-organized for target binding and catalysis; E3 binding shifts the equilibrium and enhances these pre-existing populations. We further observe that E3 binding regulates allosterically the key residues in E2, Ubc9 Asp100/Lys101 E2, for the target recognition. C1 [Tozluoglu, Melda; Karaca, Ezgi; Halilogiu, Tuerkan] Bogazici Univ, Polymer Res Ctr, Istanbul, Turkey. [Tozluoglu, Melda; Karaca, Ezgi; Halilogiu, Tuerkan] Bogazici Univ, Dept Chem Engn, Istanbul, Turkey. [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Tozluoglu, M (reprint author), Bogazici Univ, Polymer Res Ctr, Istanbul, Turkey. EM ruthnu@helix.nih.gov; turkan@prc.boun.edu.tr FU EU [517991]; Turkish Academy of Sciences (TUBA); Scientific and Technological Research Council of Turkey (TUBITAK) [107T382]; Betil Fund; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, NCI, Center for Cancer Research FX We would like to acknowledge financial support from the following sources: EU FP6-2004-ACC-SSA-2 (517991); Turkish Academy of Sciences (TUBA); The Scientific and Technological Research Council of Turkey (TUBITAK, 107T382); the Betil Fund. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number 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, NCI, 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 34 TC 7 Z9 7 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD AUG PY 2010 VL 6 IS 8 AR e1000913 DI 10.1371/journal.pcbi.1000913 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 644OU UT WOS:000281389500040 ER PT J AU Bronstein, R Levkovitz, L Yosef, N Yanku, M Ruppin, E Sharan, R Westphal, H Oliver, B Segal, D AF Bronstein, Revital Levkovitz, Liron Yosef, Nir Yanku, Michaela Ruppin, Eytan Sharan, Roded Westphal, Heiner Oliver, Brian Segal, Daniel TI Transcriptional Regulation by CHIP/LDB Complexes SO PLOS GENETICS LA English DT Article ID DROSOPHILA WING DEVELOPMENT; LIM-HOMEODOMAIN ACTIVITY; DNA-BINDING PROTEINS; GENE-EXPRESSION; DORSOVENTRAL COMPARTMENTALIZATION; APTEROUS ACTIVITY; IN-VIVO; DOMAIN; CELLS; COFACTOR AB It is increasingly clear that transcription factors play versatile roles in turning genes "on'' or "off'' depending on cellular context via the various transcription complexes they form. This poses a major challenge in unraveling combinatorial transcription complex codes. Here we use the powerful genetics of Drosophila combined with microarray and bioinformatics analyses to tackle this challenge. The nuclear adaptor CHIP/LDB is a major developmental regulator capable of forming tissue-specific transcription complexes with various types of transcription factors and cofactors, making it a valuable model to study the intricacies of gene regulation. To date only few CHIP/LDB complexes target genes have been identified, and possible tissue-dependent crosstalk between these complexes has not been rigorously explored. SSDP proteins protect CHIP/LDB complexes from proteasome dependent degradation and are rate-limiting cofactors for these complexes. By using mutations in SSDP, we identified 189 down-stream targets of CHIP/LDB and show that these genes are enriched for the binding sites of APTEROUS (AP) and PANNIER (PNR), two well studied transcription factors associated with CHIP/LDB complexes. We performed extensive genetic screens and identified target genes that genetically interact with components of CHIP/LDB complexes in directing the development of the wings (28 genes) and thoracic bristles (23 genes). Moreover, by in vivo RNAi silencing we uncovered novel roles for two of the target genes, xbp1 and Gs-alpha, in early development of these structures. Taken together, our results suggest that loss of SSDP disrupts the normal balance between the CHIP-AP and the CHIP-PNR transcription complexes, resulting in down-regulation of CHIP-AP target genes and the concomitant up-regulation of CHIP-PNR target genes. Understanding the combinatorial nature of transcription complexes as presented here is crucial to the study of transcription regulation of gene batteries required for development. C1 [Bronstein, Revital; Yanku, Michaela; Segal, Daniel] Tel Aviv Univ, Dept Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. [Levkovitz, Liron; Ruppin, Eytan] Tel Aviv Univ, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. [Levkovitz, Liron; Yosef, Nir; Ruppin, Eytan; Sharan, Roded] Tel Aviv Univ, Balvatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mammalian Mol Genet, Program Genom Dev, NIH, Bethesda, MD USA. [Oliver, Brian] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA. RP Bronstein, R (reprint author), Tel Aviv Univ, Dept Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. EM dsegal@post.tau.ac.il FU Israel Ministry of Science; National Institute of Diabetes and Digestive and Kidney Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Bethesda, Maryland, USA; TAU-NIH FX This work was supported in part by the Israel Ministry of Science (Infrastructures grant and France-Israel grant) and by the Intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. RB Is grateful for support by the TAU-NIH exchange program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 11 Z9 11 U1 2 U2 5 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 AUG PY 2010 VL 6 IS 8 AR e1001063 DI 10.1371/journal.pgen.1001063 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 644NG UT WOS:000281383800019 PM 20730086 ER PT J AU Hsiung, CA Lan, Q Hong, YC Chen, CJ Hosgood, HD Chang, IS Chatterjee, N Brennan, P Wu, C Zheng, W Chang, GC Wu, TC Park, JY Hsiao, CF Kim, YH Shen, HB Seow, A Yeager, M Tsai, YH Kim, YT Chow, WH Guo, HA Wang, WC Sung, SW Hu, ZB Chen, KY Kim, JH Chen, Y Huang, LM Lee, KM Lo, YL Gao, YT Kim, JH Liu, L Huang, MS Jung, TH Jin, GF Caporaso, N Yu, DK Kim, CH Su, WC Shu, XO Xu, P Kim, IS Chen, YM Ma, HX Shen, M Cha, SI Tan, W Chang, CH Sung, JS Zhang, MF Yang, TY Park, KH Yuenger, J Wang, CL Ryu, JS Xiang, YB Deng, QF Hutchinson, A Kim, JS Cai, QY Landi, MT Yu, CJ Park, JY Tucker, M Hung, JY Lin, CC Perng, RP Boffetta, P Chen, CY Chen, KC Yang, SY Hu, CY Chang, CK Fraumeni, JF Chanock, S Yang, PC Rothman, N Lin, DX AF Hsiung, Chao Agnes Lan, Qing Hong, Yun-Chul Chen, Chien-Jen Hosgood, H. Dean, III Chang, I-Shou Chatterjee, Nilanjan Brennan, Paul Wu, Chen Zheng, Wei Chang, Gee-Chen Wu, Tangchun Park, Jae Yong Hsiao, Chin-Fu Kim, Yeul Hong Shen, Hongbing Seow, Adeline Yeager, Meredith Tsai, Ying-Huang Kim, Young Tae Chow, Wong-Ho Guo, Huan Wang, Wen-Chang Sung, Sook Whan Hu, Zhibin Chen, Kuan-Yu Kim, Joo Hyun Chen, Ying Huang, Liming Lee, Kyoung-Mu Lo, Yen-Li Gao, Yu-Tang Kim, Jin Hee Liu, Li Huang, Ming-Shyan Jung, Tae Hoon Jin, Guangfu Caporaso, Neil Yu, Dianke Kim, Chang Ho Su, Wu-Chou Shu, Xiao-Ou Xu, Ping Kim, In-San Chen, Yuh-Min Ma, Hongxia Shen, Min Cha, Sung Ick Tan, Wen Chang, Chin-Hao Sung, Jae Sook Zhang, Mingfeng Yang, Tsung-Ying Park, Kyong Hwa Yuenger, Jeff Wang, Chih-Liang Ryu, Jeong-Seon Xiang, Yongbing Deng, Qifei Hutchinson, Amy Kim, Jun Suk Cai, Qiuyin Landi, Maria Teresa Yu, Chong-Jen Park, Ju-Yeon Tucker, Margaret Hung, Jen-Yu Lin, Chien-Chung Perng, Reury-Perng Boffetta, Paolo Chen, Chih-Yi Chen, Kun-Chieh Yang, Shi-Yi Hu, Chi-Yuan Chang, Chung-Kai Fraumeni, Joseph F., Jr. Chanock, Stephen Yang, Pan-Chyr Rothman, Nathaniel Lin, Dongxin TI The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CANCER RISK; SUSCEPTIBILITY LOCUS; PULMONARY-FIBROSIS; CHINESE POPULATION; SEQUENCE VARIANTS; GENETIC-VARIANTS; POLYMORPHISMS; TELOMERASE; MUTATIONS AB Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma. C1 [Hsiung, Chao Agnes; Hsiao, Chin-Fu; Wang, Wen-Chang; Lo, Yen-Li; Chang, Chin-Hao; Hu, Chi-Yuan; Chang, Chung-Kai] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Taiwan. [Lan, Qing; Hosgood, H. Dean, III; Chatterjee, Nilanjan; Yeager, Meredith; Chow, Wong-Ho; Caporaso, Neil; Shen, Min; Hutchinson, Amy; Landi, Maria Teresa; Tucker, Margaret; Fraumeni, Joseph F., Jr.; Chanock, Stephen; Rothman, Nathaniel] NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hong, Yun-Chul; Lee, Kyoung-Mu] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Hong, Yun-Chul; Kim, Jin Hee] Seoul Natl Univ, Inst Environm Med, Med Res Ctr, Seoul, South Korea. [Chen, Chien-Jen] Acad Sin, Genom Res Ctr, Taipei, Taiwan. [Chen, Chien-Jen; Yang, Shi-Yi] Natl Taiwan Univ, Grad Inst Epidemiol, Coll Publ Hlth, Taipei 10764, Taiwan. [Chang, I-Shou] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan. [Brennan, Paul; Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol, Beijing 100037, Peoples R China. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Carcinogenesis, Beijing 100037, Peoples R China. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100037, Peoples R China. [Wu, Chen; Huang, Liming; Yu, Dianke; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China. [Zheng, Wei; Shu, Xiao-Ou; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Dept Med,Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Inst Med & Publ Hlth, Nashville, TN 37212 USA. [Chang, Gee-Chen; Yang, Tsung-Ying] Taichung Vet Gen Hosp, Div Chest Med, Dept Internal Med, Taichung, Taiwan. [Chang, Gee-Chen] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung 40227, Taiwan. [Chang, Gee-Chen] China Med Univ, Sch Med, Taichung, Taiwan. [Wu, Tangchun; Guo, Huan; Liu, Li; Xu, Ping; Deng, Qifei] Huazhong Univ Sci & Technol, Sch Publ Hlth, Inst Occupat Med, Wuhan 430074, Peoples R China. [Wu, Tangchun; Guo, Huan; Liu, Li; Xu, Ping; Deng, Qifei] Huazhong Univ Sci & Technol, Sch Publ Hlth, Minist Educ, Key Lab Environm & Hlth, Wuhan 430074, Peoples R China. [Park, Jae Yong; Jung, Tae Hoon; Kim, Chang Ho] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Taegu, South Korea. [Park, Jae Yong] Kyungpook Natl Univ, Sch Med, Dept Biochem, Taegu, South Korea. [Park, Jae Yong] Kyungpook Natl Univ Hosp, Canc Res Ctr, Taegu, South Korea. [Kim, Yeul Hong; Sung, Jae Sook; Park, Kyong Hwa; Kim, Jun Suk] Korea Univ, Anam Hosp, Genom Res Ctr Lung & Breast Ovarian Canc, Seoul, South Korea. [Kim, Yeul Hong; Sung, Jae Sook; Kim, Jun Suk] Korea Univ, Coll Med, Dept Internal Med, Seoul 136705, South Korea. [Kim, Yeul Hong; Sung, Jae Sook; Kim, Jun Suk] Korea Univ, Coll Med, Div Brain, Seoul 136705, South Korea. [Kim, Yeul Hong; Kim, Jun Suk] Korea Univ, Coll Med, Div Oncol Hematol, Dept Internal Med, Seoul 136705, South Korea. [Shen, Hongbing; Jin, Guangfu; Ma, Hongxia; Zhang, Mingfeng] Nanjing Med Univ, Dept Epidemiol & Biostat, Ctr Canc, Nanjing, Peoples R China. [Seow, Adeline; Chen, Ying] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore. [Yeager, Meredith; Yuenger, Jeff] NCI, Core Genotyping Facil, Adv Technol Program,Dept Hlth & Human Serv, Sci Applicat Int Corporat Frederick,NIH, Frederick, MD 21701 USA. [Tsai, Ying-Huang; Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Taipei, Taiwan. [Tsai, Ying-Huang] Chang Gung Univ, Dept Resp Care, Taipei, Taiwan. [Kim, Young Tae; Park, Ju-Yeon] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Kim, Young Tae; Kim, Joo Hyun] Seoul Natl Univ Hosp, Dept Thorac & Cardiovasc Surg, Clin Res Inst, Seoul 110744, South Korea. [Sung, Sook Whan] Seoul Natl Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul, South Korea. [Sung, Sook Whan] Seoul Natl Univ, Bundang Hosp, Dept Thorac & Cardiovasc Surg, Geongi Do, South Korea. [Chen, Kuan-Yu; Yu, Chong-Jen; Yang, Pan-Chyr] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Chen, Kuan-Yu; Yu, Chong-Jen; Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Gao, Yu-Tang; Xiang, Yongbing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Huang, Ming-Shyan; Hung, Jen-Yu] Kaohsiung Med Univ Hosp, Dept Internal Med, Kaohsiung, Taiwan. [Su, Wu-Chou; Lin, Chien-Chung] Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan 70428, Taiwan. [Su, Wu-Chou; Lin, Chien-Chung] Natl Cheng Kung Univ, Coll Med, Tainan 70101, Taiwan. [Chen, Yuh-Min; Perng, Reury-Perng] Taipei Vet Gen Hosp, Chest Dept, Taipei, Taiwan. [Chen, Yuh-Min] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. [Ryu, Jeong-Seon] Inha Univ, Coll Med, Dept Internal Med, Inchon, South Korea. [Chen, Chih-Yi] China Med Univ Hosp, Ctr Canc, Taipei, Taiwan. [Chanock, Stephen] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hsiung, CA (reprint author), Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan, Taiwan. EM hsiung@nhri.org.tw; qingl@mail.nih.gov RI Chen, Chien-Jen/C-6976-2008; Kim, In-San/D-3956-2017; Tu, Yiling/C-5610-2011; Chang, I-Shou/D-2084-2010; Library, JinyoungPark/F-3767-2011; Hong, Yun-Chul/J-5725-2012; Kim, Young/J-2744-2012; Hsiung, Chao Agnes/E-3994-2010; Hsiao, Chin-Fu/E-3993-2010; 김, 인산/I-8988-2014; Tucker, Margaret/B-4297-2015 OI Yu, Chong-Jen/0000-0001-5664-9392; YANG, PAN-CHYR/0000-0001-6330-6048; Library, JinyoungPark/0000-0003-0952-1374; FU NIH, National Cancer Institute; National Research Program on Genomic Medicine (NRPGM) of Taiwan [DOH97-TD-G-111-026, DOH96-TD-G-111-017, DOH95-TD-G-111-015]; National Health Research Institutes, Taiwan [95A1-BSAP01-002]; China National High Technology [2006AA02A401]; National Natural Science Foundation [30872092, 30525031]; Ministry of Health & Welfare, Republic of Korea [A010250]; National R&D Program for Cancer Control Ministry of Health and Welfare, Republic of Korea [0720550-2]; National Cancer Institute [R37 CA70837]; Vanderbilt University [NO2-CP-11010]; China National Natural Science Foundation [30730080]; National Medical Research Council, Singapore [NMRC/0897/2004, NMRC/1075/2006]; US National Institutes of Health (NIH); National Cancer Institute (NCI) [R03 CA133939-01]; [NSC98-3112-B-400-009] FX This study was supported in part by the Intramural Research Program of the NIH, National Cancer Institute. The GWAS based on the GELAC study was supported by the National Research Program on Genomic Medicine (NRPGM) of Taiwan under grants DOH97-TD-G-111-026 and DOH96-TD-G-111-017. The computational support for the GWAS was from grant NSC98-3112-B-400-009. The individual studies were funded by the following sources: The GELAC study was supported by DOH95-TD-G-111-015 from the National Research Program on Genomic Medicine in Taiwan, and 95A1-BSAP01-002 from the National Health Research Institutes, Taiwan. The Chinese Academy of Medical Sciences Cancer Hospital study (CAMSCH) was supported by the China National High Technology Project (2006AA02A401) (DL). The Wuhan lung cancer study (WHLCS) was supported by the National Natural Science Foundation (30872092 and 30525031). The Korea University Medical Center study (KUMC) was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A010250). The Kyungpook National University Hospital study (KNUH) was supported by the National R&D Program for Cancer Control Ministry of Health and Welfare, Republic of Korea (0720550-2). The Shanghai Women's Health Study (SWHS) was supported by the National Cancer Institute extramural research grant [R37 CA70837] and, partially for biological sample collection, National Cancer Institute Intramural Research Program contract NO2-CP-11010 with Vanderbilt University. The Nanjing lung cancer study (NJLCS) was supported by the China National Natural Science Foundation, grant # 30730080 (HS). The GEL-S study was supported by the National Medical Research Council, Singapore (NMRC/0897/2004 and NMRC/1075/2006). Genotyping in GEL-S study was partially funded by US National Institutes of Health (NIH); National Cancer Institute (NCI) (R03 CA133939-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 63 Z9 67 U1 6 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2010 VL 6 IS 8 AR e1001051 DI 10.1371/journal.pgen.1001051 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 644NG UT WOS:000281383800007 ER PT J AU Meyer, TE Verwoert, GC Hwang, SJ Glazer, NL Smith, AV van Rooij, FJA Ehret, GB Boerwinkle, E Felix, JF Leak, TS Harris, TB Yang, Q Dehghan, A Aspelund, T Katz, R Homuth, G Kocher, T Rettig, R Ried, JS Gieger, C Prucha, H Pfeufer, A Meitinger, T Coresh, J Hofman, A Sarnak, MJ Chen, YDI Uitterlinden, AG Chakravarti, A Psaty, BM van Duijn, CM Kao, WHL Witteman, JCM Gudnason, V Siscovick, DS Fox, CS Kottgen, A AF Meyer, Tamra E. Verwoert, Germaine C. Hwang, Shih-Jen Glazer, Nicole L. Smith, Albert V. van Rooij, Frank J. A. Ehret, Georg B. Boerwinkle, Eric Felix, Janine F. Leak, Tennille S. Harris, Tamara B. Yang, Qiong Dehghan, Abbas Aspelund, Thor Katz, Ronit Homuth, Georg Kocher, Thomas Rettig, Rainer Ried, Janina S. Gieger, Christian Prucha, Hanna Pfeufer, Arne Meitinger, Thomas Coresh, Josef Hofman, Albert Sarnak, Mark J. Chen, Yii-Der Ida Uitterlinden, Andre G. Chakravarti, Aravinda Psaty, Bruce M. van Duijn, Cornelia M. Kao, W. H. Linda Witteman, Jacqueline C. M. Gudnason, Vilmundur Siscovick, David S. Fox, Caroline S. Koettgen, Anna CA Meta Anal Glucose Insulin Related TI Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels SO PLOS GENETICS LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CONE-ROD DYSTROPHY; FUNCTIONAL-CHARACTERIZATION; BLOOD-PRESSURE; AMELOGENESIS IMPERFECTA; SECONDARY HYPOCALCEMIA; ATHEROSCLEROSIS-RISK; MG2+ TRANSPORTER; RENAL-FUNCTION; GENETIC-LOCI AB Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using similar to 2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5x10(-8)) or suggestive associations (p<4x10(-7)) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4x10(-7). Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels. C1 [Meyer, Tamra E.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. [Meyer, Tamra E.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Houston, TX USA. [Meyer, Tamra E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Verwoert, Germaine C.; van Rooij, Frank J. A.; Felix, Janine F.; Dehghan, Abbas; Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Verwoert, Germaine C.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Verwoert, Germaine C.; van Rooij, Frank J. A.; Felix, Janine F.; Dehghan, Abbas; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.] Netherlands Genom Initiat Netherland Consortium, Leiden, Netherlands. [Hwang, Shih-Jen] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hwang, Shih-Jen] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Glazer, Nicole L.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Glazer, Nicole L.