FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Hoppin, JA
Jaramillo, R
Salo, P
Sandler, DP
London, SJ
Zeldin, DC
AF Hoppin, Jane A.
Jaramillo, Renee
Salo, Paivi
Sandler, Dale P.
London, Stephanie J.
Zeldin, Darryl C.
TI Questionnaire Predictors of Atopy in a US Population Sample: Findings
From the National Health and Nutrition Examination Survey, 2005-2006
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE hypersensitivity; immunoglobulin E; questionnaires; sensitivity and
specificity
ID ALLERGIC RHINITIS; IGE SENSITIZATION; HAY-FEVER; ASTHMA; PREVALENCE;
VALIDATION; ADULTS; TRENDS; FOOD; AGE
AB Allergic conditions and biochemical measures are both used to characterize atopy. To assess questionnaires' ability to predict biochemical measures of atopy, the authors used data on 5 allergic conditions (allergy, hay fever, eczema, rhinitis, and itchy rash) and serum-specific immunoglobulin E (IgE) levels from the 2005-2006 National Health and Nutrition Examination Survey. Atopy was defined as 1 or more positive specific IgEs (>= 0.35 kU/L). Questionnaire responses were assessed for sensitivity, specificity, and positive and negative predictive values for atopy. In this population-based US sample, 44% of participants were specific IgE-positive and 53% reported at least 1 allergic condition. Discordance between atopy and allergic conditions was considerable; 37% of persons with atopy reported no allergic condition, and 48% of persons who reported an allergic condition were not atopic. Thus, no combination of self-reported allergic conditions achieved both high sensitivity and high specificity for IgE. The positive predictive value of reported allergic conditions for atopy ranged from 50% for eczema to 72% for hay fever, while the negative predictive value ranged from 57% for eczema to 65% for any condition. Given the high proportion of asymptomatic participants who were specific IgE-positive and persons who reported allergic conditions but were specific IgE-negative, it is unlikely that questionnaires will ever capture the same participants as those found to be atopic by biochemical measures.
C1 [Hoppin, Jane A.; Sandler, Dale P.; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Jaramillo, Renee] SRA Int Inc, Durham, NC USA.
[Zeldin, Darryl C.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, NIH, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA.
EM hoppin1@niehs.nih.gov
OI Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01 ES025041]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences (grant Z01 ES025041).
NR 24
TC 27
Z9 28
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 1
PY 2011
VL 173
IS 5
BP 544
EP 552
DI 10.1093/aje/kwq392
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 726SK
UT WOS:000287746200009
PM 21273397
ER
PT J
AU Cross, AJ
Freedman, ND
Ren, JS
Ward, MH
Hollenbeck, AR
Schatzkin, A
Sinha, R
Abnet, CC
AF Cross, Amanda J.
Freedman, Neal D.
Ren, Jiansong
Ward, Mary H.
Hollenbeck, Albert R.
Schatzkin, Arthur
Sinha, Rashmi
Abnet, Christian C.
TI Meat Consumption and Risk of Esophageal and Gastric Cancer in a Large
Prospective Study
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID N-NITROSO COMPOUNDS; STOMACH-CANCER; DIETARY-INTAKE; FOOD GROUPS;
HETEROCYCLIC AMINES; NONHEME IRON; COOKED MEATS; HEME IRON; RED MEAT;
COHORT
AB OBJECTIVES: Red and processed meats could increase cancer risk through several potential mechanisms involving iron, heterocyclic amines, polycyclic aromatic hydrocarbons, and N-nitroso compounds. Although there have been multiple studies of meat and colorectal cancer, other gastrointestinal malignancies are understudied.
METHODS: We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between meat, meat components, and meat cooking by-products and risk of esophageal or gastric cancer in a large cohort study. During similar to 10 years of follow-up, we accrued 215 esophageal squamous cell carcinomas, 630 esophageal adenocarcinomas, 454 gastric cardia adenocarcinomas, and 501 gastric non-cardia adenocarcinomas.
RESULTS: Red meat intake was positively associated with esophageal squamous cell carcinoma (HR for the top versus bottom quintile = 1.79, 95% CI: 1.07-3.01, P for trend = 0.019). Individuals in the highest intake quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) had an increased risk for gastric cardia cancer (HR = 1.44, 95% CI: 1.01-2.07, P for trend = 0.104). Furthermore, those in the highest quintile of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), or heme iron intake had a suggestive increased risk for esophageal adenocarcinoma (HR = 1.35, 95% CI: 0.97-1.89, P for trend = 0.022; HR = 1.45, 95 % CI: 0.99-2.12, P for trend = 0.463; or HR = 1.47, 95% CI: 0.99-2.20, P for trend = 0.063, respectively). Benzo[a]pyrene, nitrate, and nitrite were not associated with esophageal or gastric cancer.
CONCLUSIONS: We found positive associations between red meat intake and esophageal squamous cell carcinoma, and between DiMeIQx intake and gastric cardia cancer.
C1 [Cross, Amanda J.; Freedman, Neal D.; Ward, Mary H.; Schatzkin, Arthur; Sinha, Rashmi; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Ren, Jiansong] Int Agcy Res Canc, F-69372 Lyon, France.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Cross, AJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM crossa@mail.nih.gov
RI Abnet, Christian/C-4111-2015; Sinha, Rashmi/G-7446-2015; Freedman,
Neal/B-9741-2015
OI Abnet, Christian/0000-0002-3008-7843; Sinha, Rashmi/0000-0002-2466-7462;
Freedman, Neal/0000-0003-0074-1098
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services; Community Health Administration, State of
Michigan; Florida Department of Health (FDOH)
FX This research was supported, in part, by the Intramural Research Program
of the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services.; Cancer incidence data from the
Atlanta metropolitan area were collected by the Georgia Center for
Cancer Statistics, Department of Epidemiology, Rollins School of Public
Health, Emory University. Cancer incidence data from California were
collected by the California Department of Health Services, Cancer
Surveillance Section. Cancer incidence data from the Detroit
metropolitan area were collected by the Michigan Cancer Surveillance
Program, Community Health Administration, State of Michigan. The Florida
cancer incidence data used in this report were collected by the Florida
Cancer Data System (FCDC) under contract with the Florida Department of
Health (FDOH). Cancer incidence data from Louisiana were collected by
the Louisiana Tumor Registry, Louisiana State University Medical Center
in New Orleans. Cancer incidence data from New Jersey were collected by
the New Jersey State Cancer Registry, Cancer Epidemiology Services, New
Jersey State Department of Health and Senior Services. Cancer incidence
data from North Carolina were collected by the North Carolina Central
Cancer Registry. Cancer incidence data from Pennsylvania were supplied
by the Division of Health Statistics and Research, Pennsylvania
Department of Health, Harrisburg, Pennsylvania. Cancer incidence data
from Arizona were collected by the Arizona Cancer Registry, Division of
Public Health Services, Arizona Department of Health Services. Cancer
incidence data from Texas were collected by the Texas Cancer Registry,
Cancer Epidemiology and Surveillance Branch, Texas Department of State
Health Services. We are indebted to the participants in the NIH-AARP
Diet and Health Study for their outstanding cooperation. We also thank
Sigurd Hermansen and Kerry Grace Morrissey from Westat for study
outcomes ascertainment and management and Leslie Carroll at Information
Management Services for data support and analysis.
NR 40
TC 52
Z9 54
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD MAR
PY 2011
VL 106
IS 3
BP 432
EP 442
DI 10.1038/ajg.2010.415
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730VT
UT WOS:000288064200009
PM 20978481
ER
PT J
AU Drgon, T
Johnson, CA
Nino, M
Drgonova, J
Walther, DM
Uhl, GR
AF Drgon, Tomas
Johnson, Catherine A.
Nino, Michelle
Drgonova, Jana
Walther, Donna M.
Uhl, George R.
TI "Replicated" Genome Wide Association for Dependence on Illegal
Substances: Genomic Regions Identified by Overlapping Clusters of
Nominally Positive SNPs
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE substance dependence; microarray
ID ADDICTION MOLECULAR-GENETICS; ALCOHOL DEPENDENCE; POLYSUBSTANCE ABUSERS;
MACULAR DEGENERATION; NICOTINE DEPENDENCE; VULNERABILITY LOCI; GENES;
INDIVIDUALS; POLYMORPHISMS; VALIDATION
AB Declaring "replication" from results of genome wide association (GWA) studies is straightforward when major gene effects provide genome-wide significance for association of the same allele of the same SNP in each of multiple independent samples. However, such unambiguous replication may be unlikely when phenotypes display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity, and when different samples display linkage disequilibria with different fine structures. We seek chromosomal regions that are tagged by clustered SNPs that display nominally significant association in each of several independent samples. This approach provides one "nontemplate" approach to identifying overall replication of groups of GWA results in the face of difficult genetic architectures. We apply this strategy to 1 million (1M) SNP Affymetrix and Illumina GWA results for dependence on illegal substances. This approach provides high confidence in rejecting the null hypothesis that chance alone accounts for the extent to which clustered, nominally significant SNPs from samples of the same racial/ethnic background identify the same chromosomal regions. There is more modest confidence in: (a) identification of individual chromosomal regions and genes and (b) overlap between results from samples of different racial/ethnic backgrounds. The strong overlap identified among the samples with similar racial/ethnic backgrounds, together with prior work that identified overlapping results in samples of different racial/ethnic backgrounds, support contributions to individual differences in vulnerability to addictions that come from both relatively older allelic variants that are common in many current human populations and newer allelic variants that are common in fewer current human populations. (C) 2010 Wiley-Liss, Inc.
C1 [Drgon, Tomas; Johnson, Catherine A.; Nino, Michelle; Drgonova, Jana; Walther, Donna M.; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD USA.
RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA.
EM guhl@intra.nida.nih.gov
OI Drgonova, Jana/0000-0002-4623-8466
FU NIH [HHSN268200782096C]; NIDA; DHHS; NIH Genes, Environment and Health
Initiative (GEI) [U01 HG004422]; Gene Environment Association Studies
(GENEVA); GENEVA Coordinating Center U01 [HG004446]; Collaborative Study
on the Genetics of Alcoholism (COGA) [U10 AA008401]; Collaborative
Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]; Family
Study of Cocaine Dependence (FSCD) [R01 DA013423]; Johns Hopkins
University Center for Inherited Disease Research [U01HG004438]; National
Institute on Alcohol Abuse and Alcoholism; National Institute on Drug
Abuse
FX Grant sponsor: NIH Intramural Research Program; Grant sponsor: NIDA;
Grant sponsor: DHHS; Grant sponsor: NIH Genes, Environment and Health
Initiative (GEI); Grant Number: U01 HG004422; Grant sponsor: Gene
Environment Association Studies (GENEVA); Grant sponsor: GENEVA
Coordinating Center U01; Grant Number: HG004446; Grant sponsor:
Collaborative Study on the Genetics of Alcoholism (COGA); Grant Number:
U10 AA008401; Grant sponsor: Collaborative Genetic Study of Nicotine
Dependence (COGEND); Grant Number: P01 CA089392; Grant sponsor: Family
Study of Cocaine Dependence (FSCD); Grant Number: R01 DA013423; Grant
sponsor: Johns Hopkins University Center for Inherited Disease Research;
Grant Number: U01HG004438; Grant sponsor: National Institute on Alcohol
Abuse and Alcoholism; Grant sponsor: National Institute on Drug Abuse;
Grant sponsor: NIH Contract "High throughput genotyping for studying the
genetic contributions to human disease"; Grant Number:
HHSN268200782096C.
NR 31
TC 12
Z9 12
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD MAR
PY 2011
VL 156B
IS 2
BP 125
EP 138
DI 10.1002/ajmg.b.31143
PG 14
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 718VQ
UT WOS:000287154900002
PM 21302341
ER
PT J
AU Zhang, YF
Cantor, RM
MacGibbon, K
Romero, R
Goodwin, TM
Mullin, PM
Fejzo, MS
AF Zhang, Yafeng
Cantor, Rita M.
MacGibbon, Kimber
Romero, Roberto
Goodwin, Thomas M.
Mullin, Patrick M.
Fejzo, Marlena S.
TI Familial aggregation of hyperemesis gravidarum
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE familial aggregation; genetic; hyperemesis gravidarum; nausea; pregnancy
ID EARLY-PREGNANCY; THYROTROPIN RECEPTOR; NAUSEA; EPIDEMIOLOGY; POPULATION;
SEVERITY; EXPOSURE; OUTCOMES; DISEASE; RISK
AB OBJECTIVE: This study was undertaken to determine whether there is familial aggregation of hyperemesis gravidarum (HG), making it a disease amenable to genetic study.
STUDY DESIGN: Cases with severe nausea and vomiting in a singleton pregnancy treated with intravenous hydration and unaffected friend controls completed a survey regarding family history.
RESULTS: Sisters of women with HG have a significantly increased risk of having HG themselves (odds ratio, 17.3; P = .005). Cases have a significantly increased risk of having a mother with severe nausea and vomiting; 33% of cases reported an affected mother compared to 7.7% of controls (P < .0001). Cases reported a similar frequency of affected second-degree maternal and paternal relatives (18% maternal lineage, 23% paternal lineage).
CONCLUSION: There is familial aggregation of HG. This study provides strong evidence for a genetic component to HG. Identification of the predisposing gene(s) may determine the cause of this poorly understood disease of pregnancy.
C1 [Goodwin, Thomas M.; Mullin, Patrick M.; Fejzo, Marlena S.] Univ So Calif, Keck Sch Med, Dept Maternal Fetal Med, Los Angeles, CA 90095 USA.
[Zhang, Yafeng; Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Fejzo, Marlena S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[MacGibbon, Kimber] Hyperemesis Educ & Res Fdn, Leesburg, VA USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
RP Fejzo, MS (reprint author), Univ So Calif, Keck Sch Med, Dept Maternal Fetal Med, 5535 MRL Bldg,675 Charles E Young Dr, Los Angeles, CA 90095 USA.
EM mfejzo@mednet.ucla.edu
OI MacGibbon, Kimber/0000-0002-6534-3114
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, HIH, DHHS
FX This research was supported (in part) by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, HIH, DHHS.
NR 33
TC 1
Z9 3
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2011
VL 204
IS 3
AR 230.e1
DI 10.1016/j.ajog.2010.09.018
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 730CY
UT WOS:000288010300023
PM 20974461
ER
PT J
AU Puliti, A
Rossi, PIA
Caridi, G
Corbelli, A
Ikehata, M
Armelloni, S
Li, M
Zennaro, C
Conti, V
Vaccari, CM
Cassanello, M
Calevo, MG
Emionite, L
Ravazzolo, R
Rastaldi, MP
AF Puliti, Aldamaria
Rossi, Pia Irene Anna
Caridi, Gianluca
Corbelli, Alessandro
Ikehata, Masami
Armelloni, Silvia
Li, Min
Zennaro, Cristina
Conti, Valerio
Vaccari, Carlotta Maria
Cassanello, Michela
Calevo, Maria Grazia
Emionite, Laura
Ravazzolo, Roberto
Rastaldi, Maria Pia
TI Albuminuria and Glomerular Damage in Mice Lacking the Metabotropic
Glutamate Receptor 1
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID LONG-TERM DEPRESSION; CEREBELLAR PURKINJE-CELLS; FOOT PROCESS
EFFACEMENT; PODOCYTE; EXPRESSION; RAT; ACTIVATION; STIMULATION;
PLASTICITY; DIVERSITY
AB The metabotropic glutamate (mGlu) receptor 1 (GRM1) has been shown to play an important role in neuronal cells by triggering, through calcium release from intracellular stores, various signaling pathways that finally modulate neuron excitability, synaptic plasticity, and mechanisms of feedback regulation of neurotransmitter release. Herein, we show that Grm1 is expressed in glomerular podocytes and that a glomerular phenotype is exhibited by Grm1(crv4) mice carrying a spontaneous recessive inactivating mutation of the gene. Homozygous Grm1(crv4/crv4) and, to a lesser extent, heterozygous mice show albuminuria, podocyte foot process effacement, and reduced levels of nephrin and other proteins known to contribute to the maintenance of podocyte cell structure. Overall, the present data extend the role of mGlu1 receptor to the glomerular filtration barrier. The regulatory action of mGlu1 receptor in dendritic spine morphology and in the control of glutamate release is well acknowledged in neuronal cells. Analogously, we speculate that mGlu1 receptor may regulate foot process morphology and intercellular signaling in the podocyte. (Am J Palhol 2011, 178:1257-1269; DOI: 10.1016/j.ajpath.2010.11.050)
C1 [Puliti, Aldamaria; Rossi, Pia Irene Anna; Conti, Valerio; Vaccari, Carlotta Maria; Ravazzolo, Roberto] G Gaslini Inst Children, Mol Genet Lab, Mol Genet & Cytogenet Unit, I-16148 Genoa, Italy.
[Caridi, Gianluca; Zennaro, Cristina] G Gaslini Inst Children, Lab Pathophysiol Uremia, I-16148 Genoa, Italy.
[Cassanello, Michela] G Gaslini Inst Children, Lab Study Inborn Errors Metab, I-16148 Genoa, Italy.
[Calevo, Maria Grazia] G Gaslini Inst Children, Sci Direct, I-16148 Genoa, Italy.
[Puliti, Aldamaria; Rossi, Pia Irene Anna; Vaccari, Carlotta Maria; Cassanello, Michela; Ravazzolo, Roberto] Univ Genoa, Dept Pediat, Genoa, Italy.
[Puliti, Aldamaria; Rossi, Pia Irene Anna; Vaccari, Carlotta Maria; Cassanello, Michela; Ravazzolo, Roberto] Univ Genoa, Ctr Excellence Biomed Res, Genoa, Italy.
[Corbelli, Alessandro; Ikehata, Masami; Armelloni, Silvia; Li, Min; Rastaldi, Maria Pia] Osped Maggiore Policlin, Fdn IRCCS, Renal Res Lab, Milan, Italy.
[Corbelli, Alessandro; Ikehata, Masami; Armelloni, Silvia; Li, Min; Rastaldi, Maria Pia] Fdn Amico Ric Malattie Renali, Milan, Italy.
[Emionite, Laura] Natl Canc Inst, Anim Facil, Genoa, Italy.
RP Puliti, A (reprint author), G Gaslini Inst Children, Mol Genet Lab, Mol Genet & Cytogenet Unit, Largo G Gaslini 5, I-16148 Genoa, Italy.
EM apuliti@unige.it
RI Caridi, Gianluca/F-7052-2010; Puliti, Aldamaria/K-7866-2016; IKEHATA,
MASAMI/H-8020-2016;
OI Caridi, Gianluca/0000-0001-6700-3001; Puliti,
Aldamaria/0000-0001-9310-6514; IKEHATA, MASAMI/0000-0001-9835-9991;
ZENNARO, Cristina/0000-0003-4755-1064
FU Italian Ministry of Health [RFPS-4-631972]; Progetto a Concorso
Fondazione IRCCS Policlinico; Renal Child Foundation; Fondazione D'Amico
per la Ricerca sulle Malattie Renali; Fondazione La Nuova Speranza
FX Supported by RFPS-4-631972 grant "Genetic Bases of Birth Defects" from
the Italian Ministry of Health; Progetto a Concorso 2008-2009 Fondazione
IRCCS Policlinico; Renal Child Foundation; Fondazione D'Amico per la
Ricerca sulle Malattie Renali; and Fondazione La Nuova Speranza.
NR 33
TC 17
Z9 18
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2011
VL 178
IS 3
BP 1257
EP 1269
DI 10.1016/j.ajpath.2010.11.050
PG 13
WC Pathology
SC Pathology
GA 732LD
UT WOS:000288185600032
PM 21356376
ER
PT J
AU Hicks, CW
Li, Y
Okugawa, S
Solomon, SB
Moayeri, M
Leppla, SH
Mohanty, A
Subramanian, GM
Mignone, TS
Fitz, Y
Cui, XZ
Eichacker, PQ
AF Hicks, Caitlin W.
Li, Yan
Okugawa, Shu
Solomon, Steven B.
Moayeri, Mahtab
Leppla, Stephen H.
Mohanty, Ajana
Subramanian, G. Mani
Mignone, Thi S.
Fitz, Yvonne
Cui, Xizhong
Eichacker, Peter Q.
TI Anthrax edema toxin has cAMP-mediated stimulatory effects and high-dose
lethal toxin has depressant effects in an isolated perfused rat heart
model
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE heart function
ID BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; ESCHERICHIA-COLI; CORONARY FLOW;
NITRIC-OXIDE; ISOLATED BLOOD; MOUSE HEART; PURIFICATION; DYSFUNCTION;
SHOCK
AB Hicks CW, Li Y, Okugawa S, Solomon SB, Moayeri M, Leppla SH, Mohanty A, Subramanian GM, Mignone TS, Fitz Y, Cui X, Eichacker PQ. Anthrax edema toxin has cAMP-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model. Am J Physiol Heart Circ Physiol 300: H1108-H1118, 2011. First published January 7, 2011; doi: 10.1152/ajpheart.01128.2010.-While anthrax edema toxin produces pronounced tachycardia and lethal toxin depresses left ventricular (LV) ejection fraction in in vivo models, whether these changes reflect direct cardiac effects as opposed to indirect ones related to preload or afterload alterations is unclear. In the present study, the effects of edema toxin and lethal toxin were investigated in a constant pressure isolated perfused rat heart model. Compared with control hearts, edema toxin at doses comparable to or less than a dose that produced an 80% lethality rate (LD(80)) in vivo in rats (200, 100, and 50 ng/ml) produced rapid increases in heart rate (HR), coronary flow (CF), LV developed pressure (LVDP), dP/dt(max), and rate-pressure product (RPP) that were most pronounced and persisted with the lowest dose (P <= 0.003). Edema toxin (50 ng/ml) increased effluent and myocardial cAMP levels (P <= 0.002). Compared with dobutamine, edema toxin produced similar myocardial changes, but these occurred more slowly and persisted longer. Increases in HR, CF, and cAMP with edema toxin were inhibited by a monoclonal antibody blocking toxin uptake and by adefovir, which inhibits the toxin's intracellular adenyl cyclase activity (P <= 0.05). Lethal toxin at an LD(80) dose (50 ng/ml) had no significant effect on heart function but a much higher dose (500 ng/ml) reduced all parameters (P <= 0.05). In conclusion, edema toxin produced cAMP-mediated myocardial chronotropic, inotropic, and vasodilatory effects. Vasodilation systemically with edema toxin could contribute to shock during anthrax while masking potential inotropic effects. Although lethal toxin produced myocardial depression, this only occurred at high doses, and its relevance to in vivo findings is unclear.
C1 [Hicks, Caitlin W.; Li, Yan; Solomon, Steven B.; Mohanty, Ajana; Fitz, Yvonne; Cui, Xizhong; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hicks, Caitlin W.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
[Okugawa, Shu; Moayeri, Mahtab; Leppla, Stephen H.] NIAID, NIH, Bethesda, MD 20892 USA.
[Subramanian, G. Mani; Mignone, Thi S.] Human Genome Sci, Rockville, MD USA.
[Hicks, Caitlin W.] NIH Res Scholar, Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 2C145,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM peichacker@mail.cc.nih.gov
RI Hicks, Caitlin/E-8849-2012
NR 38
TC 18
Z9 18
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD MAR
PY 2011
VL 300
IS 3
BP H1108
EP H1118
DI 10.1152/ajpheart.01128.2010
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 728ZV
UT WOS:000287914900044
PM 21217068
ER
PT J
AU Guo, J
Hall, KD
AF Guo, Juen
Hall, Kevin D.
TI Challenges of indirect calorimetry in mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Letter
C1 [Guo, Juen; Hall, Kevin D.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
NR 5
TC 4
Z9 4
U1 1
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD MAR
PY 2011
VL 300
IS 3
BP R780
EP R780
DI 10.1152/ajpregu.00763.2010
PG 1
WC Physiology
SC Physiology
GA 730XE
UT WOS:000288069900029
PM 21378217
ER
PT J
AU Matsusaka, T
Kobayashi, K
Kon, V
Pastan, I
Fogo, AB
Ichikawa, I
AF Matsusaka, Taiji
Kobayashi, Kazuto
Kon, Valentina
Pastan, Ira
Fogo, Agnes B.
Ichikawa, Iekuni
TI Glomerular sclerosis is prevented during urinary tract obstruction due
to podocyte protection
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE glomerular transmural pressure difference; angiotensin II
ID TUBULOINTERSTITIAL FIBROSIS; RENAL ABLATION; INJURY; HYPERTENSION;
NEPHROPATHY; RATS; HEMODYNAMICS; EXPRESSION; PRESSURE; NEPHRIN
AB Matsusaka T, Kobayashi K, Kon V, Pastan I, Fogo AB, Ichikawa I. Glomerular sclerosis is prevented during urinary tract obstruction due to podocyte protection. Am J Physiol Renal Physiol 300: F792-F800, 2011. First published December 22, 2010; doi:10.1152/ajprenal.00570.2010.-Urine outflow obstruction activates a variety of profibrotic factors, including the intrarenal renin-angiotensin system. However, the obstruction also nullifies the transmural hydraulic pressure difference across the glomerular capillary wall, an established inducer of glomerulosclerosis. In the present study, we investigated whether, and by what mechanism, urine outflow obstruction affects the process of progressive glomerulosclerosis. For this purpose, we tested the effect of unilateral ureteral obstruction (UUO) of 7 days duration in two distinct mouse models of glomerulosclerosis. In the human immunodeficiency virus (HIV) nephropathy model, where HIV-1 genes are selectively expressed in podocytes and develop progressive podocyte damage and glomerulosclerosis, UUO protected against sclerosis with preservation of podocytes morphologically and immunohistochemically. In contrast, the nonobstructed contralateral kidneys of these mice, as well as sham-operated HIV-1 mouse kidneys, developed severe podocyte injury and glomerulosclerosis. The protection against glomerulosclerosis imparted by ureteral obstruction was also documented in the NEP25 model of podocyte injury, in which a single injection of immunotoxin, LMB2, triggers selective podocyte injury followed by glomerulosclerosis, both of which were protected by UUO. Notably, intervention with an angiotensin II type 1 receptor antagonist provided only a partial protective effect in each of the models. These results demonstrate that urine outflow obstruction protects the glomerulus from progressive sclerosis. The results further reveal that this protection occurs at a very early stage of the pathologic process, namely, damage of podocytes.
C1 [Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Kanagawa 2591100, Japan.
[Ichikawa, Iekuni] Tokai Univ, Sch Med, Dept Bioeth, Kanagawa 2591100, Japan.
[Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Kanagawa 2591100, Japan.
[Kon, Valentina; Fogo, Agnes B.; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Fogo, Agnes B.; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Fogo, Agnes B.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.
[Kobayashi, Kazuto] Fukushima Med Univ, Sch Med, Dept Mol Genet, Inst Biomed Sci, Fukushima, Japan.
[Pastan, Ira] NCI, Lab Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Matsusaka, T (reprint author), Tokai Univ, Sch Med, Dept Internal Med, Kanagawa 2591100, Japan.
EM taijim@is.icc.u-tokai.ac.jp
FU National Institutes of Health (NIH) [DK37868, DK44757]; Japan Society
for the Promotion of Science, MEXT, HAITEKU; NIH, National Cancer
Institute, Center for Cancer Research
FX This study was supported by National Institutes of Health (NIH) Grants
DK37868 and DK44757, the Research for the Future Program and Grant-in
Aid for Scientific Research of Japan Society for the Promotion of
Science, MEXT, HAITEKU, and in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 24
TC 12
Z9 12
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD MAR
PY 2011
VL 300
IS 3
BP F792
EP F800
DI 10.1152/ajprenal.00570.2010
PG 9
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 730ZS
UT WOS:000288076700025
PM 21177778
ER
PT J
AU Backinger, CL
Augustson, EM
AF Backinger, Cathy L.
Augustson, Erik M.
TI Where There's an App, There's a Way?
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
ID SMOKING-CESSATION
C1 [Backinger, Cathy L.; Augustson, Erik M.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Backinger, CL (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4050, Bethesda, MD 20892 USA.
EM backingc@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 9
TC 14
Z9 14
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2011
VL 40
IS 3
BP 390
EP 391
DI 10.1016/j.amepre.2010.11.014
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 722PB
UT WOS:000287445700023
PM 21335276
ER
PT J
AU Maglio, PP
Mabry, PL
AF Maglio, Paul P.
Mabry, Patricia L.
TI Agent-Based Models and Systems Science Approaches to Public Health
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
C1 [Maglio, Paul P.] IBM Res Almaden, Res Serv, San Jose, CA 95120 USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
RP Maglio, PP (reprint author), IBM Res Almaden, Res Serv, 650 Harry Rd, San Jose, CA 95120 USA.
EM pmaglio@almaden.ibm.com
FU Intramural NIH HHS [Z99 OD999999]
NR 21
TC 13
Z9 13
U1 3
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2011
VL 40
IS 3
BP 392
EP 394
DI 10.1016/j.amepre.2010.11.010
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 722PB
UT WOS:000287445700024
PM 21335277
ER
PT J
AU Levinson, DF
Duan, JB
Oh, S
Wang, K
Sanders, AR
Shi, JX
Zhang, N
Mowry, BJ
Olincy, A
Amin, F
Cloninger, CR
Silverman, JM
Buccola, NG
Byerley, WF
Black, DW
Kendler, KS
Freedman, R
Dudbridge, F
Pe'er, I
Hakonarson, H
Bergen, SE
Fanous, AH
Holmans, PA
Gejman, PV
AF Levinson, Douglas F.
Duan, Jubao
Oh, Sang
Wang, Kai
Sanders, Alan R.
Shi, Jianxin
Zhang, Nancy
Mowry, Bryan J.
Olincy, Ann
Amin, Farooq
Cloninger, C. Robert
Silverman, Jeremy M.
Buccola, Nancy G.
Byerley, William F.
Black, Donald W.
Kendler, Kenneth S.
Freedman, Robert
Dudbridge, Frank
Pe'er, Itsik
Hakonarson, Hakon
Bergen, Sarah E.
Fanous, Ayman H.
Holmans, Peter A.
Gejman, Pablo V.
TI Copy Number Variants in Schizophrenia: Confirmation of Five Previous
Findings and New Evidence for 3q29 Microdeletions and VIPR2 Duplications
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 60th Annual Meeting of the American-Society-of-Human-Genetics
CY NOV 02-06, 2010
CL Washington, DC
SP Amer Soc Human Genet
ID 22Q11.2 DELETION SYNDROME; COMMON VARIANTS; GENOME; RISK; GENE;
ASSOCIATION; POPULATION; DISORDER; DISEASE; 16P11.2
AB Objective: To evaluate previously reported associations of copy number variants (CNVs) with schizophrenia and to identify additional associations, the authors analyzed CNVs in the Molecular Genetics of Schizophrenia study (MGS) and additional available data.
Method: After quality control, MGS data for 3,945 subjects with schizophrenia or schizoaffective disorder and 3,611 screened comparison subjects were available for analysis of rare CNVs (< 1% frequency). CNV detection thresholds were chosen that maximized concordance in 151 duplicate assays. Pointwise and genewise analyses were carried out, as well as analyses of previously reported regions. Selected regions were visually inspected and confirmed with quantitative polymerase chain reaction.
Results: In analyses of MGS data combined with other available data sets, odds ratios of 7.5 or greater were observed for previously reported deletions in chromosomes 1q21.1, 15q13.3, and 22q11.21, duplications in 16p11.2, and exon-disrupting deletions in NRXN1. The most consistently supported candidate associations across data sets included a 1.6-Mb deletion in chromosome 3q29 (21 genes, TFRC to BDH1) that was previously described in a mild-moderate mental retardation syndrome, exonic duplications in the gene for vasoactive intestinal peptide receptor 2 (VIPR2), and exonic duplications in C16orf72. The case subjects had a modestly higher genome-wide number of gene-containing deletions (> 100 kb and > 1 Mb) but not duplications.
Conclusions: The data strongly confirm the association of schizophrenia with 1q21.1, 15q13.3, and 22q11.21 deletions, 16p11.2 duplications, and exonic NRXN1 deletions. These CNVs, as well as 3q29 deletions, are also associated with mental retardation, autism spectrum disorders, and epilepsy. Additional candidate genes and regions, including VIPR2, were identified. Study of the mechanisms underlying these associations should shed light on the pathophysiology of schizophrenia. (Am J Psychiatry 2011; 168:302-316)
C1 [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
NorthShore Univ, HealthSyst Res Inst, Evanston, IL USA.
Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
Univ Penn, Philadelphia, PA 19104 USA.
NCI, Bethesda, MD 20892 USA.
Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
Univ Colorado Denver, Dept Psychiat, Aurora, CO USA.
Atlanta VA Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA USA.
Emory Univ, Atlanta, GA 30322 USA.
Washington Univ, Dept Psychiat, St Louis, MO 63130 USA.
Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA.
Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
Univ Iowa, Mental Hlth Clin Res Ctr, Iowa City, IA USA.
Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA.
Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23284 USA.
London Sch Hyg & Trop Med, Dept Stat Genet & Epidemiol, London, England.
Columbia Univ, Dept Comp Sci, New York, NY 10027 USA.
Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
MIT, Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA 02139 USA.
Harvard Univ, Cambridge, MA 02138 USA.
Washington VA Med Ctr, Dept Psychiat, Washington, DC USA.
Georgetown Univ, Sch Med, Washington, DC USA.
Cardiff Univ, Biostat & Bioinformat Unit, Cardiff, S Glam, Wales.
RP Levinson, DF (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Suite A-3325,701 Welch Rd, Palo Alto, CA 94304 USA.
EM dflev@stanford.edu
RI Cloninger, Claude/F-5357-2012; Bergen, Sarah/I-8313-2012; Holmans,
Peter/F-4518-2015
OI Cloninger, Claude/0000-0003-3096-4807; Bergen,
Sarah/0000-0002-5888-0034; Buccola, Nancy/0000-0003-1378-4636; Holmans,
Peter/0000-0003-0870-9412
FU Medical Research Council [G1000718]; NCRR NIH HHS [U54 RR-020278, U54
RR020278]; NIMH NIH HHS [R01 MH059565, R01 MH-59565, R01 MH-59566, R01
MH-59571, R01 MH-59586, R01 MH-59587, R01 MH-59588, R01 MH-60870, R01
MH-60879, R01 MH-61675, R01 MH-67257, R01 MH-81800, R01 MH059566, R01
MH059571, R01 MH059586, R01 MH059587, R01 MH059588, R01 MH060870, R01
MH060879, R01 MH061675, R01 MH067257, R01 MH081800, U01 MH-46276, U01
MH-46289, U01 MH-46318, U01 MH-79469, U01 MH-79470, U01 MH046276, U01
MH046276-08, U01 MH046289, U01 MH046289-08, U01 MH046318, U01
MH046318-08, U01 MH079469, U01 MH079470]
NR 42
TC 226
Z9 229
U1 3
U2 30
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD MAR
PY 2011
VL 168
IS 3
BP 302
EP 316
DI 10.1176/appi.ajp.2010.10060876
PG 15
WC Psychiatry
SC Psychiatry
GA 729AG
UT WOS:000287916900014
PM 21285140
ER
PT J
AU Merbah, M
Introini, A
Fitzgerald, W
Grivel, JC
Lisco, A
Vanpouille, C
Margolis, L
AF Merbah, Melanie
Introini, Andrea
Fitzgerald, Wendy
Grivel, Jean-Charles
Lisco, Andrea
Vanpouille, Christophe
Margolis, Leonid
TI Cervico-Vaginal Tissue Ex Vivo as a Model to Study Early Events in HIV-1
Infection
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Cervix; explants; HIV; tissue-culture; transmission
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN CERVICAL TISSUE; HUMAN
LYMPHOID-TISSUE; REVERSE-TRANSCRIPTASE INHIBITOR; HERPES-SIMPLEX-VIRUS;
FEMALE GENITAL-TRACT; ORGAN-CULTURE SYSTEM; IN-VITRO MODELS; TYPE-1
INFECTION; CXCR4-TROPIC HIV-1
AB Vaginal intercourse remains the most prevalent route of infection of women. In spite of many efforts, the detailed mechanisms of HIV-1 transmission in the female lower genital tract remain largely unknown. With all the obvious restrictions on studying these mechanisms in humans, their understanding depends on the development of adequate experimental models. Isolated cell cultures do not faithfully reproduce important aspects of cell-cell interactions in living tissues and tissue responses to pathogens. Explants and other types of ex vivo tissue models serve as a bridge between cell culture and tissues in vivo. Herein, we discuss various cervico-vaginal tissue models and their use in studying HIV vaginal transmission and consider future directions of such studies.
C1 [Merbah, Melanie; Introini, Andrea; Fitzgerald, Wendy; Grivel, Jean-Charles; Lisco, Andrea; Vanpouille, Christophe; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Intercellular Interact, Program Phys Biol, NIH, Bethesda, MD USA.
RP Margolis, L (reprint author), NICHHD, Bldg 10,Room 9D58,10 Ctr Dr,MSC 1855, Bethesda, MD 20892 USA.
EM Margolis@helix.nih.gov
OI Introini, Andrea/0000-0002-9929-8964
FU Intramural NICHD
FX This work was supported by the Intramural NICHD Program.
NR 94
TC 16
Z9 16
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD MAR
PY 2011
VL 65
IS 3
BP 268
EP 278
DI 10.1111/j.1600-0897.2010.00967.x
PG 11
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 717IP
UT WOS:000287037200014
PM 21223429
ER
PT J
AU Mestecky, J
Alexander, RC
Wei, Q
Moldoveanu, Z
AF Mestecky, Jiri
Alexander, Rashada C.
Wei, Qing
Moldoveanu, Zina
TI Methods for Evaluation of Humoral Immune Responses in Human Genital
Tract Secretions
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Antibodies; external secretions; HIV; mucosal immunity
ID IGA ANTIBODIES; SECRETORY IGA; CERVICOVAGINAL SECRETIONS; 1-INFECTED
INDIVIDUALS; MUCOSAL SURFACES; VACCINE DESIGN; IMMUNOGLOBULINS;
HETEROGENEITY; CONTRIBUTE; FLUIDS
AB The compilation of epidemiological, virological, and immunological data clearly indicates that HIV-1 infection must be considered primarily as a disease of the mucosal immune system. The earliest and most dramatic alterations of the immune system occur in the mucosal compartment. However, the mucosal immune systems of the genital and intestinal tracts display remarkable immunological differences that must be considered in the evaluation of humoral immune responses in HIV-1-infected individuals or in volunteers immunized with experimental HIV vaccines. In this regard, marked differences in the dominant Ig isotypes, molecular forms of HIV-1-specific antibodies, and their distinct effector functions in the genital versus intestinal tracts must be carefully evaluated and considered in the measurement and interpretation of humoral immune responses. Appropriate controls and alternative immunochemical assays should be used to complement and confirm results generated by ELISA, which are prone to false positivity. Special precautions and rigorous controls must be used in the evaluation of antibody-mediated virus neutralization in external secretions of the genital and intestinal tracts.
C1 [Mestecky, Jiri; Wei, Qing; Moldoveanu, Zina] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Mestecky, Jiri; Wei, Qing; Moldoveanu, Zina] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Mestecky, Jiri] Charles Univ Prague, Inst Microbiol & Immunol, Fac Med 1, Prague, Czech Republic.
[Alexander, Rashada C.] NIH, Off Extramural Res, Bethesda, MD 20892 USA.
RP Mestecky, J (reprint author), Univ Alabama, Dept Microbiol, BBRB 757,845 19th St S, Birmingham, AL 35294 USA.
EM mestecky@uab.edu
FU NIH [P01AI083027, P01AI071739, T32AI07493, DK64400]
FX We thank Ms. Patricia V. Grayson for editorial assistance. Experimental
results included in this review were supported by NIH grants
P01AI083027, P01AI071739, T32AI07493, and DK64400.
NR 49
TC 12
Z9 12
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD MAR
PY 2011
VL 65
IS 3
BP 361
EP 367
DI 10.1111/j.1600-0897.2010.00923.x
PG 7
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 717IP
UT WOS:000287037200024
PM 21087333
ER
PT J
AU Ventetuolo, CE
Ouyang, P
Bluemke, DA
Tandri, H
Barr, RG
Bagiella, E
Cappola, AR
Bristow, MR
Johnson, C
Kronmal, RA
Kizer, JR
Lima, JAC
Kawut, SM
AF Ventetuolo, Corey E.
Ouyang, Pamela
Bluemke, David A.
Tandri, Harikrishna
Barr, R. Graham
Bagiella, Emilia
Cappola, Anne R.
Bristow, Michael R.
Johnson, Craig
Kronmal, Richard A.
Kizer, Jorge R.
Lima, Joao A. C.
Kawut, Steven M.
TI Sex Hormones Are Associated with Right Ventricular Structure and
Function The MESA-Right Ventricle Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE sex; sex hormones; right ventricle
ID PULMONARY ARTERIAL-HYPERTENSION; AIR-FLOW OBSTRUCTION; HEART-FAILURE;
CARDIOVASCULAR HEALTH; MAGNETIC-RESONANCE; POSTMENOPAUSAL WOMEN;
NITRIC-OXIDE; RISK-FACTORS; TESTOSTERONE; MEN
AB Rationale: Sex hormones have effects on the left ventricle, but hormonal influences on the right ventricle (RV) are unknown.
Objectives: We hypothesized that sex hormones would be associated with RV morphology in a large cohort free of cardiovascular disease.
Methods: Sex hormones were measured by immunoassay and RV ejection fraction (RVEF), stroke volume (RVSV), mass, end-diastolic volume, and end-systolic volume (RVESV) were measured by cardiac magnetic resonance imaging in 1,957 men and 1,738 postmenopausal women. The relationship between each hormone and RV parameter was assessed by multivariate linear regression.
Measurements and Main Results: Higher estradiol levels were associated with higher RVEF (13 per 1 In[nmol/L], 0.88; 95% confidence interval [CI], 0.32 to 1.43; P = 0.002) and lower RVESV (13 per 1 In[nmo1/1], -0.87; 95% CI, -1.67 to -0.08; P = 0.03) in women using hormone therapy. In men, higher bioavailable testosterone levels were associated with higher RVSV (beta per 1 In[nmol/L], 1.97; 95% CI, 0.20 to 3.73; P = 0.03) and greater RV mass and volumes 0.01). Higher dehydroepiandrosterone levels were associated with higher RVSV (beta per 1 In[nmol/L], 1.37; 95% CI, 0.15 to 2.59; P = 0.03) and greater RV mass (0 per 1 In[nmol/L], 0.25; 95% CI, 0.00 to 0.49; P = 0.05) and volumes (P <= 0.001) in women.
Conclusions: Higher estradiol levels were associated with better RV systolic function in women using hormone therapy. Higher levels of androgens were associated with greater RV mass and volumes in both sexes.
C1 [Cappola, Anne R.; Kawut, Steven M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Ventetuolo, Corey E.; Barr, R. Graham] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY USA.
[Ouyang, Pamela; Tandri, Harikrishna; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA.
[Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Bagiella, Emilia] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
[Kawut, Steven M.] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Kawut, Steven M.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Bristow, Michael R.] Univ Colorado Denver, Anschutz Med Ctr, Dept Med, Aurora, CO USA.
[Johnson, Craig; Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
RP Kawut, SM (reprint author), Univ Penn, Sch Med, Dept Med, 711 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM kawut@mail.med.upenn.edu
RI bristow, michael/G-7850-2011;
OI Ventetuolo, Corey /0000-0002-4223-4775; Bluemke,
David/0000-0002-8323-8086
FU National Institutes of Health [R01-HL086719, R01-HL074406, RO1-HL074338,
R01-HL077612, N01-HC95159, N01-HC95169]; SWHR-ISIS; BMS; EPA; NHLBI/NIH;
Gilead; Novartis; Bayer; Pfizer; Actelion; United Therapeutics; Lung Rx;
Merck; American Lung Association
FX Supported by National Institutes of Health R01-HL086719, R01-HL074406,
RO1-HL074338, R01-HL077612, and N01-HC95159 through N01-HC95169.; C.E.V.
does not have a financial relationship with a commercial entity that has
an interest in the subject of this manuscript. P.O. received
$1,000$5,000 from the SWHR-ISIS Fund for serving on a scientific
advisory group to develop research projects in areas of need for
research into sex differences in CVD, $50,00 l -$100,000 from BMS in
industry-sponsored grants as an investigator in a multicenter trial, and
more than $100,001 in NIH grants for investigator-sponsored studies and
cohort studies. DAB. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. H.T. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. R.G.B. received more than $100,001 from the NIH and more
than $100,001 from the EPA in sponsored grants. E.B. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. A.R.C. received more than $100,001 from
the NIH in grant funding; M.R.B does not have a financial relationship
with a commercial entity that has an interest in the subject of this
manuscript. C.J. received more than $100,001 from the NHLBI/NIH in
sponsored grants as an NHLBI contract (MESA). R.A.K. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. J.R.K. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. J.A.C.L. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. S.M.K. received $1,001-$5,000 from Gilead
and $1,001-$5,000 from Novartis in consultancy fees, $1,001-$5,000 from
Bayer, and $1,001$5,000 from Gilead for serving on an advisory board,
$10,001-$50,000 from Gilead for serving on steering committees,
$10,001-$50,000 from Gilead and $10,001-$50,000 from Pfizer for serving
on a grant review committee, $1,001$5,000 from Gilead and $1,001-$5,000
from Actelion in nonpromotional lecture fees, $10,001-$50,000 from
Actelion, $10,001-$50,000 from Gilead, $10,001$50,000 from United
Therapeutics, $10,001-$50,000 from Lung Rx, and $10,001-$50,000 from
Pfizer in industry-sponsored grants as conference support,
$50,001-$100,000 from Pfizer as a collaborator on an institutional
grant, has received gratis study drugs from Merck and Bayer for an
NIH-funded grant, $50,001-$100,000 from Actelion and $50,001-$100,000
from Gilead for contracted research, more than $100,001 from the NIH,
and $1,001-$5,000 from the American Lung Association and up to $1,000
from the NIH for serving on review committees.
NR 49
TC 49
Z9 50
U1 2
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 1
PY 2011
VL 183
IS 5
BP 659
EP 667
DI 10.1164/rccm.201007-1027OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 733WU
UT WOS:000288296000019
PM 20889903
ER
PT J
AU Troendle, JF
Mills, JL
AF Troendle, James F.
Mills, James L.
TI Correction for Multiplicity in Genetic Association Studies of Triads:
The Permutational TDT
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Exchangeable; familywise error rate; linkage disequilibrium; power
ID POPULATION
AB P>New technology for large-scale genotyping has created new challenges for statistical analysis. Correcting for multiple comparison without discarding true positive results and extending methods to triad studies are among the important problems facing statisticians. We present a one-sample permutation test for testing transmission disequilibrium hypotheses in triad studies, and show how this test can be used for multiple single nucleotide polymorphism (SNP) testing. The resulting multiple comparison procedure is shown in the case of the transmission disequilibrium test to control the familywise error. Furthermore, this procedure can handle multiple possible modes of risk inheritance per SNP. The resulting permutational procedure is shown through simulation of SNP data to be more powerful than the Bonferroni procedure when the SNPs are in linkage disequilibrium. Moreover, permutations implicitly avoid any multiple comparison correction penalties when the SNP has a rare allele. The method is illustrated by analyzing a large candidate gene study of neural tube defects and an independent study of oral clefts, where the smallest adjusted p-values using the permutation procedure are approximately half those of the Bonferroni procedure. We conclude that permutation tests are more powerful for identifying disease-associated SNPs in candidate gene studies and are useful for analysis of triad studies.
C1 [Troendle, James F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD 20892 USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH DHHS, Bethesda, MD 20892 USA.
RP Troendle, JF (reprint author), NHLBI, Off Biostat Res, NIH, DHHS, Bld Rockledge 2,Room 9195, Bethesda, MD 20892 USA.
EM jt3t@nih.gov
FU NIH, NICHD
FX This research was supported in part by the Intramural Research Program
of the NIH, NICHD. We thank Dr. Lawrence Brody for his insightful
advice.
NR 9
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD MAR
PY 2011
VL 75
BP 284
EP 291
DI 10.1111/j.1469-1809.2010.00626.x
PN 2
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 719YJ
UT WOS:000287247100009
PM 21108625
ER
PT J
AU Chibnik, LB
Shulman, JM
Leurgans, SE
Schneider, JA
Wilson, RS
Tran, D
Aubin, C
Buchman, AS
Heward, CB
Myers, AJ
Hardy, JA
Huentelman, MJ
Corneveaux, JJ
Reiman, EM
Evans, DA
Bennett, DA
De Jager, PL
AF Chibnik, Lori B.
Shulman, Joshua M.
Leurgans, Sue E.
Schneider, Julie A.
Wilson, Robert S.
Tran, Dong
Aubin, Cristin
Buchman, Aron S.
Heward, Christopher B.
Myers, Amanda J.
Hardy, John A.
Huentelman, Matthew J.
Corneveaux, Jason J.
Reiman, Eric M.
Evans, Denis A.
Bennett, David A.
De Jager, Philip L.
TI CR1 Is Associated with Amyloid Plaque Burden and Age-Related Cognitive
Decline
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ALZHEIMER-DISEASE PATHOLOGY; OLDER PERSONS;
CEREBRAL INFARCTIONS; IDENTIFIES VARIANTS; IMPAIRMENT; COHORT; CLU;
CONSORTIUM; ESTABLISH
AB Objective: Recently, genome-wide association studies have identified 3 new susceptibility loci for Alzheimer's disease (AD), CLU, CR1, and PICALM. We leveraged available neuropsychological and autopsy data from 2 cohort studies to investigate whether these loci are associated with cognitive decline and AD neuropathology.
Methods: The Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP) are longitudinal studies that enroll nondemented subjects and include annual clinical evaluations and brain donation at death. We evaluated CR1 (rs6656401), CLU (rs11136000), and PICALM (rs7110631) in 1,666 subjects. We evaluated associations between genotypes and rate of change in cognitive function as well as AD-related pathology. Lastly, we used pathway analysis to determine whether relationships between single nucleotide polymorphisms and cognitive decline are mediated through AD pathology.
Results: Among our study cohort, the mean years of follow-up were 7.8 for ROS and 4.3 for MAP. Only the CR1 locus was associated with both global cognitive decline (p = 0.011) and global AD pathology (p = 0.025). More specifically, the locus affects the deposition of neuritic amyloid plaque (p = 0.009). In a mediation analysis, controlling for amyloid pathology strongly attenuated the effect of the CR1 locus on cognitive decline.
Interpretation: We found that common variation at the CR1 locus has a broad impact on cognition and generalize the role of this locus to cognitive aging in the general population. ANN NEUROL 2011;69:560-569
C1 [Chibnik, Lori B.; Shulman, Joshua M.; Tran, Dong; Aubin, Cristin; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA.
[Chibnik, Lori B.; Shulman, Joshua M.; Tran, Dong; Aubin, Cristin; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Leurgans, Sue E.; Schneider, Julie A.; Wilson, Robert S.; Buchman, Aron S.; Evans, Denis A.; Bennett, David A.] Rush Alzheimers Dis Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA.
[Heward, Christopher B.] Kronos Sci Lab, Phoenix, AZ USA.
[Myers, Amanda J.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA.
[Myers, Amanda J.] Johnnie B Byrd Sr Alzheimers Ctr & Res Inst, Tampa, FL USA.
[Hardy, John A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Hardy, John A.] Inst Neurol, Dept Mol Neurosci, Reta Lila Weston Labs, London WC1N 3BG, England.
[Huentelman, Matthew J.; Corneveaux, Jason J.; Reiman, Eric M.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA.
[Huentelman, Matthew J.; Corneveaux, Jason J.; Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA.
[Reiman, Eric M.] Univ Arizona, Banner Alzheimers Inst, Phoenix, AZ USA.
[Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ USA.
[Reiman, Eric M.] Univ Arizona, Dept Psychiat, Tucson, AZ USA.
[Shulman, Joshua M.] Harvard MIT Hlth Sci & Technol, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program, Chicago, IL USA.
RP De Jager, PL (reprint author), Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, 77 Ave Louis Pasteur,NRB 168C, Boston, MA 02115 USA.
EM pdejager@rics.bwh.harvard.edu
RI Hardy, John/C-2451-2009; Myers, Amanda/B-1796-2010
OI Myers, Amanda/0000-0002-3100-9396
FU National Institutes of Health (NIH) [R01 AG30146, R01 AG179917, R01
AG15819, P30 AG10161, K08 AG034290, R01 NS059873]; NIH Neuroscience
Blueprint [U24NS051872]; ENDGAME Consortium [UO1HL084744]; National
Institute on Aging (University of California, Irvine) [P50 AG23173];
National Institute on Aging [K01AG024079, R01 AG034504]; state of
Arizona; Kronos Life Sciences Laboratories; National Institute on Aging
(Arizona Alzhei-mer's Disease Center) [P30 AG19610, RO1 AG023193];
National Institute on Aging (Mayo Clinic Alzheimer's Disease Center)
[P50 AG16574]; National Alzheimer's Coordinating Center [U01 AG016976]
FX This work was supported by National Institutes of Health (NIH) grants
R01 AG30146, R01 AG179917, R01 AG15819, P30 AG10161, K08 AG034290, and
R01 NS059873. Additional funding was obtained from the NIH Neuroscience
Blueprint (U24NS051872), the ENDGAME Consortium (UO1HL084744), a
National Institute on Aging grant to Carl Cotman (University of
California, Irvine, P50 AG23173), National Institute on Aging
(K01AG024079), and the state of Arizona.; A.J.M. is supported by
National Institute on Aging grant R01 AG034504 and the Johnnie B. Byrd
Institute. J.A.H. has done consultancy work for and received honoraria
from Eisai and MerkSerono, and would like to thank the Verum foundation.
M.J.H., J.J.C., and E. M. R. are supported by grants from Kronos Life
Sciences Laboratories, the National Institute on Aging (Arizona
Alzhei-mer's Disease Center P30 AG19610, RO1 AG023193, Mayo Clinic
Alzheimer's Disease Center P50 AG16574, and Intramural Research
Program), the National Alzheimer's Coordinating Center (U01 AG016976),
and the state of Arizona. J.M.S. is a participant in the Clinical
Investigator Training Program, a fellowship administered by Beth Israel
Deaconess Medical Center-Harvard/Massachusetts Institute of Technology
Health Sciences and Technology, in collaboration with Pfizer Inc. and
Merck & Co. J.A.S. has done consultancy work for AVID
Radiopharmaceuticals, has provided expert testimony for Spina, McGuire,
& Okal, PC and Michael Best & Friedrich LLP, and has received payment
for manuscript preparation from BMJ Publishing Group, Limited. P.L.D.J.
has received honoraria from Biogen IDEC. R. S. W., C. B. H., and D. A.
B. work for Kronos Life Sciences Laboratories.
NR 35
TC 75
Z9 76
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2011
VL 69
IS 3
BP 560
EP 569
DI 10.1002/ana.22277
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 744FW
UT WOS:000289081300019
PM 21391232
ER
PT J
AU Shi, M
Bradner, J
Hancock, AM
Chung, KA
Quinn, JF
Peskind, ER
Galasko, D
Jankovic, J
Zabetian, CP
Kim, HM
Leverenz, JB
Montine, TJ
Ginghina, C
Kang, UJ
Cain, KC
Wang, Y
Aasly, J
Goldstein, D
Zhang, J
AF Shi, Min
Bradner, Joshua
Hancock, Aneeka M.
Chung, Kathryn A.
Quinn, Joseph F.
Peskind, Elaine R.
Galasko, Douglas
Jankovic, Joseph
Zabetian, Cyrus P.
Kim, Hojoong M.
Leverenz, James B.
Montine, Thomas J.
Ginghina, Carmen
Kang, Un Jung
Cain, Kevin C.
Wang, Yu
Aasly, Jan
Goldstein, David
Zhang, Jing
TI Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and
Progression
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID MULTIPLE SYSTEM ATROPHY; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN;
TAU-PROTEIN; FRACTALKINE-RECEPTOR; LEWY BODIES; CSF; DEMENTIA;
INFLAMMATION; MICROGLIA
AB Objective: There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of Parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or alpha-synuclein in the cerebrospinal fluid (CSF) is a potential index for Parkinson disease diagnosis, but not for PD severity.
Methods: Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (A beta(1-42)), Flt3 ligand, and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these 5 markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and alpha-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally.
Results: The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease (AD) and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/A beta(1-42) that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples.
Interpretation: We have demonstrated that this panel of 7 CSF proteins could aid in Parkinson disease diagnosis, differential diagnosis, and correlation with disease severity and progression. ANN NEUROL 2011;69:570-580
C1 [Shi, Min; Bradner, Joshua; Hancock, Aneeka M.; Montine, Thomas J.; Ginghina, Carmen; Wang, Yu; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
[Peskind, Elaine R.; Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA.
[Zabetian, Cyrus P.; Kim, Hojoong M.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA.
[Cain, Kevin C.] Univ Washington, Sch Med, Dept Biostat, Seattle, WA 98104 USA.
[Chung, Kathryn A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Peskind, Elaine R.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Zabetian, Cyrus P.; Kim, Hojoong M.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA.
[Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Houston, TX 77030 USA.
[Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA.
[Kang, Un Jung] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA.
[Wang, Yu] Huazhong Univ Sci & Technol, Dept Neurosurg, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China.
[Aasly, Jan] St Olavs Hosp, Dept Neurol, Trondheim, Norway.
[Goldstein, David] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA.
RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA.
EM zhangj@uw.edu
RI Shi, Min/G-6165-2012;
OI Shi, Min/0000-0002-6901-2558; Zabetian, Cyrus/0000-0002-7739-4306
FU NIH [NIEHS] [ES004696]; NIH [NINDS] [NS057567, NS060252, NS062684]; NIH
[NIA] [AG025327, AG033398, AG005136, AG008017]; NIH [NCRR]
[UL1RR025014]; Dana Foundation; Parkinson's Disease Foundation; Michael
J. Fox Foundation; Friends of Alzheimer's Research; Alzheimer's
Association of Western and Central Washington; Department of Veterans
Affairs; NIH; Oregon Health and Science Univeristy; American Parkinson
Disease Association; Alzheimer's center, NIH; Center of Excellence of
the National Parkinson Foundation; Michael J Fox Foundation
FX This research was supported by the NIH [ES004696 (J.Z.) from NIEHS,
NS057567 (J.Z.), NS060252 (J.Z.), NS062684 (T.J.M., C.P.Z., J.B.L. and
J.Z.) from NINDS, AG025327 (J.Z.), AG033398 (J.Z.), AG005136 (E. R. P
and T.J.M.), AG008017 (K. A. C. and J.F.Q.) from NIA and UL1RR025014 (K.
C. C) from NCRR]; Dana Foundation (J.F.Q.); Parkinson's Disease
Foundation (C.P.Z.); Michael J. Fox Foundation (C.P.Z. and J.Z.);
Friends of Alzheimer's Research (E. R. P.); Alzheimer's Association of
Western and Central Washington (E. R. P.); Department of Veterans
Affairs (C.P.Z. and E. R. P.).; K. C. C. and J.Z. received grant(s) from
the NIH. A. M. H., C. G., J. B. and M. S. were supported by the NIH
grants. K. A. C. received grant(s) from the Oregon Health and Science
Univeristy; C.P.Z. received grants from The American Parkinson Disease
Association, Department of Veterans Affairs, Michael J. Fox Foundation,
NIH, and The Parkinson's Disease Foundation. J. F. Q. received an
Alzheimer's center grant from the NIH. J. J. has grant(s) pending from
the Center of Excellence of the National Parkinson Foundation. T. J. M.
received grant funding and has grant(s) pending from the NIH. U. J. K.
has been a consultant for CVS/caremark and has grants pending from the
Michael J Fox Foundation and the NIH. All other authors had nothing to
report.
NR 54
TC 168
Z9 175
U1 4
U2 23
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2011
VL 69
IS 3
BP 570
EP 580
DI 10.1002/ana.22311
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 744FW
UT WOS:000289081300020
PM 21400565
ER
PT J
AU Bulger, EM
May, S
Kerby, JD
Emerson, S
Stiell, IG
Schreiber, MA
Brasel, KJ
Tisherman, SA
Coimbra, R
Rizoli, S
Minei, JP
Hata, JS
Sopko, G
Evans, DC
Hoyt, DB
AF Bulger, Eileen M.
May, Susanne
Kerby, Jeffery D.
Emerson, Scott
Stiell, Ian G.
Schreiber, Martin A.
Brasel, Karen J.
Tisherman, Samuel A.
Coimbra, Raul
Rizoli, Sandro
Minei, Joseph P.
Hata, J. Steven
Sopko, George
Evans, David C.
Hoyt, David B.
CA ROC Investigators
TI Out-of-hospital Hypertonic Resuscitation After Traumatic Hypovolemic
Shock A Randomized, Placebo Controlled Trial
SO ANNALS OF SURGERY
LA English
DT Article
ID UNCONTROLLED HEMORRHAGIC-SHOCK; 7.5-PERCENT SODIUM-CHLORIDE; IMPACT
MANAGEMENT ERRORS; SALINE-DEXTRAN; FLUID RESUSCITATION; NEUTROPHIL
ACTIVATION; CONSENSUS CONFERENCE; OUTCOMES CONSORTIUM; MULTICENTER
TRIAL; INJURED PATIENTS
AB Objective: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock.
Background: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury.
Methods: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age >= 15 years with hypovolemic shock (systolic blood pressure <= 70 mm Hg or systolic blood pressure 71-90 mm Hg with heart rate >= 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern.
Results: A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95% confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10% (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P < 0.01].
Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial.
C1 [Bulger, Eileen M.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA.
[Bulger, Eileen M.; May, Susanne; Emerson, Scott] Univ Washington, Dept Biostat, Seattle, WA 98104 USA.
[Kerby, Jeffery D.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA.
[Stiell, Ian G.] Univ Ottawa, Dept Emergency Med, Ottawa, ON, Canada.
[Schreiber, Martin A.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA.
[Brasel, Karen J.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA.
[Tisherman, Samuel A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
[Coimbra, Raul] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA.
[Rizoli, Sandro] Univ Toronto, Dept Surg, Toronto, ON, Canada.
[Minei, Joseph P.] Univ Texas SW Dept Surg, Dallas, TX USA.
[Hata, J. Steven] Univ Iowa, Iowa City, IA USA.
[Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA.
[Evans, David C.] Vancouver Gen Hosp, Dept Surg, Vancouver, BC, Canada.
[Hoyt, David B.] Amer Coll Surg, Chicago, IL USA.
RP Bulger, EM (reprint author), Univ Washington, Harborview Med Ctr, Dept Surg, Box 359796,325 9th Ave, Seattle, WA 98104 USA.
EM ebulger@u.washington.edu
OI Callaway, Clifton/0000-0002-3309-1573; Idris,
Ahamed/0000-0001-7113-6499; Stiell, Ian/0000-0002-2583-6408; Welsford,
Michelle/0000-0003-2682-641X; Gabriel, Erin/0000-0002-0504-8404
FU National Heart, Lung and Blood Institute [5U01 HL077863, HL077881,
HL077871, HL077872, HL077866, HL077908, HL077867, HL077885, HL077887,
HL077873, HL077865]; National Institute of Neurological Disorders and
Stroke; US Army Medical Research & Material Command; The Canadian
Institutes of Health Research-Institute of Circulatory and Respiratory
Health; Defence Research and Development Canada; Heart and Stroke
Foundation of Canada
FX The Resuscitation Outcome Consortium is supported by a series of
cooperative agreements with 10 regional clinical centers and 1 data
coordinating center (5U01 HL077863, HL077881, HL077871 HL077872,
HL077866, HL077908, HL077867, HL077885, HL077887, HL077873, HL077865)
from the National Heart, Lung and Blood Institute in partnership with
the National Institute of Neurological Disorders and Stroke, US Army
Medical Research & Material Command, The Canadian Institutes of Health
Research-Institute of Circulatory and Respiratory Health, Defence
Research and Development Canada, and the Heart and Stroke Foundation of
Canada.
NR 53
TC 106
Z9 116
U1 2
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD MAR
PY 2011
VL 253
IS 3
BP 431
EP 441
DI 10.1097/SLA.0b013e3181fcdb22
PG 11
WC Surgery
SC Surgery
GA 719VF
UT WOS:000287238900001
PM 21178763
ER
PT J
AU Dufour, F
Sasseville, AMJ
Chabaud, S
Massie, B
Siegel, RM
Langelier, Y
AF Dufour, Florent
Sasseville, A. Marie-Josee
Chabaud, Stephane
Massie, Bernard
Siegel, Richard M.
Langelier, Yves
TI The ribonucleotide reductase R1 subunits of herpes simplex virus types 1
and 2 protect cells against TNF alpha- and FasL-induced apoptosis by
interacting with caspase-8
SO APOPTOSIS
LA English
DT Article
DE FasL; ICP6; ICP10; Viral inhibitor of apoptosis; Caspase-8
ID FLICE-INHIBITORY PROTEIN; NECROSIS-FACTOR-ALPHA; SIGNALING COMPLEX;
DEATH DOMAIN; TRIGGERED APOPTOSIS; MEDIATED APOPTOSIS; BLOCKS APOPTOSIS;
UP-REGULATION; IN-VITRO; ACTIVATION
AB We previously reported that HSV-2 R1, the R1 subunit (ICP10; UL39) of herpes simplex virus type-2 ribonucleotide reductase, protects cells against apoptosis induced by the death receptor (DR) ligands tumor necrosis factor-alpha- (TNF alpha) and Fas ligand (FasL) by interrupting DR-mediated signaling at, or upstream of, caspase-8 activation. Further investigation of the molecular mechanism underlying HSV-2 R1 protection showed that extracellular-regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3-K)/Akt, NF-kappa B and JNK survival pathways do not play a major role in this antiapoptotic function. Interaction studies revealed that HSV-2 R1 interacted constitutively with caspase-8. The HSV-2 R1 deletion mutant R1(1-834)-GFP and Epstein-Barr virus (EBV) R1, which did not protect against apoptosis induced by DR ligands, did not interact with caspase-8, indicating that interaction is required for protection. HSV-2 R1 impaired caspase-8 activation induced by caspase-8 over-expression, suggesting that interaction between the two proteins prevents caspase-8 dimerization/activation. HSV-2 R1 bound to caspase-8 directly through its prodomain but did not interact with either its caspase domain or Fas-associated death domain protein (FADD). Interaction between HSV-2 R1 and caspase-8 disrupted FADD-caspase-8 binding. We further demonstrated that individually expressed HSV-1 R1 (ICP6) shares, with HSV-2 R1, the ability to bind caspase-8 and to protect cells against DR-induced apoptosis. Finally, as the long-lived Fas protein remained stable during the early period of infection, experiments with the HSV-1 UL39 deletion mutant ICP6a dagger showed that HSV-1 R1 could be essential for the protection of HSV-1-infected cells against FasL.
C1 [Dufour, Florent; Sasseville, A. Marie-Josee; Chabaud, Stephane; Langelier, Yves] Ctr Hosp Univ Montreal CRCHUM, Ctr Rech, Montreal, PQ H2L 4M1, Canada.
[Dufour, Florent; Sasseville, A. Marie-Josee; Chabaud, Stephane; Langelier, Yves] Univ Montreal, Inst Canc Montreal, Hop Notre Dame, Montreal, PQ H2L 4M1, Canada.
[Massie, Bernard; Langelier, Yves] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada.
[Massie, Bernard] Inst Rech Biotechnol, Montreal, PQ, Canada.
[Massie, Bernard] Univ Quebec, Inst Armand Frappier, Inst Natl Rech Sci, Laval, PQ, Canada.
[Siegel, Richard M.] NIAMSD, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Langelier, Yves] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
RP Langelier, Y (reprint author), Ctr Hosp Univ Montreal CRCHUM, Ctr Rech, 1560 Sherbrooke Est, Montreal, PQ H2L 4M1, Canada.
EM yves.langelier@umontreal.ca
FU Canadian Institutes of Health [67052]
FX This work was supported by Canadian Institutes of Health Research Grant
NRF # 67052. We thank Angela Pearson, Andrew D. Badley, Marcus E. Peter
and Joseph S. Pagano for their kind gifts of plasmids and antibodies,
Sandra Weller for the generous donation of ICP6 Delta, Pascal Schneider
for its kind gift of Fc: FasL, and W. Edward C. Bradley as well as
Richard Bertrand for critical manuscript editing. This is National
Research Council of Canada publication No. 52767.
NR 71
TC 24
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U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
J9 APOPTOSIS
JI Apoptosis
PD MAR
PY 2011
VL 16
IS 3
BP 256
EP 271
DI 10.1007/s10495-010-0560-2
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 726TC
UT WOS:000287748100005
PM 21107701
ER
PT J
AU Brooks, S
Linehan, WM
Srinivasan, R
Kong, HH
AF Brooks, Sara
Linehan, W. Marston
Srinivasan, Ramaprasad
Kong, Heidi H.
TI Successful Laser Treatment of Vandetanib-Associated Cutaneous
Pigmentation
SO ARCHIVES OF DERMATOLOGY
LA English
DT Letter
ID MINOCYCLINE-INDUCED HYPERPIGMENTATION; SWITCHED ALEXANDRITE LASER
C1 [Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Brooks, Sara] Georgetown Univ Hosp, Washington Hosp Ctr, Dermatol Program, Washington, DC 20007 USA.
[Linehan, W. Marston; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 12N238, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov
OI Kong, Heidi/0000-0003-4424-064X
FU Intramural NIH HHS [Z01 BC011023-01, Z01 BC010940-01]; NCI NIH HHS [Z01
BC011023-01, Z01 BC011028-01, Z01 BC011038-01, Z01 BC011089-01, Z01
BC011092-01]
NR 4
TC 2
Z9 2
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAR
PY 2011
VL 147
IS 3
BP 364
EP 365
PG 3
WC Dermatology
SC Dermatology
GA 738AH
UT WOS:000288611200028
PM 21422355
ER
PT J
AU Merikangas, KR
Jin, R
He, JP
Kessler, RC
Lee, S
Sampson, NA
Viana, MC
Andrade, LH
Hu, CY
Karam, EG
Ladea, M
Medina-Mora, ME
Ono, Y
Posada-Villa, J
Sagar, R
Wells, JE
Zarkov, Z
AF Merikangas, Kathleen R.
Jin, Robert
He, Jian-Ping
Kessler, Ronald C.
Lee, Sing
Sampson, Nancy A.
Viana, Maria Carmen
Andrade, Laura Helena
Hu, Chiyi
Karam, Elie G.
Ladea, Maria
Medina-Mora, Maria Elena
Ono, Yutaka
Posada-Villa, Jose
Sagar, Rajesh
Wells, J. Elisabeth
Zarkov, Zahari
TI Prevalence and Correlates of Bipolar Spectrum Disorder in the World
Mental Health Survey Initiative
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID COMORBIDITY SURVEY REPLICATION; MAJOR DEPRESSIVE DISORDER; SUBSTANCE USE
DISORDERS; SUBTHRESHOLD BIPOLARITY; 12-MONTH PREVALENCE; RATING-SCALE; I
DISORDER; EPIDEMIOLOGY; DISABILITY; VALIDITY
AB Context: There is limited information on the prevalence and correlates of bipolar spectrum disorder in international population-based studies using common methods.
Objectives: To describe the prevalence, impact, patterns of comorbidity, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative.
Design, Setting, and Participants: Crosssectional, face-to-face, household surveys of 61 392 community adults in 11 countries in the Americas, Europe, and Asia assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3.0, a fully structured, lay-administered psychiatric diagnostic interview.
Main Outcome Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) disorders, severity, and treatment.
Results: The aggregate lifetime prevalences were 0.6% for bipolar type I disorder (BP-I), 0.4% for BP-II, 1.4% for subthreshold BP, and 2.4% for BPS. Twelve-month prevalences were 0.4% for BP-I, 0.3% for BP-II, 0.8% for subthreshold BP, and 1.5% for BPS. Severity of both manic and depressive symptoms as well as suicidal behavior increased monotonically from subthreshold BP to BP-I. By contrast, role impairment was similar across BP subtypes. Symptom severity was greater for depressive episodes than manic episodes, with approximately 74.0% of respondents with depression and 50.9% of respondents with mania reporting severe role impairment. Three-quarters of those with BPS met criteria for at least 1 other disorder, with anxiety disorders (particularly panic attacks) being the most common comorbid condition. Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2% reported contact with the mental health system.
Conclusions: Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries.
C1 [Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[Jin, Robert; Kessler, Ronald C.; Sampson, Nancy A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Lee, Sing] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Psychiat, Shatin, Hong Kong, Peoples R China.
[Hu, Chiyi] Shenzhen Inst Mental Hlth, Shenzhen, Peoples R China.
[Hu, Chiyi] Shenzhen Kangning Hosp, Shenzhen, Peoples R China.
[Viana, Maria Carmen; Andrade, Laura Helena] Univ Sao Paulo, Sch Med, Sect Psychiat Epidemiol, Sao Paulo, Brazil.
[Andrade, Laura Helena] Univ Sao Paulo, Sch Med, Lab Med Invest 23, Inst Psychiat, Sao Paulo, Brazil.
[Karam, Elie G.] Balamand Univ, St George Hosp Univ Med Ctr, Inst Dev Res Advocacy & Appl Care, Med Inst Neuropsychol Disorders,Fac Med, Beirut, Lebanon.
[Ladea, Maria] Univ Med & Pharm Carol Davila, Dept Psychiat, Bucharest, Romania.
[Medina-Mora, Maria Elena] Natl Inst Psychiat, Mexico City, DF, Mexico.
[Ono, Yutaka] Keio Univ, Ctr Hlth, Yokohama, Kanagawa 223, Japan.
[Posada-Villa, Jose] Colegio Mayor Cundinamarca Univ, Bogota, Colombia.
[Sagar, Rajesh] All India Inst Med Sci, Dept Psychiat, Delhi, India.
[Wells, J. Elisabeth] Christchurch Sch Med & Hlth Sci, Christchurch, New Zealand.
[Zarkov, Zahari] Directorate Mental Hlth, Natl Ctr Publ Hlth Protect, Sofia, Bulgaria.
RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Bldg 35,Room 1A201,35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
RI Lee, Sing/O-2136-2015; Andrade, Laura Helena/F-3023-2010;
OI Andrade, Laura Helena/0000-0002-2362-3521; Viana, Maria
Carmen/0000-0002-0464-4845
FU Bristol-Myers Squibb; Eli Lilly and Co; GlaxoSmithKline; Johnson and
Johnson Pharmaceuticals; Ortho-McNeil Pharmaceutical; Pfizer;
Sanofi-Aventis; National Institute of Mental Health [R01MH070884,
U01-MH60220]; 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; Eli Lilly and Co Foundation; State of Sao
Paulo Research Foundation [03/00204-3]; Ministry of Health; National
Center for Public Health Protection; Shenzhen Bureau of Health; Shenzhen
Bureau of Science, Technology, and Information; Ministry of Social
Protection; World Health Organization (India); Japan Ministry of Health,
Labour and Welfare [H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013];
Lebanese Ministry of Public Health; World Health Organization (Lebanon);
Fogarty International; Janssen Cilag; Roche; Novartis; National
Institute of Psychiatry Ramon de la Fuente [4280]; National Council on
Science and Technology [CONACyT-G30544-H]; New Zealand Ministry of
Health; Alcohol Advisory Council; Health Research Council; Ministry of
Public Health (formerly the Ministry of Health); Robert Wood Johnson
Foundation [044708]; John W. Alden Trust
FX Drs Merikangas and He are with the Intramural Research Program of the
National Institute of Mental Health. Dr Kessler has been a consultant
for GlaxoSmithKline, Kaiser Permanente, Pfizer, Sanofi-Aventis, Shire
Pharmaceuticals, and Wyeth-Ayerst; has served on advisory boards for Eli
Lilly and Co and Wyeth-Ayerst; and has received research support for his
epidemiological studies from Bristol-Myers Squibb, Eli Lilly and Co,
GlaxoSmithKline, Johnson and Johnson Pharmaceuticals, Ortho-McNeil
Pharmaceutical, Pfizer, and Sanofi-Aventis.; This work was supported in
part by the Intramural Research Program of the National Institute of
Mental Health and was supported by grant R01MH070884 from the National
Institute of Mental Health, the John D. and Catherine T. MacArthur
Foundation, the Pfizer Foundation, grants R13-MH066849, R01-MH069864,
and R01 DA016558 from the US Public Health Service, grant FIRCA
R03-TW006481 from the Fogarty International Center, the Pan American
Health Organization, the Eli Lilly and Co Foundation, Ortho-McNeil
Pharmaceutical, GlaxoSmithKline, Sanofi-Aventis, and Bristol-Myers
Squibb. The Sao Paulo Megacity Mental Health Survey is supported by the
State of Sao Paulo Research Foundation Thematic Project Grant
03/00204-3. The Bulgarian Epidemiological Study of common mental
disorders is supported by the Ministry of Health and the National Center
for Public Health Protection. 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 is supported by the Ministry of Social Protection. World
Mental Health India was funded by the World Health Organization (India)
and helped by Dr R. Chandrasekaran, Jawaharlal Institute of Postgraduate
Medical Education and Research. The World Mental Health Japan Survey is
supported by Grants for Research on Psychiatric and Neurological
Diseases and Mental Health H13-SHOGAI-023, H14-TOKUBETSU-026, and
H16-KOKORO-013 from the Japan Ministry of Health, Labour and Welfare.
The Lebanese National Mental Health Survey is supported by the Lebanese
Ministry of Public Health, the World Health Organization (Lebanon),
Fogarty International, anonymous private donations to IDRAAC, Lebanon,
and unrestricted grants from Janssen Cilag, Eli Lilly and Co,
GlaxoSmithKline, Roche, and Novartis. The Mexican National Comorbidity
Survey is supported by grant INPRFMDIES 4280 from the National Institute
of Psychiatry Ramon de la Fuente and grant CONACyT-G30544-H from the
National Council on Science and Technology, with supplemental support
from the Pan American Health Organization. Te Rau Hinengaro: The New
Zealand Mental Health Survey is supported by the New Zealand Ministry of
Health, the Alcohol Advisory Council, and the Health Research Council.
The Romania WMH study projects "Policies in Mental Health Area" and
"National Study Regarding Mental Health and Services Use" were carried
out by the National School of Public Health and Health Services
Management (formerly the National Institute for Research and Development
in Health), received technical support from Metro Media Transilvania,
the National Institute of Statistics-National Centre for Training in
Statistics, SC Cheyenne Services SRL, and Statistics Netherlands, and
were funded by the Ministry of Public Health (formerly the Ministry of
Health), with supplemental support from Eli Lilly Romania SRL. The US
National Comorbidity Survey Replication is supported by grant
U01-MH60220 from the National Institute of Mental Health, with
supplemental support from the National Institute on Drug Abuse, the
Substance Abuse and Mental Health Services Administration, grant 044708
from the Robert Wood Johnson Foundation, and the John W. Alden Trust.
NR 43
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U1 11
U2 90
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 MAR
PY 2011
VL 68
IS 3
BP 241
EP 251
DI 10.1001/archgenpsychiatry.2011.12
PG 11
WC Psychiatry
SC Psychiatry
GA 731DQ
UT WOS:000288086900004
PM 21383262
ER
PT J
AU Alia-Klein, N
Parvaz, MA
Woicik, PA
Konova, AB
Maloney, T
Shumay, E
Wang, RL
Telang, F
Biegon, A
Wang, GJ
Fowler, JS
Tomasi, D
Volkow, ND
Goldstein, RZ
AF Alia-Klein, Nelly
Parvaz, Muhammad A.
Woicik, Patricia A.
Konova, Anna B.
Maloney, Thomas
Shumay, Elena
Wang, Ruiliang
Telang, Frank
Biegon, Anat
Wang, Gene-Jack
Fowler, Joanna S.
Tomasi, Dardo
Volkow, Nora D.
Goldstein, Rita Z.
TI Gene x Disease Interaction on Orbitofrontal Gray Matter in Cocaine
Addiction
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID VOXEL-BASED MORPHOMETRY; MONOAMINE-OXIDASE-A; SUBSTANCE-DEPENDENT
INDIVIDUALS; MAOA PROMOTER POLYMORPHISM; ORBITAL PREFRONTAL CORTEX;
DECISION-MAKING; USE DISORDERS; DRUG-ABUSE; HIPPOCAMPAL VOLUME; DOPAMINE
DEPLETION
AB Context: Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability.
Objective: To examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls.
Design: Cross-sectional comparison.
Setting: Clinical Research Center at Brookhaven National Laboratory.
Patients: Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high-and low-repeat alleles).
Main Outcome Measures: The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis x MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors.
Results: (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls. (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low-MAOA genotype and by lifetime cocaine use. (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables.
Conclusions: Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.
C1 [Alia-Klein, Nelly; Parvaz, Muhammad A.; Woicik, Patricia A.; Konova, Anna B.; Maloney, Thomas; Shumay, Elena; Wang, Ruiliang; Biegon, Anat; Wang, Gene-Jack; Fowler, Joanna S.; Goldstein, Rita Z.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Parvaz, Muhammad A.] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY USA.
[Konova, Anna B.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA.
[Wang, Gene-Jack; Fowler, Joanna S.] Mt Sinai Sch Med, New York, NY USA.
[Telang, Frank; Tomasi, Dardo] Natl Inst Alcohol & Alcoholism, Bethesda, MD USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA.
RP Alia-Klein, N (reprint author), Brookhaven Natl Lab, Dept Med, Med 490, Upton, NY 11973 USA.
EM nellyklein@bnl.gov
RI Tomasi, Dardo/J-2127-2015;
OI Parvaz, Muhammad/0000-0002-2671-2327
FU US Department of Energy [DE-AC-298CH10886]; National Institute on Drug
Abuse [R01DA023579, R21DA02062]; National Institute on Alcohol Abuse and
Alcoholism [2R01AA09481]; National Association for Research on
Schizophrenia and Depression
FX This research was conducted at Brookhaven National Laboratory under
contract DE-AC-298CH10886 with the US Department of Energy with
infrastructure support from its Office of Biological and Environmental
Research, and by the National Institute on Drug Abuse (R01DA023579,
R21DA02062), the National Institute on Alcohol Abuse and Alcoholism
(2R01AA09481), and the National Association for Research on
Schizophrenia and Depression.
NR 107
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U1 3
U2 10
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 MAR
PY 2011
VL 68
IS 3
BP 283
EP 294
DI 10.1001/archgenpsychiatry.2011.10
PG 12
WC Psychiatry
SC Psychiatry
GA 731DQ
UT WOS:000288086900008
PM 21383264
ER
PT J
AU He, JY
Xu, XY
Francisco, A
Ferrante, A
Krakoff, J
AF He, Jianying
Xu, Xiaoyuan
Francisco, Ann
Ferrante, Anthony
Krakoff, Jonathan
TI Markers of adipose tissue macrophage content are negatively associated
with serum HDL-C concentrations
SO ATHEROSCLEROSIS
LA English
DT Article
DE Abdonimal subcutaneous adipose; Macrophage content; HDL-C
ID LIPOPROTEIN CHOLESTEROL; OBESITY; ACCUMULATION; ENDOTOXIN; ABCA1
AB Objective: Adipose tissue macrophages are associated with adiposity and may play a role in obesity related co-morbidities. We examined whether abdominal subcutaneous adipose tissue macrophage content (ATMc) was associated with fasting serum total cholesterol (TC), high density lipoprotein (HDL-C) and triglycerides (TG) concentrations.
Methods: 52 (35 male) of Pima Indians without diabetes participated in the study. ATMc was assessed by histochemistry (CD68+ cells) (Mphi) and gene expression of macrophage-specific markers including CD68, CSF1r, CD11b and CD11c.
Results: HDL-C was negatively associated with CD68, CSF1R, CD11b and CD11c expression (r = -0.31, p = 0.02; r = -0.38, p < 0.01; r = -0.40, p < 0.01; r = -0.26, p = 0.04, respectively). After adjustment for age, sex and BMI, the associations between HDL-C and CSF1R, CD11b were still significant (r = -0.31, p = 0.01 and r = -0.3, p = 0.02), but borderline for CD68 (r = -0.24, p = 0.06).
Conclusions: ATMc is associated with lower HDL-C independent of BMI indicating a link between ATMc and cardiovascular risk factors. Published by Elsevier Ireland Ltd.
C1 [He, Jianying; Krakoff, Jonathan] NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Dept Hlth & Human Serv, Phoenix, AZ 85016 USA.
[Xu, Xiaoyuan; Francisco, Ann; Ferrante, Anthony] Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10032 USA.
RP He, JY (reprint author), 4212 N 16th St,Rm 5-35, Phoenix, AZ 85016 USA.
EM hejianying@mail.nih.gov
FU NIDDK; Columbia University Diabetes & Endocrinology Research Center
FX The study was approved and funded via the NIDDK intramural research
program and extramural program through the Columbia University Diabetes
& Endocrinology Research Center.
NR 15
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAR
PY 2011
VL 215
IS 1
BP 243
EP 246
DI 10.1016/j.atherosclerosis.2010.12.018
PG 4
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 730CN
UT WOS:000288008700038
PM 21227423
ER
PT J
AU Shimshoni, JA
Basselin, M
Li, LO
Coleman, RA
Rapoport, SI
Modi, HR
AF Shimshoni, Jakob A.
Basselin, Mireille
Li, Lei O.
Coleman, Rosalind A.
Rapoport, Stanley I.
Modi, Hiren R.
TI Valproate uncompetitively inhibits arachidonic acid acylation by rat
acyl-CoA synthetase 4: Relevance to valproate's efficacy against bipolar
disorder
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Bipolar disorder; Valproate; Arachidonic acid; Acyl-CoA synthetase; Mood
stabilizer; Acsl4; Brain; Rat
ID CYTOSOLIC PHOSPHOLIPASE A(2); CHRONIC LITHIUM; BRAIN; METABOLISM;
EXPRESSION; BINDING; PROTEIN; DRUG; LIPOPOLYSACCHARIDE;
NEUROINFLAMMATION
AB Background: The ability of chronic valproate (VPA) to reduce arachidonic acid (AA) turnover in brain phospholipids of unanesthetized rats has been ascribed to its inhibition of acyl-CoA synthetase (AcsI)mediated activation of AA to AA-CoA. Our aim was to identify a rat Acsl isoenzyme that could be inhibited by VPA in vitro. Methods: Rat Acsl3-, Acsl6v1- and Acsl6v2-, and Acsl4-flag proteins were expressed in E. coli, and the ability of VPA to inhibit their activation of long-chain fatty acids to acyl-CoA was estimated using Michaelis-Menten kinetics. Results: VPA uncompetitively inhibited Acsl4-mediated conversion of AA and of docosahexaenoic (DHA) but not of palmitic acid to acyl-CoA, but did not affect AA conversion by Acsl3, Acsl6v1 or Acsl6v2. Acsl4-mediated conversion of AA to AA-CoA showed substrate inhibition and had a 10-times higher catalytic efficiency than did conversion of DHA to DHA-CoA. Butyrate, octanoate, or lithium did not inhibit AA activation by Acsl4. Conclusions: VPA's ability to inhibit Acsl4 activation of AA and of DHA to their respective acyl-CoAs, when related to the higher catalytic efficiency of AA than DHA conversion, may account for VPA's selective reduction of AA turnover in rat brain phospholipids, and contribute to VPA's efficacy against bipolar disorder. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Shimshoni, Jakob A.; Basselin, Mireille; Rapoport, Stanley I.; Modi, Hiren R.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Li, Lei O.; Coleman, Rosalind A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
RP Modi, HR (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Rm 1S126,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM modihr@mail.nih.gov
FU National Institute on Aging, NIH; American Heart
Association-Mid-Atlantic Region; NIH [DK 59935]
FX This work was supported by the Intramural Program of the National
Institute on Aging, NIH, by NIH Grant DK 59935 (RAC), and a
post-doctoral fellowship from the American Heart
Association-Mid-Atlantic Region (L. O. L). We thank Professor Nina
Isoherranen and Dr. Edmund Reese for their helpful comments.
NR 50
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD MAR
PY 2011
VL 1811
IS 3
BP 163
EP 169
DI 10.1016/j.bbalip.2010.12.006
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 746TI
UT WOS:000289270200006
PM 21184843
ER
PT J
AU Fan, HK
Li, PF
Zingarelli, B
Borg, K
Halushka, PV
Birnbaumer, L
Cook, JA
AF Fan, Hongkuan
Li, Pengfei
Zingarelli, Basilia
Borg, Keith
Halushka, Perry V.
Birnbaumer, Lutz
Cook, James A.
TI Heterotrimeric G alpha(i) proteins are regulated by lipopolysaccharide
and are anti-inflammatory in endotoxemia and polymicrobial sepsis
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE G alpha(i) protein; Cecal ligation and puncture; LPS; Pertussis toxin;
Mastoparan
ID MOUSE PERITONEAL-MACROPHAGES; INNATE IMMUNE-RESPONSES; TOLL-LIKE
RECEPTOR-4; SELECTIVE SUPPRESSION; CHEMOKINE RECEPTOR-4; DENDRITIC
CELLS; ACTIVATION; BETA; MORTALITY; KINASE
AB Previous studies have implicated a role of heterotrimeric G alpha(i) proteins in lipopolysaccharide (LPS)-induced inflammatory responses. We hypothesized that Toll-like receptor (TLR) signaling regulates G alpha(i) proteins, which are anti-inflammatory in endotoxemia and polymicrobial sepsis. RAW 264.7 cells were stimulated with LPS and the G alpha(i)-GTP protein complex was immunoprecipitated with a G alpha(i) protein activation assay. In subsequent in vivo studies, the G alpha(i) protein inhibitor pertussis toxin (PTx) or G(i) protein agonist mastoparan (MP-7) were administrated prior to endotoxemia. LPS-induced pro-inflammatory cytokines and mortality were determined. To examine the role of G alpha(i2) in sepsis, G alpha(i2) (-/-) and wildtype (WT) mice were subjected to cecal ligation and puncture (CLP) and monitored every 24 h for 120 h. Other mice were sacrificed 24 h after CLP. Peritoneal fluid, blood, and tissue samples were collected. Plasma pro-inflammatory cytokine production, bacterial load in peritoneal fluid, blood and lung tissue, myeloperoxidase (MPO) activity in lung and liver and different immune cell populations in spleen were studied. We found that G alpha(i) proteins are rapidly activated by LPS followed by rapid inactivation. These studies provide the first direct evidence that G alpha(i) proteins are modulated by TLR signaling. In following studies, PTx augmented LPS-induced plasma TNF alpha, IL-6, whereas MP-7 suppressed LPS-induced TNF alpha and decreased LPS-induced mortality. In sepsis studies, the survival rate post-CLP was significantly decreased in the G alpha(i2) (-/-) mice compared to WT mice. CLP-induced plasma TNF alpha, IL-6, bacterial load in peritoneal fluid, blood and lung tissue and lung and liver MPO activity were significantly increased in G alpha(i2) (-/-) compared to WT mice. G alpha(i2) (-/-) mice also exhibited increased Th1 and Th2 responses compared to WT mice. Taken together, G alpha(i) proteins are activated by LPS and negatively regulate endotoxemia and sepsis. Understanding the role of G alpha(i2) protein in regulation of the inflammatory response in sepsis may provide novel targets for treatment of sepsis. (c) 2011 Elsevier B.V. All rights reserved.
C1 [Fan, Hongkuan; Li, Pengfei; Cook, James A.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Li, Pengfei] Jilin Univ, Coll Life Sci, Changchun 130033, Peoples R China.
[Zingarelli, Basilia] Cincinnati Childrens Hosp, Div Crit Care Med, Med Ctr, Cincinnati, OH 45229 USA.
[Borg, Keith; Halushka, Perry V.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Halushka, Perry V.] Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA.
[Birnbaumer, Lutz] NIEHS, Transmembrane Signaling Grp, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Fan, HK (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB Room 403, Charleston, SC 29425 USA.
EM fanhong@musc.edu
FU [GM27673]; [GM027673-S1]; [GM67202]; [AI079248]
FX This work was supported in part by GM27673 (JAC), GM027673-S1 (JAC),
GM67202 (BZ) and AI079248 (HF).
NR 33
TC 11
Z9 11
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD MAR
PY 2011
VL 1813
IS 3
BP 466
EP 472
DI 10.1016/j.bbamcr.2011.01.012
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 738GP
UT WOS:000288628600010
PM 21255617
ER
PT J
AU Millum, J
AF Millum, Joseph
TI POST-TRIAL ACCESS TO ANTIRETROVIRALS: WHO OWES WHAT TO WHOM?
SO BIOETHICS
LA English
DT Article
DE HIV/AIDS; antiretrovirals; ART; post-trial access
ID ANCILLARY-CARE RESPONSIBILITIES; VACCINE TRIALS; DEVELOPING-COUNTRIES;
THERAPY; PARTICIPANTS; INTERRUPTION; RESEARCHERS; OBLIGATION; PROVISION;
ETHICS
AB Many recent articles argue that participants who seroconvert during HIV prevention trials deserve treatment when they develop AIDS, and there is a general consensus that the participants in HIV/AIDS treatment trials should have continuing post-trial access. As a result, the primary concern of many ethicists and activists has shifted from justifying an obligation to treat trial participants, to working out mechanisms through which treatment could be provided. In this paper I argue that this shift frequently conceals an important assumption: that if there is an obligation to supply treatment, then any party who could provide it may be prevailed upon to discharge the obligation. This assumption is false. The reasons why trial participants should get ART affect who has the duty to provide it. We should not burden governments with the obligations of sponsors, nor researchers with the obligations of the international community. And we should not deprive a group of treatment because their need is less salient than that of research participants. Insisting otherwise may lead to people being wrongfully deprived of access to antiretrovirals.
C1 NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Millum, J (reprint author), NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM millumj@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 39
TC 10
Z9 10
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-9702
J9 BIOETHICS
JI Bioethics
PD MAR
PY 2011
VL 25
IS 3
BP 145
EP 154
DI 10.1111/j.1467-8519.2009.01736.x
PG 10
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 715NI
UT WOS:000286890800004
PM 19594728
ER
PT J
AU Yu, GQ
Li, HA
Ha, S
Shih, IM
Clarke, R
Hoffman, EP
Madhavan, S
Xuan, JH
Wang, Y
AF Yu, Guoqiang
Li, Huai
Ha, Sook
Shih, Ie-Ming
Clarke, Robert
Hoffman, Eric P.
Madhavan, Subha
Xuan, Jianhua
Wang, Yue
TI PUGSVM: a caBIG (TM) analytical tool for multiclass gene selection and
predictive classification
SO BIOINFORMATICS
LA English
DT Article
ID HIGH-DIMENSIONAL DATA; MOLECULAR CLASSIFICATION; EXPRESSION DATA;
CANCER; DISCOVERY; SPACES
AB Phenotypic Up-regulated Gene Support Vector Machine (PUGSVM) is a cancer Biomedical Informatics Grid (caBIG (TM)) analytical tool for multiclass gene selection and classification. PUGSVM addresses the problem of imbalanced class separability, small sample size and high gene space dimensionality, where multiclass gene markers are defined by the union of one-versus-everyone phenotypic upregulated genes, and used by a well-matched one-versus-rest support vector machine. PUGSVM provides a simple yet more accurate strategy to identify statistically reproducible mechanistic marker genes for characterization of heterogeneous diseases.
C1 [Yu, Guoqiang; Ha, Sook; Xuan, Jianhua; Wang, Yue] Virginia Polytech Inst & State Univ, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA.
[Li, Huai] NIA, Bioinformat Unit, RRB, NIH, Baltimore, MD 21224 USA.
[Shih, Ie-Ming] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21231 USA.
[Shih, Ie-Ming] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA.
[Shih, Ie-Ming] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA.
[Clarke, Robert; Madhavan, Subha] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Hoffman, Eric P.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
RP Wang, Y (reprint author), Virginia Polytech Inst & State Univ, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA.
EM yuewang@vt.edu
RI Clarke, Robert/A-6485-2008
OI Clarke, Robert/0000-0002-9278-0854
FU National Institutes of Health [HHSN261200800001E, CA109872, CA149147,
CA139246, NS029525]
FX This work is supported in part by the National Institutes of Health,
under Contract No. HHSN261200800001E and Grants CA109872, CA149147,
CA139246, NS029525.
NR 11
TC 6
Z9 6
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 MAR 1
PY 2011
VL 27
IS 5
BP 736
EP 738
DI 10.1093/bioinformatics/btq721
PG 3
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 726WU
UT WOS:000287758400027
PM 21186245
ER
PT J
AU Tost, H
Weinberger, DR
AF Tost, Heike
Weinberger, Daniel R.
TI RELN rs7341475 and Schizophrenia Risk: Confusing, yet Somehow Intriguing
SO BIOLOGICAL PSYCHIATRY
LA English
DT Letter
ID DISEASE; ASSOCIATION; EXPRESSION; VARIANT
C1 [Tost, Heike; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Tost, H (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002904-01]
NR 16
TC 1
Z9 1
U1 0
U2 3
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 MAR 1
PY 2011
VL 69
IS 5
BP E19
EP E19
DI 10.1016/j.biopsych.2010.10.022
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 727SO
UT WOS:000287822000017
PM 21532921
ER
PT J
AU Pulsipher, MA
Young, NS
Tolar, J
Risitano, AM
Deeg, HJ
Anderlini, P
Calado, R
Kojima, S
Eapen, M
Harris, R
Scheinberg, P
Savage, S
Maciejewski, JP
Tiu, RV
DiFronzo, N
Horowitz, MM
Antin, JH
AF Pulsipher, Michael A.
Young, Neal S.
Tolar, Jakub
Risitano, Antonio M.
Deeg, H. Joachim
Anderlini, Paolo
Calado, Rodrigo
Kojima, Seiji
Eapen, Mary
Harris, Richard
Scheinberg, Phillip
Savage, Sharon
Maciejewski, Jaroslaw P.
Tiu, Ramon V.
DiFronzo, Nancy
Horowitz, Mary M.
Antin, Joseph H.
TI Optimization of Therapy for Severe Aplastic Anemia Based on Clinical,
Biologic, and Treatment Response Parameters: Conclusions of an
International Working Group on Severe Aplastic Anemia Convened by the
Blood and Marrow Transplant Clinical Trials Network, March 2010
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Severe aplastic anemia; Blood and marrow transplantation;
Immunosuppressive therapy; Telomeres
ID STEM-CELL TRANSPLANTATION; ALTERNATIVE DONOR TRANSPLANTS; HIGH-DOSE
CYCLOPHOSPHAMIDE; ANTI-THYMOCYTE GLOBULIN; TERM-FOLLOW-UP; ANTITHYMOCYTE
GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; CONDITIONING REGIMEN; BONE-MARROW;
ANTILYMPHOCYTE GLOBULIN
AB Although recent advances in therapy offer the promise for improving survival in patients with severe aplastic anemia (SAA), the small size of the patient population, lack of a mechanism in North America for longitudinal follow-up of patients, and inadequate cooperation among hematologists, scientists, and transplant physicians remain obstacles to conducting large studies that would advance the field. To address this issue, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a group of international experts in March 2010 to define the most important questions in the basic science, immunosuppressive therapy (IST), and bone marrow transplantation (BMT) of SAA and propose initiatives to facilitate clinical and biologic research. Key conclusions of the working group were: ( 1) new patients should obtain accurate, expert diagnosis and early identification of biologic risk; (2) a population-based SAA outcomes registry should be established in North America to collect data on patients longitudinally from diagnosis through and after treatment; (3) a repository of biologic samples linked to the clinical data in the outcomes registry should be developed; (4) innovative approaches to unrelated donor BMT that decrease graft-versus-host disease are needed; and (5) alternative donor transplantation approaches for patients lacking HLA-matched unrelated donors must be improved. A partnership of BMT, IST, and basic science researchers will develop initiatives and partner with advocacy and funding organizations to address these challenges. Collaboration with similar study groups in Europe and Asia will be pursued. Biol Blood Marrow Transplant 17: 291-299 (2011) (C) 2011 American Society fin. Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Pulsipher, Michael A.] Univ Utah, Sch Med, Primary Childrens Med Ctr, Salt Lake City, UT 84113 USA.