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Ehret, Georg B.] Univ Hosp Geneva, Div Cardiol, Geneva, Switzerland. [Leak, Tennille S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Harris, Tamara B.] Natl Inst Aging, Lab Epidemiol Demog & Biometry, Baltimore, MD USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Stat, Boston, MA USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Kocher, Thomas] Ernst Moritz Arndt Univ Greifswald, Sch Dent, Greifswald, Germany. [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany. [Ried, Janina S.; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany. [Prucha, Hanna; Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, Munich, Germany. [Prucha, Hanna] Tech Univ Munich, Klinikum Rechts Isar, Dermatol Clin, Munich, Germany. [Pfeufer, Arne; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Munich, Germany. [Coresh, Josef; Kao, W. H. Linda; Koettgen, Anna] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Uitterlinden, Andre G.] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Koettgen, Anna] Univ Hosp Freiburg, Div Nephrol, Freiburg, Germany. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. RP Meyer, TE (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. EM akottgen@jhsph.edu RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; EHRET, Georg/A-9532-2009; Smith, Albert Vernon/K-5150-2015; Kottgen, Anna/D-2920-2012; Pfeufer, Arne/B-6634-2013; Yang, Qiong/G-5438-2014; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015 OI Aspelund, Thor/0000-0002-7998-5433; EHRET, Georg/0000-0002-5730-0675; Felix, Janine/0000-0002-9801-5774; Smith, Albert Vernon/0000-0003-1942-5845; Gieger, Christian/0000-0001-6986-9554; Dehghan, Abbas/0000-0001-6403-016X; Gudnason, Vilmundur/0000-0001-5696-0084; FU Department of Medicine at Boston University School of Medicine; Boston Medical Center FX FHS: This research was conducted in part 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. The 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 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. NR 58 TC 54 Z9 55 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2010 VL 6 IS 8 AR e1001045 DI 10.1371/journal.pgen.1001045 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 644NG UT WOS:000281383800001 ER PT J AU Saccone, NL Culverhouse, RC Schwantes-An, TH Cannon, DS Chen, XN Cichon, S Giegling, I Han, SZ Han, YH Keskitalo-Vuokko, K Kong, XY Landi, MT Ma, JZ Short, SE Stephens, SH Stevens, VL Sun, LW Wang, YF Wenzlaff, AS Aggen, SH Breslau, N Broderick, P Chatterjee, N Chen, JC Heath, AC Heliovaara, M Hoft, NR Hunter, DJ Jensen, MK Martin, NG Montgomery, GW Niu, TH Payne, TJ Peltonen, L Pergadia, ML Rice, JP Sherva, R Spitz, MR Sun, JZ Wang, JC Weiss, RB Wheeler, W Witt, SH Yang, BZ Caporaso, NE Ehringer, MA Eisen, T Gapstur, SM Gelernter, J Houlston, R Kaprio, J Kendler, KS Kraft, P Leppert, MF Li, MD Madden, PAF Nothen, MM Pillai, S Rietschel, M Rujescu, D Schwartz, A Amos, CI Bierut, LJ AF Saccone, Nancy L. Culverhouse, Robert C. Schwantes-An, Tae-Hwi Cannon, Dale S. Chen, Xiangning Cichon, Sven Giegling, Ina Han, Shizhong Han, Younghun Keskitalo-Vuokko, Kaisu Kong, Xiangyang Landi, Maria Teresa Ma, Jennie Z. Short, Susan E. Stephens, Sarah H. Stevens, Victoria L. Sun, Lingwei Wang, Yufei Wenzlaff, Angela S. Aggen, Steven H. Breslau, Naomi Broderick, Peter Chatterjee, Nilanjan Chen, Jingchun Heath, Andrew C. Heliovaara, Markku Hoft, Nicole R. Hunter, David J. Jensen, Majken K. Martin, Nicholas G. Montgomery, Grant W. Niu, Tianhua Payne, Thomas J. Peltonen, Leena Pergadia, Michele L. Rice, John P. Sherva, Richard Spitz, Margaret R. Sun, Juzhong Wang, Jen C. Weiss, Robert B. Wheeler, William Witt, Stephanie H. Yang, Bao-Zhu Caporaso, Neil E. Ehringer, Marissa A. Eisen, Tim Gapstur, Susan M. Gelernter, Joel Houlston, Richard Kaprio, Jaakko Kendler, Kenneth S. Kraft, Peter Leppert, Mark F. Li, Ming D. Madden, Pamela A. F. Noethen, Markus M. Pillai, Sreekumar Rietschel, Marcella Rujescu, Dan Schwartz, Ann Amos, Christopher I. Bierut, Laura J. TI Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; NICOTINE DEPENDENCE; HEAVY-SMOKING; SUSCEPTIBILITY LOCUS; EUROPEAN-AMERICANS; SEQUENCE VARIANTS; GENE-CLUSTER; TRAIT LOCI; RISK; BEHAVIOR AB Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values < 10(-35) and < 10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p < 10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p < 10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue. C1 [Saccone, Nancy L.; Schwantes-An, Tae-Hwi; Rice, John P.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Culverhouse, Robert C.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Culverhouse, Robert C.; Rice, John P.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Cannon, Dale S.] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84112 USA. [Chen, Xiangning; Chen, Jingchun; Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Chen, Xiangning; Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Human Mol Genet, Richmond, VA USA. [Cichon, Sven; Noethen, Markus M.] Univ Bonn, Dept Gen Life & Brain Ctr, D-5300 Bonn, Germany. [Cichon, Sven] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Giegling, Ina; Rujescu, Dan] Univ Munich LMU, Dept Psychiat, Munich, Germany. [Han, Shizhong; Yang, Bao-Zhu; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Han, Shizhong; Yang, Bao-Zhu; Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Han, Shizhong; Yang, Bao-Zhu; Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Han, Younghun; Spitz, Margaret R.; Amos, Christopher I.] Univ Texas M D Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA. [Keskitalo-Vuokko, Kaisu; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Kong, Xiangyang] GlaxoSmithKline Inc, Dept Quantitat Sci, King Of Prussia, PA USA. [Landi, Maria Teresa; Chatterjee, Nilanjan; Caporaso, Neil E.] NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Ma, Jennie Z.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Short, Susan E.] Brown Univ, Dept Sociol, Providence, RI 02912 USA. [Short, Susan E.] Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Stephens, Sarah H.; Hoft, Nicole R.; Ehringer, Marissa A.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Stevens, Victoria L.; Gapstur, Susan M.] Amer Canc Soc, Atlanta, GA 30329 USA. [Sun, Lingwei; Heath, Andrew C.; Pergadia, Michele L.; Rice, John P.; Wang, Jen C.; Madden, Pamela A. F.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Wang, Yufei; Broderick, Peter; Houlston, Richard] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England. [Wenzlaff, Angela S.; Schwartz, Ann] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Breslau, Naomi] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Heliovaara, Markku; Peltonen, Leena; Kaprio, Jaakko] Natl Inst Hlth & Welf, Helsinki, Finland. [Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hunter, David J.; Jensen, Majken K.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Niu, Tianhua; Li, Ming D.] Univ Virginia, Dept Psychiat & Biobehav Sci, Charlottesville, VA USA. [Payne, Thomas J.] Univ Mississippi, Med Ctr, Dept Otolaryngol & Commun Sci, Jackson, MS 39216 USA. [Peltonen, Leena] Inst Mol Med Finland FIMM, Helsinki, Finland. [Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England. [Peltonen, Leena] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Sherva, Richard] Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. [Weiss, Robert B.; Leppert, Mark F.] Univ Utah, Sch Med, Dept Human Genet, Eccles Inst Human Genet, Salt Lake City, UT 84132 USA. [Wheeler, William] Informat Management Serv Inc, Rockville, MD USA. [Witt, Stephanie H.; Rietschel, Marcella] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Ehringer, Marissa A.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Eisen, Tim] Cambridge Biomed Res Ctr, Cambridge, England. [Kraft, Peter] Harvard Univ, Dept Stat, Boston, MA 02115 USA. [Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Pillai, Sreekumar] Glaxo SmithKline, Res Triangle Pk, NC USA. [Rietschel, Marcella] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. RP Saccone, NL (reprint author), Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. EM nlims@genetics.wustl.edu RI Han, Shizhong/H-5785-2011; Breslau , Naomi/I-3196-2012; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Montgomery, Grant/B-7148-2008; OI Cichon, Sven/0000-0002-9475-086X; Martin, Nicholas/0000-0003-4069-8020; Houlston, Richard/0000-0002-5268-0242; Cichon, Sven/0000-0002-9475-086X; Montgomery, Grant/0000-0002-4140-8139; Broderick, Peter/0000-0002-8348-5829; Nothen, Markus/0000-0002-8770-2464; Kaprio, Jaakko/0000-0002-3716-2455 FU National Institute on Drug Abuse (NIDA) [R01 DA026911, R03 DA023166, K02 DA021237, R21 DA026901, P60 DA011015, R01 DA012845, R01 DA021913, R01 DA12854, K01DA019498, R21DA027070, R01s DA12890, DA12849, K01DA024758, R01 DA-12844, R01 DA-13783]; National Institute of General Medical Sciences (NIGM) [K25 GM69590]; American Cancer Society (ACS) [IRG-58-010-50]; National Cancer Institute (NCI) [P01 CA089392, CA55769, CA121197, CA133996, CA016672, CA127219, R01 CA60691, R01 CA87895, N01 PC35145, P30 CA22453, P01CA087969, NO1-CN-25514]; The National Human Genome Research Institute (NHGRI) [U01 HG04422-01, HHSN271200477471C, HHSN271200477451C, 5U01HG004399]; National Institutes of Health [HHSN268200782096]; NIDA/NHLBI [P01-HL72903]; GlaxoSmithKline [SCO104960, NCT00292552, RES11080]; National Institute of Environmental Health (NIEH) [P30ES007784]; NIAAA [K01 AA015336, R01 AA017889, T32 AA007464, R01 AA011949, AA11330]; NICHD [P01 HD31921]; Center of Excellence in Complex Disease Genetics of the Academy of Finland [21356, 129680]; European Community [HEALTH-F4-2007-201413]; Nordic Center of Excellence in Disease Genetic; Wellcome Trust; NIDDK [5P01DK070756]; NHLBI [5R01HL035464]; Merck Research Laboratories; German Federal Ministry of Education and Research (BMBF) [01GS8152]; NIH, NCI, Division of Cancer Epidemiology and Genetics; Georgetown University [NO1-CN-25522]; Pacific Health Research Institute [NO1-CN-25515]; Henry Ford Health System [NO1-CN-25512]; University of Minnesota [NO1-CN-25513]; Washington University [NO1-CN-25516]; University of Pittsburgh [NO1-CN-25511]; University of Utah [NO1 CN-25524]; Marshfield Clinic Research Foundation [NO1-CN-25518]; University of Alabama at Birmingham [NO1 CN-75022]; Westat, Inc. [NO1-CN-25476]; University of California, Los Angeles [NO1-CN-25404]; Environment and Health Initiative; GENEVA Coordinating Center [U01 HG004446]; NIH GEI [U01HG004438, U01HG04424]; NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' [HHSN268200782096C]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921] FX Meta-analysis was supported by the National Institute on Drug Abuse (NIDA; R01 DA026911, R03 DA023166), National Institute of General Medical Sciences (NIGMS; K25 GM69590), and the American Cancer Society (ACS; IRG-58-010-50). The Washington University COGEND contribution was supported by the National Cancer Institute (NCI; P01 CA089392), The National Human Genome Research Institute (NHGRI; U01 HG04422-01), and NIDA (K02 DA021237). COGEND genotyping at Perlegen Sciences was performed under NIDA Contract HHSN271200477471C; phenotypic and genotypic data are stored in the NIDA Center for Genetic Studies (NCGS) at http://zork.wustl.edu/under NIDA Contract HHSN271200477451C (PIs J Tischfield and J Rice); genotyping services were also provided by the Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096. Utah was supported by NIDA/NHLBI (P01-HL72903). GlaxoSmithKline funded data with (SCO104960, NCT00292552, and RES11080). MD Anderson work supported by NCI (CA55769, CA121197, CA133996, CA016672, and CA127219) and by the National Institute of Environmental Health (NIEH; P30ES007784). University of Colorado was supported by funds from NIDA (R21 DA026901, P60 DA011015, R01 DA012845, R01 DA021913), NIAAA (K01 AA015336, R01 AA017889, T32 AA007464, R01 AA011949), and NICHD (P01 HD31921). Wayne State University was funded by NCI (R01 CA60691, R01 CA87895, N01 PC35145, P30 CA22453). Finland studies were funded by NIDA (R01 DA12854), the Center of Excellence in Complex Disease Genetics of the Academy of Finland (21356 and 129680), The European Community's Seventh Framework Programme/ENGAGE Consortium (HEALTH-F4-2007-201413), Nordic Center of Excellence in Disease Genetic, and Wellcome Trust. The NAG-BigSib contribution was funded by NIDA (R01 DA12854, R56 DA12854, K08 DA019951), NIAAA (R01 AA11998, R01 AA13320, R01 AA13321), and the Australian National Health and Medical Research Council. The VA twin study was supported by NIDA (K01DA019498, R21DA027070). Studies conducted at Yale were funded by NIDA (R01s DA12890, DA12849, K01DA024758) and NIAAA (AA11330). NIDA supported studies done at UVA (R01 DA-12844, R01 DA-13783). Harvard studies (HPFS, NHS) were funded by NIDDK (5P01DK070756), NCI (P01CA087969), NHGRI (5U01HG004399), and NHLBI (5R01HL035464); genotyping for HPFS_CHD and NHS_CHD was supported by Merck Research Laboratories. The University of Bonn and Central Institute of Mental Health Mannheim studies were supported by the German Federal Ministry of Education and Research (BMBF) within the context of the German National Genome Research Network (NGFN-2 and NGFN-plus) by grants to MR (01GS8152). EAGLE and PLCO were supported by the Intramural Research Program of NIH, NCI, Division of Cancer Epidemiology and Genetics. PLCO was also supported by individual contracts from the NCI to the University of Colorado Denver (NO1-CN-25514), Georgetown University (NO1-CN-25522), Pacific Health Research Institute (NO1-CN-25515), Henry Ford Health System (NO1-CN-25512), University of Minnesota, (NO1-CN-25513), Washington University (NO1-CN-25516), University of Pittsburgh (NO1-CN-25511), University of Utah (NO1 CN-25524), Marshfield Clinic Research Foundation (NO1-CN-25518), University of Alabama at Birmingham (NO1 CN-75022), Westat, Inc. (NO1-CN-25476), University of California, Los Angeles (NO1-CN-25404).; The datasets HPFS-T2D, NHS-T2D, NCI-EAGLE, NCI-PLCO, and the Study of Addiction: Genetics and Environment (SAG), which overlaps with COGEND, are among the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI). Assistance with data cleaning for GENEVA studies, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning for GENEVA studies was also provided by the National Center for Biotechnology Information. Genotyping for GENEVA studies was performed at the Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C), and the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This analysis uses data from Add Health, a program project designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. No direct support was received from grant P01-HD31921 for this analysis. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Persons interested in obtaining data files from Add Health should contact Add Health, Carolina Population Center, 123 W. Franklin Street, Chapel Hill, NC 275162524 (addhealth@unc.edu). NR 67 TC 166 Z9 170 U1 6 U2 31 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 AUG PY 2010 VL 6 IS 8 AR e1001053 DI 10.1371/journal.pgen.1001053 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 644NG UT WOS:000281383800009 ER PT J AU Ferguson, HM Dornhaus, A Beeche, A Borgemeister, C Gottlieb, M Mulla, MS Gimnig, JE Fish, D Killeen, GF AF Ferguson, Heather M. Dornhaus, Anna Beeche, Arlyne Borgemeister, Christian Gottlieb, Michael Mulla, Mir S. Gimnig, John E. Fish, Durland Killeen, Gerry F. TI Ecology: A Prerequisite for Malaria Elimination and Eradication SO PLOS MEDICINE LA English DT Editorial Material ID GENETICALLY-MODIFIED MOSQUITOS; INSECTICIDE-TREATED NETS; VECTOR-CONTROL; ANOPHELES-GAMBIAE; WESTERN KENYA; FALCIPARUM-MALARIA; BEDNET COVERAGE; LARVAL HABITATS; AEDES-AEGYPTI; TRANSMISSION C1 [Ferguson, Heather M.; Killeen, Gerry F.] Ifakara Hlth Inst, Biomed & Environm Themat Grp, Dar Es Salaam, Tanzania. [Ferguson, Heather M.] Univ Glasgow, Fac Biomed & Life Sci, Glasgow, Lanark, Scotland. [Dornhaus, Anna] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ USA. [Beeche, Arlyne] Int Dev Res Ctr, Ottawa, ON, Canada. [Borgemeister, Christian] Int Ctr Insect Physiol & Ecol, Nairobi, Kenya. [Gottlieb, Michael] Fdn Natl Inst Hlth, Bethesda, MD USA. [Mulla, Mir S.] Univ Calif Riverside, Riverside, CA 92521 USA. [Gimnig, John E.] Ctr Dis Control & Prevent, Div Parasit Dis, Chamblee, GA USA. [Fish, Durland] Yale Univ, Sch Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT USA. [Killeen, Gerry F.] Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England. RP Ferguson, HM (reprint author), Ifakara Hlth Inst, Biomed & Environm Themat Grp, Dar Es Salaam, Tanzania. EM gkilleen@ihi.or.tz OI Ferguson, Heather/0000-0002-9625-5176 FU Biotechnology and Biological Sciences Research Council [BB/D020042/1] NR 71 TC 117 Z9 117 U1 5 U2 49 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 AUG PY 2010 VL 7 IS 8 AR e1000303 DI 10.1371/journal.pmed.1000303 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 645KV UT WOS:000281456500001 PM 20689800 ER PT J AU Gandhi, RT Zheng, L Bosch, RJ Chan, ES Margolis, DM Read, S Kallungal, B Palmer, S Medvik, K Lederman, MM Alatrakchi, N Jacobson, JM Wiegand, A Kearney, M Coffin, JM Mellors, JW Eron, JJ AF Gandhi, Rajesh T. Zheng, Lu Bosch, Ronald J. Chan, Ellen S. Margolis, David M. Read, Sarah Kallungal, Beatrice Palmer, Sarah Medvik, Kathy Lederman, Michael M. Alatrakchi, Nadia Jacobson, Jeffrey M. Wiegand, Ann Kearney, Mary Coffin, John M. Mellors, John W. Eron, Joseph J. CA AIDS Clinical Trials Grp TI The Effect of Raltegravir Intensification on Low-level Residual Viremia in HIV-Infected Patients on Antiretroviral Therapy: A Randomized Controlled Trial SO PLOS MEDICINE LA English DT Article ID IMMUNODEFICIENCY; SUBPOPULATIONS; REPLICATION; SUPPRESSION; ACTIVATION; RECOVERY; PLASMA; BLOOD; RNA AB Background: Most HIV-1-infected patients on effective antiretroviral therapy (ART) with plasma HIV-1 RNA levels below the detection limits of commercial assays have residual viremia measurable by more sensitive methods. We assessed whether adding raltegravir lowered the level of residual viremia in such patients. Methods and Findings: Patients receiving ART who had plasma HIV-1 RNA levels below 50 copies/mL but detectable viremia by single copy assay (SCA) were randomized to add either raltegravir or placebo to their ART regimen for 12 weeks; patients then crossed-over to the other therapy for an additional 