[Young, Neal S.; Calado, Rodrigo; Scheinberg, Phillip] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Tolar, Jakub] Univ Minnesota, Minneapolis, MN USA.
[Risitano, Antonio M.] Univ Naples Federico 2, Naples, Italy.
[Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kojima, Seiji] Childrens Med Ctr, Nagoya, Aichi, Japan.
[Eapen, Mary; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Harris, Richard] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Savage, Sharon] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Maciejewski, Jaroslaw P.; Tiu, Ramon V.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Pulsipher, MA (reprint author), Univ Utah, Sch Med, Primary Childrens Med Ctr, 100 N Mario Capecchi Dr, Salt Lake City, UT 84113 USA.
EM michael.pulsipher@hsc.utah.edu
RI Calado, Rodrigo/G-2619-2011; Kojima, Seiji/I-1601-2012
FU Blood and Marrow Transplant Clinical Trials Network; National Heart,
Lung, and Blood Institute; National Cancer Institute; Genzyme
FX Financial disclosure: This International Working Group was supported by
the Blood and Marrow Transplant Clinical Trials Network, the National
Heart, Lung, and Blood Institute, the National Cancer Institute, and a
grant from Genzyme. The authors gratefully acknowledge the participating
centers and co-investigators of the BMT CTN 0301 study.
NR 49
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Z9 24
U1 0
U2 2
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 MAR
PY 2011
VL 17
IS 3
BP 291
EP 299
DI 10.1016/j.bbmt.2010.10.028
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 725GM
UT WOS:000287633200002
PM 21034841
ER
PT J
AU Gao, JH
Chen, K
Miao, Z
Ren, G
Chen, XY
Gambhir, SS
Cheng, Z
AF Gao, Jinhao
Chen, Kai
Miao, Zheng
Ren, Gang
Chen, Xiaoyuan
Gambhir, Sanjiv S.
Cheng, Zhen
TI Affibody-based nanoprobes for HER2-expressing cell and tumor imaging
SO BIOMATERIALS
LA English
DT Article
DE Affibody; Bioconjugation; Nanoprobes; HER2; Molecular imaging
ID MULTIFUNCTIONAL MAGNETIC NANOPARTICLES; SEMICONDUCTOR QUANTUM DOTS; HER2
EXPRESSION; NON-CADMIUM; PHOSPHOLIPID MICELLES; LIVING SUBJECTS;
MOLECULE; THERAPY; GROWTH; TOMOGRAPHY
AB This article reports the affibody-based nanoprobes specifically target and image human epidermal growth factor receptor type 2 (HER2)-expressing cells and tumors. The affibody molecules are a promising class of targeting ligands with simple, robust, and precise structure and high affinity. Using near-infrared (NIR) quantum dots (QDs) and iron oxide (IO) nanoparticles as two representative nanomaterials, we designed anti HER2 affibody molecules with a N-terminus cysteine residue (Cysteine-Z(HER2:342)) and precisely conjugated with maleimide-functionalized nanoparticles to make nanoparticle-affibody conjugates. The in vitro and in vivo study showed the conjugates are highly specific to target and image HER2-expressing cells and tumors. This work indicated the nanoparticle-affibody conjugates may be excellent candidates as targeting probes for molecular imaging and diagnosis. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Gao, Jinhao; Chen, Kai; Miao, Zheng; Ren, Gang; Gambhir, Sanjiv S.; Cheng, Zhen] Stanford Univ, Mol Imaging Program Stanford MIPS, Canary Ctr Stanford Canc Early Detect, Dept Radiol, Stanford, CA 94305 USA.
[Gao, Jinhao; Chen, Kai; Miao, Zheng; Ren, Gang; Gambhir, Sanjiv S.; Cheng, Zhen] Stanford Univ, Sch Med, Bio X Program, Stanford, CA 94305 USA.
[Gao, Jinhao] Xiamen Univ, Dept Biol Chem, Xiamen 361005, Peoples R China.
[Gao, Jinhao] Xiamen Univ, Key Lab Chem Biol Fujian Prov, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China.
[Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, CC, NIH, Bethesda, MD 20892 USA.
[Gambhir, Sanjiv S.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
RP Cheng, Z (reprint author), Stanford Univ, Mol Imaging Program Stanford MIPS, Canary Ctr Stanford Canc Early Detect, Dept Radiol, 1201 Welch Rd,Lucas P095, Stanford, CA 94305 USA.
EM zcheng@stanford.edu
RI Gao, Jinhao/F-5092-2010; miao, zheng/A-8851-2012; Cheng,
Zhen/K-2843-2012
OI Gao, Jinhao/0000-0003-3215-7013;
FU NCI/NIH [R21 CA121842]; NCI of Cancer Nanotechnology Excellence [U54
CA119367]
FX This work was partially supported by NCI/NIH R21 CA121842 (to Z.C.) and
NCI of Cancer Nanotechnology Excellence Grant U54 CA119367 (to S.S.G.).
NR 45
TC 67
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U1 5
U2 55
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 MAR
PY 2011
VL 32
IS 8
BP 2141
EP 2148
DI 10.1016/j.biomaterials.2010.11.053
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 717QB
UT WOS:000287061400015
PM 21147502
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI Estimation and Inference for the Causal Effect of Receiving Treatment on
a Multinomial Outcome: An Alternative Approach
SO BIOMETRICS
LA English
DT Article
DE All-or-none compliance; Causal effect; Multinomial outcomes;
Noncompliance; Perfect fit; Principal stratification; Randomized trials
ID INSTRUMENTAL VARIABLES; EFFICACY; TRIALS; DESIGN
AB Recently, Cheng (2009, Biometrics 65, 96-103) proposed a model for the causal effect of receiving treatment when there is all-or-none compliance in one randomization group, with maximum likelihood estimation based on convex programming. We discuss an alternative approach that involves a model for all-or-none compliance in two randomization groups and estimation via a perfect fit or an expectation-maximization algorithm for count data. We believe this approach is easier to implement, which would facilitate the reproduction of calculations.
C1 NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 16
TC 7
Z9 7
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2011
VL 67
IS 1
BP 319
EP 323
DI 10.1111/j.1541-0420.2010.01451.x
PG 5
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 735AW
UT WOS:000288386800034
PM 20560933
ER
PT J
AU Skvorc, C
Wilson, DE
AF Skvorc, Casey
Wilson, Deborah E.
TI DEVELOPING A BEHAVIORAL HEALTH SCREENING PROGRAM FOR BSL-4 LABORATORY
WORKERS AT THE NATIONAL INSTITUTES OF HEALTH
SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE
LA English
DT Article
AB The events and aftermath of September 11, 2001, accelerated a search for personnel reliability test measures to identify individuals who could pose a threat to our nation's security and safety. The creation and administration of a behavioral health screen for BSL-4 laboratory workers at the National Institutes of Health represents a pioneering effort to proactively build a BSL-4 safety culture promoting worker cohesiveness, trust, respect, and reliability with a balance of worker privacy and public safety.
C1 [Skvorc, Casey] NIH, Biosurety Program, Div Occupat Hlth & Safety, Off Res Serv, Bethesda, MD 20892 USA.
RP Skvorc, C (reprint author), NIH, Biosurety Program, Div Occupat Hlth & Safety, Off Res Serv, 9000 Rockville Pike,13 S Dr,Bldg 13,Room 3K04, Bethesda, MD 20892 USA.
EM skvorcc@mail.nih.gov
NR 16
TC 7
Z9 7
U1 1
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1538-7135
J9 BIOSECUR BIOTERROR
JI Biosecur. Bioterror.
PD MAR
PY 2011
VL 9
IS 1
BP 23
EP 29
DI 10.1089/bsp.2010.0048
PG 7
WC Public, Environmental & Occupational Health; International Relations
SC Public, Environmental & Occupational Health; International Relations
GA 734EL
UT WOS:000288316700003
PM 21361798
ER
PT J
AU Resnik, DB
Barner, DD
Dinse, GE
AF Resnik, David B.
Barner, Dionne D.
Dinse, Gregg E.
TI DUAL-USE REVIEW POLICIES OF BIOMEDICAL RESEARCH JOURNALS
SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE
LA English
DT Review
ID SCIENCE JOURNALS
AB To address biosecurity issues, government agencies, academic institutions, and professional societies have developed policies concerning the publication of "dual-use" biomedical research-that is, research that could be readily applied to cause significant harm to the public, the environment, or national security. We conducted an e-mail survey of life science journals to determine the percentage that have a dual-use policy. Of the 155 journals that responded to our survey (response rate 39%), only 7.7% stated that they had a written dual-use policy and only 5.8% said they had experience reviewing dual-use research in the past 5 years. Among the potential predictors we investigated, the one most highly associated with a journal having a written dual-use policy was membership in the Nature Publishing Group (positive association). When considered individually, both previous experience with reviewing dual-use research and the journal's impact factor appeared to be positively associated with having a written dual-use policy, but only the former remained significant after adjusting for publishing group. Although preventing the misuse of scientific research for terrorist or criminal purposes is an important concern, few biomedical journals have dual-use review policies. Journals that are likely to review research that raises potential dual-use concerns should consider developing dual-use policies.
C1 [Resnik, David B.; Barner, Dionne D.] NIEHS, Eth Program, NIH, Res Triangle Pk, NC 27709 USA.
[Dinse, Gregg E.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, Eth Program, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS
NR 8
TC 11
Z9 11
U1 1
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1538-7135
J9 BIOSECUR BIOTERROR
JI Biosecur. Bioterror.
PD MAR
PY 2011
VL 9
IS 1
BP 49
EP 54
DI 10.1089/bsp.2010.0067
PG 6
WC Public, Environmental & Occupational Health; International Relations
SC Public, Environmental & Occupational Health; International Relations
GA 734EL
UT WOS:000288316700006
PM 21395429
ER
PT J
AU Ribeiro, JMC
Anderson, JM
Manoukis, NC
Meng, ZJ
Francischetti, IMB
AF Ribeiro, Jose M. C.
Anderson, Jennifer M.
Manoukis, Nicholas C.
Meng, Zhaojing
Francischetti, Ivo M. B.
TI A further insight into the sialome of the tropical bont tick, Amblyomma
variegatum
SO BMC GENOMICS
LA English
DT Article
ID THYROGLOBULIN TYPE-1 DOMAINS; VECTOR IXODES-SCAPULARIS; RICH SECRETORY
PROTEINS; SALIVARY-GLAND; SOFT TICK; HAEMAPHYSALIS-LONGICORNIS;
5'-NUCLEOTIDASE FAMILY; DERMACENTOR-ANDERSONI; CYSTEINE PROTEINASES;
ORNITHODOROS-MOUBATA
AB Background: Ticks-vectors of medical and veterinary importance-are themselves also significant pests. Tick salivary proteins are the result of adaptation to blood feeding and contain inhibitors of blood clotting, platelet aggregation, and angiogenesis, as well as vasodilators and immunomodulators. A previous analysis of the sialotranscriptome (from the Greek sialo, saliva) of Amblyomma variegatum is revisited in light of recent advances in tick sialomes and provides a database to perform a proteomic study.
Results: The clusterized data set has been expertly curated in light of recent reviews on tick salivary proteins, identifying many new families of tick-exclusive proteins. A proteome study using salivary gland homogenates identified 19 putative secreted proteins within a total of 211 matches.
Conclusions: The annotated sialome of A. variegatum allows its comparison to other tick sialomes, helping to consolidate an emerging pattern in the salivary composition of metastriate ticks; novel protein families were also identified. Because most of these proteins have no known function, the task of functional analysis of these proteins and the discovery of novel pharmacologically active compounds becomes possible.
C1 [Ribeiro, Jose M. C.; Anderson, Jennifer M.; Manoukis, Nicholas C.; Francischetti, Ivo M. B.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA.
[Manoukis, Nicholas C.] ARS, US Pacific Basin Agr Res Ctr, USDA, Hilo, HI USA.
[Meng, Zhaojing] Natl Canc Inst Frederick, Lab Prote & Analyt Technol, SAIC Frederick Inc, NIH, Frederick, MD USA.
RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA.
EM jribeiro@niaid.nih.gov
OI Manoukis, Nicholas/0000-0001-5062-7256
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX 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. We thank NIAID
intramural editor Brenda Rae Marshall for assistance.
NR 100
TC 48
Z9 48
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAR 1
PY 2011
VL 12
AR 136
DI 10.1186/1471-2164-12-136
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 736JJ
UT WOS:000288489900001
PM 21362191
ER
PT J
AU Hosgood, HD
Purdue, MP
Wang, SS
Zheng, T
Morton, LM
Lan, Q
Menashe, I
Zhang, YW
Cerhan, JR
Grulich, A
Cozen, W
Yeager, M
Holford, TR
Vajdic, CM
Davis, S
Leaderer, B
Kricker, A
Schenk, M
Zahm, SH
Chatterjee, N
Chanock, SJ
Rothman, N
Hartge, P
Armstrong, B
AF Hosgood, H. Dean, III
Purdue, Mark P.
Wang, Sophia S.
Zheng, Tongzhang
Morton, Lindsay M.
Lan, Qing
Menashe, Idan
Zhang, Yawei
Cerhan, James R.
Grulich, Andrew
Cozen, Wendy
Yeager, Meredith
Holford, Theodore R.
Vajdic, Claire M.
Davis, Scott
Leaderer, Brian
Kricker, Anne
Schenk, Maryjean
Zahm, Shelia H.
Chatterjee, Nilanjan
Chanock, Stephen J.
Rothman, Nathaniel
Hartge, Patricia
Armstrong, Bruce
TI A pooled analysis of three studies evaluating genetic variation in
innate immunity genes and non-Hodgkin lymphoma risk
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE non-Hodgkin lymphoma; immune; innate immunity; genetic variation; single
nucleotide polymorphisms
ID FC-GAMMA-RIIA; EPIDEMIOLOGY CONSORTIUM INTERLYMPH; NF-KAPPA-B;
IMMUNOREGULATORY GENES; INFLAMMATORY RESPONSE; ADAPTIVE IMMUNITY;
RECEPTOR-II; POLYMORPHISMS; ASSOCIATION; VARIANTS
AB P>Genetic variation in immune-related genes may play a role in the development of non-Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population-based case-control studies (1946 cases and 1808 controls). Gene-based analyses found IL1RN to be associated with NHL risk (minP = 0 center dot 03); specifically, IL1RN rs2637988 was associated with an increased risk of NHL (per-allele odds ratio = 1 center dot 15, 95% confidence interval = 1 center dot 05-1 center dot 27; P(trend) = 0 center dot 003), which was consistent across study, subtype, and gender. FCGR2A was also associated with a decreased risk of the follicular lymphoma NHL subtype (minP = 0 center dot 03). Our findings suggest that genetic variation in IL1RN and FCGR2A may play a role in lymphomagenesis. Given that conflicting results have been reported regarding the association between IL1RN SNPs and NHL risk, a larger number of innate immunity genes with sufficient genomic coverage should be evaluated systematically across many studies.
C1 [Hosgood, H. Dean, III; Purdue, Mark P.; Wang, Sophia S.; Morton, Lindsay M.; Lan, Qing; Menashe, Idan; Zahm, Shelia H.; Chatterjee, Nilanjan; Chanock, Stephen J.; Rothman, Nathaniel; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Etiol, Duarte, CA USA.
[Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Leaderer, Brian] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Cerhan, James R.] Coll Med, Mayo Clin, Rochester, MN USA.
[Grulich, Andrew] Univ New S Wales, Natl Ctr HIV Epidemiol, Sydney, NSW, Australia.
[Grulich, Andrew] Univ New S Wales, Clin Res, Sydney, NSW, Australia.
[Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA.
[Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia.
[Vajdic, Claire M.] Univ New S Wales, Lowy Canc Res, Sydney, NSW, Australia.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Davis, Scott] Univ Washington, Seattle, WA 98195 USA.
[Kricker, Anne; Armstrong, Bruce] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Schenk, Maryjean] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Schenk, Maryjean] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8120,MCS 7240, Bethesda, MD 20892 USA.
EM hosgoodd@mail.nih.gov
RI Morton, Lindsay/B-5234-2015; Armstrong, Bruce/K-9464-2015; Purdue,
Mark/C-9228-2016;
OI Morton, Lindsay/0000-0001-9767-2310; Armstrong,
Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108; Cerhan,
James/0000-0002-7482-178X; Vajdic, Claire/0000-0002-3612-8298
FU National Institutes of Health (NIH) (National Cancer Institute (NCI)
[CA62006]; 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 [990920]; Cancer Council NSW; University
of Sydney Medical Foundation; NSW Health Department
FX DNA extraction, genotyping, and statistical analysis were supported by
the Intramural Research Program of the National Institutes of Health
(NIH) (National Cancer Institute (NCI)). The NCI-SEER study was also
supported by the Intramural Research Program of the NIH (NCI), and by
Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008,
N01-PC-67009, N01-PC-67010, and N02-PC-71105. The Connecticut study was
supported by NIH grant CA62006 (TZ) from the NCI. The NSW study was
supported by the National Health and Medical Research Council of
Australia Project Grant number 990920 (BA), the Cancer Council NSW, and
the University of Sydney Medical Foundation.; We thank Mary McAdams,
Peter Hui, Michael Stagner, and Zeynep Kalaylioglu of Information
Management Services, Inc. for their programming support. For the
NCI-SEER study, we acknowledge the contributions of the staff and
scientists and the SEER centres of Iowa, Los Angeles, Detroit, and
Seattle for the conduct of the study's field effort. The NSW study was
made possible by access to new notifications to the NSW Central Cancer
Registry, which is funded by the NSW Health Department. Ann-Maree Hughes
oversaw conduct of the study and Melisa Litchfield, Maria Agaliotis,
Chris Goumas, Jackie Turner, and staff of the Hunter Valley Research
Foundation contributed to the data collection. Jenny Turner, study
pathologist, reviewed all pathology reports and original slides as
necessary.
NR 41
TC 17
Z9 19
U1 0
U2 1
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 MAR
PY 2011
VL 152
IS 6
BP 721
EP 726
DI 10.1111/j.1365-2141.2010.08518.x
PG 6
WC Hematology
SC Hematology
GA 726PV
UT WOS:000287739500005
PM 21250972
ER
PT J
AU Silveira, C
Vallochi, AL
da Silva, UR
Muccioli, C
Holland, GN
Nussenblatt, RB
Belfort, R
Rizzo, LV
AF Silveira, Claudio
Vallochi, Adriana Lima
da Silva, Ulisses Rodrigues
Muccioli, Cristina
Holland, Gary N.
Nussenblatt, Robert B.
Belfort, Rubens
Rizzo, Luiz Vicente
TI Toxoplasma gondii in the peripheral blood of patients with acute and
chronic toxoplasmosis
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OCULAR TOXOPLASMOSIS; ACQUIRED TOXOPLASMOSIS; GLOBAL REASSESSMENT;
MEMORIAL-LECTURE; DISEASE; INFECTION; DIAGNOSIS; RETINOCHOROIDITIS;
INVOLVEMENT; CULTURE
AB Background and aims Toxoplasmic retinochoroiditis may recur months or years after the primary infection. Rupture of dormant cysts in the retina is the accepted hypothesis to explain recurrence. Here, the authors present evidence supporting the presence of Toxoplasma gondii in the peripheral blood of immunocompetent patients.
Methods Direct observation by light microscopy and by immunofluorescence assay was performed, and results were confirmed by PCR amplification of parasite DNA.
Results The authors studied 20 patients from Erechim, Brazil, including acute infected patients, patients with recurrent active toxoplasmic retinochoroiditis, patients with old toxoplasmic retinal scars, and patients with circulating IgG antibodies against T gondii and absence of ocular lesions. Blood samples were analysed, and T gondii was found in the blood of acutely and chronically infected patients regardless of toxoplasmic retinochoroiditis.
Conclusions The results indicate that the parasite may circulate in the blood of immunocompetent individuals and that parasitaemia could be associated with the reactivation of the ocular disease.
C1 [Rizzo, Luiz Vicente] Hosp Israelita Albert Einstein, BR-05652000 Sao Paulo, Brazil.
[Silveira, Claudio; Muccioli, Cristina; Belfort, Rubens] Univ Fed Sao Paulo, Dept Ophthalmol, Escola Paulista Med, Sao Paulo, Brazil.
[Vallochi, Adriana Lima; da Silva, Ulisses Rodrigues; Rizzo, Luiz Vicente] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, Brazil.
[Holland, Gary N.] Univ Calif Los Angeles, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, Los Angeles, CA 90024 USA.
[Holland, Gary N.] Univ Calif Los Angeles, Dept Ophthalmol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Rizzo, Luiz Vicente] Albert Einstein Jewish Inst Educ & Res, Sao Paulo, Brazil.
[Rizzo, Luiz Vicente] Brazilian Minist Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil.
RP Rizzo, LV (reprint author), Hosp Israelita Albert Einstein, Av Albert Einstein 627-701,Chinuch Level,Josef Fe, BR-05652000 Sao Paulo, Brazil.
EM lvrizzo@einstein.br
RI Rizzo, Luiz Vicente/B-4458-2009; Belfort Jr, Rubens/E-2252-2012;
Muccioli, Cristina/C-3419-2013
OI Belfort Jr, Rubens/0000-0002-8422-3898;
FU Fundacao de Amparo a Pesquisa de Sao Paulo; Conselho Nacional de
desenvolvimento Cientifico e Tecnologico
FX This study was supported by Fundacao de Amparo a Pesquisa de Sao Paulo
and Conselho Nacional de desenvolvimento Cientifico e Tecnologico.
NR 29
TC 40
Z9 42
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAR
PY 2011
VL 95
IS 3
BP 396
EP 400
DI 10.1136/bjo.2008.148205
PG 5
WC Ophthalmology
SC Ophthalmology
GA 722NY
UT WOS:000287440400019
PM 20601663
ER
PT J
AU Simard, EP
Pfeiffer, RM
Engels, EA
AF Simard, Edgar P.
Pfeiffer, Ruth M.
Engels, Eric A.
TI Cumulative Incidence of Cancer Among Individuals With Acquired
Immunodeficiency Syndrome in the United States
SO CANCER
LA English
DT Article
DE acquired immunodeficiency syndrome; anal cancer; cancer; human
immunodeficiency virus; Hodgkin lymphoma; mortality; nonparametric
statistics
ID ANTIRETROVIRAL THERAPY ERA; HIV-INFECTION; HODGKIN LYMPHOMA;
LUNG-CANCER; AIDS; RISK; PEOPLE; VIRUS; IMMUNOSUPPRESSION; MORTALITY
AB BACKGROUND: The overall burden of cancer may increase as individuals with acquired immunodeficiency syndrome (AIDS) live longer because of highly active antiretroviral therapy (HAART), which has been widely available since 1996. METHODS: A population-based, record-linkage study identified cancers in 472,378 individuals with AIDS from 1980 to 2006. By using nonparametric competing-risk methods, the cumulative incidence of cancer was estimated across 3 calendar periods (AIDS onset in 1980-1989, 1990-1995, and 1996-2006). RESULTS: Measured at 5 years after AIDS onset, the cumulative incidence of AIDS-defining cancer (ADC) declinec sharply across the 3 AIDS calendar periods (from 18% in 1980-1989, to 11% in 1990-1995, to 4.2% in 1996-2006 [ie, the HAART era]). The cumulative incidence of Kaposi sarcoma declined from 14.3% during 1980 to 1989, to 6.7% during 1990 to 1995, and to 1.8% during 1996 to 2006. The cumulative incidence of non-Hodgkin lymphoma (NHL) declined from 3.8% during 1990 through 1995 to 2.2% during 1996 through 2006; during the HAART era, NHL was the most common ADC (53%). The cumulative incidence of non-AIDS-defining cancer (NADC) increased from 1.1% to 1.5% with no change thereafter (1%; 1996-2006), in part because of declines in competing mortality. However, cumulative incidence increased steadily over time for specific NADCs (anal cancer, Hodgkin lymphoma, and liver cancer). The cumulative incidence of lung cancer increased from 0.14% during 1980 to 1989 to 0.32% during 1990 to 1995, and no change was observed thereafter. CONCLUSIONS: Dramatically declining cumulative incidence was noted in 2 major ADCs (Kaposi sarcoma and NHL), and increases were observed in some NADCs (specifically, cancers of the anus, liver, and lung and Hodgkin lymphoma). As HIV/AIDS is increasingly managed as a chronic disease, greater attention should be focused on cancer screening and prevention. Cancer 2011;117:1089-96. Published 2010 by American Cancer Society.*
C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7076, Bethesda, MD 20892 USA.
EM engelse@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
FU National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Cancer Institute.
NR 30
TC 81
Z9 83
U1 0
U2 3
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 MAR 1
PY 2011
VL 117
IS 5
BP 1089
EP 1096
DI 10.1002/cncr.25547
PG 8
WC Oncology
SC Oncology
GA 725LM
UT WOS:000287646200028
PM 20960504
ER
PT J
AU Dieli-Conwright, CM
Sullivan-Halley, J
Patel, A
Press, M
Malone, K
Ursin, G
Burkman, R
Strom, B
Simon, M
Weiss, L
Marchbanks, P
Folger, S
Spirtas, R
Deapen, D
Bernstein, L
AF Dieli-Conwright, Christina M.
Sullivan-Halley, Jane
Patel, Alpa
Press, Michael
Malone, Kathleen
Ursin, Giske
Burkman, Ronald
Strom, Brian
Simon, Michael
Weiss, Linda
Marchbanks, Polly
Folger, Suzanne
Spirtas, Robert
Deapen, Dennis
Bernstein, Leslie
TI Does hormone therapy counter the beneficial effects of physical activity
on breast cancer risk in postmenopausal women?
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Hormone therapy; Physical activity; Breast cancer
ID RECREATIONAL EXERCISE; COHORT; HEALTH
AB Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether this association is stronger among non-hormone users or former users of menopausal hormone therapy (HT) is of interest given the marked decline in HT use since 2002. The Women's Contraceptive and Reproductive Experiences Study, a population-based case-control study of invasive breast cancer, recruited white women and black women ages 35-64 years and collected histories of lifetime recreational physical activity and HT use including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT). Among postmenopausal women (1,908 cases, 2,013 control participants), breast cancer risk declined with increasing levels of lifetime physical activity among never HT users; among short-term HT users (fewer than 5 years); and among current ET users; P(trend) values ranged from 0.004 to 0.016. In contrast, physical activity had no significant association with risk among long-term and past HT users and among current EPT users. No statistical evidence of heterogeneity was demonstrated for duration or currency of HT use. Breast cancer risk decreases with increasing lifetime physical activity levels among postmenopausal women who have not used HT, have used HT for less than 5 years, or are current ET users, yet this study was unable to demonstrate statistically that HT use modifies the relationship between physical activity and breast cancer. With profound changes in HT use occurring since 2002, it will be important in future studies to learn whether or not any association between physical activity and breast cancer among former HT users is a function of time since last HT use.
C1 [Dieli-Conwright, Christina M.; Sullivan-Halley, Jane; Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
[Patel, Alpa] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA.
[Press, Michael; Ursin, Giske; Deapen, Dennis] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Malone, Kathleen] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway.
[Burkman, Ronald] Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA.
[Strom, Brian] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Simon, Michael] Karmanos Canc Inst, Dept Med & Oncol, Detroit, MI USA.
[Weiss, Linda] NCI, Canc Ctr Program, Bethesda, MD 20892 USA.
[Marchbanks, Polly; Folger, Suzanne] Ctr Dis Control, Atlanta, GA 30333 USA.
[Spirtas, Robert] Natl Inst Child Hlth & Dev, Populat Res Ctr, Contracept & Reprod Hlth Branch, Bethesda, MD USA.
RP Dieli-Conwright, CM (reprint author), City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM cdielic@coh.org
FU National Institute of Child Health and Human Development; National
Cancer Institute (NCI) [N01 HD 3-3168]; Fred Hutchinson Cancer Research
Center [N01 HD 2-3166]; Karmanos Cancer Institute at Wayne State
University [N01 HD 3-3174]; University of Pennsylvania [N01 HD 3-3176];
University of Southern California [N01 HD 3-3175]; Centers for Disease
Control and Prevention [Y01 HD 7022]; SEER, Atlanta [N01-PC-67006];
SEER, Detroit [N01-CN-65064]; SEER, Los Angeles [N01CN- 67010]; SEER,
Seattle [N01-CN-0532]; California Department of Health Services
FX This work was supported by the National Institute of Child Health and
Human Development, with additional support from the National Cancer
Institute (NCI), through contracts with Emory University (N01 HD
3-3168), the Fred Hutchinson Cancer Research Center (N01 HD 2-3166), the
Karmanos Cancer Institute at Wayne State University (N01 HD 3-3174), the
University of Pennsylvania (N01 HD 3-3176) and the University of
Southern California (N01 HD 3-3175), and through an intra agency
agreement with the Centers for Disease Control and Prevention (Y01 HD
7022). Additional support was provided by K05 CA136967 (to LB). General
support through SEER contract numbers N01-PC-67006 (Atlanta),
N01-CN-65064 (Detroit), N01CN- 67010 (Los Angeles), and N01-CN-0532
(Seattle) is also acknowledged. The collection of cancer incidence data
for Los Angeles County used in this publication was supported by the
California Department of Health Services as part of the statewide cancer
reporting program mandated by the California Health and Safety Code
Section 103885. The findings and conclusions in this report are those of
the authors and do not necessarily represent the official position of
the Centers for Disease Control and Prevention or the State of
California, Department of Health Services.
NR 25
TC 4
Z9 4
U1 1
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAR
PY 2011
VL 22
IS 3
BP 515
EP 522
DI 10.1007/s10552-010-9719-y
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 737BH
UT WOS:000288542400020
PM 21213036
ER
PT J
AU Kitahara, CM
Platz, EA
Freeman, LEB
Hsing, AW
Linet, MS
Park, Y
Schairer, C
Schatzkin, A
Shikany, JM
de Gonzalez, AB
AF Kitahara, Cari M.
Platz, Elizabeth A.
Freeman, Laura E. Beane
Hsing, Ann W.
Linet, Martha S.
Park, Yikyung
Schairer, Catherine
Schatzkin, Arthur
Shikany, James M.
de Gonzalez, Amy Berrington
TI Obesity and Thyroid Cancer Risk among US Men and Women: A Pooled
Analysis of Five Prospective Studies
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BODY-MASS INDEX; RADIOLOGIC TECHNOLOGISTS; ANTHROPOMETRIC FACTORS;
ALCOHOL INTAKE; LARGE COHORT; HEALTH; WEIGHT; METAANALYSIS;
CARCINOGENESIS; ASSOCIATION
AB Background: Thyroid cancer incidence has risen dramatically in the United States since the early 1980s. Although the prevalence of obesity has doubled during this time period, the relationship between obesity and thyroid cancer is uncertain.
Methods: We examined the association between body mass index (BMI) and thyroid cancer risk in a pooled analysis of five prospective U.S. studies, including 413,979 women and 434,953 men. Proportional hazards models with attained age as the time metric were adjusted for education, race, marital status, smoking, alcohol intake, and (where appropriate) cohort and sex.
Results: Over follow-up (mean = 10.3 years), 768 women and 388 men were diagnosed with thyroid cancer. The risk of thyroid cancer was greater with increasing BMI [per 5 kg/m(2): HR in women, 1.16 (95% CI, 1.08-1.24); HR in men, 1.21 (95% CI, 0.97-1.49)]. There was no significant heterogeneity between studies (both P > 0.05). For women and men combined, the HRs for overweight (25.0-29.9 kg/m(2)) and obesity (>= 30 kg/m(2)) compared with normal-weight (18.5-24.9 kg/m(2)) were 1.20 (95% CI, 1.04-1.38) and 1.53 (95% CI, 1.31-1.79), respectively. We found no significant effect modification by other factors, and the results did not differ significantly by histologic type. A significant positive association for BMI in young adulthood (ages 18-20) with thyroid cancer risk was also observed [per 5-kg/m(2) increase: HR, 1.18 (95% CI, 1.03-1.35)].
Conclusion: BMI was positively associated with thyroid cancer risk in both men and women.
Impact: Our study provides strong evidence that obesity is an independent risk factor for thyroid cancer. Cancer Epidemiol Biomarkers Prev; 20(3); 464-72. (C)2011 AACR.
C1 [Kitahara, Cari M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Kitahara, Cari M.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Shikany, James M.] Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL USA.
RP Kitahara, CM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
EM kitaharac@mail.nih.gov
RI 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, NIH
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, NIH.
NR 42
TC 95
Z9 98
U1 0
U2 11
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 MAR
PY 2011
VL 20
IS 3
BP 464
EP 472
DI 10.1158/1055-9965.EPI-10-1220
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 730WO
UT WOS:000288067200007
PM 21266520
ER
PT J
AU Zapka, JM
Klabunde, CN
Arora, NK
Yuan, G
Smith, JL
Kobrin, SC
AF Zapka, Jane M.
Klabunde, Carrie N.
Arora, Neeraj K.
Yuan, Gigi
Smith, Judith Lee
Kobrin, Sarah C.
TI Physicians' Colorectal Cancer Screening Discussion and Recommendation
Patterns
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID INFORMED DECISION-MAKING; CLIENT-DIRECTED INTERVENTIONS; PRIMARY-CARE
PRACTICES; CENTERED MEDICAL HOME; SERVICES TASK-FORCE; HEALTH-CARE;
PREVENTIVE SERVICES; PATIENT PREFERENCES; SOCIETY GUIDELINES;
SELF-REPORT
AB Background: Primary care physician (PCP) actions are pivotal to colorectal cancer (CRC) screening performance, and guidelines recommend discussion with patients about test options and potential benefits and harms. This article profiles patterns of discussion about and recommendations for screening and explores potential associations with multilevel factors (patient, clinician, practice, and environment).
Methods: In 2009, we analyzed data from 1,266 physicians responding to the 2006-2007 National Survey of Primary Care Physicians' Recommendations and Practices for Breast, Cervical, Colorectal, and Lung Cancer Screening (absolute response rate = 69.3%; cooperation rate = 75.0%). Descriptive statistics examined physicians' reports of discussion and recommendations. Multivariate analyses assessed the associations of these practices with multilevel factors.
Results: Although few respondents reported discussion of all options, 46% usually discuss more than one option; the vast majority of these respondents discuss fecal occult blood testing (FOBT) and colonoscopy (49%) or FOBT, sigmoidoscopy, and colonoscopy (32%). Of physicians who discuss more than one option, a majority reported usually recommending one or more test options, most commonly colonoscopy alone (43%) and FOBT and colonoscopy (43%). Several personal characteristics (specialty), perceived patient characteristics (prefer physician to decide), practice characteristics (geographic location), and community barriers (specialist availability) were independently associated with discussion and/or recommendation patterns.
Conclusions: PCPs do not discuss the full menu of test options, but many report selecting one or two options for discussion and recommendation. To ensure that patients' perspectives and concerns are elicited and considered, patient decision-making approaches should be considered.
Impact: Attention to informed decision making in CRC screening will be important for enhancing patient-centered quality care. Cancer Epidemiol Biomarkers Prev; 20(3); 509-21. (C)2011 AACR.
C1 [Zapka, Jane M.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Klabunde, Carrie N.; Arora, Neeraj K.; Kobrin, Sarah C.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Yuan, Gigi] Informat Management Serv Inc, Silver Spring, MD USA.
[Smith, Judith Lee] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
RP Zapka, JM (reprint author), Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, 135 Cannon St, Charleston, SC 29425 USA.
EM zapka@musc.edu
FU National Cancer Institute [N02-PC-51308]; Agency for Healthcare Research
and Quality [Y3-PC-5019-01, Y3-PC-5019-02]; Centers for Disease Control
and Prevention [Y3-PC-6017-01]
FX Funding support for this study was provided by the National Cancer
Institute (contract number N02-PC-51308); the Agency for Healthcare
Research and Quality (interagency agreement numbers Y3-PC-5019-01 and
Y3-PC-5019-02); and the Centers for Disease Control and Prevention
(interagency agreement number Y3-PC-6017-01).
NR 66
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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 MAR
PY 2011
VL 20
IS 3
BP 509
EP 521
DI 10.1158/1055-9965.EPI-10-0749
PG 13
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 730WO
UT WOS:000288067200013
PM 21239688
ER
PT J
AU Gunter, MJ
Cross, AJ
Huang, WY
Stanczyk, FZ
Purdue, M
Xue, XN
Schoen, R
Limburg, PJ
Schatzkin, A
Sinha, R
Hayes, RB
AF Gunter, Marc J.
Cross, Amanda J.
Huang, Wen-Yi
Stanczyk, Frank Z.
Purdue, Mark
Xue, Xiaonan
Schoen, Robert
Limburg, Paul J.
Schatzkin, Arthur
Sinha, Rashmi
Hayes, Richard B.
TI A Prospective Evaluation of C-reactive Protein Levels and Colorectal
Adenoma Development
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CANCER SCREENING TRIAL; INFLAMMATORY CYTOKINES; CIRCULATING LEVELS;
EARLY MARKER; RISK; CELLS; PROSTATE; HEALTH; COLON; LUNG
AB Background: Inflammation is hypothesized to play a role in colorectal tumorigenesis. Circulating levels of C-reactive protein (CRP), a serologic marker of the inflammatory response, have been positively associated with colorectal cancer development in some studies; however, there are limited data on the relation of CRP with colorectal adenomas, established precursors of colorectal cancer.
Methods: A nested case-control investigation of CRP levels and incident colorectal adenoma was conducted in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized trial of 154,942 individuals designed to test the efficacy of flexible sigmoidoscopy on colorectal cancer mortality when performed once, and then repeated 3 to 5 years later. Serum CRP levels were measured in baseline blood specimens from participants who were free of polyps in the left-sided colorectum at the baseline screening procedure, but who were found at the subsequent screen to have at least one colorectal adenoma (n = 356), and in a set of polyp-free, frequency-matched controls (n = 396).
Results: In a multivariable logistic regression model that included established colorectal adenoma risk factors, a 1-unit increase in log CRP level was associated with a 15% reduction in risk of developing colorectal adenoma (OR - 0.85, 95% CI, 0.75-0.98, P(trend) - 0.01). This association did not differ according to body size, smoking behavior, gender, use of nonsteroidal antiinflammatory drugs, or adenoma location.
Conclusions: High circulating CRP levels may be protective against colorectal adenoma development.
Impact: Though at contrast with mechanistic data on inflammation and colorectal tumorigenesis, this finding is not inconsistent with prior results on CRP and colorectal adenoma and warrants further investigation. Cancer Epidemiol Biomarkers Prev; 20(3); 537-44. (C)2011 AACR.
C1 [Gunter, Marc J.; Xue, Xiaonan] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Cross, Amanda J.; Huang, Wen-Yi; Purdue, Mark; Schatzkin, Arthur; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Schoen, Robert] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Limburg, Paul J.] Mayo Clin, Coll Med, Rochester, MN USA.
[Hayes, Richard B.] NYU, Dept Environm Med, Div Epidemiol, New York, NY USA.
RP Gunter, MJ (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM marc.gunter@einstein.yu.edu
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Hayes, Richard/0000-0002-0918-661X
FU Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and by contracts from the
Division of Cancer Prevention, National Cancer Institute, NIH, DHHS.
NR 38
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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 MAR
PY 2011
VL 20
IS 3
BP 537
EP 544
DI 10.1158/1055-9965.EPI-10-1099
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 730WO
UT WOS:000288067200016
PM 21212059
ER
PT J
AU Kummar, S
Doroshow, JH
AF Kummar, Shivaani
Doroshow, James H.
TI Phase 0 Trials: Expediting the Development of Chemoprevention Agents
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID STAR P-2 TRIAL; DRUG DEVELOPMENT; BREAST-CANCER; RALOXIFENE; TAMOXIFEN
AB Phase 0 trials are first-in-human clinical trials performed under the Exploratory IND [investigational new drug] Guidance of the U. S. Food and Drug Administration. Unlike traditional phase I trials, these studies have no therapeutic or diagnostic intent but instead aim to provide only pharmacokinetic and/or pharmacodynamic data to inform the next step in developing an agent. We discuss the role that such trials, including one reported by Reid and colleagues (beginning on page 347 in this issue of the journal), can play in expanding the number of drugs that are evaluated for chemoprevention while compressing the drug-development timeline. Cancer Prev Res; 4(3); 288-92. (C)2011 AACR.
C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999, ZIA BC011078-03]
NR 13
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PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 288
EP 292
DI 10.1158/1940-6207.CAPR-11-0013
PG 5
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800002
PM 21372025
ER
PT J
AU Mai, PL
Wentzensen, N
Greene, MH
AF Mai, Phuong L.
Wentzensen, Nicolas
Greene, Mark H.
TI Challenges Related to Developing Serum-Based Biomarkers for Early
Ovarian Cancer Detection
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID SCREENING TRIAL; CA-125 LEVELS; MARKERS; PROSTATE; LUNG
AB In this issue of the journal, Cramer and colleagues and Zhu and colleagues report carefully designed phase 3 assessments of candidate ovarian cancer screening biomarkers. The main conclusion is that CA-125 remains the "best of a bad lot"; the new candidates have fallen short of expectations. We review factors impeding the development of an effective ovarian cancer screening strategy, highlight the requirements related to validating proposed screening biomarkers, and emphasize the risks from premature clinical applications of unvalidated tests, all underscoring the need for new research strategies. Cancer Prev Res; 4(3); 303-6. (C)2011 AACR.
C1 [Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, NIH, Bethesda, MD USA.
[Wentzensen, Nicolas] NCI, Hormone & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA.
RP Greene, MH (reprint author), 6120 Execut Blvd,Room EPS 7032, Rockville, MD 20852 USA.
EM greenem@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010144-10]
NR 21
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 303
EP 306
DI 10.1158/1940-6207.CAPR-11-0053
PG 4
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800006
PM 21372029
ER
PT J
AU Meyskens, FL
Curt, GA
Brenner, DE
Gordon, G
Herberman, RB
Finn, O
Kelloff, GJ
Khleif, SN
Sigman, CC
Szabo, E
AF Meyskens, Frank L., Jr.
Curt, Gregory A.
Brenner, Dean E.
Gordon, Gary
Herberman, Ronald B.
Finn, Olivera
Kelloff, Gary J.
Khleif, Samir N.
Sigman, Caroline C.
Szabo, Eva
CA C-Change Chemoprevention Clinical
TI Regulatory Approval of Cancer Risk-Reducing (Chemopreventive) Drugs:
Moving What We Have Learned into the Clinic
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID GRADE PROSTATE-CANCER; 2ND PRIMARY TUMORS; SPORADIC COLORECTAL ADENOMAS;
SURGICAL ADJUVANT BREAST; SQUAMOUS-CELL CARCINOMA; SURROGATE END-POINTS;
STAR P-2 TRIAL; INTRAEPITHELIAL NEOPLASIA; PREVENTION TRIAL; AGENT
DEVELOPMENT
AB This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high (er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs. Cancer Prev Res; 4(3); 311-23. (C)2011 AACR.
C1 [Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA.
[Curt, Gregory A.] AstraZeneca Oncol, Garret Pk, MD USA.
[Brenner, Dean E.] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Gordon, Gary] Abbott Labs Inc, Abbott Pk, IL USA.
[Herberman, Ronald B.] Intrexon Corp, Germantown, MD USA.
[Finn, Olivera] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Kelloff, Gary J.; Khleif, Samir N.; C-Change Chemoprevention Clinical] NCI, Rockville, MD USA.
[Sigman, Caroline C.] CCS Associates, Mountain View, CA USA.
RP Meyskens, FL (reprint author), UCI Canc Ctr, Bldg 44,Route 81,101 City Dr Canc Ctr, Orange, CA 92668 USA.
EM flmeyske@uci.edu
FU [P30CA62203]
FX This study was supported in part by P30CA62203 (to F.L. Meyskens).
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 311
EP 323
DI 10.1158/1940-6207.CAPR-09-0014
PG 13
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800008
PM 21372031
ER
PT J
AU Subbaramaiah, K
Howe, LR
Bhardwaj, P
Du, BH
Gravaghi, C
Yantiss, RK
Zhou, XK
Blaho, VA
Hla, T
Yang, PY
Kopelovich, L
Hudis, CA
Dannenberg, AJ
AF Subbaramaiah, Kotha
Howe, Louise R.
Bhardwaj, Priya
Du, Baoheng
Gravaghi, Claudia
Yantiss, Rhonda K.
Zhou, Xi Kathy
Blaho, Victoria A.
Hla, Timothy
Yang, Peiying
Kopelovich, Levy
Hudis, Clifford A.
Dannenberg, Andrew J.
TI Obesity Is Associated with Inflammation and Elevated Aromatase
Expression in the Mouse Mammary Gland
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID ADIPOSE STROMAL CELLS; NECROSIS-FACTOR-ALPHA; BREAST-CANCER CELLS;
BODY-MASS INDEX; FATTY-ACIDS; POSTMENOPAUSAL WOMEN; GENE-EXPRESSION;
TNF-ALPHA; TISSUE; MACROPHAGES
AB Elevated circulating estrogen levels are associated with increased risk of breast cancer in obese postmenopausal women. Following menopause, the biosynthesis of estrogens through CYP19 (aromatase)mediated metabolism of androgen precursors occurs primarily in adipose tissue, and the resulting estrogens are then secreted into the systemic circulation. The potential links between obesity, inflammation, and aromatase expression are unknown. In both dietary and genetic models of obesity, we observed necrotic adipocytes surrounded by macrophages forming crown-like structures (CLS) in the mammary glands and visceral fat. The presence of CLS was associated with activation of NF-kappa B and increased levels of proinflammatory mediators (TNF-alpha, IL-1 beta, Cox-2), which were paralleled by elevated levels of aromatase expression and activity in the mammary gland and visceral fat of obese mice. Analyses of the stromal-vascular and adipocyte fractions of the mammary gland suggested that macrophage-derived proinflammatory mediators induced aromatase and estrogen-dependent gene expression (PR, pS2) in adipocytes. Saturated fatty acids, which have been linked to obesity-related inflammation, stimulated NF-kappa B activity in macrophages leading to increased levels of TNF-alpha, IL-1 beta, and Cox-2, each of which contributed to the induction of aromatase in preadipocytes. The discovery of the obesity -> inflammation -> aromatase axis in the mammary gland and visceral fat and its association with CLS may provide insight into mechanisms underlying the increased risk of hormone receptor-positive breast cancer in obese postmenopausal women, the reduced efficacy of aromatase inhibitors in the treatment of breast cancer in these women, and their generally worse outcomes. The presence of CLS may be a biomarker of increased breast cancer risk or poor prognosis. Cancer Prev Res; 4(3); 329-46. (C)2011 AACR.
C1 [Subbaramaiah, Kotha; Bhardwaj, Priya; Du, Baoheng; Gravaghi, Claudia; Dannenberg, Andrew J.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Howe, Louise R.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA.
[Yantiss, Rhonda K.; Blaho, Victoria A.; Hla, Timothy] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Zhou, Xi Kathy] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA.
[Yang, Peiying] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
RP Dannenberg, AJ (reprint author), Weill Cornell Med Coll, Dept Med, 525 E 68th St,Room F-206, New York, NY 10065 USA.
EM ksubba@med.cornell.edu; ajdannen@med.cornell.edu
RI Hla, Timothy/G-5873-2012
OI Hla, Timothy/0000-0001-8355-4065
FU NIH [R25CA105012]; NCI [N01-CN-43302]; Breast Cancer Research
Foundation; Botwinick-Wolfensohn Foundation; New Chapter, Inc.
FX This work was supported by NIH R25CA105012, NCI N01-CN-43302, the Breast
Cancer Research Foundation, the Botwinick-Wolfensohn Foundation (in
memory of Mr. and Mrs. Benjamin Botwinick), and New Chapter, Inc.
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PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 329
EP 346
DI 10.1158/1940-6207.CAPR-10-0381
PG 18
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800010
PM 21372033
ER
PT J
AU Reid, JM
Walden, CA
Qin, R
Ziegler, KLA
Haslam, JL
Rajewski, RA
Warndahl, R
Fitting, CL
Boring, D
Szabo, E
Crowell, J
Perloff, M
Jong, L
Bauer, BA
Mandrekar, SJ
Ames, MM
Limburg, PJ
AF Reid, Joel M.
Walden, Chad A.
Qin, Rui
Ziegler, Katie L. Allen
Haslam, John L.
Rajewski, Roger A.
Warndahl, Roger
Fitting, Cindy L.
Boring, Daniel
Szabo, Eva
Crowell, James
Perloff, Marjorie
Jong, Ling
Bauer, Brent A.
Mandrekar, Sumithra J.
Ames, Matthew M.
Limburg, Paul J.
CA Canc Prevention Network
TI Phase 0 Clinical Chemoprevention Trial of the Akt Inhibitor SR13668
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID CELLS; BIOAVAILABILITY; ACTIVATION; APOPTOSIS; AGENT; EVENT
AB SR13668, an orally active Akt pathway inhibitor, has demonstrated cancer chemopreventive potential in preclinical studies. To accelerate the clinical development of this promising agent, we designed and conducted the first-ever phase 0 chemoprevention trial to evaluate and compare the effects of food and formulation on SR13668 bioavailability. Healthy adult volunteers were randomly assigned to receive a single, 38-mg oral dose of SR13668 in one of five different formulations, with or without food. On the basis of existing animal data, SR13668 in a PEG400/Labrasol oral solution was defined as the reference formulation. Blood samples were obtained pre- and post-agent administration for pharmacokinetic analyses. Area under the plasma concentration-time curve (AUC(0-infinity)) was defined as the primary endpoint. Data were analyzed and compared using established statistical methods for phase 0 trials with a limited sample size. Participants (n = 20) were rapidly accrued over a 5-month period. Complete pharmacokinetic data were available for 18 randomized participants. AUC(0-infinity) values were highest in the fed state (range = 122-439 ng/mL x hours) and were statistically significantly different across formulations (P = 0.007), with Solutol HS15 providing the highest bioavailability. SR13668 time to peak plasma concentration (3 hours; range, 2-6 hours) and half-life were (11.2 +/- 3.1 hours) were not formulation-dependent. Using a novel, highly efficient study design, we rapidly identified a lead formulation of SR13668 for further clinical testing. Our findings support application of the phase 0 trial paradigm to accelerate chemoprevention agent development. Cancer Prev Res; 4(3); 347-53. (C)2011 AACR.
C1 [Reid, Joel M.; Walden, Chad A.; Qin, Rui; Ziegler, Katie L. Allen; Warndahl, Roger; Fitting, Cindy L.; Bauer, Brent A.; Mandrekar, Sumithra J.; Ames, Matthew M.; Limburg, Paul J.] Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA.
[Haslam, John L.; Rajewski, Roger A.] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66045 USA.
[Boring, Daniel; Szabo, Eva; Perloff, Marjorie] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Crowell, James] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Jong, Ling] SRI Int, Biosci Div, Ctr Canc Res, Menlo Pk, CA 94025 USA.
RP Limburg, PJ (reprint author), 200 1st St SW, Rochester, MN 55905 USA.
EM limburg.paul@mayo.edu
RI Qin, Rui/H-5638-2012
FU NIH [N01-CN-35000, CA15083-34C3, UL1 RR024150]
FX Supported by NIH grants/contracts N01-CN-35000, CA15083-34C3, and UL1
RR024150
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 347
EP 353
DI 10.1158/1940-6207.CAPR-10-0313
PG 7
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800011
PM 21372034
ER
PT J
AU Carroll, RE
Benya, RV
Turgeon, DK
Vareed, S
Neuman, M
Rodriguez, L
Kakarala, M
Carpenter, PM
McLaren, C
Meyskens, FL
Brenner, DE
AF Carroll, Robert E.
Benya, Richard V.
Turgeon, Danielle Kim
Vareed, Shaiju
Neuman, Malloree
Rodriguez, Luz
Kakarala, Madhuri
Carpenter, Philip M.
McLaren, Christine
Meyskens, Frank L., Jr.
Brenner, Dean E.
TI Phase IIa Clinical Trial of Curcumin for the Prevention of Colorectal
Neoplasia
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID ABERRANT CRYPT FOCI; FAMILIAL ADENOMATOUS POLYPOSIS; PLACEBO-CONTROLLED
TRIAL; COLON-CANCER; LIQUID-CHROMATOGRAPHY; CELL-PROLIFERATION;
PANCREATIC-CANCER; DIETARY CURCUMIN; CHEMOPREVENTION; CARCINOGENESIS
AB Curcumin is derived from the spice tumeric and has antiinflammatory and antineoplastic effects in vitro and in animal models, including preventing aberrant crypt foci (ACF) and adenomas in murine models of colorectal carcinogenesis. Inhibiting the production of the procarcinogenic eicosanoids prostaglandin E-2 (PGE(2)) and 5-hydroxyeicosatetraenoic acid (5-HETE) can suppress carcinogenesis in rodents. Curcumin reduces mucosal concentrations of PGE(2) (via inhibition of cyclooxygenases 1 and 2) and 5-HETE (via inhibition of 5-lipoxygenase) in rats. Although preclinical data support curcumin activity in many sites, the poor bioavailability reported for this agent supports its use in the colorectum. We assessed the effects of oral curcumin (2 g or 4 g per day for 30 days) on PGE(2) within ACF (primary endpoint), 5-HETE, ACF number, and proliferation in a nonrandomized, open-label clinical trial in 44 eligible smokers with eight or more ACF on screening colonoscopy. We assessed pre- and posttreatment concentrations of PGE(2) and 5-HETE by liquid chromatography tandem mass spectroscopy in ACF and normal-tissue biopsies; ACF number via rectal endoscopy; proliferation by Ki-67 immunohistochemistry; and curcumin concentrations by high-performance liquid chromatography in serum and rectal mucosal samples. Forty-one subjects completed the study. Neither dose of curcumin reduced PGE(2) or 5-HETE within ACF or normal mucosa or reduced Ki-67 in normal mucosa. A significant 40% reduction in ACF number occurred with the 4-g dose (P < 0.005), whereas ACF were not reduced in the 2-g group. The ACF reduction in the 4-g group was associated with a significant, five-fold increase in posttreatment plasma curcumin/conjugate levels (versus pretreatment; P = 0.009). Curcumin was well tolerated at both 2 g and 4 g. Our data suggest that curcumin can decrease ACF number, and this is potentially mediated by curcumin conjugates delivered systemically. Cancer Prev Res; 4(3); 354-64. (C)2011 AACR.
C1 [Carroll, Robert E.; Benya, Richard V.] Univ Illinois, Dept Med, Chicago, IL 60612 USA.
[Carroll, Robert E.; Benya, Richard V.] Univ Illinois, Chicago Vet Adm Med Ctr, W Side Div, Chicago, IL 60612 USA.
[Turgeon, Danielle Kim; Vareed, Shaiju; Kakarala, Madhuri; Carpenter, Philip M.; Brenner, Dean E.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Neuman, Malloree; Brenner, Dean E.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Rodriguez, Luz] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Kakarala, Madhuri; Brenner, Dean E.] Vet Adm Med Ctr, Ann Arbor, MI 48105 USA.
[McLaren, Christine; Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr Orange, Irvine, CA USA.
[McLaren, Christine] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
RP Carroll, RE (reprint author), Univ Illinois, Dept Med, 840 S Wood St M-C 787, Chicago, IL 60612 USA.
EM rcarroll@uic.edu
FU NIH; National Cancer Institute [NCI-N01-CN-35160, NCI-K07-CA12884,
M01-RR000042, UL1RR024986]; Kutche Family Professorship; [P30-CA62203];
[NO-1 CN-25000]; [39]
FX This work was supported by NIH, National Cancer Institute contract
NCI-N01-CN-35160 (to R. E. Carroll), NCI-K07-CA12884 (to M. Kakarala),
and grants M01-RR000042 and UL1RR024986 to the University of Michigan,
and the Kutche Family Professorship (to D. E. Brenner). P30-CA62203 and
contract NO-1 CN-25000(39; to F. L. Meyskens, Jr)
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PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 354
EP 364
DI 10.1158/1940-6207.CAPR-10-0098
PG 11
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800012
PM 21372035
ER
PT J
AU Cramer, DW
Bast, RC
Berg, CD
Diamandis, EP
Godwin, AK
Hartge, P
Lokshin, AE
Lu, KH
McIntosh, MW
Mor, G
Patriotis, C
Pinsky, PF
Thornquist, MD
Scholler, N
Skates, SJ
Sluss, PM
Srivastava, S
Ward, DC
Zhang, Z
Zhu, CS
Urban, N
AF Cramer, Daniel W.
Bast, Robert C., Jr.
Berg, Christine D.
Diamandis, Eleftherios P.
Godwin, Andrew K.
Hartge, Patricia
Lokshin, Anna E.
Lu, Karen H.
McIntosh, Martin W.
Mor, Gil
Patriotis, Christos
Pinsky, Paul F.
Thornquist, Mark D.
Scholler, Nathalie
Skates, Steven J.
Sluss, Patrick M.
Srivastava, Sudhir
Ward, David C.
Zhang, Zhen
Zhu, Claire S.
Urban, Nicole
TI Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial Specimens
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID BIOTINYLATED RECOMBINANT ANTIBODIES; DIAGNOSTIC MARKERS; SERUM;
MANAGEMENT
AB Establishing a cancer screening biomarker's intended performance requires "phase III" specimens obtained in asymptomatic individuals before clinical diagnosis rather than "phase II" specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network or Ovarian Cancer Specialized Program of Research Excellence sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within 6 months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study. Cancer Prev Res; 4(3); 365-74. (C)2011 AACR.
C1 [Cramer, Daniel W.] Brigham & Womens Hosp, Div Epidemiol, Boston, MA 02115 USA.
[Bast, Robert C., Jr.; Lu, Karen H.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Berg, Christine D.; Pinsky, Paul F.; Zhu, Claire S.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Diamandis, Eleftherios P.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Lokshin, Anna E.] Univ Pittsburgh, Pittsburgh, PA USA.
[McIntosh, Martin W.; Thornquist, Mark D.; Urban, Nicole] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Mor, Gil] Yale Univ, New Haven, CT USA.
[Patriotis, Christos; Srivastava, Sudhir] NCI, Canc Biomarker Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Scholler, Nathalie] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Skates, Steven J.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ward, David C.] Univ Honolulu, Canc Res Ctr, Honolulu, HI USA.
[Zhang, Zhen] Johns Hopkins Univ, Baltimore, MD USA.
RP Cramer, DW (reprint author), Brigham & Womens Hosp, Div Epidemiol, 221 Longwood Ave,RFB 365, Boston, MA 02115 USA.
EM dcramer@partners.org
RI Bast, Robert/E-6585-2011; Berg , Christine/K-1047-2014; Scholler,
Nathalie/O-9003-2014;
OI Bast, Robert/0000-0003-4621-8462; Diamandis,
Eleftherios/0000-0002-1589-820X
FU Ovarian Cancer SPOREs at FHCRC [P50 CA083636]; MDACC [P50 CA83639];
FCCC/UPenn [P50 CA083638]; NCI [N01-CN-43309]; EDRN CVC [5U01 CA113916];
Ovarian Cancer SPORE at BWH [P50 CA105009]; EDRN [5U01 CA86381]; Golfers
Against Cancer; Wiley Mossy Foundation
FX This work was supported in part by the Ovarian Cancer SPOREs at FHCRC
(P50 CA083636), to N. Urban, MDACC (P50 CA83639) to R. C. Bast and
FCCC/UPenn (P50 CA083638), an NCI contract (N01-CN-43309), an EDRN CVC
(5U01 CA113916) to A. K. Godwin; an Ovarian Cancer SPORE at BWH (P50
CA105009) and an EDRN (5U01 CA86381) to D. W. Cramer; and grants from
Golfers Against Cancer and the Wiley Mossy Foundation to R. C. Bast.
NR 26
TC 118
Z9 126
U1 2
U2 17
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 365
EP 374
DI 10.1158/1940-6207.CAPR-10-0195
PG 10
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800013
PM 21372036
ER
PT J
AU Zhu, CS
Pinsky, PF
Cramer, DW
Ransohoff, DF
Hartge, P
Pfeiffer, RM
Urban, N
Mor, G
Bast, RC
Moore, LE
Lokshin, AE
McIntosh, MW
Skates, SJ
Vitonis, A
Zhang, Z
Ward, DC
Symanowski, JT
Lomakin, A
Fung, ET
Sluss, PM
Scholler, N
Lu, KH
Marrangoni, AM
Patriotis, C
Srivastava, S
Buys, SS
Berg, CD
AF Zhu, Claire S.
Pinsky, Paul F.
Cramer, Daniel W.
Ransohoff, David F.
Hartge, Patricia
Pfeiffer, Ruth M.
Urban, Nicole
Mor, Gil
Bast, Robert C., Jr.
Moore, Lee E.
Lokshin, Anna E.
McIntosh, Martin W.
Skates, Steven J.
Vitonis, Allison
Zhang, Zhen
Ward, David C.
Symanowski, James T.
Lomakin, Aleksey
Fung, Eric T.
Sluss, Patrick M.
Scholler, Nathalie
Lu, Karen H.
Marrangoni, Adele M.
Patriotis, Christos
Srivastava, Sudhir
Buys, Saundra S.
Berg, Christine D.
CA PLCO Project Team
TI A Framework for Evaluating Biomarkers for Early Detection: Validation of
Biomarker Panels for Ovarian Cancer
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID SCREENING TRIAL; PROTEOMIC PATTERNS; TUMOR-MARKERS; PROSTATE; SERUM;
LUNG; POPULATION; PREDICTION; DESIGN
AB A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used prediagnostic samples to assess the potential of the panels for early detection. We conducted a multisite systematic evaluation of biomarker panels using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial.
Using a nested case-control design, levels of 28 biomarkers were measured laboratory-blinded in 118 serum samples obtained before cancer diagnosis and 951 serum samples from matched controls. Five predictive models, each containing 6 to 8 biomarkers, were evaluated according to a predetermined analysis plan. Three sequential analyses were conducted: blinded validation of previously established models (step 1); simultaneous split-sample discovery and validation of models (step 2); and exploratory discovery of new models (step 3). Sensitivity, specificity, sensitivity at 98% specificity, and AUC were computed for the models and CA125 alone among 67 cases diagnosed within one year of blood draw and 476 matched controls. In step 1, one model showed comparable performance to CA125, with sensitivity, specificity, and AUC at 69.2%, 96.6%, and 0.892, respectively. Remaining models had poorer performance than CA125 alone. In step 2, we observed a similar pattern. In step 3, a model derived from all 28 markers failed to show improvement over CA125.
Thus, biomarker panels discovered in diagnostic samples may not validate in prediagnostic samples; utilizing prediagnostic samples for discovery may be helpful in developing validated early detection panels. Cancer Prev Res; 4(3); 375-83. (C)2011 AACR.
C1 [Berg, Christine D.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Cramer, Daniel W.; Vitonis, Allison] Brigham & Womens Hosp, Ob Gyn Epidemiol Ctr, Boston, MA 02115 USA.
[Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Ransohoff, David F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Hartge, Patricia; Pfeiffer, Ruth M.; Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Urban, Nicole; McIntosh, Martin W.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Mor, Gil] Yale Univ, Sch Med, Dept Obstet & Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT USA.
[Bast, Robert C., Jr.; Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX USA.
[Lokshin, Anna E.; Marrangoni, Adele M.] Univ Pittsburgh, Inst Med, Hillman Canc Ctr, Pittsburgh, PA USA.
[Skates, Steven J.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Zhang, Zhen] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA.
[Ward, David C.] Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
[Symanowski, James T.] Nevada Canc Inst, Las Vegas, NV USA.
[Lomakin, Aleksey] MIT, Boston, MA USA.
[Fung, Eric T.] Vermillion Inc, Fremont, CA USA.
[Scholler, Nathalie] Univ Penn, Sch Med, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA.
[Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA.
RP Berg, CD (reprint author), NCI, Canc Prevent Div, NIH, 6130 Execut Blvd,Rm 3112, Bethesda, MD 20892 USA.
EM bergc@mail.nih.gov
RI Bast, Robert/E-6585-2011; Pfeiffer, Ruth /F-4748-2011; Berg ,
Christine/K-1047-2014; Scholler, Nathalie/O-9003-2014
OI Bast, Robert/0000-0003-4621-8462;
FU National Cancer Institute; National Cancer Institute [P50 CA083636, P50
CA083639, 5U01 CA86381, R01 CA127913, U01 CA084986]; Golfers Against
Cancer; Wiley Mossy Foundation
FX This work was supported in part by contracts from the National Cancer
Institute to 10 PLCO screening centers, a coordinating center and a
central analytic laboratory; grants from the National Cancer Institute
(P50 CA083636 to NU, P50 CA083639 to R. C. Bast, 5U01 CA86381 to DWC,
R01 CA127913 and U01 CA084986 to G. Mor); and grants from Golfers
Against Cancer and the Wiley Mossy Foundation to R. C. Bast.
NR 29
TC 92
Z9 93
U1 0
U2 17
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 375
EP 383
DI 10.1158/1940-6207.CAPR-10-0193
PG 9
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800014
PM 21372037
ER
PT J
AU Kim, EH
Deng, CX
Sporn, MB
Liby, KT
AF Kim, Eun-Hee
Deng, Chu-Xia
Sporn, Michael B.
Liby, Karen T.
TI CDDO-Imidazolide Induces DNA Damage, G2/M Arrest and Apoptosis in
BRCA1-Mutated Breast Cancer Cells
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID TRITERPENOID 2-CYANO-3,12-DIOXOOLEANA-1,9-DIEN-28-OIC ACID; NITRIC-OXIDE
PRODUCTION; SYNTHETIC TRITERPENOIDS; CHECKPOINT KINASES;
PROSTATE-CANCER; IN-VIVO; BRCA1; GROWTH; DEATH; INHIBITION
AB Breast cancer-associated gene 1 (BRCA1) protein plays important roles in DNA damage and repair, homologous recombination, cell-cycle regulation, and apoptosis. The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Imidazolide, CDDO-Im) is a promising anticancer and chemopreventive agent with potent antiproliferative and apoptotic activities against a wide variety of cancer types. However, the mechanisms responsible for the selective apoptotic effects of CDDO-Im in cancer cells remain elusive. In the present work, CDDO-Im induced G2/M arrest and apoptosis in BRCA1-mutated mammary tumor cell lines. Prior to the induction of apoptosis, CDDO-Im induced DNA damage and the phosphorylation of H2AX followed by activation of the DNA damage response. Moreover, CDDO-Im also induced the generation of reactive oxygen species (ROS), which is associated with the induction of DNA damage, in both mouse and human tumor cells containing a BRCA1 mutation. The inhibition of ROS generation by uric acid prevented the induction of DNA damage by CDDO-Im. Furthermore, treatment with CDDO-Im did not induce ROS in nonmalignant MCF-10A breast epithelial cells or in E18-14C-27 breast cancer cells with wild-type BRCA1 genes and was not cytotoxic to normal mouse 3T3 fibroblasts, highlighting a selective therapeutic potential of CDDO-Im for BRCA1-associated breast cancer cells. Altogether, our results show that CDDO-Im induces ROS and subsequent DNA damage, thereby facilitating the activation of the DNA damage checkpoint, G2/M arrest, and finally apoptosis in BRCA1-mutated cancer cells. The particular relevance of these findings to the chemoprevention of cancer is discussed. Cancer Prev Res; 4(3); 425-34. (C)2011 AACR.
C1 [Liby, Karen T.] Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA.
[Kim, Eun-Hee; Sporn, Michael B.] Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03755 USA.
[Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Liby, KT (reprint author), Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA.
EM Karen.T.Liby@Dartmouth.Edu
RI deng, chuxia/N-6713-2016
FU Reata Pharmaceuticals; Breast Cancer Research Foundation; NIH [RO1
CA78814]
FX M.B. Sporn: commercial research grant, Reata Pharmaceuticals; M.B. Sporn
and K. Liby: patent interest in synthetic triterpenoids. The other
authors disclosed no potential conflicts of interest.; These studies
were supported by the Breast Cancer Research Foundation, the NIH (RO1
CA78814), and Reata Pharmaceuticals.
NR 41
TC 22
Z9 24
U1 2
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 425
EP 434
DI 10.1158/1940-6207.CAPR-10-0153
PG 10
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800019
PM 21372041
ER
PT J
AU Schwartz, AG
Wenzlaff, AS
Bock, CH
Ruterbusch, JJ
Chen, W
Cote, ML
Artis, AS
Van Dyke, AL
Land, SJ
Harris, CC
Pine, SR
Spitz, MR
Amos, CI
Levin, AM
McKeigue, PM
AF Schwartz, Ann G.
Wenzlaff, Angela S.
Bock, Cathryn H.
Ruterbusch, Julie J.
Chen, Wei
Cote, Michele L.
Artis, Amanda S.
Van Dyke, Alison L.
Land, Susan J.
Harris, Curtis C.
Pine, Sharon R.
Spitz, Margaret R.
Amos, Christopher I.
Levin, Albert M.
McKeigue, Paul M.
TI Admixture mapping of lung cancer in 1812 African-Americans
SO CARCINOGENESIS
LA English
DT Article
ID MICROSOMAL EPOXIDE HYDROLASE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY
LOCUS; NICOTINE DEPENDENCE; RECEPTOR GENES; RISK; POLYMORPHISMS;
POPULATION; DISEASE; TOBACCO
AB Lung cancer continues to be the leading cause of cancer death in the USA and the best example of a cancer with undisputed evidence of environmental risk. However, a genetic contribution to lung cancer has also been demonstrated by studies of familial aggregation, family-based linkage, candidate gene studies and most recently genome-wide association studies (GWAS). The African-American population has been underrepresented in these genetic studies and has patterns of cigarette use and linkage disequilibrium that differ from patterns in other populations. Therefore, studies in African-Americans can provide complementary data to localize lung cancer susceptibility genes and explore smoking dependence-related genes. We used admixture mapping to further characterize genetic risk of lung cancer in a series of 837 African-American lung cancer cases and 975 African-American controls genotyped at 1344 ancestry informative single-nucleotide polymorphisms. Both case-only and case-control analyses were conducted using ADMIXMAP adjusted for age, sex, pack-years of smoking, family history of lung cancer, history of emphysema and study site. In case-only analyses, excess European ancestry was observed over a wide region on chromosome 1 with the largest excess seen at rs6587361 for non-small-cell lung cancer (NSCLC) (Z-score = -4.33; P = 1.5 x 10(-5)) and for women with NSCLC (Z-score = -4.82; P = 1.4 x 10(-6)). Excess African ancestry was also observed on chromosome 3q with a peak Z-score of 3.33 (P = 0.0009) at rs181696 among ever smokers with NSCLC. These results add to the findings from the GWAS in Caucasian populations and suggest novel regions of interest.
C1 [Schwartz, Ann G.; Wenzlaff, Angela S.; Bock, Cathryn H.; Ruterbusch, Julie J.; Chen, Wei; Cote, Michele L.; Artis, Amanda S.; Van Dyke, Alison L.; Land, Susan J.] Karmanos Canc Inst, Detroit, MI 48201 USA.
[Schwartz, Ann G.; Bock, Cathryn H.; Chen, Wei; Cote, Michele L.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA.
[Land, Susan J.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Appl Genom Technol Ctr, Detroit, MI 48201 USA.
[Harris, Curtis C.; Pine, Sharon R.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Spitz, Margaret R.; Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Levin, Albert M.] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA.
[McKeigue, Paul M.] Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
RP Schwartz, AG (reprint author), Karmanos Canc Inst, 4100 John R, Detroit, MI 48201 USA.
EM schwarta@karmanos.org
FU National Institutes of Health (NIH) [R01-CA87895, R01-CA60691,
R01-CA55769, R01-CA127219, R01-CA141716, R01-CA133996, R01-CA121197,
U19-CA148127, N01-PC35145, P30CA22453]; Cancer Prevention Research
Institute of Texas [RP10043]; National Cancer Institute/NIH, Center for
Cancer Research
FX National Institutes of Health (NIH) (R01-CA87895, R01-CA60691,
R01-CA55769, R01-CA127219, R01-CA141716, , R01-CA133996, R01-CA121197,
U19-CA148127 and contract numbers N01-PC35145 and P30CA22453); Cancer
Prevention Research Institute of Texas (RP10043); Intramural Research
Program of the National Cancer Institute/NIH, Center for Cancer
Research.
NR 33
TC 11
Z9 11
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD MAR
PY 2011
VL 32
IS 3
BP 312
EP 317
DI 10.1093/carcin/bgq252
PG 6
WC Oncology
SC Oncology
GA 730IU
UT WOS:000288027800009
PM 21115650
ER
PT J
AU Sinner, MF
Ellinor, PT
Meitinger, T
Benjamin, EJ
Kaab, S
AF Sinner, Moritz F.
Ellinor, Patrick T.
Meitinger, Thomas
Benjamin, Emelia J.
Kaeaeb, Stefan
TI Genome-wide association studies of atrial fibrillation: past, present,
and future
SO CARDIOVASCULAR RESEARCH
LA English
DT Review
DE Atrial fibrillation; Genetics; Genome-wide association study; Single
nucleotide polymorphism; Arrhythmia
ID TRANSCRIPTION FACTOR ATBF1; CA2+-ACTIVATED K+ CHANNEL; QT INTERVAL
DURATION; LEFT-RIGHT ASYMMETRY; SMALL-CONDUCTANCE; CHROMOSOME 4Q25;
COMMON VARIANTS; RISK-FACTORS; PR INTERVAL; HEART-RATE
AB Genome-wide association studies (GWAS) for atrial fibrillation (AF) have identified three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 that are associated with the arrhythmia. Susceptibility loci also have been identified by GWAS for PR interval duration, a quantitative phenotype related to AF. In this review article, we have sought to summarize the latest findings for population-based genetic studies of AF, to highlight ongoing functional studies, and to explore the future directions of genetic research on AF.
C1 [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Hosp Munich, Dept Med 1, D-81377 Munich, Germany.
[Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Sinner, Moritz F.; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA.
[Sinner, Moritz F.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Prevent Med Sect, Boston, MA 02118 USA.
RP Kaab, S (reprint author), Univ Hosp Munich, Dept Med 1, Campus Grosshadern,Marchioninistr 15, D-81377 Munich, Germany.
EM skaab@med.lmu.de
RI Meitinger, Thomas/O-1318-2015;
OI Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health [1R01HL092577, 1RC1HL101056, 1R01HL102214,
1R01HL104156, 5R21DA027021, 1K24HL105780]; Bundesministerium fur Bildung
und Forschung BMBF (German Competence Network on AF AFNET [01 GI
0204/N]; German National Genome Research Network NGFN [01GS0499,
01GS0838]; Leducq Foundation [07-CVD 03]; LMU Excellence Initiative
[557/569]; German Heart Foundation
FX This work was supported by the National Institutes of Health
(1R01HL092577 to E.J.B. and P.T.E.; 1RC1HL101056, 1R01HL102214 to E.J.B;
1R01HL104156, 5R21DA027021, 1K24HL105780 to P.T.E.); Bundesministerium
fur Bildung und Forschung BMBF (German Competence Network on AF AFNET 01
GI 0204/N, German National Genome Research Network NGFN 01GS0499,
01GS0838 to S. K.; Leducq Foundation (07-CVD 03 to E.J.B., P. T. E. and
S. K.); LMU Excellence Initiative to S. K.; LMU Research grant (FoFoLe
557/569 to M.F.S.). M.F.S. is supported by the German Heart Foundation.
NR 77
TC 43
Z9 44
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR
PY 2011
VL 89
IS 4
BP 701
EP 709
DI 10.1093/cvr/cvr001
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 723DV
UT WOS:000287487400003
PM 21245058
ER
PT J
AU Mayyas, F
Sakurai, S
Ram, R
Rennison, JH
Hwang, ES
Castel, L
Lovano, B
Brennan, ML
Bibus, D
Lands, B
Barnard, J
Chung, MK
Van Wagoner, DR
AF Mayyas, Fadia
Sakurai, Seiichiro
Ram, Rashmi
Rennison, Julie H.
Hwang, Eui-Seock
Castel, Laurie
Lovano, Beth
Brennan, Marie-Luise
Bibus, Douglas
Lands, Bill
Barnard, John
Chung, Mina K.
Van Wagoner, David R.
TI Dietary omega 3 fatty acids modulate the substrate for post-operative
atrial fibrillation in a canine cardiac surgery model
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Post-operative atrial fibrillation; Omega-3 fatty acids; Heart rate;
Endothelin-1; Myeloperoxidase
ID OPEN-HEART-SURGERY; FATTY-ACIDS; FISH-OIL; STERILE PERICARDITIS;
BYPASS-SURGERY; N-3; SUPPLEMENTATION; INFLAMMATION; ASSOCIATION;
CONDUCTION
AB Aims Pre-treatment with dietary omega 3 polyunsaturated fatty acids (omega 3-PUFA) has been reported to reduce the incidence of new-onset atrial fibrillation (AF) following cardiac surgery. In a canine cardiac surgery model, we evaluated the impact of dietary omega 3-PUFA on atrial electrophysiological properties, inflammatory markers, the atrial endothelin-1 (ET-1) system, and the expression and distribution of connexin 43.
Methods and results Adult mongrel dogs received either normal chow (NC, n = 11) or chow supplemented with fish oil (FO, 0.6 g omega 3PUFA/kg/day, n = 9) for 3 weeks before surgery. A left thoracotomy was performed, and the left atrial appendage (LAA) was excised. Atrial pacing/recording wires were placed, and the pericardium/chest was closed. The atrial ratio of omega 6/omega 3 lipids decreased from 15-20 in NC to 2-3 in FO. FO treatment lowered pre-surgical and stabilized post-surgical arachidonate levels. Peak neutrophil to lymphocyte ratio was lower and decayed faster in FO-treated animals. Extensive inflammatory cell infiltration was present in NC atria, but was reduced in FO-treated dogs. FO-treated animals had lower post-surgical atrial expression of inducible nitric oxide synthase (iNOS) and reduced plasma ET-1. Expression of ET-1 and inositol trisphosphate receptor type-2 proteins in the LAA was also reduced. FO treatment prolonged post-operative atrial effective refractory period, slowed heart rate, and enhanced heart rate variability. Importantly, AF (> 30 s) was inducible in four of six NC dogs, but no FO dogs.
Conclusion Dietary FO attenuated AF inducibility following cardiac surgery by modulating autonomic tone and heart rate. FO also reduced atrial inflammation, iNOS, and ET-1 expression.
C1 [Mayyas, Fadia; Sakurai, Seiichiro; Ram, Rashmi; Rennison, Julie H.; Hwang, Eui-Seock; Castel, Laurie; Lovano, Beth; Chung, Mina K.; Van Wagoner, David R.] NE 61 Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44195 USA.
[Mayyas, Fadia; Van Wagoner, David R.] Case Western Reserve Univ, Lerner Coll Med, Dept Mol Med, Cleveland, OH 44106 USA.
[Brennan, Marie-Luise] Cleveland Clin, Dept Cell Biol, Cleveland, OH 44106 USA.
[Bibus, Douglas] Lipid Technol LLC, Austin, MN USA.
[Lands, Bill] NIH, Bethesda, MD 20892 USA.
[Barnard, John] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
[Chung, Mina K.; Van Wagoner, David R.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
RP Van Wagoner, DR (reprint author), NE 61 Cleveland Clin, Dept Mol Cardiol, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM vanwagd@ccf.org
RI Ram, Rashmi/F-9826-2012; Van Wagoner, David/C-6783-2008
OI Van Wagoner, David/0000-0001-8250-9828
FU Atrial Fibrillation Innovation Center; Wright Center Initiative of the
State of Ohio; Fondation Leducq European-North American Atrial
Fibrillation Research Alliance,; American Heart Association
FX This work was supported by the Atrial Fibrillation Innovation Center, a
Wright Center Initiative of the State of Ohio, the Fondation Leducq
European-North American Atrial Fibrillation Research Alliance, and by a
fellowship from the American Heart Association (F.M.).
NR 27
TC 30
Z9 32
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR
PY 2011
VL 89
IS 4
BP 852
EP 861
DI 10.1093/cvr/cvq380
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 723DV
UT WOS:000287487400018
PM 21123218
ER
PT J
AU Srikantan, S
Marasa, BS
Becker, KG
Gorospe, M
Abdelmohsen, K
AF Srikantan, Subramanya
Marasa, Bernard S.
Becker, Kevin G.
Gorospe, Myriam
Abdelmohsen, Kotb
TI Paradoxical microRNAs Individual gene repressors, global translation
enhancers
SO CELL CYCLE
LA English
DT Article
DE microRNA; Dicer; Drosha senescence; translation; post-transcriptional
gene regulation
ID REPLICATIVE SENESCENCE; MAMMALIAN MICRORNAS; PROTEIN-SYNTHESIS; HUMAN
CANCER; HUR LEVELS; EXPRESSION; DEGRADATION; BIOGENESIS; APOPTOSIS;
MIRNAS
AB In mammalian cells, microRNAs regulate the expression of target mRNAs generally by reducing their stability and/or translation, and thereby control diverse cellular processes such as senescence. We recently reported the differential abundance of microRNAs in young (early-passage, proliferating) relative to senescent (late-passage, non-proliferating) WI-38 human diploid fibroblasts. Here we report that the levels of the vast majority of mRNAs were unaltered in senescent compared to young WI-38 cells, while overall mRNA translation was potently reduced in senescent cells. Downregulation of Dicer or Drosha, two major enzymes in microRNA biogenesis, lowered microRNA levels, but, unexpectedly, it also reduced global translation. While a reduction in Dicer levels markedly enhanced cellular senescence, reduction of Drosha levels did not, suggesting that the Drosha/Dicer effects on translation may be independent of senescence and further suggesting that microRNAs may directly or indirectly enhance mRNA translation in WI-38 cells. We discuss possible scenarios through which Dicer/Drosha/microRNAs could enhance translation.
C1 [Srikantan, Subramanya; Marasa, Bernard S.; Gorospe, Myriam; Abdelmohsen, Kotb] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Becker, Kevin G.] NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Marasa, Bernard S.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA.
RP Abdelmohsen, K (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM abdelmohsenk@grc.nia.nih.gov
OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen,
Kotb/0000-0001-6240-5810; Becker, Kevin/0000-0002-6794-6656
FU National Institute on Aging, National Institutes of Health
FX This research was funded by the Intramural research Program of the
National Institute on Aging, National Institutes of Health.
NR 37
TC 15
Z9 15
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 1
PY 2011
VL 10
IS 5
BP 751
EP 759
DI 10.4161/cc.10.5.14825
PG 9
WC Cell Biology
SC Cell Biology
GA 728ZP
UT WOS:000287913600013
PM 21311220
ER
PT J
AU Asemu, G
Fishbein, K
Lao, QZ
Ravindran, A
Herbert, R
Canuto, HC
Spencer, RG
Soldatov, NM
AF Asemu, Girma
Fishbein, Kenneth
Lao, Qi Zong
Ravindran, Arippa
Herbert, Ron
Canuto, Holly C.
Spencer, Richard G.
Soldatov, Nikolai M.
TI Cardiac phenotype induced by a dysfunctional alpha(1C) transgene A
general problem for the transgenic approach
SO CHANNELS
LA English
DT Article
DE transgenic animals; MRI; change of phenotype
ID NECROSIS-FACTOR-ALPHA; HEART-FAILURE; MAGNETIC-RESONANCE; CA2+ CHANNELS;
MYOCARDIAL EXPRESSION; CALCIUM-CHANNELS; DEFICIENT MICE; MOUSE;
RECEPTOR; MASS
AB Based on stable integration of recombinant DNA into a host genome, transgenic technology has become an important genetic engineering methodology. An organism whose genetic characteristics have been altered by the insertion of foreign DNA is supposed to exhibit a new phenotype associated with the function of the transgene. However, successful insertion may not be sufficient to achieve specific modification of function. In this study we describe a strain of transgenic mouse, G7-882, generated by incorporation into the mouse genome of human Ca-v 1.2 alpha(1C) cDNA deprived of 3'-UTR to exclude transcription. We found that, in response to chronic infusion of isoproterenol, G7-882 develops dilated cardiomyopathy, a misleading "transgenic artifact" compatible with the expected function of the incorporated "correct" transgene. Specifically, using magnetic resonance imaging (MRI), we found that chronic beta-adrenergic stimulation of G7-882 mice caused left ventricular hypertrophy and aggravated development of dilated cardiomyopathy, although no significant changes in the kinetics, density and voltage dependence of the calcium current were observed in G7-882 cardiomyocytes as compared to cells from wild type mice. This result illustrates the possibility that even when a functional transgene is expressed, an observed change in phenotype may be due to the artifact of "incidental incorporation" leading to misleading conclusions. To exclude this possibility and thus provide a robust tool for exploring biological function, the new transgenic phenotype must be replicated in several independently generated transgenic strains.
C1 [Asemu, Girma; Fishbein, Kenneth; Lao, Qi Zong; Ravindran, Arippa; Canuto, Holly C.; Spencer, Richard G.; Soldatov, Nikolai M.] NIA, NIH, Baltimore, MD 21224 USA.
[Herbert, Ron] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
RP Soldatov, NM (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM spencerri@mail.nih.gov; soldatovn.humgenex@verizon.net
OI Fishbein, Kenneth/0000-0002-6353-4603
FU National Institute on Aging [Z01 AG000294-01, Z01 AG000927-01]
FX We thank Suresh Poosala for help with histochemistry, Bruce Ziman for
help with isolation of cardiac myocytes and Elena Schwartz for
preparation of DNA for microinjection into the pronuclei. This work was
supported by the Intramural Research Program, National Institute on
Aging (Z01 AG000294-01 to Nikolai M. Soldatov and Z01 AG000927-01 to
Richard G. Spencer).
NR 48
TC 1
Z9 1
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6950
J9 CHANNELS
JI Channels
PD MAR-APR
PY 2011
VL 5
IS 2
BP 138
EP 147
DI 10.4161/chan.5.2.14314
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 748QB
UT WOS:000289404400008
PM 21224729
ER
PT J
AU Ahn, J
Kibel, AS
Park, JY
Rebbeck, TR
Rennert, H
Stanford, JL
Ostrander, EA
Chanock, S
Wang, MH
Mittal, RD
Isaacs, WB
Platz, EA
Hayes, RB
AF Ahn, Jiyoung
Kibel, Adam S.
Park, Jong Y.
Rebbeck, Timothy R.
Rennert, Hanna
Stanford, Janet L.
Ostrander, Elaine A.
Chanock, Stephen
Wang, Ming-Hsi
Mittal, Rama D.
Isaacs, William B.
Platz, Elizabeth A.
Hayes, Richard B.
TI Prostate Cancer Predisposition Loci and Risk of Metastatic Disease and
Prostate Cancer Recurrence
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHROMOSOME 8Q24; SUSCEPTIBILITY VARIANTS;
FUNCTIONAL-ANALYSIS; COMMON VARIANT; MULTIPLE LOCI; GENES; EXPRESSION;
DIAGNOSIS; IMPLICATE
AB Purpose: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain.
Experimental Design: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights.
Results: MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence.
Conclusions: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants. Clin Cancer Res; 17(5); 1075-81. (C)2011 AACR.
C1 [Ahn, Jiyoung; Hayes, Richard B.] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA.
[Rennert, Hanna] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA.
[Kibel, Adam S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Kibel, Adam S.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Park, Jong Y.] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Chanock, Stephen] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Wang, Ming-Hsi; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Isaacs, William B.; Platz, Elizabeth A.] Johns Hopkins Sch Med, Brady Urol Inst, Baltimore, MD USA.
[Mittal, Rama D.] Sanjay Gandhi Postgrad Inst Med Sci, Dept Urol, Lucknow, Uttar Pradesh, India.
RP Ahn, J (reprint author), NYU, Sch Med, Dept Environm Med, Div Epidemiol, 650 1st Ave,518, New York, NY 10016 USA.
OI Ostrander, Elaine/0000-0001-6075-9738; Hayes,
Richard/0000-0002-0918-661X
FU NCI NIH HHS [R01 CA128813, R01 CA112028, P30 CA076292, R01 CA112028-05]
NR 36
TC 24
Z9 25
U1 2
U2 7
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 MAR 1
PY 2011
VL 17
IS 5
BP 1075
EP 1081
DI 10.1158/1078-0432.CCR-10-0881
PG 7
WC Oncology
SC Oncology
GA 728ZT
UT WOS:000287914400014
PM 21343373
ER
PT J
AU Lancet, JE
Duong, VH
Winton, EF
Stuart, RK
Burton, M
Zhang, SM
Cubitt, C
Blaskovich, MA
Wright, JJ
Sebti, S
Sullivan, DM
AF Lancet, Jeffrey E.
Duong, Vu H.
Winton, Elliott F.
Stuart, Robert K.
Burton, Michelle
Zhang, Shumin
Cubitt, Christopher
Blaskovich, Michelle A.
Wright, John J.
Sebti, Said
Sullivan, Daniel M.
TI A Phase I Clinical-Pharmacodynamic Study of the Farnesyltransferase
Inhibitor Tipifarnib in Combination with the Proteasome Inhibitor
Bortezomib in Advanced Acute Leukemias
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; RELAPSED ACUTE
LEUKEMIAS; KAPPA-B; THERAPY; TARGET; APOPTOSIS; R115777; TRIAL; OLDER
AB Purpose: To determine the safety, target inhibition, and signals of clinical activity of tipifarnib in combination with bortezomib in patients with advanced acute leukemias.
Experimental Design: In a "3 + 3" design, patients received escalating doses of tipifarnib (days 1-14) and bortezomib (days 1, 4, 8, 11) every 3 weeks until maximum tolerated dose was reached. Peripheral blood mononuclear cells (PBMC) were collected at days 1, 8, and 22 for measurement of chymotrypsin-like and farnesyltransferase activity. Purified bone marrow leukemic blasts were collected at baseline and at day 8 for measurement of NF-kappa B activity.
Results: The combination was well-tolerated, and maximum tolerated dose was not reached. Dose-limiting toxicities included diarrhea, fatigue, and sensorimotor neuropathy. Chymotrypsin-like and farnesyltransferase activity within PBMCs were decreased in a majority of patients at day 8. NF-kappa B activity within leukemic blasts was decreased in a majority of patients at day 8. Complete response with incomplete count recovery was observed in 2 patients, and additional 5 patients had stable disease.
Conclusions: Tipifarnib and bortezomib combination in patients with advanced leukemias was well-tolerated, demonstrated relevant target inhibition, and was associated with signals of clinical activity in patients with advanced and refractory acute leukemias. Future studies of this combination may be warranted in more selected groups of patients in whom these molecular targets are of particular importance. Clin Cancer Res; 17(5); 1140-6. (C)2011 AACR.
C1 [Lancet, Jeffrey E.; Duong, Vu H.; Burton, Michelle; Zhang, Shumin; Cubitt, Christopher; Blaskovich, Michelle A.; Sebti, Said; Sullivan, Daniel M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Winton, Elliott F.] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA.
[Stuart, Robert K.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Wright, John J.] NCI, IDB CTEP, Rockville, MD USA.
RP Lancet, JE (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM jeffrey.lancet@moffitt.org
OI Stuart, Robert/0000-0001-7549-8008
FU National Cancer Institute [N01 CM-62208]; National Cancer Institute/CTEP
Translational Research Initiative [26XXS043 TO2]
FX This work was supported by National Cancer Institute Grant N01 CM-62208
and National Cancer Institute/CTEP Translational Research Initiative
Contract 26XXS043 TO2.
NR 24
TC 20
Z9 20
U1 0
U2 1
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 MAR 1
PY 2011
VL 17
IS 5
BP 1140
EP 1146
DI 10.1158/1078-0432.CCR-10-1878
PG 7
WC Oncology
SC Oncology
GA 728ZT
UT WOS:000287914400021
PM 21233404
ER
PT J
AU Kelly, RJ
Rajan, A
Force, J
Lopez-Chavez, A
Keen, C
Cao, LA
Yu, YK
Choyke, P
Turkbey, B
Raffeld, M
Xi, LQ
Steinberg, SM
Wright, JJ
Kummar, S
Gutierrez, M
Giaccone, G
AF Kelly, Ronan J.
Rajan, Arun
Force, Jeremy
Lopez-Chavez, Ariel
Keen, Corrine
Cao, Liang
Yu, Yunkai
Choyke, Peter
Turkbey, Baris
Raffeld, Mark
Xi, Liqiang
Steinberg, Seth M.
Wright, John J.
Kummar, Shivaani
Gutierrez, Martin
Giaccone, Giuseppe
TI Evaluation of KRAS Mutations, Angiogenic Biomarkers, and DCE-MRI in
Patients with Advanced Non-Small-Cell Lung Cancer Receiving Sorafenib
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; REFRACTORY SOLID TUMORS; PHASE-I; RAF KINASE;
MULTIKINASE INHIBITOR; GENE-MUTATIONS; BAY-43-9006; CHEMOTHERAPY;
PHARMACOKINETICS; CARBOPLATIN
AB Purpose: Sorafenib, a multikinase inhibitor targeting Raf and VEGFR, has shown activity in unselected patients with non-small-cell lung cancer (NSCLC). At present there are no validated biomarkers indicative of sorafenib activity.
Experimental Design: Patients received sorafenib 400 mg BID daily to determine activity and tolerability and to measure its biological effects. KRAS mutation status (N = 34), angiogenesis markers (VEGF, bFGF, FLT-1, PLGF-1) and imaging with DCE-MRI (dynamic contrast enhanced MRI) to determine early changes in tumor vascular characteristics were evaluated. Three parameters K-trans, K-ep, and V-e were measured by DCE-MRI at baseline and day 14 of cycle 1. Cytokine analysis was done on days 0, 14, 28, and 54.
Results: Thirty-seven patients with previously treated stage IV NSCLC were enrolled in this single-center phase II trial. In 34 evaluable patients, 2 had partial responses and 20 had stable disease for 3 to 17 months, a disease control rate of 65%. The median progression-free survival (PFS) was 3.4 months, and median overall survival (OS) was 11.6 months. Toxicity was consistent with the known side effects of sorafenib. KRAS (32%) and EGFR mutations (22%) showed no correlation with response, PFS, or OS. K-ep, was significant in predicting an improvement in OS (P 0.035) and PFS (P 0.029). Cytokine analysis demonstrated an improved OS for bFGF day 0 (< 6 vs. > 6 pg/mL; P = 0.042), whereas a PFS benefit was seen with bFGF at day 28 (< 6 vs. > 6; P = 0.028).
Conclusions: KRAS and EGFR mutational status showed no correlation with response, PFS, or OS. Radiologic and cytokine changes may act as biomarkers indicative of early angiogenesis inhibition. Clin Cancer Res; 17(5); 1190-9. (c) 2011 AACR.
C1 [Kelly, Ronan J.; Rajan, Arun; Force, Jeremy; Lopez-Chavez, Ariel; Keen, Corrine; Kummar, Shivaani; Gutierrez, Martin; Giaccone, Giuseppe] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Cao, Liang; Yu, Yunkai] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Choyke, Peter; Turkbey, Baris] NIH, Dept Nucl Med & Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Raffeld, Mark; Xi, Liqiang] NCI, Pathol Lab, CCR, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, Bethesda, MD 20892 USA.
[Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU NCI, NIH; NIH, NCI, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the NCI, NIH. This work was supported by the Intramural Research Program
of the NIH, NCI, Center for Cancer Research.
NR 39
TC 44
Z9 45
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2011
VL 17
IS 5
BP 1190
EP 1199
DI 10.1158/1078-0432.CCR-10-2331
PG 10
WC Oncology
SC Oncology
GA 728ZT
UT WOS:000287914400026
PM 21224376
ER
PT J
AU Rosenson, RS
Brewer, HB
Chapman, MJ
Fazio, S
Hussain, MM
Kontush, A
Krauss, RM
Otvos, JD
Remaley, AT
Schaefer, EJ
AF Rosenson, Robert S.
Brewer, H. Bryan, Jr.
Chapman, M. John
Fazio, Sergio
Hussain, M. Mahmood
Kontush, Anatol
Krauss, Ronald M.
Otvos, James D.
Remaley, Alan T.
Schaefer, Ernst J.
TI HDL Measures, Particle Heterogeneity, Proposed Nomenclature, and
Relation to Atherosclerotic Cardiovascular Events
SO CLINICAL CHEMISTRY
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; CORONARY-HEART-DISEASE;
CHOLESTERYL ESTER TRANSFER; NUCLEAR-MAGNETIC-RESONANCE; TRANSFER
PROTEIN-DEFICIENCY; EXTENDED-RELEASE NIACIN; INSULIN-RESISTANCE
ATHEROSCLEROSIS; GRADIENT GEL-ELECTROPHORESIS; FRACTIONAL CATABOLIC RATE
AB BACKGROUND: A growing body of evidence from epidemiological data, animal studies, and clinical trials supports HDL as the next target to reduce residual cardiovascular risk in statin-treated, high-risk patients. For more than 3 decades, HDL cholesterol has been employed as the principal clinical measure of HDL and cardiovascular risk associated with low HDL-cholesterol concentrations. The physicochemical and functional heterogeneity of HDL present important challenges to investigators in the cardiovascular field who are seeking to identify more effective laboratory and clinical methods to develop a measurement method to quantify HDL that has predictive value in assessing cardiovascular risk.
CONTENT: In this report, we critically evaluate the diverse physical and chemical methods that have been employed to characterize plasma HDL. To facilitate future characterization of HDL subfractions, we propose the development of a new nomenclature based on physical properties for the subfractions of HDL that includes very large HDL particles (VL-HDL), large HDL particles (L-HDL), medium HDL particles (M-HDL), small HDL particles (S-HDL), and very-small HDL particles (VS-HDL). This nomenclature also includes an entry for the pre-beta-1 HDL subclass that participates in macrophage cholesterol efflux.
SUMMARY: We anticipate that adoption of a uniform nomenclature system for HDL subfractions that integrates terminology from several methods will enhance our ability not only to compare findings with different approaches for HDL fractionation, but also to assess the clinical effects of different agents that modulate HDL particle structure, metabolism, and function, and in turn, cardiovascular risk prediction within these HDL subfractions. (C) 2010 American Association for Clinical Chemistry
C1 [Rosenson, Robert S.] Mt Sinai Sch Med, New York, NY USA.
[Brewer, H. Bryan, Jr.] MedStar Res Inst, Washington, DC USA.
[Chapman, M. John; Kontush, Anatol] UPMC Paris 6, INSERM, U939, Hop Pitie, Paris, France.
[Fazio, Sergio] Vanderbilt Univ, Nashville, TN USA.
[Hussain, M. Mahmood] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Krauss, Ronald M.] Univ Calif Berkeley, Childrens Hosp, Oakland Res Inst, Berkeley, CA 94720 USA.
[Krauss, Ronald M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Otvos, James D.] Liposcience, Raleigh, NC USA.
[Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Schaefer, Ernst J.] Tufts Univ, Lipid Metab Lab, Boston, MA 02111 USA.
RP Rosenson, RS (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1030, New York, NY USA.
EM robert.rosenson@mssm.edu
RI Kontush, Anatol/J-2198-2016
FU Merck; ISIS Genzyme; NIH; Pfizer; AstraZeneca; GlaxoSmithKline; DuPont
FX Research Funding: M.J. Chapman, Merck; S. Fazio, ISIS Genzyme; M.M.
Hussain, NIH; A. Kontush, Pfizer, AstraZeneca, and GlaxoSmithKline; E.J.
Schaefer, DuPont.
NR 180
TC 187
Z9 197
U1 1
U2 25
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 MAR
PY 2011
VL 57
IS 3
BP 392
EP 410
DI 10.1373/clinchem.2010.155333
PG 19
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 727ME
UT WOS:000287803400012
PM 21266551
ER
PT J
AU Eisenhofer, G
Lenders, JWM
Timmers, H
Mannelli, M
Grebe, SK
Hofbauer, LC
Bornstein, SR
Tiebel, O
Adams, K
Bratslavsky, G
Linehan, WM
Pacak, K
AF Eisenhofer, Graeme
Lenders, Jacques W. M.
Timmers, Henri
Mannelli, Massimo
Grebe, Stefan K.
Hofbauer, Lorenz C.
Bornstein, Stefan R.
Tiebel, Oliver
Adams, Karen
Bratslavsky, Gennady
Linehan, W. Marston
Pacak, Karel
TI Measurements of Plasma Methoxytyramine, Normetanephrine, and
Metanephrine as Discriminators of Different Hereditary Forms of
Pheochromocytoma
SO CLINICAL CHEMISTRY
LA English
DT Article
ID ENDOCRINE NEOPLASIA TYPE-2; LIQUID-CHROMATOGRAPHIC DETERMINATION;
HIPPEL-LINDAU-SYNDROME; GERMLINE MUTATIONS; CLINICAL PREDICTORS;
PARAGANGLIOMA; PHENOTYPES; DIAGNOSIS; METHYLTRANSFERASE; CATECHOLAMINES
AB BACKGROUND: Pheochromocytomas are rare catecholamine-producing tumors derived in more than 30% of cases from mutations in 9 tumor-susceptibility genes identified to date, including von Hippel-Lindau tumor suppressor (VHL); succinate dehydrogenase complex, subunit B, iron sulfur (Ip) (SDHB); and succinate dehydrogenase complex, subunit D, integral membrane protein (SDHD). Testing of multiple genes is often undertaken at considerable expense before a mutation is detected. This study assessed whether measurements of plasma metanephrine, normetanephrine, and methoxytyramine, the O-methylated metabolites of catecholamines, might help to distinguish different hereditary forms of the tumor.
METHODS: Plasma concentrations of O-methylated metabolites were measured by liquid chromatography with electrochemical detection in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF 1), 66 with von Hippel-Lindau (VHL) syndrome, and 59 with mutations of SDHB or SDHD.
RESULTS: In contrast to patients with VHL, SDHB, and SDHD mutations, all patients with MEN 2 and NF1 presented with tumors characterized by increased plasma concentrations of metanephrine (indicating epinephrine production). VHL patients usually showed solitary increases in normetanephrine (indicating norepinephrine production), whereas additional or solitary increases in methoxytyramine (indicating dopamine production) characterized 70% of patients with SDHB and SDHD mutations. Patients with NF1 and MEN 2 could be discriminated from those with VHL, SDHB, and SDHD gene mutations in 99% of cases by the combination of normetanephrine and metanephrine. Measurements of plasma methoxytyramine discriminated patients with SDHB and SDHD mutations from those with VHL mutations in an additional 78% of cases.
CONCLUSIONS: The distinct patterns of plasma catecholamine O-methylated metabolites in patients with hereditary pheochromocytoma provide an easily used tool to guide cost-effective genotyping of underlying disease-causing mutations. (C) 2010 American Association for Clinical Chemistry
C1 [Eisenhofer, Graeme] Univ Dresden, Div Clin Neurochem, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
[Eisenhofer, Graeme; Lenders, Jacques W. M.; Hofbauer, Lorenz C.; Bornstein, Stefan R.] Univ Dresden, Dept Med 3, D-01307 Dresden, Germany.
[Lenders, Jacques W. M.] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Timmers, Henri] Radboud Univ Nijmegen, Dept Endocrinol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Mannelli, Massimo] Univ Florence, Dept Clin Pathophysiol, Florence, Italy.
[Grebe, Stefan K.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Adams, Karen; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, Bethesda, MD USA.
[Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Eisenhofer, G (reprint author), Univ Dresden, Div Clin Neurochem, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany.
EM Graeme.Eisenhofer@uniklinikum-dresden.de
RI Lenders, J.W.M./L-4487-2015; Hofbauer, Lorenz/G-2490-2010;
OI Hofbauer, Lorenz/0000-0002-8691-8423; Mannelli,
Massimo/0000-0002-8001-9857
FU Deutsche Forschungsgesellschaft; Center for Regenerative Therapies
Dresden; Dresden Tumor Center; Eunice Kennedy Shriver National Institute
of Child Health and Human Development; Center for Cancer Research,
National Cancer Institute
FX Research Funding: G. Eisenhofer, L. C. Hofbauer, S. R. Bornstein, O.
Tiebel, Deutsche Forschungsgesellschaft, Center for Regenerative
Therapies Dresden, and Dresden Tumor Center; K. Adams, K. Pacak, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; G. Bratslavsky, W. M. Linehan, Center for Cancer Research,
National Cancer Institute.
NR 35
TC 108
Z9 110
U1 2
U2 11
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 MAR
PY 2011
VL 57
IS 3
BP 411
EP 420
DI 10.1373/clinchem.2010.153320
PG 10
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 727ME
UT WOS:000287803400013
PM 21262951
ER
PT J
AU Torres, VE
Grantham, JJ
Chapman, AB
Mrug, M
Bae, KT
King, BF
Wetzel, LH
Martin, D
Lockhart, ME
Bennett, WM
Moxey-Mims, M
Abebe, KZ
Lin, Y
Bost, JE
AF Torres, Vicente E.
Grantham, Jared J.
Chapman, Arlene B.
Mrug, Michal
Bae, Kyongtae T.
King, Bernard F., Jr.
Wetzel, Louis H.
Martin, Diego
Lockhart, Mark E.
Bennett, William M.
Moxey-Mims, Marva
Abebe, Kaleab Z.
Lin, Yan
Bost, James E.
CA Consortium Radiologic Imaging
TI Potentially Modifiable Factors Affecting the Progression of Autosomal
Dominant Polycystic Kidney Disease
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID MAGNETIC-RESONANCE MEASUREMENTS; RENAL-FUNCTION DECLINE; DIETARY-SODIUM
INTAKE; SALT INTAKE; BLOOD-FLOW; VASOPRESSIN; CONSORTIUM; REDUCTION;
COPEPTIN; OUABAIN
AB Background and objectives The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) was created to identify markers of disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD).
Design, setting, participants, & measurements Linear mixed models were utilized to model effects of baseline parameters on changes in natural-log (ln)-transformed total kidney volume (TKV) and iothalamate clearance (GFR) across time in CRISP participants (creatinine clearance at entry >70 ml/min). Stepwise selection was used to obtain a final main effect model.
Results TKV increased from year to year, whereas GFR uncorrected for body surface area (BSA) decreased only at year 6. Higher lnTKV and urine sodium excretion (U(Na)V), lower serum HDL-cholesterol, and younger age at baseline associated with greater lnTKV growth from baseline to year 3 and to year 6. Higher lnTKV at baseline associated with greater GFR decline from year 1 to year 3 and to year 6. Higher BSA and 24-hour urine osmolality at baseline associated with greater GFR decline from year 1 to year 6. Higher U(Na)V and lower serum HDL-cholesterol at baseline associated with greater GFR decline from year 1 to year 6 by univariate analysis only. Associations seen during year 1 to year 6 (not seen during year 1 to year 3) reflect the time lag between structural and functional disease progression.
Conclusions Serum HDL-cholesterol, U(Na)V, and 24-hour urine osmolality likely affect ADPKD progression. To what extent their modification may influence the clinical course of ADPKD remains to be determined. Clin J Am Soc Nephrol 6: 640-647, 2011. doi: 10.2215/CJN.03250410
C1 [Torres, Vicente E.] Mayo Clin, Div Nephrol & Hypertens, Coll Med, Rochester, MN 55901 USA.
[Grantham, Jared J.; Wetzel, Louis H.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Chapman, Arlene B.; Martin, Diego] Emory Univ, Sch Med, Atlanta, GA USA.
[Mrug, Michal; Lockhart, Mark E.] Univ Alabama, Birmingham, AL USA.
[Bae, Kyongtae T.; Abebe, Kaleab Z.; Lin, Yan; Bost, James E.] Univ Pittsburgh, Pittsburgh, PA USA.
[Bennett, William M.] NW Renal Clin, Portland, OR USA.
[Moxey-Mims, Marva] Natl Inst Diabet & Digest & Kidney Dis KUH, Bethesda, MD USA.
RP Torres, VE (reprint author), Mayo Clin, Div Nephrol & Hypertens, Coll Med, Rochester, MN 55901 USA.
EM torres.vicente@mayo.edu
OI Abebe, Kaleab/0000-0002-3644-8419
FU CRISP [DK56956, DK56943, DK56957, DK56961]; Mayo Clinic [MO1-RR00585];
Emory University [MO1-RR00039]; University of Kansas of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health
FX This study was supported by the CRISP Study UO1 cooperative agreements
(DK56956, DK56943, DK56957, and DK56961), the Mayo Clinic General
Clinical Research Grant MO1-RR00585, the Emory University General
Clinical Research Grant MO1-RR00039, and the University of Kansas
General Clinical Research Grant (number to come) of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health. We are indebted to the study coordinators who
worked with professional grace and high competence to bring this project
to conclusion. We thank Dr. Lise Bankir (Institut National de la Sante'
et de la Recherche Medicate, UMRS 872, Centre de Recherche des
Cordeliers, Paris, France) for helpful discussions and advice.
NR 33
TC 50
Z9 50
U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAR
PY 2011
VL 6
IS 3
BP 640
EP 647
DI 10.2215/CJN.03250410
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 736GX
UT WOS:000288480100025
PM 21088290
ER
PT J
AU Long, RM
Berg, JM
AF Long, R. M.
Berg, J. M.
TI What to Expect From the Pharmacogenomics Research Network
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
C1 [Long, R. M.; Berg, J. M.] Natl Inst Gen Med Sci, NIH, Bethesda, MD USA.
RP Long, RM (reprint author), Natl Inst Gen Med Sci, NIH, Bethesda, MD USA.
EM rochelle.long@nih.gov
OI Berg, Jeremy/0000-0003-3022-0963
NR 0
TC 6
Z9 6
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2011
VL 89
IS 3
BP 339
EP 341
DI 10.1038/clpt.2010.293
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 722NS
UT WOS:000287439600008
PM 21326260
ER
PT J
AU Sadee, W
Wang, D
Papp, AC
Pinsonneault, JK
Smith, RM
Moyer, RA
Johnson, AD
AF Sadee, W.
Wang, D.
Papp, A. C.
Pinsonneault, J. K.
Smith, R. M.
Moyer, R. A.
Johnson, A. D.
TI Pharmacogenomics of the RNA World: Structural RNA Polymorphisms in Drug
Therapy
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID ALLELIC EXPRESSION IMBALANCE; OPIOID RECEPTOR GENE; GENOME-WIDE
ANALYSIS; MESSENGER-RNA; HUMAN BRAIN; HUMAN PONS; ASSOCIATION; VARIANTS;
EVENTS; CELLS
AB The use of pharmacogenomic biomarkers can enhance treatment outcomes. Regulatory polymorphisms are promising biomarkers that have proven difficult to uncover. They come in two flavors: those that affect transcription (regulatory single-nucleotide polymorphisms (rSNPs)) and those that affect RNA functions such as splicing, turnover, and translation (termed structural RNA SNPs (srSNPs)). This review focuses on the role of srSNPs in drug metabolism, transport, and response. An understanding of the nature and diversity of srSNPs and rSNPs enables clinical scientists to evaluate genetic biomarkers.
C1 [Sadee, W.; Wang, D.; Papp, A. C.; Pinsonneault, J. K.; Smith, R. M.; Moyer, R. A.] Ohio State Univ, Coll Med, Dept Pharmacol, Program Pharmacogenom, Columbus, OH 43210 USA.
[Johnson, A. D.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Sadee, W (reprint author), Ohio State Univ, Coll Med, Dept Pharmacol, Program Pharmacogenom, Columbus, OH 43210 USA.
EM Wolfgang.Sadee@osumc.edu
RI Smith, Ryan/H-6898-2012; Johnson, Andrew/G-6520-2013
FU NIDA NIH HHS [DA022199, R01 DA022199, R01 DA022199-05]; NIGMS NIH HHS
[GM092655, U01 GM092655, U01 GM092655-01]
NR 50
TC 27
Z9 30
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2011
VL 89
IS 3
BP 355
EP 365
DI 10.1038/clpt.2010.314
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 722NS
UT WOS:000287439600015
PM 21289622
ER
PT J
AU Carli, V
Mandelli, L
Postuvan, V
Roy, A
Bevilacqua, L
Cesaro, C
Baralla, F
Marchetti, M
Serretti, A
Sarchiapone, M
AF Carli, Vladimir
Mandelli, Laura
Postuvan, Vita
Roy, Alec
Bevilacqua, Laura
Cesaro, Caterina
Baralla, Francesca
Marchetti, Marco
Serretti, Alessandro
Sarchiapone, Marco
TI Self-Harm in Prisoners
SO CNS SPECTRUMS
LA English
DT Article
ID GENERAL-POPULATION; YOUNG-ADULTS; MUTILATION; BEHAVIOR; SUICIDE;
EPIDEMIOLOGY; ANXIETY; SAMPLES; INJURY; RISK
AB Introduction: Self-harm is a direct, socially unacceptable, repetitive behavior that causes minor to moderate physical injury without suicidal intent. It is also a significant and growing concern among prison inmates, although it has been rarely studied. In the present study, we aimed to investigate demographic, psychosocial, and clinical variables associated to this critical bahaviour in a high risk sample of 1,555 male prisoners.
Methods: Prisoners were interviewed about their history of self-mutilation, psychiatric history, and forensic history. The prisoners completed the Barratt Impulsivity Scale, Buss-Durkee Hostility Inventory, Eysenck Personality Questionnaire, and Childhood Trauma Questionnaire.
Results: Eighteen percent of prisoners had a history of self-harm. They more frequently reported childhood traumas, were more likely to be unmarried, previously imprisoned, tested positive for substance abuse, had a history of suicide attempt, and more likely showed violent tendencies.
Discussion: Self-harm among prisoners is common, being found in 20% of the subjects in our sample. Self-mutilation among prisoners appears to be multi-factorial with developmental, socio-demographic, psychiatric, and personality determinants.
Conclusion: Self-harm is associated with critical behaviors such as violence, substance abuse and suicide attempts, which represent major critical problems in contention environments.
C1 [Carli, Vladimir] Karolinska Inst, Natl Prevent Suicide & Mental Ill Hlth NASP, Stockholm, Sweden.
[Mandelli, Laura; Serretti, Alessandro] Univ Bologna, Inst Psychiat, I-40126 Bologna, Italy.
[Postuvan, Vita] Univ Primorska, Primorska Inst Nat Sci & Technol, Hlth Res Dept, Koper, Slovenia.
[Roy, Alec] Vet Affairs Med Ctr, Psychiat Serv, E Orange, NJ USA.
[Bevilacqua, Laura] NIH, Neurogenet Lab, Rockville, MD USA.
[Cesaro, Caterina] Karolinska Inst, NASP, Stockholm, Sweden.
[Marchetti, Marco; Sarchiapone, Marco] Univ Molise, Dept Hlth Sci, Campobasso, Italy.
[Baralla, Francesca] Univ Roma La Sapienza, Fac Psychol 2, Rome, Italy.
RP Sarchiapone, M (reprint author), Univ Molise, Dept Hlth Sci, Via De Santis, Campobasso, Italy.
EM marco.sarchiapone@gmail.com
OI Sarchiapone, Marco/0000-0001-9583-3117
NR 31
TC 4
Z9 6
U1 1
U2 12
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1092-8529
J9 CNS SPECTRUMS
JI CNS Spectr.
PD MAR
PY 2011
VL 16
IS 3
BP 75
EP 81
DI 10.1017/S1092852912000211
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 951KC
UT WOS:000304718400002
PM 24725358
ER
PT J
AU Dupont, G
Combettes, L
Bird, GS
Putney, JW
AF Dupont, Genevieve
Combettes, Laurent
Bird, Gary S.
Putney, James W.
TI Calcium Oscillations
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; PANCREATIC ACINAR-CELLS;
EMBRYONIC KIDNEY-CELLS; VASCULAR SMOOTH-MUSCLE; CA2+ OSCILLATIONS;
ENDOPLASMIC-RETICULUM; INTRACELLULAR CA2+; ARC CHANNELS; POOL MODEL;
THEORETICAL-ANALYSIS
AB Calcium signaling results from a complex interplay between activation and inactivation of intracellular and extracellular calcium permeable channels. This complexity is obvious from the pattern of calcium signals observed with modest, physiological concentrations of calcium-mobilizing agonists, which typically present as sequential regenerative discharges of stored calcium, a process referred to as calcium oscillations. In this review, we discuss recent advances in understanding the underlying mechanism of calcium oscillations through the power of mathematical modeling. We also summarize recent findings on the role of calcium entry through store-operated channels in sustaining calcium oscillations and in the mechanism by which calcium oscillations couple to downstream effectors.
C1 [Dupont, Genevieve] Univ Libre Brussels, Fac Sci CP231, Unite Chronobiol Theor, B-1050 Brussels, Belgium.
[Combettes, Laurent] Univ Paris 11, Inst Natl Sante & Rech Med Unite U442, F-91405 Orsay, France.
[Bird, Gary S.; Putney, James W.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Dupont, G (reprint author), Univ Libre Brussels, Fac Sci CP231, Unite Chronobiol Theor, Blvd Triomphe, B-1050 Brussels, Belgium.
EM susanh@bcm.edu
RI Combettes, Laurent/L-1842-2013
OI Combettes, Laurent/0000-0002-1376-4574
FU National Institutes of Health; Fonds de la Recherche Scientifique
Medicale [3.4636.04]; European Union [LSHB-CT-2004-005137]; Belgian
Federal Science Policy Office [P6/25]; ANR [RPV07094LSA]; Inserm; AP-HP;
PHC
FX Work discussed in this review originating in the laboratory of JP and GB
was supported by the Intramural Program, National Institutes of Health.
GD is Maitre de Recherche at the Belgian FNRS. GD acknowledges support
from the Fonds de la Recherche Scientifique Medicale (grant No.
3.4636.04), the European Union through the Network of Excellence BioSim
(Contract No. LSHB-CT-2004-005137), and the Belgian Program on
Interuniversity Attraction Poles, initiated by the Belgian Federal
Science Policy Office, project No. P6/25 (BIOMAGNET). LC acknowledges
support from ANR (RPV07094LSA) and PNR in Hepatogastroenterology. LC is
supported by an interface contract between Inserm and AP-HP (LE
Kremlin-Bicetre Hospital). This work was supported by a PHC Tournesol
2009 program.
NR 146
TC 47
Z9 48
U1 4
U2 21
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 MAR
PY 2011
VL 3
IS 3
AR a004226
DI 10.1101/cshperspect.a004226
PG 18
WC Cell Biology
SC Cell Biology
GA 728AP
UT WOS:000287846200003
ER
PT J
AU Reti, IM
Xu, JZ
Yanofski, J
McKibben, J
Uhart, M
Cheng, YJ
Zandi, P
Bienvenu, OJ
Samuels, J
Willour, V
Kasch-Semenza, L
Costa, P
Bandeen-Roche, K
Eaton, WW
Nestadt, G
AF Reti, Irving M.
Xu, Jerry Z.
Yanofski, Jason
McKibben, Jodi
Uhart, Magdalena
Cheng, Yu-Jen
Zandi, Peter
Bienvenu, Oscar J.
Samuels, Jack
Willour, Virginia
Kasch-Semenza, Laura
Costa, Paul
Bandeen-Roche, Karen
Eaton, William W.
Nestadt, Gerald
TI Monoamine oxidase A regulates antisocial personality in whites with no
history of physical abuse
SO COMPREHENSIVE PSYCHIATRY
LA English
DT Article
ID A GENOTYPE; GENE PROMOTER; AGGRESSIVE-BEHAVIOR; CONDUCT DISORDER;
5-FACTOR MODEL; MAOA GENOTYPE; X-CHROMOSOME; POLYMORPHISM; CHILDHOOD;
RISK
AB Objective: Preclinical and human family studies clearly link monoamine oxidase A (MAOA) to aggression and antisocial personality (ASP). The 30 base pair variable number tandem repeat in the MAOA promoter regulates MAOA levels, but its effects on ASP in humans are unclear.
Methods: We evaluated the association of the variable number tandem repeat of the MAOA promoter with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ASP disorder (ASPD) traits in a community sample of 435 participants from the Hopkins Epidemiology of Personality Disorders Study.
Results: We did not find an association between the activity of the MAOA allele and ASPD traits; however, among whites, when subjects with a history of childhood physical abuse were excluded, the remaining subjects with low-activity alleles had ASPD trait counts that were 41% greater than those with high-activity alleles (P < .05).
Conclusion: The high-activity MAOA allele is protective against ASP among whites with no history of physical abuse, lending support to a link between MAOA expression and antisocial behavior. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Reti, Irving M.; Xu, Jerry Z.; Yanofski, Jason; Uhart, Magdalena; Zandi, Peter; Bienvenu, Oscar J.; Samuels, Jack; Willour, Virginia; Kasch-Semenza, Laura; Costa, Paul; Eaton, William W.; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
[McKibben, Jodi; Cheng, Yu-Jen; Zandi, Peter; Bandeen-Roche, Karen; Eaton, William W.; Nestadt, Gerald] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Costa, Paul] NIA, NIH, Baltimore, MD 21224 USA.
RP Reti, IM (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
EM imreti@jhmi.edu
RI McKibben, Jodi/H-5973-2011;
OI Samuels, Jack/0000-0002-6715-7905; Costa, Paul/0000-0003-4375-1712
FU National Institutes of Health [RO1 MH050616-09, RO1 MH47447, K23
MH64543, K23 AA017466]; National Institute of Aging
FX This research was supported by the following: National Institutes of
Health grants RO1 MH050616-09 (Nestadt), RO1 MH47447 (Eaton), K23
MH64543 (Bienvenu), K23 AA017466 (Uhart), as well as the Intramural
Research Program of the National Institute of Aging (Costa).
NR 39
TC 21
Z9 23
U1 2
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0010-440X
J9 COMPR PSYCHIAT
JI Compr. Psychiat.
PD MAR-APR
PY 2011
VL 52
IS 2
BP 188
EP 194
DI 10.1016/j.comppsych.2010.05.005
PG 7
WC Psychiatry
SC Psychiatry
GA 725MB
UT WOS:000287647700011
PM 21295226
ER
PT J
AU Baker, R
Dauner, JG
Rodriguez, AC
Williams, MC
Kemp, TJ
Hildesheim, A
Pinto, LA
AF Baker, Rosalyn
Dauner, Joseph G.
Cecilia Rodriguez, Ana
Williams, Marcus C.
Kemp, Troy J.
Hildesheim, Allan
Pinto, Ligia A.
TI Increased plasma levels of adipokines and inflammatory markers in older
women with persistent HPV infection
SO CYTOKINE
LA English
DT Article
DE HPV; Persistent infection; Adipokines; Inflammation
ID HUMAN-PAPILLOMAVIRUS INFECTION; ADIPOSE-TISSUE; INSULIN-RESISTANCE;
ADIPONECTIN; EXPRESSION; CYTOKINES; LEPTIN; CELLS; RISK
AB We observed diminished lymphoproliferation to multiple stimuli in older women with persistent cervical human papillomavirus (HPV) infection. Adipokines are a class of inflammatory cytokines that are altered in some persistent infections. The objective was to compare the level of adipokines and inflammatory cytokines in heparinized plasma from women with persistent HPV cervical infection (Cases, N = 50, over-sampled for their weak lymphoproliferation responses) with women with no evidence of persistent HPV cervical infection (Controls, N = 50, over-sampled for their strong lymphoproliferation responses). Plasma samples were analyzed with multiplex assays for adipokines and inflammatory cytokines. Cases had significantly elevated plasma levels of resistin (p < 0.0001) and sFas (p = 0.0038) as compared to controls. Risk of persistent HPV infection increased significantly with increasing levels of resistin and 8Fas. This is the first study to demonstrate elevated levels of resistin and sFas in HPV persistently infected, older women with decreased immune function expanding the understanding of the systemic inflammation and immune alterations in individuals persistently infected with HPV. Further studies within a larger cohort are needed to define the generalities of these findings and any role adipokines have in persistent HPV infection. (c) 2010 Elsevier Ltd. All rights reserved.
C1 [Baker, Rosalyn; Dauner, Joseph G.; Williams, Marcus C.; Kemp, Troy J.; Pinto, Ligia A.] NCI, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Baker, Rosalyn] NIAID, Div Clin Res ICMOB, NIH, Bethesda, MD 20892 USA.
[Cecilia Rodriguez, Ana] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Pinto, LA (reprint author), Head NCI Frederick SAIC Frederick Inc, HPV Immunol Lab, Bldg 469,Room 205, Ft Detrick, 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, National Institutes of Health
[HHSN261200800001E]
FX We thank Helen Rager of the SAIC-Frederick Inc., Lymphokine Testing
Laboratory, for her assistance with MesoScale assay, Yuanji Pan for
statistical analyses and Roni Falk for statistical advice. 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 US Government.
NR 20
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Z9 14
U1 2
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD MAR
PY 2011
VL 53
IS 3
BP 282
EP 285
DI 10.1016/j.cyto.2010.11.014
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 727YV
UT WOS:000287840200003
PM 21167737
ER
PT J
AU Killgore, WDS
Britton, JC
Price, LM
Gold, AL
Deckersbach, T
Rauch, SL
AF Killgore, William D. S.
Britton, Jennifer C.
Price, Lauren M.
Gold, Andrea L.
Deckersbach, Thilo
Rauch, Scott L.
TI NEURAL CORRELATES OF ANXIETY SENSITIVITY DURING MASKED PRESENTATION OF
AFFECTIVE FACES
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE FMRI; neuroimaging; anxiety sensitivity; ASI; insula; specific phobia;
healthy controls
ID PANIC DISORDER; BRAIN ACTIVATION; PHYSIOLOGICAL CONDITION; HIERARCHICAL
STRUCTURE; INSULAR CORTEX; CO2 CHALLENGE; AMYGDALA; PHOBIA;
INTEROCEPTION; INDEX
AB Background: Anxiety Sensitivity (AS), the tendency to fear the thoughts, symptoms, and social consequences associated with the experience of anxiety, is associated with increased risk for developing anxiety disorders. Some evidence suggests that higher scores on the Anxiety Sensitivity Index (ASI), a measure of the AS construct, are associated with activation of the anterior insular cortex during overt emotion perception. Although the ASI provides subscale scores measuring Physical, Mental Incapacitation, and Social Concerns of AS, no study has examined the relationship between these factors and regional brain activation during affect processing. We hypothesized that insular responses to fear-related stimuli would be primarily related to the Physical Concerns subscale of the ASI, particularly for a sample of subjects with specific phobias. Methods: Adult healthy controls (HC; n = 22) and individuals with specific phobia, small animal subtype (SAP; n = 17), completed the ASI and underwent functional magnetic resonance imaging while engaged in a backward-masked affect perception task that presents emotional facial stimuli below the threshold of conscious perception. Results: Groups did not differ in ASI, state or trait anxiety scores, or insula activation. Total ASI scores were positively correlated with activation in the right middle/anterior insula for the combined sample and for the HC and SAP groups separately. Multiple regression analysis revealed that the relationship between AS and insular activation was primarily accounted for by Physical Concerns only. Conclusions: Findings support the hypothesized role of the right anterior insula in the visceral/interoceptive aspects of AS, even in response to masked affective stimuli. Depression and Anxiety 28:243-249, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Killgore, William D. S.] Harvard Univ, McLean Hosp, Sch Med, Affect Neurosci Lab,Neuroimaging Ctr, Belmont, MA 02478 USA.
[Britton, Jennifer C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Deckersbach, Thilo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Belmont, MA 02478 USA.
[Deckersbach, Thilo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Belmont, MA 02478 USA.
[Gold, Andrea L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
RP Killgore, WDS (reprint author), Harvard Univ, McLean Hosp, Sch Med, Affect Neurosci Lab,Neuroimaging Ctr, 115 Mill St, Belmont, MA 02478 USA.
EM killgore@mclean.harvard.edu
RI Britton, Jennifer/J-4501-2013;
OI Gold, Andrea/0000-0003-4447-776X; Killgore, William/0000-0002-5328-0208
FU NIMH [R01 MH070730-04]; National Institute of Health
FX The authors disclose the following financial relationships within the
past 3 years: Contract grant sponsor: NIMH; Contract grant number: R01
MH070730-04; Contract grant sponsor: National Institute of Health.
NR 41
TC 15
Z9 15
U1 6
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2011
VL 28
IS 3
BP 243
EP 249
DI 10.1002/da.20788
PG 7
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 734JZ
UT WOS:000288331700009
PM 21308886
ER
PT J
AU Cox, BJ
Turnbull, DL
Robinson, JA
Grant, BF
Stein, MB
AF Cox, Brian J.
Turnbull, Danielle L.
Robinson, Jennifer A.
Grant, Bridget F.
Stein, Murray B.
TI THE EFFECT OF AVOIDANT PERSONALITY DISORDER ON THE PERSISTENCE OF
GENERALIZED SOCIAL ANXIETY DISORDER IN THE GENERAL POPULATION: RESULTS
FROM A LONGITUDINAL, NATIONALLY REPRESENTATIVE MENTAL HEALTH SURVEY
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE avoidant personality disorder; generalized social anxiety disorder;
self-criticism; negative self-image; anxiety disorders
ID EPIDEMIOLOGIC SURVEY; SELF-CRITICISM; PHOBIA; ALCOHOL; PREVALENCE;
COMORBIDITY; RELIABILITY; DISABILITY
AB Background: The primary objective of this study was to prospectively examine the role of Avoidant Personality Disorder (AvPD) as a determinant in the outcome of Generalized Social Anxiety Disorder (GSAD) using Wave 2 of the National Epidemiologic Survey of Alcohol and Related Conditions 3 years later. Method: This study analyzed data from Waves 1 and 2 of the NESARC (n = 34,653). GSAD was operationalized based on the DSM-IV definitions of this SAD subtype. Results: Logistic regression analyses indicated that AvPD significantly predicted the persistence of GSAD, even after adjusting for a number of important sociodemographic variables and other psychiatric comorbidity. AvPD did not significantly predict outcome in non-generalized SAD. Conclusions: AvPD can influence the course of GSAD in adulthood. Specific personality dimensions may underlie and explain the similarities between AvPD and GSAD. Self-criticism could be a shared feature of both AvPD and GSAD and could represent an important psychological marker of poor prognosis in comorbid GSAD and AvPD. Depression and Anxiety 28:250-255, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Grant, Bridget F.] NIH, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA.
[Cox, Brian J.] Univ Manitoba, Dept Psychiat, Winnipeg, MB R3T 2N2, Canada.
[Cox, Brian J.; Turnbull, Danielle L.; Robinson, Jennifer A.] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada.
[Cox, Brian J.] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada.
RP Cox, BJ (reprint author), PZ 430 PsycHlth Ctr, 771 Bannatyne Ave, Winnipeg, MB R3E 3N4, Canada.
EM coxbj@cc.umanitoba.ca
FU Canadian Institutes of Health Research (CIHR); Canada Research Chairs
Program; National Institute of Mental Health (NIMH); National Institute
on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Drug
Abuse (NDA); Midcareer Development Award [K24 MH64122]
FX The authors disclose the following financial relationships within the
past 3 years: Contract grant sponsors: Canadian Institutes of Health
Research (CIHR); Canada Research Chairs Program (Cox); National
Institute of Mental Health (NIMH); National Institute on Alcohol Abuse
and Alcoholism (NIAAA); National Institute on Drug Abuse (NDA);
Midcareer Development Award; Contract grant number: K24 MH64122.
NR 29
TC 12
Z9 12
U1 7
U2 22
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2011
VL 28
IS 3
BP 250
EP 255
DI 10.1002/da.20787
PG 6
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 734JZ
UT WOS:000288331700010
PM 21308885
ER
PT J
AU Bharti, K
Gasper, M
Bertuzzi, S
Arnheiter, H
AF Bharti, Kapil
Gasper, Melanie
Bertuzzi, Stefano
Arnheiter, Heinz
TI Lack of the ventral anterior homeodomain transcription factor VAX1 leads
to induction of a second pituitary
SO DEVELOPMENT
LA English
DT Article
DE Midline defects; Septo-optic dysplasia; Adenohypophysis;
Neurohypophysis; FGF signaling; Ectopic pituitary; Mouse
ID GLAND DEVELOPMENT; EYE DEVELOPMENT; CELL TYPES; GENE; DIFFERENTIATION;
ORGANOGENESIS; SPECIFICATION; DEFICIENCY; FOREBRAIN; MOUSE
AB The pituitary gland is an endocrine organ that is developmentally derived from a fold in the oral ectoderm and a juxtaposed fold in the neural ectoderm. Here, we show that the absence of Vax1, a homeodomain transcription factor known for its role in eye and optic chiasm development, causes the rostral oral ectoderm to form an ectopic fold that eventually develops into a separate second pituitary with all the pituitary cell types and neuronal fibers characteristic of the normal pituitary. The induction of the second pituitary is associated with a localized ectopic expression of Fgf10, a gene encoding a growth factor known to recruit oral ectodermal cells into the pituitary. Interestingly, there are rare cases of pituitary duplications in humans that are also associated with optic nerve dysplasia, suggesting that VAX1 might be involved in the pathogenesis of this disorder.
C1 [Bharti, Kapil; Gasper, Melanie; Bertuzzi, Stefano; Arnheiter, Heinz] Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA.
RP Bharti, K (reprint author), Natl Inst Neurol Disorders & Stroke, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA.
EM kapilbharti@mail.nih.gov
FU NIH, NINDS
FX We thank the National Hormone Pituitary Program, NIDDK, NIH, for
antibodies; Drs Heiner Westphal, Peter Gruss, and Mathew Kelley for in
situ probes; Vinish Saini for Fig. 4L art; and Drs Susan Wray and Harold
Gainer for helpful comments on the manuscript. This work was supported
by the Intramural Research Program of the NIH, NINDS. Deposited in PMC
for release after 12 months.
NR 27
TC 19
Z9 19
U1 0
U2 3
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 MAR 1
PY 2011
VL 138
IS 5
BP 873
EP 878
DI 10.1242/dev.056465
PG 6
WC Developmental Biology
SC Developmental Biology
GA 724KX
UT WOS:000287576100008
PM 21247964
ER
PT J
AU Anderson, LH
Boulanger, CA
Smith, GH
Carmeliet, P
Watson, CJ
AF Anderson, Lisa H.
Boulanger, Corinne A.
Smith, Gilbert H.
Carmeliet, Peter
Watson, Christine J.
TI Stem Cell Marker Prominin-1 Regulates Branching Morphogenesis, but not
Regenerative Capacity, in the Mammary Gland
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE tissue-specific stem cells; mammary gland; ductal morphogenesis; tissue
regeneration
ID BREAST-CANCER; NONEPITHELIAL CELLS; PLASMA-MEMBRANE; PRIMARY CILIA;
CHOLESTEROL; EXPRESSION; CD133; PROTRUSIONS; PROTEIN
AB Prominin-1 (Prom1) is recognized as a stem cell marker in several tissues, including blood, neuroepithelium, and gut, and in human and mouse embryos and many cancers. Although Prom1 is routinely used as a marker for isolating stem cells, its biological function remains unclear. Here we use a knockout model to investigate the role of Prom1 in the mammary gland. We demonstrate that complete loss of Prom1 does not affect the regenerative capacity of the mammary epithelium. Surprisingly, we also show that in the absence of Prom1, mammary glands have reduced ductal branching, and an increased ratio of luminal to basal cells. The effects of Prom1 loss in the mammary gland are associated with decreased expression of prolactin receptor and matrix metalloproteinase-3. These experiments reveal a novel, functional role for Prom1 that is not related to stem cell activity, and demonstrate the importance of tissue-specific characterization of putative stem cell markers. Developmental Dynamics 240:674-681, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Anderson, Lisa H.; Watson, Christine J.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Anderson, Lisa H.; Boulanger, Corinne A.; Smith, Gilbert H.] Natl Canc Inst, Mammary Biol & Tumorigenesis Lab, Bethesda, MD USA.
[Carmeliet, Peter] VIB, Vesalius Res Ctr, Louvain, Belgium.
[Carmeliet, Peter] Katholieke Univ Leuven, Vesalius Res Ctr, Louvain, Belgium.
RP Watson, CJ (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England.
EM cjw53@cam.ac.uk
FU NCI; NIH; Center for Cancer Research ( NCI, NIH); Flemish Government
[FWO G.0209.07]
FX Grant sponsor: NCI; Grant sponsor: NIH; Grant sponsor: Intramural
Research Program of the Center for Cancer Research ( NCI, NIH); Grant
sponsor: Flemish Government; Grant number: FWO G.0209.07; Grant sponsor:
Flemish Government; Methusalem funding.
NR 25
TC 11
Z9 12
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD MAR
PY 2011
VL 240
IS 3
SI SI
BP 674
EP 681
DI 10.1002/dvdy.22539
PG 8
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 730KZ
UT WOS:000288033500017
PM 21337465
ER
PT J
AU Morahan, G
Mehta, M
James, I
Chen, WM
Akolkar, B
Erlich, HA
Hilner, JE
Julier, C
Nerup, J
Nierras, C
Pociot, F
Todd, JA
Rich, SS
AF Morahan, Grant
Mehta, Munish
James, Ian
Chen, Wei-Min
Akolkar, Beena
Erlich, Henry A.
Hilner, Joan E.
Julier, Cecile
Nerup, Jorn
Nierras, Concepcion
Pociot, Flemming
Todd, John A.
Rich, Stephen S.
CA Type 1 Diabet Genetics Consortium
TI Tests for Genetic Interactions in Type 1 Diabetes Linkage and
Stratification Analyses of 4,422 Affected Sib-Pairs
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; INSULIN GENE; SUSCEPTIBILITY LOCUS; MULTIPLEX
FAMILIES; MELLITUS MAPS; CONSORTIUM; COMPLEX; DISEASES; SEARCH; ALLELE
AB OBJECTIVE-Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1 diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions.
RESEARCH DESIGN AND METHODS-To address this issue, the Type 1 Diabetes Genetics Consortium recruited 3,892 families, including 4,422 affected sib-pairs. After genotyping 6,090 markers, linkage analyses of these families were performed, using a novel method and taking into account factors such as genotype at known susceptibility loci.
RESULTS-Evidence for linkage was robust at the HLA and INS loci, with logarithm of odds (LOD) scores of 398.6 and 5.5, respectively. There was suggestive support for five other loci. Stratification by other risk factors (including HLA and age at diagnosis) identified one convincing region on chromosome 6q14 showing linkage in male subjects (corrected LOD = 4.49; replication P = 0.0002), a locus on chromosome 19q in HLA identical siblings (replication P = 0.006), and four other suggestive loci.
CONCLUSIONS-This is the largest linkage study reported for any disease. Our data indicate there are no major type 1 diabetes subtypes definable by linkage analyses; susceptibility is caused by actions of HLA and an apparently random selection from a large number of modest-effect loci; and apart from HLA and INS, there is no important susceptibility factor discoverable by linkage methods. Diabetes 60:1030-1040, 2011
C1 [Morahan, Grant; Mehta, Munish] Univ Western Australia, Ctr Diabet Res, Western Australian Inst Med Res, Crawley, WA, Australia.
[Morahan, Grant; Mehta, Munish] Univ Western Australia, Ctr Med Res, Crawley, WA, Australia.
[James, Ian] Murdoch Univ, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia.
[Chen, Wei-Min; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Akolkar, Beena] NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
[Erlich, Henry A.] Roche Mol Syst, Pleasanton, CA USA.
[Hilner, Joan E.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.
[Julier, Cecile] INSERM, UMR S 958, Fac Med Denis Diderot, Paris, France.
[Julier, Cecile] Univ Paris 07, Paris, France.
[Nerup, Jorn] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Nierras, Concepcion] Juvenile Diabet Res Fdn, New York, NY USA.
[Pociot, Flemming] Univ Hosp Glostrup, Glostrup, Denmark.
[Todd, John A.] Univ Cambridge, Juvenile Diabet Res Fdn, Wellcome Trust Diabet & Inflammat Lab, Cambridge Inst Med Res, Cambridge, England.
RP Morahan, G (reprint author), Univ Western Australia, Ctr Diabet Res, Western Australian Inst Med Res, Crawley, WA, Australia.
EM gem@waimr.uwa.edu.au
OI Pociot, Flemming/0000-0003-3274-5448
FU National Health and Medical Research Council of Australia [516700];
Diabetes Research Foundation (Western Australia); National Institute of
Diabetes and Digestive and Kidney Diseases; National Institute of
Allergy and Infectious Diseases; National Human Genome Research
Institute; National Institute of Child Health and Human Development;
Juvenile Diabetes Research Foundation International [U01-DK-062418];
Juvenile Diabetes Research Foundation; National Institute for Health
Research; Wellcome Trust
FX G.M. and M.M. are supported by program Grant 516700 from the National
Health and Medical Research Council of Australia and by the Diabetes
Research Foundation (Western Australia). This research utilizes
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, the National Institute of
Allergy and Infectious Diseases, the National Human Genome Research
Institute, the National Institute of Child Health and Human Development,
and the Juvenile Diabetes Research Foundation International and is
supported by U01-DK-062418. J.A.T. is supported by the Juvenile Diabetes
Research Foundation, the National Institute for Health Research, and the
Wellcome Trust. No potential conflicts of interest relevant to this
article were reported.
NR 32
TC 17
Z9 17
U1 1
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAR
PY 2011
VL 60
IS 3
BP 1030
EP 1040
DI 10.2337/db10-1195
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730UM
UT WOS:000288060300038
PM 21266329
ER
PT J
AU Swafford, ADE
Howson, JMM
Davison, LJ
Wallace, C
Smyth, DJ
Schuilenburg, H
Maisuria-Armer, M
Mistry, T
Lenardo, MJ
Tod, JA
AF Swafford, Austin D. -E.
Howson, Joanna M. M.
Davison, Lucy J.
Wallace, Chris
Smyth, Deborah J.
Schuilenburg, Helen
Maisuria-Armer, Meeta
Mistry, Trupti
Lenardo, Michael J.
Tod, John A.
TI An Allele of IKZF1 (Ikaros) Conferring Susceptibility to Childhood Acute
Lymphoblastic Leukemia Protects Against Type 1 Diabetes
SO DIABETES
LA English
DT Article
ID DIFFERENTIATION; ASSOCIATIONS; LINKAGE; RISK; LOCI
AB OBJECTIVE-IKZF1 encoding Ikaros, an essential regulator of lymphopoiesis and immune homeostasis, has been implicated in the development of childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide association (GWA) studies have linked a region of the 3'-UTR of IKZF1 with C-ALL susceptibility, we tested whether IKZF1 is associated with the autoimmune disease type 1 diabetes.
RESEARCH DESIGN AND METHODS-rs10272724 (T > C) near IKZF1 at 7p12 was genotyped in 8,333 individuals with type 1 diabetes, 9,947 control subjects, and 3,997 families of European ancestry. Association was tested using logistic regression in the case-control data and by the transmission disequilibrium test in the families. Expression data for IKZF1 by rs10272724 genotype were obtained using quantitative PCR of mRNA/cDNA generated from peripheral blood mononuclear cells from 88 individuals, whereas expression data for five other neighboring genes were obtained from the online Genevar dataset.
RESULTS-The minor allele of rs10272724 (C) was found to be protective from type 1 diabetes (odds ratio 0.87 [95% CI 0.83-0.91]; P = 1.1 X 10(-11)). rs10272724 was not correlated with levels of two transcripts of TKZF1 in peripheral blood mononuclear cells.
CONCLUSIONS-The major susceptibility genotype for C-ALL confers protection from type 1 diabetes. Our finding strengthens the link between autoimmunity and lymphoid cancers. Further investigation is warranted for the genetic effect marked by rs10272724, its impact on IKZF1, and the role of Ikaros and other family members, Ailios (IKZF3) and Eos (IKZF4), in autoimmunity. Diabetes 60:1041-1044, 2011
C1 [Swafford, Austin D. -E.; Howson, Joanna M. M.; Davison, Lucy J.; Wallace, Chris; Smyth, Deborah J.; Schuilenburg, Helen; Maisuria-Armer, Meeta; Mistry, Trupti; Tod, John A.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 2QQ, England.
[Swafford, Austin D. -E.; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Tod, JA (reprint author), Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 2QQ, England.
EM john.todd@cimr.cam.ac.uk
OI smyth, deborah/0000-0002-6330-2669; Schuilenburg,
Helen/0000-0002-0040-6591; Wallace, Chris/0000-0001-9755-1703
FU Juvenile Diabetes Research Foundation International (JDRF); Wellcome
Trust [089989, 079895, 068545/Z102, 076113/C/04/Z, 076113]; National
Institute for Health Research Cambridge Biomedical Research Centre;
National Science Foundation; National Institutes of Health Division of
Intramural Research; U.K. Medical Research Council [G0000934]; Wellcome
Trust/JDRF [061858]; National Institutes of Health Research of England;
National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Allergy and Infectious Diseases; National Human
Genome Research Institute; National Institute of Child Health and Human
Development; Juvenile Diabetes Research Foundation [U01 DK062418]
FX This work was funded by the Juvenile Diabetes Research Foundation
International (JDRF), the Wellcome Trust, the National Institute for
Health Research Cambridge Biomedical Research Centre, the National
Science Foundation, and the National Institutes of Health Division of
Intramural Research. A.D.-E.S. is a National Institutes of Health
Cambridge Health Science Research Scholar and a National Science
Foundation Graduate Research Fellow. L.J.D is supported by a Wellcome
Trust Intermediate Clinical Fellowship. C.W. is supported by the
Wellcome Trust (089989). The Cambridge Institute for Medical Research is
in receipt of a Wellcome Trust Strategic Award (079895). The authors
thank the U.K. Medical Research Council and Wellcome Trust for funding
the collection of DNA for the British 1958 Birth Cohort (MRC Grant
G0000934, Wellcome Trust Grant 068545/Z102). They also acknowledge use
of DNA from The U.K. Blood Services collection of Common Controls (UKBS
collection), funded by the Wellcome Trust Grant 076113/C/04/Z, the
Wellcome Trust/JDRF Grant 061858, and the National Institutes of Health
Research of England. The collection was established as part of the
Wellcome Trust Case-Control Consortium (funding for the project was
provided by the Wellcome Trust under award 076113). 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, National Institute of
Allergy and Infectious Diseases, National Human Genome Research
Institute, National Institute of Child Health and Human Development, and
Juvenile Diabetes Research Foundation and supported by U01 DK062418.
Funding for the project was provided by the Wellcome Trust under award
076113.
NR 20
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U1 1
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAR
PY 2011
VL 60
IS 3
BP 1041
EP 1044
DI 10.2337/db10-0446
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730UM
UT WOS:000288060300039
PM 21270240
ER
PT J
AU DeBoer, MD
Gurka, MJ
Sumner, AE
AF DeBoer, Mark D.
Gurka, Matthew J.
Sumner, Anne E.
TI Diagnosis of the Metabolic Syndrome Is Associated With
Disproportionately High Levels of High-Sensitivity C-Reactive Protein in
Non-Hispanic Black Adolescents An analysis of NHANES 1999-2008
SO DIABETES CARE
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; TYPE-2 DIABETES-MELLITUS; INSULIN
SENSITIVITY; RACIAL-DIFFERENCES; ETHNIC-DIFFERENCES; NATIONAL-HEALTH;
UNITED-STATES; VISCERAL FAT; YOUNG-ADULTS; US CHILDREN
AB OBJECTIVE-Whereas it is known that the metabolic syndrome (MetS) has a paradoxically lower prevalence in non Hispanic black adolescents than in non Hispanic whites or Hispanics, the relative severity of MetS by race/ethnicity is unknown. Inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), is a key factor linking MetS to cardiovascular disease and type 2 diabetes. Our goal was to determine whether elevations of hsCRP vary by race/ethnicity among adolescents with MetS.
RESEARCH DESIGN AND METHODS-We used the National Health and Nutrition Examination Survey (1999-2008) and evaluated adolescents (age 12-19 years) using a pediatric/adolescent adaptation of the ATP III definition of MetS. We used linear regression to evaluate the interaction between MetS status and ethnicity with respect to hsCRP concentration.
RESULTS-For male and female adolescents, MetS was associated with elevated hsCRP levels compared with adolescents without MetS. However, the elevation in hsCRP between adolescents with and without MetS was greater in non Hispanic blacks compared with that in non Hispanic whites (P = 0.04) but not that in Hispanics (P = 0.18). hsCRP concentrations correlated with individual MetS components similarly among all ethnicities. In an evaluation of adolescents diagnosed with MetS, non Hispanic blacks had higher BMI and more hypertension than other ethnicities but there were no other racial/ethnic differences in the features of MetS.
CONCLUSIONS-Non Hispanic black adolescents have a greater differential in hsCRP between those with and those without MetS than the differential in non Hispanic whites but not that in Hispanics. Therefore, even though MetS has a low prevalence in non Hispanic blacks, MetS is a particularly good indicator of inflammation in non Hispanic black adolescents.
C1 [DeBoer, Mark D.] Univ Virginia, Dept Pediat, Charlottesville, VA 22903 USA.
[Gurka, Matthew J.] W Virginia Univ, Dept Community Med, Morgantown, WV 26506 USA.
[Sumner, Anne E.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP DeBoer, MD (reprint author), Univ Virginia, Dept Pediat, Charlottesville, VA 22903 USA.
EM deboer@virginia.edu
FU National Institutes of Health (NIH) [5K08-HD-060739-02, 1R21-DK-085363];
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
FX This work was supported by National Institutes of Health (NIH) Grants
5K08-HD-060739-02 (to MUD.) and 1R21-DK-085363 (to M.D.D. and M.J.G.).
A.E.S. was supported by the intramural program of the National Institute
of Diabetes and Digestive and Kidney Diseases, NIH.
NR 25
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U1 0
U2 6
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 MAR
PY 2011
VL 34
IS 3
BP 734
EP 740
DI 10.2337/dc10-1877
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 731YA
UT WOS:000288145400043
PM 21285387
ER
PT J
AU Shariff-Marco, S
Breen, N
Landrine, H
Reeve, BB
Krieger, N
Gee, GC
Williams, DR
Mays, VM
Ponce, NA
Alegria, M
Liu, BM
Willis, G
Johnson, TP
AF Shariff-Marco, Salma
Breen, Nancy
Landrine, Hope
Reeve, Bryce B.
Krieger, Nancy
Gee, Gilbert C.
Williams, David R.
Mays, Vickie M.
Ponce, Ninez A.
Alegria, Margarita
Liu, Benmei
Willis, Gordon
Johnson, Timothy P.
TI MEASURING EVERYDAY RACIAL/ETHNIC DISCRIMINATION IN HEALTH SURVEYS How
Best to Ask the Questions, in One or Two Stages, Across Multiple
Racial/Ethnic Groups?
SO DU BOIS REVIEW-SOCIAL SCIENCE RESEARCH ON RACE
LA English
DT Article
DE Discrimination; Racism; Prejudice; Race/Ethnicity; Differential Item
Functioning; Surveys; Split-ballot; Psychometric
ID BLACK-WOMENS-HEALTH; RACIAL-DISCRIMINATION; PERCEIVED DISCRIMINATION;
ASIAN-AMERICANS; ETHNIC DISCRIMINATION; AFRICAN-AMERICANS; IMPLICIT
MEASURES; ALLOSTATIC LOAD; BLOOD-PRESSURE; UNITED-STATES
AB While it is clear that self-reported racial/ethnic discrimination is related to illness, there are challenges in measuring self-reported discrimination or unfair treatment. In the present study, we evaluate the psychometric properties of a self-reported instrument across racial/ethnic groups in a population-based sample, and we test and interpret findings from applying two different widely-used approaches to asking about discrimination and unfair treatment. Even though we found that the subset of items we tested tap into a single underlying concept, we also found that different groups are more likely to report on different aspects of discrimination. Whether race is mentioned in the survey question affects both frequency and mean scores of reports of racial/ethnic discrimination. Our findings suggest caution to researchers when comparing studies that have used different approaches to measure racial/ethnic discrimination and allow us to suggest practical empirical guidelines for measuring and analyzing racial/ethnic discrimination. No less important, we have developed a self-reported measure of recent racial/ethnic discrimination that functions well in a range of different racial/ethnic groups and makes it possible to compare how racial/ethnic discrimination is associated with health disparities among multiple racial/ethnic groups.
C1 [Breen, Nancy; Reeve, Bryce B.; Willis, Gordon] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Landrine, Hope] E Carolina Univ, Ctr Hlth Dispar Res, Greenville, NC 27858 USA.
[Krieger, Nancy] Harvard Univ, Harvard Sch Publ Hlth, Cambridge, MA 02138 USA.
[Mays, Vickie M.] Univ Calif Los Angeles, Sch Publ Hlth, Coll Letters & Sci & Hlth Serv, Los Angeles, CA 90024 USA.
[Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA.
[Williams, David R.] Harvard Univ, Dept African & African Amer Studies, Cambridge, MA 02138 USA.
[Williams, David R.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA.
[Mays, Vickie M.] Univ Calif Los Angeles, Ctr Res Educ Training & Strateg Commun Minor Hlth, Los Angeles, CA USA.
[Ponce, Ninez A.] Univ Calif Los Angeles, Ctr Hlth Policy & Res, Los Angeles, CA USA.
[Alegria, Margarita] Harvard Univ, Harvard Med Sch, Cambridge, MA 02138 USA.
[Liu, Benmei] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Johnson, Timothy P.] Univ Illinois, Survey Res Lab, Dept Publ Adm, Chicago, IL USA.
[Johnson, Timothy P.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA.
RP Shariff-Marco, S (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA.
EM salma.shariffmarco@cpic.org
NR 68
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U1 3
U2 27
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1742-058X
J9 DU BOIS REV
JI Du Bois Rev.
PD SPR
PY 2011
VL 8
IS 1
SI SI
BP 159
EP 177
DI 10.1017/S1742058X11000129
PG 19
WC Ethnic Studies; Sociology
SC Ethnic Studies; Sociology
GA 051ZD
UT WOS:000312166600012
ER
PT J
AU Higgins, RD
Shankaran, S
AF Higgins, Rosemary D.
Shankaran, Seetha
TI Hypothermia: Novel approaches for premature infants
SO EARLY HUMAN DEVELOPMENT
LA English
DT Article; Proceedings Paper
CT 2nd International Conference on Clinical Neonatology
CY MAR 10-12, 2011
CL Torino, ITALY
DE Infant; Premature; Hypoxic-ischemic encephalopathy; Hypothermia;
Necrotizing enterocolitis
ID HYPOXIC-ISCHEMIC ENCEPHALOPATHY; MODERATE HYPOTHERMIA; NEONATAL
ENCEPHALOPATHY; REPERFUSION INJURY; NECROTIZING ENTEROCOLITIS;
INTESTINAL ISCHEMIA; ENERGY-METABOLISM; OUTCOMES; STRESS
AB Hypothermia for hypoxic ischemic encephalopathy has recently permeated clinical practice for term infants. Speculation regarding a neuroprotective benefit of hypothermia for premature infants with HIE has been raised as a need for further research. Hypothermia for other indications including necrotizing enterocolitis with the hope of tissue preservation following injury is less well studied. A summary of evidence for hypothermia and premature infants is presented in this brief report. Published by Elsevier Ireland Ltd.
C1 [Higgins, Rosemary D.] NICHD, NIH, Ctr Dev Biol & Perinatal Med, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA.
[Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Detroit, MI 48201 USA.
RP Higgins, RD (reprint author), NICHD, NIH, Ctr Dev Biol & Perinatal Med, Pregnancy & Perinatol Branch, 6100 Execut Blvd,Room 4B03B MSC 7510, Bethesda, MD 20892 USA.
EM higginsr@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 26
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U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-3782
J9 EARLY HUM DEV
JI Early Hum. Dev.
PD MAR
PY 2011
VL 87
SU S
BP S17
EP S18
DI 10.1016/j.earlhumdev.2011.01.004
PG 2
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 738GU
UT WOS:000288629100006
PM 21277717
ER
PT J
AU Glasser, JW
Hupert, N
McCauley, MM
Hatchett, R
AF Glasser, John W.
Hupert, Nathaniel
McCauley, Mary M.
Hatchett, Richard
TI Modeling and public health emergency responses: Lessons from SARS
SO EPIDEMICS
LA English
DT Article
DE Decision support modeling; Theoretical modeling; Emerging infectious
diseases; Emergency preparedness
ID ACUTE RESPIRATORY SYNDROME; EMERGING INFECTIOUS-DISEASES; TRANSMISSION
DYNAMICS; HONG-KONG; OUTBREAK; SMALLPOX; VACCINATION; INFLUENZA;
EPIDEMIC; INTERVENTIONS
AB Modelers published thoughtful articles after the 2003 SARS crisis, but had limited if any real-time impact on the global response and may even have inadvertently contributed to a lingering misunderstanding of the means by which the epidemic was controlled. The impact of any intervention depends on its efficiency as well as efficacy, and efficient isolation of infected individuals before they become symptomatic is difficult to imagine. Nonetheless, in exploring the possible impact of quarantine, the product of efficiency and efficacy was varied over the entire unit interval. Another mistake was repeatedly fitting otherwise appropriate gamma distributions to times to event regardless of whether they were stationary or not, particularly onset-isolation intervals whose progressive reduction evidently contributed to SARS control. By virtue of their unknown biology, newly-emerging diseases are more challenging than familiar human scourges. Influenza, for example, recurs annually and has been modeled more thoroughly than any other infectious disease. Moreover, models were integrated into preparedness exercises, during which working relationships were established that bore fruit during the 2009 A/H1N1 pandemic. To provide the most accurate and timely advice possible, especially about the possible impact of measures designed to control diseases caused by novel human pathogens, we must appreciate the value and difficulty of policy-oriented modeling. Effective communication of insights gleaned from modeling SARS will help to ensure that policymakers involve modelers in future outbreaks of newly-emerging infectious diseases. Accordingly, we illustrate the increasingly timely care-seeking by which, together with increasingly accurate diagnoses and effective isolation, SARS was controlled via heuristic arguments and descriptive analyses of familiar observations. Published by Elsevier B.V.
C1 [Glasser, John W.; Hupert, Nathaniel; McCauley, Mary M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Hupert, Nathaniel] Weill Cornell Med Coll, New York, NY USA.
[Hatchett, Richard] NIH, Bethesda, MD 20892 USA.
RP Glasser, JW (reprint author), 1600 Clifton Rd NE,Mail Stop A-34, Atlanta, GA 30333 USA.
EM jglasser@cdc.gov
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U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD MAR
PY 2011
VL 3
IS 1
BP 32
EP 37
DI 10.1016/j.epidem.2011.01.001
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 898AC
UT WOS:000300706200004
PM 21420657
ER
PT J
AU Healy, GN
Matthews, CE
Dunstan, DW
Winkler, EAH
Owen, N
AF Healy, Genevieve N.
Matthews, Charles E.
Dunstan, David W.
Winkler, Elisabeth A. H.
Owen, Neville
TI Sedentary time and cardio-metabolic biomarkers in US adults: NHANES
2003-06
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Epidemiology; Cardiovascular risk factors; Prevention; Population;
Sedentary; Accelerometry
ID AMERICAN-HEART-ASSOCIATION; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE;
INSULIN-RESISTANCE; UNITED-STATES; LIFE-STYLE; RISK; MORTALITY; OBESITY;
ACCELEROMETER
AB Aims Prolonged sedentary time is ubiquitous in developed economies and is associated with an adverse cardio-metabolic risk profile and premature mortality. This study examined the associations of objectively assessed sedentary time and breaks (interruptions) in sedentary time with continuous cardio-metabolic and inflammatory risk biomarkers, and whether these associations varied by sex, age, and/or race/ethnicity.
Methods and results Cross-sectional analyses with 4757 participants (>= 20 years) from the 2003/04 and 2005/06 US National Health and Nutrition Examination Survey (NHANES). An Actigraph accelerometer was used to derive sedentary time [< 100 counts per minute (cpm)] and breaks in sedentary time. Independent of potential confounders, including moderate-to-vigorous exercise, detrimental linear associations (P for trends < 0.05) of sedentary time with waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, HOMA-%B, and HOMA-%S were observed. Independent of potential confounders and sedentary time, breaks were beneficially associated with waist circumference and C-reactive protein (P for trends < 0.05). There was limited evidence of meaningful differences in associations with biomarkers by age, sex, or race/ethnicity. Notable exceptions were sex-differences in the associations of sedentary time and breaks with HDL-cholesterol, and race/ethnicity differences in the association of sedentary time with waist circumference with associations detrimental in non-Hispanic whites, null in Mexican Americans, and beneficial in non-Hispanic blacks.
Conclusion These are the first population-representative findings on the deleterious associations of prolonged sedentary time with cardio-metabolic and inflammatory biomarkers. The findings suggest that clinical communications and preventive health messages on reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk.
C1 [Healy, Genevieve N.; Dunstan, David W.; Winkler, Elisabeth A. H.; Owen, Neville] Univ Queensland, Sch Populat Hlth, Canc Prevent Res Ctr, Herston, Qld 4006, Australia.
[Healy, Genevieve N.; Dunstan, David W.; Owen, Neville] Baker IDI Heart & Diabet Inst, Melbourne, Vic 8008, Australia.
[Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
RP Healy, GN (reprint author), Univ Queensland, Sch Populat Hlth, Canc Prevent Res Ctr, Herston Rd, Herston, Qld 4006, Australia.
EM g.healy@uq.edu.au
RI Healy, Genevieve/A-7408-2008; Owen, Neville/K-5986-2012; matthews,
Charles/E-8073-2015; Dunstan, David/E-8473-2010;
OI Healy, Genevieve/0000-0001-7093-7892; matthews,
Charles/0000-0001-8037-3103; Dunstan, David/0000-0003-2629-9568; Owen,
Neville/0000-0003-2784-4820
FU National Health and Medical Research Council (NHMRC) [569861, 301200];
National Heart Foundation of Australia [PH 08B 3905]; Victorian Health
Promotion Foundation; Queensland Health Core Research Infrastructure
grant
FX This work was supported a National Health and Medical Research Council
(NHMRC #569861)/National Heart Foundation of Australia (PH 08B 3905)
Postdoctoral Fellowship to G.N.H.; a Victorian Health Promotion
Foundation Public Health Research Fellowship to D. W. D.; and Queensland
Health Core Research Infrastructure grant and NHMRC Program Grant
funding (#301200) to E.A.H.W. and N.O. All data used in this study were
collected by the National Center for Health Statistics, Centers for
Disease Control and Prevention.
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD MAR
PY 2011
VL 32
IS 5
BP 590
EP 597
DI 10.1093/eurheartj/ehq451
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 730JC
UT WOS:000288028600017
PM 21224291
ER
PT J
AU Olaku, O
White, JD
AF Olaku, Oluwadamilola
White, Jeffrey D.
TI Herbal therapy use by cancer patients: A literature review on case
reports
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Review
DE Herbs; Complementary and alternative medicine; Cancer; Treatment;
Toxicity
ID ACUTE PROMYELOCYTIC LEUKEMIA; REFRACTORY PROSTATE-CANCER; ARSENIC
TRIOXIDE; PC-SPES; ALTERNATIVE MEDICINE; BREAST-CANCER; COMPLETE
REMISSION; CELL CARCINOMA; CHINESE HERBS; COMPLEMENTARY
AB Complementary and alternative medicine use is common amongst cancer patients. In many surveys, herbal medicines are amongst the most commonly used group of treatments. Herbal remedies are believed by the general public to be safe, cause less side-effects and less likely to cause dependency.
The authors performed a literature review to assess which herbal approaches have had associated cancer case reports and determine which of these have been studied in prospective research. Eighteen case reports of patients having apparent antitumour effects from herbal therapy and 21 case reports of toxic effects of herbs used by cancer patients were identified. Clinicaltrials.gov and MEDLINE (via PubMed) were searched for each of the herbal products identified in these reports. Clinical trials in cancer populations were identified for green tea extracts or compounds (n = 34), phytoestrogens (n = 27), mistletoe (n = 8), Ganoderma lucidum (n = 1), noni (n = 1) and Silymarin (n = 1). Daikenchuto, PC-SPES, Nyoshinsan/TJ and Saw palmetto have also been studied prospectively.
In conclusion, some of the herbs with promising case report findings have undergone prospective clinical investigations but many others have either not yet been explored or the results have not been reported in English. Unconventional therapies, such as herbs and minerals, used in ancient medical traditions have led to the identification of active anticancer agents. Mechanisms to support prospective research with such approaches are discussed. Published by Elsevier Ltd.
C1 [White, Jeffrey D.] NCI, Off Canc Complementary & Alternat Med, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Olaku, Oluwadamilola] Kelly Serv Inc, Rockville, MD 20852 USA.
RP White, JD (reprint author), NCI, Off Canc Complementary & Alternat Med, NIH, Dept Hlth & Human Serv, 6116 Execut Blvd,Suite 609, Bethesda, MD 20892 USA.
EM jeffreyw@mail.nih.gov
FU National Cancer Institute
FX Funding for this manuscript was provided by the National Cancer
Institute. The National Cancer Institute did not participate in the
design, analysis, interpretation of data and writing of the manuscript.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2011
VL 47
IS 4
BP 508
EP 514
DI 10.1016/j.ejca.2010.11.018
PG 7
WC Oncology
SC Oncology
GA 736CW
UT WOS:000288468700003
PM 21185719
ER
PT J
AU Arnaud, O
Boumendjel, A
Geze, A
Honorat, M
Matera, EL
Guitton, J
Stein, WD
Bates, SE
Falson, P
Dumontet, C
Di Pietro, A
Payen, L
AF Arnaud, O.
Boumendjel, A.
Geze, A.
Honorat, M.
Matera, E. L.
Guitton, J.
Stein, W. D.
Bates, S. E.
Falson, P.
Dumontet, C.
Di Pietro, A.
Payen, L.
TI The acridone derivative MBLI-87 sensitizes breast cancer resistance
protein-expressing xenografts to irinotecan
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE ABC transporter; ABCG2; Irinotecan; Multidrug resistance; Reversion
ID GEFITINIB; ABCG2; BETA; PHARMACOGENETICS; CYCLODEXTRINS; TRANSPORTERS;
INHIBITORS; MICE
AB The breast cancer resistance protein ABCG2 confers cellular resistance to irinotecan (CPT-11) and its active metabolite SN-38. We utilised ABCG2-expressing xenografts as a model to evaluate the ability of a non-toxic ABCG2 inhibitor to increase intracellular drug accumulation. We assessed the activity of irinotecan in inuo in SCID mice: irinotecan completely inhibited the development of control pcDNA3.1 xenografts, whilst only delaying the growth of ABCG2-expressing xenografts. Addition of MBLI-87, an acridone derivative inhibitor, significantly increased the irinotecan effect against the growth of ABCG2-expressing xenografts. In vitro, MBLI-87 was as potent as GF120918 against ABCG2-mediated irinotecan efflux, and additionally was specific for ABCG2. A significant sensitisation to irinotecan was achieved despite the fact that doses remained well below the maximum tolerated dose (due to the rather limited solubility of MBLI-87). This suggested that MBLI-87 is an excellent candidate to prevent drug efflux by ABCG2, without altering plasma concentrations of irinotecan and SN-38 after IP (intra-peritoneal) injections. This could constitute a useful strategy to improve drug pharmacology, to facilitate drug penetration into normal tissue compartments protected by ABCG2, and potentially to reverse drug resistance in cancer cells. (c) 2010 Elsevier Ltd. All rights reserved.
C1 [Honorat, M.; Matera, E. L.; Dumontet, C.; Payen, L.] FNCLCC, Ctr Leon Berard, Inserm U590, F-69008 Lyon, France.
[Honorat, M.; Guitton, J.; Dumontet, C.; Payen, L.] Univ Lyon 1, ISPB, F-69008 Lyon, France.
[Boumendjel, A.] Univ Grenoble, CNRS, UMR 5063, Dept Pharmacochim Mol, F-38041 Grenoble 9, France.
[Arnaud, O.; Falson, P.; Di Pietro, A.] Univ Lyon 1, Equipe Labellisee Ligue 2009, Inst Biol & Chim Prot, UMR 5086,CNRS,IFR BioSci Gerland Lyon Sud 128, F-69367 Lyon 07, France.
[Stein, W. D.; Bates, S. E.] NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Guitton, J.] Ctr Hosp Lyon Sud, Hosp Civils Lyon, Lab Ciblage Therapeut Cancerol, F-69495 Pierre Benite, France.
[Payen, L.] Ctr Hosp Lyon Sud, Hosp Civils Lyon, Biochim Lab, F-69495 Pierre Benite, France.
RP Payen, L (reprint author), FNCLCC, Ctr Leon Berard, Inserm U590, 8 Ave Rockefeller, F-69008 Lyon, France.
EM Lea.payen@recherche.univ-lyon1.fr
FU INSERM [UMR 590]; Universite Lyon; Association pour la Recherche sur le
Cancer [ARC 4007]; Ligue Nationale contre le Cancer (Equipe labellisee
Ligue); LST (Lyon Science Transfert); Ligue Nationale contre le Cancer;
Ministere de l'Enseignement Superieur et de la Recherche
FX This work was supported by INSERM (UMR 590) and Universite Lyon 1, and
grants from Association pour la Recherche sur le Cancer (ARC 4007),
Ligue Nationale contre le Cancer (Equipe labellisee Ligue 2009) and LST
(Lyon Science Transfert). M. Honorat and O. Arnaud are respectively
recipient of doctoral fellowships from the Ligue Nationale contre le
Cancer and the Ministere de l'Enseignement Superieur et de la Recherche.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2011
VL 47
IS 4
BP 640
EP 648
DI 10.1016/j.ejca.2010.11.019
PG 9
WC Oncology
SC Oncology
GA 736CW
UT WOS:000288468700019
PM 21216589
ER
PT J
AU Bobe, G
Murphy, G
Albert, PS
Sansbury, LB
Young, MR
Lanza, E
Schatzkin, A
Colburn, NH
Cross, AJ
AF Bobe, Gerd
Murphy, Gwen
Albert, Paul S.
Sansbury, Leah B.
Young, Matthew R.
Lanza, Elaine
Schatzkin, Arthur
Colburn, Nancy H.
Cross, Amanda J.
TI Do interleukin polymorphisms play a role in the prevention of colorectal
adenoma recurrence by dietary flavonols?
SO EUROPEAN JOURNAL OF CANCER PREVENTION
LA English
DT Article
DE adenoma recurrence; flavonols; interleukins
ID HELICOBACTER-PYLORI INFECTION; CYTOKINE GENE POLYMORPHISMS; INTESTINAL
EPITHELIAL-CELLS; ANTIINFLAMMATORY DRUG-USE; HIGH-FIBER DIET; LOW-FAT;
CANCER DEVELOPMENT; US ADULTS; TRIAL; INFLAMMATION
AB Chemopreventive dietary compounds, such as flavonols, may inhibit colorectal carcinogenesis partly by altering cytokine expression and attenuating inflammation. Single nucleotide polymorphisms (SNPs) in the promoter regions of genes encoding cytokines may influence flavonol-induced changes in cytokine expression and consequently cancer risk. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between SNPs of interleukin (IL)-1 beta, 6, 8, and 10 alone or combined with flavonol intake or serum IL concentration changes, and adenoma recurrence in 808 participants from the intervention arm of the Polyp Prevention Trial, a 4-year intervention study evaluating the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Overall, SNPs in genes encoding IL-1 beta, 6, 8, and 10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, individuals homozygous for IL-10 -592 C (OR = 2.23, 95% CI: 1.07-4.66, P-interaction = 0.03) or IL-10 -819 C (OR = 2.18, 95% CI: 1.05-4.51, P-interaction = 0.05) had an elevated risk of high-risk adenoma recurrence when their serum IL-10 concentrations increased during the trial. In addition, IL-6 - 174 GG in combination with above median flavonol intake (OR = 0.14, 95% CI: 0.03-0.66) or with decreased IL-6 concentrations (OR = 0.14, 95% CI: 0.03-0.65) reduced the risk of advanced adenoma recurrence, although the interaction term was not statistically significant. In conclusion, our results suggest that IL SNPs, in combination with a flavonol-rich diet or decreased serum IL, may lower the risk of adenoma recurrence. European Journal of Cancer Prevention 20:86-95 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Bobe, Gerd; Young, Matthew R.; Lanza, Elaine; Colburn, Nancy H.] NICHHD, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA.
[Murphy, Gwen; Schatzkin, Arthur; Cross, Amanda J.] NICHHD, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Albert, Paul S.] NICHHD, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA.
[Sansbury, Leah B.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Bobe, G (reprint author), Oregon State Univ, 112 Withycombe Hall, Corvallis, OR 97331 USA.
EM gerd.bobe@oregonstate.edu
RI Murphy, Gwen/G-7443-2015
FU Office of Dietary Supplements [OD-08-007]; National Cancer Institute,
NIH, Bethesda, Maryland, USA
FX The authors would like to thank the Polyp Prevention Trial Study Group
for their outstanding contribution to this project. The authors thank
Helen Rager and Yanyu Wang from the Clinical Support Laboratory of SAIC
Frederick Inc. (Frederick, Maryland, USA) for cytokine analysis of the
serum samples. The members of the Polyp Prevention Study Group
participated in the conduct of the Polyp Prevention Trial. However, the
data presented in this paper and the conclusions drawn from them are
solely the responsibility of the above listed coauthors. National Cancer
Institute: Schatzkin A., Lanza E., Cross A.J., Corle D., Freedman L. S.,
Clifford C., Tangrea J.; Bowman Gray School of Medicine: Cooper M. R.,
Paskett E. (currently Ohio State University), Quandt S., DeGraffinreid
C., Bradham K., Kent L., Self M., Boyles D., West D., Martin L., Taylor
N., Dickenson E., Kuhn P., Harmon J., Richardson I., Lee H., Marceau E.;
University of New York at Buffalo: Lance M. P. (currently University of
Arizona), Marshall J. R. (currently Roswell Park Cancer Center), Hayes
D., Phillips J., Petrelli N., Shelton S., Randall E., Blake A., Wodarski
L., Deinzer M., Melton R.; Edwards Hines Jr. Hospital, Veterans
Administration Medical Center: Iber F. L., Murphy P., Bote E. C.,
Brandt-Whittington L., Haroon N., Kazi N., Moore M.A., Orloff S. B.,
Ottosen W. J., Patel M., Rothschild R. L., Ryan M., Sullivan J. M.,
Verma A.; Kaiser Foundation Research Institute: Caan B., Selby J.V.,
Friedman G., Lawson M., Taff G., Snow D., Belfay M., Schoenberger M.,
Sampel K., Giboney T., Randel M.; Memorial Sloan-Kettering Cancer
Center: Shike M., Winawer S., Bloch A., Mayer J., Morse R., Latkany L.,
D'Amato D., Schaffer A., Cohen L.; University of Pittsburgh: Weissfeld
J., Schoen R., Schade R.R., Kuller L., Gahagan B., Caggiula A., Lucas
C., Coyne T., Pappert S., Robinson R., Landis V., Misko S., Search L.;
University of Utah: Burt R. W., Slattery M., Viscofsky N., Benson J.,
Neilson J., McDivitt R., Briley M., Heinrich K., Samowitz W.; Walter
Reed Army Medical Center: Kikendall J.W., Mateski D.J., Wong R., Stoute
E., Jones-Miskovsky V., Greaser A., Hancock S., Chandler S.; Data and
Nutrition Coordinating Center (Westat): Cahill J., Hasson M., Daston C.,
Brewer B., Zimmerman T., Sharbaugh C., O'Brien B., Cranston L., Odaka
N., Umbel K., Pinsky J., Price H., Slonim A.; Central Pathologists:
Lewin K. (University of California, Los Angeles), Appelman H.
(University of Michigan); Laboratories: Bachorik P. S., Lovejoy K.
(Johns Hopkins University); Sowell A. (Centers for Disease Control);
Data and Safety Monitoring Committee: Greenberg E. R. (chair; Dartmouth
University), Feldman E. (Augusta, Georgia), Garza C. (Cornell
University), Summers R. (University of Iowa), Weiand S. (through June
1995; University of Minnesota), DeMets D. (beginning July 1995;
University of Wisconsin). This study was supported by the Office of
Dietary Supplements (OD-08-007) and the Intramural Research Program,
National Cancer Institute, NIH, Bethesda, Maryland, USA
NR 55
TC 3
Z9 3
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-8278
EI 1473-5709
J9 EUR J CANCER PREV
JI Eur. J. Cancer Prev.
PD MAR
PY 2011
VL 20
IS 2
BP 86
EP 95
DI 10.1097/CEJ.0b013e3283429e45
PG 10
WC Oncology
SC Oncology
GA 711JB
UT WOS:000286585600003
PM 21160427
ER
PT J
AU Xiong, YM
Bosselut, R
AF Xiong, Yumei
Bosselut, Remy
TI The enigma of CD4-lineage specification
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Review
DE CD4(+) T cells; Cell differentiation; T cells; Thymopoiesis;
Transcription factors
ID T-CELL LINEAGE; TRANSCRIPTION FACTOR GATA-3; POSITIVE SELECTION;
ZINC-FINGER; THYMOCYTE DEVELOPMENT; CD4 EXPRESSION; C-MYB;
CYTOTOXIC-LINEAGE; GENE-EXPRESSION; FACTOR TOX
AB CD4(+) T cells are essential for defenses against pathogens and affect the functions of most cells involved in the immune response. Although CD4(+) T cells generally recognize peptide antigens bound to MHC-II molecules, important subsets are restricted by other MHC or MHC-like molecules, including CD1d-restricted "invariant'' iNK T cells. This review discusses recently identified nodes in the transcriptional circuits that are involved in controlling CD4(+) T-cell differentiation, notably the commitment factor Thpok and its interplay with Runx transcriptional regulators, and focuses on how transcription factors acting upstream of Thpok, including Gata3, Tox and E-box proteins, promote the emergence of CD4-lineage-specific gene expression patterns.
C1 [Xiong, Yumei; 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, Bldg 37,Room 3015,37 Convent Dr, Bethesda, MD 20892 USA.
EM remy@helix.nih.gov
FU National Cancer Institute, Center for Cancer Research, NIH
FX The authors thank Paul Love and Melanie Vacchio for their comments on
the manuscript. They apologize to colleagues whose work was not cited
because of space limitations. Research in the authors' laboratory is
supported by the Intramural Research Program of the National Cancer
Institute, Center for Cancer Research, NIH.
NR 66
TC 7
Z9 7
U1 1
U2 4
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 MAR
PY 2011
VL 41
IS 3
BP 568
EP 574
DI 10.1002/eji.201041098
PG 7
WC Immunology
SC Immunology
GA 731HU
UT WOS:000288097700002
PM 21341258
ER
PT J
AU Andrade, MV
Iwaki, S
Ropert, C
Gazzinelli, RT
Cunha-Melo, JR
Beaven, MA
AF Andrade, Marcus V.
Iwaki, Shoko
Ropert, Catherine
Gazzinelli, Ricardo T.
Cunha-Melo, Jose R.
Beaven, Michael A.
TI Amplification of cytokine production through synergistic activation of
NFAT and AP-1 following stimulation of mast cells with antigen and IL-33
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Ag; Cytokine; IL-33; Mast Cells; Signaling mechanisms
ID RECEPTOR ACCESSORY PROTEIN; I-KAPPA-B; INFLAMMATORY MEDIATORS; BASOPHIL
ACTIVATION; SIGNALING PATHWAYS; INDUCED ARTHRITIS; T-LYMPHOCYTES; ST2
RECEPTOR; KINASE TAK1; IGE
AB IL-33 is associated with atopic and autoimmune diseases and, as reported here, it interacts synergistically with Ag to markedly enhance production of inflammatory cytokines in rodent mast cells even in the absence of degranulation. Investigation of the underlying mechanisms revealed that synergy in signaling occurred at the level of TGF-beta-activated kinase 1, which was then transmitted downstream through JNK, p38 MAP kinase, and AP-1. Stimulation of the Ca2(+)/calcineurin/NFAT pathway by Ag, which IL-33 did not, was critical for the synergy between Ag and IL-33. For example, selective stimulation of the NFAT pathway by thapsigargin also markedly enhanced responses to IL-33 in a calcineurin-dependent manner. As indicated by luciferase-reporter assays, IL-33 failed to stimulate the transcriptional activities of NFAT and AP-1 but augmented the activation of these transcription factors by Ag or thapsigargin. Robust stimulation of NF-kappa B transcriptional activity by IL-33 was also essential for the synergy. These and pharmacologic data suggested that the enhanced production of cytokines resulted in part from amplification of the activation of AP-1 and NFAT as well as co-operative interactions among transcription factors. IL-33 may retune mast cell responses to Ag toward enhanced cytokine production and thus determine the symptoms and severity of Ag-dependent allergic and autoimmune diseases.
C1 [Andrade, Marcus V.; Iwaki, Shoko; Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Andrade, Marcus V.] Univ Fed Minas Gerais, Sch Med, Dept Internal Med, Belo Horizonte, MG, Brazil.
[Cunha-Melo, Jose R.] Univ Fed Minas Gerais, Sch Med, Dept Surg, Belo Horizonte, MG, Brazil.
[Ropert, Catherine; Gazzinelli, Ricardo T.] Fiocruz MS, Rene Rachou Inst, Immunopathol Lab, Belo Horizonte, MG, Brazil.
RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Rm 8N109,Bldg 10, Bethesda, MD 20892 USA.
EM beavenm@nhlbi.nih.gov
RI ANDRADE, MARCUS/A-4764-2008; Ropert, Catherine/G-2463-2012; Cunha-Melo,
Jose Renan/C-6262-2013; Vacinas, Inct/J-9431-2013
OI ANDRADE, MARCUS/0000-0002-3716-0919;
FU NHLBI, National Institutes of Health; National Institutes of Health [RO1
TW006612]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
(CNPq); Fundacao de Amparo a Pesquisa do Estado de Minas Gerais
(FAPEMIG), Brazil
FX This work was supported by the Intramural Research Program, NHLBI,
National Institutes of Health (M. V. A., S. I., and M. A. B.); National
Institutes of Health grant RO1 TW006612 (GRIP) (M. V. A.); Conselho
Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao
de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil (M. V.
A., C. R., R. T. G., J. R. C.-M.). M. V. A. performed much of this work
while on leave from the Faculty of Medicine, Universidade Federal de
Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. The authors
also thank Dr. Mauro M. Texeira, Department of Biochemistry and
Immunology, Federal University of Minas Gerais, Brazil, for suggestions
and initial supply of IL-33, and Leigh Samsel, FACS Core Facility,
National Heart, Lung and Blood Institute, for assistance with the
Affymetrix cytokine assay system.
NR 56
TC 32
Z9 36
U1 0
U2 4
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 MAR
PY 2011
VL 41
IS 3
BP 760
EP 772
DI 10.1002/eji.201040718
PG 13
WC Immunology
SC Immunology
GA 731HU
UT WOS:000288097700021
PM 21308681
ER
PT J
AU Perez-Leighton, CE
Schmidt, TM
Abramowitz, J
Birnbaumer, L
Kofuji, P
AF Perez-Leighton, Claudio E.
Schmidt, Tiffany M.
Abramowitz, Joel
Birnbaumer, Lutz
Kofuji, Paulo
TI Intrinsic phototransduction persists in melanopsin-expressing ganglion
cells lacking diacylglycerol-sensitive TRPC subunits
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE circadian entrainment; intrinsically photosensitive ganglion cell;
mouse; retina
ID PHYSIOLOGICAL DIVERSITY; SIGNALING PATHWAY; MOUSE RETINA; IN-VITRO;
CHANNELS; PHOTORECEPTORS; DROSOPHILA; GENE; PHOTOSENSITIVITY;
IDENTIFICATION
AB In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate various non-image-forming photic responses, such as circadian photoentrainment, pupillary light reflex and pineal melatonin suppression. ipRGCs directly respond to environmental light by activation of the photopigment melanopsin followed by the opening of an unidentified cation-selective channel. Studies in heterologous expression systems and in the native retina have strongly implicated diacylglycerol-sensitive transient receptor potential channels containing TRPC3, TRPC6 and TRPC7 subunits in melanopsin-evoked depolarization. Here we show that melanopsin-evoked electrical responses largely persist in ipRGCs recorded from early postnatal (P6-P8) and adult (P22-P50) mice lacking expression of functional TRPC3, TRPC6 or TRPC7 subunits. Multielectrode array (MEA) recordings performed at P6-P8 stages under conditions that prevent influences from rod/cone photoreceptors show comparable light sensitivity for the melanopsin-evoked responses in these mutant mouse lines in comparison to wild-type (WT) mice. Patch-clamp recordings from adult mouse ipRGCs lacking TRPC3 or TRPC7 subunits show intrinsic light-evoked responses equivalent to those recorded in WT mice. Persistence of intrinsic light-evoked responses was also noted in ipRGCs lacking TRPC6 subunits, although with significantly smaller magnitudes. These results demonstrate that the melanopsin-evoked depolarization in ipRGCs is not mediated by either TRPC3, TRPC6 or TRPC7 channel subunits alone. They also suggest that the melanopsin signaling pathway includes TRPC6-containing heteromeric channels in mature retinas.
C1 [Perez-Leighton, Claudio E.; Schmidt, Tiffany M.; Kofuji, Paulo] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA.
[Abramowitz, Joel; Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Neurobiol Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Kofuji, P (reprint author), Univ Minnesota, Dept Neurosci, 321 Church St SE,6-145 Jackson Hall, Minneapolis, MN 55455 USA.
EM kofuj001@umn.edu
RI Schmidt, Tiffany/A-9660-2012; Schmidt, Tiffany /L-7598-2014; Abramowitz,
Joel/A-2620-2015;
OI Schmidt, Tiffany/0000-0002-4791-6775; Schmidt, Tiffany
/0000-0002-4791-6775; Kofuji, Paulo/0000-0002-4840-9986; Perez-Leighton,
Claudio/0000-0003-1817-6314
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01-ES-101684]; NIH [R01EY012949, R21-EY018885, T32
EY0707133]
FX This study was supported in part by the Intramural Research Programs of
the National Institutes of Health, National Institute of Environmental
Health Sciences (Z01-ES-101684), and by grants NIH R01EY012949,
R21-EY018885 and T32 EY0707133. We thank Darwin Hang for excellent
technical assistance.
NR 54
TC 27
Z9 27
U1 0
U2 6
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 MAR
PY 2011
VL 33
IS 5
BP 856
EP 867
DI 10.1111/j.1460-9568.2010.07583.x
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 727MN
UT WOS:000287804500006
PM 21261756
ER
PT J
AU Berger, VW
Knoll, D
AF Berger, Vance W.
Knoll, Diana
TI Levels of Evidence: Further Insight on Gugiu and Gugiu
SO EVALUATION & THE HEALTH PROFESSIONS
LA English
DT Editorial Material
C1 [Berger, Vance W.; Knoll, Diana] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM vance917@gmail.com
NR 7
TC 3
Z9 3
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0163-2787
J9 EVAL HEALTH PROF
JI Eval. Health Prof.
PD MAR
PY 2011
VL 34
IS 1
BP 124
EP 126
DI 10.1177/0163278710391466
PG 3
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 715XA
UT WOS:000286926300005
PM 21177639
ER
PT J
AU Ganatra, MB
Vainauskas, S
Hong, JM
Taylor, TE
Denson, JPM
Esposito, D
Read, JD
Schmeisser, H
Zoon, KC
Hartley, JL
Taron, CH
AF Ganatra, Mehul B.
Vainauskas, Saulius
Hong, Julia M.
Taylor, Troy E.
Denson, John-Paul M.
Esposito, Dominic
Read, Jeremiah D.
Schmeisser, Hana
Zoon, Kathryn C.
Hartley, James L.
Taron, Christopher H.
TI A set of aspartyl protease-deficient strains for improved expression of
heterologous proteins in Kluyveromyces lactis
SO FEMS YEAST RESEARCH
LA English
DT Article
DE aspartic protease; protein expression; protein degradation; yapsin;
Kluyveromyces lactis
ID SACCHAROMYCES-CEREVISIAE; CELL-WALL; PROTEOLYTIC DEGRADATION; SECRETORY
PATHWAY; PICHIA-PASTORIS; GENE ENCODES; YEAST; MUTANTS; FAMILY;
OVEREXPRESSION
AB Secretion of recombinant proteins is a common strategy for heterologous protein expression using the yeast Kluyveromyces lactis. However, a common problem is degradation of a target recombinant protein by secretory pathway aspartyl proteases. In this study, we identified five putative pfam00026 aspartyl proteases encoded by the K. lactis genome. A set of selectable marker-free protease deletion mutants was constructed in the prototrophic K. lactis GG799 industrial expression strain background using a PCR-based dominant marker recycling method based on the Aspergillus nidulans acetamidase gene (amdS). Each mutant was assessed for its secretion of protease activity, its health and growth characteristics, and its ability to efficiently produce heterologous proteins. In particular, despite having a longer lag phase and slower growth compared with the other mutants, a Delta yps1 mutant demonstrated marked improvement in both the yield and the quality of Gaussia princeps luciferase and the human chimeric interferon Hy3, two proteins that experienced significant proteolysis when secreted from the wild-type parent strain.
C1 [Ganatra, Mehul B.; Vainauskas, Saulius; Hong, Julia M.; Read, Jeremiah D.; Taron, Christopher H.] New England Biolabs Inc, Div Gene Express, Ipswich, MA 01938 USA.
[Taylor, Troy E.; Denson, John-Paul M.; Esposito, Dominic; Hartley, James L.] NCI, Prot Express Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Schmeisser, Hana; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Taron, CH (reprint author), New England Biolabs Inc, Div Gene Express, 240 Cty Rd, Ipswich, MA 01938 USA.
EM taron@neb.com
FU New England Biolabs; NIAID; NIH
FX C.H.T. thanks Dr Donald Comb of New England Biolabs for financial
support. This work was partially supported by the intramural research
program, NIAID, NIH. The authors thank Tom Zhao and Barbara Taron for
comments and critical review of the manuscript.
NR 40
TC 7
Z9 8
U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1567-1356
J9 FEMS YEAST RES
JI FEMS Yeast Res.
PD MAR
PY 2011
VL 11
IS 2
BP 168
EP 178
DI 10.1111/j.1567-1364.2010.00703.x
PG 11
WC Biotechnology & Applied Microbiology; Microbiology; Mycology
SC Biotechnology & Applied Microbiology; Microbiology; Mycology
GA 720YA
UT WOS:000287317400003
PM 21166768
ER
PT J
AU Hubbard, JJ
Kottilil, S
AF Hubbard, Jonathan J.
Kottilil, Shyam
TI Extra-hepatic replication of the hepatitis C virus: current issues and
future directions
SO FUTURE VIROLOGY
LA English
DT Editorial Material
ID BLOOD MONONUCLEAR-CELLS; NON-HODGKINS-LYMPHOMA; MIXED CRYOGLOBULINEMIA;
PERIPHERAL-BLOOD; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; VIROLOGICAL
RESPONSE; HCV INFECTION; B-CELLS; LIVER; MANIFESTATIONS
C1 [Hubbard, Jonathan J.; Kottilil, Shyam] NIAID, Immunopathogenesis Sect, Lab Immunoregulat, NIH,Dept Hlth & Human Sci, Bethesda, MD 20892 USA.
RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Lab Immunoregulat, NIH,Dept Hlth & Human Sci, Bldg 10,Room 11N204,9000 Rockv Lle Pike, Bethesda, MD 20892 USA.
NR 47
TC 0
Z9 0
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0794
J9 FUTURE VIROL
JI Future Virol.
PD MAR
PY 2011
VL 6
IS 3
BP 275
EP 278
DI 10.2217/FVL.11.7
PG 4
WC Virology
SC Virology
GA 745RH
UT WOS:000289182900001
ER
PT J
AU Feld, JJ
Modi, AA
El-Diwany, R
Rotman, Y
Thomas, E
Ahlenstiel, G
Titerence, R
Koh, C
Cherepanov, V
Heller, T
Ghany, MG
Park, Y
Hoofnagle, JH
Liang, TJ
AF Feld, Jordan J.
Modi, Apurva A.
El-Diwany, Ramy
Rotman, Yaron
Thomas, Emmanuel
Ahlenstiel, Golo
Titerence, Rachel
Koh, Christopher
Cherepanov, Vera
Heller, Theo
Ghany, Marc G.
Park, Yoon
Hoofnagle, Jay H.
Liang, T. Jake
TI S-Adenosyl Methionine Improves Early Viral Responses and
Interferon-Stimulated Gene Induction in Hepatitis C Nonresponders
SO GASTROENTEROLOGY
LA English
DT Article
DE Interferon Signaling; Transcription Factor; Chronic Hepatitis
ID PLUS RIBAVIRIN; ARGININE METHYLATION; RANDOMIZED-TRIAL; VIRUS-INFECTION;
PEGINTERFERON; THERAPY; RETREATMENT; INHIBITION; TELAPREVIR; ACTIVATION
AB BACKGROUND & AIMS: Less than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after pegylated interferon (peginterferon) and ribavirin therapy. S-adenosyl methionine (SAMe) improves interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early antiviral response and interferon signaling in nonresponders to previous antiviral therapy and investigated the mechanisms involved. METHODS: Nonresponders with HCV genotype 1 were given peginterferon alfa-2a and ribavirin for 2 weeks (course A, baseline/control). After 1 month, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. RESULTS: The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar with and without SAMe. However, the second phase slope of viral decline was improved with SAMe (course A, 0.11 +/- 0.04 log(10) IU/mL/wk; course B, 0.27 +/- 0.06; P = .009); 11 patients (53%) achieved an early virological response, and 10 (48%) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater during course B. In cultured cells, SAMe increased induction of ISGs and the antiviral effects of interferon by increasing STAT1 methylation, possibly affecting STAT1-DNA binding. CONCLUSIONS: The addition of SAMe to peginterferon and ribavirin improves the early viral kinetics and increases ISG induction in nonresponders to previous therapy. SAMe might be a useful adjunct to peginterferon-based therapies in chronic HCV infection.
C1 [Feld, Jordan J.; Modi, Apurva A.; El-Diwany, Ramy; Rotman, Yaron; Thomas, Emmanuel; Ahlenstiel, Golo; Titerence, Rachel; Koh, Christopher; Heller, Theo; Ghany, Marc G.; Park, Yoon; Hoofnagle, Jay H.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Feld, Jordan J.; Cherepanov, Vera] Univ Toronto, McLaughlin Rotman Ctr Global Hlth, Univ Hlth Network, Toronto Western Hosp Liver Ctr, Toronto, ON, Canada.
RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM jakel@intra.niddk.nih.gov
OI Rotman, Yaron/0000-0002-7549-8216; El-Diwany, Ramy/0000-0002-3224-6414;
Ahlenstiel, Golo/0000-0003-0026-1457
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX Supported by the Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases. Pharmavite LLC provided
SAMe for the study but had no involvement in study design, data
analysis, or manuscript preparation.
NR 32
TC 31
Z9 33
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 830
EP U219
DI 10.1053/j.gastro.2010.09.010
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700024
PM 20854821
ER
PT J
AU Lok, AS
Everhart, JE
Wright, EC
Di Bisceglie, AM
Kim, HY
Sterling, RK
Everson, GT
Lindsay, KL
Lee, WM
Bonkovsky, HL
Dienstag, JL
Ghany, MG
Morishima, C
Morgan, TR
AF Lok, Anna S.
Everhart, James E.
Wright, Elizabeth C.
Di Bisceglie, Adrian M.
Kim, Hae-Young
Sterling, Richard K.
Everson, Gregory T.
Lindsay, Karen L.
Lee, William M.
Bonkovsky, Herbert L.
Dienstag, Jules L.
Ghany, Marc G.
Morishima, Chihiro
Morgan, Timothy R.
CA Halt-C Trial Grp
TI Maintenance Peginterferon Therapy and Other Factors Associated With
Hepatocellular Carcinoma in Patients With Advanced Hepatitis C
SO GASTROENTEROLOGY
LA English
DT Article
DE Interferon Therapy; Hepatitis C Clinical Trial; Interferon
Nonresponders; Liver Cancer
ID SUSTAINED VIROLOGICAL RESPONSE; LOW-DOSE PEGINTERFERON;
INTERFERON-ALPHA; PROLONGED THERAPY; RISK-FACTORS; CIRRHOSIS; TRIAL;
METAANALYSIS; PROGRESSION; SURVIVAL
AB BACKGROUND & AIMS: Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance therapy with pegylated interferon (peginterferon) does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer posttreatment follow-up period. METHODS: The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores >= 3) who did not have a sustained virologic response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7) years. RESULTS: Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.24-0.83); in treated and control patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44; 95% CI, 0.77-2.69). Treated patients with a >= 2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03). CONCLUSIONS: Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk of HCC than controls.
C1 [Lok, Anna S.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA.
[Sterling, Richard K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA.
[Everson, Gregory T.] Univ Colorado, Denver Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Aurora, CO USA.
[Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
RP Lok, AS (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol, 3912 Taubman Ctr,SPC 5362, Ann Arbor, MI 48109 USA.