12 weeks while continuing pre-study ART. The primary endpoint was the plasma HIV-1 RNA by SCA averaged between weeks 10 and 12 (10/12) compared between treatment groups. Fifty-three patients were enrolled. The median screening HIV-1 RNA was 1.7 copies/mL. The HIV-1 RNA level at weeks 10/12 did not differ significantly between the raltegravir-intensified (n = 25) and the placebo (n = 24) groups (median 1.2 versus 1.7 copies/mL, p = 0.55, Wilcoxon rank sum test), nor did the change in HIV-1 RNA level from baseline to week 10/12 (median -0.2 and -0.1 copies/mL, p = 0.71, Wilcoxon rank sum test). There was also no significant change in HIV-1 RNA level from weeks 10/12 to weeks 22/24 after patients crossed-over. There was a greater CD4 cell count increase from baseline to week 12 in the raltegravir-intensified group compared with the placebo group (+42 versus -44 cells/mm(3), p = 0.082, Wilcoxon rank sum test), which reversed after the cross-over. This CD4 cell count change was not associated with an effect of raltegravir intensification on markers of CD4 or CD8 cell activation in blood. Conclusion: In this randomized, double-blind cross-over study, 12 weeks of raltegravir intensification did not demonstrably reduce low-level plasma viremia in patients on currently recommended ART. This finding suggests that residual viremia does not arise from ongoing cycles of HIV-1 replication and infection of new cells. New therapeutic strategies to eliminate reservoirs that produce residual viremia will be required to eradicate HIV-1 infection. C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp & Ragon Inst, Boston, MA USA. [Zheng, Lu; Bosch, Ronald J.; Chan, Ellen S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Margolis, David M.; Eron, Joseph J.] Univ N Carolina, Chapel Hill, NC USA. [Read, Sarah] NIAID, Bethesda, MD 20892 USA. [Kallungal, Beatrice] Social & Sci Syst, Silver Spring, MD USA. [Palmer, Sarah] Karolinska Inst, Stockholm, Sweden. [Medvik, Kathy; Lederman, Michael M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Alatrakchi, Nadia] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jacobson, Jeffrey M.] Drexel Univ, Philadelphia, PA 19104 USA. [Wiegand, Ann; Kearney, Mary] NCI, Frederick, MD 21701 USA. [Coffin, John M.] Tufts Univ, Boston, MA 02111 USA. [Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp & Ragon Inst, Boston, MA USA. EM rgandhi@partners.org OI Margolis, David/0000-0001-5714-0002 FU National Institute of Allergy and Infectious Diseases [U01AI068636, AI 068634]; National Institutes of Health [5U01A1068636-04, 25XS119]; F.M. Kirby Foundation; Merck Sharp Dohme, Corp; CTU [5UO1 AI069502-03, AI 069501, AI69423-03, U01 AI069452, 1U01AI069472, AI069556, AI 069494-01, AI069495, AI069471, AI069532, AI-27665, AI069434, AI069419, U01 AI069472-04, AI069424, AI069450, AI69511-02, 5U01 AI069484, AI069470]; CFAR [AI50410]; CTSA [RR025747]; GCRC [M01 RR-00032, RR025780, 5-MO1 RR00044]; CTSC [RR024996] FX The project was supported by Award Number U01AI068636 from the National Institute of Allergy and Infectious Diseases. The project was also supported by a grant from the National Institute of Allergy and Infectious Diseases to the Statistical and Data Analysis Center (AI 068634). In addition, JWM was supported by the following National Institutes of Health grants: 5U01A1068636-04 and NIH 25XS119. JMC was a research professor of the American Cancer Society, with support from the F.M. Kirby Foundation. The content is solely the responsibility of the authors and does not represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The study was also supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme, Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme, Corp.; We would like to thank all the members of the ACTG 5244 team, including Randi Leavitt, Barbara Philpotts, Betty A. Donoval, Robert Levaro, Ana Martinez, Lisa M. Demeter, Richard D'Aquila, and Carla Pettinelli. We would like to express our special appreciation to Jennifer Janik for her excellent work as the study data manager and to Heather Springer and Amy Jennings for their outstanding work on coordinating the laboratory data for the study. We gratefully acknowledge the hard work of the study staff at all the ACTG sites who screened and enrolled participants in this trial: Annie Luetkemeyer, MD and Joann Volinski, RN- UCSF, San Francisco General Hospital ( Site 801) CTU Grant # 5UO1 AI069502-03; MetroHealth ( Site 2503) CTU Grant # AI 069501; David Currin RN and Cheryl Marcus RN, BSN -University of North Carolina AIDS Clinical Trials Unit ( Site 3201) CTU Grant # AI69423-03, CFAR Grant # AI50410, CTSA Grant # RR025747; Melinda Robertson, RN and Rebecca Creamer- Alabama Therapeutics CRS ( Site 5801) CTU Grant # U01 AI069452, GCRC Grant # M01 RR-00032; Amy Sbrolla, R. N. and Nicole Burgett-Yandow, R. N., B. S. N.-Harvard Massachusetts General Hospital ( Site 101) CTU Grant# 1U01AI069472; Jane Norris, PA-C and Sandra Valle, PA-C-Stanford University ( Site 501) CTU Grant # AI069556; Deborah McMahon, MD and Sally McNulty, BA, RN - University of Pittsburgh ( Site 1001) CTU Grant # AI 069494-01; Teresa Spitz, RN, CCRC and Judy Frain, RN, BSN-Washington University in St. Louis ( Site 2101) CTU Grant # AI069495; Babafemi Taiwo, M. B. B. S., M. D. and Karen Coleman, R. N.-Northwestern University ( Site 2701) CTU Grant # AI069471; HIV Prevention & Treatment CRS ( Site 30329); Margarita Vasquez, RN and Judith A. Aberg, M. D.-New York University/NYC HHC at Bellevue Hospital Center ( Site 401) CTU Grant # AI069532, AI-27665; University of Washington, Seattle ( Site 1401) CTU Grant # AI069434; Todd Stroberg, R. N., and Valery Hughes N. P.-Cornell CTU ( Site 7804) CTU Grant # AI069419 CTSC# RR024996; Mary Albrecht, MD and Amanda Youmans, RN, ANP -Beth Israel Deaconess (Partners/Harvard) ( Site 103) CTU Grant # U01 AI069472-04; Harbor UCLA Medical Center ( Site 603) CTU Grant # AI069424; M. Graham Ray, R. N., M. S. N. and Steven C. Johnson, M. D. -Colorado ACTU ( Site 6101) CTU Grant #AI069450 and GCRC Grant # RR025780; Amneris Luque MD and Mary Adams, RN- University of Rochester ( Site 1101) CTU Grant # AI69511-02 ( as of 2/12/08), GCRC Grant # 5-MO1 RR00044; Nathan M. Thielman, MD and Martha Silberman, RN- Duke University Medical Center ( Site 1601) CTU Grant # 5U01 AI069484; Harlem Family Health Center ( Site 31483) CTU Grant # AI069470. Finally, we would like to thank all the patients who participated in this study. NR 21 TC 131 Z9 131 U1 2 U2 8 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 AUG PY 2010 VL 7 IS 8 AR e1000321 DI 10.1371/journal.pmed.1000321 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 645KV UT WOS:000281456500008 ER PT J AU Estes, JD Harris, LD Klatt, NR Tabb, B Pittaluga, S Paiardini, M Barclay, GR Smedley, J Pung, R Oliveira, KM Hirsch, VM Silvestri, G Douek, DC Miller, CJ Haase, AT Lifson, J Brenchley, JM AF Estes, Jacob D. Harris, Levelle D. Klatt, Nichole R. Tabb, Brian Pittaluga, Stefania Paiardini, Mirko Barclay, G. Robin Smedley, Jeremy Pung, Rhonda Oliveira, Kenneth M. Hirsch, Vanessa M. Silvestri, Guido Douek, Daniel C. Miller, Christopher J. Haase, Ashley T. Lifson, Jeffrey Brenchley, Jason M. TI Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections SO PLOS PATHOGENS LA English DT Article ID VERSUS-HOST-DISEASE; CD4(+) T-CELLS; SOOTY MANGABEYS; IMMUNE ACTIVATION; ANTIRETROVIRAL THERAPY; HIV-INFECTION; BACTERIAL TRANSLOCATION; COLLAGEN DEPOSITION; AIDS PATHOGENESIS; SIV INFECTION AB The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4(+) T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication. C1 [Estes, Jacob D.; Tabb, Brian; Lifson, Jeffrey] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Harris, Levelle D.; Klatt, Nichole R.; Hirsch, Vanessa M.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Paiardini, Mirko; Silvestri, Guido] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Barclay, G. Robin] Univ Edinburgh, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland. [Smedley, Jeremy; Pung, Rhonda] NCI, Lab Anim Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Oliveira, Kenneth M.] AdvanDX Inc, Woburn, MA USA. [Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Ctr Comparat Med, Davis, CA 95616 USA. [Haase, Ashley T.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. RP Estes, JD (reprint author), NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA. EM estesj@mail.nih.gov; jbrenchl@mail.nih.gov OI Smedley, Jeremy/0000-0003-3369-4662 FU NIAID, NIH; National Cancer Institute, National Institutes of Health [HHSN266200400088C] FX These studies were supported by the intramural NIAID, NIH program and with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN266200400088C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 191 Z9 192 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD AUG PY 2010 VL 6 IS 8 AR e1001052 DI 10.1371/journal.ppat.1001052 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 644SM UT WOS:000281399900025 PM 20808901 ER PT J AU Rivero, A Vezilier, J Weill, M Read, AF Gandon, S AF Rivero, Ana Vezilier, Julien Weill, Mylene Read, Andrew F. Gandon, Sylvain TI Insecticide Control of Vector-Borne Diseases: When Is Insecticide Resistance a Problem? SO PLOS PATHOGENS LA English DT Review ID TRIATOMA-INFESTANS HEMIPTERA; CULEX-PIPIENS MOSQUITOS; AFRICAN MALARIA VECTOR; PEACH-POTATO APHIDS; GLUTATHIONE S-TRANSFERASES; FEMALE ANOPHELES-GAMBIAE; SPHAERICUS BINARY TOXIN; HCH DIELDRIN RESISTANT; AN-STEPHENSI MOSQUITOS; HIGH WOLBACHIA DENSITY AB Many of the most dangerous human diseases are transmitted by insect vectors. After decades of repeated insecticide use, all of these vector species have demonstrated the capacity to evolve resistance to insecticides. Insecticide resistance is generally considered to undermine control of vector-transmitted diseases because it increases the number of vectors that survive the insecticide treatment. Disease control failure, however, need not follow from vector control failure. Here, we review evidence that insecticide resistance may have an impact on the quality of vectors and, specifically, on three key determinants of parasite transmission: vector longevity, competence, and behaviour. We argue that, in some instances, insecticide resistance is likely to result in a decrease in vector longevity, a decrease in infectiousness, or in a change in behaviour, all of which will reduce the vectorial capacity of the insect. If this effect is sufficiently large, the impact of insecticide resistance on disease management may not be as detrimental as previously thought. In other instances, however, insecticide resistance may have the opposite effect, increasing the insect's vectorial capacity, which may lead to a dramatic increase in the transmission of the disease and even to a higher prevalence than in the absence of insecticides. Either way-and there may be no simple generality-the consequence of the evolution of insecticide resistance for disease ecology deserves additional attention. C1 [Rivero, Ana; Vezilier, Julien] Ctr Rech IRD, CNRS, Genet & Evolut Malad Infectieuses UMR 2724, Montpellier, France. [Weill, Mylene] Univ Montpellier 2, CNRS, Inst Sci Evolut Montpellier, UMR 5554, Montpellier, France. [Read, Andrew F.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Read, Andrew F.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Gandon, Sylvain] CNRS, Ctr Ecol Fonct & Evolut, UMR 5175, F-34033 Montpellier, France. RP Rivero, A (reprint author), Ctr Rech IRD, CNRS, Genet & Evolut Malad Infectieuses UMR 2724, Montpellier, France. EM ana.rivero@ird.fr RI Rivero, Ana/I-5559-2013; Vezilier, Julien /N-7227-2014 OI Weill, Mylene/0000-0002-4043-1601; Rivero, Ana/0000-0002-7056-5846; Vezilier, Julien /0000-0002-8043-9130 FU ANR SEST; GABBA; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center; National Institutes of Health; ANR; ERC FX This work is financed by an ANR SEST to A. Rivero, a GABBA grant to J. Vezilier, the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, the Fogarty International Center and the National Institutes of Health to A. Read, and by an ANR Jeune Chercheur and an ERC Starting Grant to S. Gandon. The funders had no role in the study design, data collection and analysis, decision to publish, or in preparation of the manuscript. NR 127 TC 85 Z9 88 U1 6 U2 53 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD AUG PY 2010 VL 6 IS 8 AR e1001000 DI 10.1371/journal.ppat.1001000 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 644SM UT WOS:000281399900003 PM 20700451 ER PT J AU Carlson, BA Yoo, MH Shrimali, RK Irons, R Gladyshev, VN Hatfield, DL Park, JM AF Carlson, Bradley A. Yoo, Min-Hyuk Shrimali, Rajeev K. Irons, Robert Gladyshev, Vadim N. Hatfield, Dolph L. Park, Jin Mo TI Session 2: Micronutrients and the immune system Role of selenium-containing proteins in T-cell and macrophage function SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Article; Proceedings Paper CT 3rd International Immunonutrition Workshop CY OCT, 2009 CL Girona, SPAIN DE Macrophage; Selenium; Selenocysteine; T-cells ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; GENE-EXPRESSION; KAPPA-B; SELENOPROTEINS; SELENOCYSTEINE; ACTIVATION; MECHANISMS; INFECTION; RESPONSES; MICE AB Selenium (Se) has been known for many years to have played a role in boosting the immune function, but the manner in which this element acts at the molecular level in host defence and inflammatory diseases is poorly understood. To elucidate the role of Se-containing proteins in the immune function, we knocked out the expression of this protein class in T-cells or macrophages of mice by targeting the removal of the selenocysteine tRNA gene using loxP-Cre technology. Mice with selenoprotein-less T-cells manifested reduced pools of mature and functional T-cells in lymphoid tissues and an impairment in T-cell-dependent antibody responses. Furthermore, selenoprotein deficiency in T-cells led to an inability of these cells to suppress reactive oxygen species production, which in turn affected their ability to proliferate in response to T-cell receptor stimulation. Selenoprotein-less macrophages, on the other hand, manifested mostly normal inflammatory responses, but this deficiency resulted in an altered regulation in extracellular matrix-related gene expression and a diminished migration of macrophages in a protein gel matrix. These observations provided novel insights into the role of selenoproteins in the immune function and tissue homeostasis. C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Shrimali, Rajeev K.; Irons, Robert; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. [Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Carlson, BA (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. EM carlsonb@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS; NCI NIH HHS [R01 CA080946-10, R01 CA080946]; NIA NIH HHS [R01 AG021518-09, R01 AG021518]; NIGMS NIH HHS [R01 GM065204-09, R01 GM065204, R01 GM061603-10, R01 GM061603] NR 41 TC 31 Z9 34 U1 0 U2 10 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PD AUG PY 2010 VL 69 IS 3 BP 300 EP 310 DI 10.1017/S002966511000176X PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 632QC UT WOS:000280439600006 PM 20576203 ER PT J AU Slotta, DJ McFarland, MA Markey, SP AF Slotta, Douglas J. McFarland, Melinda A. Markey, Sanford P. TI MassSieve: Panning MS/MS peptide data for proteins SO PROTEOMICS LA English DT Article DE Bioinformatics; MS; Parsimony; Protein identification ID SHOTGUN PROTEOMIC DATA; STATISTICAL-MODEL; IDENTIFICATIONS; ACCURACY; SEARCH AB We present Mass Sieve, a Java-based platform for visualization and parsimony analysis of single and comparative LC-MS/MS database search engine results. The success of mass spectrometric peptide sequence assignment algorithms has led to the need for a tool to merge and evaluate the increasing data set sizes that result from LC-MS/MS-based shotgun proteomic experiments. Mass Sieve supports reports from multiple search engines with differing search characteristics, which can increase peptide sequence coverage and/or identify conflicting or ambiguous spectral assignments. C1 [Slotta, Douglas J.; McFarland, Melinda A.; Markey, Sanford P.] NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. RP Slotta, DJ (reprint author), NCBI NLM NIH, 45 Ctr Dr,Rm 5AS21, Bethesda, MD 20892 USA. EM slottad@ncbi.nlm.nih.gov RI McFarland, Melinda/A-1866-2013 FU National Institute of Mental Health, National Institutes of Health FX The authors thank Dr. J. Kowalak and A. Makusky for helpful discussions throughout this project. This work was supported in part by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 9 TC 28 Z9 28 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD AUG PY 2010 VL 10 IS 16 BP 3035 EP 3039 DI 10.1002/pmic.200900370 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645TB UT WOS:000281488000012 PM 20564260 ER PT J AU Robinson, OJ Standing, HR DeVito, EE Cools, R Sahakian, BJ AF Robinson, Oliver J. Standing, Holly R. DeVito, Elise E. Cools, Roshan Sahakian, Barbara J. TI Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males SO PSYCHOPHARMACOLOGY LA English DT Article DE Dopamine; Reward; Punishment; Reversal learning; Tyrosine; Phenylalanine ID PARKINSONS-DISEASE; TYROSINE DEPLETION; NUCLEUS-ACCUMBENS; MONOAMINE DEPLETION; AMPHETAMINE; MOOD; VOLUNTEERS; SEROTONIN; BEHAVIOR; RELEASE AB The neurotransmitter dopamine has frequently been implicated in reward processing but is also, increasingly, implicated in punishment processing. We have previously shown that both patients with Parkinson's disease and healthy individuals with low dopamine (DA) synthesis are better at reversal learning based on punishment than reward. Here, we extend these prior findings by examining the effects of artificially reducing DA synthesis in healthy individuals performing this previously employed task. In a double-blind, placebo-controlled crossover design, we applied the acute tyrosine and phenylalanine depletion (ATPD) procedure to reduce global DA synthesis in 15 female and 14 male subjects. Each subject performed the reward- and punishment-based reversal-learning paradigm. There was a significant three-way interaction between ATPD, the valence of the outcome signalling reversal and the gender of the participants. Examination of punishment and reward-based reversals separately revealed that this was driven by a significant improvement in punishment processing in female but not male subjects following DA depletion. Reducing DA synthesis in healthy individuals shifted sensitivity of performance from reward to punishment processing. Gender differences in DA synthesis might underlie the selectivity of this effect to female subjects. Such gender biases may go some way towards explaining the gender biases in certain psychiatric disorders such as depression and Parkinson's disease. C1 [Robinson, Oliver J.; Standing, Holly R.; DeVito, Elise E.; Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat & Behav, Cambridge CB2 2QQ, England. [Robinson, Oliver J.; Standing, Holly R.; DeVito, Elise E.; Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Clin Neurosci Inst, Cambridge CB2 2QQ, England. [Robinson, Oliver J.