EM aslok@umich.edu
OI Yang, Shuman/0000-0002-9638-0890
FU University of Massachusetts Medical Center, Worcester, Massachusetts
[N01-DK-9-2326]; University of Connecticut Health Center, Farmington,
Connecticut [M01RR-06192]; Saint Louis University School of Medicine, St
Louis, Missouri [N01-DK-9-2324]; Massachusetts General Hospital, Boston,
Massachusetts (Harvard Clinical and Translational Science Center)
[N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University of Colorado
Denver School of Medicine, Aurora, Colorado [N01-DK-9-2327, M01RR-00051,
1 UL1 RR 025780-01]; University of California-Irvine, Irvine, California
[N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical
Center, Dallas, Texas (North and Central Texas Clinical and
Translational Science Initiative) [N01-DK-9-2321, M01RR-00633, 1 UL1
RR024982-01]; University of Southern California, Los Angeles, California
[N01-DK-9-2325, M01RR-00043]; University of Michigan Medical Center, Ann
Arbor, Michigan (Michigan Center for Clinical and Health Research)
[N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth
University Health System, Richmond, Virginia [N01-DK-9-2322,
M01RR-00065]; University of Washington, Seattle, Washington
[N01-DK-9-2318]; New England Research Institutes, Watertown,
Massachusetts [N01-DK-9-2328]; Hoffmann-La Roche, Inc; National
Institute of Diabetes and Digestive and Kidney Diseases; National Center
for Research Resources, National Institutes of Health; National
Institutes of Health
FX In addition to the authors of this manuscript, the following individuals
were instrumental in the planning, conduct, and/or care of patients
enrolled in this study at each of the participating institutions:
University of Massachusetts Medical Center, Worcester, Massachusetts
(contract N01-DK-9-2326): Gyongyi Szabo, MD, Barbara F. Banner, MD,
Maureen Cormier, RN, and Donna Giansiracusa, RN; University of
Connecticut Health Center, Farmington, Connecticut (grant M01RR-06192):
Gloria Borders, RN, and Michelle Kelley, RN, ANP; Saint Louis University
School of Medicine, St Louis, Missouri (contract N01-DK-9-2324): Bruce
Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, and
Debra King, RN; Massachusetts General Hospital, Boston, Massachusetts
(contract N01-DK-9-2319, grant M01RR-01066; grant 1 UL1 RR025758-01,
Harvard Clinical and Translational Science Center): Raymond T. Chung,
MD, Andrea E. Reid, MD, Atul K. Bhan, MD, Wallis A. Molchen, and David
P. Lundmark; University of Colorado Denver School of Medicine, Aurora,
Colorado (contract N01-DK-9-2327, grant M01RR-00051, grant 1 UL1 RR
025780-01): Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell Nash,
MD, Jennifer DeSanto, RN, and Carol McKinley, RN; University of
California-Irvine, Irvine, California (contract N01-DK-9-2320, grant
M01RR-00827): John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD,
MPH, Muhammad Sheikh, MD, and Choon Park, RN; University of Texas
Southwestern Medical Center, Dallas, Texas (contract N01-DK-9-2321,
grant M01RR-00633, grant 1 UL1 RR024982-01, North and Central Texas
Clinical and Translational Science Initiative): Thomas E. Rogers, MD,
Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein,
RN, BSN, and Nancy Liston, MPH; University of Southern California, Los
Angeles, California (contract N01-DK-9-2325, grant M01RR-00043):
Sugantha Govindarajan, MD, Carol B. Jones, RN, and Susan L. Milstein,
RN; University of Michigan Medical Center, Ann Arbor, Michigan (contract
N01-DK-9-2323, grant M01RR-00042, grant 1 UL1 RR024986, Michigan Center
for Clinical and Health Research): Robert J. Fontana, MD, Joel K.
Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, and R. Tess Bonham, BS;
Virginia Commonwealth University Health System, Richmond, Virginia
(contract N01-DK-9-2322, grant M01RR-00065): Mitchell L. Shiffman, MD,
Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, and
Paula Smith, RN; Liver Diseases Branch, National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health,
Bethesda, Maryland: T. Jake Liang, MD, David Kleiner, MD, PhD, Yoon
Park, RN, Elenita Rivera, RN, and Vanessa Haynes-Williams, RN; National
Institute of Diabetes and Digestive and Kidney Diseases, Division of
Digestive Diseases and Nutrition, Bethesda, Maryland: Leonard B. Seeff,
MD, Patricia R. Robuck, PhD, and Jay H. Hoofnagle, MD; University of
Washington, Seattle, Washington (contract N01-DK-9-2318): David R.
Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC,
ASCP, and Natalia Antonov, MEd; New England Research Institutes,
Watertown, Massachusetts (contract N01-DK-9-2328): Kristin K. Snow, MSc,
ScD, Anne M. Stoddard, ScD, and Margaret C. Bell, MS, MPH; Inova Fairfax
Hospital, Falls Church, Virginia: Zachary D. Goodman, MD, PhD, Fanny
Monge, and Michelle Parks; Data and Safety Monitoring Board Members:
Gary L. Davis, MD (Chair), Guadalupe Garcia-Tsao, MD, Michael Kutner,
PhD, Stanley M. Lemon, MD, and Robert P. Perrillo, MD.; The authors
disclose the following: Dr Lok is a consultant and receives research
support from Hoffmann-La Roche, Inc; Dr Di Bisceglie is a consultant and
receives research support from Hoffmann-La Roche, Inc; Dr Sterling is a
consultant and receives research support from Hoffmann-La Roche, Inc; Dr
Everson is a consultant and receives research support from Hoffmann-La
Roche, Inc; Dr Lindsay was a consultant and received research support
from Hoffmann-La Roche, Inc, during this study and is now an employee of
Tibotec, Inc (a subsidiary of Johnson and Johnson; Titusville, NJ); Dr
Lee receives research support from Hoffmann-La Roche, Inc; Dr Bonkovsky
receives research support from Hoffmann-La Roche, Inc; and Dr Morgan
receives research support from Hoffmann-La Roche, Inc. The remaining
authors disclose no conflicts.; Supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (contract numbers are listed
in the acknowledgments). Additional support was provided by the National
Institute of Allergy and Infectious Diseases, the National Cancer
Institute, the National Center for Minority Health and Health
Disparities, and General Clinical Research Center and Clinical and
Translational Science Center grants from the National Center for
Research Resources, National Institutes of Health (grant numbers are
listed in the acknowledgments). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Center for Research Resources or the National Institutes of
Health. Additional funding to conduct this study was supplied by
Hoffmann-La Roche, Inc, through a Cooperative Research and Development
Agreement with the National Institutes of Health.
NR 29
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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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 840
EP U230
DI 10.1053/j.gastro.2010.11.050
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700025
PM 21129375
ER
PT J
AU Chandra, M
Zhou, H
Li, Q
Muallem, S
Hofmann, SL
Soyombo, AA
AF Chandra, Manjari
Zhou, Hua
Li, Qin
Muallem, Shmuel
Hofmann, Sandra L.
Soyombo, Abigail A.
TI A Role for the Ca2+ Channel TRPML1 in Gastric Acid Secretion, Based on
Analysis of Knockout Mice
SO GASTROENTEROLOGY
LA English
DT Article
DE Apical Membrane Trafficking; Mucolipin-1; Vesicles; Stomach
ID MUCOLIPIDOSIS TYPE-IV; A-MEDIATED PHOSPHORYLATION; PARIETAL-CELLS;
CATION CHANNEL; HCL SECRETION; IDENTIFICATION; MODEL; TUBULOVESICLES;
TRANSFORMATION; ACHLORHYDRIA
AB BACKGROUND & AIMS: Mutations in TRPML1, a lysosomal Ca2+-permeable TRP channel, lead to mucolipidosis type IV, a neurodegenerative lysosomal storage disease. An unusual feature of mucolipidosis type IV is constitutive achlorhydria. We produced Trpml1(-/-) (null) mice to investigate the requirement for this protein in gastric acid secretion. METHODS: Trpml1-null mice were generated by gene targeting. The expression of Trpml1 and its role in acid secretion by gastric parietal cells were analyzed using biochemical, histologic, and ultrastructural approaches. RESULTS: Trpml1 is expressed by parietal cells and localizes predominantly to the lysosomes; it was dynamically palmitoylated and dephosphorylated in vivo following histamine stimulation of acid secretion. Trpml1-null mice had significant impairments in basal and histamine-stimulated gastric acid secretion and markedly reduced levels of the gastric proton pump. Histologic and ultrastructural analyses revealed that Trpml1(-/-) parietal cells were enlarged, had multivesicular and multi-lamellated lysosomes, and maintained an abnormal intracellular canalicular membrane. The intralysosomal Ca2+ content and receptor-mediated Ca2+ signaling were, however, unaffected in Trpml1(-/-) gastric glands, indicating that Trpml1 does not function in the regulation of lysosomal Ca2+. CONCLUSIONS: Loss of Trpml1 causes reduced levels and mislocalization of the gastric proton pump and alters the secretory canaliculi, causing hypochlorhydria and hypergastrinemia. The lysosomal enlargement and defective intracellular canaliculi formation observed in Trpml1(-/-) parietal cells indicate that Trpml1 functions in the formation and trafficking of the tubulovesicles. This study provides direct evidence for the regulation of gastric acid secretion by a TRP channel; TRPML1 is an important protein in parietal cell apical membrane trafficking.
C1 [Chandra, Manjari; Zhou, Hua; Hofmann, Sandra L.; Soyombo, Abigail A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Li, Qin; Muallem, Shmuel] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
[Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Soyombo, AA (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, 6000 Harry Hines Blvd, Dallas, TX 75390 USA.
EM abigail.soyombo@utsouthwestern.edu
FU National Institutes of Health [KO1 NS053766, R37 NS0368678]
FX Supported by National Institutes of Health grants KO1 NS053766 (to
A.A.S.) and R37 NS0368678 (to S.L.H.).
NR 39
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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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 857
EP U249
DI 10.1053/j.gastro.2010.11.040
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700027
PM 21111738
ER
PT J
AU Woo, HG
Wang, XW
Budhu, A
Kim, YH
Kwon, SM
Tang, ZY
Sun, ZT
Harris, CC
Thorgeirsson, SS
AF Woo, Hyun Goo
Wang, Xin Wei
Budhu, Anuradha
Kim, Yun Hee
Kwon, So Mee
Tang, Zhao-You
Sun, Zongtang
Harris, Curtis C.
Thorgeirsson, Snorri S.
TI Association of TP53 Mutations With Stem Cell-Like Gene Expression and
Survival of Patients With Hepatocellular Carcinoma
SO GASTROENTEROLOGY
LA English
DT Article
DE Liver Cancer; p53; Gene Expression Patterns; Cancer Stem Cells
ID P53 MUTATION; LIVER-CANCER; STEM/PROGENITOR CELLS; HEPATOCARCINOGENESIS;
CLASSIFICATION; IDENTIFICATION; SIGNATURE; PROFILES; DNA
AB BACKGROUND & AIMS: Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds. METHODS: TP53 mutations were investigated in a total of 409 HCC patients, including Chinese (n = 336) and white (n = 73) patients, using the direct sequencing method. RESULTS: A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%). HCC patients with TP53 mutations had a shorter overall survival time compared with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence interval [CI]: 1.37 2.52; P < .001). The hot spot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% CI: 1.51-2.94; P < .001) and multivariate analyses (HR, 1.79; 95% CI: 1.29-2.51; P < .001). Gene expression analysis revealed the existence of stem cell-like traits in tumors with TP53 mutations. These findings were validated in breast and lung tumor samples with TP53 mutations. CONCLUSIONS: TP53 mutations, particularly the hot spot mutations R249S and V157F, are associated with poor prognosis for patients with HCC. The acquisition of stem cell-like gene expression traits might contribute to the aggressive behavior of tumors with TP53 mutation.
C1 [Woo, Hyun Goo; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Woo, Hyun Goo; Kim, Yun Hee; Kwon, So Mee] Ajou Univ, Sch Med, Dept Physiol, Suwon 441749, South Korea.
[Wang, Xin Wei; Budhu, Anuradha; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China.
[Tang, Zhao-You] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China.
[Sun, Zongtang] Chinese Acad Med Sci, Inst Canc, Natl Lab Mol Oncol, Beijing 100037, Peoples R China.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
RI Wang, Xin/B-6162-2009
FU NIH, National Cancer Institute, Center for Cancer Research; Ajou
University School of Medicine, Suwon, Korea [3-2010027-0]
FX Supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research, and a research grant of the Ajou
University School of Medicine, Suwon, Korea (3-2010027-0, 2010).
NR 39
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U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 1063
EP U524
DI 10.1053/j.gastro.2010.11.034
PG 16
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700046
PM 21094160
ER
PT J
AU Dlugos, AM
Hamidovic, A
Hodgkinson, C
Shen, PH
Goldman, D
Palmer, AA
de Wit, H
AF Dlugos, A. M.
Hamidovic, A.
Hodgkinson, C.
Shen, P. H.
Goldman, D.
Palmer, A. A.
de Wit, H.
TI OPRM1 gene variants modulate amphetamine-induced euphoria in humans
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Amphetamine; energy; euphoria; stimulation; inter-individual
differences; mu-opioid receptor
ID MU-OPIOID RECEPTOR; HEALTHY-VOLUNTEERS; NUCLEUS-ACCUMBENS; FUNCTIONAL
POLYMORPHISM; A118G POLYMORPHISM; LOCOMOTOR-ACTIVITY; KNOCKOUT MICE;
COCAINE; ASSOCIATION; METHAMPHETAMINE
AB The mu-opioid receptor is involved in the rewarding effects of not only opioids like morphine but also psychostimulants like amphetamine. This study aimed to investigate associations between subjective response to amphetamine and genetic polymorphisms and haplotypes in the mu-opioid receptor including the exonic variant rs1799971 (Asp40Asn). One hundred and sixty-two Caucasian volunteers participated in three sessions receiving either placebo or d-amphetamine (10 and 20 mg). Associations between levels of self-reported Euphoria, Energy and Stimulation [Addiction Research Center Inventory 49-item questionnaire (ARCI-49)] after d-amphetamine ingestion and polymorphisms in OPRM1 were investigated. The intronic single nucleotide polymorphisms (SNPs) rs510769 and rs2281617 were associated with significantly higher ratings of Euphoria, Energy and Stimulation after 10 mg amphetamine. Feelings of Euphoria, Energy and Stimulation were also found to be associated with a two-SNP haplotype formed with rs1799971 and rs510769 and a three-SNP haplotype formed with rs1918760, rs2281617 and rs1998220. These results support the hypothesis that genetic variability in the mu-opioid receptor gene influences the subjective effects of amphetamine and may suggest new strategies for prevention and treatment of psychostimulant abuse.
C1 [Dlugos, A. M.; Hamidovic, A.; Palmer, A. A.; de Wit, H.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Dlugos, A. M.] Univ Munster, Dept Psychiat, Munster, Germany.
[Hodgkinson, C.; Shen, P. H.; Goldman, D.] NIAAA, Lab Neurogenet, NIH, Bethesda, MD USA.
[Palmer, A. A.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
RP de Wit, H (reprint author), Univ Chicago, Dept Psychiat & Behav Neurosci, 5841 S Maryland Ave,MC3077, Chicago, IL 60637 USA.
EM hdew@uchicago.edu
RI Palmer, Abraham/L-2158-2014; Goldman, David/F-9772-2010;
OI Palmer, Abraham/0000-0003-3634-0747; Goldman, David/0000-0002-1724-5405;
de Wit, Harriet/0000-0002-7211-8994
FU [DA021336]; [DA02812]; [MO RR00055]
FX We gratefully thank Dr Andrew Skol for his invaluable input and
technical support. We also thank Ms. Margo Meverden and Ms. Patricia
Kriegel for their skillful technical assistance. This work was supported
by DA021336, DA02812 and MO RR00055. Authors have no conflict of
interest.
NR 57
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U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD MAR
PY 2011
VL 10
IS 2
BP 199
EP 209
DI 10.1111/j.1601-183X.2010.00655.x
PG 11
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 724SB
UT WOS:000287595400008
PM 21029375
ER
PT J
AU Nyante, SJ
Black, A
Kreimer, AR
Duggan, MA
Carreon, JD
Kessel, B
Buys, SS
Ragard, LR
Johnson, KA
Dunn, BK
Lamerato, L
Commins, JM
Berg, CD
Sherman, ME
AF Nyante, Sarah J.
Black, Amanda
Kreimer, Aimee R.
Duggan, Maire A.
Carreon, J. Daniel
Kessel, Bruce
Buys, Saundra S.
Ragard, Lawrence R.
Johnson, Karen A.
Dunn, Barbara K.
Lamerato, Lois
Commins, John M.
Berg, Christine D.
Sherman, Mark E.
TI Pathologic findings following false-positive screening tests for ovarian
cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer
screening trial
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Ovary; Screening; Transvaginal ultrasound; CA-125; False-positive;
Histopathology
ID POSTMENOPAUSAL WOMEN; RELATIVE FREQUENCY; RANDOMIZED-TRIAL; VOLUME;
NEOPLASMS; AUTOPSY; BENIGN; TUMORS
AB Objective. In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 produced a large number of false-positive tests. We examined relationships between histopathologic diagnoses, false-positive test group, and participant and screening test characteristics.
Methods. The PLCO ovarian cancer screening arm included 39,105 women aged 55-74 years assigned to annual CA-125 and TVU. Histopathologic diagnoses from women with false-positive tests and subsequent surgery were reviewed in this analysis: all CA125+ (n = 121); all CA125+/TVU+ (n = 46); and a random sample of TVU+ (n = 373). Demographic and ovarian cancer risk factor data were self-reported. Pathologic diagnoses were abstracted from surgical pathology reports. We compared participant characteristics and pathologic diagnoses by category of false-positive using Pearson chi(2), Fisher's exact, or Wilcoxon-Mann-Whitney tests.
Results. Women with a false-positive TVU were younger (P<0.001), heavier (P<0.001), and reported a higher frequency of prior hysterectomy (P<0.001). Serous cystadenoma, the most common benign ovarian diagnosis, was more frequent among women with TVU+ compared to CA-125+ and CA-125+/TVU+ (P<0.001). Benign non-ovarian findings were commonly associated with all false-positives, although more frequently with CA-125+ than TVU+ or CA-125+/IVU+ groups (P = 0.019). Non-ovarian cancers were diagnosed most frequently among CA-125+ (P<0.001).
Conclusions. False-positive ovarian cancer screening tests were associated with a range of histopathologic diagnoses, some of which may be related to patient and screening test characteristics. Further research into the predictors of false-positive ovarian cancer screening tests may aid efforts to reduce false-positive results. Published by Elsevier Inc.
C1 [Nyante, Sarah J.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Duggan, Maire A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 2T9, Canada.
[Kessel, Bruce] Univ Hawaii, Honolulu, HI 96813 USA.
[Kessel, Bruce] Pacific Hlth Res Inst, Honolulu, HI 96813 USA.
[Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Ragard, Lawrence R.] WESTAT Corp, Rockville, MD 20850 USA.
[Johnson, Karen A.; Dunn, Barbara K.; Berg, Christine D.] NCI, Canc Prevent Div, NIH, Rockville, MD 20852 USA.
[Lamerato, Lois] Henry Ford Hosp, Detroit, MI 48202 USA.
[Commins, John M.] Informat Management Serv Inc, Rockville, MD 20852 USA.
RP Nyante, SJ (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Suite 550,EPS-5029,MSC 7234, Rockville, MD 20852 USA.
EM sarah.nyante@nih.gov
RI Berg , Christine/K-1047-2014; Kreimer, Aimee/H-1687-2015;
OI Kessel, Bruce/0000-0001-9979-2068
FU Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and by contracts from the
Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The
authors thank Drs. Christine Berg and Philip Prorok, Division of Cancer
Prevention, National Cancer Institute, the Screening Center
investigators and staff of the Prostate, Lung, Colorectal, and Ovarian
(PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information
Management Services, Inc., Ms. Barbara O'Brien and staff, Westat, Inc.
Most importantly, we acknowledge the study participants for their
contributions to making this study possible.
NR 26
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Z9 7
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 120
IS 3
BP 474
EP 479
DI 10.1016/j.ygyno.2010.11.015
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 724GH
UT WOS:000287563600028
PM 21144559
ER
PT J
AU Sinner, MF
Lubitz, SA
Pfeufer, A
Makino, S
Beckmann, BM
Lunetta, KL
Steinbeck, G
Perz, S
Rahman, R
Sonni, A
Greenberg, SM
Furie, KL
Wichmann, HE
Meitinger, T
Peters, A
Benjamin, EJ
Rosand, J
Ellinor, PT
Kaab, S
AF Sinner, Moritz F.
Lubitz, Steven A.
Pfeufer, Arne
Makino, Seiko
Beckmann, Britt-Maria
Lunetta, Kathryn L.
Steinbeck, Gerhard
Perz, Siegfried
Rahman, Rosanna
Sonni, Akshata
Greenberg, Steven M.
Furie, Karen L.
Wichmann, H. -Erich
Meitinger, Thomas
Peters, Annette
Benjamin, Emelia J.
Rosand, Jonathan
Ellinor, Patrick T.
Kaeaeb, Stefan
TI Lack of replication in polymorphisms reported to be associated with
atrial fibrillation
SO HEART RHYTHM
LA English
DT Article
DE Atrial fibrillation; Arrhythmia; Genetics; Single nucleotide
polymorphism; Replication; Meta-analysis
ID GENOME-WIDE ASSOCIATION; GENETIC SUSCEPTIBILITY; FAMILIAL AGGREGATION;
CHROMOSOME 4Q25; COMMON VARIANTS; CHANNEL GENES; HEART-DISEASE;
RISK-FACTORS; LONE; POPULATION
AB BACKGROUND Atrial fibrillation (AF) is the most common sustained arrhythmia and has a substantial heritable component. Numerous associations between single nucleotide polymorphisms (SNPs) and AF have been described, but few have been replicated.
OBJECTIVE We sought to systematically replicate SNPs that are reported to be associated with AF in two large study samples of European descent.
METHODS We searched PubMed for studies reporting associations between SNPs and AF published before July 1, 2007. SNPs were genotyped in two independent case-control samples from Germany and the United States. Associations between SNPs and AF were assessed using logistic regression models adjusting for age, sex, and hypertension. A meta-analysis of the results from the two studies was performed.
RESULTS We identified 21 SNPs and the angiotensin-converting enzyme insertion/deletion polymorphism that were reported to be associated with AF in the literature. Nine of these genetic variants were not represented on common genome-wide SNP arrays. We successfully genotyped 21 of these 22 variants in 2,145 cases with AF from the German Competence Network for Atrial Fibrillation and 4,073 controls from the KORA S4 study and 16 variants in 790 cases and 1,330 controls from the Massachusetts General Hospital. None of the SNPs replicated in independent populations with AF.
CONCLUSION Our results suggest that previously reported associations to AF were likely false positives and highlight the need for systematic replication of genetic associations in large, independent cohorts to accurately detect variants associated with disease.
C1 [Sinner, Moritz F.; Beckmann, Britt-Maria; Steinbeck, Gerhard; Kaeaeb, Stefan] LMU Munchen, Univ Hosp Grosshadern, Dept Med 1, D-81366 Munich, Germany.
[Sinner, Moritz F.; Lubitz, Steven A.; Makino, Seiko; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Lubitz, Steven A.; Meitinger, Thomas] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, Munich, Germany.
[Pfeufer, Arne] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Perz, Siegfried] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Neuherberg, Germany.
[Rahman, Rosanna; Sonni, Akshata; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA.
[Rahman, Rosanna; Sonni, Akshata; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Wichmann, H. -Erich] LMU Munchen, IBE, Chair Epidemiol, D-81366 Munich, Germany.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Whitaker Cardiovasc Inst,Cardiol Div, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Whitaker Cardiovasc Inst,Prevent Med Div, Boston, MA 02118 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
RP Kaab, S (reprint author), LMU Munchen, Klinikum Grosshadern, Dept Med 1, D-81366 Munich, Germany.
EM Stefan.Kaab@med.uni-muenchen.de
RI Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; Peters,
Annette/A-6117-2011; Meitinger, Thomas/O-1318-2015;
OI Lunetta, Kathryn/0000-0002-9268-810X; Benjamin,
Emelia/0000-0003-4076-2336
FU LMU [577/569]; German National Genome Research Network NGFN [01 GS 0499,
01 GS 0838]; German Federal Ministry of research [01 EZ 0874]; German
Competence Network on AF (AFNET) [01 GI 0204/N]; Leducq Foundation
[07-CVD 03]; LMU Excellence Initiative; BMBF German Federal Ministry of
research [01EZ0874]; Deane Institute for Integrative Research in Atrial
Fibrillation and Stroke; National Institutes of Health [R01NS059727,
5P50NS051343, T32HL007575, R01HL092577]; BMBF; State of Bavaria
FX MF Sinner, SA Lubitz, PT Ellinor, and S Kaab contributed equally to this
study. This study was funded by an LMU Research Grant FoFoLe 577/569 to
Dr. Sinner; the German National Genome Research Network NGFN 01 GS 0499,
01 GS 0838, German Federal Ministry of research 01 EZ 0874, German
Competence Network on AF (AFNET) 01 GI 0204/N, Leducq Foundation 07-CVD
03, and LMU Excellence Initiative to Dr. Kaab; the German National
Genome Research Network NGFN 01GR0803 and the BMBF German Federal
Ministry of research 01EZ0874 to Dr. Pfeufer; the Deane Institute for
Integrative Research in Atrial Fibrillation and Stroke to Dr. Ellinor;
and the National Institutes of Health to Dr. Rosand (R01NS059727), Dr.
Furie (5P50NS051343), Dr. Lubitz (T32HL007575), and Drs. Ellinor and
Benjamin (R01HL092577). The KORA platform is funded by the BMBF and by
the State of Bavaria.
NR 48
TC 11
Z9 11
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD MAR
PY 2011
VL 8
IS 3
BP 403
EP 409
DI 10.1016/j.hrthm.2010.11.003
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 726PA
UT WOS:000287736200018
PM 21056700
ER
PT J
AU Purdue, MP
Lan, Q
Menashe, I
Zheng, TZ
Zhang, YW
Yeager, M
Hosgood, HD
Zahm, SH
Chanock, SJ
Rothman, N
Baris, D
AF Purdue, Mark P.
Lan, Qing
Menashe, Idan
Zheng, Tongzhang
Zhang, Yawei
Yeager, Meredith
Hosgood, H. Dean, III
Zahm, Shelia H.
Chanock, Stephen J.
Rothman, Nathaniel
Baris, Dalsu
TI Variation in innate immunity genes and risk of multiple myeloma
SO HEMATOLOGICAL ONCOLOGY
LA English
DT Article
DE epidemiology; myeloma; genetics
ID HEPATOCYTE GROWTH-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; LYMPH-NODE
METASTASIS; NON-HODGKIN-LYMPHOMA; ASSOCIATION ANALYSES; DENDRITIC CELLS;
TUMOR-GROWTH; CANCER; POLYMORPHISMS; POPULATION
AB Multiple myeloma (MM) is a B-cell lymphoid malignancy suspected to be associated with immunologic factors. Given recent findings associating single-nucleotide polymorphisms (SNPs) in innate immunity genes with non-Hodgkin lymphoma, we conducted an investigation of innate immune gene variants using specimens from a population-based case-control study of MM conducted in Connecticut women. Tag SNPs (N = 1461) summarizing common variation in 149 gene regions were genotyped in non-Hispanic Caucasian subjects (103 cases, 475 controls). Odds ratios (OR) and 95% confidence intervals (CI) relating SNP associations with MM were computed using unconditional logistic regression, while the MinP test was used to investigate associations with MM at the gene level. We calculated permutation-adjusted P-values and false discovery rates (FDR) to account for the number of comparisons performed in SNP-level and gene-level tests, respectively. Three genes were associated with MM when controlling for a FDR of <= 10%: SERPINE1 (P(MinP) < 0.0001; FDR = 0.02), CCR7 (P(MinP) = 0.0006; FDR = 0.06) and HGF (P(MinP) = 0.001; FDR = 0.08). Two SNPs demonstrated robust associations: SERPINE1 rs2227667 (P = 2.1 x 10(-5), P(permutation) = 0.03) and HGF rs17501108 (P = 5.0 x 10(-5), P(permutation) = 0.07). Our findings suggest that genetic variants in SERPINE1 and HGF, and possibly CCR7, are associated with MM risk, and warrant further investigation in other studies. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Purdue, Mark P.; Lan, Qing; Menashe, Idan; Yeager, Meredith; Hosgood, H. Dean, III; Zahm, Shelia H.; Chanock, Stephen J.; Rothman, Nathaniel; Baris, Dalsu] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Zheng, Tongzhang; Zhang, Yawei] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8114,6120 Execut Blvd, Rockville, MD 20892 USA.
EM purduem@mail.nih.gov
RI Zahm, Shelia/B-5025-2015; Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU National Cancer Institute, National Institutes of Health [N01-CO-12400]
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 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 US Government.
NR 47
TC 12
Z9 13
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0278-0232
J9 HEMATOL ONCOL
JI Hematol. Oncol.
PD MAR
PY 2011
VL 29
IS 1
BP 42
EP 46
DI 10.1002/hon.954
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 732HA
UT WOS:000288174400008
PM 20658475
ER
PT J
AU Meuleman, P
Bukh, J
Verhoye, L
Farhoudi, A
Vanwolleghem, T
Wang, RY
Desombere, I
Alter, H
Purcell, RH
Leroux-Roels, G
AF Meuleman, Philip
Bukh, Jens
Verhoye, Lieven
Farhoudi, Ali
Vanwolleghem, Thomas
Wang, Richard Y.
Desombere, Isabelle
Alter, Harvey
Purcell, Robert H.
Leroux-Roels, Geert
TI In Vivo Evaluation of the Cross-Genotype Neutralizing Activity of
Polyclonal Antibodies Against Hepatitis C Virus
SO HEPATOLOGY
LA English
DT Article
ID CELL-CULTURE SYSTEMS; HUMAN LIVER; ENVELOPE PROTEIN; INFECTION;
REPLICATION; MOUSE; VITRO; MICE; PSEUDOPARTICLES; CHIMPANZEES
AB Control of hepatitis C virus (HCV) infection remains a huge challenge of global medical importance. Using a variety of in vitro approaches, neutralizing antibodies (nAbs) have been identified in patients with acute and chronic hepatitis C. The exact role these nAbs play in the resolution of acute HCV infection still remains elusive. We have previously shown that purified polyclonal antibodies isolated from plasma obtained in 2003 from a chronic HCV patient (Patient H) can protect human liver chimeric mice from a subsequent challenge with the autologous HCV strain isolated from Patient H in 1977 (H77). In this study we investigated whether polyclonal antibodies isolated from Patient H in 2006 (H06), which display high cross-genotype neutralizing activity in both the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems, were also able to prevent HCV infection of different genotypes (gt) in vivo. Following passive immunization with H06-antibodies, chimeric mice were challenged with the consensus strains H77C (gt1a), ED43 (gt4a), or HK6a (gt6a). In accordance with previous results, H06-antibodies prevented infection of chimeric mice with the autologous virus. However, the outcome of a homologous challenge is highly influenced by the amount of challenge virus injected. Depending on the viral genotype used, H06-antibodies were able to protect up to 50% of chimeric mice from a heterologous challenge. Animals in which the antibody pretreatment failed displayed a clear delay in the kinetics of viral infection. Sequence analysis of the recovered viruses did not suggest antibody-induced viral escape. Conclusion: Polyclonal anti-HCV antibodies isolated from a chronic HCV patient can protect against an in vivo challenge with different HCV genotypes. However, the in vivo protective efficacy of cross-genotype neutralizing antibodies was less than predicted by cell culture experiments. (HEPATOLOGY 2011;53:755-762)
C1 [Meuleman, Philip; Verhoye, Lieven; Farhoudi, Ali; Vanwolleghem, Thomas; Desombere, Isabelle; Leroux-Roels, Geert] Ghent Univ & Hosp, Ctr Vaccinol, B-9000 Ghent, Belgium.
[Bukh, Jens; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis Program CO HEP C, Dept Infect Dis, Hvidovre, Denmark.
[Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark.
[Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, DK-1168 Copenhagen, Denmark.
[Wang, Richard Y.; Alter, Harvey] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Meuleman, P (reprint author), Ghent Univ & Hosp, Ctr Vaccinol, Bldg A,1st Floor,Pintelaan 185, B-9000 Ghent, Belgium.
EM Philip.Meuleman@ugent.be
RI Meuleman, Philip/H-2899-2013
OI Meuleman, Philip/0000-0001-6821-234X
FU Ghent University [01G00507]; European Union; Belgian State via the
Interuniversity Attraction Poles Program [P6/36]; Research Foundation -
Flanders [31500910]; NIAID, NIH; Lundbeck Foundation; Research
Foundation - Flanders, Flanders (FWO-Vlaanderen)
FX Supported by the Ghent University by a Concerted Action Grant
(01G00507), by the European Union (6th framework, HEPACIVAC), by the
Belgian State via the Interuniversity Attraction Poles Program (P6/36,
HEPRO), by The Research Foundation - Flanders (project 31500910), and by
the Intramural Research Program of the NIAID, NIH. JB is the recipient
of a professorship at the University of Copenhagen with external funding
from the Lundbeck Foundation. PM was supported by a postdoctoral
fellowship and TV by a Ph.D. grant from The Research Foundation -
Flanders, Flanders (FWO-Vlaanderen).
NR 32
TC 64
Z9 64
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAR
PY 2011
VL 53
IS 3
BP 755
EP 762
DI 10.1002/hep.24171
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 732SY
UT WOS:000288211200006
PM 21319203
ER
PT J
AU Brunt, EM
Kleiner, DE
Wilson, LA
Belt, P
Neuschwander-Tetri, BA
AF Brunt, Elizabeth M.
Kleiner, David E.
Wilson, Laura A.
Belt, Patricia
Neuschwander-Tetri, Brent A.
CA NASH Clinical Res Network
TI Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score and the
Histopathologic Diagnosis in NAFLD: Distinct Clinicopathologic Meanings
SO HEPATOLOGY
LA English
DT Article
ID IN-VIVO; STEATOHEPATITIS; INDEX
AB The diagnosis of nonalcoholic steatohepatitis (NASH) is defined by the presence and pattern of specific histological abnormalities on liver biopsy. A separate system of scoring the features of nonalcoholic fatty liver disease (NAFLD) called the NAFLD Activity Score (NAS) was developed as a tool to measure changes in NAFLD during therapeutic trials. However, some studies have used threshold values of the NAS, specifically NAS >= 5, as a surrogate for the histologic diagnosis of NASH. To evaluate whether this unintended use of the NAS is valid, biopsy and clinical data from the 976 adults in NASH Clinical Research Network (CRN) studies were reviewed. Biopsies were evaluated centrally by the NASH CRN Pathology Committee. Definite steatohepatitis (SH) was diagnosed in 58.1%, borderline SH in 19.5% and "not SH" in 22%. The NAS was >= 5 in 50% and <= 4 in 49%; in this cohort only 75% of biopsies with definite SH had an NAS >= 5, whereas 28% of borderline SH and 7% of "not SH" biopsies had NAS >= 5. Of biopsies with an NAS >= 5, 86% had SH and 3% "not SH". NAS <= 4 did not indicate benign histology; 29% had SH and only 42% had "not SH." Higher values of the NAS were associated with higher levels of alanine aminotransferase and aspartate aminotransferase, whereas the diagnosis of SH was associated with features of the metabolic syndrome. Conclusion: The diagnosis of definite SH or the absence of SH based on evaluation of patterns as well as individual lesions on liver biopsies does not always correlate with threshold values of the semiquantitative NAS. Clinical trials and observational studies should take these different performance characteristics into account. (HEPATOLOGY 2011;53:810-820)
C1 [Brunt, Elizabeth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Kleiner, David E.] NCI, Dept Lab Med, Washington, DC USA.
[Wilson, Laura A.; Belt, Patricia] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Neuschwander-Tetri, Brent A.] St Louis Univ, Dept Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA.
RP Brunt, EM (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA.
EM ebrunt@wustl.edu
RI Vaughn, Ivana/B-6138-2016;
OI Vaughn, Ivana/0000-0002-7201-0289; Kleiner, David/0000-0003-3442-4453
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734,
U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Institute
of Child Health and Human Development (NICHD); General Clinical Research
Centers [UL1RR024989, M01RR000750, M01RR00188, UL1RR02413101,
M01RR000827, UL1RR02501401, M01RR000065, M01RR020359, UL1RR025741]
FX The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731,
U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730,
U01DK061713), and the National Institute of Child Health and Human
Development (NICHD). Several clinical centers use support from General
Clinical Research Centers or Clinical and Translational Science Awards
in conduct of NASH CRN Studies (grants UL1RR024989, M01RR000750,
M01RR00188, UL1RR02413101, M01RR000827, UL1RR02501401, M01RR000065,
M01RR020359, UL1RR025741).
NR 9
TC 244
Z9 253
U1 4
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAR
PY 2011
VL 53
IS 3
BP 810
EP 820
DI 10.1002/hep.24127
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 732SY
UT WOS:000288211200012
PM 21319198
ER
PT J
AU Chakarova, CF
Khanna, H
Shah, AZ
Patil, SB
Sedmak, T
Murga-Zamalloa, CA
Papaioannou, MG
Nagel-Wolfrum, K
Lopez, I
Munro, P
Cheetham, M
Koenekoop, RK
Rios, RM
Matter, K
Wolfrum, U
Swaroop, A
Bhattacharya, SS
AF Chakarova, Christina F.
Khanna, Hemant
Shah, Amna Z.
Patil, Suresh B.
Sedmak, Tina
Murga-Zamalloa, Carlos A.
Papaioannou, Myrto G.
Nagel-Wolfrum, Kerstin
Lopez, Irma
Munro, Peter
Cheetham, Michael
Koenekoop, Robert K.
Rios, Rosa M.
Matter, Karl
Wolfrum, Uwe
Swaroop, Anand
Bhattacharya, Shomi S.
TI TOPORS, implicated in retinal degeneration, is a cilia-centrosomal
protein
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DOMINANT RETINITIS-PIGMENTOSA; INTRAFLAGELLAR TRANSPORT; PHOTORECEPTOR
CELLS; TOPOISOMERASE-I; SUBCELLULAR-LOCALIZATION; CONNECTING CILIUM;
NUCLEAR-BODIES; USHER-SYNDROME; COMPLEX; MUTATIONS
AB We recently reported that mutations in the widely expressed nuclear protein TOPORS (topoisomerase I-binding arginine/serine rich) are associated with autosomal dominant retinal degeneration. However, the precise localization and a functional role of TOPORS in the retina remain unknown. Here, we demonstrate that TOPORS is a novel component of the photoreceptor sensory cilium, which is a modified primary cilium involved with polarized trafficking of proteins. In photoreceptors, TOPORS localizes primarily to the basal bodies of connecting cilium and in the centrosomes of cultured cells. Morpholino-mediated silencing of topors in zebrafish embryos demonstrates in another species a comparable retinal problem as seen in humans, resulting in defective retinal development and failure to form outer segments. These defects can be rescued by mRNA encoding human TOPORS. Taken together, our data suggest that TOPORS may play a key role in regulating primary cilia-dependent photoreceptor development and function. Additionally, it is well known that mutations in other ciliary proteins cause retinal degeneration, which may explain why mutations in TOPORS result in the same phenotype.
C1 [Chakarova, Christina F.; Shah, Amna Z.; Papaioannou, Myrto G.; Munro, Peter; Cheetham, Michael; Matter, Karl; Bhattacharya, Shomi S.] UCL, Inst Ophthalmol, London EC1V 9EL, England.
[Khanna, Hemant; Patil, Suresh B.; Murga-Zamalloa, Carlos A.; Swaroop, Anand] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA 01605 USA.
[Sedmak, Tina; Nagel-Wolfrum, Kerstin; Wolfrum, Uwe] Johannes Gutenberg Univ Mainz, Inst Zool, D-55099 Mainz, Germany.
[Lopez, Irma; Koenekoop, Robert K.] McGill Univ, Ctr Hlth, McGill Ocular Genet Lab, Montreal, PQ H3H 1P3, Canada.
[Rios, Rosa M.; Bhattacharya, Shomi S.] CABIMER, Seville 41902, Spain.
[Swaroop, Anand] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Bhattacharya, SS (reprint author), UCL, Inst Ophthalmol, London EC1V 9EL, England.
EM smbcssb@ucl.ac.uk
RI Cheetham, Michael/B-4672-2011; Shah, Amna/C-4471-2013; Chakarova,
Christina/C-9479-2013; Matter, Karl/C-4880-2008; rios, rosa
m/G-5742-2015;
OI Matter, Karl/0000-0001-8026-7220; rios, rosa m/0000-0001-5778-6946;
Swaroop, Anand/0000-0002-1975-1141; Cheetham,
Michael/0000-0001-6429-654X
FU Foundation Fighting Blindness, EVI-GENORET [LSHG-CT-2005-512036]; The
Special Trustees of Moorfields Eye Hospital London; National Institute
of Health Research (UK); Biomedical Research Centre for Ophthalmology,
Fight for Sight (UK); Midwest Eye Banks and Transplantation Center,
National Institutes of Health [EY007961]; Foundation Fighting Blindness,
Biotechnology and Biological Sciences Research Council; Foundation
Fighting Blindness-Canada; Fonds de la Recherche en Santee du Quebec;
Deutsche Forschungsgemeinschaft (DFG); FAUN-Stiftung, Nuermberg; EU;
Gradiertenforderung of the Johannes Gutenberg University of Mainz,
Germany
FX This work was supported by grants from the Foundation Fighting
Blindness, EVI-GENORET (LSHG-CT-2005-512036), The Special Trustees of
Moorfields Eye Hospital London, National Institute of Health Research
(UK) Biomedical Research Centre for Ophthalmology, Fight for Sight (UK),
Midwest Eye Banks and Transplantation Center, National Institutes of
Health (EY007961), Foundation Fighting Blindness, Biotechnology and
Biological Sciences Research Council, Research to Prevent Blindness,
Foundation Fighting Blindness-Canada and Fonds de la Recherche en Santee
du Quebec, the Deutsche Forschungsgemeinschaft (DFG), the FAUN-Stiftung,
Nuermberg, EU FP7 'SYSCILIA' and a scholarship of the
Gradiertenforderung of the Johannes Gutenberg University of Mainz,
Germany.
NR 50
TC 20
Z9 20
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 1
PY 2011
VL 20
IS 5
BP 975
EP 987
DI 10.1093/hmg/ddq543
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 716SJ
UT WOS:000286993500011
PM 21159800
ER
PT J
AU Oexle, K
Ried, JS
Hicks, AA
Tanaka, T
Hayward, C
Bruegel, M
Gogele, M
Lichtner, P
Muller-Myhsok, B
Doring, A
Illig, T
Schwienbacher, C
Minelli, C
Pichler, I
Fiedler, GM
Thiery, J
Rudan, I
Wright, AF
Campbell, H
Ferrucci, L
Bandinelli, S
Pramstaller, PP
Wichmann, HE
Gieger, C
Winkelmann, J
Meitinger, T
AF Oexle, Konrad
Ried, Janina S.
Hicks, Andrew A.
Tanaka, Toshiko
Hayward, Caroline
Bruegel, Mathias
Goegele, Martin
Lichtner, Peter
Mueller-Myhsok, Bertram
Doering, Angela
Illig, Thomas
Schwienbacher, Christine
Minelli, Cosetta
Pichler, Irene
Fiedler, G. Martin
Thiery, Joachim
Rudan, Igor
Wright, Alan F.
Campbell, Harry
Ferrucci, Luigi
Bandinelli, Stefania
Pramstaller, Peter P.
Wichmann, H. -Erich
Gieger, Christian
Winkelmann, Juliane
Meitinger, Thomas
TI Novel association to the proprotein convertase PCSK7 gene locus revealed
by analysing soluble transferrin receptor (sTfR) levels
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; IRON HOMEOSTASIS; COMMON VARIANTS; TMPRSS6;
HEMOJUVELIN; HEMOCHROMATOSIS; METABOLISM; CONSORTIUM; MUTATIONS;
OVERLOAD
AB The level of body iron storage and the erythropoietic need for iron are indicated by the serum levels of ferritin and soluble transferrin receptor (sTfR), respectively. A meta-analysis of five genome-wide association studies on sTfR and ferritin revealed novel association to the PCSK7 and TMPRSS6 loci for sTfR and the HFE locus for both parameters. The PCSK7 association was the most significant (rs236918, P = 1.1 x 10E-27) suggesting that proprotein convertase 7, the gene product of PCSK7, may be involved in sTfR generation and/or iron homeostasis. Conditioning the sTfR analyses on transferrin saturation abolished the HFE signal and substantially diminished the TMPRSS6 signal while the PCSK7 association was unaffected, suggesting that the former may be mediated by transferrin saturation whereas the PCSK7-associated effect on sTfR generation appears to be more direct.
C1 [Oexle, Konrad; Winkelmann, Juliane; Meitinger, Thomas] Tech Univ Munich, MRI, Inst Human Genet, Munich, Germany.
[Winkelmann, Juliane] Tech Univ Munich, MRI, Dept Neurol, Munich, Germany.
[Ried, Janina S.; Doering, Angela; Illig, Thomas; Wichmann, H. -Erich; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Hicks, Andrew A.; Goegele, Martin; Schwienbacher, Christine; Minelli, Cosetta; Pichler, Irene; Pramstaller, Peter P.] Univ Lubeck, Inst Med Genet, European Acad Bozen Bolzano EURAC, Lubeck, Germany.
[Tanaka, Toshiko; Ferrucci, Luigi] Harbor Hosp, NIA, Baltimore, MD USA.
[Hayward, Caroline; Wright, Alan F.] Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Bruegel, Mathias; Fiedler, G. Martin; Thiery, Joachim] Univ Klinikum Leipzig, Inst Lab Med, Leipzig, Germany.
[Lichtner, Peter; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Schwienbacher, Christine] Univ Ferrara, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy.
[Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
[Rudan, Igor; Campbell, Harry] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-80804 Munich, Germany.
RP Oexle, K (reprint author), Klinikum Rechts Der Isar, Inst Humangenet, Trogerstr 32, D-81675 Munich, Germany.
EM oexle@humangenetik.med.tum.de
RI Rudan, Igor/I-1467-2012; Muller-Myhsok, Bertram/A-3289-2013;
Pramstaller, Peter/C-2357-2008; Meitinger, Thomas/O-1318-2015; Hayward,
Caroline/M-8818-2016; Hicks, Andrew/E-9518-2017;
OI Rudan, Igor/0000-0001-6993-6884; Hayward, Caroline/0000-0002-9405-9550;
Hicks, Andrew/0000-0001-6320-0411; Pichler, Irene/0000-0001-8251-0757;
Winkelmann, Juliane/0000-0003-2667-9691; Gieger,
Christian/0000-0001-6986-9554; Fiedler, Georg Martin/0000-0001-5689-4574
FU German Research Counsil (DFG) [WI 1820/4-1]; German Federal Ministry of
Education and Research (BMBF); State of Bavaria; German National Genome
Research Network [NGFN-2, NGFNPlus: 01GS0823]; Munich Center of Health
Sciences (MC Health) as part of LMUinnovativ; Ministry of Health and
Department of Educational Assistance; University and Research of the
Autonomous Province of Bolzano; South Tyrolean Sparkasse Foundation;
Italian Ministry of Health [ICS110.1/RF97.71]; US National Institute on
Aging [263 MD 9164, 263 MD 821336]; Medical Research Council; Croatian
Ministry of Science, Education and Sport [216-1080315-0302]
FX J.W., K.O. and T.M. were supported by a grant (#WI 1820/4-1) from the
German Research Counsil (DFG). The KORA research platform was initiated
and financed by the Helmholtz Center Munich, German Research Center for
Environmental Health, which is funded by the German Federal Ministry of
Education and Research (BMBF) and by the State of Bavaria. Part of the
financing was provided by the German National Genome Research Network
(NGFN-2 and NGFNPlus: 01GS0823). KORA research was also supported within
the Munich Center of Health Sciences (MC Health) as part of
LMUinnovativ. The MICROS study was supported by the Ministry of Health
and Department of Educational Assistance, University and Research of the
Autonomous Province of Bolzano and the South Tyrolean Sparkasse
Foundation. The InCHIANTI study baseline (1998-2000) was supported as a
'targeted project' (ICS110.1/RF97.71) by the Italian Ministry of Health
and in part by the US National Institute on Aging (Contracts: 263 MD
9164 and 263 MD 821336). The CROATIA-VIS study was supported by the
Medical Research Council and a grant, #216-1080315-0302 (to I.R.) from
the Croatian Ministry of Science, Education and Sport.
NR 29
TC 34
Z9 34
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 1
PY 2011
VL 20
IS 5
BP 1042
EP 1047
DI 10.1093/hmg/ddq538
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 716SJ
UT WOS:000286993500018
PM 21149283
ER
PT J
AU Ma, CA
Wang, HY
Temmerman, S
Zhao, YG
Wu, LM
Hornung, RL
Wara, D
Jain, A
AF Ma, Chi A.
Wang, Hong-Ying
Temmerman, Stephane
Zhao, Yongge
Wu, Liming
Hornung, Ronald L.
Wara, Diane
Jain, Ashish
TI Dendritic Cells from Humans with Hypomorphic Mutations in IKBKG/NEMO
Have Impaired Mitogen-Activated Protein Kinase Activity
SO HUMAN MUTATION
LA English
DT Article
DE IKBKG; NEMO; IKK gamma; MAPK; toll-like receptor; ubiquitination
ID NF-KAPPA-B; ANHIDROTIC ECTODERMAL DYSPLASIA; ESSENTIAL MODULATOR
MUTATION; UBIQUITIN-DEPENDENT KINASE; IKK-GAMMA NEMO; IMMUNE-DEFICIENCY;
ZINC-FINGER; PATHWAY; TAK1; IMMUNODEFICIENCY
AB The covalent attachment of lysine 63-linked polyubiquitin to the zinc-finger domain of IKBKG/NEMO (also known as IKK gamma) is necessary for full activation of NF-kappa B. Impairments of this biochemical mechanism explain the deleterious effects of hypomorphic NEMO mutations on NF-kappa B signaling function in humans suffering from X-linked ectodermal dysplasia and immunodeficiency. Nevertheless, the biological function of the NEMO zinc-finger domain in the regulation of mitogen-activated protein kinase (MAPK) activity is poorly understood. Here we show that dendritic cells from patients with EDI caused by a C-terminal E391X deletion of the zinc finger of NEMO exhibit impaired MAPK activation in response to lipopolysaccharide (LPS) stimulation. Interestingly, DCs from patients with a C417R missense mutation within the zinc finger domain of NEMO in which ubiquitination of NEMO is preserved are also defective in JNK and ERK activity following LPS stimulation. Our findings indicate that the structural integrity of the NEMO ZF domain is more important than its polyubiquitination for full activation of the MAPK. Furthermore, phosphorylation and polyubiquitination of upstream TAK1 were significantly reduced in the E391X zinc-finger deleted patients, indicating that the NEMO zinc finger may play an important role in assembling the proximal signaling complex for MAPK activation. Hum Mutat 32:318-324, 2011. Published 2011 Wiley-Liss, Inc.
C1 [Ma, Chi A.; Wang, Hong-Ying; Temmerman, Stephane; Zhao, Yongge; Wu, Liming; Jain, Ashish] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Hornung, Ronald L.] SAIC Frederick Inc, Clin Serv Program, NCI Frederick, Frederick, MD USA.
[Wara, Diane] Univ Calif San Francisco, Pediat Specialties Clin, San Francisco, CA 94143 USA.
RP Jain, A (reprint author), NIAID, Host Def Lab, NIH, CRC 5-3940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ajain@niaid.nih.gov
RI Wu, Liming/C-4004-2011
FU NIH Clinical Center and the National Institute of Allergy and Infectious
Disease; National Cancer Institute, National Institutes of Health
[N01-CO-12400]; NIAID/NIH
FX Contract grant sponsors: The Intramural NIH Research Programs of the NIH
Clinical Center and the National Institute of Allergy and Infectious
Disease; The National Cancer Institute, National Institutes of Health;
Contract grant number: N01-CO-12400.; We thank Warren Strober for
helpful discussions, and Mary Derry for editorial assistance. 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 and supported by the intramural program of NIAID/NIH. 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 33
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD MAR
PY 2011
VL 32
IS 3
BP 318
EP 324
DI 10.1002/humu.21439
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 730LF
UT WOS:000288034100009
PM 21309033
ER
PT J
AU Hamburg, NM
Palmisano, J
Larson, MG
Sullivan, LM
Lehman, BT
Vasan, RS
Levy, D
Mitchell, GF
Vita, JA
Benjamin, EJ
AF Hamburg, Naomi M.
Palmisano, Joseph
Larson, Martin G.
Sullivan, Lisa M.
Lehman, Birgitta T.
Vasan, Ramachandran S.
Levy, Daniel
Mitchell, Gary F.
Vita, Joseph A.
Benjamin, Emelia J.
TI Relation of Brachial and Digital Measures of Vascular Function in the
Community The Framingham Heart Study
SO HYPERTENSION
LA English
DT Article
DE cohort study; endothelium; epidemiology; risk factors; vascular function
ID FLOW-MEDIATED DILATION; ENDOTHELIUM-DEPENDENT VASODILATION; INCIDENT
CARDIOVASCULAR EVENTS; CROSS-SECTIONAL RELATIONS; NITRIC-OXIDE;
RISK-FACTORS; AORTIC STIFFNESS; PREDICTIVE-VALUE; AMPLITUDE; DISEASE
AB Impaired vascular function contributes to the development of clinical cardiovascular disease. The relation between vasodilator function assessed noninvasively in the brachial and digital arteries remains incompletely defined. In the Framingham Offspring, Third Generation and Omni Cohorts, we measured flow-mediated dilation (FMD; n=7031; age 48 +/- 13 years; age range, 19 to 88 years; 54% women) and peripheral arterial tonometry (PAT) ratio (n=4352; 55 +/- 16 years; age range, 19 to 90 years; 51% women). Abnormal vascular function for each measure was defined by the sex-specific fifth percentile in a reference group free of conventional cardiovascular risk factors. The prevalence of abnormal FMD but not abnormal PAT ratio was higher with advancing age. In multivariable models, higher body mass index was associated with a higher prevalence of both abnormal FMD and PAT ratio. Additional correlates of abnormal FMD included increasing age and higher systolic blood pressure. In contrast, correlates of abnormal PAT ratio included lower systolic blood pressure, increasing total/high-density lipoprotein cholesterol ratio, diabetes, smoking, and lipid-lowering medication. Whereas women had higher FMD and PAT ratios compared with men, using sex-specific reference values, women had a higher prevalence of abnormal brachial and digital vascular function. In participants who had concurrent testing (n=1843), PAT ratio was not significantly associated with FMD in multivariable models. In this large, community-based cohort, brachial and digital measures of vascular function had differing relations with cardiovascular risk factors and were nearly uncorrelated with each other. These results suggest that FMD and PAT provide distinct information regarding vascular function in conduit versus smaller digital vessels. (Hypertension. 2011;57:390-396.). Online Data Supplement
C1 [Hamburg, Naomi M.; Vasan, Ramachandran S.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Cardiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Prevent Med Sect, Boston, MA 02118 USA.
[Hamburg, Naomi M.; Vasan, Ramachandran S.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Palmisano, Joseph; Sullivan, Lisa M.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Stat, Boston, MA 02118 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc, Holliston, MA USA.
[Larson, Martin G.; Lehman, Birgitta T.; Vasan, Ramachandran S.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Larson, Martin G.; Lehman, Birgitta T.; Vasan, Ramachandran S.; Levy, Daniel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
RP Hamburg, NM (reprint author), Boston Univ, Cardiol Sect, 88 E Newton St,C818, Boston, MA 02118 USA.
EM naomi.hamburg@bmc.org
OI Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797;
Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin,
Emelia/0000-0003-4076-2336
FU National Institutes of Health (NIH)/National Heart, Lung and Blood
Institute (NHLBI) [N01-HC25195]; NIH [HL70100, HL076784, AG028321,
HL080124, 2K24-HL4334, HL083781, HL102299]; Donald W. Reynolds
Foundation; Itamar Medical
FX The Framingham Heart Study is funded by National Institutes of Health
(NIH)/National Heart, Lung and Blood Institute (NHLBI) contract
N01-HC25195. The project was supported NIH grants HL70100, HL076784,
AG028321, HL080124, 2K24-HL4334, and the Donald W. Reynolds Foundation.
N.M.H. is supported by NIH grants HL083781 and HL102299. The work was
supported by an unrestricted research grant to E.J.B. from Itamar
Medical. The grant was used to conduct statistical analyses following
guidelines established by the NHLBI:
www.nhlbi.nih.gov/funding/policies/thirdparty.htm.
NR 29
TC 143
Z9 148
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAR
PY 2011
VL 57
IS 3
BP 390
EP U81
DI 10.1161/HYPERTENSIONAHA.110.160812
PG 11
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 722AX
UT WOS:000287402700014
PM 21263120
ER
PT J
AU Miles, JJ
Douek, DC
Price, DA
AF Miles, John J.
Douek, Daniel C.
Price, David A.
TI Bias in the alpha beta T-cell repertoire: implications for disease
pathogenesis and vaccination
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Review
DE T cells; T-cell receptor; TCR repertoire
ID COMPLEX CLASS-I; MYELIN BASIC-PROTEIN; EPSTEIN-BARR-VIRUS; HUMAN
CYTOMEGALOVIRUS EPITOPE; ANTIGEN RECEPTOR GENES; TCR-ALPHA;
MULTIPLE-SCLEROSIS; IMMUNE-RESPONSE; SELF-ANTIGEN; INFLUENZA-A
AB The naive T-cell repertoire is vast, containing millions of unique T-cell receptor (TCR) structures. Faced with such diversity, the mobilization of TCR structures from this enormous pool was once thought to be a stochastic, even chaotic, process. However, steady and systematic dissection over the last 20 years has revealed that this is not the case. Instead, the TCR repertoire deployed against individual antigens is routinely ordered and biased. Often, identical and near-identical TCR repertoires can be observed across different individuals, suggesting that the system encompasses an element of predictability. This review provides a catalog of alpha beta TCR bias by disease and by species, and discusses the mechanisms that govern this inherent and widespread phenomenon. Immunology and Cell Biology (2011) 89, 375-387; doi:10.1038/icb.2010.139; published online 8 February 2011
C1 [Miles, John J.; Price, David A.] Cardiff Univ, T Cell Modulat Lab, Dept Infect Immun & Biochem, Sch Med, Cardiff CF14 4XN, Wales.
[Miles, John J.] Queensland Inst Med Res, Cellular Immunol Lab, Dept Infect Dis & Immunol, Herston, Qld 4006, Australia.
[Douek, Daniel C.; Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Miles, JJ (reprint author), Cardiff Univ, T Cell Modulat Lab, Dept Infect Immun & Biochem, Sch Med, Heath Pk, Cardiff CF14 4XN, Wales.
EM milesjj@cardiff.ac.uk
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Medical Research Council [G0501963]
NR 153
TC 84
Z9 85
U1 4
U2 15
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 MAR
PY 2011
VL 89
IS 3
BP 375
EP 387
DI 10.1038/icb.2010.139
PG 13
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 737AU
UT WOS:000288539800009
PM 21301479
ER
PT J
AU Grade, M
Hummon, AB
Camps, J
Emons, G
Spitzner, M
Gaedcke, J
Hoermann, P
Ebner, R
Becker, H
Difilippantonio, MJ
Ghadimi, BM
Beissbarth, T
Caplen, NJ
Ried, T
AF Grade, Marian
Hummon, Amanda B.
Camps, Jordi
Emons, Georg
Spitzner, Melanie
Gaedcke, Jochen
Hoermann, Patrick
Ebner, Reinhard
Becker, Heinz
Difilippantonio, Michael J.
Ghadimi, B. Michael
Beissbarth, Tim
Caplen, Natasha J.
Ried, Thomas
TI A genomic strategy for the functional validation of colorectal cancer
genes identifies potential therapeutic targets
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE colorectal cancer; RNAi; functional genomics; systems biology;
therapeutic targets
ID IN-VITRO; TRANSCRIPTIONAL DEREGULATION; PROTEOMIC ANALYSIS;
BREAST-CANCER; HMGA PROTEINS; EXPRESSION; SIRNA; CARCINOMAS; PATHWAY;
TROP-2
AB Genes that are highly overexpressed in tumor cells can be required for tumor cell survival and have the potential to be selective therapeutic targets. In an attempt to identify such targets, we combined a functional genomics and a systems biology approach to assess the consequences of RNAi-mediated silencing of overexpressed genes that were selected from 140 gene expression profiles from colorectal cancers (CRCs) and matched normal mucosa. In order to identify credible models for in-depth functional analysis, we first confirmed the overexpression of these genes in 25 different CRC cell lines. We then identified five candidate genes that profoundly reduced the viability of CRC cell lines when silenced with either siRNAs or short-hairpin RNAs (shRNAs), i.e., HMGA1, TACSTD2, RRM2, RPS2 and NOL5A. These genes were further studied by systematic analysis of comprehensive gene expression profiles generated following siRNA-mediated silencing. Exploration of these RNAi-specific gene expression signatures allowed the identification of the functional space in which the five genes operate and showed enrichment for cancer-specific signaling pathways, some known to be involved in CRC. By comparing the expression of the RNAi signature genes with their respective expression levels in an independent set of primary rectal carcinomas, we could recapitulate these defined RNAi signatures, therefore, establishing the biological relevance of our observations. This strategy identified the signaling pathways that are affected by the prominent oncogenes HMGAI and TACSTD2, established a yet unknown link between RRM2 and PLK1 and identified RPS2 and NOL5A as promising potential therapeutic targets in CRC.
C1 [Grade, Marian; Hummon, Amanda B.; Camps, Jordi; Hoermann, Patrick; Ebner, Reinhard; Difilippantonio, Michael J.; Ried, Thomas] NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Grade, Marian; Emons, Georg; Spitzner, Melanie; Gaedcke, Jochen; Becker, Heinz; Ghadimi, B. Michael; Beissbarth, Tim] Univ Gottingen, Univ Med Gottingen, Dept Gen & Visceral Surg, Gottingen, Germany.
[Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Ried, T (reprint author), NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, 50 S Dr,Bldg 50,Room 1408, Bethesda, MD 20892 USA.
EM riedt@mail.nih.gov
RI Beissbarth, Tim/B-3129-2013; Caplen, Natasha/H-2768-2016
OI Beissbarth, Tim/0000-0001-6509-2143; Caplen, Natasha/0000-0002-0001-9460
FU National Institutes of Health; Deutsche Forschungsgemeinschaft [KFO
179]; Deutsche Krebshilfe; National Cancer Institute
FX Grant sponsors: Intramural research program of the National Institutes
of Health, National Cancer Institute, Deutsche Forschungsgemeinschaft;
Grant number: KFO 179; Grant sponsor: Deutsche Krebshilfe (M.G.)
NR 47
TC 12
Z9 12
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2011
VL 128
IS 5
BP 1069
EP 1079
DI 10.1002/ijc.25453
PG 11
WC Oncology
SC Oncology
GA 716HS
UT WOS:000286960300007
PM 20473941
ER
PT J
AU Chen, HC
You, SL
Hsieh, CY
Schiffman, M
Lin, CY
Pan, MH
Chou, YC
Liaw, KL
Hsing, AW
Chen, CJ
AF Chen, Hui-Chi
You, San-Lin
Hsieh, Chang-Yao
Schiffman, Mark
Lin, Ching-Yu
Pan, Mei-Hung
Chou, Yi-Chun
Liaw, Kai-Li
Hsing, Ann W.
Chen, Chien-Jen
CA CBCSP-HPV Study Grp
TI Prevalence of genotype-specific human papillomavirus infection and
cervical neoplasia in Taiwan: a community-based survey of 10,602 women
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human papillomavirus; cervical neoplasia; genotype; impact; cohort
ID RANDOMIZED CONTROLLED-TRIAL; CYTOLOGICALLY NORMAL WOMEN; CANCER
SCREENING-PROGRAM; NONVACCINE HPV TYPES; AGED 16-26 YEARS; PARTICLE
VACCINE; YOUNG-WOMEN; NATURAL-HISTORY; CHINESE WOMEN; DOUBLE-BLIND
AB Human papillomavirus (HPV) causes cervical neoplasia; but limited data are available from Asia. We conducted a large-scale community-based cohort study in Taiwan to estimate prevalence of genotype-specific HPV infection and cervical neoplasia. Following written informed consent, cervical cells for cytology and HPV testing were collected from 11,923 participants (aged 30-65 years old, mean 46.3) in 1991-1992. Genotyping was performed using MY11/GP6+ PCR-based HPV Blot (EasyChip) for 39 HPV types. The overall HPV prevalence was 16.2% for 10,602 eligible participants, and 13.8% for 10,190 cytologically normal participants. The most common carcinogenic types were HPV52 (2.5%), HPV16 (2.0%), HPV56 (1.8%), HPV18 (1.6%), HPV33 (1.2%), HPV58 (1.3%) and HPV39 (1.0%). Among the 56 prevalent invasive and in situ cases, HPV16 (48.2%) was most common, followed by HPV58 (25.0%), HPV52 (19.6%), HPV31 (8.9%), HPV33 (8.9%) and HPV18 (3.6%). HPV16 and HPV58 caused cytological HSIL+ at younger ages than HPV52. Approximately half of the cervical cancer cases and high-grade precursors in Taiwan could be prevented by prophylactic vaccines against HPV16 and HPV18 infection. Up to 40% more could be prevented by targeting HPV58, HPV52, HPV33 and HPV31, arguing for the introduction of vaccines including more types.
C1 [Chen, Hui-Chi; You, San-Lin; Pan, Mei-Hung; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan.
[Chen, Hui-Chi; You, San-Lin; Chou, Yi-Chun; Chen, Chien-Jen] Natl Taiwan Univ, Grad Inst Epidemiol, Taipei 10764, Taiwan.
[Hsieh, Chang-Yao] Natl Taiwan Univ Hosp, Dept Obstet & Gynecol, Taipei, Taiwan.
[Schiffman, Mark; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Lin, Ching-Yu] Taipei Med Univ, Sch Med Lab Sci & Biotechnol, Taipei, Taiwan.
RP Chen, CJ (reprint author), Acad Sinica, Genom Res Ctr, 128 Acad Rd,Sect 2, Taipei 11529, Taiwan.
EM cjchen@ntu.edu.tw
RI Chen, Chien-Jen/C-6976-2008;
OI Lin, Ching-Yu/0000-0001-8269-797X
FU Bureau of Health Promotion, Department of Health [93-028]; National
Science Council [94-2314-B-001-011, 95-2314-B-001-007,
96-2314-B-001-004, 97-2314-B-001-001-MY3]
FX Grant sponsor: Bureau of Health Promotion, Department of Health; Grant
number: 93-028; Grant sponsor: National Science Council; Grant numbers:
94-2314-B-001-011, 95-2314-B-001-007, 96-2314-B-001-004,
97-2314-B-001-001-MY3
NR 42
TC 12
Z9 13
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2011
VL 128
IS 5
BP 1192
EP 1203
DI 10.1002/ijc.25685
PG 12
WC Oncology
SC Oncology
GA 716HS
UT WOS:000286960300019
PM 20853317
ER
PT J
AU Watcho, P
Stavniichuk, R
Tane, P
Shevalye, H
Maksimchyk, Y
Pacher, P
Obrosova, IG
AF Watcho, Pierre
Stavniichuk, Roman
Tane, Pierre
Shevalye, Hanna
Maksimchyk, Yury
Pacher, Pal
Obrosova, Irina G.
TI Evaluation of PMI-5011, an ethanolic extract of Artemisia dracunculus
L., on peripheral neuropathy in streptozotocin-diabetic mice
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Article
DE diabetic neuropathy; PMI-5011; oxidative-nitrosative stress
ID ALDOSE REDUCTASE INHIBITOR; NERVE CONDUCTION-VELOCITY; SKELETAL-MUSCLE
CULTURE; ALPHA-LIPOIC ACID; NF-KAPPA-B; OXIDATIVE STRESS; BLOOD-FLOW;
EPINEURIAL ARTERIOLES; ANTIOXIDANT TREATMENT; COMPLICATIONS TRIAL
AB We previously reported that PMI-5011, an ethanolic extract of Artemisia dracunculus L., alleviates peripheral neuropathy in high fat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and pro-inflammatory changes in the peripheral nervous system. This study evaluated PMI-5011 on established functional, structural, and biochemical changes associated with Type I diabetic peripheral neuropathy.C57Bl6/J mice with streptozotocin-induced diabetes of a 12-week duration, developed motor and sensory nerve conduction velocity deficits, thermal and mechanical hypoalgesia, tactile allodynia, and intra-epidermal nerve fiber loss. PMI-5011 (500 mg/kg/day for 7 weeks) alleviated diabetes-induced nerve conduction slowing, small sensory nerve fiber dysfunction, and increased intra-epidermal nerve fiber density. PMI-5011 blunted sciatic nerve and spinal cord 12/15-lipoxygenase activation and oxidative-nitrosative stress, without ameliorating hyperglycemia or reducing sciatic nerve sorbitol pathway intermediate accumulation. In conclusion, PMI-5011, a safe and non-toxic botanical extract, may find use in the treatment of diabetic peripheral neuropathy.
C1 [Watcho, Pierre; Stavniichuk, Roman; Shevalye, Hanna; Maksimchyk, Yury; Obrosova, Irina G.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Watcho, Pierre; Tane, Pierre] Univ Dschang, Dept Chem, Dschang, Cameroon.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Obrosova, IG (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM obrosoig@pbrc.edu
RI Pacher, Pal/B-6378-2008;
OI Pacher, Pal/0000-0001-7036-8108; Shevalye, Hanna/0000-0002-2963-1717
FU American Diabetes Association [7-05-RA-102]; National Institutes of
Health [DK074517, DK077141, NCCAM/OD P50AT002776, P20 RR021945,
1P30-DK072476]; National Institutes of Health/National Institute of
Alcohol Abuse and Alcoholism; Agence Universitaire de la Francophonie
(AUF)
FX The study was supported by the American Diabetes Association Research
Grant 7-05-RA-102 (I.G.O.), the National Institutes of Health Grants
DK074517, DK077141, and DK074517 (all to I.G.O.), and the Intramural
Research Program of the National Institutes of Health/National Institute
of Alcohol Abuse and Alcoholism (to P.P.). Dr Pierre Watcho, University
of Dschang, Cameroon, was a recipient of a fellowship grant from the
Agence Universitaire de la Francophonie (AUF). The preparation of
PMI-5011 kindly provided by Dr Ilya Raskin and Dr David Ribnicky, was
supported by the National Institutes of Health Grant NCCAM/OD
P50AT002776 to the Botanical Research Center at the Pennington
Biomedical Research Center and The Biotech Center of Rutgers University.
The Cell Biology and Bioimaging Core utilized in this work is supported
in part by COBRE (NIH P20 RR021945) and CNRU (NIH 1P30-DK072476) center
grants from the National Institutes of Health. The authors thank Dr
Douglas E. Wright from the University of Kansas Medical Center, (Kansas
City, KS, USA) and Dr Gary L. Pittenger from Eastern Virginia Medical
School (Norfolk, VA, USA), for valuable recommendations regarding
intra-epidermal nerve fiber density measurements.
NR 45
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U1 0
U2 1
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD MAR
PY 2011
VL 27
IS 3
BP 299
EP 307
DI 10.3892/ijmm.2011.597
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 727FQ
UT WOS:000287783600001
PM 21225225
ER
PT J
AU Swamynathan, S
Kenchegowda, D
Piatigorsky, J
Swamynathan, S
AF Swamynathan, Sudha
Kenchegowda, Doreswamy
Piatigorsky, Joram
Swamynathan, Shivalingappa
TI Regulation of Corneal Epithelial Barrier Function by Kruppel-like
Transcription Factor 4
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BASEMENT-MEMBRANE; MOUSE CORNEA; STROMAL EDEMA; GOBLET CELLS; KLF4;
EXPRESSION; GENE; MECHANISMS; INTEGRINS; JUNCTIONS
AB PURPOSE. Previously, the authors showed that KO-conditional null (Klf4CN) corneas display epithelial fragility. Here, they investigated the mechanism by which KLF4 regulates corneal epithelial barrier function.
METHODS. Klf4CN mice were generated by breeding Le-Cre with KLF4-LoxP mice. Fluorescein staining was used to test the corneal barrier function. RT-PCR, immunoblots, and immunofluorescence were used to detect the expression of cell junctional proteins. The effect of Klf4 on promoter activities was measured by transient cotransfection assays. Trans-epithelial electrical resistance (TEER was used to measure the barrier-forming ability of control or anti-KLF4 siRNA-treated cells.
RESULTS. Increased fluorescein staining and decreased tight junction protein Tjp1 expression demonstrated that the KOCN corneal epithelial barrier function is defective. Expression of desmosomal components Dsp, Dsg-1a, and Dsg-1b was downregulated in the I:OWN corneas, and their corresponding promoter activities were upregulated by Klf4 in transient cotransfection assays. Hemidesmosomal alpha 3- and beta 4-integrin levels were not affected even though there were fewer hemidesmosomes in the KOCN corneas. The basement membrane components laminin-alpha 5, -alpha 3, -beta 3, and -beta 1-1 were downregulated, suggesting that the disrupted basement membrane is responsible for fewer hemidesmosomes in the KOCN cornea. Tight junction proteins OCLN1 and TJP1 were downregulated in anti-KLF4 siRNA-treated cells, which failed to develop epithelial barrier function as measured by TEER.
CONCLUSIONS. Klf4 contributes to corneal epithelial barrier function by upregulating the expression of functionally related subsets of cell junctional proteins and basement membrane components. (Invest Ophthalmol Sci. 2011;52:1762-1769) DOI:10.1167/iovs.10-6134
C1 [Swamynathan, Shivalingappa] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Inst Eye & Ear, Pittsburgh, PA 15213 USA.
[Swamynathan, Shivalingappa] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA.
[Swamynathan, Shivalingappa] Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Pittsburgh, PA 15213 USA.
[Piatigorsky, Joram] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Swamynathan, S (reprint author), Univ Pittsburgh, Sch Med, Dept Ophthalmol, Inst Eye & Ear, 203 Lothrop St,Room 1025, Pittsburgh, PA 15213 USA.
EM swamynathansk@upmc.edu; swamynathansk@upmc.edu
RI Kenchegowda, Doreswamy/F-2498-2012;
OI Kenchegowda, Doreswamy/0000-0003-0049-324X; Swamynathan,
Shivalingappa/0000-0002-9158-1511
FU NEI [EY016875]; Department of Ophthalmology, University of Pittsburgh
School of Medicine; NEI/NIH [5P30 EY08098-19]; Research to Prevent
Blindness; Eye and Ear Foundation, Pittsburgh
FX Supported by the NEI K22 Career Development Award EY016875 (SKS);
startup funds from the Department of Ophthalmology, University of
Pittsburgh School of Medicine (SKS); NEI/NIH Core Grant for Vision
Research 5P30 EY08098-19; Research to Prevent Blindness; the Eye and Ear
Foundation, Pittsburgh; and the intramural research program of the NEI,
NIH.
NR 48
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U1 1
U2 5
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2011
VL 52
IS 3
BP 1762
EP 1769
DI 10.1167/iovs.10-6134
PG 8
WC Ophthalmology
SC Ophthalmology
GA 742SR
UT WOS:000288965300068
PM 21051695
ER
PT J
AU Wassmann, C
AF Wassmann, Claudia
TI About Faces: Physiognomy in Nineteenth-Century Britain
SO ISIS
LA English
DT Book Review
C1 [Wassmann, Claudia] Max Planck Inst Human Dev, Berlin, Germany.
[Wassmann, Claudia] NIH, Bethesda, MD 20892 USA.
RP Wassmann, C (reprint author), Max Planck Inst Human Dev, Berlin, Germany.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0021-1753
J9 ISIS
JI Isis
PD MAR
PY 2011
VL 102
IS 1
BP 190
EP 191
PG 2
WC History & Philosophy Of Science
SC History & Philosophy of Science
GA 754PO
UT WOS:000289868600062
ER
PT J
AU D'Souza, I
Ma, W
Notobartolo, C
AF D'Souza, Ivor
Ma, Wei
Notobartolo, Cindy
TI Real-Time Location Systems for Hospital Emergency Response
SO IT PROFESSIONAL
LA English
DT Article
AB Real-time location systems can help hospitals execute a coordinated response during a disaster. However, before implementing an RTLS in such a setting, management must consider the various technologies and the associated benefits, drawbacks, and challenges.
C1 [D'Souza, Ivor; Ma, Wei] Natl Lib Med, Applicat Branch, Bethesda, MD 20894 USA.
[Notobartolo, Cindy] Johns Hopkins Med, ED Trauma Safety & Secur Suburban Hosp, Baltimore, MD USA.
RP D'Souza, I (reprint author), Natl Lib Med, Applicat Branch, Bethesda, MD 20894 USA.
EM ivor@nih.gov; Wei_Ma@nih.gov; CNotobartolo@SuburbanHospital.org
NR 4
TC 8
Z9 8
U1 2
U2 4
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1520-9202
J9 IT PROF
JI IT Prof.
PD MAR-APR
PY 2011
VL 13
IS 2
BP 37
EP 43
PG 7
WC Computer Science, Information Systems; Computer Science, Software
Engineering; Telecommunications
SC Computer Science; Telecommunications
GA 946CB
UT WOS:000304325500009
ER
PT J
AU Mascarenhas, L
Bond, MC
Seibel, NL
AF Mascarenhas, Leo
Bond, Mason C.
Seibel, Nita L.
TI Expanded Access Through Cancer Trials Support Unit to Children's
Oncology Group Sarcoma Trial AEWS1031 for Adolescents and Young Adults
SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY
LA English
DT Editorial Material
C1 [Mascarenhas, Leo] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol & Oncol, Los Angeles, CA 90027 USA.
[Bond, Mason C.] Univ British Columbia, British Columbia Childrens Hosp, Div Oncol Hematol Bone Marrow Transplant, Vancouver, BC V5Z 1M9, Canada.
[Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, Clin Invest Branch, Bethesda, MD 20892 USA.
RP Mascarenhas, L (reprint author), Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol & Oncol, 4650 Sunset Blvd,Mailstop 54, Los Angeles, CA 90027 USA.
EM lmascarenhas@chla.usc.edu
NR 11
TC 2
Z9 2
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2156-5333
EI 2156-535X
J9 J ADOLESC YOUNG ADUL
JI J. Adolesc. Young Adult Oncol.
PD MAR
PY 2011
VL 1
IS 1
BP 61
EP 63
DI 10.1089/jayao.2011.1502
PG 3
WC Oncology
SC Oncology
GA V39GB
UT WOS:000209398400013
PM 26812570
ER
PT J
AU Rutten, LJF
Davis, K
Squiers, L
Augustson, E
Blake, K
AF Rutten, Lila J. Finney
Davis, Kia
Squiers, Linda
Augustson, Erik
Blake, Kelly
TI Physician Awareness and Referral to National Smoking Cessation Quitlines
and Web-Based Resources
SO JOURNAL OF CANCER EDUCATION
LA English
DT Letter
ID INTERVENTIONS; DISPARITIES; SERVICES
C1 [Squiers, Linda] RTI Int, Res Triangle Pk, NC USA.
[Augustson, Erik] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA.
[Blake, Kelly] NCI, Hlth Commun Informat Res Branch, Bethesda, MD 20892 USA.
[Rutten, Lila J. Finney; Davis, Kia] NCI Frederick, SAIC Frederick Inc, Clin Monitoring Res Program, Frederick, MD USA.
RP Rutten, LJF (reprint author), 5705 Ind Lane,Room 201, Frederick, MD 21704 USA.
EM finneyl@mail.nih.gov
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]
NR 7
TC 6
Z9 6
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD MAR
PY 2011
VL 26
IS 1
BP 79
EP 81
DI 10.1007/s13187-010-0163-1
PG 3
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 723JN
UT WOS:000287502900013
PM 20924737
ER
PT J
AU Franco, I
Bailey, LO
Bakos, AD
Springfield, SA
AF Franco, Idalid
Bailey, LeeAnn O.
Bakos, Alexis D.
Springfield, Sanya A.
TI The Continuing Umbrella of Research Experiences (CURE): A Model for
Training Underserved Scientists in Cancer Research
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Minority; Diversity; Training; Cancer; Research; Biomedical research;
Underrepresented; Underserved
ID MINORITY
AB Mentoring is a critical aspect of research and training; and the adoption of a successful mentoring model for guiding researchers through the educational pipeline is lacking. The Continuing Umbrella of Research Experiences (CURE) program was established in the Comprehensive Minority Biomedical Branch; which is part of the National Cancer Institute. This program offers unique training and career development opportunities to enhance diversity in cancer research. The CURE initiative focuses on broadening the cadre of underserved investigators engaging in cancer research. CURE begins with high school students and fosters scientific, academic and research excellence throughout the trainee's educational progression. The program supports students throughout the entirety of their training career. During this period, the trainee matures into a competitive early stage investigator; capable of securing advanced research project funding in academic and industry workforces. Thus, the CURE program provides a comprehensive vehicle for training and reinforces the critical mass of underserved investigators conducting cancer research.
C1 [Bailey, LeeAnn O.; Bakos, Alexis D.] NCI, Ctr Reduce Canc Hlth Dispar, Divers Training Branch, Rockville, MD 20852 USA.
[Franco, Idalid] Univ Calif Los Angeles, Dept Gen & Internal Med, Los Angeles, CA 90025 USA.
RP Bailey, LO (reprint author), NCI, Ctr Reduce Canc Hlth Dispar, Divers Training Branch, 6116 Execut Blvd,Suite 602, Rockville, MD 20852 USA.
EM baileyl@mail.nih.gov
FU Intramural NIH HHS [NIH0011073090]; PHS HHS [NIH0011073090]
NR 10
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U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD MAR
PY 2011
VL 26
IS 1
BP 92
EP 96
DI 10.1007/s13187-010-0126-6
PG 5
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 723JN
UT WOS:000287502900015
PM 20568030
ER
PT J
AU Park, JJ
Gondre-Lewis, MC
Eiden, LE
Loh, YP
AF Park, Joshua J.
Gondre-Lewis, Marjorie C.
Eiden, Lee E.
Loh, Y. Peng
TI A distinct trans-Golgi network subcompartment for sorting of synaptic
and granule proteins in neurons and neuroendocrine cells
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Synaptic vesicles; Large dense-core vesicles; PC12 cells; Protein
trafficking
ID VESICULAR ACETYLCHOLINE TRANSPORTER; DENSE CORE VESICLES; PC12 CELLS;
SECRETORY PATHWAY; CHROMOGRANIN-A; NERVOUS-SYSTEM; MONOAMINE
TRANSPORTER-2; CARBOXYPEPTIDASE-E; PLASMA-MEMBRANE; IN-VITRO
AB Golgi-to-plasma-membrane trafficking of synaptic-like microvesicle (SLMV) proteins, vesicular acetylcholine transporter (VAChT) and synaptophysin (SYN), and a large dense-core vesicle (LDCV) protein, chromogranin A (CgA), was investigated in undifferentiated neuroendocrine PC12 cells. Live cell imaging and 20 degrees C block-release experiments showed that VAChT-GFP, SYN-GFP and CgA-RFP specifically and transiently cohabitated in a distinct sorting compartment during cold block and then separated into synaptic protein transport vesicles (SPTVs) and LDCVs, after release from temperature block. We found that in this trans-Golgi subcompartment there was colocalization of SPTV and LDCV proteins, most significantly with VAMP4 and Golgin97, and to some degree with TGN46, but not at all with TGN38. Moreover, some SNAP25 and VAMP2, two subunits of the exocytic machinery, were also recruited onto this compartment. Thus, in neuroendocrine cells, synaptic vesicle and LDCV proteins converge briefly in a distinct trans-Golgi network subcompartment before sorting into SPTVs and LDCVs, ultimately for delivery to the plasma membrane. This specialized sorting compartment from which SPTVs and LDCVs bud might facilitate the acquisition of common exocytic machinery needed on the membranes of these vesicles.
C1 [Gondre-Lewis, Marjorie C.] Howard Univ, Dept Anat, Coll Med, Washington, DC 20059 USA.
[Park, Joshua J.; Loh, Y. Peng] 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, Coll Med, Toledo, OH 43614 USA.
[Eiden, Lee E.] NIMH, Mol Neurosci Sect, NIH, Bethesda, MD 20892 USA.
RP Gondre-Lewis, MC (reprint author), Howard Univ, Dept Anat, Coll Med, Washington, DC 20059 USA.
EM mgondre-lewis@howard.edu; lohp@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU NICHD, NIH; NICHD [K22]; ARRA; Howard University Medical Alumni
Association (HUMAA) Endowed Chair in the Basic Sciences; NINDS/NIH
[NS065385]
FX We thank the lab members in SCN, NICHD for technical assistance and
helpful discussions. We thank Zu-Hang Sheng (NINDS, NIH) for the
synaptophysin constructs and Jennifer Lippincott-Schwartz (NICHD, NIH)
for the GPI-GFP construct and her helpful discussions. We thank Vincent
Schram and Chip Dye in the NICHD Microscopy Imaging Core for technical
support. This research was supported by the Intramural Research Program
of the NICHD, NIH. J.J.P. is supported by NICHD K22 and ARRA grants. M.
G. L. is supported by the Howard University Medical Alumni Association
(HUMAA) Endowed Chair in the Basic Sciences, an intramural SEED grant,
and NINDS/NIH Grant # NS065385. Deposited in PMC for release after 12
months.
NR 48
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U1 0
U2 5
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 MAR 1
PY 2011
VL 124
IS 5
BP 735
EP 744
DI 10.1242/jcs.076372
PG 10
WC Cell Biology
SC Cell Biology
GA 720UC
UT WOS:000287307000009
PM 21321327
ER
PT J
AU Singh, SR
Burnicka-Turek, O
Chauhan, C
Hou, SX
AF Singh, Shree Ram
Burnicka-Turek, Ozanna
Chauhan, Chhavi
Hou, Steven X.
TI Spermatogonial stem cells, infertility and testicular cancer
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Review
DE spermatogonial stem cell; infertility; SSC transplantation; SSC culture;
SSC plasticity; testicular cancer
ID LONG-TERM CULTURE; MALE GERM-CELLS; ADULT HUMAN TESTIS; SELF-RENEWAL;
MOUSE TESTIS; UNDIFFERENTIATED SPERMATOGONIA; GENE-EXPRESSION; IN-VITRO;
TRANSCRIPTION FACTOR; SEMINIFEROUS EPITHELIUM
AB Introduction
Spermatogonial stem cells
Regulation of SSC maintenance and differentiation
SSC culture, transplantation and plasticity
SSC in infertility
SSC in testicular germ cell tumours
Conclusions
The spermatogonial stem cells (SSCs) are responsible for the transmission of genetic information from an individual to the next generation. SSCs play critical roles in understanding the basic reproductive biology of gametes and treatments of human infertility. SSCs not only maintain normal spermatogenesis, but also sustain fertility by critically balancing both SSC self-renewal and differentiation. This self-renewal and differentiation in turn is tightly regulated by a combination of intrinsic gene expression within the SSC as well as the extrinsic gene signals from the niche. Increased SSCs self-renewal at the expense of differentiation result in germ cell tumours, on the other hand, higher differentiation at the expense of self-renewal can result in male sterility. Testicular germ cell cancers are the most frequent cancers among young men in industrialized countries. However, understanding the pathogenesis of testis cancer has been difficult because it is formed during foetal development. Recent studies suggest that SSCs can be reprogrammed to become embryonic stem (ES)-like cells to acquire pluripotency. In the present review, we summarize the recent developments in SSCs biology and role of SSC in testicular cancer. We believe that studying the biology of SSCs will not only provide better understanding of stem cell regulation in the testis, but eventually will also be a novel target for male infertility and testicular cancers.
C1 [Singh, Shree Ram; Burnicka-Turek, Ozanna; Chauhan, Chhavi; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Ft Detrick, MD 21702 USA.
RP Singh, SR (reprint author), NCI, Mouse Canc Genet Program, NIH, Ft Detrick, MD 21702 USA.
EM singhshr@mail.nih.gov
RI Singh, Shree Ram/B-7614-2008; Chauhan, Chhavi/A-9398-2011
OI Singh, Shree Ram/0000-0001-6545-583X;
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. We apologize
to scientific colleagues whose work could not be cited or was cited
indirectly, because of space limitations.
NR 166
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U1 1
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD MAR
PY 2011
VL 15
IS 3
BP 468
EP 483
DI 10.1111/j.1582-4934.2010.01242.x
PG 16
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 740ME
UT WOS:000288798000003
PM 21155977
ER
PT J
AU Kwon, JM
Guillet, R
Shankaran, S
Laptook, AR
McDonald, SA
Ehrenkranz, RA
Tyson, JE
O'Shea, TM
Goldberg, RN
Donovan, EF
Fanaroff, AA
Poole, WK
Higgins, RD
Walsh, MC
AF Kwon, Jennifer M.
Guillet, Ronnie
Shankaran, Seetha
Laptook, Abbot R.
McDonald, Scott A.
Ehrenkranz, Richard A.
Tyson, Jon E.
O'Shea, T. Michael
Goldberg, Ronald N.
Donovan, Edward F.
Fanaroff, Avroy A.
Poole, W. Kenneth
Higgins, Rosemary D.
Walsh, Michele C.
CA Eunice Kennedy Shriver Natl Inst
TI Clinical Seizures in Neonatal Hypoxic-Ischemic Encephalopathy Have No
Independent Impact on Neurodevelopmental Outcome: Secondary Analyses of
Data from the Neonatal Research Network Hypothermia Trial
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE neonatal seizures; whole-body hypothermia; neurodevelopmental outcome;
hypoxic-ischemic encephalopathy
ID ELECTROGRAPHIC SEIZURES; DEVELOPING BRAIN; EPILEPSY; RISK; STROKE
AB It remains controversial as to whether neonatal seizures have additional direct effects on the developing brain separate from the severity of the underlying encephalopathy. Using data collected from infants diagnosed with hypoxic-ischemic encephalopathy, and who were enrolled in an National Institute of Child Health and Human Development trial of hypothermia, we analyzed associations between neonatal clinical seizures and outcomes at 18 months of age. Of the 208 infants enrolled, 102 received whole body hypothermia and 106 were controls. Clinical seizures were generally noted during the first 4 days of life and rarely afterward. When adjustment was made for study treatment and severity of encephalopathy, seizures were not associated with death, or moderate or severe disability, or lower Bayley Mental Development Index scores at 18 months of life. Among infants diagnosed with hypoxic-ischemic encephalopathy, the mortality and morbidity often attributed to neonatal seizures can be better explained by the underlying severity of encephalopathy.
C1 [Kwon, Jennifer M.] Univ Rochester, Div Child Neurol, Dept Neurol, Rochester, NY 14642 USA.
[Kwon, Jennifer M.] Univ Rochester, Dept Pediat, Rochester, NY 14642 USA.
[Guillet, Ronnie] Univ Rochester, Div Neonatol, Dept Pediat, Rochester, NY 14642 USA.
[Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[McDonald, Scott A.; Poole, W. Kenneth] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[O'Shea, T. Michael] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Donovan, Edward F.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Fanaroff, Avroy A.; Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Kwon, JM (reprint author), Univ Rochester, Div Child Neurol, Dept Neurol, Box 631,601 Elmwood Ave, Rochester, NY 14642 USA.
EM jennifer_kwon@urmc.rochester.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development; [U10 HD21364]; [U10 HD21373];
[U10 HD21385]; [U10 HD21397]; [U10 HD27851]; [U10 HD27853]; [U10
HD27856]; [U10 HD27871]; [U10 HD27880]; [U10 HD27904]; [U10
HD34216]; [U10 HD36790]; [U10 HD40461]; [U10 HD40492]; [U10
HD40498]; [U10 HD40521]; [U10 HD40689]
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: The National Institutes of
Health and the Eunice Kennedy Shriver National Institute of Child Health
and Human Development provided grant support for the Neonatal Research
Network's Whole-Body Hypothermia Trial. This work was supported in part
by the following grants: U10 HD21364 (Case); U10 HD21373 (Houston); U10
HD21385 (Wayne); U10 HD21397 (Miami); U10 HD27851 (Emory); U10 HD27853
(Cinn); U10 HD27856 (Indiana); U10 HD27871 (Yale); U10 HD27880
(Stanford); U10 HD27904 (Brown); U10 HD34216 (Alabama); U10 HD36790
(RTI); U10 HD40461 (UCSD); U10 HD40492 (Duke); U10 HD40498 (Wake); U10
HD40521 (Rochester); U10 HD40689 (Dallas); GCRC M01 RR30 (Duke); GCRC
M01 RR39 (Emory); GCRC M01 RR44 (Rochester); GCRC M01 RR70 (Stanford);
GCRC M01 RR80 (Case); GCRC M01 RR633 (Dallas); GCRC M01 RR750 (Indiana);
GCRC M01 RR6022 (Yale); GCRC M01 RR7122 (Wake); GCRC M01 RR8084 (Cinn);
and GCRC M01 RR16587 (Miami).
NR 19
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U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD MAR
PY 2011
VL 26
IS 3
BP 322
EP 328
DI 10.1177/0883073810380915
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 731TD
UT WOS:000288131400008
PM 20921569
ER
PT J
AU Cao, XL
Wang, QE
Li, Y
Bai, G
Ren, H
Xu, CM
Ito, Y
AF Cao, Xueli
Wang, Qiaoe
Li, Yan
Bai, Ge
Ren, Hong
Xu, Chunming
Ito, Yoichiro
TI Isolation and purification of series bioactive components from Hypericum
perforatum L. by counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Counter-current chromatography; Hypericum perforatum L.; Hyperforin;
Hypericin; Rutin; Hyperoside
ID ST-JOHNS-WORT; PERFORMANCE LIQUID-CHROMATOGRAPHY; IN-VITRO;
MASS-SPECTROMETRY; EXTRACTION; HYPERFORIN; NAPHTHODIANTHRONES;
CONSTITUENTS; SEPARATION; FLAVONOIDS
AB Counter-current chromatography (CCC) combined with pre-separation by ultrasonic solvent extraction was successively used for the separation of series bioactive compounds from the crude extract of Hypericum perforatum L The petroleum ether extract was separated by the solvent system of n-heptane-methanol-acetonitrile (1.5:0.5:0.5, v/v) and n-heptane-methanol (1.5:1, v/v) in gradient elution, yielding a phloroglucinol compound, hyperforin with HPLC purity over 98%. The ethyl acetate extract was separated by using the solvent system composed of hexane-ethyl acetate-methanol-water (1:1:1:1 and 1:3:1:3, v/v) in gradient through both reverse phase and normal phase elution mode, yielding a naphthodianthrone compound, hypericin with HPLC purity about 95%. The n-butanol extract was separated with the solvent system composed of n-butanol-ethyl acetate-water (1:4:5 and 1.5:3.5:5, v/v) in elution and back-extrusion mode, yielding two of flavones, rutin and hyperoside, with HPLC purity over 95%. HPLC-MS, reference sample and UV spectrum were selectively used in separation to search for target compounds from HPLC-DAD profiles of different sub-extracts. The structures of isolated compounds were further identified by ESI-MS, (HNMR)-H-1 and (CNMR)-C-13. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Cao, Xueli; Wang, Qiaoe; Li, Yan; Bai, Ge; Ren, Hong; Xu, Chunming] Beijing Technol & Business Univ, Beijing Key Lab Plant Resource Res & Dev, Beijing 100037, Peoples R China.
[Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
RP Cao, XL (reprint author), Beijing Technol & Business Univ, Beijing Key Lab Plant Resource Res & Dev, Beijing 100037, Peoples R China.
EM caoxl@th.btbu.edu.cn
FU Beijing Natural Scientific Foundation [2102016]
FX Financial support from the Beijing Natural Scientific Foundation (No.
2102016) is gratefully acknowledged.
NR 33
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U1 5
U2 38
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD MAR 1
PY 2011
VL 879
IS 7-8
BP 480
EP 488
DI 10.1016/j.jchromb.2011.01.007
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 730TK
UT WOS:000288057100004
PM 21306961
ER
PT J
AU Jumpertz, R
Guijarro, A
Pratley, RE
Piomelli, D
Krakoff, J
AF Jumpertz, Reiner
Guijarro, Ana
Pratley, Richard E.
Piomelli, Daniele
Krakoff, Jonathan
TI Central and Peripheral Endocannabinoids and Cognate Acylethanolamides in
Humans: Association with Race, Adiposity, and Energy Expenditure
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PPAR-ALPHA; OBESITY; SYSTEM; OLEOYLETHANOLAMIDE; ANANDAMIDE; ACTIVATION;
INSULIN
AB Context: Peripheral and central endocannabinoids and cognate acylethanolamides (AEs) may play important but distinct roles in regulating energy balance.
Objective: We hypothesized that in humans central/peripheral endocannabinoids are differently associated with adiposity and energy expenditure and differ by race.
Design: We examined associations of arachindonoylethanolamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide (OEA) assayed in plasma and cerebrospinal fluid (CSF) with race, adiposity, and energy expenditure.
Setting/Participants: In this monitored clinical inpatient study, CSF was obtained by lumbar puncture in 27 individuals (12 Caucasian, 11 American Indian, and four African-American). Twenty-four hour and sleep energy expenditure were measured by indirect calorimetry in a respiratory chamber.
Main Outcome Measure: Samples were analyzed from a previous study originally designed to test a blood-brain barrier leptin transport deficit in human obesity.
Results: CSF (but not peripheral) 2-arachidonoylglycerol was significantly increased in American Indians compared with Caucasians (18.48 +/- 6.17 vs. 10.62 +/- 4.58 pmol/ml, P < 0.01). In the whole group, peripheral AEs were positively but in CSF negatively associated with adiposity. However, in multivariate models adjusted for the other peripheral and CSF AEs, peripheral arachindonoylethanolamide was the only AE significantly associated with adiposity. Interestingly, CSF OEA concentrations were positively associated with adjusted 24 hour and sleep energy expenditure (r = 0.47, P < 0.05; r = 0.42, P < 0.05), but peripheral OEA was not.
Conclusions: These data indicate a central alteration of the endocannabinoid system in American Indians and furthermore show that AEs in both compartments play an important but distinct role in human energy balance regulation. (J Clin Endocrinol Metab 96: 787-791, 2011)
C1 [Jumpertz, Reiner] NIDDKD, Obes & Diabet Clin Res Sect, NIH, US Dept HHS, Phoenix, AZ 85016 USA.
[Guijarro, Ana; Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA.
[Pratley, Richard E.] Univ Vermont, Colchester Res Facil, Burlington, VT 05446 USA.
RP Jumpertz, R (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, NIH, US Dept HHS, 4212 N 16th St, Phoenix, AZ 85016 USA.
EM jumpertzr@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 19
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U1 0
U2 2
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 MAR
PY 2011
VL 96
IS 3
BP 787
EP 791
DI 10.1210/jc.2010-2028
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730GA
UT WOS:000288020600049
PM 21177788
ER
PT J
AU Feuillan, PP
Ng, D
Han, JC
Sapp, JC
Wetsch, K
Spaulding, E
Zheng, YQC
Caruso, RC
Brooks, BP
Johnston, JJ
Yanovski, JA
Biesecker, LG
AF Feuillan, Penelope P.
Ng, David
Han, Joan C.
Sapp, Julie C.
Wetsch, Katie
Spaulding, Emma
Zheng, Yuqian C.
Caruso, Rafael C.
Brooks, Brian P.
Johnston, Jennifer J.
Yanovski, Jack A.
Biesecker, Leslie G.
TI Patients with Bardet-Biedl Syndrome Have Hyperleptinemia Suggestive of
Leptin Resistance
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID VISCERAL ADIPOSE-TISSUE; HUMAN OBESITY SYNDROME; SYNDROME GENE;
IDENTIFICATION; GROWTH; ASSOCIATION; MUTATIONS; PHENOTYPE; PROTEINS;
GENOMICS
AB Objective: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder of the primary cilium associated with obesity. In BBS mouse models, ciliary dysfunction leads to impaired leptin signaling and hyperleptinemia before obesity onset. To study the pathophysiology of obesity in BBS, we compared patients with BBS and body mass index Z-score (BMI-Z)-matched controls.
Design and Methods: Fifty patients with BBS were matched 2: 1 by age, sex, race, and BMI-Z with 100 controls. Patients with BBS and controls were compared for differences in body composition (dual-energy x-ray absorptiometry, abdominal magnetic resonance imaging), blood pressure Z-score (BP-Z; standardized for age, sex, and height), and fasting concentrations of leptin, lipids, insulin, and glucose. Patients with BBS were also compared by genotype.
Results: Leptin, triglycerides, intraabdominal fat mass, and diastolic BP-Z were significantly greater in patients with BBS than in the controls. BBS1 (27%) and BBS10 (30%) mutations were the most prevalent. Patients with BBS10 mutations had significantly higher BMI-Z, greater visceral adiposity, and greater insulin resistance than those with BBS1 mutations.