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [DeVito, Elise E.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Cools, Roshan] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP Robinson, OJ (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat & Behav, POB 189,Level E4,Hills Rd, Cambridge CB2 2QQ, England. EM oliver.j.robinson@googlemail.com RI Robinson, Oliver/B-3646-2011; Cools, Roshan/D-1905-2010 OI Robinson, Oliver/0000-0002-3100-1132; FU Medical Research Council (MRC); Wellcome Trust [076274/Z/04/Z]; NIAAA [T32-AA015496] FX This work was completed within the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and the Wellcome Trust. Additional funding for this study came from Wellcome Trust Programme Grant 076274/Z/04/Z awarded to T.W. Robbins, B.J. Everitt, A.C. Roberts, and B.J. Sahakian O.J. Robinson was supported by an MRC PhD studentship. E.E. DeVito was supported by a Pinsent Darwin PhD Studentship and NIAAA Postdoctoral Fellowship (T32-AA015496) and O.J. Robinson was supported by an MRC PhD studentship. We thank the nurses and administrative staff at the Wellcome Trust Clinical Research Facility (Addenbrooke's Hospital, Cambridge, UK) and Mike Franklin for amino acid analysis and all participants. NR 37 TC 21 Z9 21 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2010 VL 211 IS 2 BP 187 EP 195 DI 10.1007/s00213-010-1880-1 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 616IA UT WOS:000279201200007 PM 20495788 ER PT J AU Epstein, DH Preston, KL AF Epstein, David H. Preston, Kenzie L. TI Daily life hour by hour, with and without cocaine: an ecological momentary assessment study SO PSYCHOPHARMACOLOGY LA English DT Article DE Cocaine; Abstinence; Addiction; Behavior; Human; Ecological momentary assessment ID INTRAVENOUS COCAINE; ABSTINENCE; WITHDRAWAL; SLEEP; MOOD AB Effects of an intervention cannot be understood without precise knowledge of the baseline behavior on which the intervention is superimposed. For misusers of illicit drugs, patterns of daily activities and moods have not been studied in a way that is amenable to statistical aggregation. The aim of the study was to compare hour-by-hour daily activities in cocaine-dependent outpatients during urine-verified periods of use and abstinence. In a cohort design, a volunteer sample of 112 methadone-maintained cocaine- and heroin-abusing outpatients provided ecological momentary assessment (EMA) data on handheld computers for 10,781 person-days. EMA responses to questions about current location, activities, companions, moods, and recent exposure to putative drug-use triggers were compared across periods of use and abstinence using SAS Proc Glimmix (for binary outcomes) and Proc Mixed (for continuous outcomes). Periods of cocaine use were associated with idle, solitary, affectively negative afternoons but, unexpectedly, were also associated with a greater likelihood of early-morning or late-evening work. The whole-day concomitants of cocaine use were often distinct from the acute predecessors of use seen in prior analyses from the same sample. Several measures of negative mood increased during abstinence. Weeks of cocaine use and abstinence in outpatients are associated with distinct patterns of mood and behavior; the detailed hourly data reported here should help inform treatment interventions aimed at changing daily activities. The findings also argue against the contention that cocaine abstinence symptoms decrease monotonically from the day of cessation. C1 [Epstein, David H.; Preston, Kenzie L.] Natl Inst Drug Abuse, Treatment Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program,NIH,Dept Hlth & Hlth Serv, Baltimore, MD 21224 USA. RP Epstein, DH (reprint author), Natl Inst Drug Abuse, Treatment Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program,NIH,Dept Hlth & Hlth Serv, Room 01B-606,251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM depstein@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU National Institute on Drug Abuse (NIDA), National Institutes of Health FX This research was supported the Intramural Research Program (IRP) of the National Institute on Drug Abuse (NIDA), National Institutes of Health. We wish to thank the NIDA IRP Archway Clinic staff for data collection.; This research was supported by the NIDA Intramural Research Program. NR 21 TC 25 Z9 27 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2010 VL 211 IS 2 BP 223 EP 232 DI 10.1007/s00213-010-1884-x PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 616IA UT WOS:000279201200010 PM 20532873 ER PT J AU Suto, N Ecke, LE You, ZB Wise, RA AF Suto, Nobuyoshi Ecke, Laurel E. You, Zhi-Bing Wise, Roy A. TI Extracellular fluctuations of dopamine and glutamate in the nucleus accumbens core and shell associated with lever-pressing during cocaine self-administration, extinction, and yoked cocaine administration SO PSYCHOPHARMACOLOGY LA English DT Article DE Accumbens; Cocaine; Dopamine; Glutamate; Self-administration; Extinction ID DRUG-SEEKING BEHAVIOR; CUE-INDUCED REINSTATEMENT; RAT; TRANSMISSION; RELEASE; STRIATUM; MICRODIALYSIS; REINFORCEMENT; SENSITIZATION; PROJECTIONS AB Dopamine and glutamate in the nucleus accumbens (NAS) are differentially implicated in cocaine-directed behavior. We sought to compare extracellular fluctuations of dopamine and glutamate in core and shell of NAS associated with operant responding during cocaine self-administration, extinction, and yoked cocaine administration. Rats were trained to lever-press for cocaine or saline under FR1 before undergoing microdialysis testing during cocaine self-administration, extinction, or yoked cocaine administration. Microdialysis samples were collected every 20 min and were analyzed for dopamine and glutamate with high-performance liquid chromatography. Rats actively lever-pressed during cocaine self-administration and extinction. However, lever-pressing was minimal during yoked cocaine administration in both cocaine-trained and saline-trained rats. Dopamine was elevated throughout cocaine self-administration and yoked cocaine administration. The extent of cocaine-evoked dopamine was greater in shell than in core, greater in cocaine-trained than in saline-trained rats, and greater during self-administration than during yoked administration. Dopamine was also elevated in core (first 60 min) and in shell (first 40 min) during extinction. Basal concentration of glutamate, but not dopamine, was lower in cocaine-trained than in saline-trained rats. In cocaine-trained rats, glutamate was elevated during cocaine self-administration and extinction but was depressed below baseline during yoked cocaine administration. The extent and direction of glutamate fluctuation was similar between core and shell. In saline-trained rats, glutamate was not affected by yoked cocaine. Distinct patterns of dopamine and glutamate fluctuations in core and shell appear to underlie characteristic patterns of lever-pressing associated with cocaine self-administration, extinction, and yoked cocaine administration. C1 [Suto, Nobuyoshi; Ecke, Laurel E.; You, Zhi-Bing; Wise, Roy A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH DHHS, Baltimore, MD 21224 USA. RP Suto, N (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, POB 21247, Catonsville, MD 21228 USA. EM nsuto@mprc.umaryland.edu RI Wise, Roy/A-6465-2012 FU Intramural Research Program; National Institute on Drug Abuse; National Institutes of Health; Department of Health and Human Services FX This study was supported by funding from the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, and Department of Health and Human Services. We thank Dr. Stephan Steidl for critical reading of the manuscript, Dr. David Epstein for statistical advice, and Eric Thorndike for technical assistance with analyses of self-administration data. NR 52 TC 39 Z9 39 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2010 VL 211 IS 3 BP 267 EP 275 DI 10.1007/s00213-010-1890-z PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 624SI UT WOS:000279840600003 PM 20544343 ER PT J AU Bolch, WE Lee, C Wayson, M Johnson, P AF Bolch, Wesley E. Lee, Choonsik Wayson, Michael Johnson, Perry TI Hybrid computational phantoms for medical dose reconstruction: Response to Kramer and Cassola SO RADIATION AND ENVIRONMENTAL BIOPHYSICS LA