Conclusions: Patients with BBS had higher leptin than expected for their degree of adiposity, consistent with the notion that ciliopathy-induced leptin signaling dysfunction is associated with leptin resistance. The preferential deposition of fat intraabdominally in patients with BBS may indicate a predisposition for metabolic complications, including hypertension and hypertriglyceridemia. The observation of disparate results in the BBS10 vs. BBS1 mutation groups is the first demonstration of physiological differences among patients with BBS caused by mutations in distinct genes. These results suggest that the obesity of BBS is distinct from nonsyndromic obesity. (J Clin Endocrinol Metab 96: E528-E535, 2011)
C1 [Feuillan, Penelope P.; Ng, David; Sapp, Julie C.; Wetsch, Katie; Spaulding, Emma; Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Han, Joan C.; Zheng, Yuqian C.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA.
[Caruso, Rafael C.; Brooks, Brian P.] NHGRI, NEI, NIH, Bethesda, MD 20892 USA.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,Room 4A56, Bethesda, MD 20892 USA.
EM leslieb@helix.nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU National Human Genome Research Institute; National Institute of Child
Health and Human Development, National Institutes of Health
FX This study was supported by funds from the Intramural Research Programs
of the National Human Genome Research Institute and National Institute
of Child Health and Human Development, National Institutes of Health.
NR 42
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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 MAR
PY 2011
VL 96
IS 3
BP E528
EP E535
DI 10.1210/jc.2010-2290
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730GA
UT WOS:000288020600015
PM 21209035
ER
PT J
AU Lee, TK
Murthy, SRK
Cawley, NX
Dhanvantari, S
Hewitt, SM
Lou, H
Lau, T
Ma, S
Huynh, T
Wesley, RA
Ng, IO
Pacak, K
Poon, RT
Loh, YP
AF Lee, Terence K.
Murthy, Saravana R. K.
Cawley, Niamh X.
Dhanvantari, Savita
Hewitt, Stephen M.
Lou, Hong
Lau, Tracy
Ma, Stephanie
Huynh, Thanh
Wesley, Robert A.
Ng, Irene O.
Pacak, Karel
Poon, Ronnie T.
Loh, Y. Peng
TI An N-terminal truncated carboxypeptidase E splice isoform induces tumor
growth and is a biomarker for predicting future metastasis in human
cancers
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID PATHWAY SORTING RECEPTOR; SQUAMOUS-CELL CARCINOMA; NUDE-MOUSE MODEL;
HEPATOCELLULAR-CARCINOMA; SECRETORY GRANULES; MOLECULAR MARKERS;
ENZYME-ACTIVITY; CPE(FAT) MICE; EXPRESSION; GENE
AB Metastasis is a major cause of mortality in cancer patients. However, the mechanisms governing the metastatic process remain elusive, and few accurate biomarkers exist for predicting whether metastasis will occur, something that would be invaluable for guiding therapy. We report here that the carboxypeptidase E gene (CPE) is alternatively spliced in human tumors to yield an N-terminal truncated protein (CPE-Delta N) that drives metastasis. mRNA encoding CPE-Delta N was found to be elevated in human metastatic colon, breast, and hepatocellular carcinoma (HCC) cell lines. In HCC cells, cytosolic CPE-Delta N was translocated to the nucleus and interacted with histone deacetylase 1/2 to upregulate expression of the gene encoding neural precursor cell expressed, developmentally downregulated gene 9 (Nedd9) which has been shown to promote melanoma metastasis. Nedd9 upregulation resulted in enhanced in vitro proliferation and invasion. Quantification of mRNA encoding CPE-Delta N in HCC patient samples predicted intrahepatic metastasis with high sensitivity and specificity, independent of cancer stage. Similarly, high CPE-Delta N mRNA copy numbers in resected pheochromocytomas/paragangliomas (PHEOs/PGLs), rare neuroendocrine tumors, accurately predicted future metastasis or recurrence. Thus, CPE-Delta N induces tumor metastasis and should be investigated as a potentially powerful biomarker for predicting future metastasis and recurrence in HCC and PHEO/PGL patients.
C1 [Murthy, Saravana R. K.; Cawley, Niamh X.; Lou, Hong; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Lee, Terence K.; Lau, Tracy; Poon, Ronnie T.] Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China.
[Lee, Terence K.; Ma, Stephanie; Ng, Irene O.] Univ Hong Kong, Dept Pathol, Pokfulam, Hong Kong, Peoples R China.
[Dhanvantari, Savita] Lawson Hlth Res Inst, London, ON, Canada.
[Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Huynh, Thanh; Pacak, Karel] NICHD, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD USA.
[Wesley, Robert A.] NIH, Off Deputy Director Clin Care, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bldg 49,Room 5A-22,49 Convent Dr, Bethesda, MD 20892 USA.
EM poontp@hkucc.hku.hk; lohp@mail.nih.gov
RI Dhanvantari, Savita/B-5362-2015;
OI Hewitt, Stephen/0000-0001-8283-1788; Ma, Stephanie Kwai
Yee/0000-0002-2029-7943; Lee, Kin Wah/0000-0003-0682-322X
FU NICHD, NIH; Natural Sciences and Engineering Research Council of Canada;
University of Hong Kong
FX We thank Tamara Prodanov and Alicja Woronowicz (NICHD) for helpful
discussions, Rebecca McGirr (Lawson Health Research Institute) for
technical assistance, David Carter (London Regional Genomics Centre) for
microarray analysis, Jana Wo and Simon Yau (University of Hong Kong) for
animal work and qRT-PCR of the clinical tumor samples, respectively, and
Chikao Morimoto (Tokyo University) for NEDD9 N-terminal antibody. We
thank Steven Coon (NICHD) for assisting in Northern blots. This research
was supported by the Intramural Research Program of the NICHD, NIH; a
Natural Sciences and Engineering Research Council of Canada Discovery
Grant to S. Dhanvantari; and University of Hong Kong research grants to
R.T. Poon and I.O. Ng. I.O. Ng is Loke Yew Professor in Pathology.
NR 51
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U1 0
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 MAR
PY 2011
VL 121
IS 3
BP 880
EP 892
DI 10.1172/JCI40433
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 729YQ
UT WOS:000287991000010
PM 21285511
ER
PT J
AU Yang, DK
Li, Q
So, I
Huang, CL
Ando, H
Mizutani, A
Seki, G
Mikoshiba, K
Thomas, PJ
Muallem, S
AF Yang, Dongki
Li, Qin
So, Insuk
Huang, Chou-Long
Ando, Hideaki
Mizutani, Akihiro
Seki, George
Mikoshiba, Katsuhiko
Thomas, Philip J.
Muallem, Shmuel
TI IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK
kinase pathway
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; WNK KINASES; PANCREATIC-DUCT;
NA-K-2CL COTRANSPORTER; BICARBONATE SECRETION; PROTEIN PHOSPHATASE-1;
FLUID SECRETION; CYSTIC-FIBROSIS; BINDING PROTEIN; HCO3-SECRETION
AB Fluid and HCO3- secretion are fundamental functions of epithelia and determine bodily fluid volume and ionic composition, among other things. Secretion of ductal fluid and HCO3- in secretory glands is fueled by Na+/HCO3- cotransport mediated by basolateral solute carrier family 4 member 4 (NBCe1-B) and by Cl-/HCO3- exchange mediated by luminal solute carrier family 26, member 6 (S1c26a6) and CFTR. However, the mechanisms governing ductal secretion are not known. Here, we have shown that pancreatic ductal secretion in mice is suppressed by silencing of the NBCe1-B/CFTR activator inositol-1,4,5-trisphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and by inhibition of protein phosphatase 1 (PP1). In contrast, silencing the with-no-lysine (WNK) kinases and Ste20-related proline/alanine-rich kinase (SPAK) increased secretion. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression. IRBIT opposed the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities. Silencing of SPAK and IRBIT in the same ducts rescued ductal secretion due to silencing of IRBIT alone. These findings stress the pivotal role of IRBIT in epithelial fluid and HCO3- secretion and provide a molecular mechanism by which IRBIT coordinates these processes. They also have implications for WNK/SPAK kinase-regulated processes involved in systemic fluid homeostasis, hypertension, and cystic fibrosis.
C1 [Yang, Dongki; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Yang, Dongki; Li, Qin; Thomas, Philip J.; Muallem, Shmuel] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
[So, Insuk] Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul, South Korea.
[Huang, Chou-Long] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA.
[Huang, Chou-Long] Univ Texas SW Med Ctr Dallas, Div Nephrol, Dallas, TX 75390 USA.
[Ando, Hideaki; Mizutani, Akihiro; Mikoshiba, Katsuhiko] RIKEN, Inst Phys & Chem Res, Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama, Japan.
[Ando, Hideaki; Mikoshiba, Katsuhiko] JST, ICORP SORST, Calcium Oscillat Project, Wako, Saitama, Japan.
[Seki, George] Univ Tokyo, Fac Med, Dept Internal Med, Bunkyo Ku, Tokyo 113, Japan.
RP Muallem, S (reprint author), NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA.
EM shmuel.muallem@nih.gov
RI Thomas, Philip/F-7115-2012; So, Insuk/J-2762-2012; Mikoshiba,
Katsuhiko/N-7943-2015; Ando, Hideaki/D-3876-2017
FU NIDCR/Division of Intramural Research; NIH [DE 12309, DK076638]; Cystic
Fibrosis Foundation
FX We thank Anna DePaoli-Roach (Indiana University School of Medicine) for
the gift of I-2/pCMV-neo. Eric Delpire (Vanderbilt University Medical
Center, Nashville, Tennessee, USA) provided the plasmid coding PP1, and
Melanie Cobb (University of Texas Southwestern Medical Center) provided
the plasmid encoding mSPAK. This work was supported by an intramural
grant from the NIDCR/Division of Intramural Research, NIH grants DE
12309 and DK076638, and a grant from the Cystic Fibrosis Foundation.
NR 39
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U1 1
U2 1
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 MAR
PY 2011
VL 121
IS 3
BP 956
EP 965
DI 10.1172/JCI43475
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 729YQ
UT WOS:000287991000016
PM 21317537
ER
PT J
AU Zeng, M
Smith, AJ
Wietgrefe, SW
Southern, PJ
Schacker, TW
Reilly, CS
Estes, JD
Burton, GF
Silvestri, G
Lifson, JD
Carlis, JV
Haase, AT
AF Zeng, Ming
Smith, Anthony J.
Wietgrefe, Stephen W.
Southern, Peter J.
Schacker, Timothy W.
Reilly, Cavan S.
Estes, Jacob D.
Burton, Gregory F.
Silvestri, Guido
Lifson, Jeffrey D.
Carlis, John V.
Haase, Ashley T.
TI Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion
in HIV-1 and SIV infections
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID FIBROBLASTIC RETICULAR CELLS; GROWTH-FACTOR-BETA; COLLAGEN DEPOSITION;
IN-VIVO; INTRACELLULAR-LOCALIZATION; LYMPHATIC TISSUES; IMMUNE
ACTIVATION; MESSENGER-RNAS; NAIVE; HOMEOSTASIS
AB The hallmark of HIV-1 and SW infections is CD4(+) T cell depletion. Both direct cell killing and indirect mechanisms related to immune activation have been suggested to cause the depletion of T cells. We have now identified a mechanism by which immune activation-induced fibrosis of lymphoid tissues leads to depletion of naive T cells in HIV-1 infected patients and SW-infected rhesus macaques. The T regulatory cell response to immune activation increased procollagen production and subsequent deposition as fibrils via the TGF-beta 1 signaling pathway and chitinase 3-like-1 activity in fibroblasts in lymphoid tissues from patients infected with HIV-1. Collagen deposition restricted T cell access to the survival factor IL-7 on the fibroblastic reticular cell (FRC) network, resulting in apoptosis and depletion of T cells, which, in turn, removed a major source of lymphotoxin-beta, a survival factor for FRCs during SW infection in rhesus macaques. The resulting loss of FRCs and the loss of IL-7 produced by FRCs may thus perpetuate a vicious cycle of depletion of T cells and the FRC network. Because this process is cumulative, early treatment and antifibrotic therapies may offer approaches to moderate T cell depletion and improve immune reconstitution during HIV-1 infection.
C1 [Zeng, Ming; Smith, Anthony J.; Wietgrefe, Stephen W.; Southern, Peter J.; Haase, Ashley T.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA.
[Schacker, Timothy W.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA.
[Reilly, Cavan S.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Estes, Jacob D.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Burton, Gregory F.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA.
[Silvestri, Guido] Yerkes Natl Primate Res Ctr, Atlanta, GA USA.
[Silvestri, Guido] Emory Univ, Atlanta, GA 30322 USA.
[Carlis, John V.] Univ Minnesota, Inst Technol, Dept Comp Sci & Engn, Minneapolis, MN USA.
RP Haase, AT (reprint author), Univ Minnesota, Sch Med, Dept Microbiol, Box 196,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM haase001@umn.edu
RI Zeng, Ming/G-4231-2012
FU NIH [AI028246, AI048484, AI056997]; Yerkes base grant [P51-00165];
National Cancer Institute, NIH [HHSN261200800001E]
FX We thank the Yerkes National Primate Research Center; D. Masopust and V.
Vezys for providing CD3-depleting antibodies; C. O'Neill and T. Leonard
for help in preparing the manuscript and figures; Jeffrey Browning for
providing soluble LT beta R-Ig and control IgG; and Ben Ng from Carl
Zeiss for help in generating the 3D images. We also thank all of the
donor participants in this study. This work was supported in part by NIH
research grants AI028246, AI048484, and AI056997 to A.T. Haase; in part
by Yerkes base grant P51-00165 to G. Silvestri; and in part by federal
funds from the National Cancer Institute, NIH, under contract no.
HHSN261200800001E.
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U2 12
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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 MAR
PY 2011
VL 121
IS 3
BP 998
EP 1008
DI 10.1172/JCI45157
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 729YQ
UT WOS:000287991000020
PM 21393864
ER
PT J
AU Milush, JM
Mir, KD
Sundaravaradan, V
Gordon, SN
Engram, J
Cano, CA
Reeves, JD
Anton, E
O'Neill, E
Butler, E
Hancock, K
Cole, KS
Brenchley, JM
Else, JG
Silvestri, G
Sodora, DL
AF Milush, Jeffrey M.
Mir, Kiran D.
Sundaravaradan, Vasudha
Gordon, Shari N.
Engram, Jessica
Cano, Christopher A.
Reeves, Jacqueline D.
Anton, Elizabeth
O'Neill, Eduardo
Butler, Ebonee
Hancock, Kathy
Cole, Kelly S.
Brenchley, Jason M.
Else, James G.
Silvestri, Guido
Sodora, Donald L.
TI Lack of clinical AIDS in SIV-infected sooty mangabeys with significant
CD4(+) T cell loss is associated with double-negative T cells
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; NONHUMAN PRIMATE HOSTS; IMMUNE
ACTIVATION; RHESUS MACAQUES; TYPE-1 INFECTION; HIV DISEASE;
GASTROINTESTINAL-TRACT; NATURAL HOSTS; VIRAL LOAD; DEPLETION
AB SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4(+) T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3(+)CD4(-)CD8(-) T cells (double-negative T cells) partially compensates for CD4(+) T cell function in these animals. Passaging plasma from an SW-infected sooty mangabey with very few CD4(+) T cells to SW-negative animals resulted in rapid loss of CD4(+) T cells. Nonetheless, all sooty mangabeys generated SW-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4(+) T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4(+) T cell-like helper functions upon SIV-induced CD4(+) T cell depletion in this species.
C1 [Mir, Kiran D.; Sundaravaradan, Vasudha; Sodora, Donald L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Milush, Jeffrey M.; Mir, Kiran D.; Cano, Christopher A.; Sodora, Donald L.] Univ Texas SW Med Ctr Dallas, Dept Med, Div Infect Dis, Dallas, TX 75390 USA.
[Milush, Jeffrey M.] UCSF, Dept Med, Div Expt Med, San Francisco, CA USA.
[Gordon, Shari N.; Engram, Jessica] Univ Penn, Philadelphia, PA 19104 USA.
[Reeves, Jacqueline D.; Anton, Elizabeth] Monogram Biosci, San Francisco, CA USA.
[O'Neill, Eduardo; Butler, Ebonee; Hancock, Kathy] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Cole, Kelly S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Else, James G.; Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
RP Sodora, DL (reprint author), Seattle Biomed Res Inst, 307 Westlake Ave N,Suite 500, Seattle, WA 98109 USA.
EM don.sodora@seattlebiomed.org
RI Reeves, Jacqueline/I-5379-2012;
OI Milush, Jeffrey M./0000-0002-0773-6411
FU NIH [P51-RR00165, R56 AI087468, R01 DE017541]; Pendleton Trust
FX We acknowledge the excellent animal care and veterinary staff at the
Yerkes National Primate Center; F. Scott, A. Mobley, and S. Ehnert for
technical assistance; M.P. Martin for helpful comments and discussions;
L. Al-Harthi for discussions and supplying anti-V alpha 24 antibody; and
A. Durudas, D. Kosub, M. Gasper, H. Jaspan, L. Chen, and D. Fong for
helpful comments. Work was supported by the NIH, including grants to the
Yerkes Primate Center (P51-RR00165) as well as to D. Sodora (R56
AI087468 and R01 DE017541), and the Pendleton Trust.
NR 50
TC 43
Z9 43
U1 0
U2 0
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 MAR
PY 2011
VL 121
IS 3
BP 1102
EP 1110
DI 10.1172/JCI44876
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 729YQ
UT WOS:000287991000028
PM 21317533
ER
PT J
AU Kim, HY
Eyheramonho, MB
Pichavant, M
Cambaceres, CG
Matangkasombut, P
Cervio, G
Kuperman, S
Moreiro, R
Konduru, K
Manangeeswaran, M
Freeman, GJ
Kaplan, GG
DeKruyff, RH
Umetsu, DT
Rosenzweig, SD
AF Kim, Hye Young
Belen Eyheramonho, Maria
Pichavant, Muriel
Gonzalez Cambaceres, Carlos
Matangkasombut, Ponpan
Cervio, Guillermo
Kuperman, Silvina
Moreiro, Rita
Konduru, Krishnamurthy
Manangeeswaran, Mohanraj
Freeman, Gordon J.
Kaplan, Gerardo G.
DeKruyff, Rosemarie H.
Umetsu, Dale T.
Rosenzweig, Sergio D.
TI A polymorphism in TIM1 is associated with susceptibility to severe
hepatitis A virus infection in humans
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID KILLER T-CELLS; ACUTE LIVER-FAILURE; AIRWAY HYPERREACTIVITY; MUCIN
DOMAIN; NKT CELLS; PHOSPHATIDYLSERINE RECEPTOR; FULMINANT-HEPATITIS;
APOPTOTIC CELLS; HIV-1 INFECTION; ATOPIC DISEASE
AB During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However,, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy.
C1 [Kim, Hye Young; Pichavant, Muriel; Matangkasombut, Ponpan; DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat,Div Immunol, Boston, MA 02115 USA.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Immunol, Buenos Aires, DF, Argentina.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Liver Transplantat, Buenos Aires, DF, Argentina.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Transfus Med, Buenos Aires, DF, Argentina.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Lab Med, Buenos Aires, DF, Argentina.
[Konduru, Krishnamurthy; Manangeeswaran, Mohanraj; Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Umetsu, DT (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Immunol,Karp Labs, Rm 10127,1 Blackfan Circle, Boston, MA 02115 USA.
EM dale.umetsu@childrens.harvard.edu; srosenzweig@niaid.nih.gov
FU Fortabat Endowment of the David Rockefeller Center for Latin American
Studies at Harvard University; NIH [P01 AI054456]; FDA
FX We thank Leslie Kalish for help with the statistical analysis; and Mirta
Ciocca, Miriam Cuarterolo, Oscar Imventarza, Javier Goni, Ana Del Pozo,
Jorge Sasbon, Stefania Pittaluga, and Maria T. de Davila for valuable
comments and support. These studies were supported by the de Fortabat
Endowment of the David Rockefeller Center for Latin American Studies at
Harvard University, by a grant from the NIH (P01 AI054456), and with FDA
intramural funds. The findings and conclusions in this article have not
been formally disseminated by the FDA and should not be construed to
represent any Agency determination or policy.
NR 47
TC 36
Z9 38
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 MAR
PY 2011
VL 121
IS 3
BP 1111
EP 1118
DI 10.1172/JCI44182
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 729YQ
UT WOS:000287991000029
PM 21339644
ER
PT J
AU Publicover, J
Goodsell, A
Nishimura, S
Vilarinho, S
Wang, ZE
Avanesyan, L
Spolski, R
Leonard, WJ
Cooper, S
Baron, JL
AF Publicover, Jean
Goodsell, Amanda
Nishimura, Stephen
Vilarinho, Silvia
Wang, Zhi-en
Avanesyan, Lia
Spolski, Rosanne
Leonard, Warren J.
Cooper, Stewart
Baron, Jody L.
TI IL-21 is pivotal in determining age-dependent effectiveness of immune
responses in a mouse model of human hepatitis B
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; VIRUS-INFECTION; TRANSGENIC MICE;
NATURAL-HISTORY; T-CELLS; TOLERANCE; GENERATION; EXPRESSION; ANTIGEN;
DISEASE
AB HBV is a noncytopathic hepadnavirus and major human pathogen that causes immune-mediated acute and chronic hepatitis. The immune response to HBV antigens is age dependent: viral clearance occurs in most adults, while neonates and children usually develop chronic infection and liver disease. Here, we characterize an animal model for HBV infection that recapitulates the key differences in viral clearance between early life and adulthood and find that IL-21 may be part of an effective primary hepatic immune response to HBV. In our model, adult mice showed higher HBV-dependent IL-21 production in liver, compared with that of young mice. Conversely, absence of the IL-21 receptor in adult mice resulted in antigen persistence akin to that of young mice. In humans, levels of IL-21 transcripts were greatly increased in blood samples from acutely infected adults who clear the virus. These observations suggest a different model for the dichotomous, age-dependent outcome of HBV infection in humans, in which decreased IL-21 production in younger patients may hinder generation of crucial CD8(+) T and B cell responses. These findings carry implications for therapeutic augmentation of immune responses to HBV and potentially other persistent liver viruses.
C1 [Publicover, Jean; Goodsell, Amanda; Vilarinho, Silvia; Wang, Zhi-en; Baron, Jody L.] UCSF, Dept Med, San Francisco, CA USA.
[Publicover, Jean; Goodsell, Amanda; Vilarinho, Silvia; Cooper, Stewart; Baron, Jody L.] UCSF, UCSF Liver Ctr, San Francisco, CA USA.
[Nishimura, Stephen] UCSF, Dept Pathol, San Francisco, CA USA.
[Avanesyan, Lia; Cooper, Stewart] Calif Pacific Med Ctr & Res Inst, Liver Immunol Lab, San Francisco, CA USA.
[Avanesyan, Lia; Cooper, Stewart] Calif Pacific Med Ctr & Res Inst, Div Hepatol, San Francisco, CA USA.
[Avanesyan, Lia; Cooper, Stewart] Calif Pacific Med Ctr & Res Inst, Ctr Liver Dis, San Francisco, CA USA.
[Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Baron, JL (reprint author), 513 Parnassus Ave,S-357C,Box 0538, San Francisco, CA 94158 USA.
EM jody.baron@ucsf.edu
FU NIH NIAID [RO1AI068090]; UCSF Liver Center [P30DK026743]; Cancer
Research Institute; Burroughs Wellcome Fund; Ibrahim El-Hefni Technical
Training Foundation; National Research Service Award [T32DK060414]; A.P.
Gianinni Foundation; Division of Intramural Research, National Heart,
Lung, and Blood Institute
FX We would like to thank Anna Bogdanova, Christine Van Horn, and Gerald
Willkom for technical support and mouse colony management. We would also
like to acknowledge Kahee Jo and Arthur Rayz for their thankless
volunteer work in the laboratory. We graciously thank Mark Ansel, Jason
Cyster, Don Ganem, Mehrdad Matloubian, and Peggy Weintrub for advice and
Samuel Baron, Lewis Lanier, Marion Peters, and Jay Ryan for advice and
critical comments on the manuscript. We would also like to thank Lee
Reinhardt, Joao Pereira, Courtney Crane, and Ann Erickson for technical
advice. Lastly, we would like to thank the patients and healthy
volunteers for their blood donation used in this study. This work was
supported by NIH NIAID (RO1AI068090), UCSF Liver Center (P30DK026743),
Cancer Research Institute, Burroughs Wellcome Fund, and Ibrahim El-Hefni
Technical Training Foundation. Throughout this work, J. Publicover was
supported by National Research Service Award Hepatology Training grant
(T32DK060414) and A.P. Gianinni Foundation. W.J. Leonard and R. Spolski
were supported by the Division of Intramural Research, National Heart,
Lung, and Blood Institute.
NR 26
TC 61
Z9 69
U1 0
U2 2
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 MAR
PY 2011
VL 121
IS 3
BP 1154
EP 1162
DI 10.1172/JCI44198
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 729YQ
UT WOS:000287991000033
PM 21393863
ER
PT J
AU Aplenc, R
Blaney, SM
Strauss, LC
Balis, FM
Shusterman, S
Ingle, AM
Agrawal, S
Sun, JF
Wright, JJ
Adamson, PC
AF Aplenc, Richard
Blaney, Susan M.
Strauss, Lewis C.
Balis, Frank M.
Shusterman, Suzanne
Ingle, Ashish Mark
Agrawal, Shruti
Sun, Junfeng
Wright, John J.
Adamson, Peter C.
TI Pediatric Phase I Trial and Pharmacokinetic Study of Dasatinib: A Report
From the Children's Oncology Group Phase I Consortium
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; CYTOGENETIC RESPONSES; IMATINIB-RESISTANT
AB Purpose Dasatinib is an orally available tyrosine kinase inhibitor with low nanomolar activity against SRC family kinases, BCR-ABL, c-KIT, EPHA2, and the PDGF-beta receptor. Dasatinib was found to have selective activity in several tumor models in the Pediatric Preclinical Testing Program.
Patients and Methods A phase I study of dasatinib in pediatric patients with refractory solid tumors or imatinib-refractory, Philadelphia chromosome-positive leukemia was performed. Dose levels of 50, 65, 85, and 110 mg/m(2)/dose, administered orally twice daily for 28 days, with courses repeated without interruption, were studied. Pharmacokinetic studies were performed with the initial dose.
Results A total of 39 patients (solid tumors, n = 28; chronic myeloid leukemia [CML], n = 9; acute lymphoblastic leukemia, n = 2) were enrolled. No dose-limiting toxicities (DLTs) were observed at the 50, 65, and 85 mg/m(2) dose levels. At 110 mg/m(2), two of six patients experienced DLT including grade 2 diarrhea and headache. In children with leukemia, grade 4 hypokalemia (50 mg/m(2)), grade 3 diarrhea (85 mg/m(2)), and grade 2 creatinine elevation (50 mg/m(2)) were observed. DLT in later courses included pleural effusions, hemangiomatosis, and GI hemorrhage. There were three complete cytogenetic responses, three partial cytogenetic responses, and two partial/minimal cytogenetic responses observed in evaluable patients with CML.
Conclusion Overall, drug disposition and tolerability of dasatinib were similar to those observed in adult patients. J Clin Oncol 29:839-844. (C) 2011 by American Society of Clinical Oncology
C1 [Aplenc, Richard] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
Baylor Coll Med, Houston, TX 77030 USA.
Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA USA.
Stat & Data Ctr, Childrens Oncol Grp, Arcadia, CA USA.
Univ Nebraska Med Ctr, Omaha, NE USA.
NCI, Canc Therapeut & Evaluat Program, Bethesda, MD 20892 USA.
RP Aplenc, R (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, 4018 CTRB,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM raplenc@mail.med.upenn.edu
FU National Cancer Institute [U01 CA97452]; NCRR [M01 RR00188]
FX Supported by National Cancer Institute Grants No. U01 CA97452 and NCRR
M01 RR00188.
NR 12
TC 41
Z9 45
U1 0
U2 1
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 MAR 1
PY 2011
VL 29
IS 7
BP 839
EP 844
DI 10.1200/JCO.2010.30.7231
PG 6
WC Oncology
SC Oncology
GA 726NO
UT WOS:000287729900024
PM 21263099
ER
PT J
AU Robbins, PF
Morgan, RA
Feldman, SA
Yang, JC
Sherry, RM
Dudley, ME
Wunderlich, JR
Nahvi, AV
Helman, LJ
Mackall, CL
Kammula, US
Hughes, MS
Restifo, NP
Raffeld, M
Lee, CCR
Levy, CL
Li, YF
El-Gamil, M
Schwarz, SL
Laurencot, C
Rosenberg, SA
AF Robbins, Paul F.
Morgan, Richard A.
Feldman, Steven A.
Yang, James C.
Sherry, Richard M.
Dudley, Mark E.
Wunderlich, John R.
Nahvi, Azam V.
Helman, Lee J.
Mackall, Crystal L.
Kammula, Udai S.
Hughes, Marybeth S.
Restifo, Nicholas P.
Raffeld, Mark
Lee, Chyi-Chia Richard
Levy, Catherine L.
Li, Yong F.
El-Gamil, Mona
Schwarz, Susan L.
Laurencot, Carolyn
Rosenberg, Steven A.
TI Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and
Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID MODIFIED T-CELLS; ADOPTIVE IMMUNOTHERAPY; CANCER REGRESSION;
OVARIAN-CANCER; ANTIGEN; THERAPY; EXPRESSION; RESPONSES; ANTIBODY; STAGE
AB Purpose Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma.
Patients and Methods A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1-positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).
Results Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma.
Conclusion These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.
C1 [Robbins, Paul F.] NCI, NIH, Surg Branch, CRC 3 5744, Bethesda, MD 20892 USA.
RP Robbins, PF (reprint author), NCI, NIH, Surg Branch, CRC 3 5744, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM Paul_Robbins@nih.gov
RI Restifo, Nicholas/A-5713-2008; Lee, Chyi-Chia/I-1938-2013;
OI Lee, Chyi-Chia/0000-0002-5306-7781; Restifo, Nicholas
P./0000-0003-4229-4580
NR 26
TC 556
Z9 582
U1 7
U2 50
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 MAR 1
PY 2011
VL 29
IS 7
BP 917
EP 924
DI 10.1200/JCO.2010.32.2537
PG 8
WC Oncology
SC Oncology
GA 726NO
UT WOS:000287729900035
PM 21282551
ER
PT J
AU Kulke, MH
Siu, LL
Tepper, JE
Fisher, G
Jaffe, D
Haller, DG
Ellis, LM
Benedetti, JK
Bergsland, EK
Hobday, TJ
Van Cutsem, E
Pingpank, J
Oberg, K
Cohen, SJ
Posner, MC
Yao, JC
AF Kulke, Matthew H.
Siu, Lillian L.
Tepper, Joel E.
Fisher, George
Jaffe, Deborah
Haller, Daniel G.
Ellis, Lee M.
Benedetti, Jacqueline K.
Bergsland, Emily K.
Hobday, Timothy J.
Van Cutsem, Eric
Pingpank, James
Oberg, Kjell
Cohen, Steven J.
Posner, Mitchell C.
Yao, James C.
TI Future Directions in the Treatment of Neuroendocrine Tumors: Consensus
Report of the National Cancer Institute Neuroendocrine Tumor Clinical
Trials Planning Meeting
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PROGRESSION-FREE SURVIVAL; NUCLEOTIDE POLYMORPHISM ANALYSIS; METASTATIC
CARCINOID-TUMORS; PANCREATIC ENDOCRINE TUMORS; PHASE-II; SOMATOSTATIN
ANALOG; ALLELIC ALTERATIONS; PROGNOSTIC-FACTORS; GRADING SYSTEM;
OCTREOTIDE LAR
AB Neuroendocrine tumors (NETs) arise from a variety of anatomic sites and share the capacity for production of hormones and vasoactive peptides. Because of their perceived rarity, NETs have not historically been a focus of rigorous clinical research. However, the diagnosed incidence of NETs has been increasing, and the estimated prevalence in the United States exceeds 100,000 individuals. The recent completion of several phase III studies, including those evaluating octreotide, sunitinib, and everolimus, has demonstrated that rigorous evaluation of novel agents in this disease is both feasible and can lead to practice-changing outcomes. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trials planning meeting to identify key unmet needs, develop appropriate study end points, standardize clinical trial inclusion criteria, and formulate priorities for future NET studies for the US cooperative group program. Emphasis was placed on the development of well-designed clinical trials with clearly defined efficacy criteria. Key recommendations include the evaluation of pancreatic NET separately from NETs of other sites and the exclusion of patients with poorly differentiated histologies from trials focused on low-grade histologies. Studies evaluating novel agents for the control of hormonal syndromes should avoid somatostatin analog washout periods when possible and should include quality-of-life end points. Because of the observed long survival after progression of many patients, progression-free survival is recommended as a feasible and relevant primary end point for both phase III studies and phase II studies where a delay in progression is expected in the absence of radiologic responses. J Clin Oncol 29: 934-943. (C) 2011 by American Society of Clinical Oncology
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA.
Stanford Univ, Sch Med, Stanford, CA 94305 USA.
Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
NCI, Coordinating Ctr Clin Trials, Off Director, Rockville, MD USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, Houston, TX 77030 USA.
Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA.
Mayo Clin, Coll Med, Rochester, MN USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
Univ Hosp, Uppsala, Sweden.
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
FU National Cancer Institute, Bethesda, MD; Novartis; Pfizer; Genentech;
Ipsen; sanofi-aventis; Lexicon
FX Supported in part by a grant from the National Cancer Institute,
Bethesda, MD.; Research Funding: Lillian L. Siu, Novartis, Pfizer;
George Fisher, Genentech, Ipsen, Novartis, sanofi-aventis; Emily K.
Bergsland, Novartis, Genentech, Lexicon; Timothy J. Hobday, Novartis;
Eric Van Cutsem, Novartis, Pfizer; James C. Yao, Novartis, Genentech
NR 49
TC 129
Z9 135
U1 0
U2 4
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 MAR 1
PY 2011
VL 29
IS 7
BP 934
EP 943
DI 10.1200/JCO.2010.33.2056
PG 10
WC Oncology
SC Oncology
GA 726NO
UT WOS:000287729900037
PM 21263089
ER
PT J
AU Adelberg, D
Apolo, AB
Madan, RA
Gulley, JL
Pierpoint, A
Kohler, DR
Trepel, JB
Steinberg, SM
Figg, WD
Dahut, WL
AF Adelberg, D.
Apolo, A. B.
Madan, R. A.
Gulley, J. L.
Pierpoint, A.
Kohler, D. R.
Trepel, J. B.
Steinberg, S. M.
Figg, W. D.
Dahut, W. L.
TI A phase I study of TRC105 (anti-CD105 monoclonal antibody) in metastatic
castration-resistant prostate cancer (mCRPC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 171
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700172
PM 27968432
ER
PT J
AU Agochukwu, N
Linehan, W
Bratslavsky, G
AF Agochukwu, N.
Linehan, W.
Bratslavsky, G.
TI Econimic burden of reoperative renal surgery: Do the means justify the
ends?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NIH, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 364
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700362
PM 27968521
ER
PT J
AU Balar, AV
Milowsky, MI
Apolo, AB
Ostrovnaya, I
Iasonos, A
Trout, A
Regazzi, AM
Garcia-Grossman, IR
Gallagher, DJ
Bajorin, DF
AF Balar, A. V.
Milowsky, M. I.
Apolo, A. B.
Ostrovnaya, I.
Iasonos, A.
Trout, A.
Regazzi, A. M.
Garcia-Grossman, I. R.
Gallagher, D. J.
Bajorin, D. F.
TI Phase II trial of gemcitabine, carboplatin, and bevacizumab in
chemotherapy-naive patients (Pts) with advanced/metastatic urothelial
carcinoma (UC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 248
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700249
PM 27968540
ER
PT J
AU Bilusic, M
Gulley, JL
Heery, C
Apolo, AB
Arlen, PM
Rauckhorst, M
McMahon, S
Dahut, WL
Schlom, J
Madan, RA
AF Bilusic, M.
Gulley, J. L.
Heery, C.
Apolo, A. B.
Arlen, P. M.
Rauckhorst, M.
McMahon, S.
Dahut, W. L.
Schlom, J.
Madan, R. A.
TI A randomized phase II study of flutamide with or without PSA-TRICOM in
nonmetastatic castration-resistant prostate cancer (CRPC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
Neogenix Oncol Inc, Rockville, MD USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 163
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700164
ER
PT J
AU Chokshi, S
Ranjan, A
Benjamin, CJ
Chung, PH
Rastinehad, A
Dreher, MR
Wood, BJ
Pinto, PA
AF Chokshi, S.
Ranjan, A.
Benjamin, C. J.
Chung, P. H.
Rastinehad, A.
Dreher, M. R.
Wood, B. J.
Pinto, P. A.
TI Comparison of low-temperature-sensitive liposome encapsulated docetaxel
and doxorubicin in a murine model of prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Dept Radiol & Imaging Sci, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 31
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700032
PM 27968376
ER
PT J
AU Heery, C
Pinto, PA
Schlom, J
Tsang, KY
Madan, RA
Poole, D
Vergati, M
Rodriguez, BW
Merino, M
Gulley, JL
AF Heery, C.
Pinto, P. A.
Schlom, J.
Tsang, K. Y.
Madan, R. A.
Poole, D.
Vergati, M.
Rodriguez, B. Walter
Merino, M.
Gulley, J. L.
TI Intraprostatic vaccine administration in patients with locally recurrent
prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 141
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700142
PM 27968587
ER
PT J
AU Huang, X
Ning, YM
Gulley, JL
Kluetz, PG
Adelberg, D
Mulquin, M
Madan, RA
Bassim, C
Figg, WD
Dahut, WL
AF Huang, X.
Ning, Y. M.
Gulley, J. L.
Kluetz, P. G.
Adelberg, D.
Mulquin, M.
Madan, R. A.
Bassim, C.
Figg, W. D.
Dahut, W. L.
TI Phase II trial of bevacizumab (A), lenalidomide (R), docetaxel (D), and
prednisone (P) in patients (pts)with metastatic castration-resistant
prostate cancer (mCRPC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, US FDA, Silver Spring, MD USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
Natl Inst Dent & Craniolfacial Res, NIH, Bethesda, MD USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 138
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700139
PM 27968512
ER
PT J
AU Shuch, B
Bratslavsky, G
Shih, JH
Finley, D
Castor, B
Linehan, W
Pantuck, AJ
Said, J
Belldegrun, AS
AF Shuch, B.
Bratslavsky, G.
Shih, J. H.
Finley, D.
Castor, B.
Linehan, W.
Pantuck, A. J.
Said, J.
Belldegrun, A. S.
TI Impact of pathologic tumor characteristics in patients with sarcomatoid
renal cell carcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Urol Oncol Branch, Chevy Chase, MD USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
Univ Calif Los Angeles, Inst Urol Oncol, Los Angeles, CA USA.
Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 343
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700342
PM 27968689
ER
PT J
AU Sorbellini, M
Giubellino, A
Srivastava, G
Sourbier, C
Jagoda, E
Williams, M
Choyke, PL
Pinto, PA
Linehan, W
Bottaro, DP
AF Sorbellini, M.
Giubellino, A.
Srivastava, G.
Sourbier, C.
Jagoda, E.
Williams, M.
Choyke, P. L.
Pinto, P. A.
Linehan, W.
Bottaro, D. P.
TI Use of a MET-specific photoprobe to identify bladder tumors in an
orthotopic xenograft model of bladder cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 260
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700260
PM 27968576
ER
PT J
AU Sorbellini, M
Giubellino, A
Srivastava, G
Sourbier, C
Pinto, PA
Linehan, W
Bottaro, DP
AF Sorbellini, M.
Giubellino, A.
Srivastava, G.
Sourbier, C.
Pinto, P. A.
Linehan, W.
Bottaro, D. P.
TI Effect of the orally available MET inhibitor PF-2341066 on tumor burden
and metastasis in an orthotopic xenograft model of bladder cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 263
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700263
PM 27968590
ER
PT J
AU Sorbellini, M
McNeil, B
Cohen, B
Athauda, G
Giubellino, A
Coleman, J
Netto, GJ
Getzenberg, RH
Linehan, W
Bottaro, DP
AF Sorbellini, M.
McNeil, B.
Cohen, B.
Athauda, G.
Giubellino, A.
Coleman, J.
Netto, G. J.
Getzenberg, R. H.
Linehan, W.
Bottaro, D. P.
TI Urinary Met level as a novel biomarker for urothelial carcinoma of the
bladder
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, NIH, Bethesda, MD 20892 USA.
Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Johns Hopkins Univ, Baltimore, MD USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 257
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700257
PM 27968502
ER
PT J
AU Vourganti, S
Linehan, W
Bratslavsky, G
AF Vourganti, S.
Linehan, W.
Bratslavsky, G.
TI Comparison of partial nephrectomy for tumors greater than 7 cm to
radical nephrectomy and effect on overall survival
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 [Vourganti, S.; Linehan, W.; Bratslavsky, G.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 323
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700322
PM 27968628
ER
PT J
AU Williams, H
AF Williams, H.
TI Role of heat shock protein 90 inhibition with 17-(allylamino)-17
(demethoxygeldenamycin) in muscle-invasive bladder cancer cells
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 [Williams, H.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 273
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700273
PM 27968560
ER
PT J
AU Summers, RM
Baecher, N
Yao, JH
Liu, JM
Pickhardt, PJ
Choi, JR
Hill, S
AF Summers, Ronald M.
Baecher, Nicolai
Yao, Jianhua
Liu, Jiamin
Pickhardt, Perry J.
Choi, J. Richard
Hill, Suvimol
TI Feasibility of Simultaneous Computed Tomographic Colonography and Fully
Automated Bone Mineral Densitometry in a Single Examination
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE radiology; population studies; bone densitometry; bone QCT; osteoporosis
ID OLDER US ADULTS; CT COLONOGRAPHY; COLORECTAL ADENOMAS; AIDED DETECTION;
CALCIUM SUPPLEMENTATION; QUANTITATIVE CT; 2ND READER; NHANES-III;
DENSITY; OSTEOPOROSIS
AB Purpose: To show the feasibility of calculating the bone mineral density (BMD) from computed tomographic colonography (CTC) scans using fully automated software.
Materials and Methods: Automated BMD measurement software was developed that measures the BMD of the first and second lumbar vertebrae on computed tomography and calculates the mean of the 2 values to provide a per patient BMD estimate. The software was validated in a reference population of 17 consecutive women who underwent quantitative computed tomography and in a population of 475 women from a consecutive series of asymptomatic patients enrolled in a CTC screening trial conducted at 3 medical centers.
Results: The mean (SD) BMD was 133.6 (34.6) mg/mL (95% confidence interval, 130.5-136.7; n = 475). In women aged 42 to 60 years (n = 316) and 61 to 79 years (n = 159), the mean (SD) BMDs were 143.1 (33.5) and 114.7 (28.3) mg/mL, respectively (P < 0.0001). Fully automated BMD measurements were reproducible for a given patient with 95% limits of agreement of -9.79 to 8.46 mg/mL for the mean difference between paired assessments on supine and prone CTC.
Conclusions: Osteoporosis screening can be performed simultaneously with screening for colorectal polyps.
C1 [Summers, Ronald M.; Baecher, Nicolai; Yao, Jianhua; Liu, Jiamin; Hill, Suvimol] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Choi, J. Richard] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10,Room 1C224D MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU iCAD; E-Z-EM; National Institutes of Health Clinical Center
FX This article was supported in part by the Intramural Research Program of
the National Institutes of Health Clinical Center.; Authors Summers and
Yao have pending and/or awarded patents for the subject matter described
in the article and receive royalty income for a patent license from
iCAD. Author Summers is a Johnson & Johnson stockholder. His laboratory
is supported in part by a cooperative research and development agreement
with iCAD. Viatronix supplied the V3D Colon software to National
Institutes of Health free of charge. Author Pickhardt is on the medical
advisory boards of Viatronix, Inc and Medicsight, Inc, a consultant to
Philips, and cofounder of VirtuoCTC. Author Choi is on the medical
advisory boards of Viatronix, Inc and QI and has received research
support from E-Z-EM. All other authors have no conflicts of interest.
NR 36
TC 26
Z9 26
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0363-8715
EI 1532-3145
J9 J COMPUT ASSIST TOMO
JI J. Comput. Assist. Tomogr.
PD MAR-APR
PY 2011
VL 35
IS 2
BP 212
EP 216
DI 10.1097/RCT.0b013e3182032537
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 736MM
UT WOS:000288498800009
PM 21412092
ER
PT J
AU Ford, ES
Cowie, CC
Li, CY
Handelsman, Y
Bloomgarden, ZT
AF Ford, Earl S.
Cowie, Catherine C.
Li, Chaoyang
Handelsman, Yehuda
Bloomgarden, Zachary T.
TI Iron-deficiency anemia, non-iron-deficiency anemia and HbA1c among
adults in the US
SO JOURNAL OF DIABETES
LA English
DT Article
DE hemoglobin A1c protein; hemoglobins; iron-deficiency anemia
ID GLYCOSYLATED HEMOGLOBIN; DIABETES-MELLITUS
AB Background: Conditions that affect erythrocyte turnover affect HbA1c concentrations. Although many forms of anemia are associated with lowering of HbA1c, iron deficiency tends to increase HbA1c. We examined the effect of iron and hemoglobin (Hb) status on HbA1c and on the relationship between concentrations of fasting glucose and HbA1c in a national sample of adults in the US.
Methods: Cross-sectional data from 8296 adults aged >= 20 years who participated in NHANES 1999-2002 were used.
Results: The prevalence of low Hb (defined as <120 and <118 g/L in women aged 20-69 and >= 70 years, respectively, and <137, <133, and <124 g/L in men aged 20-49, 50-69, and >= 70 years, respectively) was 5.5%. There was a significant positive correlation between Hb concentrations and HbA1c concentrations after adjusting for age, gender, and race or ethnicity, with HbA1c rising from a mean of 5.28% among participants with Hb <100 g/L to 5.72% among participants with Hb >= 170 g/L. The adjusted mean concentrations of HbA1c were 5.56% and 5.46% among participants with and without iron deficiency, respectively (P = 0.095). However, there was no evidence of differences in the relationship between fasting glucose and HbA1c when groups of anemic and non-anemic individuals with and without iron deficiency were examined individually.
Conclusions: Caution should be used when diagnosing diabetes and prediabetes among people with high or low Hb when the HbA1c level is near 6.5% or 5.7%, respectively, as changes in erythrocyte turnover may alter the test result. However, the trend for HbA1c to increase with iron deficiency does not appear to require screening for iron deficiency in ascertaining the reliability of HbA1c in the diagnosis of diabetes and prediabetes in a given individual.
C1 [Ford, Earl S.; Li, Chaoyang] Ctr Dis Control & Prevent, Div Adult & Community Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA.
[Cowie, Catherine C.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Handelsman, Yehuda] Metab Inst Amer, Tarzana, CA USA.
[Bloomgarden, Zachary T.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Ford, ES (reprint author), Ctr Dis Control & Prevent, Div Adult & Community Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway,MS K66, Atlanta, GA 30341 USA.
EM Eford@cdc.gov
NR 19
TC 28
Z9 29
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1753-0393
J9 J DIABETES
JI J. Diabetes
PD MAR
PY 2011
VL 3
IS 1
BP 67
EP 73
DI 10.1111/j.1753-0407.2010.00100.x
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 982RO
UT WOS:000307063300010
PM 20942846
ER
PT J
AU Huang, CM
Wang, KL
Cheng, HM
Chuang, SY
Sung, SH
Yu, WC
Ting, CT
Lakatta, EG
Yin, FCP
Chou, PS
Chen, CH
AF Huang, Chi-Ming
Wang, Kang-Ling
Cheng, Hao-Min
Chuang, Shao-Yuan
Sung, Shih-Hsien
Yu, Wen-Chung
Ting, Chih-Tai
Lakatta, Edward G.
Yin, Frank C. P.
Chou, Pesus
Chen, Chen-Huan
TI Central versus ambulatory blood pressure in the prediction of all-cause
and cardiovascular mortalities
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE ambulatory blood pressure; central blood pressure; mortality; pulse
pressure; target organ damage
ID LEFT-VENTRICULAR MASS; CENTRAL PULSE PRESSURE; ARTERIAL-HYPERTENSION;
MEASUREMENTS-WILL; DISEASE; EVENTS; POPULATION; WELL
AB Objectives Central systolic (SBP-C) and/or pulse pressure (PP-C) better predicts cardiovascular events than does peripheral blood pressure. The present study compared the prognostic significance of office central blood pressure with multiple measurements of out-of-office ambulatory peripheral blood pressure, with reference to office peripheral systolic (SBP-B) or pulse pressure (PP-B).
Methods In a community-based population of 1014 healthy participants, SBP-C and PP-C were estimated using carotid tonometry, and 24-h systolic (SBP-24 h) and pulse pressure (PP-24 h) were obtained from 24-h ambulatory blood pressure monitoring. Associations of SBP-B, PP-B, SBP-C, PP-C, SBP-24 h, and PP-24 h with all-cause and cardiovascular mortalities over a median follow-up of 15 years were examined by Cox regression analysis.
Results In multivariate analyses accounting for age, sex, BMI, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein cholesterol ratio, only PP-C (hazard ratio 1.16, 95% confidence interval 1.01-1.32, per one standard deviation increment) was significantly predictive of all-cause mortality, whereas all but PP-B were significantly predictive of cardiovascular mortality. When SBP-B was simultaneously included in the models, SBP-24 h (2.01, 1.42-2.85) and SBP-C (1.71, 1.21-2.40) remained significantly predictive of cardiovascular mortality. When SBP-C was simultaneously included in the models, SBP-24 h (1.71, 1.16-2.52) remained significantly predictive of cardiovascular mortality.
Conclusion Office central blood pressure is more valuable than office peripheral blood pressure in the prediction of all-cause and cardiovascular mortalities. Out-of-office ambulatory peripheral blood pressure (SBP-24 h) may be superior to central blood pressure in the prediction of cardiovascular mortality, but PP-C may better predict all-cause mortality than SBP-24 h or PP-24 h. J Hypertens 29:454-459 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Huang, Chi-Ming] Yuanshan Vet Hosp, Dept Med, Yilan, Taiwan.
[Sung, Shih-Hsien; Yu, Wen-Chung] Taipei Vet Gen Hosp, Dept Med, Taipei, Taiwan.
[Wang, Kang-Ling; Cheng, Hao-Min; Chen, Chen-Huan] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan.
[Chuang, Shao-Yuan] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Ting, Chih-Tai] Taichung Vet Gen Hosp, Cardiovasc Ctr, Taichung, Taiwan.
[Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Intramural Res Program, Baltimore, MD 21224 USA.
[Yin, Frank C. P.] Washington Univ, Dept Biomed Engn, St Louis, MO USA.
[Chou, Pesus; Chen, Chen-Huan] Natl Yang Ming Univ, Dept Publ Hlth, Taipei 112, Taiwan.
[Chen, Chen-Huan] Natl Yang Ming Univ, Cardiovasc Res Ctr, Taipei 112, Taiwan.
RP Chen, CH (reprint author), Taipei Vet Gen Hosp, Dept Med Res & Educ, 201,Sec 2,Shih Pai Rd, Taipei, Taiwan.
EM chench@vghtpe.gov.tw
RI Chuang, Shao-Yuan/B-3478-2011
FU National Science Council [NSC 99-2314-B-010-034-MY3]; Taipei Veterans
General Hospital [V99C1-091]; Research and Development [NO1-AG-1-2118];
National Institute on Aging, National Institutes of Health
FX The present work was supported in part by a grant from the National
Science Council (NSC 99-2314-B-010-034-MY3), an intramural grant from
the Taipei Veterans General Hospital (Grant No. V99C1-091), and Research
and Development contract NO1-AG-1-2118 and the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health.
NR 23
TC 56
Z9 58
U1 1
U2 3
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 MAR
PY 2011
VL 29
IS 3
BP 454
EP 459
DI 10.1097/HJH.0b013e3283424b4d
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 719UO
UT WOS:000287236600010
PM 21252703
ER
PT J
AU van Panhuys, N
Prout, M
Forbes, E
Min, B
Paul, WE
Le Gros, G
AF van Panhuys, Nicholas
Prout, Melanie
Forbes, Elizabeth
Min, Booki
Paul, William E.
Le Gros, Graham
TI Basophils Are the Major Producers of IL-4 during Primary Helminth
Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IN-VIVO; T-CELLS; MAST-CELLS; IMMUNE-RESPONSES; CARRIER PROTEINS; TYPE-2
IMMUNITY; DIFFERENTIATION; ANTIGEN; INTERLEUKIN-4; IGE
AB IL-4 production by leukocytes is a key regulatory event that occurs early in the type 2 immune response, which induces allergic reactions and mediates expulsion of parasites. CD4(+) T cells and basophils are thought to be the key cell types that produce IL-4 during a type 2 response. In this study, we assessed the relative contribution of both CD4(+) T cell-and basophil-IL-4 production during primary and secondary responses to Nippostrongylus brasiliensis using a murine IL-4-enhanced GFP reporter system. During infection, IL-4-producing basophils were detected systemically, and tissue recruitment occurred independent of IL-4/STAT6 signaling. We observed that basophil recruitment to a tissue environment was required for their full activation. Basophil induction in response to secondary infection exhibited accelerated kinetics in comparison with primary infection. However, total basophil numbers were not enhanced, as predicted by previous models of protective immunity. Overall, the induction and migration of IL-4-producing basophils into peripheral tissues was found to be a prominent characteristic of the primary but not memory responses to N. brasiliensis infection, in which CD4(+) T cells were identified as the major source of IL-4. Whereas basophils were the major initial producers of IL-4, we determined that normal Th2 differentiation occurs independently of basophils, and depletion of basophils led to an enhancement of inflammatory cell recruitment to the site of infection. The Journal of Immunology, 2011, 186: 2719-2728.
C1 [van Panhuys, Nicholas] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[van Panhuys, Nicholas; Prout, Melanie; Forbes, Elizabeth; Le Gros, Graham] Malaghan Inst Med Res, Wellington 6012, New Zealand.
[Min, Booki] Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA.
RP van Panhuys, N (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10-11N308, Bethesda, MD 20892 USA.
EM vanpanhuysn@niaid.nih.gov
RI Le Gros, Graham/C-6725-2011; Forbes-Blom, Elizabeth/I-3648-2013; van
Panhuys, Nicholas/E-1812-2011;
OI van Panhuys, Nicholas/0000-0003-2199-852X
FU Health Research Council of New Zealand; Marjorie Barclay Trust; Marsden
Fund; AMI Insurance Ltd.; National Institute of Allergy and Infectious
Diseases/National Institutes of Health [Z01 AI000493.22]; National
Institutes of Health [AI080908]; New Zealand Foundation for Research,
Science and Technology
FX This work was supported by Research Program funding from the Health
Research Council of New Zealand, the Marjorie Barclay Trust, the Marsden
Fund, AMI Insurance Ltd., and the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases/National
Institutes of Health through Project Z01 AI000493.22. This work was
supported in part by National Institutes of Health Grant AI080908 (to
B.M.). N.v.P. is funded by the New Zealand Foundation for Research,
Science and Technology.
NR 40
TC 37
Z9 38
U1 0
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2011
VL 186
IS 5
BP 2719
EP 2728
DI 10.4049/jimmunol.1000940
PG 10
WC Immunology
SC Immunology
GA 721LT
UT WOS:000287356900007
PM 21270410
ER
PT J
AU Novy, P
Huang, XP
Leonard, WJ
Yang, YP
AF Novy, Patricia
Huang, Xiaopei
Leonard, Warren J.
Yang, Yiping
TI Intrinsic IL-21 Signaling Is Critical for CD8 T Cell Survival and Memory
Formation in Response to Vaccinia Viral Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IN-VIVO; SECONDARY EXPANSION; CD8-T-CELL MEMORY; CLONAL EXPANSION;
RECEPTOR SIGNALS; CD4-T-CELL HELP; DENDRITIC CELLS; ACTIVATION;
DIFFERENTIATION; IMMUNITY
AB CD4 T cell help plays an important role in promoting CD8 T cell immunity to pathogens. In models of infection with vaccinia virus (VV) and Listeria monocytogenes, CD4 T cell help is critical for the survival of activated CD8 T cells during both the primary and memory recall responses. Still unclear, however, is how CD4 T cell help promotes CD8 T cell survival. In this study, we first showed that CD4 T cell help for the CD8 T cell response to VV infection was mediated by IL-21, a cytokine produced predominantly by activated CD4 T cells, and that direct action of IL-21 on CD8 T cells was critical for the VV-specific CD8 T cell response in vivo. We next demonstrated that this intrinsic IL-21 signaling was essential for the survival of activated CD8 T cells and the generation of long-lived memory cells. We further revealed that IL-21 promoted CD8 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 pathways and subsequent upregulation of the prosurvival molecules Bcl-2 and Bcl-x(L). These results identify a critical role for intrinsic IL-21 signaling in CD8 T cell responses to an acute viral infection in vivo and may help design effective vaccine strategies. The Journal of Immunology, 2011, 186: 2729-2738.
C1 [Huang, Xiaopei; Yang, Yiping] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Novy, Patricia; Yang, Yiping] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
[Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA.
RP Yang, YP (reprint author), Duke Univ, Med Ctr, Dept Med, Box 103005, Durham, NC 27710 USA.
EM yang0029@mc.duke.edu
FU National Institutes of Health [CA136934, CA11807, CA047741, AI079366,
AI083000]; Alliance for Cancer Gene Therapy; National Heart, Lung, and
Blood Institute
FX This work was supported by National Institutes of Health Grants
CA136934, CA11807, CA047741, AI079366, and AI083000 (to Y.Y.), an
Alliance for Cancer Gene Therapy grant (to Y.Y.), and the Intramural
Research Program, National Heart, Lung, and Blood Institute (to W.J.L.).
NR 53
TC 42
Z9 43
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 MAR 1
PY 2011
VL 186
IS 5
BP 2729
EP 2738
DI 10.4049/jimmunol.1003009
PG 10
WC Immunology
SC Immunology
GA 721LT
UT WOS:000287356900008
PM 21257966
ER
PT J
AU Zhang, H
Cui, YZ
Voong, N
Sabatino, M
Stroncek, DF
Morisot, S
Civin, CI
Wayne, AS
Levine, BL
Mackall, CL
AF Zhang, Hua
Cui, Yongzhi
Voong, Nga
Sabatino, Marianna
Stroncek, Dave F.
Morisot, Sebastien
Civin, Curt I.
Wayne, Alan S.
Levine, Bruce L.
Mackall, Crystal L.
TI Activating Signals Dominate Inhibitory Signals in CD137L/IL-15 Activated
Natural Killer Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE natural killer cells; activating NK receptor; killer cell
immunoglobulin-like receptor; cytotoxicity
ID MHC-CLASS-I; NK CELLS; IMMUNOGLOBULIN SUPERFAMILY; TUMOR-CELLS; RECEPTOR
BLOCKADE; SELF-TOLERANCE; NKP30 RECEPTOR; HLA-C; LIGANDS; CYTOTOXICITY
AB Natural killer (NK) cells can mediate potent antitumor effects, but factors regulating the efficiency of tumor lysis remain unclear. Studies in allogeneic stem cell transplantation highlight an important role for killer cell immunoglobulin-like receptor (KIR) mismatch in overcoming human leukocyte antigen-mediated inhibitory signals. However, other activating and inhibitory signals also modulate tumor lysis by NK cells. We used rhIL15 and artificial antigen presenting cells expressing CD137L and IL15R alpha to activate and expand peripheral blood NK cells (CD137L/IL15 NK) up to 1000-fold in 3 weeks. Compared with resting NK cells, CD137L/IL15 NK cells show modest increases in KIR expression and substantial increases in NKG2D, tumor necrosis factor-related apoptosis-inducing ligand, and natural cytotoxicity receptors (NCRs: NKp30, NKp44, NKp46). Compared with resting NK cells, CD137L/IL15 NK cells mediate enhanced cytotoxicity against allogeneic and autologous tumors and KIR signaling did not substantially inhibit cytotoxicity. Rather, tumor lysis by CD137L/IL15 activated NK cells was predominantly driven by NCR signaling as blockade of NCRs dramatically diminished the lysis of a wide array of tumor targets. Furthermore, tumor lysis by CD137L/IL15 NK cells was tightly linked to NCR expression levels that peaked on day 8 to 10 after NK activation, and cytotoxicity diminished on subsequent days as NCR expression declined. We conclude that KIR mismatch is not a prerequisite for tumor killing by CD137L/IL15 NK cells and that NCR expression provides a biomarker for predicting potency of CD137L/IL15 NK cells in studies of NK cell-based immunotherapy.
C1 [Mackall, Crystal L.] NCI, Immunol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Voong, Nga] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Sabatino, Marianna; Stroncek, Dave F.] NIH Clin Ctr, Dept Transfus Med, Cell Proc Sect, Bethesda, MD USA.
[Morisot, Sebastien; Civin, Curt I.] Univ Maryland, Sch Med, Ctr Stem Cell Biol & Regenerat Med, Baltimore, MD 21201 USA.
[Morisot, Sebastien; Civin, Curt I.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
[Levine, Bruce L.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
RP Mackall, CL (reprint author), NCI, Immunol Sect, Pediat Oncol Branch, Bldg 10-CRC,1W-3750,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA.
EM cm35c@nih.gov
RI Levine, Bruce/D-1688-2009
FU National Institutes of Health
FX Supported by the Intramural Research Program of the National Institutes
of Health.
NR 44
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U1 4
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAR
PY 2011
VL 34
IS 2
BP 187
EP 195
DI 10.1097/CJI.0b013e31820d2a21
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 719FG
UT WOS:000287186200008
PM 21304401
ER
PT J
AU Mbulaiteye, SM
Goedert, JJ
AF Mbulaiteye, Sam M.
Goedert, James J.
TI Human Herpesvirus 8 Seropositivity in Rural Uganda: Maturation of
Sero-epidemiological Studies
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID SARCOMA-ASSOCIATED HERPESVIRUS; SICKLE-CELL-DISEASE; KAPOSIS-SARCOMA;
AFRICAN POPULATION; TRANSMISSION; INFECTION; SEROPREVALENCE; CHILDREN;
TRANSFUSION; PREVALENCE
C1 [Mbulaiteye, Sam M.; Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Goedert, JJ (reprint author), 6120 Execut Blvd,Execut Plaza S,Rm 7068,MSC 7248, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
FU Intramural NIH HHS
NR 26
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2011
VL 203
IS 5
BP 575
EP 577
DI 10.1093/infdis/jiq094
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 717FD
UT WOS:000287028000002
PM 21273189
ER
PT J
AU Johnson, KE
Redd, AD
Quinn, TC
Collinson-Streng, AN
Cornish, T
Kong, XR
Sharma, R
Tobian, AAR
Tsai, B
Sherman, ME
Kigozi, G
Serwadda, D
Wawer, MJ
Gray, RH
AF Johnson, Kristine E.
Redd, Andrew D.
Quinn, Thomas C.
Collinson-Streng, Aleisha N.
Cornish, Toby
Kong, Xiangrong
Sharma, Rajni
Tobian, Aaron A. R.
Tsai, Benjamin
Sherman, Mark E.
Kigozi, Godfrey
Serwadda, David
Wawer, Maria J.
Gray, Ronald H.
TI Effects of HIV-1 and Herpes Simplex Virus Type 2 Infection on Lymphocyte
and Dendritic Cell Density in Adult Foreskins from Rakai, Uganda
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL; CD4(+)
T-CELLS; MALE CIRCUMCISION; GASTROINTESTINAL-TRACT; HSV-2 REACTIVATION;
SIV INFECTION; TARGET-CELLS; MEN; DEPLETION
AB Methods. Immunostained CD1a(+) dendritic cell and CD4(+) and CD8(+) T cell densities were quantified in foreskin samples obtained from medical circumcision in Rakai, Uganda (35 HIV-infected, HSV-2-infected men; 5 HIV-infected, HSV-2-uninfected men; 22 HIV-uninfected, HSV-2-infected men; and 29 HIV-uninfected, HSV-2-uninfected men.
Results. CD1A(+) dendritic cell densities did not vary by HIV or HSV-2 status. Compared with densities in HIV-uninfected, HSV-2-uninfected men (mean, 26.8 cells/mm(2)), CD4(+) T cell densities were similar in the HIV-infected, HSV-2-infected group (mean, 28.7 cells/mm(2)), were significantly decreased in the HIV-infected, HSV-2-uninfected group (mean, 11.2; P < .05), and were increased in the HIV-uninfected, HSV-2-infected group (mean, 68.7; P < .05). Dermal CD8(+) T cell densities were higher in the HIV and HSV-2-coinfected group (mean, 102.9) than in the HIV-uninfected, HSV-2-uninfected group (mean, 10.0; P < .001), the HIV-infected, HSV-2-uninfected group (mean, 27.3; P < .001), and the HIV-uninfected, HSV-2-infected group (mean, 25.3; P < .005).
Discussion. The increased CD4(+) cellular density in the HIV-uninfected, HSV-2-infected men may help to explain why HSV-2-infected men are at increased risk of HIV acquisition. The absence of this increase in men coinfected with both HIV and HSV-2 is likely in part the result of the progressive loss of CD4(+) cells in HIV infection. Conversely, HIV and HSV-2 coinfection appears to synergistically increase CD8(+) T cell densities.
C1 [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Div Infect Dis,Dept Med, Baltimore, MD 21205 USA.
[Cornish, Toby; Sharma, Rajni; Tobian, Aaron A. R.; Tsai, Benjamin] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Kong, Xiangrong; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA.
[Redd, Andrew D.; Quinn, Thomas C.; Collinson-Streng, Aleisha N.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, NIH, Rockville, MD USA.
[Kigozi, Godfrey; Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Div Infect Dis,Dept Med, Rangos Bldg,Rm 530,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn@jhmi.edu
RI Cornish, Toby/A-4394-2015
OI Cornish, Toby/0000-0002-1902-2109
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [K23AI083100]; Division of Intramural Research,
National Institute of Allergy; Division of Infectious Diseases, National
Cancer Institute, National Institutes of Health
FX Bristol-Myers Squibb virology fellowship and support from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health (K23AI083100) to KEJ; and Divisions of Intramural Research,
National Institute of Allergy and Infectious Diseases, National Cancer
Institute, National Institutes of Health.
NR 25
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U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2011
VL 203
IS 5
BP 602
EP 609
DI 10.1093/infdis/jiq091
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 717FD
UT WOS:000287028000006
PM 21220779
ER
PT J
AU Goepfert, PA
Elizaga, ML
Sato, A
Qin, L
Cardinali, M
Hay, CM
Hural, J
DeRosa, SC
DeFawe, OD
Tomaras, GD
Montefiori, DC
Xu, YX
Lai, LL
Kalams, SA
Baden, LR
Frey, SE
Blattner, WA
Wyatt, LS
Moss, B
Robinson, HL
AF Goepfert, Paul A.
Elizaga, Marnie L.
Sato, Alicia
Qin, Li
Cardinali, Massimo
Hay, Christine M.
Hural, John
DeRosa, Stephen C.
DeFawe, Olivier D.
Tomaras, Georgia D.
Montefiori, David C.
Xu, Yongxian
Lai, Lilin
Kalams, Spyros A.
Baden, Lindsey R.
Frey, Sharon E.
Blattner, William A.
Wyatt, Linda S.
Moss, Bernard
Robinson, Harriet L.
CA Natl Inst Allergy Infect Dis
TI Phase 1 Safety and Immunogenicity Testing of DNA and Recombinant
Modified Vaccinia Ankara Vaccines Expressing HIV-1 Virus-like Particles
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID T-CELL RESPONSES; SIMIAN IMMUNODEFICIENCY; DNA/MVA VACCINE;
RHESUS-MONKEYS; TYPE-1 CLADE; MUCOSAL CHALLENGE; IMMUNE-RESPONSES;
PLASMID DNA; ALVAC-SIV; ENV
AB Methods. GeoVax pGA2/JS7 DNA (D) and MVA/HIV62 (M) vaccines encode noninfectious virus-like particles. Intramuscular needle injections were used to deliver placebo, 2 doses of DNA followed by 2 doses of rMVA (DDMM), one dose of DNA followed by 2 doses of rMVA (DMM), or 3 doses of rMVA (MMM) to HIV-seronegative participants.
Results. Local and systemic symptoms were mild or moderate. Immune response rates for CD4 + and CD8 + T cells were highest in the DDMM group and lowest in the MMM group (77% vs 43% CD4 + and 42% vs 17% CD8 +). In contrast, response rates for Env binding and neutralizing Ab were highest in the MMM group. The DMM group had intermediate response rates. A 1/10th-dose DDMM regimen induced similar T cell but reduced Ab response rates compared with the full-dose DDMM.
Conclusions. MVA62 was well tolerated and elicited different patterns of T cell and Ab responses when administered alone or in combination with the JS7 DNA vaccine.
C1 [Goepfert, Paul A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Elizaga, Marnie L.; Sato, Alicia; Qin, Li] Fred Hutchinson Canc Res Ctr, Core Operat Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA.
[Hural, John; DeRosa, Stephen C.; DeFawe, Olivier D.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA.
Univ Washington, Seattle, WA 98195 USA.
[Cardinali, Massimo; Wyatt, Linda S.; Moss, Bernard] NIAID, Bethesda, MD 20892 USA.
[Blattner, William A.] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
[Hay, Christine M.] Univ Rochester, Dept Med, New York, NY USA.
[Tomaras, Georgia D.; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Lai, Lilin] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Kalams, Spyros A.] Vanderbilt Univ, Sch Med, Dept Internal Med, Nashville, TN 37212 USA.
[Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Frey, Sharon E.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO 63103 USA.
RP Goepfert, PA (reprint author), Univ Alabama, Dept Med, 908 20th St S,CCB 328, Birmingham, AL 35294 USA.
EM paulg@uab.edu
RI Tomaras, Georgia/J-5041-2016
FU National Institute of Allergy and Infectious Diseases
FX This trial was conducted by the HIV Vaccine Trials Network and was
sponsored by the National Institute of Allergy and Infectious Diseases.
We gratefully acknowledge the participation and support of many
colleagues and staff at each site and are particularly grateful for the
participation of the 120 study participants. We also thank Molly
Swenson, Carter Bentley, and Huguette Redinger for their tireless
support in the daily operations of the protocol.
NR 35
TC 69
Z9 70
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2011
VL 203
IS 5
BP 610
EP 619
DI 10.1093/infdis/jiq105
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 717FD
UT WOS:000287028000007
PM 21282192
ER
PT J
AU Redd, AD
Gray, RH
Quinn, TC
AF Redd, Andrew D.
Gray, Ronald H.
Quinn, Thomas C.
TI Is Microbial Translocation a Cause or Consequence of HIV Disease
Progression?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
ID IMMUNE ACTIVATION; INFECTION; THERAPY; ABSENCE
C1 [Redd, Andrew D.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA.
[Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21215 USA.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, John G Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21215 USA.
EM tquinn@jhmi.edu
FU Intramural NIH HHS [ZIA AI000361-29]
NR 16
TC 16
Z9 16
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2011
VL 203
IS 5
BP 744
EP 745
DI 10.1093/infdis/jiq107
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 717FD
UT WOS:000287028000022
PM 21220777
ER
PT J
AU Oh, KS
Emmert, S
Tamura, D
DiGiovanna, JJ
Kraemer, KH
AF Oh, Kyu-Seon
Emmert, Steffen
Tamura, Deborah
DiGiovanna, John J.
Kraemer, Kenneth H.
TI Multiple Skin Cancers in Adults with Mutations in the XP-E (DDB2) DNA
Repair Gene
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
ID PIGMENTOSUM GROUP-E; UV-DAMAGED DNA; COMPLEMENTATION GROUP-E;
XERODERMA-PIGMENTOSUM; BINDING PROTEIN; 6-4 PHOTOPRODUCTS; CELL STRAINS;
RECOGNITION; P48; CLASSIFICATION
C1 [Oh, Kyu-Seon; Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Bethesda, MD 20892 USA.
[Emmert, Steffen] Goettingen Univ, Dept Dermatol, Gottingen, Germany.
RP Oh, KS (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
FU Intramural NIH HHS [ZIA BC004517-35]
NR 20
TC 11
Z9 11
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2011
VL 131
IS 3
BP 785
EP 788
DI 10.1038/jid.2010.352
PG 5
WC Dermatology
SC Dermatology
GA 719SQ
UT WOS:000287229700035
PM 21107348
ER
PT J
AU Young, H
AF Young, Howard
TI One small molecule: a new way to treat the flu?
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Editorial Material
DE interferons; secreted regulatory products; cytokines
ID FLAVONE ACETIC-ACID; AGENT 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID;
INTRACELLULAR DNA; INDUCTION; ACTIVATION; SENSOR; GENES; DMXAA
C1 NCI Frederick, Frederick, MD 21702 USA.
RP Young, H (reprint author), NCI Frederick, Chandler St,Bldg 560-31-23, Frederick, MD 21702 USA.
EM younghow@mail.nih.gov
NR 11
TC 0
Z9 0
U1 1
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2011
VL 89
IS 3
BP 327
EP 328
DI 10.1189/jlb.1010580
PG 2
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 727NL
UT WOS:000287807700003
PM 21357247
ER
PT J
AU Fejzo, MS
MacGibbon, KW
Romero, R
Goodwin, TM
Mullin, PM
AF Fejzo, Marlena S.
MacGibbon, Kimber W.
Romero, Roberto
Goodwin, T. Murphy
Mullin, Patrick M.
TI Recurrence Risk of Hyperemesis Gravidarum
SO JOURNAL OF MIDWIFERY & WOMENS HEALTH
LA English
DT Article
DE hyperemesis gravidarum; nausea; vomiting; pregnancy; recurrence
ID THYROTROPIN RECEPTOR; LARGE COHORT; PREGNANCY; HOSPITALIZATIONS;
OUTCOMES; NAUSEA; WOMEN
AB Methods: Women who registered on a Web site sponsored by the Hyperemesis Education and Research Foundation as having had one HG-complicated pregnancy were contacted to follow-up on a subsequent pregnancy. Participants completed an online survey.
Results: One hundred women responded. Fifty-seven had become pregnant again, 2 were trying to conceive, 37 were not willing to get pregnant again because of HG, and 4 did not have a second pregnancy for other reasons. Among the 57 women who responded that they had become pregnant again, 81% reported having severe nausea and vomiting in their second pregnancy. Among the women reporting recurrent HG, 98% reported losing weight and taking prescribed medication for HG, 83% reported treatment with intravenous fluids, 20% reported treatment with total parenteral nutrition or nasogastric tube feeding, and 48% reported hospitalization for HG.
Discussion: This study demonstrates both a high recurrence rate of HG and a large percentage of women who change reproductive plans because of their experiences with HG.
C1 [Fejzo, Marlena S.; Goodwin, T. Murphy; Mullin, Patrick M.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[MacGibbon, Kimber W.] Hyperemesis Educ & Res Fdn, Leesburg, VA USA.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
RP Fejzo, MS (reprint author), Univ Calif Los Angeles, 5535 MRL,675 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM nvpstudy@usc.edu
OI MacGibbon, Kimber/0000-0002-6534-3114
FU National Institute of Child Health and Human Development, National
Institute of Health, Department of Health and Human Services
FX This research was supported in part by funds granted to T. Murphy
Goodwin by the Intramural Research Program of the National Institute of
Child Health and Human Development, National Institute of Health,
Department of Health and Human Services.
NR 23
TC 7
Z9 7
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-9523
J9 J MIDWIFERY WOM HEAL
JI J. Midwifery Women Health
PD MAR-APR
PY 2011
VL 56
IS 2
BP 132
EP 136
DI 10.1111/j.1542-2011.2010.00019.x
PG 5
WC Nursing
SC Nursing
GA 740AM
UT WOS:000288763900008
PM 21429077
ER
PT J
AU Liu, Y
Knobloch, HS
Grinevich, V
Aguilera, G
AF Liu, Y.
Knobloch, H. S.
Grinevich, V.
Aguilera, G.
TI Stress Induces Parallel Changes in Corticotrophin-Releasing Hormone
(CRH) Transcription and Nuclear Trans location of Transducer of
Regulated CAMP Response Element-Binding Activity 2 in Hypothalamic CRH
Neurones
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Article
DE TORC2; hypothalamus; corticotrophin-releasing hormone; transcription
ID GENE-EXPRESSION; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; CREB ACTIVITY;
CELL-LINE; IN-VIVO; RAT; PHOSPHORYLATION; GLUCOCORTICOIDS;
IDENTIFICATION; VASOPRESSIN
AB Recent studies in vitro have shown that the cAMP response element-binding (CREB) co-activator, transducer of regulated CREB activity (TORO, is required for transcriptional activation of the corticotrophin-releasing hormone (CRH) gene. To determine the physiological importance of TORC2 regulating CRH transcription during stress, we examined the localisation of TORC2 in CRH neurones, as well as the relationship between changes in CRH heterogeneous nuclear (hn)RNA, nuclear translocation of TORC2 and binding of TORC2 to the CRH promoter. Immunohistochemistry revealed TORC2 immunoreactivity (irTORC2) in the dorsolateral (magnocellular) and dorsomedial (parvocellular) regions of the hypothalamic paraventricular nucleus (PVN). Although staining was mostly cytosolic under basal conditions, there was a marked increase in nuclear irTORC2 in the dorsomedial region after 30 min of restraint, concomitant with increases in CRH hnRNA levels. Levels of nuclear irTORC2 and CRH hnRNA had returned to basal 4 h after stress. Double-staining immunohistochemistry showed TORC2 co-staining in 100% of detected CRH neurones, and nuclear translocation after 30 min of restraint in 61%. Cellular distribution of TORC2 in the dorsolateral PVN was unaffected by restraint. Chromatin immunoprecipitation experiments showed recruitment of TORC2 and phosphorylated CREB (pCREB) by the CRH promoter after 30 min of restraint, but 4 h after stress only pCREB was associated with the CRH promoter. The demonstration that TORC2 translocates to the nucleus of hypothalamic CRH neurones and interacts with the CRH promoter in conjunction with the activation of CRH transcription during restraint stress, provides strong evidence for the involvement of TORC2 in the physiological regulation of CRH transcription.
C1 [Liu, Y.; Aguilera, G.] PDEGEN, Sect Endocrine Physiol, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Knobloch, H. S.; Grinevich, V.] Max Planck Inst, Dept Mol Neurobiol, Heidelberg, Germany.
RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, PDEGEN, CRC, NIH Bldg 10,Rm 11E-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Greti_Aguilera@nih.gov
FU National Institute of Child Health and Human Development; Max Planck
Society
FX This work was supported by the Intramural Research Program, National
Institute of Child Health and Human Development and the Max Planck
Society. The authors thank Drs Sergey Khrulev and Gunter Giese for
technical help with triple staining and confocal microscopy.
NR 29
TC 13
Z9 13
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD MAR
PY 2011
VL 23
IS 3
BP 216
EP 223
DI 10.1111/j.1365-2826.2010.02101.x
PG 8
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 731KK
UT WOS:000288105000003
PM 21121974
ER
PT J
AU Cole, JT
Yarnell, A
Kean, WS
Gold, E
Lewis, B
Ren, M
McMullen, DC
Jacobowitz, DM
Pollard, HB
O'Neill, JT
Grunberg, NE
Dalgard, CL
Frank, JA
Watson, WD
AF Cole, Jeffrey T.
Yarnell, Angela
Kean, William S.
Gold, Eric
Lewis, Bobbi
Ren, Ming
McMullen, David C.
Jacobowitz, David M.
Pollard, Harvey B.
O'Neill, J. Timothy
Grunberg, Neil E.
Dalgard, Clifton L.
Frank, Joseph A.
Watson, William D.
TI Craniotomy: True Sham for Traumatic Brain Injury, or a Sham of a Sham?
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE craniotomy; cytokines; magnetic resonance imaging; Neurological Severity
Scale; traumatic brain injury
ID CONTROLLED CORTICAL IMPACT; MARROW STROMAL CELLS; RAT-BRAIN; COGNITIVE
DEFICITS; METABOLISM; MICE; MODEL; CHEMOKINES; ASTROCYTES; RESPONSES
AB Neurological dysfunction after traumatic brain injury (TBI) is caused by both the primary injury and a secondary cascade of biochemical and metabolic events. Since TBI can be caused by a variety of mechanisms, numerous models have been developed to facilitate its study. The most prevalent models are controlled cortical impact and fluid percussion injury. Both typically use "sham" (craniotomy alone) animals as controls. However, the sham operation is objectively damaging, and we hypothesized that the craniotomy itself may cause a unique brain injury distinct from the impact injury. To test this hypothesis, 38 adult female rats were assigned to one of three groups: control (anesthesia only); craniotomy performed by manual trephine; or craniotomy performed by electric dental drill. The rats were then subjected to behavioral testing, imaging analysis, and quantification of cortical concentrations of cytokines. Both craniotomy methods generate visible MRI lesions that persist for 14 days. The initial lesion generated by the drill technique is significantly larger than that generated by the trephine. Behavioral data mirrored lesion volume. For example, drill rats have significantly impaired sensory and motor responses compared to trephine or naive rats. Finally, of the seven tested cytokines, KC-GRO and IFN-gamma showed significant increases in both craniotomy models compared to naive rats. We conclude that the traditional sham operation as a control confers profound proinflammatory, morphological, and behavioral damage, which confounds interpretation of conventional experimental brain injury models. Any experimental design incorporating "sham" procedures should distinguish among sham, experimentally injured, and healthy/naive animals, to help reduce confounding factors.
C1 [Cole, Jeffrey T.; Kean, William S.; McMullen, David C.; Watson, William D.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Silver Spring, MD USA.
[Yarnell, Angela; Grunberg, Neil E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Silver Spring, MD USA.
[Ren, Ming; O'Neill, J. Timothy] Uniformed Serv Univ Hlth Sci, Dept Pediat, Silver Spring, MD USA.
[Jacobowitz, David M.; Pollard, Harvey B.; Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Silver Spring, MD USA.
[Gold, Eric; Lewis, Bobbi; Frank, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Cole, JT (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol, B-3012,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM jeffrey.cole@usuhs.mil
FU Department of Defense [60885-CNRM]; Comprehensive National Neuroscience
Program (CNNP [W81XWH-07-0679]
FX This work was supported by a grant from the Department of Defense
(60885-CNRM), and was performed at the Center for Neurosciences and
Regenerative Medicine (CNRM) and at the National Institutes of Health
(NIH). Additional support for this work was provided by the
Comprehensive National Neuroscience Program (CNNP, award number
W81XWH-07-0679), and the Intramural Research Program in the Clinical
Center at the NIH.
NR 49
TC 79
Z9 81
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR
PY 2011
VL 28
IS 3
BP 359
EP 369
DI 10.1089/neu.2010.1427
PG 11
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 734WD
UT WOS:000288370600003
PM 21190398
ER
PT J
AU Johnson, MA
Dwyer, JT
Jensen, GL
Miller, JW
Speakman, JR
Starke-Reed, P
Volpi, E
AF Johnson, Mary Ann
Dwyer, Johanna T.
Jensen, Gordon L.
Miller, Joshua W.
Speakman, John R.
Starke-Reed, Pamela
Volpi, Elena
TI Challenges and New Opportunities for Clinical Nutrition Interventions in
the Aged
SO JOURNAL OF NUTRITION
LA English
DT Article
ID FOLIC-ACID FORTIFICATION; CALORIE RESTRICTION MIMETICS; MUSCLE
PROTEIN-METABOLISM; ESSENTIAL AMINO-ACIDS; NEURAL-TUBE DEFECTS; EXTENDS
LIFE-SPAN; FOOD INSECURITY; OLDER-ADULTS; INSULIN-RESISTANCE; COGNITIVE
IMPAIRMENT
AB Nutritional status plays a critical role in the prevention and management of many chronic health conditions that are common in the elderly and are likely to become more prevalent as the population ages. This paper highlights several aspects of nutrition that require additional basic science and clinical application research to improve the health and wellbeing of older adults. Topics addressed are selected demographic and health indices, the uncertain benefits of energy restriction in aged humans compared with other species, the impact of food insecurity on health, the relationship between dietary protein and sarcopenia, the prevention and management of obesity while maintaining muscle mass and functional status, and controversy regarding high intakes of folic acid. Research needs regarding the safety, efficacy, and application of clinical interventions related to these topics also are discussed. J. Nutr. 141: 535-541, 2011.
C1 [Johnson, Mary Ann] Univ Georgia, Dept Food & Nutr, Athens, GA 30602 USA.
[Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Dwyer, Johanna T.] Tufts Univ, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Jensen, Gordon L.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Miller, Joshua W.] Univ Calif Davis, Dept Med Pathol & Lab Med, Davis, CA 95817 USA.
[Speakman, John R.] Univ Aberdeen, Dept Zool, Aberdeen AB24 2TZ, Scotland.
[Starke-Reed, Pamela] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA.
[Volpi, Elena] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA.
RP Johnson, MA (reprint author), Univ Georgia, Dept Food & Nutr, Athens, GA 30602 USA.
EM drmaryannjohnson@gmail.com; DwyerJ1@od.nih.gov
RI Volpi, Elena/I-4459-2012; John, Speakman/A-9494-2008;
OI John, Speakman/0000-0002-2457-1823; Volpi, Elena/0000-0001-8776-0384;
Dwyer, Johanna/0000-0002-0783-1769
FU Medical Nutrition Council; ASN Aging and Chronic Disease RIS; ASN; Egg
Nutrition Center
FX Published as a supplement to The Journal of Nutrition. Presented as part
of the symposium entitled "Aging 2010: Challenges and New Opportunities
for Intervention in the Clinical Nutrition Problems in the Aged" given
at the Experimental Biology 2010 meeting, April 24, 2010, in Anaheim,
CA. The symposium was cosponsored by the Medical Nutrition Council and
the ASN Aging and Chronic Disease RIS, and supported by an educational
grant from the Medical Nutrition Council. The symposium was chaired by
Johanna Dwyer, Mary Ann Johnson, and Edward Saltzman. Guest Editor for
this symposium publication was Elizabeth Gardner. Guest Editor
disclosure: Elizabeth Gardner had no relationships to disclose.;
Supported in part by unrestricted educational grants from the Medical
Nutrition Council, ASN, and the Egg Nutrition Center.
NR 90
TC 7
Z9 7
U1 1
U2 8
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD MAR
PY 2011
VL 141
IS 3
BP 535
EP 541
DI 10.3945/jn.110.131425
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 726LU
UT WOS:000287724600031
PM 21270372
ER
PT J
AU Sancarlo, D
D'Onofrio, G
Franceschi, M
Scarcelli, C
Niro, V
Addante, F
Copetti, M
Ferrucci, L
Fontana, L
Pilotto, A
AF Sancarlo, D.
D'Onofrio, G.
Franceschi, M.
Scarcelli, C.
Niro, V.
Addante, F.
Copetti, M.
Ferrucci, L.
Fontana, L.
Pilotto, A.
TI Validation of a modified-multidimensional prognostic index (m-MPI)
including the mini nutritional assessment short-form (MNA-SF) for the
prediction of one-year mortality in hospitalized elderly patients
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Multidimensional Prognostic Index (MPI); Mini Nutritional Assessment
Short Form (MNA-SF); mortality; prognosis; Comprehensive Geriatric
Assessment (CGA); survival
ID COMPREHENSIVE GERIATRIC ASSESSMENT; LONG-TERM MORTALITY; OLDER PATIENTS;
PEOPLE; UNDERNUTRITION; MALNUTRITION; HISTORY; DEFICIT; DEATH; CARE
AB The mortality prediction represents a key factor in the managing of elderly hospitalized patients. Since in older subjects mortality results from a combination of biological, functional, nutritional, psychological and environmental factors, a Multidimensional Prognostic Index (MPI) that predict short- and long-term mortality based on a standardized comprehensive geriatric assessment (CGA) has recently been developed and validated.
This study compares the accuracy in predicting the mortality of the MPI with a modified version of the MPI (m-MPI) that included the Mini Nutritional Assessment-Short Form (MNA-SF) instead of the standard MNA.
This prospective study with a one-year follow-up included 4088 hospitalized patients aged 65 years and older. A standardized CGA that included information on functional (Activities of Daily Living, ADL and Instrumental-ADL), cognitive (Short Portable Mental Status Questionnaire), risk of pressure sore (Exton-Smith Scale), comorbidities (CIRS Index), medications, living status and nutritional status (MNA and MNA-SF) was used to calculate the MPI using a previously validated algorithm.
Higher MPI values were significantly associated with higher mortality rates with a close agreement between the estimated and the observed mortality both after 1-month (MPI1=2.8% versus m-MPI1=2.8%,p=0.946; MPI2=8.9% versus m-MPI2=9%,p=0.904; MPI3=21.9% versus m-MPI3=21.9,p=0.978) and 1-year of follow-up (MPI1=10.8% versus m-MPI1=10.5%,p=0.686; MPI2=27.3% versus m-MPI2=28%, p=0.495; MPI3=52.8% versus m-MPI3=52.7%,p=0.945). The estimated areas under the receiver operating characteristics (ROC) curves suggested a clinically negligible difference between the two indices.
The m-MPI is as sensitive as the MPI in stratifying hospitalized elderly patients into groups at varying risk of short- and long-term mortality, but with fewer items.
C1 [Sancarlo, D.; D'Onofrio, G.; Franceschi, M.; Scarcelli, C.; Niro, V.; Addante, F.; Pilotto, A.] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, I-71013 San Giovanni Rotondo, FG, Italy.
[Sancarlo, D.; D'Onofrio, G.; Franceschi, M.; Scarcelli, C.; Niro, V.; Addante, F.; Pilotto, A.] IRCCS Casa Sollievo Sofferenza, Gerontol Geriatr Res Lab, Dept Med Sci, I-71013 San Giovanni Rotondo, FG, Italy.
[Copetti, M.] IRCCS Casa Sollievo Sofferenza, Biostat Unit, I-71013 San Giovanni Rotondo, Italy.
[Ferrucci, L.] Harbor Hosp Ctr, Natl Inst Aging, Longitudinal Studies Sect, Baltimore, MD USA.
[Fontana, L.] Ist Super Sanita, Div Nutr & Aging, I-00161 Rome, Italy.
[Fontana, L.] Washington Univ, Div Geriatr & Nutr Sci, St Louis, MO USA.
RP Pilotto, A (reprint author), IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, Viale Cappuccini 1, I-71013 San Giovanni Rotondo, FG, Italy.
EM alberto.pilotto@operapadrepio.it
RI Copetti, Massimiliano/K-3186-2016; D'Onofrio, Grazia/K-9740-2016;
Sancarlo, Daniele/C-1056-2017
OI Copetti, Massimiliano/0000-0002-7960-5947; D'Onofrio,
Grazia/0000-0002-5905-6063; Sancarlo, Daniele/0000-0001-9541-6364
FU Ministero della Salute (Italy); IRCCS; National Institute of Aging,
Baltimore, USA
FX This work was fully supported by grants from Ministero della Salute
(Italy), IRCCS Research Program 2009-2011, Line 2: "Malattie complesse"
and by the Intramural Research Program of the National Institute of
Aging, Baltimore, USA".
NR 26
TC 18
Z9 19
U1 1
U2 11
PU SPRINGER FRANCE
PI PARIS
PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE
SN 1279-7707
EI 1760-4788
J9 J NUTR HEALTH AGING
JI J. Nutr. Health Aging
PD MAR
PY 2011
VL 15
IS 3
BP 169
EP 173
DI 10.1007/s12603-010-0293-5
PG 5
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA 739WU
UT WOS:000288752900003
PM 21369662
ER
PT J
AU Sebastian, A
Matsushita, T
Kawanami, A
Mackem, S
Landreth, GE
Murakami, S
AF Sebastian, Arjun
Matsushita, Takehiko
Kawanami, Aya
Mackem, Susan
Landreth, Gary E.
Murakami, Shunichi
TI Genetic Inactivation of ERK1 and ERK2 in Chondrocytes Promotes Bone
Growth and Enlarges the Spinal Canal
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE ERK; chondrocytes; bone growth; synchondrosis; achondroplasia
ID FACTOR RECEPTOR-3; GERMLINE MUTATIONS; TRANSGENIC MICE; MAPK PATHWAY;
ACHONDROPLASIA; DWARFISM; KINASE; PROLIFERATION; OSSIFICATION;
EXPRESSION
AB Activating mutations in FGFR3 cause the most common forms of human dwarfism: achondroplasia and thanatophoric dysplasia. In mouse models of achondroplasia, recent studies have implicated the ERK MAPK pathway, a pathway activated by FGFR3, in creating reduced bone growth. Our recent studies have indicated that increased Fgfr3 and ERK MAPK signaling in chondrocytes also causes premature synchondrosis closure in the cranial base and vertebrae, accounting for the sometimes fatal stenosis of the foramen magnum and spinal canal in achondroplasia. Conversely, whether the decrease or inactivation of ERK1 and ERK2 promotes bone growth and delays synchondrosis closure remains to be investigated. In this study, we inactivated ERK2 in the chondrocytes of ERK1-null mice using the Col2a1-Cre and Col2a1-CreER transgenes. We found that the genetic inactivation of ERK1 and ERK2 in chondrocytes enhances the growth of cartilaginous skeletal elements. We also found that the postnatal inactivation of ERK1 and ERK2 in chondrocytes delays synchondrosis closure and enlarges the spinal canal. These observations make ERK1 and ERK2 an attractive target for the treatment of achondroplasia and other FGFR3-related skeletal syndromes. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:375-379, 2011
C1 [Sebastian, Arjun; Matsushita, Takehiko; Kawanami, Aya; Murakami, Shunichi] Case Western Reserve Univ, Dept Orthopaed, Cleveland, OH 44106 USA.
[Mackem, Susan] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.
[Landreth, Gary E.] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA.
[Murakami, Shunichi] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
RP Murakami, S (reprint author), Case Western Reserve Univ, Dept Orthopaed, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM shun@case.edu
FU Crile Fellowship; March of Dimes Birth Defects Foundation [6-FY06-341];
NIH [R21DE017406, R01AR055556]
FX We thank Richard Behringer for Col2a1-Cre mice. We also thank Valerie
Schmedlen for editorial assistance. This work was supported by Crile
Fellowship to A.S. and research grant no. 6-FY06-341 from the March of
Dimes Birth Defects Foundation and NIH grants R21DE017406 and
R01AR055556 to S.M.
NR 29
TC 21
Z9 23
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD MAR
PY 2011
VL 29
IS 3
BP 375
EP 379
DI 10.1002/jor.21262
PG 5
WC Orthopedics
SC Orthopedics
GA 719BF
UT WOS:000287173500011
PM 20922792
ER
PT J
AU Ogge, G
Romero, R
Lee, DC
Gotsch, F
Than, NG
Lee, J
Chaiworapongsa, T
Dong, Z
Mittal, P
Hassan, SS
Kim, CJ
AF Ogge, Giovanna
Romero, Roberto
Lee, Deug-Chan
Gotsch, Francesca
Than, Nandor Gabor
Lee, JoonHo
Chaiworapongsa, Tinnakom
Dong, Zhong
Mittal, Pooja
Hassan, Sonia S.
Kim, Chong Jai
TI Chronic chorioamnionitis displays distinct alterations of the amniotic
fluid proteome
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE amniotic fluid; proteome; chronic chorioamnionitis; preterm birth
ID PLACENTAL PROTEIN-14; SPONTANEOUS LABOR; GLYCODELIN-A; INTRAAMNIOTIC
INFECTION; ENDOMETRIAL PROTEIN; PRETERM LABOR; T-CELLS; PROSTAGLANDIN
CONCENTRATIONS; UREAPLASMA-UREALYTICUM; ZONA-PELLUCIDA
AB Acute chorioamnionitis of infectious origin and chronic chorioamnionitis of immunological origin are two major placental lesions of spontaneous preterm birth with elevated amniotic fluid interleukin-6 and CXCL10 concentrations, respectively. The changes in the amniotic fluid proteome associated with intra-amniotic infection and acute chorioamnionitis are well defined, yet alterations unique to chronic chorioamnionitis remain to be elucidated. This study was conducted to determine those amniotic fluid proteins changing specifically in the presence of chronic chorioamnionitis. Amniotic fluid obtained from acute chorioamnionitis, chronic chorioamnionitis and gestational age-matched controls were analysed by two-dimensional (2D) difference in gel electrophoresis and MALDI-TOF analyses. The type of histological inflammation was used to define each condition in preterm labour cases (n = 125) and term not in labour cases (n = 22), and the amniotic fluid concentrations of interleukin-6, CXCL8, CXCL10 and prostaglandin F-2 alpha were also measured by specific immunoassays. Among preterm labour cases, 31 differentially expressed proteins were identified in chronic chorioamnionitis cases as compared to both acute chorioamnionitis and control cases. Importantly, glycodelin-A, which maintains maternal tolerance against an allogeneic fetus, was decreased in chronic chorioamnionitis, while haptoglobin was increased. We report the amniotic fluid proteome of chronic chorioamnionitis for the first time, and the findings herein strongly suggest that there is a pathophysiological association between the changes of immunomodulatory proteins in the amniotic fluid and chronic chorioamnionitis, a histological manifestation of maternal anti-fetal allograft rejection. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Ogge, Giovanna; Romero, Roberto; Lee, Deug-Chan; Gotsch, Francesca; Than, Nandor Gabor; Lee, JoonHo; Chaiworapongsa, Tinnakom; Dong, Zhong; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Ogge, Giovanna; Romero, Roberto; Lee, Deug-Chan; Gotsch, Francesca; Than, Nandor Gabor; Lee, JoonHo; Chaiworapongsa, Tinnakom; Dong, Zhong; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto; Chaiworapongsa, Tinnakom; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
RP Kim, CJ (reprint author), Wayne State Univ, Sch Med, Hutzel Womens Hosp, Dept Pathol, Room 4620,3990 John R, Detroit, MI 48201 USA.
EM cjkim@med.wayne.edu
RI Ogge, Giovanna/G-6109-2011
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This work was supported (in part) by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS. The authors
would like to thank Dr Hongjin Huang for her excellent technical support
in proteomic analysis. The authors are grateful to the patients who
agreed to participate in our studies, the nurses, laboratory staff and
clinicians who made this work possible.
NR 59
TC 23
Z9 23
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD MAR
PY 2011
VL 223
IS 4
BP 553
EP 565
DI 10.1002/path.2825
PG 13
WC Oncology; Pathology
SC Oncology; Pathology
GA 725UQ
UT WOS:000287672100011
PM 21294128
ER
PT J
AU Dougherty, KA
Schall, JI
Rovner, AJ
Stallings, VA
Zemel, BS
AF Dougherty, Kelly A.
Schall, Joan I.
Rovner, Alisha J.
Stallings, Virginia A.
Zemel, Babette S.