English DT Letter ID RADIATION PROTECTION DOSIMETRY; ADULT HUMAN PHANTOMS C1 [Bolch, Wesley E.; Wayson, Michael; Johnson, Perry] Univ Florida, Dept Nucl & Radiol Engn, ALRADS, Gainesville, FL 32611 USA. [Bolch, Wesley E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. [Lee, Choonsik] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Bolch, WE (reprint author), Univ Florida, Dept Nucl & Radiol Engn, ALRADS, Gainesville, FL 32611 USA. EM wbolch@ufl.edu RI Lee, Choonsik/C-9023-2015 OI Lee, Choonsik/0000-0003-4289-9870 NR 6 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-634X J9 RADIAT ENVIRON BIOPH JI Radiat. Environ. Biophys. PD AUG PY 2010 VL 49 IS 3 BP 501 EP 502 DI 10.1007/s00411-010-0278-0 PG 2 WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging GA 628QT UT WOS:000280136400028 ER PT J AU Kempner, ES Miller, JH AF Kempner, E. S. Miller, J. H. TI Radiation target analyses of free and immobilized glucose 6-phosphate dehydrogenase SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article DE Radiation; Target analysis; Immobilized enzyme; Glucose 6-phosphate dehydrogenase ID FREE-RADICAL SCAVENGERS; INACTIVATION ANALYSIS; MOLECULAR-WEIGHT; SIZE; ENERGY; REDUCTASE; MEMBRANE; PROTEINS; ENZYME; FORMS AB The sensitivity of the enzyme glucose 6-phosphate dehydrogenase to ionizing radiation was examined under several conditions, including the presence of several free-radical scavengers. The enzyme was also irradiated when covalently bound to polyacrylamide beads whose structure is very similar to the polypeptide backbone of proteins. All the enzyme forms were irradiated in the frozen state with high-energy electrons from a linear accelerator. Surviving enzyme activity and surviving monomers were determined; the data were analyzed by target theory. Free-radical scavengers reduced the radiation target size of both the activity and monomers of the free enzyme, but not that of the immobilized enzyme activity. The target size of the activity of the free enzyme was that of a dimer mass, but in the case of the immobilized enzyme it was equal to the smaller mass of the monomer. Free-radical scavengers reduce the target size by modifying radiation energy transfer. The target size of the polyacrylamide-bound enzyme activity was expected to be very large since the connection between polyacrylamide and protein is a peptide bond which permits transfer of radiation-deposited energy. Several explanations concerning energy transfer are suggested for this result. Published by Elsevier Ltd. C1 [Kempner, E. S.; Miller, J. H.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Kempner, ES (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM eskempner@yahoo.com FU National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health FX We thank Dr. Robert Horowits for helpful suggestions. This work was supported by the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health. NR 28 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-806X J9 RADIAT PHYS CHEM JI Radiat. Phys. Chem. PD AUG PY 2010 VL 79 IS 8 BP 816 EP 818 DI 10.1016/j.radphyschem.2010.03.017 PG 3 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA 606LF UT WOS:000278425800002 ER PT J AU Natera-Naranjo, O Aschrafi, A Gioio, AE Kaplan, BB AF Natera-Naranjo, Orlangie Aschrafi, Armaz Gioio, Anthony E. Kaplan, Barry B. TI Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE superior cervical ganglion; primary neurons; microRNA; microarray profiling; real-time PCR; target mRNAs ID KAPPA-OPIOID RECEPTOR; MESSENGER-RNA; SYNAPTIC PLASTICITY; PROTEIN-SYNTHESIS; POSTTRANSCRIPTIONAL REGULATION; RT-PCR; EXPRESSION; TRANSLATION; DENDRITES; TARGETS AB microRNAs (miRNAs) constitute a novel class of small, noncoding RNAs that act as negative post-transcriptional regulators of gene expression. Although the nervous system is a prominent site of miRNA expression, little is known about the spatial expression profiles of miRNAs in neurons. Here, we employed compartmentalized Campenot cell culture chambers to obtain a pure axonal RNA fraction of superior cervical ganglia (SCG) neurons, and determined the miRNA expression levels in these subcellular structural domains by microarray analysis and by real-time reverse-transcription polymerase chain reaction. The data revealed stable expression of a number of mature miRNAs that were enriched in the axons and presynaptic nerve terminals. Among the 130 miRNAs identified in the axon, miR-15b, miR-16, miR-204, and miR-221 were found to be highly abundant in distal axons as compared with the cell bodies of primary sympathetic neurons. Moreover, a number of miRNAs encoded by a common primary transcript (pri-miRNA) were differentially expressed in the distal axons, suggesting that there is a differential subcellular transport of miRNAs derived from the same coding region of the genome. Taken together, the data provide an important resource for future studies on the regulation of axonal protein synthesis and the role played by miRNAs in the maintenance of axonal structure and function as well as neuronal growth and development. C1 [Natera-Naranjo, Orlangie; Aschrafi, Armaz; Gioio, Anthony E.; Kaplan, Barry B.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, 10 Ctr Dr,Room 4A15, Bethesda, MD 20892 USA. EM kaplanb@mail.nih.gov RI Aschrafi, Armaz/E-2202-2012 FU National Institute of Mental Health FX This work was supported by the Division of Intramural Research Programs of the National Institute of Mental Health. We thank Dr. Lauren Taylor (Invitrogen) for assistance with the miRNA microarray studies and Dr. Marie Mameza (University of Maryland School of Medicine) for her assistance in the RT-PCR analyses of axonal and somal RNA preparations. We also thank Dr. Amar N. Kar (NIMH) for his assistance in the bioinformatic analysis of miRNA target genes. NR 41 TC 83 Z9 86 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD AUG PY 2010 VL 16 IS 8 BP 1516 EP 1529 DI 10.1261/rna.1833310 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624XJ UT WOS:000279855200008 PM 20584895 ER PT J AU Robertson, KL Verhoeven, AB Thach, DC Chang, EL AF Robertson, Kelly L. Verhoeven, Anne Brooks Thach, Dzung C. Chang, Eddie L. TI Monitoring viral RNA in infected cells with LNA flow-FISH SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE LNA; RNA; flow cytometry; fluorescence in situ hybridization; viral nucleic acids ID IN-SITU HYBRIDIZATION; FLUORESCENT INSITU HYBRIDIZATION; LOCKED NUCLEIC-ACIDS; MESSENGER-RNA; VIRUS-INFECTION; CYTOMETRIC DETECTION; PROBES; DNA; PCR; QUANTIFICATION AB We previously showed the feasibility of using locked nucleic acid (LNA) for flow cytometric-fluorescence in situ hybridization (LNA flow-FISH) detection of a target cellular mRNA. Here we demonstrate how the method can be used to monitor viral RNA in infected cells. We compared the results of the LNA flow-FISH with other methods of quantifying virus replication, including the use of an enhanced green fluorescent protein (EGFP) viral construct and quantitative reverse-transcription polymerase chain reaction. We found that an LNA probe complementary to Sindbis virus RNA is able to track the increase in viral RNA over time in early infection. In addition, this method is comparable to the EGFP construct in sensitivity, with both peaking around 3 h and at the same level of infected cells. Finally, we observed that the LNA flow-FISH method responds to the decrease in levels of viral RNA caused by antiviral medication. This technique represents a straightforward way to monitor viral infection in cells and is easily applicable to any virus. C1 [Robertson, Kelly L.; Chang, Eddie L.] USN, Res Lab, Lab Biosensors & Biomat, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. [Verhoeven, Anne Brooks] George Mason Univ, Dept Mol & Microbiol, Manassas, VA 20110 USA. [Thach, Dzung C.] NIAID, Infect Dis Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Chang, EL (reprint author), USN, Res Lab, Lab Biosensors & Biomat, Ctr Biomol Sci & Engn, Code 6910,4555 Overlook Ave SW, Washington, DC 20375 USA. EM eddie.chang@nrl.navy.mil FU Office of Naval Research; JSTO-CBD/DTRA [4.10004.08.NRL] FX This work was supported in part by the Office of Naval Research and in part by JSTO-CBD/DTRA Project Number 4.10004.08.NRL. NR 43 TC 20 Z9 20 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD AUG PY 2010 VL 16 IS 8 BP 1679 EP 1685 DI 10.1261/rna.2016410 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624XJ UT WOS:000279855200021 PM 20584898 ER PT J AU Ten Hagen, KG AF Ten Hagen, Kelly G. TI Developmental glycobiology SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Editorial Material C1 Natl Inst Dent & Craniofacial Res, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA. RP Ten Hagen, KG (reprint author), Natl Inst Dent & Craniofacial Res, Dev Glycobiol Unit, NIH, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM Kelly.Tenhagen@nih.gov NR 1 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 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD AUG PY 2010 VL 21 IS 6 BP 599 EP 599 DI 10.1016/j.semcdb.2010.06.003 PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 634TK UT WOS:000280608100009 PM 20599515 ER EF