TI Attenuated Maximal Muscle Strength and Peak Power in Children With
Sickle Cell Disease
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE anaerobic performance; handgrip; force plate; growth; body composition
ID ENERGY-EXPENDITURE; BODY-COMPOSITION; ANEMIA; PERFORMANCE; ADOLESCENTS;
VELOCITY; YOUNG
AB Dominant hand maximal handgrip strength evaluated with a handgrip dynamometer and peak power evaluated with a force plate, adjusted for body size and composition, were compared in African-American children aged 5 to 13 years, with and without type SS sickle cell disease (SCD-SS). Children with SCD-SS (n = 35; age, 9.0 +/- 2.0 y) compared with healthy control children (n = 103; age, 8.6 +/- 1.8 y) did not differ by age, sex, or pubertal status, yet had significantly lower Z scores for height, weight, body mass index, upper arm muscle area, upper arm fat area, fat mass-for-height and lean mass-for-height. Children with SCD-SS had significantly lower handgrip strength (12.7 +/- 3.3 vs. 15.2 +/- 5.1 kg, P < 0.008), peak power (882 +/- 298 vs. 1167 +/- 384 W, P < 0.001), and growth and body composition adjusted Z scores for handgrip strength (0.6 +/- 1.3 standard deviations, P < 0.004) and peak power (male children = 1.0 +/- 0.8 standard deviations, P < 0.0002; female children = 1.0 +/- 1.7 standard deviations, P < 0.006). Maximal muscle strength and peak power are attenuated in children with SCD-SS compared with healthy control children beyond expectation for growth and body composition deficits suggesting that additional factors contribute to attenuation in anaerobic performance.
C1 [Dougherty, Kelly A.; Schall, Joan I.; Stallings, Virginia A.; Zemel, Babette S.] Childrens Hosp Philadelphia, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA.
[Stallings, Virginia A.; Zemel, Babette S.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Rovner, Alisha J.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD USA.
RP Dougherty, KA (reprint author), Childrens Hosp Philadelphia, Dept Pediat, Div Gastroenterol Hepatol & Nutr, 3535 Market St,Room 1556, Philadelphia, PA 19104 USA.
EM doughertyk@email.chop.edu
FU Comprehensive Sickle Cell Center (NIH) [5 U54 HL070596]; Clinical
Translational Research Center [UL1-RR-024134]; CHOP Nutrition Center
FX Supported by Comprehensive Sickle Cell Center (NIH 5 U54 HL070596),
Clinical Translational Research Center (UL1-RR-024134), and CHOP
Nutrition Center.
NR 24
TC 9
Z9 9
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD MAR
PY 2011
VL 33
IS 2
BP 93
EP 97
DI 10.1097/MPH.0b013e318200ef49
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 725MM
UT WOS:000287648800016
PM 21228717
ER
PT J
AU Wiener, LS
Kohrt, BA
Battles, HB
Pao, M
AF Wiener, Lori S.
Kohrt, Brie-Anne
Battles, Haven B.
Pao, Maryland
TI The HIV Experience: Youth Identified Barriers for Transitioning from
Pediatric to Adult Care
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Article
DE adolescents; healthcare; HIV; AIDS; transition; young adults
ID ACTIVE ANTIRETROVIRAL THERAPY; HEALTH-CARE; YOUNG-ADULTS; ADOLESCENTS;
INFECTION; CHILDREN; ADHERENCE; ISSUES; PERSPECTIVES; DISORDERS
AB Objective The aim of this study was to explore the experiences of youth living with HIV who transitioned from pediatric to adult care. Methods Semi-structured telephone interviews were conducted with 59 youth (mean age = 22 years) living with HIV about the transition experience, demographics, and health status. Results Of youth who transitioned to adult care, immune function (CD4) trended downward, 45% found the transition more difficult than anticipated, and 32% could not find emotional support services. Youth identified the need for increased continuity of care, assistance with logistics, improved communication with providers and caregivers, and individualized management of their transition process. Conclusion Without adequate preparation, the transition process can be compromised with potentially serious health consequences. Youth living with HIV seek adult providers that can provide developmentally appropriate transition interventions that address loss, disclosure, and sexual behavior along with medical needs.
C1 [Wiener, Lori S.; Kohrt, Brie-Anne; Battles, Haven B.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pao, Maryland] NIMH, NIH, Bethesda, MD 20892 USA.
RP Wiener, LS (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
RI Hanghoj, Signe/E-2440-2012
FU Intramural NIH HHS
NR 48
TC 37
Z9 37
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD MAR
PY 2011
VL 36
IS 2
BP 141
EP 154
DI 10.1093/jpepsy/jsp129
PG 14
WC Psychology, Developmental
SC Psychology
GA 726RK
UT WOS:000287743600003
PM 20040607
ER
PT J
AU Han, JC
Damaso, L
Welch, S
Balagopal, P
Hossain, J
Mauras, N
AF Han, Joan C.
Damaso, Ligeia
Welch, Susan
Balagopal, Prabhakaran
Hossain, Jobayer
Mauras, Nelly
TI Effects of Growth Hormone and Nutritional Therapy in Boys with
Constitutional Growth Delay: A Randomized Controlled Trial
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID IDIOPATHIC SHORT STATURE; ENERGY DENSITY; ADULT HEIGHT; CHILDREN;
PUBERTY; COMPENSATION; METABOLISM; RESISTANCE; FOOD; MEN
AB Objective To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM).
Study design We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age, 9.3 +/- 1.3 years) with CDGM (height standard deviation score, -2.0 +/- 0.5; bone age delay, 1.8 +/- 0.8 years; body mass index standard deviation score, -1.2 +/- 1.0; peak stimulated GH, 15.7 +/- 7.7 ng/mL), who were randomized (n = 10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. t tests and repeated measures analyses of variance compared energy intake, total energy expenditure (TEE), growth, hormones, and nutrition markers.
Results Energy intake was increased at 6 months within the nutrition group (P = .04), but not the observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/nutrition group at 12 months (P < .01), but not in the GH group versus baseline. Height, weight, lean body mass, hormones, and nutrition markers increased comparably in both groups throughout 18 months.
Conclusion Boys with CDGM use energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients. (J Pediatr 2011;158:427-32).
C1 [Han, Joan C.; Damaso, Ligeia; Welch, Susan; Mauras, Nelly] Nemours Childrens Clin, Div Endocrinol, Jacksonville, FL 32207 USA.
[Han, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Mauras, N (reprint author), Nemours Childrens Clin, Div Endocrinol, 807 Childrens Way, Jacksonville, FL 32207 USA.
EM nmauras@nemours.org
FU Genentech Center for Clinical Research in Endocrinology; National
Institutes of Health
FX M.M. received a research grant from the Genentech Center for Clinical
Research in Endocrinology to conduct this study. J.H. is a commissioned
officer in the US Public Health Service and is supported by the
Intramural Research Program of the National Institutes of Health.
Genentech provided growth hormone and Ross Laboratories provided the
nutritional supplement for these studies. The authors declare no
conflicts of interest.
NR 32
TC 2
Z9 3
U1 0
U2 2
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 MAR
PY 2011
VL 158
IS 3
BP 427
EP 432
DI 10.1016/j.jpeds.2010.09.006
PG 6
WC Pediatrics
SC Pediatrics
GA 719TI
UT WOS:000287231800018
PM 20961566
ER
PT J
AU Cao, Y
Chen, AM
Jones, RL
Radcliffe, J
Dietrich, KN
Caldwell, KL
Peddada, S
Rogan, WJ
AF Cao, Yang
Chen, Aimin
Jones, Robert L.
Radcliffe, Jerilynn
Dietrich, Kim N.
Caldwell, Kathleen L.
Peddada, Shyamal
Rogan, Walter J.
TI Efficacy of Succimer Chelation of Mercury at Background Exposures in
Toddlers: A Randomized Trial
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID PRENATAL METHYLMERCURY EXPOSURE; SEYCHELLES CHILD-DEVELOPMENT; FISH
CONSUMPTION; CLINICAL-TRIAL; THERAPY; LEAD; DMSA; DMPS; AGE; ACID
AB Objective To examine whether succimer, a mercaptan compound known to reduce blood lead concentration in children, reduces blood mercury concentration.
Study design We used samples from a randomized clinical trial of succimer chelation for lead-exposed children. We measured mercury levels in pre-treatment samples from 767 children. We also measured mercury levels in blood samples drawn 1 week after treatment began (n = 768) and in a 20% random sample of the children who received the maximum 3 courses of treatment (n = 67). A bootstrap-based isotonic regression method was used to compare the trend with time in the difference between the adjusted mean mercury concentrations in the succimer group and that in the placebo group.
Results The adjusted mean organic mercury concentration in the succimer group relative to the placebo group fell from 99% at baseline to 82% after 3 courses of treatment (P for trend = .048), but this resulted from the prevention of the age-related increase in the succimer group.
Conclusion Succimer chelation for low level organic mercury exposure in children has limited efficacy. (J Pediatr 2011;158:480-5).
C1 [Cao, Yang; Rogan, Walter J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Cao, Yang] Second Mil Med Univ, Fac Hlth Serv, Dept Hlth Stat, Shanghai, Peoples R China.
[Chen, Aimin; Dietrich, Kim N.] Univ Cincinnati, Coll Med, Dept Environm Hlth, Div Epidemiol & Biostat, Cincinnati, OH 45267 USA.
[Jones, Robert L.; Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Inorgan & Radiat Analyt Toxicol Branch, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
[Radcliffe, Jerilynn] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Radcliffe, Jerilynn] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Peddada, Shyamal] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA.
RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM rogan@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012; Rogan, Walter/I-6034-2012;
OI Rogan, Walter/0000-0002-9302-0160; Cao, Yang/0000-0002-3552-9153
FU National Institute of Environmental Health Sciences; National Center for
Minority Health and Health Disparities at the National Institutes of
Health; Center for Environmental Health at the Centers for Disease
Control
FX Supported by the National Institute of Environmental Health Sciences
Intramural Research Program, National Center for Minority Health and
Health Disparities at the National Institutes of Health, and Center for
Environmental Health at the Centers for Disease Control. Chemet and
placebo were gifts from McNeil Labs, Fort Washington, PA. The authors
declare no conflicts of interest.
NR 38
TC 12
Z9 12
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2011
VL 158
IS 3
BP 480
EP U164
DI 10.1016/j.jpeds.2010.08.036
PG 7
WC Pediatrics
SC Pediatrics
GA 719TI
UT WOS:000287231800029
PM 20889164
ER
PT J
AU Kim, BJ
Romero, R
Lee, SM
Park, CW
Park, JS
Jun, JK
Yoon, BH
AF Kim, Byoung Jae
Romero, Roberto
Lee, Seung Mi
Park, Chan-Wook
Park, Joong Shin
Jun, Jong Kwan
Yoon, Bo Hyun
TI Clinical significance of oligohydramnios in patients with preterm labor
and intact membranes
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine
CY FEB 05-10, 2007
CL San Francisco, CA
SP Soc Maternal Fetal Med (SMFM)
DE Amniocentesis-to-delivery interval; intra-amniotic inflammation;
oligohydramnios; prematurity; preterm labor
ID AMNIOTIC-FLUID INTERLEUKIN-6; INFLAMMATORY RESPONSE SYNDROME;
NECROSIS-FACTOR-ALPHA; PREMATURE RUPTURE; INTRAAMNIOTIC
INFECTION/INFLAMMATION; INTRAUTERINE INFECTION; PRELABOR RUPTURE;
COMPLEMENT ACTIVATION; NORMAL-PREGNANCY; CEREBRAL-PALSY
AB Objective: To determine the frequency and clinical significance of oligohydramnios in patients with preterm labor and intact membranes.
Study design: An amniotic fluid index (AFI) was determined before amniocentesis (< 24 h) in 272 patients with preterm labor and intact membranes (< 35 weeks of gestation). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and assayed for matrix metalloproteinase-8 (MMP-8). Non-parametric statistical techniques and survival analysis were used.
Results: 1) The overall prevalence of oligohydramnios (AFI of <= 5 cm) in patients with preterm labor and intact membranes was 2.6% (7/272); 2) patients with oligohydramnios had a higher frequency of AF infection and/or inflammation than those without oligohydramnios [85.7% (6/7) vs. 32.8% (87/265); P < 0.01]; 3) patients with oligohydramnios had a higher median AF MMP-8 concentration than those without oligohydramnios [median 664.2 (range 16.6-3424.7) ng/mL vs. median 2.3 (range < 0.3-6142.6) ng/mL; P < 0.01]; 4) women with preterm labor and oligohydramnios had a shorter interval to delivery than those without oligohydramnios [median 18 h (range 0-74 h) vs. median 311 h (range 0-3228 h); P < 0.01], and this difference remained significant after adjusting for gestational age and the presence or absence of AF infection/inflammation.
Conclusion: Patients with preterm labor and oligohydramnios are at increased risk for impending preterm delivery and intra-amniotic inflammation and, therefore, may benefit from careful surveillance.
C1 [Kim, Byoung Jae; Lee, Seung Mi; Park, Chan-Wook; Park, Joong Shin; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Kim, Byoung Jae] Seoul Metropolitan Govt Seoul Natl Univ, Boramae Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Lee, Seung Mi; Park, Chan-Wook; Park, Joong Shin; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ Hosp, Dept Obstet & Gynecol, Seoul 110744, South Korea.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
EM yoonbh@snu.ac.kr
RI Park, Chan-Wook/J-5498-2012; Yoon, Bo Hyun/H-6344-2011; Jun, Jong
Kwan/D-5776-2012;
OI Jun, Jong Kwan/0000-0002-0242-1736; Park, Joong Shin/0000-0002-5246-0477
FU Intramural NIH HHS [ZIA HD002400-18]
NR 57
TC 8
Z9 13
U1 0
U2 2
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD MAR
PY 2011
VL 39
IS 2
BP 131
EP 136
DI 10.1515/JPM.2010.168
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 733EP
UT WOS:000288245600004
PM 21265728
ER
PT J
AU Watts, DH
Huang, S
Culnane, M
Kaiser, KA
Scheuerle, A
Mofenson, L
Stanley, K
Newell, ML
Mandelbrot, L
Delfraissy, JF
Cunningham, CK
AF Watts, D. Heather
Huang, Sharon
Culnane, Mary
Kaiser, Kathleen A.
Scheuerle, Angela
Mofenson, Lynne
Stanley, Kenneth
Newell, Marie-Louise
Mandelbrot, Laurent
Delfraissy, Jean-Francois
Cunningham, Coleen K.
TI Birth defects among a cohort of infants born to HIV-infected women on
antiretroviral medication
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Antiretrovirals; birth defects; HIV
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONGENITAL-ABNORMALITIES; IN-UTERO;
THERAPY; ZIDOVUDINE; PREGNANCY; EXPOSURE; CHILDREN; HEART; TRANSMISSION
AB Objective: To determine rate of and risk factors for birth defects in infants born to HIV-infected women receiving nucleoside and protease inhibitor antiretroviral (ARV) therapy.
Methods: Birth defects were evaluated among infants on the Pediatric AIDS Clinical Trials Group 316 trial that studied addition of peripartum nevirapine to established ARV regimen for prevention of mother-to-child transmission. Maternal therapy was categorized by trimester of earliest exposure. Birth defects were coded using conventions of the Antiretroviral Pregnancy Registry.
Results: Birth defects were detected in 60/1414 (4.2%; 95% CI 3.3-5.4%) infants including 30/636 (4.7%; 95% CI 3.2-6.7%) with first trimester ARV exposure and 30/778 (3.9%; 95% CI 2.6-5.5%) with exposure only after the first trimester (P=0.51). Rates of classes of defects were similar between first trimester compared to later exposure groups except heart defects which occurred in 16 (2.5%; 95% CI 1.4-4.1%) with first trimester ARV exposure and in six (0.8%; 95% CI 0.3-1.7%) infants with later exposure (P=0.02). Exposure to ARV was not associated with specific types of heart defects. Two cases of cardiomyopathy were noted.
Conclusion: ARV use in early pregnancy was not associated with an increased risk of birth defects overall. The possible association of ARV exposure with heart defects requires further surveillance.
C1 [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, PAMA, CRMC, Bethesda, MD 20892 USA.
[Huang, Sharon; Stanley, Kenneth] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Culnane, Mary] NIAID, Bethesda, MD 20892 USA.
[Kaiser, Kathleen A.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Scheuerle, Angela] Tesserae Genet, Dallas, TX USA.
[Newell, Marie-Louise] UCL, Inst Child Hlth, London, England.
[Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr, Durban, South Africa.
[Mandelbrot, Laurent] Univ Paris Diderot, Colombes, France.
[Delfraissy, Jean-Francois] Agence Natl Rech SIDA, Paris, France.
[Cunningham, Coleen K.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
RP Watts, DH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, PAMA, CRMC, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA.
EM hw59i@nih.gov
OI Mofenson, Lynne/0000-0002-2818-9808; Newell,
Marie-Louise/0000-0002-1074-7699
FU Statistical and Data Analysis Center at Harvard School of Public Health,
under the National Institute of Allergy and Infectious Diseases [5 U01
AI41110]; Pediatric AIDS Clinical Trials Group (PACTG) [1 U01 AI068616];
IMPAACT Group; National Institute of Allergy and Infectious Diseases
(NIAID); NICHD [N01-DK-9-001/HHSN267200800001C]
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) [U01 AI068632x, the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Mental Health (NIMH) [AI068632].
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH. 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 (PACTG) and #1 U01 AI068616 with the IMPAACT
Group. Support of the sites was provided by the National Institute of
Allergy and Infectious Diseases (NIAID) the NICHD International and
Domestic Pediatric and Maternal HIV Clinical Trials Network funded by
NICHD (contract number N01-DK-9-001/HHSN267200800001C). In addition to
those listed in the masthead, the International PACTG 316 team includes
Brigitte Bazin, MD (ANRS France), Paula Britto, MS (Statistical and Data
Analysis Center, Harvard School of Public Health, Boston, MA), Yvonne
Bryson, MD (UCLA School of Medicine, Los Angeles, CA), Nina Sublette,
ACRN, MSN (Regional Medical Center, Memphis, TN), Bethann
Cunningham-Schrader and Kathleen A. Kaiser, AAS, COTA, MS (Frontier
Science and Technology Research Foundation, Buffalo, NY), Mobeen
Rathore, MD (University of Florida, Jacksonville, FL), Scharla Estep,
MS, RPh (NIAID, Bethesda, MD), Maria Gigliotti, MS (Boehringer
Ingelheim), Adolfo Gonzalez-Garcia, MD (University of Miami), Mark
Mirochnick, MD (Boston University, Boston, MA), Claire Rekacewicz, MD
(ARNS, Villejuif, France), Maureen Shannon, MS, FNP (San Francisco
General Hospital, San Francisco, CA) and John L. Sullivan, MD
(University of Massachusetts, Worcester, MA). The European Collaborative
Study (ECS) includes investigators and study sites throughout Europe
(listed below). Collaborating investigators include PACTG: Dr. Heather
Watts and Dr. Lynne Mofenson (NICHD), Dr. Beverly E. Sha and Ruth M.
Davis, RN (Rush-Presbyterian/ St. Lukes Chicago), Dr. Arlene D.
Bardeguez and Jocelyn Grandchamp, RN (University of Med. and Dentistry
of NJ), Lisa Melton and Audra Deveikis (Long Beach Memorial), Dr.
William T. Shearer and Dr. Hunter A. Hammill (Baylor College of
Medicine), Dr. Ram Yogev and Donna Stanislawski (Children's Memorial and
PrenticeWomen's Hospital), Dr. Charles D. Mitchell and Patricia Bryan,
RN (University of Miami), Dr. William Borkowsky and Maryann Minter, RN
(Bellevue Hospital), Dr. Diane Wara and Maureen Shannon, RN, MS FNP, CNM
(UCSF Moffitt Hospital), Dr. Diane Wara and Dr. Karen Beckerman (San
Francisco General), Dr. Ana Puga and Dr. Winston Bliss (Children's
Diagnostic and Treatment Center), Dr. Jane Pitt and Dr. Gina Brown
(Columbia University), Dr. Gary Kaufman and Laureen Katz, RN (Boston
Medical Center), Andrew D. Hull and Stephen A. Spector (UCSD Medical
Center), Dr. Elizabeth Livingston and Lori Ferguson, RN (Duke
University), Dr. Mobeen Rathore and Dr. Isaac Delke (University of
Florida Health Sciences Center), Dr. Wilma Lim and Betsy Pitkin, RN
(University of North Carolina at Chapel Hill), Dr. Jorge Gandia and Dr.
Eleanor Jimenez (San Juan City Hospital), Dr. Sohail Rana and Marilyn
Dennis (Howard University Hospital), Dr. Alice Stek and Dr. Andrea
Kovacs (University of Southern California), Dr. Elizabeth J.; McFarland
and Carol Salbenlatt, RN (Children's Hospital), Dr. Myron J. Levin and
Dr. Adriana Weinberg (The Denver Medical Center), Susan Laverty, RN and
Dr. Geoffrey A. Weinberg (University of Rochester), Dr. Hannah Gay and
Netta Boudreaux, RN (University of Mississippi Medical Center), Dr.
Susanne R. Lavoie and Tima Y. Smith, RN (Medical College of Virginia),
Dr. Edwin Thorpe and Ms. Nina Sublette (The Regional Medical Center),
Dr. Dan Lancaster and Dr. Debra Terry (Methodist Hospital Central), Dr.
Gregory J. Wilson and Peggy Bender, FNP (Vanderbilt University Medical
Center), I. Heyer, RN, BSN and Dr. L. Lugo (University of Puerto Rico),
Harold W. Lischner, MSN and Kelly R. Hassey, MSN, CRNP (St.
Christopher's Hospital for Children), Deb Goldman, ARNP and Dr. Jane
Hitti (Children's Hospital and Medical Center), Dr. Robert Maupin and
Dr. Thomas Alchediak (Tulane University Hospital), Dr. Katherine
Luzuriaga and Sheila Noone, RN, PhD (University of Massachusetts Medical
School), Dr. Juan C. Salazar and Dr. Winston Campbell (University of
Connecticut), Gail Karas, RN and Dr. Juan C. Salazar (Connecticut
Children's Medical Center), Dr. George Wendel and Dr. Janet Squires
(Children's Medical Center), Dr. Theodore Jones and Dr. Ellen Moore
(Children's Hospital of Michigan), Dr. Mobeen Rathore and Dr. Isaac
Delke (University of Florida Health Sciences Center), Dr. Jaime Deville
and Maryanne Dillon, BSN (University of California Medical Center), Dr.
Ruth Tuomala (Brigham and Women's Hospital), Dr. Sandra Burchett
(Children's Hospital), Dr. John Farley and Barbara Davis, RN, M Ed.
(University of Maryland), Dr. Kenneth Rich and Dr. Mark Vajaranant
(University of Illinois), Dr. Indu Pathak and Dr. Hamida Khakoo
(Metropolitan Hospital Center), Dr. Nancy Wade and Dr. Renee Samelson
(Children's Hospital at Albany Medical Center), Emily Barr and Dr. John
Nosovitch (State University of New York Upstate Medical University), Pam
Daniel and Patty Kohler, RN (University of Cincinnati), Dr. Margaret
Keller and Marie Beall (Harbor University of California Medical Center),
Angela Ranzini and Marian Lake (St. Peter's Medical Center), Dr. Robert
Pass and Dr. Marilyn Crain (University of Alabama), Dr. Valerie Whiteman
and Dr. Ellen Tidaldi (Temple University School of Medicine), Carla
Duff, RN and Dr. John Sleaseman (University of Florida, Gainesville),
Dr. Hector Cintron and Wanda Figueroa (Ramon Ruiz), Dr. George Johnson
and Moya Clarken, RN (Medical University of South Carolina), Dr. Savita
Pahwa (North Shore LIJ Research Institute), Dr. Sunanda Gaur and
Patricia Whitley Williams (Robert Wood Johnson AIDS Program), Dr.
Michael Hughes and Dr. David Shapiro (Statistical and Data Analysis
Center, Harvard School of Public Health). European Collaborative Study:
Dr. I. Grosch-Worner, Dr. K. Seel (Charite Virchow-Klinikum, Berlin,
Germany); Dr. J. Jimenez (Hospital 12 De Octubre, Madrid, Spain); Dr. A.
B. Bohlin, Dr. S. Lindgren (Huddinge and Karolinska Hospitals, Sweden);
Dr. A. Mur, Dr. A. Paya (Hospital del Mar, Barcelona, Spain); Dr. O.
Coll, Dr. C. Fortuny (Hospital Clinic, Barcelona, Spain); Dr. M.
Casellas Caro (Hospital Vall D'Hebron, Barcelona, Spain); Dr. M. Leyes,
Dr. L. Ciria (Hospital Son Dureta, Mallorca); Prof. P. Martinelli, Dr.
W. Buffolano, Dr. M. Sansone (II Policlinico, Naples, Italy); Dr. C.
Tibaldi, Dr. N. Ziarati (S Anna Hospital, Torino, Italy); Dr. S.
Alberico, Dr. C. Salvatore (Burlo Garofolo Hospital, Trieste, Italy);
Prof. M. Temmerman (University of Ghent); Dr. I. Hoesli, Dr. C. Rudin
(University of Basel); Dr. X. Carnet, Dr. J.; Pich(Clinical Pharmacology
Unit, University of Barcelona); Dr. M. Ravizza, Prof. G. Pardi, Dr. L.
Mangiarotti (San Paolo Hospital, Milan, Italy); Dr. V. Savasi, Dr. A. E.
Semprini, Prof. E. Ferrazzi (Sacco Hospital, Milan, Italy); Dr. M.
Sharland, Ms. T. Chester (St. George's Hospital, London UK), Dr. A.
Fakoya (Newham General Hospital, London, UK), Dr. G. Scaravelli (PUI,
Rome, Italy), Dr. W. Coroleou, Dr. Cavalle Gelabret (H. Germans Trials I
pujol, Badalona, Spain) Prof. C. Loveday (University College London,
UK); France: Scientific Committee: Annie Metro (ANRS), Marie-Jeanne
Mayaux, Stephane Blanche, Christine Rouzioux, Marc Tardieu [Enquete
Pediatrique Francaise (EPF)]; Jean-Pierre Aboulker (Service Commun 10,
INSERM); Bertrand Baumelou (Boehringer Ingelheim, France); Clinicians:
Veronique Chambrin, Hassina Razafimahefa (Hopital Antoine Beclere,
Clamart), Laurent Mandelbrot, Guislaine Firtion (Hopital Cochin-Port
Royal, Paris), Nicole Ciraru-Vigneron, Claudine Bruner (Hopital
Lariboisiere, Paris), Alain Berrebi, Joelle Tricoire (Hopital Purpan,
Toulouse), Claude Hocke, Daniele Douard (Hopital Pellegrin, Bordeaux),
Catherine Crenn-Hebert, Corinne Floch-Tulal (Hopital Louis-Mourier,
Colombes), Etienne Wilmer, Annick Ottenvalter (Hopital Robert Debre,
Paris), Marie-Aude Khuong, Jean-Marc Retbi (Hopital Delafontaine,
SaintDenis), Vincent Jeantils, Eric Lachassine (Hopital Jean-Verdier,
Bondy), Sophie Matheron, Jean-Louis Benifla (Hopital
Bichat-Claude-Bernard, Paris), Cristianne Huraux-Rendu, Joelle Teboul
(Hopital Henri-Mondor, Creteil), Deborah Fried, Brigitte Heller-Roussin
(Hopital Intercommunal Montreuil), Brigitte Clavier, Veronique Brossard
(Hopital Charles Nicolle, Rouen), Andre Bongain, Fabrice Monpoux
(Hopital de l'Archet, Nice), Michel Levardon, Fabienne Mazy (Hopital
Beaujon, Clichy), Veronique Cayol, Catherine Dolfus (Hopital
Saint-Antoine-Trousseau, Paris), Paul Benos, Joelle Nicolas (Hopital
Arnaud De Villeneuve, Montpellier), Daniel Raudrant, Laurent Cotte
(Hopital de l'Hotel Dieu, Lyon), Cecile Francois, Francoise Mechinaud
(Hopital de l'Hotel-Dieu, Nantes), Rose Nguyen, Adrien May (Hopital
Louise Michel, Evry), Benedicte Mougeon, Alain Devidas (Hopital Gilles
de Corbeil, Corbeil); Brazil: Dr. Susie Andries Nogueira, Dr. Marcia
Bondarowisky (Federal University of Rio de Janeiro, Brazil), Esau
Custodio Joao Filho, MD, Marcos Machado D'Ippolito, MD (Hospital dos
Servidores in Rio de Janiero, Brazil); Bahamas: Dr. M. Perry Gomez, Dr.
P. McNeil (Princes Margaret Hospital, Bahamas).
NR 22
TC 18
Z9 18
U1 0
U2 8
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD MAR
PY 2011
VL 39
IS 2
BP 163
EP 170
DI 10.1515/JPM.2010.139
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 733EP
UT WOS:000288245600009
PM 21142844
ER
PT J
AU Johnstone, TB
Gu, ZL
Yoshimura, RF
Villegier, AS
Hogenkamp, DJ
Whittemore, ER
Huang, JC
Tran, MB
Belluzzi, JD
Yakel, JL
Gee, KW
AF Johnstone, Timothy B.
Gu, Zhenglin
Yoshimura, Ryan F.
Villegier, Anne-Sophie
Hogenkamp, Derk J.
Whittemore, Edward R.
Huang, Jin-Cheng
Tran, Minhtam B.
Belluzzi, James D.
Yakel, Jerrel L.
Gee, Kelvin W.
TI Allosteric Modulation of Related Ligand-Gated Ion Channels
Synergistically Induces Long-Term Potentiation in the Hippocampus and
Enhances Cognition
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID CONTAINING GABA(A) RECEPTORS; NICOTINIC ACETYLCHOLINE-RECEPTORS;
ADULT-RAT BRAIN; ALPHA-5 SUBUNIT; ALZHEIMERS-DISEASE; IN-VIVO;
SYNAPTIC-TRANSMISSION; COST-EFFECTIVENESS; INVERSE AGONISTS; TONIC
INHIBITION
AB alpha 5 Subunit-containing GABA(A) receptors (GABA(A)Rs) and alpha 7 neuronal nicotinic-acetylcholine receptors (nAChRs) are members of the Cys-loop family of ligand-gated ion channels (LGICs) that mediate cognitive and attentional processes in the hippocampus. alpha 5 GABA(A)Rs alter network activity by tonic inhibition of CA1/CA3 pyramidal cells of the hippocampus. Postsynaptic alpha 7 nAChRs in the hippocampus regulate inhibitory GABAergic interneuron activity required for synchronization of pyramidal neurons in the CA1, whereas presynaptic alpha 7 nAChRs regulate glutamate release. Can simultaneous allosteric modulation of these LGICs produce synergistic effects on cognition? We show that combined transient application of two allosteric modulators that individually 1) inhibit alpha 5 GABA(A)Rs and 2) enhance alpha 7 nAChRs causes long-term potentiation (LTP) of mossy fiber stimulation-induced excitatory postsynaptic currents (EPSC) from CA1 pyramidal neurons of rat hippocampal slices. The LTP effect evoked by two compounds is replicated by 3-(2,5-difluorophenyl)-6-(N-ethylindol-5-yl)-1,2,4-triazolo[4,3-b] pyridazine (522-054), a compound we designed to simultaneously inhibit alpha 5 GABA(A)Rs and enhance alpha 7 nAChRs. Selective antagonists for either receptor block sustained EPSC potentiation produced by 522-054. In vivo, 522-054 enhances performance in the radial arm maze and facilitates attentional states in the five-choice serial reaction time trial with similar receptor antagonist sensitivity. These observations may translate into therapeutic utility of dual action compounds in diseases of hippocampal-based cognitive impairment.
C1 [Johnstone, Timothy B.] Univ Calif Irvine, Coll Med, Sch Med, Dept Pharmacol, Irvine, CA 92697 USA.
[Gu, Zhenglin; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Johnstone, TB (reprint author), Univ Calif Irvine, Coll Med, Sch Med, Dept Pharmacol, Rm 360 Med Surge 2, Irvine, CA 92697 USA.
EM tbjohnst@uci.edu
FU National Institutes of Health National Institutes of Aging [AG028800,
AG032972]; National Institutes of Health National Institute of
Environmental Health Science
FX This work was supported by the National Institutes of Health National
Institutes of Aging [Grants AG028800, AG032972]; and the Intramural
Research Program of the National Institutes of Health National Institute
of Environmental Health Science.
NR 49
TC 9
Z9 10
U1 0
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAR
PY 2011
VL 336
IS 3
BP 908
EP 915
DI 10.1124/jpet.110.176255
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 723AI
UT WOS:000287477200035
PM 21159751
ER
PT J
AU Lachapelle, S
Gagne, JP
Garand, C
Desbiens, M
Coulombe, Y
Bohr, VA
Hendzel, MJ
Masson, JY
Poirier, GG
Lebel, M
AF Lachapelle, Sophie
Gagne, Jean-Philippe
Garand, Chantal
Desbiens, Myriam
Coulombe, Yan
Bohr, Vilhelm A.
Hendzel, Michael J.
Masson, Jean-Yves
Poirier, Guy G.
Lebel, Michel
TI Proteome-wide Identification of WRN-Interacting Proteins in Untreated
and Nuclease-Treated Samples
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE LC-MS/MS; proteomics; Werner syndrome; ribosomal protein; nuclease
treatments
ID WERNER-SYNDROME PROTEIN; DE-LANGE-SYNDROME; DNA-DAMAGE; HOMOLOGOUS
RECOMBINATION; SYNDROME HELICASE; CHROMOSOMAL REARRANGEMENTS; FUNCTIONAL
INTERACTION; REPLICATION ARREST; STATISTICAL-MODEL; SYNDROME CELLS
AB Werner syndrome (WS) is characterized by the premature onset of several age-associated pathologies. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA repair, replication, telomere maintenance, and transcription. Here, we present the results of a large-scale proteome analysis to determine protein partners of WRN. We expressed fluorescent tagged-WRN (eYFP-WRN) in human 293 embryonic kidney cells and detected interacting proteins by co-immunoprecipitation from cell extract. We identified by mass spectrometry 220 nuclear proteins that complexed with WRN. This number was reduced to 40 when broad-spectrum nucleases were added to the lysate. We consider these 40 proteins as directly interacting with WRN. Some of these proteins have previously been shown to interact with WRN, whereas most are new partners. Among the top 15 hits, we find the new interactors TMPO, HNRNPU, RPS3, RALY, RPS9 DDX21, and HNRNPM. These proteins are likely important components in understanding the function of WRN in preventing premature aging and deserve further investigation. We have confirmed endogenous WRN interaction with endogenous RPS3, a ribosomal protein with endonuclease activities involved in oxidative DNA damage recognition. Our results suggest that the use of nucleases during cell lysis severely restricts interacting protein partners and thus enhances specificity.
C1 [Lachapelle, Sophie; Garand, Chantal; Desbiens, Myriam; Coulombe, Yan; Masson, Jean-Yves; Lebel, Michel] Univ Laval, Hop Hotel Dieu Quebec, Ctr Rech Cancerol, Quebec City, PQ G1R 2J6, Canada.
[Gagne, Jean-Philippe; Poirier, Guy G.] Univ Laval, CHU Laval, Fac Med, Quebec City, PQ G1V 4G2, Canada.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Hendzel, Michael J.] Univ Alberta, Fac Med, Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
[Hendzel, Michael J.] Univ Alberta, Fac Med, Dept Oncol, Edmonton, AB T6G 1Z2, Canada.
[Poirier, Guy G.] Univ Laval, Fac Med, Quebec Genom Ctr, Quebec City, PQ G1V 4G2, Canada.
RP Lebel, M (reprint author), Univ Laval, Hop Hotel Dieu Quebec, Ctr Rech Cancerol, 9 McMahon Sreet, Quebec City, PQ G1R 2J6, Canada.
EM michel.lebel@crhdq.ulaval.ca
OI Hendzel, Michael/0000-0002-9603-7945
FU Canadian Institutes of Health Research
FX This work was supported by the Canadian Institutes of Health Research to
G.G.P., J.-Y.M., and M.L. J.-Y.M. and M.L. are senior scholars from the
Fonds de la Recherche en Sante du Quebec.
NR 62
TC 15
Z9 15
U1 2
U2 7
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 MAR
PY 2011
VL 10
IS 3
BP 1216
EP 1227
DI 10.1021/pr100990s
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 729JD
UT WOS:000287944000026
PM 21210717
ER
PT J
AU Pincus, SM
Alam, S
Rubinow, DR
Bhuvaneswar, CG
Schmidt, PJ
AF Pincus, Steven M.
Alam, Shaista
Rubinow, David R.
Bhuvaneswar, Chaya G.
Schmidt, Peter J.
TI Predicting response to leuprolide of women with premenstrual dysphoric
disorder by daily mood rating dynamics
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Mood disorders; Premenstrual dysphoric disorder; Response to therapy;
Approximate entropy; Cyclicity
ID APPROXIMATE ENTROPY; LUTEINIZING-HORMONE; DEPOT LEUPROLIDE;
CONTROLLED-TRIAL; SYMPTOMS; IRREGULARITY; REGULARITY; EPIDEMIOLOGY;
PULSATILITY; SERTRALINE
AB Approximately 60-70 percent of women with premenstrual dysphoric disorder (PMDD) show symptomatic improvement in response to the GnRH agonist leuprolide acetate, which suppresses ovarian function. However, it has been very difficult to either predict or understand why some women respond, while others do not. We applied several complementary statistical methods to the dynamics of pretreatment mood rating data to determine possible predictors of response for women with PMDD. We compared responders (n = 33) to nonresponders (n = 12) in clinical trials of leuprolide (three months in duration) as a treatment for PMDD, on the basis of pre-trial daily self-ratings of sadness, anxiety, and irritability. We analyzed both sequential irregularity (approximate entropy, ApEn) and a quantification of spikiness of these series, as well as a composite measure that equally weighted these two statistics. Both ApEn and Spikiness were significantly smaller for responders than nonresponders (P <= 0.005): the composite measure was smaller for responders compared with nonresponders (P <= 0.002) and discriminated between the subgroups with high sensitivity and specificity. In contrast, mean symptom levels were indistinct between the subgroups. Relatively regular and non-spiky pre-trial dynamics of mood ratings predict a positive response to leuprolide by women with PMDD with high probability, moreover based on typically less than 3 months of daily records. The statistical measures may have broad and direct applicability to behavioral studies for many psychiatric disorders, facilitating both accurate diagnosis and the prediction of response to treatment. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Alam, Shaista; Schmidt, Peter J.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA.
[Rubinow, David R.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA.
[Bhuvaneswar, Chaya G.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Pincus, SM (reprint author), 990 Moose Hill Rd, Guilford, CT 06437 USA.
EM stevepincus@alum.mit.edu
FU National Institute of Mental Health
FX This work was supported by the National Institute of Mental Health's
Intramural Research Program. The NIMH had no further role in study
design; in the collection, analysis and interpretation of data; and in
the decision to submit the manuscript for publication.
NR 51
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Z9 7
U1 0
U2 4
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 MAR
PY 2011
VL 45
IS 3
BP 386
EP 394
DI 10.1016/j.jpsychires.2010.07.006
PG 9
WC Psychiatry
SC Psychiatry
GA 739ND
UT WOS:000288723800013
PM 20708199
ER
PT J
AU Dietrich, M
Jacques, PF
Polak, JF
Keyes, MJ
Pencina, MJ
Evans, JC
Wolf, PA
Selhub, J
Vasan, RS
D'Agostino, RB
AF Dietrich, Marion
Jacques, Paul F.
Polak, Joseph F.
Keyes, Michelle J.
Pencina, Michael J.
Evans, Jane C.
Wolf, Philip A.
Selhub, Jacob
Vasan, Ramachandran S.
D'Agostino, Ralph B.
TI Segment-Specific Association Between Plasma Homocysteine Level and
Carotid Artery Intima-Media Thickness in the Framingham Offspring Study
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Atherosclerosis; bifurcation segment (bulb); ultrasonography; plaque
formation
ID CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; SERUM TOTAL
HOMOCYSTEINE; VASCULAR AGING EVA; B-MODE ULTRASOUND; ATHEROSCLEROTIC
PLAQUES; FOLIC-ACID; MYOCARDIAL-INFARCTION; WALL THICKNESS; STROKE
AB Elevated plasma total homocysteine (tHcy) level is an established risk factor for cardiovascular disease. The relationship between tHcy and carotid artery intima-media thickness (IMT) at the internal carotid artery (ICA)/bulb-IMT and common carotid artery (CCA)-IMT had not been systematically studied, however. Because the ICA/bulb segment is more prone to plaque formation than the CCA segment, differential associations with tHcy at these sites might suggest mechanisms of tHcy action. We examined the cross-sectional segment-specific relationships of tHcy to ICA/bulb-IMT and CCA-IMT in 2499 participants from the Framingham Offspring Study who were free of cardiovascular disease. In multivariate linear regression analysis, ICA/bulb-IMT was significantly higher in the fourth tHcy quartile category compared with the other quartile categories, in both the age- and sex-adjusted and the multivariate-adjusted models (P for trend <.0001 and <.01, respectively). We observed a significant age-by-tHcy interaction for ICA/bulb-IMT (P = .03) and thus stratified the analyses by median age (58 years). A significant positive trend between tHcy and ICA/bulb-IMT was seen in individuals age >= 58 years (P for trend <.01), but not in younger individuals (P for trend = .24) in multivariate-adjusted models. For CCA-IMT, no significant trends were observed in any of the analyses. The segment-specific association between elevated tHcy level and ICA/bulb-IMT suggests an association between tHcy and plaque formation.
C1 [Dietrich, Marion; Jacques, Paul F.; Selhub, Jacob] Tufts Univ, Jean Mayer USDA HNRCA, Boston, MA 02111 USA.
[Polak, Joseph F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA.
[Polak, Joseph F.] Tufts Med Ctr, Dept Med, Boston, MA USA.
[Keyes, Michelle J.; Pencina, Michael J.; Evans, Jane C.; D'Agostino, Ralph B.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Wolf, Philip A.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Wolf, Philip A.; Vasan, Ramachandran S.; D'Agostino, Ralph B.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer USDA HNRCA, 711 Washington St, Boston, MA 02111 USA.
EM mariondietric@msn.com
OI Ramachandran, Vasan/0000-0001-7357-5970
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[NO1-HC-25195, 2K24 HL04334, RO1 HL069003, RO1 HL081352]; US Department
of Agriculture [58-1950-4-401]
FX Supported by National Institutes of Health, National Heart, Lung, and
Blood Institute Grants NO1-HC-25195, 2K24 HL04334, RO1 HL069003, and RO1
HL081352.; This article is based on work supported by the US Department
of Agriculture (58-1950-4-401). Any opinions, findings, conclusions, or
recommendations expressed in this article are those of the authors and
do not necessarily reflect the view of the US Department of Agriculture.
NR 43
TC 8
Z9 11
U1 2
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD MAR-APR
PY 2011
VL 20
IS 2
BP 155
EP 161
DI 10.1016/j.jstrokecerebrovasdis.2009.10.012
PG 7
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 730PV
UT WOS:000288047400011
PM 20580253
ER
PT J
AU Shamseddeen, W
Asarnow, JR
Clarke, G
Vitiello, B
Wagner, KD
Birmaher, B
Keller, MB
Emslie, G
Iyengar, S
Ryan, ND
McCracken, JT
Porta, G
Mayes, T
Brent, DA
AF Shamseddeen, Wael
Asarnow, Joan Rosenbaum
Clarke, Gregory
Vitiello, Benedetto
Wagner, Karen Dineen
Birmaher, Boris
Keller, Martin B.
Emslie, Graham
Iyengar, Satish
Ryan, Neal D.
McCracken, James T.
Porta, Giovanna
Mayes, Taryn
Brent, David A.
TI Impact of Physical and Sexual Abuse on Treatment Response in the
Treatment of Resistant Depression in Adolescent Study (TORDIA)
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE depression; cognitive behavioral therapy; abuse; selective serotonin
reuptake inhibitor
ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL;
COGNITIVE-BEHAVIORAL THERAPY; NATIONAL COMORBIDITY SURVEY; CHILDHOOD
MALTREATMENT; CLINICAL-TRIAL; PTSD SYMPTOMS; PSYCHOSOCIAL ORIGINS;
PSYCHIATRIC-DISORDER; YOUNG ADULTHOOD
AB Objective: We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method: Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor (SSRI) trial (N = 334) were randomized to one of the following: an alternative SSRI; an alternative SSRI plus cognitive behavior therapy (CBT); venlafaxine; or venlafaxine plus CBT. Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy. Results: Those without a history of physical abuse (PA) or sexual abuse (SA) had a higher 12-week response rate to combination therapy compared with medication mono-therapy (62.8% versus 37.6%; odds ratio [OR] = 2.8, 95% confidence interval [CI] = 1.6-4.7, p < .001). Those with a history of SA had similar response rates to combination versus medication monotherapy (48.3% versus 42.3%; OR = 1.3, 95% CI = 0.4-3.7; p = .66), whereas those with history of PA had a much lower rate of response to combination therapy (18.4% versus 52.4%, OR = 0.1; 95% CI = 0.02-0.43). Even after adjusting for other clinical predictors, a history of PA moderated treatment outcome. Conclusion: These results should be considered within the limitations of a post hoc analysis, lack of detailed assessment of abuse and other forms of trauma, and neuropsychological status. Depressed patients with history of abuse, especially PA may require specialized clinical approaches. Further work is needed to understand by what mechanisms a history of abuse affects treatment response. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(3):293-301. Clinical Trial Registry Information: Treatment of SSIZI-Resistant Depression in Adolescents (TORDIA); NCT00018902; http://www.clinicaltrials.gov.
C1 [Brent, David A.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
[Shamseddeen, Wael] Rosalind Franklin Univ Med & Sci, N Chicago, IL USA.
[Asarnow, Joan Rosenbaum; McCracken, James T.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Clarke, Gregory] Kaiser Permanente Ctr Hlth Res, Portland, OR USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
[Wagner, Karen Dineen] Univ Texas Med Branch, Galveston, TX USA.
[Keller, Martin B.] Brown Univ, Providence, RI 02912 USA.
[Emslie, Graham; Mayes, Taryn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Brent, DA (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, 3811 Ohara St,Room 315,Bellefield Towers, Pittsburgh, PA 15213 USA.
EM brentda@upmc.edu
FU National Institute of Mental Health (NIMH) [MH61835, MH61856, MH61864,
MH61869, MH61958, MH62014, MH66371]; Philip Morris; Bristol-Myers
Squibb; National Institute of Mental Health; Dey Pharma, L.P.; Pfizer;
Seaside Pharmaceuticals; Aspect; Biobehaviorol Diagnostics; Eli Lilly
and Co., Forest; GlaxoSmithKline; GlaxoSmithKline, and Somerset
FX This work was supported by National Institute of Mental Health (NIMH)
grants MH61835 (Pittsburgh); MH61856 (Galveston); MH61864 (UCLA);
MH61869 (Portland); MH61958 (Dallas); and MH62014 (Brown), and MH66371
(Pittsburgh). NIMH program staff participated in the design,
implementation, analysis, and preparation of reports of the study.; Dr.
Asarnow has served as a consultant for Pfizer. She has received funding
from Philip Morris. A family member receives funding from Bristol-Myers
Squibb, and has served as a consultant for Roche, Novartis,
Sanofi-Adventis, and Janssen. Dr. Wagner has received research support
from the National Institute of Mental Health, and has served on the
advisory board for Forest. Dr. Birmaher receives research support from
the Notional Institute of Mental Health. He has served as a consultant
for Schering Plough. He has participated in advisory board forums
sponsored by Dey Pharma, L.P., and Forest. He has received royalties
from Random House and Lippincott Williams and Wilkins. Dr. Keller has
served as a consultant or received honoraria from Abbott, CENEREX,
Cephalon, Cypress Bioscience, Cyberonics, Forest, Janssen, JDS,
Medtronic, Organon, Novartis, Pfizer, Roche, Solvey, Wyeth, and Sierra
Neuropharmaceuticals. He has received research support from Pfizer. He
has served on the advisory boards for Abbott, Bristol-Myers Squibb,
CENEREX, Cyberonics, Cypress Bioscience, Forest, Janssen, Neuronetics,
Novartis, Organon, and Pfizer. Dr. McCracken has received research
support from Seaside Pharmaceuticals, Bristol-Myers Squibb, and Aspect.
He has served as a consultant to BioMarin and Shionogi. He has received
honoraria from the American Academy of Child and Adolescent Psychiatry,
the Tourette Syndrome Association, CME Outfitters, and Veritas. Dr.
Emslie has received research support from Biobehaviorol Diagnostics, Eli
Lilly and Co., Forest, GlaxoSmithKline, and Somerset. He has served as a
consultant for Biobehavioral Diagnostics, Eli Lilly and Co., Forest,
GlaxoSmithKline, Pfizer, and Wyeth. Dr. Brent has received research
support from the National Institute of Mental Health. He has received
royalties from Guilford Press. He serves as an editor for UpToDate
Psychiatry. Drs. Shamseddeen, Clarke, Vitiello, Iyengar, and Ryan, and
Ms. Mayes and Ms. Porta report no biomedical financial interests or
potential conflicts of interest.
NR 45
TC 30
Z9 32
U1 5
U2 13
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 MAR
PY 2011
VL 50
IS 3
BP 293
EP 301
DI 10.1016/j.jaac.2010.11.019
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 727FR
UT WOS:000287783700011
PM 21334569
ER
PT J
AU McHugh, M
Osei-Anto, A
Klabunde, CN
Galen, BA
AF McHugh, Megan
Osei-Anto, Awo
Klabunde, Carrie N.
Galen, Barbara A.
TI Adoption of CT Colonography by US Hospitals
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE CT colonography; colorectal cancer; medical imaging; technology adoption
ID COLORECTAL-CANCER; QUALITATIVE METHODS; UNITED-STATES; TASK-FORCE;
SERVICES; HEALTH
AB Purpose: Computed tomographic colonography (CTC) is a new noninvasive technology proposed as an option for colorectal cancer screening. The purpose of this study was to identify the percentage of US hospitals that offered CTC between 2005 and 2008 and factors that motivated or impeded adoption.
Methods: Data on the provision of colorectal cancer screening services by nonfederal, general hospitals were analyzed using the 2005 to 2008 American Hospital Association annual surveys. Additionally, in 2009, exploratory interviews were conducted with representatives from radiology departments at 9 hospitals; 6 that provided CTC and 3 that did not.
Results: In 2008, 17% of hospitals offered CTC, up from 13% in 2005. Sixty-nine percent of hospitals that offered CTC in 2008 also offered optical colonoscopy services. Factors motivating the adoption of CTC included a desire to provide an alternative screening option for frail, elderly patients and patients with failed optical colonoscopy; long waits for optical colonoscopy; and promising evidence on CTC published in peer-reviewed literature. Lack of reimbursetnent was a commonly cited barrier.
Conclusions: Growth of CT colonographic services at US hospitals occurred even in the absence of Medicare coverage or agreement among national guideline-setting organizations regarding CTC's use in screening. Almost one-third of hospitals that offer CTC do not offer optical colonoscopy and may not be prepared to provide adequate follow-up for patients with failed CTC.
C1 [McHugh, Megan] Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA.
[Osei-Anto, Awo] Hlth Res & Educ Trust, Chicago, IL USA.
[Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Galen, Barbara A.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA.
RP McHugh, M (reprint author), Northwestern Univ, Inst Healthcare Studies, Feinberg Sch Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mmchugh@gwmail.gwu.edu
FU NCI NIH HHS [HHSN261200900139P]; PHS HHS [HHSN261200900139P]
NR 19
TC 7
Z9 7
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD MAR
PY 2011
VL 8
IS 3
BP 169
EP 174
DI 10.1016/j.jacr.2010.08.008
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 961FH
UT WOS:000305449000008
PM 21371666
ER
PT J
AU Matthews, MM
Hsu, FC
Walkup, MP
Barry, LC
Patel, KV
Blair, SN
AF Matthews, Margaret M.
Hsu, Fang-Chi
Walkup, Michael P.
Barry, Lisa C.
Patel, Kushang V.
Blair, Steven N.
TI Depressive Symptoms and Physical Performance in the Lifestyle
Interventions and Independence for Elders Pilot Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE exercise; physical performance; depression
ID LOWER-EXTREMITY FUNCTION; OLDER-ADULTS; CONTROLLED-TRIAL; SELF-EFFICACY;
EXERCISE; DECLINE; OSTEOARTHRITIS; POPULATION; DISABILITY; PEOPLE
AB OBJECTIVES
To determine whether the presence of high depressive symptoms (Center for Epidemiologic Studies Depression Scale (CES-D) score >= 14) diminished physical performance benefits after a comprehensive physical activity intervention in older adults.
DESIGN
A post hoc analysis of data from the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a single-blind randomized controlled trial comparing a moderate-intensity physical activity intervention (PA) with a successful aging control (SA).
SETTING
Multicenter U.S. institutions participating in the LIFE-P trial.
PARTICIPANTS
Four hundred twenty-four sedentary, noninstitutionalized adults aged 70 to 89.
MEASUREMENTS
Depressive symptoms were assessed using the CES-D. Physical performance tests included the Short Physical Performance Battery (SPPB) and 400-m walk time (400 mw) at baseline and 6 and 12 months.
RESULTS
Of the participants, 15.8% had high depressive symptom scores (CES-D >= 14). For participants with low depressive symptoms, SPPB scores improved more in the PA than the SA group over 12 months (adjusted score difference +0.70; P <.001 at 6 months and +0.58; P=.004 at 12 months), and 400 mw times improved in the PA group at 6 months (adjusted score difference -0.41 minutes; P=.02). For participants with high depressive symptoms, the difference in improvement fell short of statistical significance on the SPPB between the PA and SA groups (adjusted score difference +0.76 (P=.18) at 6 months and +0.94 (P=.12) at 12 months).
CONCLUSION
The presence of high depressive symptoms did not substantially diminish physical performance benefits realized after a PA intervention in sedentary older adults.
C1 [Matthews, Margaret M.] Univ S Carolina, Sch Med, Div Geriatr, Columbia, SC 29203 USA.
[Blair, Steven N.] Univ S Carolina, Sch Publ Hlth, Dept Exercise Sci, Columbia, SC 29208 USA.
[Hsu, Fang-Chi; Walkup, Michael P.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Barry, Lisa C.] Yale Univ, Sch Med, Program Geriatr, New Haven, CT USA.
[Patel, Kushang V.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Matthews, MM (reprint author), Univ S Carolina, Sch Med, Div Geriatr, 3010 Farrow Rd,Suite 300A, Columbia, SC 29203 USA.
EM Margaret.Matthews@palmettohealth.org
FU NIH, National Institute on Aging (NIA) [UO1 AG22376]
FX The LIFE-P study is funded by NIH, National Institute on Aging (NIA)
Cooperative Agreement UO1 AG22376 and sponsored in part by the
Intramural Research Program, NIA, NIH.
NR 30
TC 16
Z9 16
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2011
VL 59
IS 3
BP 495
EP 500
DI 10.1111/j.1532-5415.2011.03319.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 732UQ
UT WOS:000288215600015
PM 21391940
ER
PT J
AU Nelson, RG
AF Nelson, Robert G.
TI Is Treatment of Nephropathy in Type 1 Diabetes Efficacious but
Ineffective?
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID STAGE RENAL-DISEASE; PIMA-INDIANS; MORTALITY; PROTEINURIA; PROGNOSIS;
MELLITUS; YOUNG
C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA.
RP Nelson, RG (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM rnelson@nih.gov
RI Nelson, Robert/B-1470-2012
FU Intramural NIH HHS
NR 14
TC 2
Z9 2
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 MAR
PY 2011
VL 22
IS 3
BP 402
EP 404
DI 10.1681/ASN.2011010076
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 740GE
UT WOS:000288778800004
PM 21355059
ER
PT J
AU Bothwell, SP
Chan, E
Bernardini, IM
Kuo, YM
Gahl, WA
Nussbaum, RL
AF Bothwell, Susan P.
Chan, Emily
Bernardini, Isa M.
Kuo, Yien-Ming
Gahl, William A.
Nussbaum, Robert L.
TI Mouse Model for Lowe Syndrome/Dent Disease 2 Renal Tubulopathy
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID PROTEIN OCRL1 INTERACTS; TRANS-GOLGI NETWORK; OCULOCEREBRORENAL
SYNDROME; DENT-DISEASE; PROXIMAL TUBULE; MUTATIONS; MEGALIN; MICE;
5-PHOSPHATASE; GENE
AB The Lowe oculocerebrorenal syndrome is an X-linked disorder characterized by congenital cataracts, cognitive disability, and proximal tubular dysfunction. Both this syndrome and Dent Disease 2 result from loss-of-function mutations in the OCRL gene, which encodes a type II phosphatidylinositol bisphosphate 5-phosphatase. Ocrl-deficient mice are unaffected, however, which we believe reflects a difference in how humans and mice cope with the enzyme deficiency. Inpp5b and INPP5B, paralogous autosomal genes that encode another type II phosphoinositide 5-phosphatase in mice and humans, respectively, might explain the distinct phenotype in the two species because they are the closest paralogs to Ocrl and OCRL in their respective genomes yet differ between the two species with regard to expression and splicing. Here, we generated Ocrl(-/-) mice that express INPP5B but not Inpp5b. Similar to the human syndromes, all showed reduced postnatal growth, low molecular weight proteinuria, and aminoaciduria. Thus, we created an animal model for OCRL and Dent Disease 2 tubulopathy by humanizing a modifier paralog in mice already carrying the mutant disease gene
C1 [Bothwell, Susan P.; Chan, Emily; Kuo, Yien-Ming; Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Bothwell, Susan P.; Chan, Emily; Kuo, Yien-Ming; Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Bernardini, Isa M.; Gahl, William A.] Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD USA.
RP Nussbaum, RL (reprint author), 513 Parnassus Ave,UCSF Box 0794, San Francisco, CA 94143 USA.
EM Robert.nussbaum@ucsf.edu
FU Intramural NIH HHS
NR 43
TC 17
Z9 18
U1 0
U2 4
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 MAR
PY 2011
VL 22
IS 3
BP 443
EP 448
DI 10.1681/ASN.2010050565
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 740GE
UT WOS:000288778800012
PM 21183592
ER
PT J
AU Boger, CA
Chen, MH
Tin, A
Olden, M
Koettgen, A
de Boer, IH
Fuchsberger, C
O'Seaghdha, CM
Pattaro, C
Teumer, A
Liu, CT
Glazer, NL
Li, M
O'Conne, JR
Tanaka, T
Peralta, CA
Kutalik, Z
Luan, J
Zhao, JH
Hwang, SJ
Akylbekova, E
Kramer, H
van der Harst, P
Smith, AV
Lohman, K
de Andrade, M
Hayward, C
Kollerits, B
Tonjes, A
Aspelund, T
Ingelsson, E
Eiriksdottir, G
Launer, LJ
Harris, TB
Shuldiner, AR
Mitchell, BD
Arking, DE
Franceschini, N
Boerwinkle, E
Egan, J
Hernandez, D
Reilly, M
Townsend, RR
Lumley, T
Siscovick, DS
Psaty, BM
Kestenbaum, B
Haritunians, T
Bergmann, S
Vollenweider, P
Waeber, G
Mooser, V
Waterworth, D
Johnson, AD
Florez, JC
Meigs, JB
Lu, XN
Turner, ST
Atkinson, EJ
Leak, TS
Aasarod, K
Skorpen, F
Syvanen, AC
Illig, T
Baumert, J
Koenig, W
Kramer, BK
Devuyst, O
Mychaleckyj, JC
Minelli, C
Bakker, SJL
Kedenko, L
Paulweber, B
Coassin, S
Endlich, K
Kroemer, HK
Biffar, R
Stracke, S
Volzke, H
Stumvol, M
Magi, R
Campbell, H
Vitart, V
Hastie, ND
Gudnason, V
Kardia, SLR
Liu, YM
Polasek, O
Curhan, G
Kronenberg, F
Prokopenko, I
Rudan, I
Arnlov, J
Hallan, S
Navis, G
Parsa, A
Ferrucci, L
Coresh, J
Shlipak, MG
Bul, SB
Paterson, AD
Wichmann, HE
Wareham, NJ
Loos, RJF
Rotter, JI
Pramstaller, PP
Cupples, LA
Beckmann, JS
Yang, QO
Heid, IM
Rettig, R
Dreisbach, AW
Bochud, M
Fox, CS
Kao, WHL
AF Boeger, Carsten A.
Chen, Ming-Huei
Tin, Adrienne
Olden, Matthias
Koettgen, Anna
de Boer, Ian H.
Fuchsberger, Christian
O'Seaghdha, Conall M.
Pattaro, Cristian
Teumer, Alexander
Liu, Ching-Ti
Glazer, Nicole L.
Li, Man
O'Conne, Jeffrey R.
Tanaka, Toshiko
Peralta, Carmen A.
Kutalik, Zoltan
Luan, Jian'an
Zhao, Jing Hua
Hwang, Shih-Jen
Akylbekova, Ermeg
Kramer, Holly
van der Harst, Pim
Smith, Albert V.
Lohman, Kurt
de Andrade, Mariza
Hayward, Caroline
Kollerits, Barbara
Toenjes, Anke
Aspelund, Thor
Ingelsson, Erik
Eiriksdottir, Gudny
Launer, Lenore J.
Harris, Tamara B.
Shuldiner, Alan R.
Mitchell, Braxton D.
Arking, Dan E.
Franceschini, Nora
Boerwinkle, Eric
Egan, Josephine
Hernandez, Dena
Reilly, Muredach
Townsend, Raymond R.
Lumley, Thomas
Siscovick, David S.
Psaty, Bruce M.
Kestenbaum, Bryan
Haritunians, Talin
Bergmann, Sven
Vollenweider, Peter
Waeber, Gerard
Mooser, Vincent
Waterworth, Dawn
Johnson, Andrew D.
Florez, Jose C.
Meigs, James B.
Lu, Xiaoning
Turner, Stephen T.
Atkinson, Elizabeth J.
Leak, Tennille S.
Aasarod, Knut
Skorpen, Frank
Syvaenen, Ann-Christine
Illig, Thomas
Baumert, Jens
Koenig, Wolfgang
Kraemer, Bernhard K.
Devuyst, Olivier
Mychaleckyj, Josyf C.
Minelli, Cosetta
Bakker, Stephan J. L.
Kedenko, Lyudmyla
Paulweber, Bernhard
Coassin, Stefan
Endlich, Karlhans
Kroemer, Heyo K.
Biffar, Reiner
Stracke, Sylvia
Voelzke, Henry
Stumvol, Michael
Maegi, Reedik
Campbell, Harry
Vitart, Veronique
Hastie, Nicholas D.
Gudnason, Vilmundur
Kardia, Sharon L. R.
Liu, Yongmei
Polasek, Ozren
Curhan, Gary
Kronenberg, Florian
Prokopenko, Inga
Rudan, Igor
Aernloev, Johan
Hallan, Stein
Navis, Gerjan
Parsa, Afshin
Ferrucci, Luigi
Coresh, Josef
Shlipak, Michael G.
Bul, Shelley B.
Paterson, Andrew D.
Wichmann, H. -Erich
Wareham, Nicholas J.
Loos, Ruth J. F.
Rotter, Jerome I.
Pramstaller, Peter P.
Cupples, L. Adrienne
Beckmann, Jacques S.
Yang, Qiong
Heid, Iris M.
Rettig, Rainer
Dreisbach, Albert W.
Bochud, Murielle
Fox, Caroline S.
Kao, W. H. L.
CA CKDGen Consortium
DCCT EDIC
TI CUBN Is a Gene Locus for Albuminuria
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; TYPE-1
DIABETES-MELLITUS; LOW-GRADE ALBUMINURIA; RENAL-FUNCTION;
ALBUMIN/CREATININE RATIO; ATHEROSCLEROSIS RISK; LINKAGE ANALYSIS;
PROXIMAL TUBULE; DESIGN
AB Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
C1 [Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA.
[Boeger, Carsten A.; Olden, Matthias] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Tin, Adrienne; Koettgen, Anna; Li, Man; Kao, W. H. L.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Tin, Adrienne; Koettgen, Anna; Li, Man; Kao, W. H. L.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Olden, Matthias; Heid, Iris M.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, Regensburg, Germany.
[Koettgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany.
[de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[Fuchsberger, Christian; Pattaro, Cristian; Minelli, Cosetta; Pramstaller, Peter P.] European Acad Bolzano Bozen EURAC, Inst Med Genet, Bolzano, Italy.
[Fuchsberger, Christian; Pattaro, Cristian; Minelli, Cosetta; Pramstaller, Peter P.] Med Univ Lubeck, Affiliated Inst, D-23538 Lubeck, Germany.
[O'Seaghdha, Conall M.] Harvard Univ, Sch Med, Boston, MA USA.
[O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany.
[Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] NHLBIs Framingham Heart Study, Boston, MA USA.
[Glazer, Nicole L.; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Glazer, Nicole L.; Lumley, Thomas] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[O'Conne, Jeffrey R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco Med Sch, San Francisco, CA 94143 USA.
[Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Kutalik, Zoltan; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Luan, Jian'an; Zhao, Jing Hua; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Akylbekova, Ermeg] Jackson State Univ, Jackson, MS USA.
[Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Kramer, Holly] Loyola Univ, Maywood, IL USA.
[van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Holtasmara, Kopavogur, Iceland.
[Lohman, Kurt; Liu, Yongmei] Wake Forest Univ, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[de Andrade, Mariza; Atkinson, Elizabeth J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Hayward, Caroline; Vitart, Veronique; Hastie, Nicholas D.] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Kollerits, Barbara; Coassin, Stefan; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria.
[Toenjes, Anke; Stumvol, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Geriatr Res & Educ Clin Ctr, Vet Adm Med Ctr, Baltimore, MD 21201 USA.
[Arking, Dan E.] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Franceschini, Nora] Univ N Carolina, Chapel Hill, NC USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Egan, Josephine] NIA, Lab Clin Invest, Baltimore, MD 21224 USA.
[Hernandez, Dena] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Reilly, Muredach] Univ Penn, Div Cardiol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA.
[Townsend, Raymond R.] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Dept Epidemiol, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Dept Hlth Serv, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Vollenweider, Peter; Waeber, Gerard] Univ Vaudois, Ctr Hosp, Dept Internal Med, Lausanne, Switzerland.
[Mooser, Vincent; Waterworth, Dawn] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA.
[Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA.
[Leak, Tennille S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Aasarod, Knut; Hallan, Stein] St Olavs Univ Hosp, Trondheim, Norway.
[Aasarod, Knut; Skorpen, Frank; Hallan, Stein] Norwegian Univ Sci & Technol, Fac Med, N-7034 Trondheim, Norway.
[Syvaenen, Ann-Christine] Uppsala Univ, Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
[Illig, Thomas; Baumert, Jens; Wichmann, H. -Erich; Heid, Iris M.] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Koenig, Wolfgang] Univ Ulm Klinikum, Zentrum Innere Med, Med Klin Kardiol 2, Ulm, Germany.
[Kraemer, Bernhard K.] Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany.
[Devuyst, Olivier] Catholic Univ Louvain, Sch Med, NEER Unit, B-1200 Brussels, Belgium.
[Mychaleckyj, Josyf C.] Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Bakker, Stephan J. L.; Navis, Gerjan] Univ Groningen, Dept Internal Med, Univ Med Ctr, Groningen, Netherlands.
[Kedenko, Lyudmyla; Paulweber, Bernhard] Paracelsus Med Univ, Dept Internal Med 1, Salzburg, Austria.
[Endlich, Karlhans] Ernst Moritz Arndt Univ Greifswald, Inst Anat & Cell Biol, Greifswald, Germany.
[Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Inst Pharmacol, Greifswald, Germany.
[Biffar, Reiner] Ernst Moritz Arndt Univ Greifswald, Clin Prosthodont Dent Gerostomatol & Mat Sci, Greifswald, Germany.
[Stracke, Sylvia] Ernst Moritz Arndt Univ Greifswald, Nephrol Clin Internal Med A, Greifswald, Germany.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Maegi, Reedik; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Maegi, Reedik; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England.
[Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia.
[Curhan, Gary] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Sch Med, Edinburgh, Midlothian, Scotland.
[Aernloev, Johan] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Bul, Shelley B.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth, Toronto, ON M5G 1X5, Canada.
[Paterson, Andrew D.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Beckmann, Jacques S.] Univ Lausanne, Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Vaudois, Ctr Hosp, Serv Med Genet, Lausanne, Switzerland.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany.
[Dreisbach, Albert W.] Univ Mississippi, Div Nephrol, Jackson, MS 39216 USA.
[Bochud, Murielle] Univ Lausanne, IUMSP, Lausanne, Switzerland.
[Bochud, Murielle] Univ Vaudois, Ctr Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBIs Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov; wkao@jhsph.edu
RI Kronenberg, Florian/B-1736-2008; Yang, Qiong/G-5438-2014; Pramstaller,
Peter/C-2357-2008; Bakker, Stephan/J-4023-2015; Gudnason,
Vilmundur/K-6885-2015; Bull, Shelley/A-1920-2013; Polasek,
Ozren/B-6002-2011; Prokopenko, Inga/H-3241-2014; Paterson,
Andrew/A-4088-2011; Smith, Albert/K-5150-2015; Hayward,
Caroline/M-8818-2016; Feitosa, Mary/K-8044-2012; Arnlov,
Johan/N-9886-2013; Singleton, Andrew/C-3010-2009; Fuchsberger,
Christian/C-9646-2010; Aspelund, Thor/F-4826-2011; Aspelund,
Thor/C-5983-2008; Beckmann, Jacques S /A-9772-2008; Kottgen,
Anna/D-2920-2012; Cavalieri, Margherita/G-8053-2012; Rudan,
Igor/I-1467-2012; Giallauria, Francesco/B-5681-2013; Endlich,
Karlhans/G-5485-2013; Johnson, Andrew/G-6520-2013; Colaus,
PsyColaus/K-6607-2013
OI Mitchell, Braxton/0000-0003-4920-4744; Bergmann,
Sven/0000-0002-6785-9034; Felix, Janine/0000-0002-9801-5774; Magi,
Reedik/0000-0002-2964-6011; Kramer, Holly/0000-0002-6374-837X; Cupples,
L. Adrienne/0000-0003-0273-7965; Zgaga, Lina/0000-0003-4089-9703;
Kronenberg, Florian/0000-0003-2229-1120; Bakker,
Stephan/0000-0003-3356-6791; Gudnason, Vilmundur/0000-0001-5696-0084;
Polasek, Ozren/0000-0002-5765-1862; Prokopenko,
Inga/0000-0003-1624-7457; Paterson, Andrew/0000-0002-9169-118X; Smith,
Albert/0000-0003-1942-5845; Hayward, Caroline/0000-0002-9405-9550;
Feitosa, Mary/0000-0002-0933-2410; Fuchsberger,
Christian/0000-0002-5918-8947; Aspelund, Thor/0000-0002-7998-5433;
Beckmann, Jacques S /0000-0002-9741-1900; Rudan,
Igor/0000-0001-6993-6884; Giallauria, Francesco/0000-0003-4119-9397;
FU NIH [R01 AG18728, R01 HL088119, U01 GM074518-04, U01 HL072515-06, U01
HL084756, NIH K12RR023250, NIH P30 DK072488, NIH P60 DK079637,
HHSN268200625226C]; University of Maryland General Clinical Research
Center [M01 RR 16500]; Baltimore Veterans Administration Medical Center
Geriatrics Research and Education Clinical Center; Paul Beeson Physician
Faculty; National Heart, Lung, and Blood Institute [N01-HC-55015,
N01-HC55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, N01-HC-85079,
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, U01 HL080295, R01 HL087652, R01 AG027002]; National Human
Genome Research Institute [U01HG004402]; National Institutes of Health
and NIH Roadmap for Medical Research [ULIRR025005]; National Center for
Research Resources [M01RR00425]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; Medical Research Council UK;
Cancer Research UK
FX AMISH: The Amish studies are supported by grants and contracts from the
NIH including R01 AG18728 (Amish Longevity Study), R01 HL088119 (Amish
Calcification Study), U01 GM074518-04 (PAPI Study), U01 HL072515-06
(HAPI Study), U01 HL084756 and NIH K12RR023250 (University of Maryland
MCRDP), NIH P30 DK072488 (Clinical Nutrition Research Unit of Maryland),
and NIH P60 DK079637 (Baltimore Diabetes Research and Training Center).
The University of Maryland General Clinical Research Center, grant M01
RR 16500, the Baltimore Veterans Administration Medical Center
Geriatrics Research and Education Clinical Center, and the Paul Beeson
Physician Faculty Scholars in Aging Program. We thank our Amish research
volunteers for their long-standing partnership in research, and the
research staff at the Amish Research Clinic for their hard work and
dedication.; ARIC: The Atherosclerosis Risk in Communities study is
carried out as a collaborative study supported by National Heart, Lung,
and Blood Institute contracts N01-HC-55015, N01-HC55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367, and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HHSN268200625226C. The authors thank the staff and participants of the
ARIC study for their important contributions. Infrastructure was partly
supported by grant numbers ULIRR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research.; CHS: The
Cardiovascular Health Study (CHS) research reported in this article was
supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129,
N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133, grants U01
HL080295 and R01 HL087652, and R01 AG027002 from the National Heart,
Lung and Blood Institute, with additional contribution from the National
Institute of Neurologic Disorders and Stroke. A full list of principal
CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was
supported in part by National Center for Research Resources grant
M01RR00425 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center.; CoLaus: The CoLaus authors thank Mande
Barreau, Mathieu Firmann, Vladimir Mayor, Anne-Lise Bastian, Binasa
Ramie, Martine Moranville, Martine Baumer, Marcy Sagette, Jeanne
Ecoffey, and Sylvie Mermoud for data collection. The CoLaus study
received financial contributions from GlaxoSmithKline, the Faculty of
Biology and Medicine of Lausanne, the Swiss National Science Foundation
(33CSCO-122661, 3200BO-111361/2, 3100AO-116323/1, and 310000-112552),
the Swiss School of Public Health Plus, the Giorgi-Cavaglieri
Foundation, and the European Framework Project 6 (EuroDia, AnEuploidy,
and Hypergenes projects).; EPIC: The EPIC Norfolk Study is funded by
program grants from the Medical Research Council UK and Cancer Research
UK, and by additional support from the European Union, Stroke
Association, British Heart Foundation, Department of Health, Food
Standards Agency, and the Wellcome Trust.
NR 81
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U1 5
U2 13
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2011
VL 22
IS 3
BP 555
EP 570
DI 10.1681/ASN.2010060598
PG 16
WC Urology & Nephrology
SC Urology & Nephrology
GA 740GE
UT WOS:000288778800023
PM 21355061
ER
PT J
AU Schiffman, M
Wentzensen, N
Wacholder, S
Kinney, W
Gage, JC
Castle, PE
AF Schiffman, Mark
Wentzensen, Nicolas
Wacholder, Sholom
Kinney, Walter
Gage, Julia C.
Castle, Philip E.
TI Human Papillomavirus Testing in the Prevention of Cervical Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Review
ID ATYPICAL SQUAMOUS-CELLS; RANDOMIZED CONTROLLED-TRIAL; LIQUID-BASED
CYTOLOGY; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL INCIDENCE
RATES; 2006 CONSENSUS GUIDELINES; ASCUS-LSIL TRIAGE; COLLABORATIVE
REANALYSIS; INDIVIDUAL DATA; FOLLOW-UP
AB Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.
C1 [Schiffman, Mark; Wentzensen, Nicolas; Wacholder, Sholom; Gage, Julia C.; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kinney, Walter] Kaiser Permanente Med Ctr, Div Gynecol Oncol, Oakland, CA USA.
[Castle, Philip E.] Amer Soc Clin Pathologists, Washington, DC USA.
RP Schiffman, M (reprint author), Rm 7012,6120 Execut Blvd, Rockville, MD 20852 USA.
EM schiffmm@mail.nih.gov
FU National Cancer Institute [N01-CP-11005]; National Institutes of Health
Office for Research on Women's Health; Ministry of Health of Costa Rica
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute.; Drs Schiffman and Wacholder participate
in the Costa Rican HPV Vaccine Trial, a long-standing collaboration
between investigators in Costa Rica and the National Cancer Institute
(NCI). The trial is sponsored and funded by the NCI (grant
N01-CP-11005), with funding support from the National Institutes of
Health Office for Research on Women's Health, and conducted with support
from the Ministry of Health of Costa Rica. Vaccine was provided for the
trial by GSK Biologicals, under a Clinical Trials Agreement with the
NCI. GlaxoSmithKline also provided support for aspects of the trial
associated with regulatory submission needs of the company. GSK had no
role in this review. Dr Castle has a formal agreement with Roche
Diagnostics to help analyze its Food and Drug Administration clinical
trial data, without compensation. The funding source has not dictated
the comment of this review.
NR 131
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U2 37
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR
PY 2011
VL 103
IS 5
BP 368
EP 383
DI 10.1093/jnci/djq562
PG 16
WC Oncology
SC Oncology
GA 730GC
UT WOS:000288020800007
PM 21282563
ER
PT J
AU Fletcher, O
Johnson, N
Orr, N
Hosking, FJ
Gibson, LJ
Walker, K
Zelenika, D
Gut, I
Heath, S
Palles, C
Coupland, B
Broderick, P
Schoemaker, M
Jones, M
Williamson, J
Chilcott-Burns, S
Tomczyk, K
Simpson, G
Jacobs, KB
Chanock, SJ
Hunter, DJ
Tomlinson, IP
Swerdlow, A
Ashworth, A
Ross, G
Silva, ID
Lathrop, M
Houlston, RS
Peto, J
AF Fletcher, Olivia
Johnson, Nichola
Orr, Nick
Hosking, Fay J.
Gibson, Lorna J.
Walker, Kate
Zelenika, Diana
Gut, Ivo
Heath, Simon
Palles, Claire
Coupland, Ben
Broderick, Peter
Schoemaker, Minouk
Jones, Michael
Williamson, Jill
Chilcott-Burns, Sarah
Tomczyk, Katarzyna
Simpson, Gemma
Jacobs, Kevin B.
Chanock, Stephen J.
Hunter, David J.
Tomlinson, Ian P.
Swerdlow, Anthony
Ashworth, Alan
Ross, Gillian
Silva, Isabel dos Santos
Lathrop, Mark
Houlston, Richard S.
Peto, Julian
TI Novel Breast Cancer Susceptibility Locus at 9q31.2: Results of a
Genome-Wide Association Study
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID COLORECTAL-CANCER; CONFER SUSCEPTIBILITY; COMMON VARIANTS; IDENTIFIES 2;
RISK; WOMEN; AGE; POLYMORPHISM; RS6983267; MENARCHE
AB Background Genome-wide association studies have identified several common genetic variants associated with breast cancer risk. It is likely, however, that a substantial proportion of such loci have not yet been discovered.
Methods We compared 296 114 tagging single-nucleotide polymorphisms in 1694 breast cancer case subjects (92% with two primary cancers or at least two affected first-degree relatives) and 2365 control subjects, with validation in three independent series totaling 11 880 case subjects and 12 487 control subjects. Odds ratios (ORs) and associated 95% confidence intervals (CIs) in each stage and all stages combined were calculated using unconditional logistic regression. Heterogeneity was evaluated with Cochran Q and I(2) statistics. All statistical tests were two-sided.
Results We identified a novel risk locus for breast cancer at 9q31.2 (rs865686: OR = 0.89, 95% CI = 0.85 to 0.92, P = 1.75 x 10(-10)). This single-nucleotide polymorphism maps to a gene desert, the nearest genes being Kruppel-like factor 4 (KLF4, 636 kb centromeric), RAD23 homolog B (RAD23B, 794 kb centromeric), and actin-like 7A (ACTL7A, 736 kb telomeric). We also identified two variants (rs3734805 and rs9383938) mapping to 6q25.1 estrogen receptor 1 (ESR1), which were associated with breast cancer in subjects of northern European ancestry (rs3734805: OR = 1.19, 95% CI = 1.11 to 1.27, P = 1.35 x 10(-7); rs9383938: OR = 1.18, 95% CI = 1.11 to 1.26, P = 1.41 x 10(-7)). A variant mapping to 10q26.13, approximately 300 kb telomeric to the established risk locus within the second intron of FGFR2, was also associated with breast cancer risk, although not at genome-wide statistical significance (rs10510102: OR = 1.12, 95% CI = 1.07 to 1.17, P = 1.58 x 10(-6)).
Conclusions These findings provide further evidence on the role of genetic variation in the etiology of breast cancer. Fine mapping will be needed to identify causal variants and to determine their functional effects.
C1 [Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, Noncommunicable Dis Epidemiol Unit, London WC1E 7HT, England.
[Fletcher, Olivia; Johnson, Nichola; Orr, Nick; Palles, Claire; Coupland, Ben; Williamson, Jill; Chilcott-Burns, Sarah; Tomczyk, Katarzyna; Simpson, Gemma; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Hosking, Fay J.; Broderick, Peter; Houlston, Richard S.] Inst Canc Res, Sect Canc Genet, Surrey, England.
[Zelenika, Diana; Gut, Ivo; Heath, Simon; Lathrop, Mark] IG CEA, Ctr Natl Genotypage, Evry, France.
[Schoemaker, Minouk; Jones, Michael; Swerdlow, Anthony] Inst Canc Res, Epidemiol Sect, Surrey, England.
[Jacobs, Kevin B.] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Jacobs, Kevin B.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Jacobs, Kevin B.] BioInformed LLC, Gaithersburg, MD USA.
[Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Tomlinson, Ian P.] Wellcome Trust Ctr Human Genet, Oxford, England.
[Ross, Gillian] Royal Marsden NHS Fdn Trust, London, England.
[Lathrop, Mark] Fdn Jean Dausett CEPH, Paris, France.
[Peto, Julian] Inst Canc Res, Canc Res UK Genet & Epidemiol Grp, Surrey, England.
RP Peto, J (reprint author), London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, Noncommunicable Dis Epidemiol Unit, Keppel St, London WC1E 7HT, England.
EM julian.peto@lshtm.ac.uk
RI Heath, Simon/J-4138-2012;
OI Broderick, Peter/0000-0002-8348-5829; Schoemaker,
Minouk/0000-0001-8403-2234; Hosking, Fay/0000-0002-1101-039X; dos Santos
Silva, Isabel/0000-0002-6596-8798; Houlston, Richard/0000-0002-5268-0242
FU Cancer Research UK [C150/A5660, C1178/A3947]; Breakthrough Breast
Cancer; Institut National de Cancer; Cridlan Trust; National Health
Service; Wellcome Trust [076113, 085475]
FX Cancer Research UK (C150/A5660 and C1178/A3947 to J.P. and I.d.S.S.);
Breakthrough Breast Cancer (A. A. and O.F.); the Institut National de
Cancer (M. L.); the Cridlan Trust (G. R.). We acknowledge National
Health Service funding to the NIHR Biomedical Research Centre and the
National Cancer Research Network (NCRN). Funding for the project was
provided by the Wellcome Trust under award 076113 and 085475.
NR 33
TC 136
Z9 141
U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR
PY 2011
VL 103
IS 5
BP 425
EP 435
DI 10.1093/jnci/djq563
PG 11
WC Oncology
SC Oncology
GA 730GC
UT WOS:000288020800011
PM 21263130
ER
PT J
AU Koshiol, J
Rotunno, M
Gillison, ML
Van Doorn, LJ
Chaturvedi, AK
Tarantini, L
Song, HB
Quint, WGV
Struijk, L
Goldstein, AM
Hildesheim, A
Taylor, PR
Wacholder, S
Bertazzi, PA
Landi, MT
Caporaso, NE
AF Koshiol, Jill
Rotunno, Melissa
Gillison, Maura L.
Van Doorn, Leen-Jan
Chaturvedi, Anil K.
Tarantini, Letizia
Song, Hebin
Quint, Wim G. V.
Struijk, Linda
Goldstein, Alisa M.
Hildesheim, Allan
Taylor, Philip R.
Wacholder, Sholom
Bertazzi, Pietro Alberto
Landi, Maria Teresa
Caporaso, Neil E.
TI Assessment of Human Papillomavirus in Lung Tumor Tissue
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; RECURRENT RESPIRATORY PAPILLOMATOSIS; INVASIVE
CERVICAL-CANCER; BROAD-SPECTRUM; RISK-FACTORS; PCR ASSAY; INFECTION;
HPV; ADENOCARCINOMA; WOMEN
AB Lung cancer kills more than 1 million people worldwide each year. Whereas several human papillomavirus (HPV)-associated cancers have been identified, the role of HPV in lung carcinogenesis remains controversial.
We selected 450 lung cancer patients from an Italian population-based case-control study, the Environment and Genetics in Lung Cancer Etiology. These patients were selected from those with an adequate number of unstained tissue sections and included all those who had never smoked and a random sample of the remaining patients. We used real-time polymerase chain reaction (PCR) to test specimens from these patients for HPV DNA, specifically for E6 gene sequences from HPV16 and E7 gene sequences from HPV18. We also tested a subset of 92 specimens from all never-smokers and a random selection of smokers for additional HPV types by a PCR-based test for at least 54 mucosal HPV genotypes. DNA was extracted from ethanol- or formalin-fixed paraffin-embedded tumor tissue under strict PCR clean conditions. The prevalence of HPV in tumor tissue was investigated.
Specimens from 399 of 450 patients had adequate DNA for analysis. Most patients were current (220 patients or 48.9%) smokers, and 92 patients (20.4%) were women. When HPV16 and HPV18 type-specific primers were used, two specimens were positive for HPV16 at low copy number but were negative on additional type-specific HPV16 testing. Neither these specimens nor the others examined for a broad range of HPV types were positive for any HPV type.
When DNA contamination was avoided and state-of-the-art highly sensitive HPV DNA detection assays were used, we found no evidence that HPV was associated with lung cancer in a representative Western population. Our results provide the strongest evidence to date to rule out a role for HPV in lung carcinogenesis in Western populations.
C1 [Koshiol, Jill] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Gillison, Maura L.; Song, Hebin] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, James Canc Hosp, Columbus, OH 43210 USA.
[Gillison, Maura L.; Song, Hebin] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA.
[Van Doorn, Leen-Jan; Quint, Wim G. V.; Struijk, Linda] DDL Diagnost Lab, Voorburg, Netherlands.
[Tarantini, Letizia; Bertazzi, Pietro Alberto] Univ Milan, EPOCA Res Ctr, Dept Occupat & Environm Hlth, Milan, Italy.
[Tarantini, Letizia; Bertazzi, Pietro Alberto] Fdn IRCCS Osped Maggiore Policlin Mangiagalli & R, Epidemiol Unit, Milan, Italy.
RP Koshiol, J (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,Rm 7070, Bethesda, MD 20892 USA.
EM koshiolj@mail.nih.gov
RI Turn, Z/C-5114-2011; Song, H/C-9965-2011; Hildesheim, Allan/B-9760-2015;
Chaturvedi, Anil/J-2024-2015; bertazzi, pietro alberto/D-5039-2017
OI Hildesheim, Allan/0000-0003-0257-2363; Chaturvedi,
Anil/0000-0003-2696-8899; bertazzi, pietro alberto/0000-0003-3475-2449
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute
at the National Institutes of Health; National Cancer Institute at the
National Institutes of Health; Office of Preventive Oncology, National
Cancer Institute at the National Institutes of Health, Bethesda, MD
FX This work was supported by an Intramural Research Award from the
Division of Cancer Epidemiology and Genetics, National Cancer Institute
at the National Institutes of Health, and a National Cancer Institute
Director's Innovation Award, National Cancer Institute at the National
Institutes of Health to J.K.; General Funds from the Intramural Research
Program of the National Cancer Institute at the National Institutes of
Health; and the Cancer Prevention Fellowship Program, Office of
Preventive Oncology, National Cancer Institute at the National
Institutes of Health, Bethesda, MD. The Division of Cancer Epidemiology
and Genetics reviewed and approved the EAGLE case-control study and
cleared the article for publication but had no role in the analysis,
decision to publish, or preparation of the article.
NR 38
TC 50
Z9 51
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR
PY 2011
VL 103
IS 6
BP 501
EP 507
DI 10.1093/jnci/djr003
PG 7
WC Oncology
SC Oncology
GA 737FQ
UT WOS:000288554900010
PM 21293027
ER
PT J
AU Swisher, M
Jonas, R
Tian, X
Lee, ES
Lo, CW
Leatherbury, L
AF Swisher, Matthew
Jonas, Richard
Tian, Xin
Lee, Elaine S.
Lo, Cecilia W.
Leatherbury, Linda
TI Increased postoperative and respiratory complications in patients with
congenital heart disease associated with heterotaxy
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID PRIMARY CILIARY DYSKINESIA; PEDIATRIC CARDIAC-SURGERY; ATRIAL ISOMERISM;
FONTAN PROCEDURE; DEFECTS; EXPERIENCE; VENTRICLE; DISORDERS; OUTCOMES
AB Objective: Patients with heterotaxy and complex congenital heart disease underwent cardiac surgery with high mortality and morbidity. Recent studies have revealed an association among heterotaxy, congenital heart disease, and primary ciliary dyskinesia. We undertook a retrospective review of patients undergoing cardiac surgery at Children's National Medical Center between 2004 and 2008 to explore the hypothesis that there is increased mortality and respiratory complications in heterotaxy patients.
Methods: Retrospective review was performed on postsurgical outcomes of 87 patients with heterotaxy and congenital heart disease exhibiting the full spectrum of situs abnormalities associated with heterotaxy. As controls patients, 634 cardiac surgical patients with congenital heart disease, but without laterality defects, were selected, and surgical complexities were similar with a median Risk Adjustment in Congenital Heart Surgery-1 score of 3.0 for both groups.
Results: We found the mean length of postoperative hospital stay (17 vs 11 days) and mechanical ventilation (11 vs 4 days) were significantly increased in the heterotaxy patients. Also elevated were rates of tracheostomies (6.9% vs 1.6%; odds ratio, 4.6), extracorporeal membrane oxygenation support (12.6% vs 4.9%: odds ratio, 2.8), prolonged ventilatory courses (23% vs 12.3%; odds ratio, 2.1) and postsurgical deaths (16.1% vs 4.7%; odds ratio, 3.9).
Conclusions: Our findings show heterotaxy patients had more postsurgical events with increased postsurgical mortality and risk for respiratory complications as compared to control patients with similar Risk Adjustment in Congenital Heart Surgery-1 surgical complexity scores. We speculate that increased respiratory complications maybe due to ciliary dysfunction. Further studies are needed to explore the basis for the increased surgical risks for heterotaxy patients undergoing cardiac surgery. (J Thorac Cardiovasc Surg 2011;141:637-44)
C1 [Jonas, Richard; Leatherbury, Linda] Childrens Natl Med Ctr, Childrens Natl Heart Inst, Washington, DC 20010 USA.
[Swisher, Matthew; Lee, Elaine S.; Lo, Cecilia W.; Leatherbury, Linda] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Lo, Cecilia W.] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA USA.
RP Leatherbury, L (reprint author), Childrens Natl Med Ctr, Childrens Natl Heart Inst, W Wing Suite 300,111 Michigan Ave NW, Washington, DC 20010 USA.
EM lleather@cnmc.org
FU National Institutes of Health [IH ZO1 HL005701]; Howard Hughes Medical
Institute
FX Supported by funds from the National Institutes of Health (grant No. IH
ZO1-HL005701). M. Swisher was generously supported by a fellowship from
the Howard Hughes Medical Institute.
NR 21
TC 28
Z9 29
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD MAR
PY 2011
VL 141
IS 3
BP 637
EP U299
DI 10.1016/j.jtcvs.2010.07.082
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 722OK
UT WOS:000287443000007
ER
PT J
AU Rastinehad, AR
Baccala, AA
Chung, PH
Proano, JM
Kruecker, J
Xu, S
Locklin, JK
Turkbey, B
Shih, J
Bratslavsky, G
Linehan, WM
Glossop, ND
Yan, PK
Kadoury, S
Choyke, PL
Wood, BJ
Pinto, PA
AF Rastinehad, Ardeshir R.
Baccala, Angelo A., Jr.
Chung, Paul H.
Proano, Juan M.
Kruecker, Jochen
Xu, Sheng
Locklin, Julia K.
Turkbey, Baris
Shih, Joanna
Bratslavsky, Gennady
Linehan, W. Marston
Glossop, Neil D.
Yan, Pingkun
Kadoury, Samuel
Choyke, Peter L.
Wood, Bradford J.
Pinto, Peter A.
TI D'Amico Risk Stratification Correlates With Degree of Suspicion of
Prostate Cancer on Multiparametric Magnetic Resonance Imaging
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; prostatic neoplasms; biopsy; magnetic resonance imaging;
ultrasonography
ID RADICAL PROSTATECTOMY; GLEASON SCORE; BIOPSY; MRI; RADIATION; TIME
AB Purpose: We determined whether there is a correlation between D'Amico risk stratification and the degree of suspicion of prostate cancer on multiparametric magnetic resonance imaging based on targeted biopsies done with our electromagnetically tracked magnetic resonance imaging/ultrasound fusion platform.
Materials and Methods: A total of 101 patients underwent 3 Tesla multiparametric magnetic resonance imaging of the prostate, consisting of T2, dynamic contrast enhanced, diffusion weighted and spectroscopy images in cases suspicious for or with a diagnosis of prostate cancer. All prostate magnetic resonance imaging lesions were then identified and graded by the number of positive modalities, including low-2 or fewer, moderate-3 and high-4 showing suspicion on multiparametric magnetic resonance imaging. The biopsy protocol included standard 12-core biopsy, followed by real-time magnetic resonance imaging/ultrasound fusion targeted biopsies of the suspicious magnetic resonance lesions. Cases and lesions were stratified by the D'Amico risk stratification.
Results: In this screening population 90.1% of men had a negative digital rectal examination. Mean +/- SD age was 62.7 +/- 8.3 years and median prostate specific antigen was 5.8 ng/ml. Of the cases 54.5% were positive for cancer on protocol biopsy. Chi-square analysis revealed a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification (p <0.0001). Within cluster resampling demonstrated a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification for magnetic resonance targeted core biopsies and magnetic resonance lesions (p <0.01)
Conclusions: Our data support the notion that using multiparametric magnetic resonance prostate imaging one may assess the degree of risk associated with magnetic resonance visible lesions in the prostate.
C1 [Rastinehad, Ardeshir R.; Baccala, Angelo A., Jr.; Chung, Paul H.; Proano, Juan M.; Shih, Joanna; Bratslavsky, Gennady; Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Locklin, Julia K.; Wood, Bradford J.] NIH, Ctr Intervent Oncol, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Glossop, Neil D.; Wood, Bradford J.] Philips Healthcare, Toronto, ON, Canada.
[Kruecker, Jochen; Xu, Sheng; Yan, Pingkun; Kadoury, Samuel] Philips Res N Amer, Briarcliff Manor, NY USA.
RP Pinto, PA (reprint author), 10 Ctr Dr,Bldg 10,Room 2-5952, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research; National Institutes of Health and Philips Healthcare
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research, and a
Cooperative Research and Development Agreement between National
Institutes of Health and Philips Healthcare.
NR 16
TC 70
Z9 70
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD MAR
PY 2011
VL 185
IS 3
BP 815
EP 820
DI 10.1016/j.juro.2010.10.076
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 718OM
UT WOS:000287133900020
PM 21239006
ER
PT J
AU Link, CL
Steers, WD
Kusek, JW
McKinlay, JB
AF Link, Carol L.
Steers, William D.
Kusek, John W.
McKinlay, John B.
TI The Association of Adiposity and Overactive Bladder Appears to Differ by
Gender: Results From the Boston Area Community Health Survey
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urinary bladder, overactive; urination disorders; obesity; female; male
ID BENIGN PROSTATIC HYPERPLASIA; URINARY-TRACT SYMPTOMS; LIFE-STYLE
FACTORS; WOMEN; INCONTINENCE; PREVALENCE; DISORDERS; ABUSE; DIET; MEN
AB Purpose: We investigate the association of different measures of adiposity (waist circumference, hip circumference, waist-to-hip ratio and body mass index) with overactive bladder (urinary frequency and urgency), whether the association varies by gender or age and whether it persists when models are adjusted for other confounders.
Materials and Methods: Data were from the Boston Area Community Health epidemiological survey, a random sample of 5,503 Boston, Massachusetts, residents 30 to 79 years old with equal representation from 3 racial/ethnic groups (black, Hispanic and white). Statistical analysis involved nonparametric loess models and multivariate logistic regression.
Results: We noted distinct patterns by gender for the association of various adiposity measures with overactive bladder. Waist-to-hip ratio was not significantly associated with overactive bladder in either gender. In women the prevalence of overactive bladder increased as waist (OR adjusted for other confounders 1.10/10 cm increase) or hip circumference (OR 1.12/10 cm increase) or body mass index (OR 1.03/kg/m(2) increase) increased. In men the prevalence of overactive bladder decreased as adiposity increased (OR 0.65/10 cm increase in waist circumference, OR 0.71/10 cm increase in hip circumference and OR 0.87/kg/m(2) in body mass index) but only to a certain point (waist circumference 100 cm, hip circumference 115 cm and body mass index 27.5 kg/m(2), respectively). At that point the prevalence of overactive bladder increased with increasing adiposity (OR 1.19/10 cm increase in waist circumference, OR 1.16/10 cm increase in hip circumference and OR 1.08/kg/m(2) in body mass index).
Conclusions: The relationship between adiposity and overactive bladder varies by gender.
C1 [Link, Carol L.; McKinlay, John B.] New England Res Inst, Watertown, MA 02472 USA.
[Steers, William D.] Univ Virginia Hlth Syst, Charlottesville, VA USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD USA.
RP Link, CL (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA.
EM clink@neriscience.com
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, Maryland [U01 DK56842];
Elsevier/American Urological Association; American Board of Urology;
National Institutes of Health; Food and Drug Administration; Allergan;
American Board of Obstetrics and Gynecology; New England Research
Institutes
FX Supported by Cooperative Agreement U01 DK56842 from the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, Maryland.; Financial interest and/or
other relationship with Elsevier/American Urological Association,
American Board of Urology, National Institutes of Health, Food and Drug
Administration, Allergan, and American Board of Obstetrics and
Gynecology.; Financial interest and/or other relationship with New
England Research Institutes.
NR 29
TC 19
Z9 21
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD MAR
PY 2011
VL 185
IS 3
BP 955
EP 963
DI 10.1016/j.juro.2010.10.048
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 718OM
UT WOS:000287133900073
PM 21247604
ER
PT J
AU Ogden, KM
Ramanathan, HN
Patton, JT
AF Ogden, Kristen M.
Ramanathan, Harish N.
Patton, John T.
TI Residues of the Rotavirus RNA-Dependent RNA Polymerase Template Entry
Tunnel That Mediate RNA Recognition and Genome Replication
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MINUS-STRAND SYNTHESIS; VIRUS CRNA PROMOTER; INFLUENZA-VIRUS; MUTATIONAL
ANALYSIS; MESSENGER-RNA; INITIATION; MECHANISM; FIDELITY; SEQUENCE;
FEATURES
AB To replicate its segmented, double-stranded RNA (dsRNA) genome, the rotavirus RNA-dependent RNA polymerase, VP1, must recognize viral plus-strand RNAs (+RNAs) and guide them into the catalytic center. VP1 binds to the conserved 3' end of rotavirus +RNAs via both sequence-dependent and sequence-independent contacts. Sequence-dependent contacts permit recognition of viral +RNAs and specify an autoinhibited positioning of the template within the catalytic site. However, the contributions to dsRNA synthesis of sequence-dependent and sequence-independent VP1-RNA interactions remain unclear. To analyze the importance of VP1 residues that interact with +RNA on genome replication, we engineered mutant VP1 proteins and assayed their capacity to synthesize dsRNA in vitro. Our results showed that, individually, mutation of residues that interact specifically with RNA bases did not diminish replication levels. However, simultaneous mutations led to significantly lower levels of dsRNA product, presumably due to impaired recruitment of +RNA templates. In contrast, point mutations of sequence-independent RNA contact residues led to severely diminished replication, likely as a result of improper positioning of templates at the catalytic site. A noteworthy exception was a K419A mutation that enhanced the initiation capacity and product elongation rate of VP1. The specific chemistry of Lys419 and its position at a narrow region of the template entry tunnel appear to contribute to its capacity to moderate replication. Together, our findings suggest that distinct classes of VP1 residues interact with +RNA to mediate template recognition and dsRNA synthesis yet function in concert to promote viral RNA replication at appropriate times and rates.
C1 [Ogden, Kristen M.; Ramanathan, Harish N.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Dr, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI RAMANATHAN, HARISH/B-1274-2013; Patton, John/P-1390-2014
OI RAMANATHAN, HARISH/0000-0001-6073-2981;
FU National Institute of Allergy and Infectious Diseases at the National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases at the National
Institutes of Health.
NR 45
TC 6
Z9 6
U1 2
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 MAR
PY 2011
VL 85
IS 5
BP 1958
EP 1969
DI 10.1128/JVI.01689-10
PG 12
WC Virology
SC Virology
GA 716MT
UT WOS:000286974900005
PM 21147920
ER
PT J
AU Prentoe, J
Jensen, TB
Meuleman, P
Serre, SBN
Scheel, TKH
Leroux-Roels, G
Gottwein, JM
Bukh, J
AF Prentoe, Jannick
Jensen, Tanja B.
Meuleman, Philip
Serre, Stephanie B. N.
Scheel, Troels K. H.
Leroux-Roels, Geert
Gottwein, Judith M.
Bukh, Jens
TI Hypervariable Region 1 Differentially Impacts Viability of Hepatitis C
Virus Strains of Genotypes 1 to 6 and Impairs Virus Neutralization
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CELL-CULTURE-SYSTEMS; SCAVENGER RECEPTOR-BI; IN-VIVO; ENVELOPE PROTEIN;
LOW-DENSITY; INFECTION; CHIMPANZEES; ANTIBODY; PSEUDOPARTICLES;
GLYCOPROTEIN
AB Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma Huh7.5 cells. The 2a(Delta HVR1), 5a(Delta HVR1), and 6a(Delta HVR1) Core-NS2 recombinants retained viability in Huh7.5 cells, whereas 1a(Delta HVR1), 1b(Delta HVR1), 2b(Delta HVR1), 3a(Delta HVR1), and 4a(Delta HVR1) recombinants were severely attenuated. However, except for recombinant 4a(Delta HVR1), viruses eventually spread, and reverse genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a(Delta HVR1), 1b(Delta HVR1), 2b(Delta HVR1), and 3a(Delta HVR1) recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at similar to 1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles for the original viruses with these genotypes. In contrast, all HVR1-deleted viruses were highly sensitive with similar neutralization profiles. In vivo relevance for the role of HVR1 in protecting HCV from neutralization was demonstrated by ex vivo neutralization of 2a and 2a(Delta HVR1) produced in human liver chimeric mice. Due to the high density and neutralization susceptibility of HVR1-deleted viruses, we investigated whether a correlation existed between density and neutralization susceptibility for the original viruses with genotypes 1 to 6. Only the 2a virus displayed such a correlation. Our findings indicate that HVR1 of HCV shields important conserved neutralization epitopes with implications for viral persistence, immunotherapy, and vaccine development.
C1 [Prentoe, Jannick; Jensen, Tanja B.; Serre, Stephanie B. N.; Scheel, Troels K. H.; Gottwein, Judith M.; Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program COHEP C, DK-2650 Hvidovre, Denmark.
[Prentoe, Jannick; Jensen, Tanja B.; Serre, Stephanie B. N.; Scheel, Troels K. H.; Gottwein, Judith M.; Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, Copenhagen Hepatitis Program COHEP C, DK-2650 Hvidovre, Denmark.
[Prentoe, Jannick; Jensen, Tanja B.; Serre, Stephanie B. N.; Scheel, Troels K. H.; Gottwein, Judith M.; Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
[Meuleman, Philip] Ghent Univ Hosp, Ctr Vaccinol, B-9000 Ghent, Belgium.
[Bukh, Jens] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Bukh, J (reprint author), Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program COHEP C, Kettegaards Alle 30, DK-2650 Hvidovre, Denmark.
EM jbukh@sund.ku.dk
RI Meuleman, Philip/H-2899-2013;
OI Meuleman, Philip/0000-0001-6821-234X; Prentoe,
Jannick/0000-0003-2203-9478; Scheel, Troels/0000-0003-1545-4067
FU Faculty of Health Sciences, University of Copenhagen; Lundbeck
Foundation; The Danish Cancer Society; Novo Nordisk Foundation; The
Danish Medical Research Council; A. P. Moeller and the Chastine
Mc-Kinney Moeller Foundation; Leo Nielsen and Karen Margrethe Nielsen
Foundation; Copenhagen University Hospital, Hvidovre, Denmark; Ghent
University [01G00507]; Belgian State via the Interuniversity Attraction
Poles Program [P6/36-HEPRO]; The Research Foundation-Flanders
(FWO-Vlaanderen) [31500910]
FX This study was supported by Ph.D. stipends from the Faculty of Health
Sciences, University of Copenhagen (J.P., T.B.J., and T.K.H.S.), by
research grants from the Lundbeck Foundation (J.B.), The Danish Cancer
Society (J.M.G. and J.B.), the Novo Nordisk Foundation (J.M.G. and
J.B.), The Danish Medical Research Council (J.B.), A. P. Moeller and the
Chastine Mc-Kinney Moeller Foundation (T.K.H.S., J.M.G., and J.B.), the
Leo Nielsen and Karen Margrethe Nielsen Foundation (J.P. and J.B.), and
Copenhagen University Hospital, Hvidovre, Denmark (T.B.J., T.K.H.S.,
J.M.G., and J.B.), by a Concerted Action Grant (01G00507) from Ghent
University, and by the Belgian State via the Interuniversity Attraction
Poles Program (P6/36-HEPRO). P.M. is a postdoctoral fellow supported by
The Research Foundation-Flanders (FWO-Vlaanderen; project 31500910).
NR 38
TC 75
Z9 77
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 MAR
PY 2011
VL 85
IS 5
BP 2224
EP 2234
DI 10.1128/JVI.01594-10
PG 11
WC Virology
SC Virology
GA 716MT
UT WOS:000286974900027
PM 21123377
ER
PT J
AU Andrew, AJ
Miyagi, E
Strebel, K
AF Andrew, Amy J.
Miyagi, Eri
Strebel, Klaus
TI Differential Effects of Human Immunodeficiency Virus Type 1 Vpu on the
Stability of BST-2/Tetherin
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CLATHRIN-MEDIATED ENDOCYTOSIS; CELL-SURFACE; HIV-1 VPU; RESTRICTION
FACTOR; PARTICLE RELEASE; MOLECULAR-CLONING; DOWN-MODULATION; INHIBITS
HIV-1; PROTEIN; TETHERIN
AB BST-2/CD317/tetherin is a host factor that inhibits the release of HIV-1 and other unrelated viruses. A current model proposes that BST-2 physically tethers virions to the surface of virus-producing cells. The HIV-1-encoded Vpu protein effectively antagonizes the activity of BST-2. How Vpu accomplishes this task remains unclear; however, it is known that Vpu has the ability to down-modulate BST-2 from the cell surface. Here we analyzed the effects of Vpu on BST-2 by performing a series of kinetic studies with HeLa, 293T, and CEMx174 cells. Our results indicate that the surface downregulation of BST-2 is not due to an accelerated internalization or reduced recycling of internalized BST-2 but instead is caused by interference with the resupply of newly synthesized BST-2 from within the cell. While our data confirm previous reports that the high-level expression of Vpu can cause the endoplasmic reticulum (ER)-associated degradation of BST-2, we found no evidence that Vpu targets endogenous BST-2 in the ER in the course of a viral infection. Instead, we found that Vpu acts in a post-ER compartment and increases the turnover of newly synthesized mature BST-2. Our observation that Vpu does not affect the recycling of BST-2 suggests that Vpu does not act directly at the cell surface but may interfere with the trafficking of newly synthesized BST-2 to the cell surface, resulting in the accelerated targeting of BST-2 to the lysosomal compartment for degradation.
C1 [Andrew, Amy J.; Miyagi, Eri; Strebel, Klaus] NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA.
EM kstrebel@nih.gov
FU NIH; NIAID, NIH
FX This work was supported in part by a grant from the NIH Intramural AIDS
Targeted Antiviral Program to K.S. and by the Intramural Research
Program of the NIAID, NIH.
NR 45
TC 31
Z9 32
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 MAR
PY 2011
VL 85
IS 6
BP 2611
EP 2619
DI 10.1128/JVI.02080-10
PG 9
WC Virology
SC Virology
GA 735AT
UT WOS:000288386500013
PM 21191020
ER
PT J
AU Di Nisio, M
Di Iorio, A
Porreca, E
Abate, M
Ferrante, N
Bandinelli, S
Guralnik, J
Molino-Lova, R
Cuccurullo, F
Ferrucci, L
AF Di Nisio, Marcello
Di Iorio, Angelo
Porreca, Ettore
Abate, Michele
Ferrante, Noemi
Bandinelli, Stefania
Guralnik, Jack
Molino-Lova, Raffaele
Cuccurullo, Franco
Ferrucci, Luigi
TI Obesity, Poor Muscle Strength, and Venous Thromboembolism in Older
Persons: The InCHIANTI Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Venous thrombosis; Obesity; Poor muscle strength; Elderly
ID DEEP-VEIN THROMBOSIS; RISK-FACTORS; SARCOPENIC OBESITY;
PULMONARY-EMBOLISM; INFLAMMATION; ADULTS; EPIDEMIOLOGY; PERSPECTIVE;
PERFORMANCE; WALKING
AB Background. Both obesity and the decline in muscle strength, which often occur with aging, are accompanied by functional and metabolic changes that may affect the risk of thrombosis. This study evaluated whether obesity and poor muscle strength are associated with venous thromboembolism (VIE).
Methods. Objectively confirmed VTEs were assessed at baseline and more than a 6-year follow-up in 1,045 participants more than or equal to 60 years enrolled in the InCHIANTI study.
Results. At baseline, 97 participants had a positive history of VTE. Obese participants were almost twice more likely (odds ratio 1.76: 95% confidence interval 1.03-3.01) and obese with poor muscle strength were threefold more likely (odds ratio 2.99; 95% confidence interval 1.56-5.73) to have VTE compared with lean participants with normal strength. Fifty-five VTEs occurred during follow-up. History of VIE, obesity, and/or poor strength independently predicted new VTE events. In participants with previous VTE, the odds ratio (95% confidence interval) for thrombosis was 6.64 (1.92-22.95) with poor strength, 9.69 (3.13-30.01) in the obese, and 14.57 (5.16-41.15) in the obese with poor strength as compared with lean participants with normal strength.
Conclusion. Obesity with or without poor muscle strength is a risk factor for VIE among older persons and significantly amplifies the risk of recurrent thrombosis.
C1 [Di Nisio, Marcello; Porreca, Ettore; Ferrante, Noemi; Cuccurullo, Franco] Univ G Annunzio Fdn, Ctr Aging Sci CeSI, Dept Med & Aging, Chieti, Italy.
[Di Iorio, Angelo] Univ G dAnnunzio, Dept Med & Aging, Geriatr Unit, Lab Clin Epidemiol, Chieti Pescara, Italy.
[Abate, Michele] Univ G Annunzio Fdn, Dept Clin Sci & Bioimaging, Chieti, Italy.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Guralnik, Jack] NIH, NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Molino-Lova, Raffaele] Fdn Don Carlo Gnocchi, Inst Recovery & Care Sci Character, Florence, Italy.
[Ferrucci, Luigi] NIH, NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD USA.
RP Di Nisio, M (reprint author), SSma Annunziata Hosp, Dept Internal Med, Via Vestini 31, I-66013 Chieti, Italy.
EM mdinisio@unich.it
FU Italian Ministry of Health; U.S. National Institute on Aging
[263_MD_9164_13, 263_MD_821336, ICS 110.1/RS97.71]; Intramural Research
Program; National Institute on Aging, National Institutes of Health, USA
FX Italian Ministry of Health and in part by the U.S. National Institute on
Aging (Contracts 263_MD_9164_13 and 263_MD_821336) to the InCHIANTI
Study (ICS 110.1/RS97.71), Intramural Research Program, National
Institute on Aging, National Institutes of Health, USA.
NR 30
TC 7
Z9 7
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAR
PY 2011
VL 66
IS 3
BP 320
EP 325
DI 10.1093/gerona/glq207
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 735LK
UT WOS:000288415800009
PM 21112964
ER
PT J
AU Stenholm, S
Sallinen, J
Koster, A
Rantanen, T
Sainio, P
Heliovaara, M
Koskinen, S
AF Stenholm, Sari
Sallinen, Janne
Koster, Annemarie
Rantanen, Taina
Sainio, Paivi
Heliovaara, Markku
Koskinen, Seppo
TI Association between Obesity History and Hand Grip Strength in Older
Adults-Exploring the Roles of Inflammation and Insulin Resistance as
Mediating Factors
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Muscle strength; Obesity; Inflammation; Insulin resistance; Aging
ID HOMEOSTASIS MODEL ASSESSMENT; DEPENDENT DIABETES-MELLITUS; MUSCLE
STRENGTH; SARCOPENIC OBESITY; GLUCOSE-TOLERANCE; PHYSICAL FUNCTION;
BODY-COMPOSITION; WEIGHT HISTORY; ADIPOSE-TISSUE; ELDERLY-MEN
AB Background. To examine the association between obesity history and hand grip strength, and whether the association is partly explained by subclinical inflammation and insulin resistance.
Methods. Data are from 2,021 men and women aged 55 years and older participating in the representative population-based Health 2000 Survey in Finland. Body mass and body height, maximal hand grip strength, C-reactive protein, and insulin resistance based on homeostasis model assessment (HOMA-IR) were measured in a health examination. Recalled weight at 20, 30, 40, and 50 years of age were recorded to obtain a hierarchical classification of obesity history. Obesity was defined as body mass index >= 30 kg/m(2).
Results. Earlier onset of obesity was associated with lower hand grip strength (p < .001) after controlling for age, sex, education, smoking, alcohol use, physical activity, several chronic diseases, and current body weight. Based on adjusted logistic regression models, the odds (95% confidence interval) for very low relative hand grip strength were 2.76 (1.78-4.28) for currently obese, 5.57 (3.02-10.28) for obese since age 01 50 years, 6.53 (2.98-14.30) for obese since age of 40 years, and 10.36 (3.55-30.24) for obese since age of 30 years compared with never obese participants. The associations remained highly significant even after adjusting for current C-reactive protein and HOMA-IR, but these variables had only minor role in explaining the association between obesity history and hand grip strength.
Conclusions. Long-term exposure to obesity is associated with poor hand grip strength later in life. Maintaining healthy body weight throughout the life span may help to maintain adequate muscle strength in old age. Prospective studies with information on prior muscle strength are needed to examine in detail the causal association between obesity history and muscle strength.
C1 [Stenholm, Sari; Sainio, Paivi; Heliovaara, Markku; Koskinen, Seppo] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, FI-20720 Turku, Finland.
[Sallinen, Janne] VTT Tech Res Ctr Finland, Kuopio, Finland.
[Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ Med Ctr, Sch Publ Hlth & Primary Care CAPHRI, Dept Internal Med, Maastricht, Netherlands.
[Rantanen, Taina] Univ Jyvaskyla, Gerontol Res Ctr, Dept Hlth Sci, SF-40351 Jyvaskyla, Finland.
RP Stenholm, S (reprint author), Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Peltolantie 3, FI-20720 Turku, Finland.
EM sari.stenholm@thl.fi
RI Koster, Annemarie/E-7438-2010; Stenholm, Sari/G-6940-2011; Rantanen,
Taina/O-6579-2016
OI Rantanen, Taina/0000-0002-1604-1945
FU Juho Vainio Foundation, Finland; National Institutes of Health, National
Institute on Aging
FX This study was supported in part by a grant from the Juho Vainio
Foundation, Finland, and in part by the Intramural Research Program of
the National Institutes of Health, National Institute on Aging.
NR 42
TC 33
Z9 35
U1 2
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAR
PY 2011
VL 66
IS 3
BP 341
EP 348
DI 10.1093/gerona/glq226
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 735LK
UT WOS:000288415800012
PM 21310808
ER
PT J
AU Flaherty, JH
Dong, BR
Wu, HM
Zhang, YL
Guralnik, JM
Malmstrom, TK
Morley, JE
AF Flaherty, Joseph H.
Dong, Birong
Wu, Hongmei
Zhang, Yanling
Guralnik, Jack M.
Malmstrom, Theodore K.
Morley, John E.
TI Observational Study of 1-Year Mortality Rates Before and After a Major
Earthquake Among Chinese Nonagenarians
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Earthquake; Nonagenarians; Mortality
ID ACUTE MYOCARDIAL-INFARCTION; MENTAL-STATE-EXAMINATION;
CORONARY-HEART-DISEASE; COGNITIVE IMPAIRMENT; WENCHUAN EARTHQUAKE;
CARDIAC DEATH; DEMENTIA; STRESS; RISK; CENTENARIANS
AB Background. Little is known about mortality among nonagenarians after an earthquake.
Methods. Using secondary data analyses from the 2005 study called the Project of Longevity and Aging in Dujiangyan (n = 870), 1-year mortality rates were compared among a pre-earthquake group and a post-earthquake group of nonagenarians. All participants were from Dujiangyan, 50 km from the epicenter of the May 12, 2008 earthquake, in China. The pre-earthquake group was a subset of the 870 Project of Longevity and Aging in Dujiangyan participants, ages 93-95 years at the beginning of "Time Frame 1" (July 2005 through June 2006; n = 228). The post-earthquake group was a different subset of the 870 Project of Longevity and Aging in Dujiangyan participants, ages 93-95 years and alive at the beginning of Time Frame 2 (July 2008 through June 2009; n = 235). Time Frame 2 excluded a 7-week period following the earthquake in order to account for deaths due to trauma. Pre-earthquake health assessment data from the 2005 Project of Longevity and Aging in Dujiangyan study were used to calculate unadjusted/adjusted hazard ratios (HRs) for mortality.
Results. One-year mortality rates were 8.3% (19/228) and 16.2% (38/235) in the pre-earthquake group and the post-earthquake group, respectively (p =.01). In unadjusted analyses, only "being in the post-earthquake group" was associated with death (HR = 2.04; 95% confidence interval [CI], 1.17-3.53; p=.011). In the multivariable Cox regression model, being in the post-earthquake group continued to be the strongest risk factor associated with mortality (HR = 2.47; 95% Cl, 1.39-4.40; p =.002). Other significant risk factors included impaired cognition (HR = 1.97; 95% Cl, 1.10-3.53; p =.024), serum albumin (HR = 0.90; 95% Cl, 0.82-0.98; p < .015), and serum triglycerides (HR = 1.51:95% Cl, 1.15-1.99; p =.003).
Conclusion. The May 12, 2008 earthquake in Wenchuan, China, was associated with a twofold increase in the I-year mortality among a group of nonagenarians who lived nearby.
C1 [Flaherty, Joseph H.; Malmstrom, Theodore K.; Morley, John E.] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO 63104 USA.
[Flaherty, Joseph H.; Morley, John E.] St Louis VA Med Ctr, Geriatr Res Educ & Clin Ctr, St Louis, MO USA.
[Dong, Birong; Wu, Hongmei; Zhang, Yanling] Sichuan Univ, W China Hosp, Dept Geriatr, Chengdu 610064, Peoples R China.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Malmstrom, Theodore K.] St Louis Univ, Sch Med, Dept Neurol & Psychiat, St Louis, MO USA.
RP Flaherty, JH (reprint author), St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, Missouri 1402 S Grand Blvd,Room M238, St Louis, MO 63104 USA.
EM flahertyinchina@yahoo.com
RI morley, john/F-9177-2011
OI morley, john/0000-0001-6444-2965
FU fund for discipline development of West China Hospital of Sichuan
University [HK05001]; National Institute of Aging. National Institute of
Health
FX B.D. was supported by the fund for discipline development of West China
Hospital of Sichuan University (No. HK05001). J.M.G. was supported in
part by the Intramural Research Program, National Institute of Aging.
National Institute of Health.
NR 36
TC 6
Z9 6
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAR
PY 2011
VL 66
IS 3
BP 355
EP 361
DI 10.1093/gerona/glq229
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 735LK
UT WOS:000288415800014
PM 21310809
ER
PT J
AU Kim, A
Kilimnik, G
Guo, C
Sung, J
Jo, J
Periwal, V
Witkowski, P
Dilorio, P
Hara, M
AF Kim, Abraham
Kilimnik, German
Guo, Charles
Sung, Joshua
Jo, Junghyo
Periwal, Vipul
Witkowski, Piotr
Dilorio, Philip
Hara, Manami
TI Computer-assisted Large-scale Visualization and Quantification of
Pancreatic Islet Mass, Size Distribution and Architecture
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Editorial Material
DE Cellular Biology; beta-cells; islets; large-scale analysis; pancreas
C1 [Kim, Abraham; Kilimnik, German; Guo, Charles; Sung, Joshua; Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Jo, Junghyo; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Witkowski, Piotr] Univ Chicago, Dept Surg, Chicago, IL 60637 USA.
[Dilorio, Philip] Univ Massachusetts, Diabet Div, Amherst, MA 01003 USA.
RP Hara, M (reprint author), Univ Chicago, Dept Med, Chicago, IL 60637 USA.
EM mhara@midway.uchicago.edu
NR 0
TC 3
Z9 3
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAR
PY 2011
IS 49
DI 10.3791/2471
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36LY
UT WOS:000209214600005
ER
PT J
AU Yang, B
Pham, TH
Goldbach-Mansky, R
Gadina, M
AF Yang, Barbara
Pham, Tuyet-Hang
Goldbach-Mansky, Raphaela
Gadina, Massimo
TI Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1
beta using a Whole Blood Stimulation Assay
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Editorial Material
C1 [Yang, Barbara; Gadina, Massimo] NIAMSD, Translat Immunol Sect, Off Sci & Technol, Bethesda, MD 20892 USA.
[Pham, Tuyet-Hang; Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, Off Clin Director, Bethesda, MD 20892 USA.
RP Gadina, M (reprint author), NIAMSD, Translat Immunol Sect, Off Sci & Technol, Bethesda, MD 20892 USA.
EM gadinama@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAR
PY 2011
IS 49
DI 10.3791/2662
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36LY
UT WOS:000209214600016
ER
PT J
AU Gipson, DS
Trachtman, H
Kaskel, FJ
Radeva, MK
Gassman, J
Greene, TH
Moxey-Mims, MM
Hogg, RJ
Watkins, SL
Fine, RN
Middleton, JP
Vehaskari, VM
Hogan, SL
Vento, S
Flynn, PA
Powell, LM
McMahan, JL
Siegel, N
Friedman, AL
AF Gipson, Debbie S.
Trachtman, Howard
Kaskel, Frederick J.
Radeva, Milena K.
Gassman, Jennifer
Greene, Tom H.
Moxey-Mims, Marva M.
Hogg, Ronald J.
Watkins, Sandra L.
Fine, Richard N.
Middleton, John P.
Vehaskari, V. M.
Hogan, Susan L.
Vento, Suzzane
Flynn, Patti A.
Powell, Leslie M.
McMahan, June L.
Siegel, Norman
Friedman, Aaron L.
TI Clinical trials treating focal segmental glomerulosclerosis should
measure patient quality of life
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE focal segmental glomerulosclerosis; proteinuria; quality of life;
randomized controlled trial
ID CHRONIC KIDNEY-DISEASE; NEPHROTIC SYNDROME; MYCOPHENOLATE-MOFETIL; SERUM
CREATININE; HEALTH-STATUS; CHILDREN; DIALYSIS; OUTCOMES; THERAPY; ADULTS
AB Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2-40 years, with an estimated glomerular filtration rate >40 ml/min per 1.73 m(2), a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self-or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m(2), and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials. Kidney International (2011) 79, 678-685; doi: 10.1038/ki.2010.485; published online 22 December 2010
C1 [Gipson, Debbie S.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Trachtman, Howard; Vento, Suzzane] Cohen Childrens Hosp, Dept Pediat, Div Nephrol, New York, NY USA.
[Kaskel, Frederick J.; Flynn, Patti A.] Childrens Hosp, Montefiore Med Ctr, New York, NY USA.
[Radeva, Milena K.; Gassman, Jennifer; McMahan, June L.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
[Greene, Tom H.] Univ Utah, Div Epidemiol, Salt Lake City, UT USA.
[Moxey-Mims, Marva M.] NIDDK, NIH, Div Kidney Urol & Hematol, Bethesda, MD USA.
[Hogg, Ronald J.] Childrens Hosp, Scott & White Med Ctr, Dept Pediat, Temple, TX USA.
[Watkins, Sandra L.] Univ Washington, Dept Pediat, Div Nephrol, Seattle, WA 98195 USA.
[Fine, Richard N.] SUNY Stony Brook, Sch Med, Med Ctr, Stony Brook, NY 11794 USA.
[Middleton, John P.] Duke Univ, Dept Med, Div Nephrol, Durham, NC USA.
[Vehaskari, V. M.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Vehaskari, V. M.] Childrens Hosp, Res Inst Children, New Orleans, LA USA.
[Vehaskari, V. M.] LSU Hlth Sci Ctr, New Orleans, LA USA.
[Hogan, Susan L.; Powell, Leslie M.] Univ N Carolina, UNC Kidney Ctr, Div Nephrol & Hypertens Chapel Hill, Chapel Hill, NC USA.
[Friedman, Aaron L.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
RP Gipson, DS (reprint author), Univ Michigan, CS Mott Childrens Hosp, 1500 E Med Ctr Dr,SPC 5257,F6865, Ann Arbor, MI 48109 USA.
EM dgipson@umich.edu
OI Trachtman, Howard/0000-0001-7447-9489
FU NIH/NIDDK [U01-DK063385, DK063490, DK063455, DK063549]
FX This study was sponsored by the NIH/NIDDK grants U01-DK063385, DK063490,
DK063455, and DK063549. A portion of the pediatric quality-of-life data
were previously published in an abstract form by the American Society of
Nephrology Renal Week, 2009. This study represents the participation of
the following institutions and investigators: Anjali Acharia, Jacobi
Medical Center; Steven Alexander, Stanford Children's Hospital; Amira
Al-Uzri, Doernbecher Children's Hospital, Oregon; Sharon Andreoli,
Indiana University Riley Hospital; Gerald Appel, Columbia University
Presbyterian Medical Center -Internal Medicine; Mazen Arar, University
of Texas Health Science Center at San Antonio; Bettina Ault, University
of Tennessee Health Science, Memphis; William Baker, Blue Ridge
Nephrology Associates; Noosha Baqi, Saint Barnabas Medical Center, NJ;
Sharon Bartosh, University of Wisconsin; Lorraine Bell, Montreal
Children's Hospital; Nadine Benador, University of California San Diego;
Corrine Benchimol, Mount Sinai School of Medicine-Peds; Mark Benfield,
University of Alabama at Birmingham; Danilo Bernardo, Valley
Hypertension Nephrology; Phillip Berry, Specially for Children; Andrew
Bland, Renalcare Associates of Peoria, IL; Tom Blydt-Hansen, Children's
Hospital, Winnipeg; Karl Brandspigel, Albemarle Nephrology Associates;
Milos Budisavljevic, Medical University of South Carolina; Brad Carter,
Kidney Specialists of Central Oklahoma; Daniel Cattran, Toronto General
Hospital; Deepa Chand, Cleveland Clinic; Chandran Chandra, St Joseph
Regional Medical Center; Kaye Christopher, Nephrology Associates of
Hartsville; Howard Corey, Morristown Memorial Hospital, NJ; Eileen
Ellis, Arkansas Children's Hospital; Demetrius Ellis, Children's
Hospital of Pittsburgh; Babatunde Fariyike, Babatunde Fariyike
Nephrology; Robert Fildes, Fairfax Hospital for Children; Elie Firzli,
St Joseph's Hospital and Medical Center; Danny Fischer, Kidney and
Hypertension Center, Cincinnati; Joseph Flynn, Children's Hospital,
Seattle; John Foreman, Duke University Medical Center-Peds; Susan Furth,
Johns Hopkins Pediatrics Nephrology; Debbie Gipson, University of North
Carolina, Chapel Hill; Larry Greenbaum, Emory University; Ted Groshong,
University of Missouri-Columbia; Anne Guillot, University of Vermont;
Robert A. Gutman, Durham Nephrology; German Hernandez, Texas Tech
University Health Sciences Center; Jeffrey Hoggard, Eastern Nephrology
Associates; Robert Holleman, University of South Carolina; Mohammad
Ilyas, University of Florida Jacksonville; J.; Ashley Jefferson,
University of Washington Medical Center; Eunice John, University of
Illinois at Chicago; Valerie Johnson, Cornell Medical College New York
Presbyterian Hospital; Joshua Kaplan, University of Medicine and
Dentistry of New Jersey; Frederick Kaskel, Montefiore Medical Center;
Michelle Krause, University of Arkansas, Internal Medicine Nephrology;
Juan Kupferman, Maimonides Medical Center; Marc Lande, University of
Rochester; Jerome Lane, Children's Memorial Hospital, Chicago; Gary
Lerner, Children's Hospital Los Angeles; Jen-Jar Lin, University of
Michigan; John Mahan, Ohio State University-Peds; Susan Massengill,
Carolinas Medical Center-Peds; Douglas Matsell, Children's Hospital
British Columbia; Tej Mattoo, Children's Hospital of Michigan; Lawrence
Mcgee, Spartanburg Nephrology; Susan Mendley, University of Maryland
Hospital; Richard Merrill, Kidney Center, Greenville, NC; John
Middleton, Duke University Medical Center-Internal Medicine; Julian
Midgley, Alberta Children's Hospital; Asha Moudgil, Children's National
Medicl Center; Dianne Muchant, University of Louisville; Jerome Murphy,
Children's Hospital Central California; James Musgrave, University of
Hawaii School of Medicine; Martin Nash, Columbia University Babies' And
Children's Hospital; Richard Neiberger, University of Florida,
Gainesville; Victoria Norwood, University of Virginia Children's Medical
Center; Luis Ortiz, Medical College of Georgia; Cynthia Pan, Children's
Hospital of Wisconsin; Ana Paredes, Miami Children's Hospital; Rupal
Patel, Baylor College of Medicine-Internal Medicine; Dechu Puliyanda,
Cedars-Sinai Medical Center; Majid Rasoulpour, Connecticut Children's
Medical Center; Shobha Sahney, Loma Linda University; Virginia Savin,
Medical College of Wisconsin; Jon Scheinman, University of Kansas;
Jeffrey Schelling, Case Western Reserve University, Internal Medicine,
Nephrology; Morris Schoeneman, Suny Health Sci Center at Brooklyn; Mouin
Seikaly, Children's Medical Center of Dallas; Muhammed Shakeel,
Nephrology and Internal Medicine, Anderson, SC; Ganesh Shidham, Ohio
State University Medical Center; Ajay Singh, Brigham and Women's
Hospital; Michael Somers, Children's Hospital Boston; James Springate,
Women's and Children's Hospital of Buffalo; Frederic Strife, Cincinnati
Children's Hospital Medical Center; Rita Swinford, University of Texas
Southwestern Houston-Internal Medicine; Howard Trachtman, Cohen
Children's Medical Center, NY; Martin Turman, University of Oklahoma
Health Sciences Center; Matti Vehaskari, Children's Hospital, New
Orleans; Brad Warady, Children's Mercy Hospital, Kansas City, MO; Steven
Wassner, Penn State Children's Hospital; Lynne Weiss, Robert Wood
Johnson Medical School, NJ; Robert Weiss, Westchester Medical Center,
NY; Dilys Whyte, SUNY at Stony Brook; Craig Wong, UNM Children's
Hospital; Ellen Wood, Cardinal Glennon Children's Hospital in St Louis;
Jonathon Woods, Southeastern Neph Associates Wilmington; Ora Yadin,
Mattel's Children's Hospital UCLA; Verna Yiu, University of Alberta
Pediatric Nephrology, Edmonton; Gaston Zilleruelo, University of Miami.
NR 39
TC 23
Z9 23
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAR
PY 2011
VL 79
IS 6
BP 678
EP 685
DI 10.1038/ki.2010.485
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 727MO
UT WOS:000287804600013
PM 21178977
ER
PT J
AU Stumpel, DJPM
Schotte, D
Lange-Turenhout, EAM
Schneider, P
Seslija, L
de Menezes, RX
Marquez, VE
Pieters, R
den Boer, ML
Stam, RW
AF Stumpel, D. J. P. M.
Schotte, D.
Lange-Turenhout, E. A. M.
Schneider, P.
Seslija, L.
de Menezes, R. X.
Marquez, V. E.
Pieters, R.
den Boer, M. L.
Stam, R. W.
TI Hypermethylation of specific microRNA genes in MLL-rearranged infant
acute lymphoblastic leukemia: major matters at a micro scale
SO LEUKEMIA
LA English
DT Article
DE acute lymphoblastic leukemia; MLL; methylation; microRNA
ID EXPRESSION; METHYLATION; TARGETS; BIOLOGY; CANCER; CELLS;
OVEREXPRESSION; LEUKEMOGENESIS; CHROMATIN; PROFILES
AB MLL-rearranged acute lymphoblastic leukemia (ALL) in infants (< 1 year) is the most aggressive type of childhood leukemia. To develop more suitable treatment strategies, a firm understanding of the biology underlying this disease is of utmost importance. MLL-rearranged ALL displays a unique gene expression profile, partly explained by erroneous histone modifications. We recently showed that t(4;11)-positive infant ALL is also characterized by pronounced promoter CpG hypermethylation. In this study, we investigated whether this widespread hypermethylation also affected microRNA (miRNA) expression. We identified 11 miRNAs that were downregulated in t(4;11)-positive infant ALL as a consequence of CpG hypermethylation. Seven of these miRNAs were re-activated after exposure to the de-methylating agent Zebularine. Interestingly, five of these miRNAs are associated either with MLL or MLL fusions, and for miR-152 we found both MLL and DNA methyltransferase 1 (DNMT1) as potential targeted genes. Finally, a high degree of methylation of the miR-152 CpG island was strongly correlated with a poor clinical outcome. Our data suggests that inhibitors of methylation have a potential beyond re-expression of hypermethylated protein-coding genes in t(4;11)-positive infant ALL. In this study, we provide additional evidence that they should be tested for their efficacy in MLL-rearranged infant ALL in in vivo models. Leukemia (2011) 25, 429-439; doi:10.1038/leu.2010.282; published online 30 November 2010
C1 [Stumpel, D. J. P. M.; Schotte, D.; Lange-Turenhout, E. A. M.; Schneider, P.; Seslija, L.; de Menezes, R. X.; Pieters, R.; den Boer, M. L.; Stam, R. W.] Erasmus MC, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, NL-3015 GE Rotterdam, Netherlands.
[Marquez, V. E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
RP Stam, RW (reprint author), Erasmus MC, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Room Ee15-14A,Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM r.stam@erasmusmc.nl
FU Sophia Foundation for Medical Research [495]; Dutch Cancer Society;
Netherlands Organization for Scientific Research; Pediatric Oncology
Foundation Rotterdam; NIH, National Cancer Institute; Center for Cancer
Research
FX We wish to express gratitude to the members and participating hospitals
of the INTERFANT-99 study for supporting our research by providing
leukemic samples. Members of INTERFANT-99 are: Campbell M (PINDA),
Felice M (Argentina), Ferster A (CLCG), Hann I and Vora A (UKCCSG), Hovi
L (NOPHO), Janka-Schaub G (COALL), Li CK (Hong Kong), Mann G (BFM-A),
LeBlanc T (FRALLE), Pieters R (DCOG), de Rossi G and Biondi A (AIEOP),
Rubnitz J (SJCRH), Schrappe M (BFM-G), Silverman L (DFCI), Stary J
(CPH), Suppiah R (ANZCHOG), Szczepanski T (PPLLSG), Valsecchi M and de
Lorenzo P (CORS). This study was financially supported by grants from
the Sophia Foundation for Medical Research (SSWO Grant 495, RWS/RP), the
Dutch Cancer Society (EMCR 2005-2662, MLdB/RP), The Netherlands
Organization for Scientific Research (NWO-Vidi Grant, MLdB) and the
Pediatric Oncology Foundation Rotterdam (MLdB/RP). Furthermore, this
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute and Center for Cancer Research (VEM).
NR 42
TC 42
Z9 44
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAR
PY 2011
VL 25
IS 3
BP 429
EP 439
DI 10.1038/leu.2010.282
PG 11
WC Oncology; Hematology
SC Oncology; Hematology
GA 732CB
UT WOS:000288159500005
PM 21116279
ER
PT J
AU Zabow, G
Dodd, SJ
Shapiro, E
Moreland, J
Koretsky, AP
AF Zabow, Gary
Dodd, Stephen J.
Shapiro, Erik
Moreland, John
Koretsky, Alan P.
TI Microfabricated High-Moment Micrometer-Sized MRI Contrast Agents
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE contrast agent; microfabrication; microparticle; nanoparticle; MPIO
ID SINGLE MAMMALIAN-CELLS; IRON-OXIDE PARTICLES; SUSCEPTIBILITY ARTIFACTS;
TRANSVERSE RELAXATION; MAGNETIZED SPHERES; CELLULAR MRI; SPIN-ECHO;
RESOLUTION
AB While chemically synthesized superparamagnetic microparticles have enabled much new research based on MRI tracking of magnetically labeled cells, signal-to-noise levels still limit the potential range of applications. Here it is shown how, through top-down microfabrication, contrast agent relaxivity can be increased several-fold, which should extend the sensitivity of such cell-tracking studies. Microfabricated agents can benefit from both higher magnetic moments and higher uniformity than their chemically synthesized counterparts, implying increased label visibility and more quantitative image analyses. To assess the performance of microfabricated micrometer-sized contrast agent particles, analytic models and numerical simulations are developed and tested against new microfabricated agents described in this article, as well as against results of previous imaging studies of traditional chemically synthesized microparticle agents. Experimental data showing signal effects of 500-nm thick, 2-mu m diameter, gold-coated iron and gold-coated nickel disks verify the simulations. Additionally, it is suggested that measures of location better than the pixel resolution can be obtained and that these are aided using well-defined contrast agent particles achievable through microfabrication techniques. Magn Reson Med 65:645-655, 2011. (c) 2010 Wiley-Liss, Inc.
C1 [Zabow, Gary; Dodd, Stephen J.; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Zabow, Gary; Moreland, John] Natl Inst Stand & Technol, Electromagnet Div, Boulder, CO USA.
[Shapiro, Erik] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA.
RP Zabow, G (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,MSC 1065,Bldg 10,Room B1D728, Bethesda, MD 20892 USA.
EM zabowg@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NINDS NIH
FX Grant sponsor: NINDS NIH Intramural Research Program.
NR 30
TC 6
Z9 6
U1 1
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD MAR
PY 2011
VL 65
IS 3
BP 645
EP 655
DI 10.1002/mrm.22647
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 729DW
UT WOS:000287929800006
PM 20928829
ER
PT J
AU Frazier, EP
Isenberg, JS
Shiva, S
Zhao, L
Schlesinger, P
Dimitry, J
Abu-Asab, MS
Tsokos, M
Roberts, DD
Frazier, WA
AF Frazier, Elfaridah P.
Isenberg, Jeff S.
Shiva, Sruti
Zhao, Lei
Schlesinger, Paul
Dimitry, Julie
Abu-Asab, Mones S.
Tsokos, Maria
Roberts, David D.
Frazier, William A.
TI Age-dependent regulation of skeletal muscle mitochondria by the
thrombospondin-1 receptor CD47
SO MATRIX BIOLOGY
LA English
DT Article
DE Mitochondrial biogenesis; Skeletal muscles; Mitochondria; CD47 receptor;
Fast twitch fibers; Slow-twitch fibers
ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; ISCHEMIA-REPERFUSION INJURY;
NITRIC-OXIDE; CALORIE RESTRICTION; GENE-EXPRESSION; CELL RESPONSES;
PROTEIN-KINASE; METABOLIC DISEASE; TISSUE SURVIVAL; MICE
AB CD47, a receptor for thrombospondin-1, limits two important regulatory axes: nitric oxide-cGMP signaling and cAMP signaling, both of which can promote mitochondrial biogenesis. Electron microscopy revealed increased mitochondria( densities in skeletal muscle from both CD47 null and thrombospondin-1 null mice. We further assessed the mitochondria status of CD47-null vs WT mice. Quantitative RT-PCR of RNA extracted from tissues of 3 month old mice revealed dramatically elevated expression of mRNAs encoding mitochondrial proteins and PGC-1 alpha in both fast and slow-twitch skeletal muscle from CD47-null mice, but modest to no elevation in other tissues. These observations were confirmed by Western blotting of mitochondria! proteins. Relative amounts of electron transport enzymes and ATP/O-2 ratios of isolated mitochondria were not different between mitochondria from CD47-null and WT cells. Young CD47-null mice displayed enhanced treadmill endurance relative to WTs and CD47-null gastrocnemius had undergone fiber type switching to a slow-twitch pattern of myoglobin and myosin heavy chain expression. In 12 month old mice, both skeletal muscle mitochondrial volume density and endurance had decreased to wild type levels. Expression of myosin heavy chain isoforms and myoglobin also reverted to a fast twitch pattern in gastrocnemius. Both CD47 and TSP1 null mice are leaner than WTs, use less oxygen and produce less heat than WT mice. CD47-null cells produce substantially less reactive oxygen species than WT cells. These data indicate that loss of signaling from the TSP1-CD47 system promotes accumulation of normally functioning mitochondria in a tissue-specific and age-dependent fashion leading to enhanced physical performance, lower reactive oxygen species production and more efficient metabolism. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Frazier, Elfaridah P.; Zhao, Lei; Schlesinger, Paul; Dimitry, Julie; Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Frazier, Elfaridah P.; Zhao, Lei; Schlesinger, Paul; Dimitry, Julie; Frazier, William A.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Sch Med, Dept Med, Vasc Med Inst, Pittsburgh, PA 15213 USA.
[Shiva, Sruti] Univ Pittsburgh, Sch Med, Dept Pharmacol, Vasc Med Inst, Pittsburgh, PA 15213 USA.
[Shiva, Sruti] Univ Pittsburgh, Sch Med, Dept Biol Chem, Vasc Med Inst, Pittsburgh, PA 15213 USA.
[Abu-Asab, Mones S.; Tsokos, Maria; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Frazier, WA (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM frazier@wustl.edu
RI Roberts, David/A-9699-2008;
OI Roberts, David/0000-0002-2481-2981; Abu-Asab, Mones/0000-0002-4047-1232
FU NHLBI [R01 HL054390]; NIH, NCI, Center for Cancer Research; [K22
CA128616]
FX Funding was provided by R01 HL054390 from the NHLBI to WAF, the
Intramural Research Program of the NIH, NCI, Center for Cancer Research
to DDR and MT, and K22 CA128616 to JSI. EPF is a postdoctoral fellow of
the American Heart Association.
NR 66
TC 21
Z9 21
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
J9 MATRIX BIOL
JI Matrix Biol.
PD MAR
PY 2011
VL 30
IS 2
BP 154
EP 161
DI 10.1016/j.matbio.2010.12.004
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 743IE
UT WOS:000289011100009
PM 21256215
ER
PT J
AU Kuzin, A
Kundu, M
Brody, T
Odenwald, WF
AF Kuzin, Alexander
Kundu, Mukta
Brody, Thomas
Odenwald, Ward F.
TI Functional analysis of conserved sequences within a temporally
restricted neural precursor cell enhancer
SO MECHANISMS OF DEVELOPMENT
LA English
DT Article
DE Drosophila CNS development; Gene regulation; cis-Regulatory enhancers;
DNA sequence conservation
ID DEVELOPING NERVOUS-SYSTEM; DNA-BINDING SITE; DROSOPHILA-MELANOGASTER;
TRANSCRIPTION-FACTORS; DEVELOPMENTAL ENHANCERS; OVERLAP EXTENSION;
PATTERN-FORMATION; GENETIC-ANALYSIS; ELEMENT VECTORS; PROSPERO GENE
AB Many of the key regulators of Drosophila CNS neural identity are expressed in defined temporal orders during neuroblast (NB) lineage development. To begin to understand the structural and functional complexity of enhancers that regulate ordered NB gene expression programs, we have undertaken the mutational analysis of the temporally restricted nerfin-1 NB enhancer. Our previous studies have localized the enhancer to a region just proximal to the nerfin-1 transcription start site. Analysis of this enhancer, using the phylogenetic footprint program EvoPrinter, reveals the presence of multiple sequence blocks that are conserved among drosophilids. cis-Decoder alignments of these conserved sequence blocks (CSBs) has identified shorter elements that are conserved in other Drosophila NB enhancers. Mutagenesis of the enhancer reveals that although each CSB is required for wild-type expression, neither position nor orientation of the CSBs within the enhancer is crucial for enhancer function; removal of less-conserved or non-conserved sequences flanking CSB clusters also does not significantly alter enhancer activity. While all three conserved E-box transcription factor (TF) binding sites (CAGCTG) are required for full function, adding an additional site at different locations within non-conserved sequences interferes with enhancer activity. Of particular note, none of the mutations resulted in ectopic reporter expression outside of the early NB expression window, suggesting that the temporally restricted pattern is defined by transcriptional activators and not by direct DNA binding repressors. Our work also points to an unexpectedly large number of TFs required for optimal enhancer function-mutant TF analysis has identified at least four that are required for full enhancer regulation. Published by Elsevier Ireland Ltd.
C1 [Kuzin, Alexander; Kundu, Mukta; Brody, Thomas; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
RP Kuzin, A (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM alex.kuzin@ninds.nih.gov; brodyt@ninds.nih.gov; ward@codon.nih.gov
FU NIH, NINDS
FX The authors thank Jermaine Ross and Antonios Ekatomatis for their
technical assistance and the editorial expertise of Judith Brody. We
also acknowledge the Bloomington Drosophila Stock Center and Chris Doe
for providing mutant fly stocks. This research was supported by the
Intramural Research Program of the NIH, NINDS.
NR 86
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4773
J9 MECH DEVELOP
JI Mech. Dev.
PD MAR-APR
PY 2011
VL 128
IS 3-4
BP 165
EP 177
DI 10.1016/j.mod.2011.02.001
PG 13
WC Developmental Biology
SC Developmental Biology
GA 739TC
UT WOS:000288739900001
PM 21315151
ER
PT J
AU Lee, C
Kim, KP
Long, D
Fisher, R
Tien, C
Simon, SL
Bouville, A
Bolch, WE
AF Lee, Choonsik
Kim, Kwang Pyo
Long, Daniel
Fisher, Ryan
Tien, Chris
Simon, Steven L.
Bouville, Andre
Bolch, Wesley E.
TI Organ doses for reference adult male and female undergoing computed
tomography estimated by Monte Carlo simulations
SO MEDICAL PHYSICS
LA English
DT Article
DE computed tomography; organ dose; Monte Carlo transport; hybrid phantom
ID HYBRID COMPUTATIONAL PHANTOMS; TUBE CURRENT MODULATION; MULTIDETECTOR
CT; RADIATION-DOSIMETRY; HUMAN ANATOMY; MODELS; PATIENT; MORPHOMETRY;
TOOL
AB Purpose: To develop a computed tomography (CT) organ dose estimation method designed to readily provide organ doses in a reference adult male and female for different scan ranges to investigate the degree to which existing commercial programs can reasonably match organ doses defined in these more anatomically realistic adult hybrid phantoms
Methods: The x-ray fan beam in the SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code MCNPX2.6. The simulated CT scanner model was validated through comparison with experimentally measured lateral free-in-air dose profiles and computed tomography dose index (CTDI) values. The reference adult male and female hybrid phantoms were coupled with the established CT scanner model following arm removal to simulate clinical head and other body region scans. A set of organ dose matrices were calculated for a series of consecutive axial scans ranging from the top of the head to the bottom of the phantoms with a beam thickness of 10 mm and the tube potentials of 80, 100, and 120 kVp. The organ doses for head, chest, and abdomen/pelvis examinations were calculated based on the organ dose matrices and compared to those obtained from two commercial programs, CT-EXPO and CTDOSIMETRY. Organ dose calculations were repeated for an adult stylized phantom by using the same simulation method used for the adult hybrid phantom.
Results: Comparisons of both lateral free-in-air dose profiles and CTDI values through experimental measurement with the Monte Carlo simulations showed good agreement to within 9%. Organ doses for head, chest, and abdomen/pelvis scans reported in the commercial programs exceeded those from the Monte Carlo calculations in both the hybrid and stylized phantoms in this study, sometimes by orders of magnitude.
Conclusions: The organ dose estimation method and dose matrices established in this study readily provides organ doses for a reference adult male and female for different CT scan ranges and technical parameters. Organ doses from existing commercial programs do not reasonably match organ doses calculated for the hybrid phantoms due to differences in phantom anatomy, as well as differences in organ dose scaling parameters. The organ dose matrices developed in this study will be extended to cover different technical parameters, CT scanner models, and various age groups. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3544658]
C1 [Lee, Choonsik; Simon, Steven L.; Bouville, Andre] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
[Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Yongin 446701, South Korea.
[Long, Daniel; Fisher, Ryan; Tien, Chris; Bolch, Wesley E.] Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32611 USA.
RP Lee, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
EM leechoonsik@mail.nih.gov
NR 50
TC 37
Z9 37
U1 0
U2 4
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD MAR
PY 2011
VL 38
IS 3
BP 1196
EP 1206
DI 10.1118/1.3544658
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 728MY
UT WOS:000287879400009
PM 21520832
ER
PT J
AU Cadieux, N
Parra, M
Cohen, H
Maric, D
Morris, SL
Brennan, MJ
AF Cadieux, Nathalie
Parra, Marcela
Cohen, Hannah
Maric, Dragan
Morris, Sheldon L.
Brennan, Michael J.
TI Induction of cell death after localization to the host cell mitochondria
by the Mycobacterium tuberculosis PE_PGRS33 protein
SO MICROBIOLOGY-SGM
LA English
DT Article
ID PE-PGRS PROTEINS; GENOME SEQUENCE; VII SECRETION; MACROPHAGES;
EXPRESSION; NECROSIS; APOPTOSIS; VIRULENCE; SYSTEM; FAMILY
AB PE_PGRS33 is the most studied member of the unique PE family of mycobacterial proteins. These proteins are composed of a PE domain (Pro-Glu motif), a linker region and a PGRS domain (polymorphic GC-rich-repetitive sequence). Previous studies have shown that PE_PGRS33 is surface-exposed, constitutively expressed during growth and infection, involved in creating antigenic diversity, and able to induce death in transfected or infected eukaryotic cells. In this study, we showed that PE_PGRS33 co-localizes to the mitochondria of transfected cells, a phenomenon dependent on the linker region and the PGRS domain, but not the PE domain. Using different genetic fusions and chimeras, we also demonstrated a direct correlation between localization to the host mitochondria and the induction of cell death. Finally, although all constructs localizing to the mitochondria did induce apoptosis, only the wild-type PE_PGRS33 with its own PE domain also induced primary necrosis, indicating a potentially important role for the PE domain. Considering the importance of primary necrosis in Mycobacterium tuberculosis dissemination during natural infection, the PE_PGRS33 protein may play a crucial role in the pathogenesis of tuberculosis.
C1 [Cadieux, Nathalie; Brennan, Michael J.] AERAS Global TB Vaccine Fdn, Rockville, MD USA.
[Cadieux, Nathalie; Parra, Marcela; Cohen, Hannah; Morris, Sheldon L.; Brennan, Michael J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, NIH, Flow Cytometry Core Facil, Bethesda, MD USA.
RP Cadieux, N (reprint author), AERAS Global TB Vaccine Fdn, Rockville, MD USA.
EM ncadieux@aeras.org
FU National Vaccine Program Office of the Department of Health and Human
Services
FX We would like to thank Veerabadran Dheenadhayalan, Karen Meysick and
Jackie Muller for invaluable discussions during this study. This work
was supported in part by a grant from the National Vaccine Program
Office of the Department of Health and Human Services to M. j. B.
NR 45
TC 29
Z9 30
U1 0
U2 5
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 MAR
PY 2011
VL 157
BP 793
EP 804
DI 10.1099/mic.0.041996-0
PN 3
PG 12
WC Microbiology
SC Microbiology
GA 740ZN
UT WOS:000288833000018
PM 21081760
ER
PT J
AU Moore, ER
Mead, DJ
Dooley, CA
Sager, J
Hackstadt, T
AF Moore, Elizabeth R.
Mead, David J.
Dooley, Cheryl A.
Sager, Janet
Hackstadt, Ted
TI The trans-Golgi SNARE syntaxin 6 is recruited to the chlamydial
inclusion membrane
SO MICROBIOLOGY-SGM
LA English
DT Article
ID TRACHOMATIS INCLUSION; ENDOCYTIC PATHWAY; INFECTED-CELLS; RAB GTPASES;
EPITHELIAL-CELLS; PLASMA-MEMBRANE; HOST PROTEINS; PSITTACI;
SPHINGOMYELIN; TRAFFICKING
AB Chlamydia trachomatis is an obligate intracellular pathogen that replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusion is isolated from the endocytic pathway but fusogenic with Golgi-derived exocytic vesicles containing sphingomyelin and cholesterol. Sphingolipids are incorporated into the chlamydial cell wall and are considered essential for chlamydial development and viability. The mechanisms by which chlamydiae obtain eukaryotic lipids are poorly understood but require chlamydial protein synthesis and presumably modification of the inclusion membrane to initiate this interaction. A polarized cell model of chlamydial infection has demonstrated that chlamydiae preferentially intercept basolaterally directed, sphingomyelin-containing exocytic vesicles. Here we examine the localization and potential function of trans-Golgi and/or basolaterally associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in chlamydia-infected cells. The trans-Golgi SNARE protein syntaxin 6 is recruited to the chlamydial inclusion in a manner that requires chlamydial protein synthesis and is conserved among all chlamydial species examined. The localization of syntaxin 6 to the chlamydial inclusion requires a tyrosine motif or plasma membrane retrieval signal (YGRL). Thus in addition to expression of at least two inclusion membrane proteins that contain SNARE-like motifs, chlamydiae also actively recruit eukaryotic SNARE-family proteins.
C1 [Moore, Elizabeth R.; Mead, David J.; Dooley, Cheryl A.; Sager, Janet; Hackstadt, Ted] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact Sect, Hamilton, MT 59840 USA.
RP Hackstadt, T (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact Sect, 903 S 4th St, Hamilton, MT 59840 USA.
EM thackstadt@niaid.nih.gov
FU NIAID/NIH
FX This work was supported by the Intramural Research Program of the
NIAID/NIH. We thank Dr Jeffrey Pessin (Albert Einstein College of
Medicine, Bronx, NY) for the eGFP-syntaxin 6 construct and Dr Harlan
Caldwell (NIAID Rocky Mountain Laboratories, Hamilton, MT) for the
antibody against C. pneumoniae. We would also like to thank Tina Clark
for excellent technical assistance.
NR 57
TC 26
Z9 26
U1 1
U2 8
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 MAR
PY 2011
VL 157
BP 830
EP 838
DI 10.1099/mic.0.045856-0
PN 3
PG 9
WC Microbiology
SC Microbiology
GA 740ZN
UT WOS:000288833000021
PM 21109560
ER
PT J
AU Lopez-Barragan, MJ
Quinones, M
Cui, KR
Lemieux, J
Zhao, KJ
Su, XZ
AF Lopez-Barragan, Maria Jose
Quinones, Mariam
Cui, Kairong
Lemieux, Jacob
Zhao, Keji
Su, Xin-zhuan
TI Effect of PCR extension temperature on high-throughput sequencing
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE New generation sequencing; Malaria; Genome; Amplification bias;
Nucleosome
ID HUMAN MALARIA PARASITE; PLASMODIUM-FALCIPARUM; GENOME; SUITE; DNA
AB The DNA amplification process can be a source of bias and artifacts, especially when amplifying genomic areas with extreme AT or GC content. The human malaria parasite Plasmodium falciparum has an AT-rich genome, and some of its highly AT-rich regions have been shown to be refractory to polymerase chain reaction (PCR) amplification. Biased amplification may lead to erroneous conclusions for studies investigating genome-wide gene expression, nucleosome position, and copy number variation. Here we compare genome-wide nucleosome coverage in libraries amplified at three different extension temperatures and show that reduction in PCR extension temperature from 70 degrees C to 60 degrees C can greatly increase the fraction of coverage at AT-rich regions of the P. falciparum genome. Our method will improve the efficiency and coverage in sequencing an AT-rich genome. Published by Elsevier B.V.
C1 [Lopez-Barragan, Maria Jose; Lemieux, Jacob; Su, Xin-zhuan] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
[Quinones, Mariam] NIAID, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA.
[Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Su, XZ (reprint author), NIH, Lab Malaria & Vector Res, Bldg 10, Bethesda, MD 20892 USA.
EM xsu@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU Divisions of Intramural Research at the National Institute of Allergy
and Infectious Diseases; National Heart, Lung and Blood Institute
FX We thank Artem Barski, Qingsong Tang, and Gang Wei for assistance with
the Illumina sequencing. This work was supported by the Divisions of
Intramural Research at the National Institute of Allergy and Infectious
Diseases and National Heart, Lung and Blood Institute. We thank NIAID
intramural editor Brenda Rae Marshall for assistance.
NR 18
TC 8
Z9 8
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
EI 1872-9428
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD MAR
PY 2011
VL 176
IS 1
BP 64
EP 67
DI 10.1016/j.molbiopara.2010.11.013
PG 4
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA 720MM
UT WOS:000287284800010
PM 21112355
ER
PT J
AU Kim, E
Hyrc, KL
Speck, J
Salles, FT
Lundberg, YW
Goldberg, MP
Kachar, B
Warchol, ME
Ornitz, DM
AF Kim, Euysoo
Hyrc, Krzysztof L.
Speck, Judith
Salles, Felipe T.
Lundberg, Yunxia W.
Goldberg, Mark P.
Kachar, Bechara
Warchol, Mark E.
Ornitz, David M.
TI Missense mutations in Otopetrin 1 affect subcellular localization and
inhibition of purinergic signaling in vestibular supporting cells
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Vestibular; Otoconia; Otopetrin; Calcium; Purinergic signaling
ID OTOCONIAL AGENESIS; INNER-EAR; CALCIUM; RECEPTORS; MICE
AB Otopetrin 1 (Otop1) encodes a protein that is essential for the development of otoconia. Otoconia are the extracellular calcium carbonate containing crystals that are important for vestibular mechanosensory transduction of linear motion and gravity. There are two mutant alleles of Otop1 in mice, titled (tit) and mergulhador (mlh), which result in non-syndromic otoconia agenesis and a consequent balance defect. Biochemically, Otop1 has been shown to modulate purinergic control of intracellular calcium in vestibular supporting cells, which could be one of the mechanisms by which Otop1 participates in the mineralization of otoconia. To understand how tit and mlh mutations affect the biochemical function of Otop1, we examined the purinergic response of COS7 cells expressing mutant Otop1 proteins, and dissociated sensory epithelial cells from tit and mlh mice. We also examined the subcellular localization of Otop1 in whole sensory epithelia from tit and mlh mice. Here we show that tit and mlh mutations uncouple Otop1 from inhibition of P2Y receptor function. Although the in vitro biochemical function of the Otop1 mutant proteins is normal, in vivo they behave as null alleles. We show that in supporting cells the apical membrane localization of the mutant Otop1 proteins is lost. These data suggest that the tit and mlh mutations primarily affect the localization of Otop1, which interferes with its ability to interact with other proteins that are important for its cellular and biochemical function. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Kim, Euysoo; Ornitz, David M.] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
[Hyrc, Krzysztof L.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Speck, Judith; Warchol, Mark E.] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA.
[Salles, Felipe T.; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
[Lundberg, Yunxia W.] Boys Town Natl Res Hosp, Dept Genet, Omaha, NE 68131 USA.
[Goldberg, Mark P.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA.
RP Ornitz, DM (reprint author), Washington Univ, Sch Med, Dept Dev Biol, Campus Box 8103,660 S Euclid Ave, St Louis, MO 63110 USA.
EM dornitz@wustl.edu
RI Salles, Felipe/H-7544-2013;
OI Hyrc, Krzysztof/0000-0002-8830-6324; Ornitz, David/0000-0003-1592-7629
FU NIH [DC02236, NS032636, NS036265, DC008603]; Neuroscience Blueprint Core
grant [P30 NS057105]; Bakewell Family Science Foundation; Microscopy and
Digital Imaging (MDI) Core [P30 DC004665]; Ornitz Family Charitable
Trust
FX We thank C. Smith for technical help. This work was funded by NIH grants
DC02236 (D.M.O.), NS032636 and NS036265 (M.P.G.), DC008603 (Y.W.L.),
Neuroscience Blueprint Core grant (P30 NS057105), Bakewell Family
Science Foundation, Microscopy and Digital Imaging (MDI) Core (P30
DC004665) and the Ornitz Family Charitable Trust.
NR 14
TC 9
Z9 10
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 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD MAR
PY 2011
VL 46
IS 3
BP 655
EP 661
DI 10.1016/j.mcn.2011.01.005
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 731ZW
UT WOS:000288150900010
PM 21236346
ER
PT J
AU Monti, P
Perfumo, C
Bisio, A
Ciribilli, Y
Menichini, P
Russo, D
Umbach, DM
Resnick, MA
Inga, A
Fronza, G
AF Monti, Paola
Perfumo, Chiara
Bisio, Alessandra
Ciribilli, Yari
Menichini, Paola
Russo, Debora
Umbach, David M.
Resnick, Michael A.
Inga, Alberto
Fronza, Gilberto
TI Dominant-Negative Features of Mutant TP53 in Germline Carriers Have
Limited Impact on Cancer Outcomes
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID WILD-TYPE P53; N3-ADENINE METHYLATING AGENT; YEAST FUNCTIONAL ASSAY;
BASE EXCISION-REPAIR; LI-FRAUMENI; CELL-LINES; ME-LEX; MUTATION;
PROTEIN; FAMILY
AB Germline TP53 mutations result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni-like, and nonsyndromic predisposition with or without family history. To explore genotype/phenotype associations, we previously adopted a functional classification of all germline TP53 mutant alleles based on transactivation. Severe deficiency (SD) alleles were associated with more severe cancer proneness syndromes, and a larger number of tumors, compared with partial deficiency (PD) alleles. Because mutant p53 can exert dominant-negative (DN) effects, we addressed the relationship between DN and clinical manifestations. We reasoned that DN effects might be stronger in familial cancer cases associated with germline TP53 mutations, where mutant alleles coexist with the wild-type allele since conception. We examined 104 p53 mutant alleles with single amino acid substitutions described in the IARC germline database for (i) transactivation capability and (ii) capacity to reduce the activity of the wild-type allele (i.e., DN effect) using a quantitative yeast-based assay. The functional classifications of p53 alleles were then related to clinical variables. We confirmed that a classification based on transactivation alone can identify familial cancer cases with more severe clinical features. Classification based on DN effects allowed us to highlight similar associations but did not reveal distinct clinical subclasses of SD alleles, except for a correlation with tumor tissue prevalence. We conclude that in carriers of germline TP53 mutations transactivation-based classification of TP53 alleles appears more important for genotype/phenotype correlations than DN effects and that haplo-insufficiency of the TP53 gene is an important factor in cancer proneness in humans. Mol Cancer Res; 9(3); 271-9. (C) 2011 AACR.
C1 [Monti, Paola; Perfumo, Chiara; Menichini, Paola; Russo, Debora; Fronza, Gilberto] Natl Inst Canc Res, Dept Epidemiol & Prevent, Mol Mutagenesis & DNA Repair Unit, Genoa, Italy.
[Bisio, Alessandra; Ciribilli, Yari; Inga, Alberto] Univ Trent, Ctr Integrat Biol, Lab Transcript Networks, Trento, Italy.
[Umbach, David M.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Resnick, Michael A.] NIEHS, Chromosome Stabil Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Fronza, G (reprint author), Natl Canc Res Inst IST, Dept Epidemiol & Prevent, Mol Mutagenesis & DNA Repair Unit, Largo Rosanna Benzi 10, I-16132 Genoa, Italy.
EM gilberto.fronza@istge.it
RI Bisio, Alessandra/C-8214-2011
FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [9086, 5506];
NIH, National Institute of Environmental Health Sciences
FX The work was supported in part by Associazione Italiana per la Ricerca
sul Cancro (AIRC: IG#9086 to A. Inga, and IG#5506 to G. Fronza) and in
part by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences.
NR 38
TC 18
Z9 18
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD MAR
PY 2011
VL 9
IS 3
BP 271
EP 279
DI 10.1158/1541-7786.MCR-10-0496
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 735NL
UT WOS:000288424100003
PM 21343334
ER
PT J
AU Zhu, WG
Lee, CY
Johnson, RL
Wichterman, J
Huang, RL
DePamphilis, ML
AF Zhu, Wenge
Lee, Chrissie Y.
Johnson, Ronald L.
Wichterman, Jennifer
Huang, Ruili
DePamphilis, Melvin L.
TI An Image-Based, High-Throughput Screening Assay for Molecules that
Induce Excess DNA Replication in Human Cancer Cells
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID PROTEIN-KINASE INHIBITORS; CDT1-GEMININ INTERACTION; IN-VITRO; TUBULIN
POLYMERIZATION; BIOLOGICAL-ACTIVITIES; ANTIALCOHOLISM DRUG; PROTEASOME
ACTIVITY; MITOTIC SLIPPAGE; BREAST-CANCER; BONE-MARROW
AB Previous studies have shown DNA re-replication can be induced in cells derived from human cancers under conditions in which it is not possible for cells derived from normal tissues. Because DNA re-replication induces cell death, this strategy could be applied to the discovery of potential anticancer therapeutics. Therefore, an imaging assay amenable to high-throughput screening was developed that measures DNA replication in excess of four genomic equivalents in the nuclei of intact cells and indexes cell proliferation. This assay was validated by screening a library of 1,280 bioactive molecules on both normal and tumor-derived cells where it proved more sensitive than current methods for detecting excess DNA replication. This screen identified known inducers of excess DNA replication, such as inhibitors of microtubule dynamics, and novel compounds that induced excess DNA replication in both normal and cancer cells. In addition, two compounds were identified that induced excess DNA replication selectively in cancer cells and one that induced endocycles selectively in cancer cells. Thus, this assay provides a new approach to the discovery of compounds useful for investigating the regulation of genome duplication and for the treatment of cancer. Mol Cancer Res; 9(3); 294-310. (C) 2011 AACR.
C1 [Zhu, Wenge; Lee, Chrissie Y.; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Johnson, Ronald L.; Wichterman, Jennifer; Huang, Ruili] NIH, NIH Chem Genom Ctr, Rockville, MD USA.
RP DePamphilis, ML (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM depamphm@mail.nih.gov
FU NIH Roadmap for Medical Research; National Human Genome Research
Institute; National Institute of Child Health and Human Development; NIH
[4R00CA136555]
FX This work was supported by the NIH Roadmap for Medical Research, the
intramural research programs of the National Human Genome Research
Institute and the National Institute of Child Health and Human
Development, and NIH grant 4R00CA136555 awarded to W. Zhu.
NR 61
TC 12
Z9 12
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD MAR
PY 2011
VL 9
IS 3
BP 294
EP 310
DI 10.1158/1541-7786.MCR-10-0570
PG 17
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 735NL
UT WOS:000288424100005
PM 21257818
ER
PT J
AU Strader, MB
Costantino, N
Elkins, CA
Chen, CY
Patel, I
Makusky, AJ
Choy, JS
Court, DL
Markey, SP
Kowalak, JA
AF Strader, Michael Brad
Costantino, Nina
Elkins, Christopher A.
Chen, Cai Yun
Patel, Isha
Makusky, Anthony J.
Choy, John S.
Court, Donald L.
Markey, Sanford P.
Kowalak, Jeffrey A.
TI A Proteomic and Transcriptomic Approach Reveals New Insight into
beta-methylthiolation of Escherichia coli Ribosomal Protein S12
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID TRANSFER-RNA; MASS-SPECTROMETRY; POSTTRANSLATIONAL MODIFICATION;
STRUCTURAL INSIGHTS; GENE-EXPRESSION; MESSENGER-RNA; 70S RIBOSOME; MIAB
PROTEIN; FNR; METHYLATION
AB beta-methylthiolation is a novel post-translational modification mapping to a universally conserved Asp 88 of the bacterial ribosomal protein S12. This S12 specific modification has been identified on orthologs from multiple bacterial species. The origin and functional significance was investigated with both a proteomic strategy to identify candidate S12 interactors and expression microarrays to search for phenotypes that result from targeted gene knockouts of select candidates. Utilizing an endogenous recombinant E. coli S12 protein with an affinity tag as bait, mass spectrometric analysis identified candidate S12 binding partners including RimO (previously shown to be required for this post-translational modification) and YcaO, a conserved protein of unknown function. Transcriptomic analysis of bacterial strains with deleted genes for RimO and YcaO identified an overlapping transcriptional phenotype suggesting that YcaO and RimO likely share a common function. As a follow up, quantitative mass spectrometry additionally indicated that both proteins dramatically impacted the modification status of S12. Collectively, these results indicate that the YcaO protein is involved in beta-methylthiolation of S12 and its absence impairs the ability of RimO to modify S12. Additionally, the proteomic data from this study provides direct evidence that the E. coli specific beta-methylthiolation likely occurs when S12 is assembled as part of a ribosomal subunit. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.005199, 1-10, 2011.
C1 [Strader, Michael Brad; Chen, Cai Yun; Makusky, Anthony J.; Markey, Sanford P.; Kowalak, Jeffrey A.] NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA.
[Costantino, Nina; Court, Donald L.] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
[Elkins, Christopher A.; Patel, Isha] US FDA, Laurel, MD 20708 USA.
[Choy, John S.] NCI, Bethesda, MD 20892 USA.
RP Strader, MB (reprint author), NIMH, Lab Neurotoxicol, Bldg 10 Ctr Dr,Room 3D42,10 Ctr Dr,MSC 1262, Bethesda, MD 20892 USA.
EM straderm@mail.nih.gov
FU National Institute of Mental Health [1ZIAMH000274]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health(1ZIAMH000274).
NR 45
TC 7
Z9 9
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD MAR
PY 2011
VL 10
IS 3
AR M110.005199
DI 10.1074/mcp.M110.005199
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 728AY
UT WOS:000287847200022
PM 21169565
ER
PT J
AU Dickson, PI
Pariser, AR
Groft, SC
Ishihara, RW
McNeil, DE
Tagle, D
Griebel, DJ
Kaler, SG
Mink, JW
Shapiro, EG
Bjoraker, KJ
Krivitzky, L
Provenzale, JM
Gropman, A
Orchard, P
Raymond, G
Cohen, BH
Steiner, RD
Goldkind, SF
Nelson, RM
Kakkis, E
Patterson, MC
AF Dickson, P. I.
Pariser, A. R.
Groft, S. C.
Ishihara, R. W.
McNeil, D. E.
Tagle, D.
Griebel, D. J.
Kaler, S. G.
Mink, J. W.
Shapiro, E. G.
Bjoraker, K. J.
Krivitzky, L.
Provenzale, J. M.
Gropman, A.
Orchard, P.
Raymond, G.
Cohen, B. H.
Steiner, R. D.
Goldkind, S. F.
Nelson, R. M.
Kakkis, E.
Patterson, M. C.
TI Research challenges in central nervous system manifestations of inborn
errors of metabolism
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Review
DE Inborn errors of metabolism; Central nervous system; Rare disease;
Orphan drug designation; Translational research
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; UREA CYCLE
DISORDERS; X-LINKED ADRENOLEUKODYSTROPHY; ENZYME REPLACEMENT THERAPY;
INFANTILE KRABBES-DISEASE; HURLER-SYNDROME; MUCOPOLYSACCHARIDOSIS-I;
MENKES-DISEASE; INITIAL-EXPERIENCE
AB The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants. Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups. Published by Elsevier Inc.
C1 [Ishihara, R. W.; Griebel, D. J.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, Silver Spring, MD 20993 USA.
[Dickson, P. I.] Harbor UCLA, Dept Pediat, LA Biomed Res Inst, Torrance, CA 90502 USA.
[Groft, S. C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA.
[McNeil, D. E.] US FDA, Off Orphan Prod Dev, Off Commissioner, Silver Spring, MD 20993 USA.
[Tagle, D.] NINDS, NIH, Ctr Neurosci, Bethesda, MD 20892 USA.
[Kaler, S. G.] NICHHD, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA.
[Mink, J. W.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
[Mink, J. W.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Shapiro, E. G.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA.
[Shapiro, E. G.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Bjoraker, K. J.] Univ Colorado, Childrens Hosp Denver, Aurora, CO 80045 USA.
[Krivitzky, L.] Natl Rehabil Hosp, Childrens Res Inst, Ctr Res Neurosci, Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Provenzale, J. M.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Provenzale, J. M.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA.
[Provenzale, J. M.] Emory Univ, Sch Med, Dept Oncol, Atlanta, GA 30322 USA.
[Provenzale, J. M.] Emory Univ, Sch Med, Dept Biomed Engn, Atlanta, GA 30322 USA.
[Gropman, A.] Childrens Natl Med Ctr, Neurogenet Program, Washington, DC 20010 USA.
[Orchard, P.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Orchard, P.] Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA.
[Raymond, G.] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21205 USA.
[Raymond, G.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA.
[Cohen, B. H.] Cleveland Clin, Neurol Inst, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA.
[Steiner, R. D.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA.
[Steiner, R. D.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Doembecher Childrens Hosp, Portland, OR 97239 USA.
[Goldkind, S. F.] US FDA, Off Good Clin Practice, Off Commissioner, Silver Spring, MD 20993 USA.
[Nelson, R. M.] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA.
[Kakkis, E.] Kakkis EveryLife Fdn, Novato, CA 94949 USA.
[Patterson, M. C.] Mayo Clin, Div Child & Adolescent Neurol, Rochester, MN 55905 USA.
RP Pariser, AR (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, 10903 New Hampshire Ave,WO22-6474, Silver Spring, MD 20993 USA.
EM Pdickson@ucla.edu; Anne.pariser@fda.hhs.gov; Stephen.groft@nih.gov;
Richard.ishihara@fda.hhs.gov; Dawn.mcneil@fda.hhs.gov;
Tagled@ninds.nih.gov; Donna.griebel@fda.hhs.gov; Kalers@mail.nih.gov;
Jonathan_Mink@rochester.edu; Shapi004@umn.edu;
Bjoraker.kendra@tchden.org; LKrivitz@cnmc.org; Prove001@mc.duke.edu;
Agropman@cnmc.org; Orcha001@umn.edu; Raymond@kennedykrieger.org;
Bhcohenmd@aol.com; Steinerr@ohsu.edu; Sara.goldkind@fda.hhs.gov;
Robert.nelson@fda.hhs.gov; Ekakkis@kakkis.org; Patterson.marc@mayo.edu
OI Steiner, Robert/0000-0003-4177-4590; Patterson, Marc/0000-0002-1116-126X
FU NIH Office Rare Diseases Research, National Institute of Neurological
Disorders and Stroke; FDA Center for Drug Evaluation and Research,
Division of Gastroenterology; National Institute of Child Health and
Development Intramural Research Program; Batten Disease Support and
Research Association [R01NS060022]; Lysosomal Disease Network;
NS065768-01; Urea Cycle Disorders Consortium NIH [RR019453]; National
Institute of Neurological Disorders and Stroke [NS054242]; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[HD057136]; Food and Drug Administration [FD003450]; Genzyme
Corporation; Stem Cells Inc.
FX The Research Challenges in CNS Manifestations of Inborn Errors of
Metabolism workshop was funded by the NIH Office Rare Diseases Research,
National Institute of Neurological Disorders and Stroke, and the FDA
Center for Drug Evaluation and Research, Division of Gastroenterology
Products. Research presented was funded by: National Institute of Child
Health and Development Intramural Research Program (SGK), Batten Disease
Support and Research Association (JWM, R01NS060022), the Lysosomal
Disease Network U54 (EGS, NS065768-01), the Urea Cycle Disorders
Consortium NIH U54 (RR019453), the National Institute of Neurological
Disorders and Stroke (PID, NS054242), the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (GR, HD057136),
the Food and Drug Administration (PID, FD003450), Genzyme Corporation,
and Stem Cells Inc.
NR 44
TC 8
Z9 9
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2011
VL 102
IS 3
BP 326
EP 338
DI 10.1016/j.ymgme.2010.11.164
PG 13
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 727CA
UT WOS:000287773800156
PM 21176882
ER
PT J
AU Patel, SR
Hendrickson, JE
Smith, NH
Cadwell, CM
Ozato, K
Morse, HC
Yoshimi, R
Zimring, JC
AF Patel, Seema R.
Hendrickson, Jeanne E.
Smith, Nicole H.
Cadwell, Chantel M.
Ozato, Keiko
Morse, Herbert C., III
Yoshimi, Ryusuke
Zimring, James C.
TI Alloimmunization against RBC or PLT antigens is independent of TRIM21
expression in a murine model
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Transfusion; Alloimmunization; TRIM21; Red blood cell; Platelet
ID SICKLE-CELL DISEASE; RED-BLOOD-CELLS; TRANSFUSION; INFLAMMATION; GENE;
MICE
AB Generation of alloantibodies to transfused RBCs can be a serious medical problem for patients who require chronic RBC transfusion therapy. Patients with sickle cell disease have a substantially increased rate of alloimmunization compared to other chronically transfused populations. A recent study has forwarded the hypothesis that a polymorphism in an immunoregulatory gene in close proximity to beta-globin (TRIM21 rs660) plays a role in the increased rates of RBC alloimmunization in sickle cell patients. In particular, it was hypothesized that rs660C/T decreases expression of TRIM21, resulting in loss of a negative feedback pathway in immune responses and increased RBC alloimmunization. To test the effects of TRIM21 expression on alloimmunization, we analyzed antibody responses to alloantigens on RBCs and platelets transfused into wild-type and TRIM21 KO mice. No significant increases were seen in the frequency or magnitude of humoral immunization to alloantigens on transfused RBCs or platelets in adult or juvenile TRIM21 KO recipients compared to wild-type controls. Moreover, recipient inflammation with poly (I:C) enhanced RBC alloimmunization to similar degrees in both TRIM21 KO and wild-type control recipients. Together, these data rule out the hypothesis that decreased TRIM21 expression enhances transfusion induced humoral alloimmunization, in the context of a reductionist murine model. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Patel, Seema R.; Hendrickson, Jeanne E.; Smith, Nicole H.; Cadwell, Chantel M.; Zimring, James C.] Emory Univ, Dept Pathol & Lab Med, Sch Med, Ctr Transfus & Cellular Therapies, Atlanta, GA 30322 USA.
[Hendrickson, Jeanne E.; Zimring, James C.] Emory Univ, Aflac Canc Ctr, Sch Med, Atlanta, GA 30322 USA.
[Hendrickson, Jeanne E.; Zimring, James C.] Emory Univ, Blood Disorders Serv, Div Pediat Hematol Oncol, Atlanta, GA 30322 USA.
[Morse, Herbert C., III] NIAID, NIH, Rockville, MD USA.
[Ozato, Keiko; Yoshimi, Ryusuke] NICHD, NIH, Bethesda, MD USA.
RP Zimring, JC (reprint author), Emory Univ, Dept Pathol & Lab Med, Sch Med, Ctr Transfus & Cellular Therapies, Woodruff Mem Bldg,Suite 7107A,101 Woodruff Circle, Atlanta, GA 30322 USA.
EM jzimrin@emory.edu
OI Zimring, James/0000-0002-1063-4010; Yoshimi,
Ryusuke/0000-0002-3945-307X; Morse, Herbert/0000-0002-9331-3705
FU NIH, National Institute of Allergy and Infectious Disease; NIH
[P01HL086773]
FX Creation of the TRIM21 knockout mice was previously performed with
support from the Intramural Research Program of the NIH, National
Institute of Allergy and Infectious Diseases. The current studies were
supported by NIH Grant P01HL086773.
NR 15
TC 8
Z9 9
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 MAR
PY 2011
VL 48
IS 6-7
BP 909
EP 913
DI 10.1016/j.molimm.2010.12.017
PG 5
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 737OO
UT WOS:000288578300012
PM 21269695
ER
PT J
AU Bernstein, HD
AF Bernstein, Harris D.
TI The double life of a bacterial lipoprotein
SO MOLECULAR MICROBIOLOGY
LA English
DT Editorial Material
ID OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI; BORRELIA-BURGDORFERI;
IDENTIFICATION; SURFACE; TRANSLOCATION; BIOGENESIS; COMPLEX;
LOCALIZATION; MECHANISM
AB P>It has been known for many years that the small lipoprotein Lpp, which is the most abundant protein in E. coli, exists in two forms. The 'bound' form of the protein is tethered to the outer membrane (OM) by its N-terminal lipid moiety and covalently attached to the cell wall by its C-terminal lysine residue. The exact location of the 'free' form, however, has never been determined. In this issue of Molecular Microbiology, Cowles et al. demonstrate that the free form of Lpp is an integral OM protein whose C-terminus is exposed on the cell surface. The new study provides the first example of a lipoprotein that has a dual localization and adds to a growing body of evidence that lipoproteins can span the OM despite the lack of an obvious transmembrane segment. Furthermore, the new results raise intriguing questions about the assembly of both lipoproteins and other types of OM proteins.
C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
FU Intramural NIH HHS [ZIA DK052037-04]
NR 28
TC 7
Z9 7
U1 1
U2 3
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 MAR
PY 2011
VL 79
IS 5
BP 1128
EP 1131
DI 10.1111/j.1365-2958.2011.07538.x
PG 4
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 724PP
UT WOS:000287589000003
PM 21338414
ER
PT J
AU Kohn, DB
Dotti, G
Brentjens, R
Savoldo, B
Jensen, M
Cooper, LJN
June, CH
Rosenberg, S
Sadelain, M
Heslop, HE
AF Kohn, Donald B.
Dotti, Gianpietro
Brentjens, Renier
Savoldo, Barbara
Jensen, Michael
Cooper, Laurence J. N.
June, Carl H.
Rosenberg, Steven
Sadelain, Michel
Heslop, Helen E.
TI CARs on Track in the Clinic
SO MOLECULAR THERAPY
LA English
DT News Item
ID CHIMERIC ANTIGEN RECEPTOR; CYTOTOXIC T-LYMPHOCYTES; ADOPTIVE TRANSFER;
ANTITUMOR-ACTIVITY; PRESENTING CELLS; ADVERSE EVENT; SPECIFICITY;
SURVIVAL; THERAPY; GENE
C1 [Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Kohn, Donald B.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA.
[Dotti, Gianpietro; Savoldo, Barbara; Heslop, Helen E.] Methodist Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Dotti, Gianpietro; Savoldo, Barbara; Heslop, Helen E.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Brentjens, Renier; Sadelain, Michel] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Brentjens, Renier; Sadelain, Michel] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10021 USA.
[Jensen, Michael] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA.
[Cooper, Laurence J. N.] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA.
[June, Carl H.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[June, Carl H.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Rosenberg, Steven] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Kohn, DB (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, 290D BSRB,615 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM dkohn@mednet.ucla.edu
RI Kohn, Donald/N-5085-2016
OI Kohn, Donald/0000-0003-1840-6087
NR 43
TC 76
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U1 1
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAR
PY 2011
VL 19
IS 3
BP 432
EP 438
DI 10.1038/mt.2011.1
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 728YY
UT WOS:000287911600001
PM 21358705
ER
PT J
AU Parkhurst, MR
Yang, JC
Langan, RC
Dudley, ME
Nathan, DAN
Feldman, SA
Davis, JL
Morgan, RA
Merino, MJ
Sherry, RM
Hughes, MS
Kammula, US
Phan, GQ
Lim, RM
Wank, SA
Restifo, NP
Robbins, PF
Laurencot, CM
Rosenberg, SA
AF Parkhurst, Maria R.
Yang, James C.
Langan, Russell C.
Dudley, Mark E.
Nathan, Debbie-Ann N.
Feldman, Steven A.
Davis, Jeremy L.
Morgan, Richard A.
Merino, Maria J.
Sherry, Richard M.
Hughes, Marybeth S.
Kammula, Udai S.
Phan, Giao Q.
Lim, Ramona M.
Wank, Stephen A.
Restifo, Nicholas P.
Robbins, Paul F.
Laurencot, Carolyn M.
Rosenberg, Steven A.
TI T Cells Targeting Carcinoembryonic Antigen Can Mediate Regression of
Metastatic Colorectal Cancer but Induce Severe Transient Colitis
SO MOLECULAR THERAPY
LA English
DT Article
ID VERSUS-HOST-DISEASE; PHASE-I; ANTITUMOR-ACTIVITY; IMMUNE-RESPONSES;
TUMOR-ANTIGEN; MOUSE MODELS; GENE-THERAPY; RECEPTOR; LYMPHOCYTES; TCR
AB Autologous T lymphocytes genetically engineered to express a murine T cell receptor (TCR) against human carcinoembryonic antigen (CEA) were administered to three patients with metastatic colorectal cancer refractory to standard treatments. All patients experienced profound decreases in serum CEA levels (74-99%), and one patient had an objective regression of cancer metastatic to the lung and liver. However, a severe transient inflammatory colitis that represented a dose limiting toxicity was induced in all three patients. This report represents the first example of objective regression of metastatic colorectal cancer mediated by adoptive T cell transfer and illustrates the successful use of a TCR, raised in human leukocyte antigen (HLA) transgenic mice, against a human tumor associated antigen. It also emphasizes the destructive power of small numbers of highly avid T cells and the limitations of using CEA as a target for cancer immunotherapy.
C1 [Parkhurst, Maria R.; Yang, James C.; Langan, Russell C.; Dudley, Mark E.; Nathan, Debbie-Ann N.; Feldman, Steven A.; Davis, Jeremy L.; Morgan, Richard A.; Sherry, Richard M.; Hughes, Marybeth S.; Kammula, Udai S.; Phan, Giao Q.; Restifo, Nicholas P.; Robbins, Paul F.; Laurencot, Carolyn M.; Rosenberg, Steven A.] NCI, NIH, Surg Branch, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Lim, Ramona M.; Wank, Stephen A.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
RP Parkhurst, MR (reprint author), NCI, NIH, Surg Branch, Bldg CRC Rm 4-5744,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Maria_Parkhurst@nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU NCI
FX This work was funded through the NCI intramural program. The authors
thank Arnold Mixon and Shawn Farid for performing FACS analyses; Linda
Parker, Azam Nahvi, and Laura Deviller for expanding the CEA TCR
transduced T cells in vitro for adoptive transfer; Hui Xu and Mary A.
Black for producing GMP quality retrovirus encoding the CEA TCR; Yong Li
for assisting with DNA analyses; Patricia Fetsch for immunohistochemical
staining; Susan Schwarz and John Riley for performing ELISPOT assays;
and all the clinical fellows and nursing staff in the Clinical Center of
The National Institutes of Health who provided these patients with
outstanding care.
NR 32
TC 248
Z9 256
U1 5
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAR
PY 2011
VL 19
IS 3
BP 620
EP 626
DI 10.1038/mt.2010.272
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 728YY
UT WOS:000287911600022
PM 21157437
ER
PT J
AU Lungu, C
Karp, BI
Alter, K
Zolbrod, R
Hallett, M
AF Lungu, Codrin
Karp, Barbara I.
Alter, Katharine
Zolbrod, Regina
Hallett, Mark
TI Long-Term Follow-up of Botulinum Toxin Therapy for Focal Hand Dystonia:
Outcome at 10 Years or More
SO MOVEMENT DISORDERS
LA English
DT Article
DE botulinum; dystonia; focal hand dystonia; safety; efficacy
ID WRITERS CRAMP; MOVEMENT-DISORDERS; CERVICAL DYSTONIA; INJECTIONS;
EFFICACY; IMMUNOGENICITY; NEUROTOXIN; EXPERIENCE; SAFETY; TRIAL
AB Background: Previous studies have explored the efficacy and safety of botulinum neurotoxin (BoNT) treatment for Focal hand dystonia (FHD), but none have followed a large number of patients for 10 years or more.
Methods: Retrospective study, with benefit and weakness assessed on a 0 to 4 subjective scale. Demographic, clinical and treatment characteristics were analyzed using t tests and Pearson correlations.
Results: Twenty FHD patients had 10 years or longer treatment. Interinjection intervals were variable. Musicians were more likely to wait longer between injections and had less complex dystonia. There was a trend for larger benefit in women and with shorter intervals. The dose increased over time. Dystonia characteristics did not predict response or side-effects, but benefit magnitude predicted longer compliance. No serious side-effects or antibody-mediated resistance occurred.
Conclusion: This is the longest reported period of BoNT treatment in the largest FHD cohort. BoNT therapy for FHD remains safe and effective after more than a decade of treatment. (C) 2011 Movement Disorder Society
C1 [Lungu, Codrin; Zolbrod, Regina; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Med Neurol Branch, NIH, Bethesda, MD USA.
[Karp, Barbara I.] NIH, Combined Neurosci IRB, Bethesda, MD 20892 USA.
[Alter, Katharine] NIH, Phys Disabil Sect, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NIH Med Neurol, Bldg 10,Rm 7D37,MSC 1428,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU Intramural NIH HHS [Z01 NS003032-02, ZIA NS003032-03, Z01 NS003032-01]
NR 24
TC 27
Z9 28
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAR
PY 2011
VL 26
IS 4
BP 750
EP 753
DI 10.1002/mds.23504
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 762AO
UT WOS:000290444800033
PM 21506157
ER
PT J
AU Rada, B
Gardina, P
Myers, TG
Leto, TL
AF Rada, B.
Gardina, P.
Myers, T. G.
Leto, T. L.
TI Reactive oxygen species mediate inflammatory cytokine release and
EGFR-dependent mucin secretion in airway epithelial cells exposed to
Pseudomonas pyocyanin
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; CYSTIC-FIBROSIS LUNG; OXIDATIVE STRESS;
GENE-EXPRESSION; DUAL OXIDASE; AERUGINOSA LIPOPOLYSACCHARIDE; G-CSF;
INFECTION; ACTIVATION; RESPONSES
AB Despite the long-appreciated in vivo role of the redox-active virulence factor pyocyanin in Pseudomonas airway infections and the importance of airway epithelial cells in combating bacterial pathogens, little is known about pyocyanin's effect on airway epithelial cells. We find that exposure of bronchiolar epithelial cells to pyocyanin results in MUC2/MUC5AC induction and mucin secretion through release of inflammatory cytokines and growth factors (interleukin (IL)-1 beta, IL-6, heparin-bound epidermal growth factor, tissue growth factor-alpha, tumor necrosis factor-alpha) that activate the epidermal growth factor receptor pathway. These changes are mediated by reactive oxygen species produced by pyocyanin. Microarray analysis identified 286 pyocyanin-induced genes in airway epithelial cells, including many inflammatory mediators elevated in cystic fibrosis (granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte CSF, chemokine (C-X-C motif) ligand 1 (CXCL1), serum amyloid, IL-23) and several novel pyocyanin-responsive genes of potential importance in the infection process (IL-24, CXCL2, CXCL3, CCL20, CXCR4). This comprehensive study uncovers numerous details of pyocyanin's proinflammatory action and establishes airway epithelial cells as key responders to this microbial toxin.
C1 [Rada, B.; Leto, T. L.] NIAID, Mol Def Sect, Lab Host Def, NIH, Rockville, MD USA.
[Gardina, P.; Myers, T. G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Leto, TL (reprint author), NIAID, Mol Def Sect, Lab Host Def, NIH, Rockville, MD USA.
EM tleto@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases.
NR 49
TC 42
Z9 42
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAR
PY 2011
VL 4
IS 2
BP 158
EP 171
DI 10.1038/mi.2010.62
PG 14
WC Immunology
SC Immunology
GA 720SY
UT WOS:000287302700006
PM 20962773
ER
PT J
AU Meylan, F
Song, YJ
Fuss, I
Villarreal, S
Kahle, E
Malm, IJ
Acharya, K
Ramos, HL
Lo, L
Mentink-Kane, MM
Wynn, TA
Migone, TS
Strober, W
Siegel, RM
AF Meylan, F.
Song, Y-J
Fuss, I.
Villarreal, S.
Kahle, E.
Malm, I-J
Acharya, K.
Ramos, H. L.
Lo, L.
Mentink-Kane, M. M.
Wynn, T. A.
Migone, T-S
Strober, W.
Siegel, R. M.
TI The TNF-family cytokine TL1A drives IL-13-dependent small intestinal
inflammation
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; DENDRITIC CELLS; CROHNS-DISEASE; EXPERIMENTAL
COLITIS; ULCERATIVE-COLITIS; NKT CELLS; GENE-EXPRESSION; RETINOIC-ACID;
CUTTING EDGE; DEATH DOMAIN
AB The tumor necrosis factor (TNF)-family cytokine TL1A (TNFSF15) costimulates T cells through its receptor DR3 (TNFRSF25) and is required for autoimmune pathology driven by diverse T-cell subsets. TL1A has been linked to human inflammatory bowel disease (IBD), but its pathogenic role is not known. We generated transgenic mice that constitutively express TL1A in T cells or dendritic cells. These mice spontaneously develop IL-13-dependent inflammatory small bowel pathology that strikingly resembles the intestinal response to nematode infections. These changes were dependent on the presence of a polyclonal T-cell receptor (TCR) repertoire, suggesting that they are driven by components in the intestinal flora. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) were present in increased numbers despite the fact that TL1A suppresses the generation of inducible Tregs. Finally, blocking TL1A-DR3 interactions abrogates 2,4,6 trinitrobenzenesulfonic acid (TNBS) colitis, indicating that these interactions influence other causes of intestinal inflammation as well. These results establish a novel link between TL1A and interleukin 13 (IL-13) responses that results in small intestinal inflammation, and also establish that TL1A-DR3 interactions are necessary and sufficient for T cell-dependent IBD.
C1 [Meylan, F.; Song, Y-J; Villarreal, S.; Kahle, E.; Malm, I-J; Acharya, K.; Siegel, R. M.] NIAMS, Immunoregulat Sect, Autoimmun Branch, Bethesda, MD USA.
[Fuss, I.; Strober, W.] NIAID, Mucosal Immunol Sect, Lab Host Def, Bethesda, MD 20892 USA.
[Ramos, H. L.] NIAMS, Mol Immunol & Inflammat Branch, Bethesda, MD USA.
[Lo, L.; Migone, T-S] Human Genome Sci, Rockville, MD USA.
[Mentink-Kane, M. M.; Wynn, T. A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
RP Siegel, RM (reprint author), NIAMS, Immunoregulat Sect, Autoimmun Branch, Bethesda, MD USA.
EM siegelr@mail.nih.gov
RI Wynn, Thomas/C-2797-2011
FU NIAMS; Crohn's and Colitis Foundation of America
FX We thank Anthony Cruz for technical assistance, Jin-Moo Lee for
providing the TL1A cDNA, Pat Korty and Ethan Shevach for assistance with
generating monoclonal antibodies, Lionel Feigenbaum and the NCI
transgenic facility for producing the mice, Brian Kelsall and Yasmine
Belkaid for reagents and discussions, Eddie C-Y Wang for DR3-deficient
mice, Anuk Das for providing the anti-mouse IL-13 mAb, Joel Tocker for
providing the anti-mouse IL-17 mAb, Pascal Schneider for ACRP-TL1A
fusion protein, and Jim Simone and the NIAMS flow cytometry facility for
cell sorting. This work was supported by NIAMS intramural research
funding and a fellowship to F.M. from the Crohn's and Colitis Foundation
of America.
NR 60
TC 59
Z9 61
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAR
PY 2011
VL 4
IS 2
BP 172
EP 185
DI 10.1038/mi.2010.67
PG 14
WC Immunology
SC Immunology
GA 720SY
UT WOS:000287302700007
PM 20980995
ER
PT J
AU Davis, EE
Zhang, Q
Liu, Q
Diplas, BH
Davey, LM
Hartley, J
Stoetzel, C
Szymanska, K
Ramaswami, G
Logan, CV
Muzny, DM
Young, AC
Wheeler, DA
Cruz, P
Morgan, M
Lewis, LR
Cherukuri, P
Maskeri, B
Hansen, NF
Mullikin, JC
Blakesley, RW
Bouffard, GG
Gyapay, G
Rieger, S
Tonshoff, B
Kern, I
Soliman, NA
Neuhaus, TJ
Swoboda, KJ
Kayserili, H
Gallagher, TE
Lewis, RA
Bergmann, C
Otto, EA
Saunier, S
Scambler, PJ
Beales, PL
Gleeson, JG
Maher, ER
Attie-Bitach, T
Dollfus, H
Johnson, CA
Green, ED
Gibbs, RA
Hildebrandt, F
Pierce, EA
Katsanis, N
AF Davis, Erica E.
Zhang, Qi
Liu, Qin
Diplas, Bill H.
Davey, Lisa M.
Hartley, Jane
Stoetzel, Corinne
Szymanska, Katarzyna
Ramaswami, Gokul
Logan, Clare V.
Muzny, Donna M.
Young, Alice C.
Wheeler, David A.
Cruz, Pedro
Morgan, Margaret
Lewis, Lora R.
Cherukuri, Praveen
Maskeri, Baishali
Hansen, Nancy F.
Mullikin, James C.
Blakesley, Robert W.
Bouffard, Gerard G.
Gyapay, Gabor
Rieger, Susanne
Toenshoff, Burkhard
Kern, Ilse
Soliman, Neveen A.
Neuhaus, Thomas J.
Swoboda, Kathryn J.
Kayserili, Hulya
Gallagher, Tomas E.
Lewis, Richard A.
Bergmann, Carsten
Otto, Edgar A.
Saunier, Sophie
Scambler, Peter J.
Beales, Philip L.
Gleeson, Joseph G.
Maher, Eamonn R.
Attie-Bitach, Tania
Dollfus, Helene
Johnson, Colin A.
Green, Eric D.
Gibbs, Richard A.
Hildebrandt, Friedhelm
Pierce, Eric A.
Katsanis, Nicholas
CA NISC Comparative Sequencing Progra
TI TTC21B contributes both causal and modifying alleles across the
ciliopathy spectrum
SO NATURE GENETICS
LA English
DT Article
ID BARDET-BIEDL-SYNDROME; RETROGRADE INTRAFLAGELLAR TRANSPORT;
JOUBERT-SYNDROME; RETINAL DEGENERATION; CENTROSOMAL PROTEIN;
MECKEL-SYNDROME; IN-VIVO; MUTATIONS; GENE; NEPHRONOPHTHISIS
AB Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to similar to 5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders.
C1 [Davis, Erica E.; Diplas, Bill H.; Davey, Lisa M.; Katsanis, Nicholas] Duke Univ, Med Ctr, Dept Cell Biol, Ctr Human Dis Modeling, Durham, NC 27710 USA.
[Davis, Erica E.; Katsanis, Nicholas] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[Zhang, Qi; Liu, Qin; Pierce, Eric A.] Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
[Hartley, Jane; Maher, Eamonn R.] Univ Birmingham, Inst Biomed Res, Dept Med & Mol Genet, Birmingham, W Midlands, England.
[Stoetzel, Corinne; Dollfus, Helene] Univ Strasbourg, Avenir INSERM, Lab Genet Med EA3949, Strasbourg, France.
[Szymanska, Katarzyna; Logan, Clare V.; Johnson, Colin A.] St James Univ Hosp, Sect Ophthalmol & Neurosci, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England.
[Ramaswami, Gokul; Otto, Edgar A.; Hildebrandt, Friedhelm] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Muzny, Donna M.; Wheeler, David A.; Morgan, Margaret; Lewis, Lora R.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Young, Alice C.; Cruz, Pedro; Cherukuri, Praveen; Maskeri, Baishali; Hansen, Nancy F.; Mullikin, James C.; Blakesley, Robert W.; Bouffard, Gerard G.; Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Gyapay, Gabor] Genoscope Ctr Natl Sequencage, Evry, France.
[Rieger, Susanne; Toenshoff, Burkhard] Univ Childrens Hosp, Heidelberg, Germany.
[Kern, Ilse] Univ Hosp Geneva, Dept Pediat, Geneva, Switzerland.
[Soliman, Neveen A.] Cairo Univ, Dept Pediat, Kasralainy Sch Med, Cairo, Egypt.
[Neuhaus, Thomas J.] Univ Childrens Hosp Zurich, Div Nephrol, Zurich, Switzerland.
[Swoboda, Kathryn J.] Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA.
[Swoboda, Kathryn J.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Kayserili, Hulya] Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
[Gallagher, Tomas E.] Univ Hawaii Manoa, Honolulu, HI 96822 USA.
[Lewis, Richard A.] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
[Lewis, Richard A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Lewis, Richard A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Lewis, Richard A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Bergmann, Carsten] Bioscientia, Ctr Human Genet, Ingelheim, Germany.
[Bergmann, Carsten] Rhein Westfal TH Aachen, Dept Human Genet, Aachen, Germany.
[Saunier, Sophie] Univ Paris 05, Hop Necker Enfants Malades, INSERM, U983, Paris, France.
[Scambler, Peter J.; Beales, Philip L.] UCL, Mol Med Unit, Inst Child Hlth, London, England.
[Gleeson, Joseph G.] Univ Calif San Diego, Howard Hughes Med Inst, Dept Neurosci, La Jolla, CA 92093 USA.
[Attie-Bitach, Tania] Univ Paris 05, Hop Necker Enfants Malades, INSERM, U781, Paris, France.
[Attie-Bitach, Tania] Univ Paris 05, Hop Necker Enfants Malades, Dept Genet, Paris, France.
[Hildebrandt, Friedhelm] Howard Hughes Med Inst, Ann Arbor, MI USA.
[Hildebrandt, Friedhelm] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Katsanis, Nicholas] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Katsanis, Nicholas] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
RP Katsanis, N (reprint author), Duke Univ, Med Ctr, Dept Cell Biol, Ctr Human Dis Modeling, Durham, NC 27710 USA.
EM katsanis@cellbio.duke.edu
RI Scambler, Peter/C-4998-2008; MAHER, EAMONN/A-9507-2008; Katsanis,
Nicholas/E-1837-2012
OI Logan, Clare/0000-0003-4323-1602; Scambler, Peter/0000-0002-1487-4628;
MAHER, EAMONN/0000-0002-6226-6918; Soliman, Neveen/0000-0002-8942-1973;
Otto, Edgar/0000-0002-2387-9973; Pierce, Eric/0000-0002-2354-4102;
Katsanis, Nicholas/0000-0002-2480-0171;
FU US National Institutes of Health [R01HD04260]; National Institute of
Child Health and Development [R01DK072301, R01DK075972, R01DK068306,
R01DK064614, R01DK069274]; National Institute of Diabetes, Digestive and
Kidney disorders [F32 DK079541]; National Eye Institute [RO1EY12910];
Macular Vision Research Foundation; Foundation Fighting Blindness; F.M.
Kirby Foundation; Rosanne Silbermann Foundation; Polycystic Kidney
Disease (PKD) Foundation; German Kidney Foundation; German Research
Foundation (DFG) [BE 3910/5-1, SFB/TRR57]; UNADEV; Retina France;
Programme Hospitalier de Recherche Clinique; L'Agence nationale de la
recherche; Medical Research Council (MRC); National Human Genome
Research Institute
FX We are grateful to the individuals affected with ciliopathies and their
families for their continued participation and enthusiasm. We thank N.
Elkhartoufi for technical assistance, P. Parvex for subject recruitment,
D. Parker for critical reading of the manuscript and Yorkshire Regional
Genetics Service for help in obtaining control DNA samples. This
research was supported by funds from the US National Institutes of
Health grant R01HD04260 from the National Institute of Child Health and
Development (N. K.), R01DK072301, R01DK075972 (N. K.), R01DK068306,
R01DK064614, R01DK069274 (F. H.) and National Research Service Award
(NRSA) fellowship F32 DK079541 (E. E. D.) from the National Institute of
Diabetes, Digestive and Kidney disorders, RO1EY12910 from the National
Eye Institute (E. A. P.), the Macular Vision Research Foundation (N. K.)
the Foundation Fighting Blindness (N. K., R. A. L., E. A. P. and Q. L.),
the F.M. Kirby Foundation (E. A. P.), the Rosanne Silbermann Foundation
(E. A. P.), the Polycystic Kidney Disease (PKD) Foundation (C. B.),
German Kidney Foundation (C. B.), German Research Foundation (DFG BE
3910/5-1 and SFB/TRR57; C. B.), UNADEV, Retina France, Programme
Hospitalier de Recherche Clinique 2007, L'Agence nationale de la
recherche 2009 (H. D.) and a Medical Research Council (MRC) research
training fellowship (J.H.). This work was also supported in part by the
Intramural Research Program of the National Human Genome Research
Institute. R. A. L. is a Senior Scientific Investigator of Research to
Prevent Blindness, New York, New York. P. L. B. is a Wellcome Trust
Senior Research Fellow. F. H. is an Investigator of the Howard Hughes
Medical Institute, a Doris Duke Distinguished Clinical Scientist and the
Frederick G. L. Huetwell Professor. N. K. is a Distinguished George W.
Brumley Professor.
NR 31
TC 140
Z9 150
U1 2
U2 9
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 MAR
PY 2011
VL 43
IS 3
BP 189
EP U28
DI 10.1038/ng.756
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 726BR
UT WOS:000287693800008
PM 21258341
ER
PT J
AU John, S
Sabo, PJ
Thurman, RE
Sung, MH
Biddie, SC
Johnson, TA
Hager, GL
Stamatoyannopoulos, JA
AF John, Sam
Sabo, Peter J.
Thurman, Robert E.
Sung, Myong-Hee
Biddie, Simon C.
Johnson, Thomas A.
Hager, Gordon L.
Stamatoyannopoulos, John A.
TI Chromatin accessibility pre-determines glucocorticoid receptor binding
patterns
SO NATURE GENETICS
LA English
DT Article
ID PROTEIN-DNA INTERACTIONS; IN-VIVO; HYPERSENSITIVE SITES; MMTV PROMOTER;
GENE; CELLS; INTERPLAY
AB Development, differentiation and response to environmental stimuli are characterized by sequential changes in cellular state initiated by the de novo binding of regulated transcriptional factors to their cognate genomic sites(1-3). The mechanism whereby a given regulatory factor selects a limited number of in vivo targets from a myriad of potential genomic binding sites is undetermined. Here we show that up to 95% of de novo genomic binding by the glucocorticoid receptor(4), a paradigmatic ligand-activated transcription factor, is targeted to preexisting foci of accessible chromatin. Factor binding invariably potentiates chromatin accessibility. Cell-selective glucocorticoid receptor occupancy patterns appear to be comprehensively predetermined by cell-specific differences in baseline chromatin accessibility patterns, with secondary contributions from local sequence features. The results define a framework for understanding regulatory factor-genome interactions and provide a molecular basis for the tissue selectivity of steroid pharmaceuticals and other agents that intersect the living genome.
C1 [Sabo, Peter J.; Thurman, Robert E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[John, Sam; Sung, Myong-Hee; Biddie, Simon C.; Johnson, Thomas A.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stamatoyannopoulos, John A.] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA.
RP Stamatoyannopoulos, JA (reprint author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM hagerg@exchange.nih.gov; jstam@uw.edu
OI Biddie, Simon/0000-0002-8253-0253
FU US NIH, National Cancer Institute, Center for Cancer Research; US NIH
[1RC2HG005654]
FX We would like to thank T. Miranda, S. Morris, K. Nalley and L. Grontved
for critical reading of the manuscript. We also thank M. Weaver, K. Lee,
F. Neri, D. Bates and M. Diegel for technical assistance with the DNase
I library preparation and sequencing. This research was supported in
part by the Intramural Research Program of the US NIH, National Cancer
Institute, Center for Cancer Research and funding from US NIH grant
1RC2HG005654 to J.A.S.
NR 30
TC 372
Z9 378
U1 5
U2 31
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 MAR
PY 2011
VL 43
IS 3
BP 264
EP U116
DI 10.1038/ng.759
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 726BR
UT WOS:000287693800019
PM 21258342
ER
PT J
AU PrabhuDas, M
Adkins, B
Gans, H
King, C
Levy, O
Ramilo, O
Siegrist, CA
AF PrabhuDas, Mercy
Adkins, Becky
Gans, Hayley
King, Christopher
Levy, Ofer
Ramilo, Octavio
Siegrist, Claire-Anne
TI Challenges in infant immunity: implications for responses to infection
and vaccines
SO NATURE IMMUNOLOGY
LA English
DT Article
ID RECENT THYMIC EMIGRANTS; CD4(+) T-CELLS; ADAPTIVE IMMUNITY; VACCINATION;
AGE; DEFICIENCY; EXPRESSION; NEWBORNS; INNATE
C1 [PrabhuDas, Mercy] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Adkins, Becky] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Gans, Hayley] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
[King, Christopher] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
[Levy, Ofer] Childrens Hosp Boston, Dept Med, Boston, MA USA.
[Levy, Ofer] Harvard Univ, Sch Med, Boston, MA USA.
[Ramilo, Octavio] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Columbus, OH USA.
[Ramilo, Octavio] Ohio State Univ, Columbus, OH 43210 USA.
[Siegrist, Claire-Anne] Univ Geneva, Ctr Vaccinol & Neonatal Immunol, Geneva, Switzerland.
RP PrabhuDas, M (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mprabhudas@niaid.nih.gov
NR 25
TC 135
Z9 135
U1 2
U2 5
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 MAR
PY 2011
VL 12
IS 3
BP 189
EP 194
DI 10.1038/ni0311-189
PG 6
WC Immunology
SC Immunology
GA 721KZ
UT WOS:000287354400002
PM 21321588
ER
PT J
AU Yang, XP
Ghoreschi, K
Steward-Tharp, SM
Rodriguez-Canales, J
Zhu, JF
Grainger, JR
Hirahara, K
Sun, HW
Wei, L
Vahedi, G
Kanno, Y
O'Shea, JJ
Laurence, A
AF Yang, Xiang-Ping
Ghoreschi, Kamran
Steward-Tharp, Scott M.
Rodriguez-Canales, Jaime
Zhu, Jinfang
Grainger, John R.
Hirahara, Kiyoshi
Sun, Hong-Wei
Wei, Lai
Vahedi, Golnaz
Kanno, Yuka
O'Shea, John J.
Laurence, Arian
TI Opposing regulation of the locus encoding IL-17 through direct,
reciprocal actions of STAT3 and STAT5
SO NATURE IMMUNOLOGY
LA English
DT Article
ID T(H)17 CELL-DIFFERENTIATION; CD4(+) T-CELLS; TGF-BETA; IN-VIVO; RETINOIC
ACID; HELPER-CELLS; LINEAGE; GENE; TRANSCRIPTION; CYTOKINE
AB Interleukin 2 (IL-2), a cytokine linked to human autoimmune disease, limits IL-17 production. Here we found that deletion of the gene encoding the transcription factor STAT3 in T cells abrogated IL-17 production and attenuated autoimmunity associated with IL-2 deficiency. Whereas STAT3 induced IL-17 and the transcription factor ROR gamma t and inhibited the transcription factor Foxp3, IL-2 inhibited IL-17 independently of Foxp3 and ROR gamma t. STAT3 and STAT5 bound to multiple common sites across the locus encoding IL-17. The induction of STAT5 binding by IL-2 was associated with less binding of STAT3 at these sites and the inhibition of associated active epigenetic marks. 'Titration' of the relative activation of STAT3 and STAT5 modulated the specification of cells to the IL-17-producing helper T cell (T(H)17 cell) subset. Thus, the balance rather than the absolute magnitude of these signals determined the propensity of cells to make a key inflammatory cytokine.
C1 [Yang, Xiang-Ping; Ghoreschi, Kamran; Steward-Tharp, Scott M.; Hirahara, Kiyoshi; Sun, Hong-Wei; Vahedi, Golnaz; Kanno, Yuka; O'Shea, John J.; Laurence, Arian] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Rodriguez-Canales, Jaime] NCI, Laser Capture Microdissect Core Lab Pathol, NIH, Bethesda, MD 20892 USA.
[Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Grainger, John R.] NIAID, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Wei, Lai] NEI, Clin Immunol Sect, NIH, Bethesda, MD 20892 USA.
RP Laurence, A (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM laurencea@mail.nih.gov
RI Yang, Xiangping/B-4833-2011; Laurence, Arian/A-8770-2009; Zhu,
Jinfang/B-7574-2012; Kanno, Yuka/B-5802-2013; cheng, yong/I-4270-2012;
Wei, Lai/D-1088-2014; Hirahara, Kiyoshi/E-2460-2017;
OI Kanno, Yuka/0000-0001-5668-9319; Laurence, Arian/0000-0003-0942-8292;
Grainger, John/0000-0002-4052-5923; Hirahara,
Kiyoshi/0000-0002-9128-9449; Rodriguez-Canales,
Jaime/0000-0002-0885-2377
FU National Institute of Arthritis, Musculoskeletal and Skin Diseases;
National Institute of Allergy and Infectious Diseases
FX We thank J. Simone, J. Lay and the National Institute of Arthritis,
Musculoskeletal and Skin Diseases Laboratory Animal Care and Use Section
staff for technical support; D. Levy (New York University) for mice with
loxP-flanked Stat3 alleles; C. Dong (MD Anderson) for IL-17F-RFP
reporter mice; W. Ouyang (Genentech) for monoclonal anti-IL-22; and S.
Kuchen, F. C. Eberle and K. Tarbell for comments on the manuscript.
Supported by the Intramural Research programs of National Institute of
Arthritis, Musculoskeletal and Skin Diseases and National Institute of
Allergy and Infectious Diseases.
NR 50
TC 259
Z9 269
U1 0
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 MAR
PY 2011
VL 12
IS 3
BP 247
EP U84
DI 10.1038/ni.1995
PG 9
WC Immunology
SC Immunology
GA 721KZ
UT WOS:000287354400012
PM 21278738
ER
PT J
AU Andre, F
McShane, LM
Michiels, S
Ransohoff, DF
Altman, DG
Reis, JS
Hayes, DF
Pusztai, L
AF Andre, Fabrice
McShane, Lisa M.
Michiels, Stefan
Ransohoff, David F.
Altman, Douglas G.
Reis-Filho, Jorge S.
Hayes, Daniel F.
Pusztai, Lajos
TI Biomarker studies: a call for a comprehensive biomarker study registry
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIALS; BREAST-CANCER; PROGNOSTIC-FACTOR;
EXPRESSION; EFFICACY; CHEMOTHERAPY; CLASSIFIERS; STATEMENT; MARKERS;
BIASES
AB Tumor biomarker studies may generate insights into the biological characteristics that drive the clinical behavior of a cancer. Publication bias and hidden multiple hypotheses testing distort the assessment of the true value of biomarkers. Publication bias from preferential reporting of 'positive' findings is well recognized. Hidden multihypothesis testing arises from several biomarkers being tested by different teams using the same samples. The more hypotheses (that is, biomarker association with outcome) tested, the greater the risk of false-positive findings. These biases inflate the potential clinical validity and utility of published biomarkers while negative results often remain hidden. Trial registries have been developed where all phase II and phase III trials should be listed regardless of study outcome. However, such steps have not been taken to reduce such bias in tumor biomarker research. We propose that a registry should be created for biomarker studies initially focused on studies that use specimens from randomized trials. Further development could include nonrandomized studies and deposition of raw data similar to existing genomic data repositories. The benefits of a comprehensive biomarker study registry include more balanced evaluation of proposed markers, fewer false positive leads in research, and hopefully more rapid identification of promising candidate biomarkers.
C1 [Andre, Fabrice] Inst Gustave Roussy, Dept Med Oncol, F-94805 Villejuif, France.
[Andre, Fabrice] Inst Gustave Roussy, INSERM, U981, F-94805 Villejuif, France.
[McShane, Lisa M.] US Natl Canc Inst, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA.
[Michiels, Stefan] Inst Jules Bordet, Breast Canc Translat Res Lab, B-1000 Brussels, Belgium.
[Pusztai, Lajos] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77230 USA.
[Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Reis-Filho, Jorge S.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Altman, Douglas G.] Univ Oxford, Wolfson Coll, Ctr Stat Med, Oxford OX2 6UD, England.
[Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
[Ransohoff, David F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
RP Andre, F (reprint author), Inst Gustave Roussy, Dept Med Oncol, 39 Rue Camilles Desmoulins, F-94805 Villejuif, France.
EM fandre@igr.fr
RI Altman, Douglas/A-9714-2012; Michiels, Stefan/L-1516-2013
OI Michiels, Stefan/0000-0002-6963-2968
NR 24
TC 60
Z9 60
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD MAR
PY 2011
VL 8
IS 3
BP 171
EP 176
DI 10.1038/nrclinonc.2011.4
PG 6
WC Oncology
SC Oncology
GA 728ZS
UT WOS:000287914200011
PM 21364690
ER
PT J
AU Matzinger, P
Kamala, T
AF Matzinger, Polly
Kamala, Tirumalai
TI Tissue-based class control: the other side of tolerance
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; VASOACTIVE-INTESTINAL-PEPTIDE;
MYELIN BASIC-PROTEIN; MELANOCYTE-STIMULATING HORMONE; DELAYED-TYPE
HYPERSENSITIVITY; TUMOR-NECROSIS-FACTOR; TH2 IMMUNE-RESPONSES; EXPRESS
SUBSTANCE-P; TOLL-LIKE RECEPTORS
AB In this Essay, we offer a new perspective on how immune responses are regulated. We do not cover how they are turned on and off, but focus instead on the second major aspect of an immune response: the control of effector class. Although it is generally thought that the class of an immune response is tailored to fit the invading pathogen, we suggest here that it is primarily tailored to fit the tissue in which the response occurs. To this end, we cover such topics as the nature of T helper (T(H)) cell subsets (current and yet to be discovered), the nature of privileged sites, the difference between oral tolerance and oral vaccination, why the route of immunization matters, whether the T(H)1-type response is really the immune system's primary defense, and whether there might be a different role for some regulatory T cells.
C1 [Matzinger, Polly; Kamala, Tirumalai] NIAID, Ghost Lab, Lab Cellular & Mol Immunol, T Cell Tolerance & Memory Sect,NIH, Bethesda, MD 20892 USA.
RP Matzinger, P (reprint author), NIAID, Ghost Lab, Lab Cellular & Mol Immunol, T Cell Tolerance & Memory Sect,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pcm@helix.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland, USA
FX We thank A. Bendelac, T. Honjo, B. Jabri, Y. Rosenberg, F. Di Rosa, R.
Schwartz, N. Singh, the 'ghosts' (K. Abdi, A. Perez-Diez, A. Morgun and
N. Shulzhenko) and especially P. Chappert for commenting on the
manuscript. T. K. would like to express special thanks to D. Usharauli
for his encouragement and support during the preparation of this Essay.
We apologize to the authors whose work we didn't cite owing to lack of
space. This work was supported by the intramural program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland, USA.
NR 151
TC 142
Z9 143
U1 4
U2 26
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 MAR
PY 2011
VL 11
IS 3
BP 221
EP 230
DI 10.1038/nri2940
PG 10
WC Immunology
SC Immunology
GA 726OG
UT WOS:000287732500015
PM 21350581
ER
PT J
AU Schneider, EH
Gao, JL
Gaur, SS
Murphy, PM
AF Schneider, E. H.
Gao, J. -L
Gaur, S. S.
Murphy, P. M.
TI Characterization of a Formyl Peptide Receptor Expressed on Human Lens
Epithelial Cells
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 77th Annual Meeting on
German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology
CY MAR 30-APR 01, 2011
CL Frankfurt, GERMANY
SP German Soc Expt & Clin Pharmacol & Toxicol
C1 [Schneider, E. H.; Gao, J. -L; Gaur, S. S.; Murphy, P. M.] NIAID, NIH, Mol Signalling Sect, Lab Mol Immunol, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2011
VL 383
SU 1
BP 16
EP 16
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 737MO
UT WOS:000288573100061
ER
PT J
AU Upadhyay, A
Larson, MG
Guo, CY
Vasan, RS
Lipinska, I
O'Donnell, CJ
Kathiresan, S
Meigs, JB
Keaney, JF
Rong, JA
Benjamin, EJ
Fox, CS
AF Upadhyay, Ashish
Larson, Martin G.
Guo, Chao-Yu
Vasan, Ramachandran S.
Lipinska, Izabella
O'Donnell, Christopher J.
Kathiresan, Sekar
Meigs, James B.
Keaney, John F., Jr.
Rong, Jian
Benjamin, Emelia J.
Fox, Caroline S.
TI Inflammation, kidney function and albuminuria in the Framingham
Offspring cohort
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE albuminuria; chronic kidney disease; C-reactive protein; inflammation
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; CARDIOVASCULAR MORTALITY;
RENAL-INSUFFICIENCY; TISSUE DISTRIBUTION; OXIDATIVE STRESS; ALL-CAUSE;
BIOMARKERS; RISK; ASSOCIATION
AB Background. Inflammation and chronic kidney disease (CKD) are both associated with cardiovascular disease (CVD). Whether inflammatory biomarkers are associated with kidney function and albuminuria after accounting for traditional CVD risk factors is not completely understood.
Methods. The sample comprised Framingham Offspring cohort participants (n = 3294, mean age 61, 53% women) who attended the seventh examination cycle (1998-2001). Inflammatory biomarkers [C-reactive protein (CRP), tumour necrosis factor (TNF)-alpha, interleukin-6, TNF receptor 2 (TNFR2), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), P-selectin, CD-40 ligand, osteoprotegerin, urinary isoprostanes, myeloperoxidase and fibrinogen] were measured on fasting blood samples. Serum creatinine-based estimated glomerular filtration rate (eGFR) and serum cystatin C concentration were used to assess kidney function. Urinary albumin-to-creatinine ratio (UACR) was used to assess albuminuria. Linear or logistic regression was used to test associations between biomarkers and kidney measures.
Results. Chronic kidney disease (CKD), defined as eGFR < 59/64 mL/min/1.73 m(2) in women/men, was present in 8.8% (n = 291) of participants. TNF-alpha, interleukin-6, TNFR2, MCP-1, osteoprotegerin, myeloperoxidase and fibrinogen were higher among individuals with CKD; all biomarkers except for urinary isoprostanes were elevated in higher cystatin C quartiles; and TNF-alpha, interleukin-6, TNFR2, ICAM-1 and osteoprotegerin were elevated in higher UACR quartiles-all assessed after multivariable adjustment. Almost 6% and 17% of variability in TNFR2 were explained by CKD status and higher cystatin C quartiles, respectively.
Conclusions. Biomarkers of inflammation are associated with kidney function and albuminuria. In particular, substantial variability in soluble TNFR2 is explained by CKD and cystatin C.
C1 [Upadhyay, Ashish] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[Upadhyay, Ashish] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Larson, Martin G.; Guo, Chao-Yu; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Rong, Jian; Benjamin, Emelia J.; Fox, Caroline S.] Boston Univ, Framingham, MA USA.
[Larson, Martin G.; Guo, Chao-Yu; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Rong, Jian; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Lipinska, Izabella] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA.
[Lipinska, Izabella; O'Donnell, Christopher J.; Kathiresan, Sekar; Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Keaney, John F., Jr.] UMass Mem Hlth Care, Div Cardiovasc Med, Worcester, MA USA.
[Rong, Jian; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
RP Upadhyay, A (reprint author), Tufts Med Ctr, Div Nephrol, Boston, MA USA.
EM aupadhyay@tuftsmedicalcenter.org
OI Larson, Martin/0000-0002-9631-1254; Upadhyay,
Ashish/0000-0002-0536-5776; Ramachandran, Vasan/0000-0001-7357-5970;
Benjamin, Emelia/0000-0003-4076-2336
FU NHLBI NIH HHS [R01 HL064753, N01 HC025195, N01-HC-25195, R01
HL043302-10, R01 HL064753-01, R01 HL076784, R01 HL076784-01,
R01-HL-076784, R01-HL-64753, R01-HL04334, R01-HL70139]; NIA NIH HHS
[AG028321, R01 AG028321, R01 AG028321-01]; NIDDK NIH HHS [K24 DK080140,
K24 DK080140-01, K24-DK080140]
NR 32
TC 56
Z9 59
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAR
PY 2011
VL 26
IS 3
BP 920
EP 926
DI 10.1093/ndt/gfq471
PG 8
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 726SN
UT WOS:000287746500024
PM 20682604
ER
PT J
AU Brooks, JA
Houlden, H
Melchers, A
Islam, AJ
Ding, JH
Li, A
Paudel, R
Revesz, T
Holton, JL
Wood, N
Lees, A
Singleton, AB
Scholz, SW
AF Brooks, Janet A.
Houlden, Henry
Melchers, Anna
Islam, Ansha J.
Ding, Jinhui
Li, Abi
Paudel, Reema
Revesz, Tamas
Holton, Janice L.
Wood, Nick
Lees, Andrew
Singleton, Andrew B.
Scholz, Sonja W.
TI Mutational analysis of parkin and PINK1 in multiple system atrophy
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Multiple system atrophy; Parkinson's disease; PINK1; Parkin
ID DISEASE
AB Multiple system atrophy (MSA) and Parkinson's disease (PD) are progressive neurodegenerative disorders with overlapping clinical, biochemical and genetic features. To test the hypothesis that the PD genes parkin and PINK1 also play a role in the pathogenesis of MSA, we performed a mutational screening study involving 87 pathologically proven MSA cases. In parkin we identified eight sequence variants and four heterozygous deletions and in PINK1 we identified nine variants of which two silent mutations have not been previously reported (p.Gly189Gly and p.Arg337Arg). The frequencies of the observed variants were not significantly different from previously published control data and none of the possibly pathogenic variants were found in a homozygous state. Our results indicate that genetic variants at the parkin and PINK1 loci do not play a critical role in the pathogenesis of MSA. Published by Elsevier Inc.
C1 [Brooks, Janet A.; Islam, Ansha J.; Ding, Jinhui; Singleton, Andrew B.; Scholz, Sonja W.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Houlden, Henry; Melchers, Anna; Li, Abi; Paudel, Reema; Revesz, Tamas; Holton, Janice L.; Wood, Nick; Lees, Andrew; Scholz, Sonja W.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Houlden, Henry; Melchers, Anna; Li, Abi; Paudel, Reema; Revesz, Tamas; Holton, Janice L.; Wood, Nick; Lees, Andrew; Scholz, Sonja W.] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England.
RP Scholz, SW (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A-1014, Bethesda, MD 20892 USA.
EM scholzs@mail.nih.gov
RI Singleton, Andrew/C-3010-2009; Lees, Andrew/A-6605-2009; Houlden,
Henry/C-1532-2008; Wood, Nicholas/C-2505-2009; Holton,
Janice/F-6831-2011; Revesz, Tamas/A-8732-2010
OI Scholz, Sonja/0000-0002-6623-0429; Houlden, Henry/0000-0002-2866-7777;
Wood, Nicholas/0000-0002-9500-3348; Holton, Janice/0000-0002-3882-5249;
Revesz, Tamas/0000-0003-2501-0259
FU National Institute on Aging; National Institute on Neurological
Disorders and Stroke, Department of Health and Human Services
[Z01-AG000957-06]; Medical Research Council (MRC) [G108/638]; Michael J.
Fox Foundation; Reta Lila Weston Institute for Neurological Studies;
Sarah Matheson Trust for Multiple System Atrophy; National Organization
for Rare Disorders (NORD); Ataxia UK; Progressive Supranuclear Palsy
(Europe) Association
FX We thank the patients and their families for supporting our research.
DNA panels from the NINDS Human Genetics Resource Center DNA and Cell
Line Repository (http://ccr.coriell.org/ninds) were used in this study,
as well as clinical data. We would like to thank the following
submitters that contributed samples to these DNA panels: Drs. Russell
Buono, Petra Kaufman, Eric Sorenson, Catherine Lomen-Hoerth, David
Simon, John Hardy, Robert Brown, Okun Mandel, Micheline Gravel, Peter
Bosch, Paul Gordon, Dennis Dickson, Zbigniew Wszolek, Matthew Farrer,
Daniel Newman, Laura Sams, Angela Gresham, Edward Kasarskis, Kapil
Sethi, Frederick Wooten, Anthony Crawley, Nickolas Maragakis, Robert
Miller, Robert Hamill, Jayaraman Rao, Burton Scott, Ray Watts, and Kevin
Boylan. This research was funded in part by the Intramural Research
Program of the National Institute on Aging and the National Institute on
Neurological Disorders and Stroke, Department of Health and Human
Services; project numbers Z01-AG000957-06 (J.A.B, A.J.I., J.D., S.W.S.,
A.B.S.). We gratefully acknowledge support by the Medical Research
Council (MRC) (H.H. G108/638 Clinician Scientist Fellowship; N.W.), the
Michael J. Fox Foundation (H.H.), the Reta Lila Weston Institute for
Neurological Studies (T.R., A.L., J.H.), the Sarah Matheson Trust for
Multiple System Atrophy (H.H., T.R., J.H.), the National Organization
for Rare Disorders (NORD) (H.H.), Ataxia UK (H.H.) and the Progressive
Supranuclear Palsy (Europe) Association (T.R., J.H., A.L.).
NR 7
TC 2
Z9 2
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAR
PY 2011
VL 32
IS 3
AR 548.e5
DI 10.1016/j.neurobiolaging.2009.11.020
PG 3
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 755PE
UT WOS:000289944800027
PM 20034704
ER
PT J
AU Yoon, JS
Lee, JH
Son, TG
Mughal, MR
Greig, NH
Mattson, MP
AF Yoon, Jeong Sean
Lee, Jong-Hwan
Son, Tae Gen
Mughal, Mohamed R.
Greig, Nigel H.
Mattson, Mark P.
TI Pregabalin suppresses calcium-mediated proteolysis and improves stroke
outcome
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Calcium; Calpain; Cerebral ischemia; Neuronal death; Pregabalin;
Presynaptic calcium channels
ID CEREBRAL-ARTERY OCCLUSION; ALPHA-II-SPECTRIN; ALPHA(2)-DELTA SUBUNIT;
CHANNEL; CALPAIN; MODEL; MECHANISM; BINDING; TARGET; MICE
AB Pregabalin, a Ca(2+) channel alpha(2)delta-subunit antagonist with analgesic and antiepileptic activity, reduced neuronal loss and improved functional outcome in a mouse model of focal ischemic stroke. Pregabalin administration (5-10 mg/kg, i.p.) 30-90 min after transient middle cerebral artery occlusion/reperfusion reduced infarct volume, neuronal death in the ischemic penumbra and neurological deficits at 24 h post-stroke. Pregabalin significantly decreased the amount of Ca(2+)/calpain-mediated et-spectrin proteolysis in the cerebral cortex measured at 6 h post-stroke. Together with the extensive clinical experience with pregabalin for other neurological indications, our findings suggest the potential for a therapeutic benefit of pregabalin in stroke patients. (C) 2010 Published by Elsevier Inc.
C1 [Yoon, Jeong Sean; Lee, Jong-Hwan; Son, Tae Gen; Mughal, Mohamed R.; Greig, Nigel H.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Lee, Jong Hwan/D-8530-2011; Mattson, Mark/F-6038-2012
FU National Institute on Aging Intramural Research Program
FX This work was supported by the National Institute on Aging Intramural
Research Program.
NR 23
TC 9
Z9 9
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 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD MAR
PY 2011
VL 41
IS 3
BP 624
EP 629
DI 10.1016/j.nbd.2010.11.011
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 718JZ
UT WOS:000287118700004
PM 21111818
ER
PT J
AU Vovk, A
Cox, RW
Stare, J
Suput, D
Saad, ZS
AF Vovk, Andrej
Cox, Robert W.
Stare, Janez
Suput, Dusan
Saad, Ziad S.
TI Segmentation priors from local image properties: Without using bias
field correction, location-based templates, or registration
SO NEUROIMAGE
LA English
DT Article
DE Segmentation; Classification; Texture; Features; Bias field; Priors;
Multivariate classification; Support vector machines
ID MAGNETIC-RESONANCE IMAGES; BRAIN MR-IMAGES; CORTICAL THICKNESS;
INTENSITY NONUNIFORMITY; AUTOMATIC CORRECTION; PROBABILISTIC ATLAS;
WILLIAMS-SYNDROME; MODEL; CLASSIFICATION; SHAPE
AB We present a novel approach for generating information about a voxel's tissue class membership based on its signature-a collection of local image textures estimated over a range of neighborhood sizes. The approach produces a form of tissue class priors that can be used to initialize and regularize image segmentation. The signature-based approach is a departure from current location-based methods, which derive tissue class likelihoods based on a voxel's location in standard template space. To use location-based priors, one needs to register the volume in question to the template space, and estimate the image intensity bias field. Two optimizations, over more than a thousand parameters, are needed when high order nonlinear registration is employed. In contrast, the signature-based approach is independent of volume orientation, voxel position, and largely insensitive to bias fields. For these reasons, the approach does not require the use of population derived templates. The prior information is generated from variations in image texture statistics as a function of spatial scale, and an SVM approach is used to associate signatures with tissue types. With the signature-based approach, optimization is needed only during the training phase for the parameter estimation stages of the SVM hyperplanes, and associated PDFs: a training process separate from the segmentation step. We found that signature-based priors were superior to location-based ones aligned under favorable conditions, and that signature-based priors result in improved segmentation when replacing location-based ones in FAST (Zhang et al., 2001), a widely used segmentation program. The software implementation of this work is freely available as part of AFNI http://afni.nimh.nih.gov. Published by Elsevier Inc.
C1 [Cox, Robert W.; Saad, Ziad S.] NIMH, NIH, Bethesda, MD 20892 USA.
[Vovk, Andrej; Suput, Dusan] Univ Ljubljana, Fac Med, Inst Pathophysiol, Ljubljana, Slovenia.
[Stare, Janez] Univ Ljubljana, Fac Med, Inst Biostat & Med Informat, Ljubljana, Slovenia.
RP Saad, ZS (reprint author), NIMH, NIH, 10 Ctr DR Room 1D80, Bethesda, MD 20892 USA.
EM saadz@mail.nih.gov
FU NIMH, NIH; NINDS, NIH; ARRS [P30019]
FX This research was supported by the NIMH and NINDS Intramural Research
Programs of the NIH, and by the Slovenian research grant ARRS P30019.
The authors extend their thanks for the lively discussions and fruitful
suggestions of Drs. Larry Frank (UCSD) and Souheil Inati (NIMH).
NR 57
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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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAR 1
PY 2011
VL 55
IS 1
BP 142
EP 152
DI 10.1016/j.neuroimage.2010.11.082
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 716YH
UT WOS:000287008900012
PM 21146620
ER
PT J
AU von Leupoldt, A
Chan, PYS
Bradley, MM
Lang, PJ
Davenport, PW
AF von Leupoldt, Andreas
Chan, Pei-Ying S.
Bradley, Margaret M.
Lang, Peter J.
Davenport, Paul W.
TI The impact of anxiety on the neural processing of respiratory sensations
SO NEUROIMAGE
LA English
DT Article
DE Anxiety; Brain; Dyspnea; Perception; Respiratory-related evoked
potential
ID OBSTRUCTIVE PULMONARY-DISEASE; INSPIRATORY RESISTIVE LOADS; SYMPTOM
PERCEPTION; EVOKED-POTENTIALS; MENTAL-DISORDERS; PANIC-ATTACKS; FATAL
ASTHMA; COPD; OCCLUSION; DYSPNEA
AB Previous studies demonstrated that anxiety considerably impacts the reported perceptions of respiratory sensations. A novel feature of the current study is exploring the impact of anxiety on the neural processing of respiratory sensations elicited by short inspiratory occlusions during different affective contexts. Using high-density EEG, respiratory-related evoked potentials (RREP) were recorded in 23 low and 23 matched higher anxious individuals when viewing unpleasant or neutral picture series. Low anxious individuals showed the expected pattern of reduced magnitudes of later RREP components P2 and P3 during the unpleasant compared to the neutral affective context (p < 0.05 and p < 0.01). in contrast, higher anxious individuals showed greater magnitudes of P2 and P3 during the unpleasant compared to the neutral affective context (p's < 0.05). Moreover, higher anxiety levels were correlated with greater magnitudes for P2 (r = 0.44, p < 0.01) and P3 (r = 0.54, p < 0.001) during the unpleasant relative to the neutral affective context. Earlier components of the RREP (Nf, P1, N1) were not affected by anxiety. This study demonstrates that anxiety affects the later, higher-order neural processing of respiratory sensations, but not its earlier, first-order sensory processing. These findings might represent a neural mechanism that underlies the increased perception of respiratory sensations in anxious individuals. (c) 2010 Elsevier Inc. All rights reserved.
C1 [von Leupoldt, Andreas] Univ Hamburg, Dept Psychol, D-20146 Hamburg, Germany.
[von Leupoldt, Andreas; Chan, Pei-Ying S.; Davenport, Paul W.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA.
[von Leupoldt, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany.
[von Leupoldt, Andreas; Bradley, Margaret M.; Lang, Peter J.] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL USA.
[Chan, Pei-Ying S.] Chang Gung Univ, Dept Occupat Therapy, Tao Yuan, Taiwan.
RP von Leupoldt, A (reprint author), Univ Hamburg, Dept Psychol, Von Melle Pk 5, D-20146 Hamburg, Germany.
EM andreas.vonleupoldt@uni-hamburg.de
FU German Research Society (Deutsche Forschungsgemeinschaft, DFG) [LE
1843/9-1]; National Institute of Mental Health [P50 MH 72850]
FX This work was supported by the German Research Society (Deutsche
Forschungsgemeinschaft, DFG) by a stipend to Andreas von Leupoldt
(Heisenberg-Stipendium, LE 1843/9-1) and a grant from the National
Institute of Mental Health (P50 MH 72850) to Peter J. Lang. The authors
wish to thank Andreas Keil for his valuable support of the present
study.
NR 44
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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 MAR 1
PY 2011
VL 55
IS 1
BP 247
EP 252
DI 10.1016/j.neuroimage.2010.11.050
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 716YH
UT WOS:000287008900023
PM 21111831
ER
PT J
AU Gao, XA
Chen, HL
Schwarzschild, MA
Ascherio, A
AF Gao, Xiang
Chen, Honglei
Schwarzschild, Michael A.
Ascherio, Alberto
TI Use of ibuprofen and risk of Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NONNARCOTIC ANALGESIC USE; WOMEN;
METAANALYSIS; NSAIDS; QUESTIONNAIRE; CONSUMPTION; CAFFEINE; SMOKING;
TARGET
AB Background: Neuroinflammation may contribute to the pathogenesis of Parkinson disease (PD). Use of nonsteroidal anti-inflammatory drugs (NSAID) in general, and possibly ibuprofen in particular, has been shown to be related to lower PD risk in previous epidemiologic studies.
Methods: We prospectively examined whether use of ibuprofen or other NSAIDs is associated with lower PD risk among 136,197 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) free of PD at baseline (1998 for NHS and 2000 for HPFS). NSAIDs use was assessed via questionnaire. Results were combined in a meta-analysis with those of published prospective investigations.
Results: We identified 291 incident PD cases during 6 years of follow-up. Users of ibuprofen had a significantly lower PD risk than nonusers (relative risk [RR], adjusted for age, smoking, caffeine, and other covariates = 0.62; 95% confidence interval [CI] 0.42-0.93; p = 0.02). There was a dose-response relationship between tablets of ibuprofen taken per week and PD risk (p trend = 0.01). In contrast, PD risk was not significantly related to use of aspirin (RR = 0.99; 95% CI 0.78-1.26), other NSAIDs (RR = 1.26; 95% CI 0.86-1.84), or acetaminophen (RR = 0.86; 95% CI 0.62-1.18). Similar results were obtained in the meta-analyses: the pooled RR was 0.73 (95% CI 0.63-0.85; p < 0.0001) for ibuprofen use, whereas use of other types of analgesics was not associated with lower PD risk.
Conclusions: The association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD. Neurology (R) 2011; 76: 863-869
C1 [Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Gao, Xiang] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Gao, XA (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM xiang.gao@channing.harvard.edu
OI Chen, Honglei/0000-0003-3446-7779
FU NIH/NINDS [R01 NS048517]; NIH [K24NS060991]; US Department of Defense;
Michael J. Fox Foundation; Parkinson Disease Foundation; RJG Parkinson's
Disease Foundation; American Parkinson Disease Association; American
Federation for Aging Research
FX Supported by NIH/NINDS grant R01 NS048517, NIH K24NS060991, and in part
by the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences. None of the sponsors participated in the
design of this study or in the collection, analysis, or interpretation
of the data.; Dr. Gao has received research support from the NIH/NINDS.
Dr. Chen has received intramural funding from the NIH. Dr. Schwarzschild
has received research support from the NIH/NINDS, the US Department of
Defense, the Michael J. Fox Foundation, the Parkinson Disease
Foundation, the RJG Parkinson's Disease Foundation, the American
Parkinson Disease Association, and the American Federation for Aging
Research. Dr. Ascherio serves on a scientific advisory board for the
Michael J. Fox Foundation; serves on the editorial boards of Neurology
(R), Annals of Neurology, and the American Journal of Epidemiology; has
received speaker honoraria from Merck Serono; and receives research
support from the NIH, the US Department of Defense, and the Michael J.
Fox Foundation.
NR 41
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U1 1
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR
PY 2011
VL 76
IS 10
BP 863
EP 869
DI 10.1212/WNL.0b013e31820f2d79
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 731NZ
UT WOS:000288117500007
PM 21368281
ER
PT J
AU Phelps, CH
AF Phelps, Creighton H.
TI William Markesbery, MD: Some Personal Recollections
SO NEUROMOLECULAR MEDICINE
LA English
DT Biographical-Item
C1 NIA, Alzheimers Dis Ctr Program, Div Neurosci, Bethesda, MD 20892 USA.
RP Phelps, CH (reprint author), NIA, Alzheimers Dis Ctr Program, Div Neurosci, 7201 Wisconsin Ave,Suite 350, Bethesda, MD 20892 USA.
EM phelpsc@nia.nih.gov
NR 0
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U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1535-1084
J9 NEUROMOL MED
JI Neuromol. Med.
PD MAR
PY 2011
VL 13
IS 1
BP 23
EP 24
DI 10.1007/s12017-010-8119-5
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 726VB
UT WOS:000287753400008
PM 20574737
ER
PT J
AU Snyder, DS
AF Snyder, D. Stephen
TI A Remembrance: His Legacy and Science
SO NEUROMOLECULAR MEDICINE
LA English
DT Biographical-Item
C1 NIA, Div Neurosci, NIH, Bethesda, MD 20892 USA.
RP Snyder, DS (reprint author), NIA, Div Neurosci, NIH, Gateway Bldg,Room 350,7201 Wisconsin Ave, Bethesda, MD 20892 USA.
EM ss82f@nih.gov
NR 0
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U1 0
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PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1535-1084
J9 NEUROMOL MED
JI Neuromol. Med.
PD MAR
PY 2011
VL 13
IS 1
BP 25
EP 26
DI 10.1007/s12017-010-8125-7
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 726VB
UT WOS:000287753400009
PM 20607623
ER
PT J
AU Ching, KH
Burbelo, PD
Kimball, RM
Clawson, LL
Corse, AM
Iadarola, MJ
AF Ching, Kathryn H.
Burbelo, Peter D.
Kimball, Richard M.
Clawson, Lora L.
Corse, Andrea M.
Iadarola, Michael J.
TI Recombinant expression of the AChR-alpha1 subunit for the detection of
conformation-dependent epitopes in Myasthenia Gravis
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Myasthenia Gravis; Autoantibodies; Autoantigens; AChR; Luciferase
Immunoprecipitation Systems (LIPS)
ID ACETYLCHOLINE-RECEPTOR ANTIBODY; MAIN IMMUNOGENIC REGION;
MONOCLONAL-ANTIBODIES; LIMBIC ENCEPHALITIS; RENILLA LUCIFERASE;
AUTOANTIBODIES; LOCALIZATION; MODULATION; DISORDERS; RESPONSES
AB Detection of autoantibodies associated with neurological disease typically involves immunoprecipitation of radioactively labeled native proteins. We explored whether single receptor subunits, fused to Renilla luciferase (Rue), could detect patient autoantibodies in Luciferase Immunoprecipitation Systems. Myasthenia Gravis patient sera were tested for conformational autoantibodies to only the alpha 1-subunit of the nicotinic acetylcholine receptor (AChR). Using a panel of 10 AChR-alpha 1 fragments, AChR-alpha 1-Delta 5-Ruc demonstrated the highest immunoreactivity with a conformational-specific antibody and the highest sensitivity in a pilot cohort. Testing a larger cohort with AChR-alpha 1-Delta 5-Ruc demonstrated 21% sensitivity and 97% specificity. A point mutation within Rue increased the diagnostic performance of AChR-alpha 1-Delta 5 (32% sensitivity, 97% specificity). The (125)I-alpha-bungarotoxin multi-subunit AChR assay demonstrated 63% sensitivity and 97% specificity. These findings highlight the difficulty in detecting Myasthenia Gravis conformational epitopes across assay formats and lay the foundation for detecting autoantibodies to defined recombinant chains of the AChR and potentially other neurotransmitter receptors. Published by Elsevier B.V.
C1 [Ching, Kathryn H.] NIDCR, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA.
[Kimball, Richard M.; Clawson, Lora L.; Corse, Andrea M.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA.
RP Ching, KH (reprint author), NIDCR, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bldg 49,Room 1C20,49 Convent Dr, Bethesda, MD 20892 USA.
EM chingk@nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health; Biomarkers Subsection of the Center of
Regenerative Medicine (CNRM)
FX This research was supported by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research, National
Institutes of Health and by the Biomarkers Subsection of the Center of
Regenerative Medicine (CNRM).
NR 31
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U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD MAR
PY 2011
VL 21
IS 3
BP 204
EP 213
DI 10.1016/j.nmd.2010.12.003
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 742GZ
UT WOS:000288930600006
PM 21195619
ER
PT J
AU LaGasse, LL
Gaskins, RB
Bada, HS
Shankaran, S
Liu, J
Lester, BM
Bauer, CR
Higgins, RD
Das, A
Roberts, M
AF LaGasse, Linda L.
Gaskins, Ronnesia B.
Bada, Henrietta S.
Shankaran, Seetha
Liu, Jing
Lester, Barry M.
Bauer, Charles R.
Higgins, Rosemary D.
Das, Abhik
Roberts, Mary
TI Prenatal cocaine exposure and childhood obesity at nine years
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Prenatal cocaine exposure; Prenatal alcohol exposure; Childhood obesity;
Growth; Fetal origins
ID MATERNAL LIFE-STYLE; BODY-MASS INDEX; UNITED-STATES;
SOCIOECONOMIC-STATUS; INTRAUTERINE GROWTH; BLOOD-PRESSURE; BIRTH-WEIGHT;
RISK-FACTORS; MISSING DATA; OVERWEIGHT
AB Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI]>= 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcohol were 4 times more likely to be obese (OR 4.11, CI 2.04-9.76) than children not exposed to either drug. No increase in obesity prevalence was found in children exposed to alcohol but not cocaine (OR 1.08, Cl .59-1.93) or both (OR 1.21, CI 0.66-2.22). Alcohol exposure may attenuate the effect of cocaine exposure on obesity. Increased obesity associated with cocaine but not alcohol exposure was first observed at 7 years. BMI was also elevated from 3 to 9 years in children exposed to cocaine but not alcohol, due to increasing weight but normal height. Prenatal exposure to cocaine may alter the neuroendocrine system and metabolic processes resulting in increased weight gain and childhood obesity. (C) 2010 Elsevier Inc. All rights reserved.
C1 [LaGasse, Linda L.; Gaskins, Ronnesia B.; Liu, Jing; Lester, Barry M.; Roberts, Mary] Brown Univ, Brown Ctr Study Children Risk, Warren Alpert Med Sch, Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA.
[Bada, Henrietta S.] Univ Kentucky Hosp, Lexington, KY USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Bauer, Charles R.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Das, Abhik] RTI Int, Rockville, MD USA.
RP LaGasse, LL (reprint author), Brown Univ, Brown Ctr Study Children Risk, Warren Alpert Med Sch, Women & Infants Hosp Rhode Isl, 101 Dudley St, Providence, RI 02905 USA.
EM Linda_Lagasse@brown.edu
FU National Institute on Drug Abuse (NIDA); National Institute of Child
Health and Human Development (NICHD); National Institute of Mental
Health (NIMH); Warren Alpert Medical School of Brown University
[U10-DA-024119, U10-HD-27904, N01-2-3159]; Wayne State University
[U10-DA-024117, U10-HD-21385]; University of Tennessee [U10-DA-024118,
U10-HD-21415]; University of Miami [U10-DA-024118, U10-HD-21397]; RTI
International [U01-HD-36790]; National Institute on Drug Abuse; National
Institute of Child Health and Human Development
FX This study is part of the MLS which was conducted with support from the
National Institute on Drug Abuse (NIDA) through cooperative agreements
with the National Institute of Child Health and Human Development
(NICHD) and the National Institute of Mental Health (NIMH).
Participating institutions, grant awards, investigators and key research
personnel include: Warren Alpert Medical School of Brown University,
U10-DA-024119, U10-HD-27904, N01-2-3159 (Barry M. Lester, PhD., Cynthia
Miller-Loncar PhD, Linda LaGasse, PhD., and Jean Twomey, PhD); Wayne
State University, U10-DA-024117, U10-HD-21385 (Seetha Shankaran, MD,
Eunice Woldt, MSN, and Jay Ann Nelson, BSN); University of Tennessee,
U10-DA-024118, U10-HD-21415 (Henrietta S. Bada, MD, Toni Whitaker, MD,
Charlotte Bursi, MSSW, Leann Pollard BA and Jonathan Rowland, BS);
University of Miami, U10-DA-024118, U10-HD-21397 (Charles R. Bauer, MD,
Ann L Graziotti ARNP and Susan Gautier, MS); RTI International,
U01-HD-36790 (W. Kenneth Poole, PhD, Abhik Das, PhD, Jane Hammond, PhD,
Debra Fleischmann BS); National Institute on Drug Abuse (Nicolette Borek
PhD and Vincent L Smeriglio PhD); 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,
NIMH) have input into the design and conduct of the study.
NR 57
TC 7
Z9 8
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAR-APR
PY 2011
VL 33
IS 2
BP 188
EP 197
DI 10.1016/j.ntt.2010.11.002
PG 10
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 766YC
UT WOS:000290821500001
PM 21109003
ER
PT J
AU Kumar, D
Abdulovic, AL
Viberg, J
Nilsson, AK
Kunkel, TA
Chabes, A
AF Kumar, Dinesh
Abdulovic, Amy L.
Viberg, Jorgen
Nilsson, Anna Karin
Kunkel, Thomas A.
Chabes, Andrei
TI Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DNA-POLYMERASE-EPSILON; DEOXYRIBONUCLEOSIDE TRIPHOSPHATE POOLS; DAMAGE
CHECKPOINT PATHWAYS; S-PHASE CHECKPOINT; RIBONUCLEOTIDE REDUCTASE;
MUTATIONAL SPECIFICITY; MISMATCH REPAIR; SACCHAROMYCES-CEREVISIAE;
ESCHERICHIA-COLI; CELL-CYCLE
AB The mechanisms by which imbalanced dNTPs induce mutations have been well characterized within a test tube, but not in vivo. We have examined mechanisms by which dNTP imbalances induce genome instability in strains of Saccharomyces cerevisiae with different amino acid substitutions in Rnr1, the large subunit of ribonucleotide reductase. These strains have different dNTP imbalances that correlate with elevated CAN1 mutation rates, with both substitution and insertion-deletion rates increasing by 10- to 300-fold. The locations of the mutations in a strain with elevated dTTP and dCTP are completely different from those in a strain with elevated dATP and dGTP. Thus, imbalanced dNTPs reduce genome stability in a manner that is highly dependent on the nature and degree of the imbalance. Mutagenesis is enhanced despite the availability of proofreading and mismatch repair. The mutations can be explained by imbalanced dNTP-induced increases in misinsertion, strand misalignment and mismatch extension at the expense of proofreading. This implies that the relative dNTP concentrations measured in extracts are truly available to a replication fork in vivo. An interesting mutational strand bias is observed in one rnr1 strain, suggesting that the S-phase checkpoint selectively prevents replication errors during leading strand replication.
C1 [Kumar, Dinesh; Viberg, Jorgen; Nilsson, Anna Karin; Chabes, Andrei] Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
[Abdulovic, Amy L.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Abdulovic, Amy L.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Chabes, Andrei] Umea Univ, Lab Mol Infect Med Sweden MIMS, SE-90187 Umea, Sweden.
RP Chabes, A (reprint author), Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
EM andrei.chabes@medchem.umu.se
OI Chabes, Andrei/0000-0003-1708-8259
FU Division of Intramural Research of the National Institutes of Health
[Z01 ES065070]; Stiftelsen J.C. Kempes Minnes Stipendiefond; Swedish
Foundation for Strategic Research; Swedish Research Council; Swedish
Cancer Society
FX Division of Intramural Research of the National Institutes of Health
(Project Z01 ES065070 to T.A.K.); Stiftelsen J.C. Kempes Minnes
Stipendiefond (to D.K. and J.V.); Swedish Foundation for Strategic
Research (to A.C.); Swedish Research Council (to A.C.); The Swedish
Cancer Society (to A.C.). Funding for open access charge: The Swedish
Research Council.
NR 65
TC 68
Z9 70
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAR
PY 2011
VL 39
IS 4
BP 1360
EP 1371
DI 10.1093/nar/gkq829
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730FP
UT WOS:000288019400023
PM 20961955
ER
PT J
AU Shardell, MD
Alley, DE
Hicks, GE
El-Kamary, SS
Miller, RR
Semba, RD
Ferrucci, L
AF Shardell, Michelle D.
Alley, Dawn E.
Hicks, Gregory E.
El-Kamary, Samer S.
Miller, Ram R.
Semba, Richard D.
Ferrucci, Luigi
TI Low-serum carotenoid concentrations and carotenoid interactions predict
mortality in US adults: the Third National Health and Nutrition
Examination Survey
SO NUTRITION RESEARCH
LA English
DT Article
DE alpha-carotene; beta-carotene; beta-cryptoxanthin; carotenoids; human
subjects; lycopene; lutein; mortality; NHANES; zeaxanthin
ID TOTAL PLASMA CAROTENOIDS; ARTERY RISK DEVELOPMENT; BETA-CAROTENE;
LUNG-CANCER; CARDIOVASCULAR-DISEASE; MEDITERRANEAN DIET; METABOLIC
SYNDROME; OXIDATIVE STRESS; UNITED-STATES; LYCOPENE
AB Evidence regarding the health benefits of carotenoids is controversial. Effects of serum carotenoids and their interactions on mortality have not been examined in a representative sample of US adults. The objective was to examine whether serum carotenoid concentrations predict mortality among US adults. The study consisted of adults aged >= 20 years enrolled in the Third National Health and Nutrition Examination Survey, 1988 to 1994, with measured serum carotenoids and mortality follow-up through 2006 (N = 13 293). Outcomes were all-cause, cardiovascular disease, and cancer mortality. In adjusted Cox proportional hazards models, participants in the lowest total carotenoid quartile (<1.01 mu mol/L) had significantly higher all-cause mortality (mortality rate ratio, 1.38; 95% confidence interval, 1.15-1.65; P = .005) than those in the highest total carotenoid quartile (>1.75 mu mol/L). For alpha-carotene, the highest quartile (>0.11 mu mol/L) had the lowest all-cause mortality rates (P < .001). For lycopene, the middle 2 quartiles (0.29-0.58 mu mol/L) had the lowest all-cause mortality rates (P = .047). Analyses with continuous carotenoids confirmed associations of serum total carotenoids, alpha-carotene, and lycopene with all-cause mortality (P < .001). In a random survival forest analysis, very low lycopene was the carotenoid most strongly predictive of all-cause mortality, followed by very low total carotenoids. alpha-Carotene/beta-cryptoxanthin, alpha-carotene/lutein+zeaxanthin and lycopene/lutein +zeaxanthin interactions were significantly related to all-cause mortality (P < .05). Low alpha-carotene was the only carotenoid associated with cardiovascular disease mortality (P = .002). No carotenoids were significantly associated with cancer mortality. Very low serum total carotenoid, alpha-carotene, and lycopene concentrations may be risk factors for mortality, but carotenoids show interaction effects on mortality. Interventions of balanced carotenoid combinations are needed for confirmation. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Shardell, Michelle D.] Univ Maryland, Sch Med, Div Biostat & Bioinformat, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE USA.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Shardell, MD (reprint author), Univ Maryland, Sch Med, Div Biostat & Bioinformat, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
EM mshardel@epi.umaryland.edu
FU NIH [K12 HD043489, K12HD055931, K23 AG019161, R21HD057274, R01 HL094507,
R01 AG027012]
FX This research was supported by NIH grants K12 HD043489, K12HD055931, K23
AG019161, R21HD057274, R01 HL094507, R01 AG027012. The authors have no
conflicts of interest to report.
NR 48
TC 42
Z9 43
U1 1
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD MAR
PY 2011
VL 31
IS 3
BP 178
EP 189
DI 10.1016/j.nutres.2011.03.003
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 754BF
UT WOS:000289825400002
PM 21481711
ER
PT J
AU Spong, CY
Queenan, JT
AF Spong, Catherine Y.
Queenan, John T.
TI Uterine Scar Assessment How Should It Be Done Before Trial of Labor
After Cesarean Delivery?
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID RUPTURE; RISK
C1 [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA.
RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA.
EM spongc@dir49.nichd.nih.gov; jqueenan@greenjournal.org
NR 6
TC 6
Z9 6
U1 1
U2 2
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 MAR
PY 2011
VL 117
IS 3
BP 521
EP 522
DI 10.1097/AOG.0b013e31820ce593
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 725MR
UT WOS:000287649400001
PM 21343752
ER
PT J
AU Abu-Asab, MS
Chaouchi, M
Alesci, S
Galli, S
Laassri, M
Cheema, AK
Atouf, F
VanMeter, J
Amri, H
AF Abu-Asab, Mones S.
Chaouchi, Mohamed
Alesci, Salvatore
Galli, Susana
Laassri, Majid
Cheema, Amrita K.
Atouf, Fouad
VanMeter, John
Amri, Hakima
TI Biomarkers in the Age of Omics: Time for a Systems Biology Approach
SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
LA English
DT Review
ID BREAST-CANCER PATIENTS; PROSTATE-CANCER; MUTATOR PHENOTYPE; EVOLUTION;
DISCOVERY; HETEROGENEITY; DISEASE; MICROARRAYS; CARCINOMAS; LIKELIHOOD
AB Limitations to biomarker discovery are not only technical or bioinformatic but conceptual as well. In our attempt to offer a solution, we are highlighting three issues that we think are limiting progress in biomarkers discovery. First, the confusion stemming from the imposition of a pathology-type immunohistochemical marker (IHCM) concept on omics data without fully understanding the characteristics and limitations of IHCMs as applied in clinical pathology. Second, the lack of serious consideration for the scope of disease heterogeneity. Third, the refusal of the biomedical community to borrow from other biological disciplines their well established methods for dealing with heterogeneity. Therefore, real progress in biomarker discovery will be attained when we recognize that an omics biomarker cannot be assigned and validated without a priori data modeling and subtyping of the disease itself to reveal the extent of its heterogeneity, and its omics' clonal aberrations (drivers) underlying its subtypes and pathways' diversity. To further support our viewpoints, we are contributing a novel a systems biology method such as parsimony phylogenetic approach for disease modeling prior to biomarker circumscription. As an analytical approach that has been successfully used for a half of a century in other biological disciplines, parsimony phylogenetics simultaneously achieves several objectives: it provides disease modeling in a hierarchical phylogenetic classification, identifies biomarkers as the shared derived expressions or mutations-synapomorphies, constructs the omics profiles of specimens based on the most parsimonious arrangement of their heterogeneous data, and permits network profiling of affected signaling pathways as the biosignature of disease classes.
C1 [Chaouchi, Mohamed; Amri, Hakima] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA.
[Abu-Asab, Mones S.; Galli, Susana] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Alesci, Salvatore] Pfizer, Discovery Translat Med, Collegeville, PA USA.
[Laassri, Majid] US FDA, Lab Methods Dev, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Cheema, Amrita K.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA.
[Atouf, Fouad] US Pharmacopeia, Biol & Biotechnol, Rockville, MD USA.
[VanMeter, John] Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20007 USA.
RP Amri, H (reprint author), Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA.
EM amrih@georgetown.edu
OI Abu-Asab, Mones/0000-0002-4047-1232
FU Intramural NIH HHS [Z99 CA999999]
NR 57
TC 33
Z9 33
U1 1
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1536-2310
J9 OMICS
JI OMICS
PD MAR
PY 2011
VL 15
IS 3
BP 105
EP 112
DI 10.1089/omi.2010.0023
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 730XY
UT WOS:000288072100003
PM 21319991
ER
PT J
AU Patel, JB
Appaiah, HN
Burnett, RM
Bhat-Nakshatri, P
Wang, G
Mehta, R
Badve, S
Thomson, MJ
Hammond, S
Steeg, P
Liu, Y
Nakshatri, H
AF Patel, J. B.
Appaiah, H. N.
Burnett, R. M.
Bhat-Nakshatri, P.
Wang, G.
Mehta, R.
Badve, S.
Thomson, M. J.
Hammond, S.
Steeg, P.
Liu, Y.
Nakshatri, H.
TI Control of EVI-1 oncogene expression in metastatic breast cancer cells
through microRNA miR-22
SO ONCOGENE
LA English
DT Article
DE breast cancer; metastasis; microRNA; miR-22; let-7
ID GENE-EXPRESSION; SIGNATURE; SURVIVAL; REPRESSION; MIGRATION; PROGNOSIS;
INSIGHTS; THERAPY; ESCAPE; LEADS
AB Metastasis in breast cancer carries a disproportionately worse prognosis than localized primary disease. To identify microRNAs (miRNA) involved in metastasis, the expression of 254 miRNAs was measured across the following cell lines using microarray analysis: MDA-MB-231 breast cancer cells, cells that grew as a tumor in the mammary fat pad of nude mice (TMD-231), metastatic disease to the lungs (LMD-231), bone (BMD-231) and adrenal gland (ADMD-231). A brain-seeking variant of this cell line (231-BR) was used additionally in validation studies. Twenty miRNAs were upregulated and seven were downregulated in metastatic cancer cells compared with TMD-231 cells. The expression of the tumor suppressor miRNAs let-7 and miR-22 was consistently downregulated in metastatic cancer cells. These metastatic cells expressed higher levels of putative/proven miR-22 target oncogenes ERBB3, CDC25C and EVI-1. Introduction of miR-22 into cancer cells reduced the levels of ERBB3 and EVI-1 as well as phospho-AKT, an EVI-1 downstream target. The miR-22 primary transcript is located in the 50-untranslated region of an open reading frame C17orf91, and the promoter/enhancer of C17orf91 drives miR-22 expression. We observed elevated C17orf91 expression in non-basal subtype compared with basal subtype breast cancers. In contrast, elevated expression of EVI-1 was observed in basal subtype and was associated with poor outcome in estrogen receptor-negative breast cancer patients. These results suggest that metastatic cancer cells increase specific oncogenic signaling proteins through downregulation of miRNAs. Identifying such metastasis-specific oncogenic pathways may help to manipulate tumor behavior and aid in the design of more effective targeted therapies. Oncogene (2011) 30, 1290-1301; doi:10.1038/onc.2010.510; published online 8 November 2010
C1 [Patel, J. B.; Appaiah, H. N.; Bhat-Nakshatri, P.; Nakshatri, H.] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA.
[Wang, G.; Liu, Y.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Mehta, R.; Badve, S.] Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA.
[Thomson, M. J.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
[Hammond, S.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA.
[Steeg, P.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Nakshatri, H.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
RP Nakshatri, H (reprint author), Indiana Univ, Sch Med, Dept Surg, 980 W Walnut St C218E, Indianapolis, IN 46202 USA.
EM hnakshat@iupui.edu
RI Xie, Huangming/B-2260-2012; Nidumanda, HITESH/B-5744-2015; Mehta,
Rutika/S-2052-2016
OI Mehta, Rutika/0000-0003-4277-0153
FU Indiana University Simon Cancer Center; Komen for Cure [BCTR0601111];
National Institutes of Health [T32 DK07519, T32 CA111198]
FX This work is supported by Indiana University Simon Cancer Center Pilot
grant and by Komen for Cure grant BCTR0601111 to HN. JBP and RMB are
supported by National Institutes of Health Training Grants T32 DK07519
and T32 CA111198, respectively. HN is Marian J Morrison Professor of
Breast Cancer Research.
NR 48
TC 55
Z9 60
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAR
PY 2011
VL 30
IS 11
BP 1290
EP 1301
DI 10.1038/onc.2010.510
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 736JX
UT WOS:000288492100004
PM 21057539
ER
PT J
AU Arlen, PM
AF Arlen, Philip M.
TI Prostate Cancer Immunotherapy: the Role for Sipuleucel-T and Other
Immunologic Approaches THE GARCIA AND DREICER ARTICLE REVIEWED
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID COMBINATION THERAPY; VACCINE; SURVIVAL; CHEMOTHERAPY; ANTIGEN
C1 NCI, Bethesda, MD 20892 USA.
RP Arlen, PM (reprint author), NCI, Bethesda, MD 20892 USA.
NR 13
TC 2
Z9 2
U1 0
U2 0
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD MAR
PY 2011
VL 25
IS 3
BP 261
EP 262
PG 2
WC Oncology
SC Oncology
GA 800EO
UT WOS:000293342800007
PM 21548469
ER
PT J
AU Patel, BB
Li, XM
Dixon, MP
Blagoi, EL
Nicolas, E
Seeholzer, SH
Cheng, D
He, YA
Coudry, RA
Howard, SD
Riddle, DM
Cooper, HS
Boman, BM
Conrad, P
Crowell, JA
Bellacosa, A
Knudson, A
Yeung, AT
Kopelovich, L
AF Patel, Bhavinkumar B.
Li, Xin-Ming
Dixon, Maketa P.
Blagoi, Elena L.
Nicolas, Emmanuelle
Seeholzer, Steven H.
Cheng, David
He, Yin A.
Coudry, Renata A.
Howard, Sharon D.
Riddle, Dawn M.
Cooper, Harry S.
Boman, Bruce M.
Conrad, Peggy
Crowell, James A.
Bellacosa, Alfonso
Knudson, Alfred
Yeung, Anthony T.
Kopelovich, Levy
TI APC(+/-) alters colonic fibroblast proteome in FAP
SO ONCOTARGET
LA English
DT Article
DE Adenomatous polyposis; APC; tumor suppressor; colon fibroblasts;
heterozygosity; proteomics
ID FAMILIAL ADENOMATOUS POLYPOSIS; HUMAN-SKIN FIBROBLASTS; RAS SUPPRESSOR
RSU-1; CANCER-CELLS; KINASE ACTIVATION; INDUCED APOPTOSIS; OXIDATIVE
STRESS; EPITHELIAL-CELLS; GENE-EXPRESSION; DJ-1
AB Here we compared the proteomes of primary fibroblast cultures derived from morphologically normal colonic mucosa of familial adenomatous polyposis (FAP) patients with those obtained from unaffected controls. The expression signature of about 19% of total fibroblast proteins separates FAP mutation carriers from unaffected controls (P < 0.01). More than 4,000 protein spots were quantified by 2D PAGE analysis, identifying 368 non-redundant proteins and 400 of their isoforms. Specifically, all three classes of cytoskeletal filaments and their regulatory proteins were altered as were oxidative stress response proteins. Given that FAP fibroblasts showed heightened sensitivity to transformation by KiMSV and SV40 including elevated levels of the p53 protein, events controlled in large measure by the Ras suppressor protein-1 (RSU-1) and oncogenic DJ-1, here we show decreased RSU1 and augmented DJ-1 expression in both fibroblasts and crypt-derived epithelial cells from morphologically normal colonic mucosa of FAP gene-carriers. The results indicate that heterozygosity for a mutant APC tumor suppressor gene alters the proteomes of both colon-derived normal fibroblasts in a gene-specific manner, consistent with a "one-hit" effect.
C1 [Riddle, Dawn M.; Yeung, Anthony T.] Fox Chase Canc Ctr, Cell Culture Facil, Philadelphia, PA 19111 USA.
[Howard, Sharon D.; Boman, Bruce M.] Thomas Jefferson Univ, Div Genet & Prevent Med, Philadelphia, PA 19107 USA.
[Conrad, Peggy] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Crowell, James A.; Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Yeung, AT (reprint author), Fox Chase Canc Ctr, Cell Culture Facil, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
EM Anthony.Yeung@fccc.edu; kopelovl@mail.nih.gov
FU National Cancer Institute [NO1-CN-15103, N01-CN-43309, DK063014,
P30CA006927, CA119242]; Ewing Trust; Fannie E. Rippel Foundation;
Sholler Foundation; Commonwealth of Pennsylvania; Pew Charitable Trust;
Kresge Foundation
FX Supported by the National Cancer Institute, Contract No. NO1-CN-15103
(A.K), and N01-CN-43309, Grant DK063014 (B.B), Institutional Core Grant
P30CA006927, CA119242 and the Ewing Trust (T.Y), the Fannie E. Rippel
Foundation, The Sholler Foundation, Tobacco Settlement Funds from the
Commonwealth of Pennsylvania, the Pew Charitable Trust, and the Kresge
Foundation.
NR 50
TC 12
Z9 12
U1 1
U2 5
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2011
VL 2
IS 3
BP 197
EP 208
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 802KH
UT WOS:000293509000011
PM 21411865
ER
PT J
AU Djamshidian, A
O'Sullivan, SS
Lees, A
Averbeck, BB
AF Djamshidian, Atbin
O'Sullivan, Sean S.
Lees, Andrew
Averbeck, Bruno B.
TI Stroop test performance in impulsive and non impulsive patients with
Parkinson's disease
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson's disease; Impulsive compulsive behaviour; Stroop test
ID RISK
AB Impulsive personalities are considered to have a general impairment in cognitive flexibility and cortical inhibition. To examine this hypothesis we used a trial by trial Stroop task in impulsive and non impulsive patients with Parkinson's disease (PD) and recorded errors and reaction times (RT). We tested 28 impulsive PD (PD + ICB) and 24 non impulsive PD (PD-ICB) patients prior to and after dopaminergic medication. These results were compared with 24 age matched normal controls.
We found an increased error rate in all PD patients prior to their usual medication which resolved after medication. Furthermore patients on medication showed enhanced cognitive flexibility and shorter RT. There was no difference between non impulsive and impulsive PD patients. This suggests that the impulsive behaviours may not affect response inhibition tasks and the response inhibition required in the Stroop test does not engage the same processes that differentiate impulsive and non-impulsive PD patients, which likely involve mesolimbic dopamine. Published by Elsevier Ltd.
C1 [Averbeck, Bruno B.] NIMH, NIH, Neuropsychol Lab, Bethesda, MD 20892 USA.
[Averbeck, Bruno B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Lees, Andrew] Univ London, Dept Mol Neurosci, London, England.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Lees, Andrew] Univ London, Reta Lila Weston Inst Neurol Studies, London, England.
RP Averbeck, BB (reprint author), NIMH, NIH, Neuropsychol Lab, Bldg 49 Room 1B80,49 Convent Dr MSC 4415, Bethesda, MD 20892 USA.
EM bruno.averbeck@nih.gov
RI O'Sullivan, Sean/C-9333-2012; Lees, Andrew/A-6605-2009;
OI O'Sullivan, Sean/0000-0002-0583-7956; Djamshidian,
Atbin/0000-0001-7174-6000
FU NIH, NIMH
FX The authors wish to thank the patients and families who participated in
the study. This work was supported in part by the Intramural Research
Program of the NIH, NIMH.
NR 15
TC 26
Z9 28
U1 0
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD MAR
PY 2011
VL 17
IS 3
BP 212
EP 214
DI 10.1016/j.parkreldis.2010.12.014
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 736FC
UT WOS:000288475100017
PM 21247790
ER
PT J
AU Persky, S
AF Persky, Susan
TI Employing immersive virtual environments for innovative experiments in
health care communication
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Communication; Health care; Virtual environments; Virtual reality;
Methods
ID STANDARDIZED PATIENTS; SOCIAL-INFLUENCE; MEDICAL VISIT; PATIENT;
REALITY; BEHAVIOR; SKILLS; TOOL; TECHNOLOGY; TRIAL
AB Objective: This report reviews the literature for studies that employ immersive virtual environment technology methods to conduct experimental studies in health care communication. Advantages and challenges of using these tools for research in this area are also discussed.
Methods: A literature search was conducted using the Scopus database. Results were hand searched to identify the body of studies, conducted since 1995, that are related to the report objective.
Results: The review identified four relevant studies that stem from two unique projects. One project focused on the impact of a clinician's characteristics and behavior on health care communication, the other focused on the characteristics of the patient. Both projects illustrate key methodological advantages conferred by immersive virtual environments, including, ability to maintain simultaneously high experimental control and realism, ability to manipulate variables in new ways, and unique behavioral measurement opportunities.
Conclusion: Though implementation challenges exist for immersive virtual environment-based research methods, given the technology's unique capabilities, benefits can outweigh the costs in many instances.
Practice implications: Immersive virtual environments may therefore prove an important addition to the array of tools available for advancing our understanding of communication in health care. Published by Elsevier Ireland Ltd.
C1 NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
RP Persky, S (reprint author), NHGRI, Social & Behav Res Branch, 31 Ctr Dr,Room B1B36, Bethesda, MD 20892 USA.
EM perskys@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
The funding source had no role in preparation or writing of the report
or in the decision to submit the paper for publication. This manuscript
was written in the course of employment by the United States Government
and it is not subject to copyright in the United States.
NR 49
TC 12
Z9 12
U1 1
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD MAR
PY 2011
VL 82
IS 3
SI SI
BP 313
EP 317
DI 10.1016/j.pec.2010.12.007
PG 5
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 741BJ
UT WOS:000288837800006
PM 21232902
ER
PT J
AU Murphy, E
Lagranha, C
Deschamps, A
Kohr, M
Nguyen, T
Wong, RN
Sun, JH
Steenbergen, C
AF Murphy, Elizabeth
Lagranha, Claudia
Deschamps, Anne
Kohr, Mark
Nguyen, Tiffany
Wong, Renee
Sun, Junhui
Steenbergen, Charles
TI Mechanism of Cardioprotection: What Can We Learn from Females?
SO PEDIATRIC CARDIOLOGY
LA English
DT Article
DE Cardioprotection; Estrogen signaling; G-protein-coupled receptor;
Nuclear estrogen receptors
ID ESTROGEN-RECEPTOR-BETA; ALPHA-KETOGLUTARATE DEHYDROGENASE;
ISCHEMIA-REPERFUSION INJURY; CORONARY-HEART-DISEASE;
ISCHEMIA/REPERFUSION INJURY; REACTIVE OXYGEN; S-NITROSYLATION; OXIDATIVE
STRESS; SEX-DIFFERENCES; PLUS PROGESTIN
AB This review examines the mechanism of estrogen signaling in cardiomyocytes, with an emphasis on mechanisms that might be important in cardioprotection. It investigates estrogen signaling mediated by the nuclear estrogen receptors alpha and beta and the G-protein-coupled receptor (GPR 30/GPER). Estrogen signaling via nitric oxide and the PI3K pathway are discussed.
C1 [Murphy, Elizabeth; Lagranha, Claudia; Deschamps, Anne; Kohr, Mark; Nguyen, Tiffany; Wong, Renee; Sun, Junhui] NHLBI, NIH, Bethesda, MD 20892 USA.
[Kohr, Mark; Steenbergen, Charles] Johns Hopkins Univ, Baltimore, MD USA.
RP Murphy, E (reprint author), NHLBI, NIH, Room 8N202,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
RI Sun, Junhui/C-3499-2011;
OI Kohr, Mark/0000-0002-6034-5962; Deschamps, Anne/0000-0001-7415-1408
FU NHLBI NIH HHS [F32 HL096142, R01 HL039752, R01 HL039752-24]
NR 39
TC 10
Z9 10
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0172-0643
J9 PEDIATR CARDIOL
JI Pediatr. Cardiol.
PD MAR
PY 2011
VL 32
IS 3
SI SI
BP 354
EP 359
DI 10.1007/s00246-010-9877-4
PG 6
WC Cardiac & Cardiovascular Systems; Pediatrics
SC Cardiovascular System & Cardiology; Pediatrics
GA 737IU
UT WOS:000288563300016
PM 21279340
ER
PT J
AU Eggly, S
Meert, KL
Berger, J
Zimmerman, J
Anand, KJS
Newth, CJL
Harrison, R
Carcillo, J
Dean, JM
Willson, DF
Nicholson, C
AF Eggly, Susan
Meert, Kathleen L.
Berger, John
Zimmerman, Jerry
Anand, Kanwaljeet J. S.
Newth, Christopher J. L.
Harrison, Rick
Carcillo, Joseph
Dean, J. Michael
Willson, Douglas F.
Nicholson, Carol
CA Eunice Kennedy Shriver Natl Inst C
TI A framework for conducting follow-up meetings with parents after a
child's death in the pediatric intensive care unit
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE parental bereavement; pediatric; guidelines for physician-parent
follow-up visit; facilitating healthy bereavement; professional
gratification; physician/staff burnout
ID OF-LIFE CARE; PALLIATIVE CARE; COMPASSION FATIGUE; HOSPITAL DOCTORS;
HEALTH-CARE; SELF-CARE; END; PERSPECTIVES; BEREAVEMENT; PHYSICIANS
AB Objective: To describe a framework to assist pediatric intensive care unit physicians in conducting follow-up meetings with parents after their child's death. Many childhood deaths occur in pediatric intensive care units. Parents of children who die in pediatric intensive care units often desire a follow-up meeting with the physician(s) who cared for their child.
Data Sources: Prior research conducted by the Collaborative Pediatric Critical Care Research Network on the experiences and perspectives of bereaved parents and pediatric intensive care unit physicians regarding the desirability, content, and conditions of follow-up meetings.
Results: The framework includes suggestions for inviting families to follow-up meetings (i.e., developing an institutional system, invitation timing, and format); preparing for the meeting (i.e., assessing family preferences; determining location, attendees, and discussion topics; reviewing medical and psychosocial history); structure of the meeting (i.e., opening, closing, and developing a meeting agenda); communicating effectively during the meeting; and follow-up for both parents and physicians.
Conclusion: This framework is based on the experience and perspectives of bereaved parents and pediatric intensive care unit physicians. Future research should be conducted to determine the extent to which physician-parent follow-up meetings provide a benefit to parents, families, physicians, and other healthcare providers participating in these encounters. (Pediatr Crit Care Med 2011; 12:147-152)
C1 [Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Eggly, Susan] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA.
[Berger, John] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Zimmerman, Jerry] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA.
[Anand, Kanwaljeet J. S.] Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72202 USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA.
[Harrison, Rick] Univ Calif Los Angeles, Dept Pediat, Mattel Childrens Hosp, Los Angeles, CA 90024 USA.
[Carcillo, Joseph] Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15213 USA.
[Dean, J. Michael] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Willson, Douglas F.] Univ Virginia, Dept Pediat, Childrens Hosp, Charlottesville, VA USA.
[Nicholson, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
RP Meert, KL (reprint author), Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
EM kmeert@med.wayne.edu
OI Anand, Kanwaljeet/0000-0001-6498-1483; Eggly, Susan/0000-0002-8137-6098
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U10HD050096, U10HD049981, U10HD500009, U10HD049945,
U10HD049983, U10HD050012, U01HD049934]; Department of Health and Human
Services
FX This study was funded, in part, by cooperative agreements U10HD050096
(KLM), U10HD049981 (JB), U10HD500009 (KJSA), U10HD049945 (JZ),
U10HD049983 (JC), U10HD050012 (CJLN), and U01HD049934 (MD) from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the Department of Health and Human Services.
NR 50
TC 13
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U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1529-7535
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD MAR
PY 2011
VL 12
IS 2
BP 147
EP 152
DI 10.1097/PCC.0b013e3181e8b40c
PG 6
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA 730BY
UT WOS:000288006100004
PM 20625339
ER
PT J
AU Fredholm, BB
IJzerman, AP
Jacobson, KA
Linden, J
Muller, CE
AF Fredholm, Bertil B.
IJzerman, Adriaan P.
Jacobson, Kenneth A.
Linden, Joel
Mueller, Christa E.
TI International Union of Basic and Clinical Pharmacology. LXXXI.
Nomenclature and Classification of Adenosine Receptors-An Update
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID PROTEIN-COUPLED RECEPTOR; BIOLUMINESCENCE ENERGY-TRANSFER; POTENTIAL
THERAPEUTIC APPLICATIONS; COTRANSFECTED FIBROBLAST CELLS;
CAFFEINE-INDUCED ANXIETY; DOPAMINE D-1 RECEPTORS; HIGHER-ORDER
OLIGOMERS; HAMSTER OVARY CELLS; A(1) RECEPTOR; A(2A) RECEPTOR
AB In the 10 years since our previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors, no developments have led to major changes in the recommendations. However, there have been so many other developments that an update is needed. The fact that the structure of one of the adenosine receptors has recently been solved has already led to new ways of in silico screening of ligands. The evidence that adenosine receptors can form homo- and heteromultimers has accumulated, but the functional significance of such complexes remains unclear. The availability of mice with genetic modification of all the adenosine receptors has led to a clarification of the functional roles of adenosine, and to excellent means to study the specificity of drugs. There are also interesting associations between disease and structural variants in one or more of the adenosine receptors. Several new selective agonists and antagonists have become available. They provide improved possibilities for receptor classification. There are also developments hinting at the usefulness of allosteric modulators. Many drugs targeting adenosine receptors are in clinical trials, but the established therapeutic use is still very limited.
C1 [Fredholm, Bertil B.] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden.
[IJzerman, Adriaan P.] Leiden Amsterdam Ctr Drug Res, Div Med Chem, Leiden, Netherlands.
[Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
[Linden, Joel] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA USA.
[Mueller, Christa E.] Univ Bonn, Inst Pharmaceut, PharmaCtr Bonn, D-5300 Bonn, Germany.
RP Fredholm, BB (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, Nanna Svartz 2, S-17177 Stockholm, Sweden.
EM bertil.fredholm@ki.se
RI Jacobson, Kenneth/A-1530-2009; Muller, Christa/C-7748-2014;
OI Jacobson, Kenneth/0000-0001-8104-1493; Muller,
Christa/0000-0002-0013-6624; IJzerman, Ad/0000-0002-1182-2259
FU Swedish Science Council [2553]; Dutch Top Institute Pharma [D1-105];
National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases; Bundesministerium fur Bildung und
Forschung
FX This work was supported by the Swedish Science Council [Project 2553]
(to B.B.F.); the Dutch Top Institute Pharma [Project D1-105] (to
A.P.IJ.); by the Intramural Research Program of the National Institutes
of Health National Institute of Diabetes and Digestive and Kidney
Diseases (to K.A.J.); and the Bundesministerium fur Bildung und
Forschung within the BioPharma-Neuroallianz project (to C.E.M.).
NR 276
TC 438
Z9 450
U1 8
U2 36
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD MAR
PY 2011
VL 63
IS 1
BP 1
EP 34
DI 10.1124/pr.110.003285
PG 34
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 721LS
UT WOS:000287356800001
PM 21303899
ER
PT J
AU Peremyslov, V
Mockler, TC
Filichkin, SA
Fox, SE
Jaiswal, P
Makarova, KS
Koonin, EV
Dolja, VV
AF Peremyslov, Valera V.
Mockler, Todd C.
Filichkin, Sergei A.
Fox, Samuel E.
Jaiswal, Pankaj
Makarova, Kira S.
Koonin, Eugene V.
Dolja, Valerian V.
TI Expression, Splicing, and Evolution of the Myosin Gene Family in Plants
SO PLANT PHYSIOLOGY
LA English
DT Article
ID CLASS-XI MYOSINS; F-ACTIN ORGANIZATION; ROOT HAIR;
NICOTIANA-BENTHAMIANA; ENDOPLASMIC-RETICULUM; ARABIDOPSIS-THALIANA; TIP
GROWTH; CELLS; MOTILITY; LEAVES
AB Plants possess two myosin classes, VIII and XI. The myosins XI are implicated in organelle transport, filamentous actin organization, and cell and plant growth. Due to the large size of myosin gene families, knowledge of these molecular motors remains patchy. Using deep transcriptome sequencing and bioinformatics, we systematically investigated myosin genes in two model plants, Arabidopsis (Arabidopsis thaliana) and Brachypodium (Brachypodium distachyon). We improved myosin gene models and found that myosin genes undergo alternative splicing. We experimentally validated the gene models for Arabidopsis myosin XI-K, which plays the principal role in cell interior dynamics, as well as for its Brachypodium ortholog. We showed that the Arabidopsis gene dubbed HDK (for headless derivative of myosin XI-K), which emerged through a partial duplication of the XI-K gene, is developmentally regulated. A gene with similar architecture was also found in Brachypodium. Our analyses revealed two predominant patterns of myosin gene expression, namely pollen/stamen-specific and ubiquitous expression throughout the plant. We also found that several myosins XI can be rhythmically expressed. Phylogenetic reconstructions indicate that the last common ancestor of the angiosperms possessed two myosins VIII and five myosins XI, many of which underwent additional lineage-specific duplications.
C1 [Peremyslov, Valera V.; Mockler, Todd C.; Filichkin, Sergei A.; Fox, Samuel E.; Jaiswal, Pankaj; Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
[Mockler, Todd C.; Jaiswal, Pankaj; Dolja, Valerian V.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
[Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Dolja, VV (reprint author), Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
EM doljav@science.oregonstate.edu
RI Mockler, Todd/L-2609-2013; Jaiswal, Pankaj/H-7599-2016
OI Mockler, Todd/0000-0002-0462-5775; Jaiswal, Pankaj/0000-0002-1005-8383
FU National Institutes of Health [GM087658]
FX This work was supported by the National Institutes of Health (grant no.
GM087658 to V. V. D.).
NR 38
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U1 0
U2 17
PU AMER SOC PLANT BIOLOGISTS
PI ROCKVILLE
PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
SN 0032-0889
J9 PLANT PHYSIOL
JI Plant Physiol.
PD MAR
PY 2011
VL 155
IS 3
BP 1191
EP 1204
DI 10.1104/pp.110.170720
PG 14
WC Plant Sciences
SC Plant Sciences
GA 727ZY
UT WOS:000287843800012
PM 21233331
ER
PT J
AU Kim, YA
Wuchty, S
Przytycka, TM
AF Kim, Yoo-Ah
Wuchty, Stefan
Przytycka, Teresa M.
TI Identifying Causal Genes and Dysregulated Pathways in Complex Diseases
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID PROTEIN INTERACTION NETWORK; PHOSPHORYLATION NETWORKS; BREAST-CANCER;
GROWTH-FACTOR; EGF RECEPTOR; TGF-BETA; EXPRESSION; RESOURCE; DATABASE;
DISCOVERY
AB In complex diseases, various combinations of genomic perturbations often lead to the same phenotype. On a molecular level, combinations of genomic perturbations are assumed to dys-regulate the same cellular pathways. Such a pathway-centric perspective is fundamental to understanding the mechanisms of complex diseases and the identification of potential drug targets. In order to provide an integrated perspective on complex disease mechanisms, we developed a novel computational method to simultaneously identify causal genes and dys-regulated pathways. First, we identified a representative set of genes that are differentially expressed in cancer compared to non-tumor control cases. Assuming that disease-associated gene expression changes are caused by genomic alterations, we determined potential paths from such genomic causes to target genes through a network of molecular interactions. Applying our method to sets of genomic alterations and gene expression profiles of 158 Glioblastoma multiforme (GBM) patients we uncovered candidate causal genes and causal paths that are potentially responsible for the altered expression of disease genes. We discovered a set of putative causal genes that potentially play a role in the disease. Combining an expression Quantitative Trait Loci (eQTL) analysis with pathway information, our approach allowed us not only to identify potential causal genes but also to find intermediate nodes and pathways mediating the information flow between causal and target genes. Our results indicate that different genomic perturbations indeed dys-regulate the same functional pathways, supporting a pathway-centric perspective of cancer. While copy number alterations and gene expression data of glioblastoma patients provided opportunities to test our approach, our method can be applied to any disease system where genetic variations play a fundamental causal role.
C1 [Kim, Yoo-Ah; Wuchty, Stefan; Przytycka, Teresa M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Kim, YA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM przytyck@ncbi.nlm.nih.gov
FU National Institutes of Health, the National Library of Medicine;
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Library of Medicine, and by
the National Institutes of Health. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 60
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U1 2
U2 4
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 MAR
PY 2011
VL 7
IS 3
AR e1001095
DI 10.1371/journal.pcbi.1001095
PG 13
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 743CU
UT WOS:000288995500003
PM 21390271
ER
PT J
AU Metzger, VT
Lloyd-Smith, JO
Weinberger, LS
AF Metzger, Vincent T.
Lloyd-Smith, James O.
Weinberger, Leor S.
TI Autonomous Targeting of Infectious Superspreaders Using Engineered
Transmissible Therapies
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; VIRUS TYPE-1 INFECTION; HIV-1 INFECTION;
GENE-THERAPY; LENTIVIRAL VECTOR; SAN-FRANCISCO; VIRAL LOAD; REPLICATION;
RISK; STRATEGIES
AB Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk 'superspreader' populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals - analogous to 'transmissible immunization' that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multiscale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by, similar to 30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by, <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression.
C1 [Metzger, Vincent T.; Weinberger, Leor S.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Weinberger, Leor S.] Univ Calif San Diego, Div Infect Dis, Dept Med, La Jolla, CA 92093 USA.
RP Metzger, VT (reprint author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
EM jlloydsmith@ucla.edu; lsw@ucsd.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU Bill and Melinda Gates Foundation; W.M. Keck Foundation; National
Science Foundation [EF-0928690]; NIH
FX LSW acknowledges the support of the Pew Scholars Program in the
Biomedical Sciences and JOL-S acknowledges support of the De Logi Chair
in Biological Sciences and the RAPIDD program of the Science &
Technology Directorate of the US Department of Homeland Security. This
work was supported by the Bill and Melinda Gates Foundation (JOL-S &
LSW), the W.M. Keck Foundation (LSW), National Science Foundation grant
EF-0928690 (JOL-S), and the NIH Director's New Innovator Award (LSW).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 49
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U1 0
U2 5
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 MAR
PY 2011
VL 7
IS 3
AR e1002015
DI 10.1371/journal.pcbi.1002015
PG 12
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 743CU
UT WOS:000288995500034
PM 21483468
ER
PT J
AU Takeuchi, N
Hogeweg, P
Koonin, EV
AF Takeuchi, Nobuto
Hogeweg, Paulien
Koonin, Eugene V.
TI On the Origin of DNA Genomes: Evolution of the Division of Labor between
Template and Catalyst in Model Replicator Systems
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID RNA WORLD; COMPLEX-FORMATION; DEOXYRIBOZYMES; COMPETITION; CELLS; LIFE;
COMPARTMENTS; HYPERCYCLES; TRANSITION; DIVERSITY
AB The division of labor between template and catalyst is a fundamental property of all living systems: DNA stores genetic information whereas proteins function as catalysts. The RNA world hypothesis, however, posits that, at the earlier stages of evolution, RNA acted as both template and catalyst. Why would such division of labor evolve in the RNA world? We investigated the evolution of DNA-like molecules, i.e. molecules that can function only as template, in minimal computational models of RNA replicator systems. In the models, RNA can function as both template-directed polymerase and template, whereas DNA can function only as template. Two classes of models were explored. In the surface models, replicators are attached to surfaces with finite diffusion. In the compartment models, replicators are compartmentalized by vesicle-like boundaries. Both models displayed the evolution of DNA and the ensuing division of labor between templates and catalysts. In the surface model, DNA provides the advantage of greater resistance against parasitic templates. However, this advantage is at least partially offset by the disadvantage of slower multiplication due to the increased complexity of the replication cycle. In the compartment model, DNA can significantly delay the intra-compartment evolution of RNA towards catalytic deterioration. These results are explained in terms of the trade-off between template and catalyst that is inherent in RNA-only replication cycles: DNA releases RNA from this trade-off by making it unnecessary for RNA to serve as template and so rendering the system more resistant against evolving parasitism. Our analysis of these simple models suggests that the lack of catalytic activity in DNA by itself can generate a sufficient selective advantage for RNA replicator systems to produce DNA. Given the widespread notion that DNA evolved owing to its superior chemical properties as a template, this study offers a novel insight into the evolutionary origin of DNA.
C1 [Takeuchi, Nobuto; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Hogeweg, Paulien] Univ Utrecht, Theoret Biol & Bioinformat Grp, Utrecht, Netherlands.
RP Takeuchi, N (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM takeuchi@ncbi.nlm.nih.gov
RI Hogeweg, paulien/D-1242-2011
FU NIH, National Library of Medicine
FX This research was supported in part by the Intramural Research Program
of the NIH, National Library of Medicine.
NR 48
TC 26
Z9 26
U1 0
U2 9
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 MAR
PY 2011
VL 7
IS 3
AR e1002024
DI 10.1371/journal.pcbi.1002024
PG 19
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 743CU
UT WOS:000288995500043
PM 21455287
ER
PT J
AU Olsson, M
Meadows, JRS
Truve, K
Pielberg, GR
Puppo, F
Mauceli, E
Quilez, J
Tonomura, N
Zanna, G
Docampo, MJ
Bassols, A
Avery, AC
Karlsson, EK
Thomas, A
Kastner, DL
Bongcam-Rudloff, E
Webster, MT
Sanchez, A
Hedhammar, A
Remmers, EF
Andersson, L
Ferrer, L
Tintle, L
Lindblad-Toh, K
AF Olsson, Mia
Meadows, Jennifer R. S.
Truve, Katarina
Pielberg, Gerli Rosengren
Puppo, Francesca
Mauceli, Evan
Quilez, Javier
Tonomura, Noriko
Zanna, Giordana
Jose Docampo, Maria
Bassols, Anna
Avery, Anne C.
Karlsson, Elinor K.
Thomas, Anne
Kastner, Daniel L.
Bongcam-Rudloff, Erik
Webster, Matthew T.
Sanchez, Armand
Hedhammar, Ake
Remmers, Elaine F.
Andersson, Leif
Ferrer, Lluis
Tintle, Linda
Lindblad-Toh, Kerstin
TI A Novel Unstable Duplication Upstream of HAS2 Predisposes to a
Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese
Shar-Pei Dogs
SO PLOS GENETICS
LA English
DT Article
ID CUTANEOUS MUCINOSIS; CELL-PROLIFERATION; HYALURONAN; DISORDER; CD44;
PROTEOGLYCAN; INFLAMMATION; ASSOCIATION; DIPYRONE; DISEASE
AB Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (p(raw) = 2.3 x 10(-6), p(genome) = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p, < 0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation.
C1 [Olsson, Mia; Meadows, Jennifer R. S.; Pielberg, Gerli Rosengren; Webster, Matthew T.; Andersson, Leif; Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden.
[Truve, Katarina; Andersson, Leif] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, S-75007 Uppsala, Sweden.
[Puppo, Francesca; Kastner, Daniel L.; Remmers, Elaine F.] NHGRI, Bethesda, MD 20892 USA.
[Mauceli, Evan; Tonomura, Noriko; Karlsson, Elinor K.; Lindblad-Toh, Kerstin] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA.
[Quilez, Javier; Sanchez, Armand] Univ Autonoma Barcelona, Vet Mol Genet Serv, Dept Anim & Food Sci, E-08193 Barcelona, Spain.
[Zanna, Giordana; Ferrer, Lluis] Univ Autonoma Barcelona, Dept Anim Med & Surg, E-08193 Barcelona, Spain.
[Jose Docampo, Maria; Bassols, Anna] Univ Autonoma Barcelona, Dept Biochem & Mol Biol, E-08193 Barcelona, Spain.
[Avery, Anne C.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Karlsson, Elinor K.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
[Thomas, Anne] ANTAGENE Lab, Limonest, France.
[Bongcam-Rudloff, Erik] Uppsala Univ, Linnaeus Ctr Bioinformat, Uppsala, Sweden.
[Hedhammar, Ake] Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden.
[Tintle, Linda] Wurtsboro Vet Clin, Wurtsboro, NY USA.
RP Olsson, M (reprint author), Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden.
EM mia.olsson@imbim.uu.se; wvc@warwick.net; kersli@broadinstitute.org
RI Docampo, Maria Jose/A-4957-2009; Bassols, Anna/K-7961-2014; Quilez,
Javier/J-7107-2015; Sanchez, Armand/L-7905-2015;
OI Bassols, Anna/0000-0003-4213-2274; Quilez, Javier/0000-0002-0108-2672;
Sanchez, Armand/0000-0001-9160-1124; Karlsson,
Elinor/0000-0002-4343-3776; Docampo, Maria Jose/0000-0003-1242-222X;
Webster, Matthew/0000-0003-1141-2863
FU Swedish Research Council; FORMAS; Swedish Research Council for
Environment, Agricultural Sciences, and Spatial Planning; Swedish
Foundation for Strategic Research; National Institute of Arthritis and
Musculoskeletal and Skin Diseases; National Human Genome Research
Institute of the National Institutes of Health; Chinese Shar-Pei
Charitable Trust; European Commission [GA-201370]; European Science
Foundation
FX This work was supported by the Swedish Research Council; FORMAS; the
Swedish Research Council for Environment, Agricultural Sciences, and
Spatial Planning; the Swedish Foundation for Strategic Research; in part
by the Intramural Research Program of the National Institute of
Arthritis and Musculoskeletal and Skin Diseases and the National Human
Genome Research Institute of the National Institutes of Health, the
Chinese Shar-Pei Charitable Trust and the European Commission (FP7-LUPA,
GA-201370). KL-T is the recipient of a EURYI award from the European
Science Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 68
Z9 68
U1 1
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 MAR
PY 2011
VL 7
IS 3
AR e1001332
DI 10.1371/journal.pgen.1001332
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 743DD
UT WOS:000288996600014
PM 21437276
ER
PT J
AU Perelman, P
Johnson, WE
Roos, C
Seuanez, HN
Horvath, JE
Moreira, MAM
Kessing, B
Pontius, J
Roelke, M
Rumpler, Y
Schneider, MPC
Silva, A
O'Brien, SJ
Pecon-Slattery, J
AF Perelman, Polina
Johnson, Warren E.
Roos, Christian
Seuanez, Hector N.
Horvath, Julie E.
Moreira, Miguel A. M.
Kessing, Bailey
Pontius, Joan
Roelke, Melody
Rumpler, Yves
Schneider, Maria Paula C.
Silva, Artur
O'Brien, Stephen J.
Pecon-Slattery, Jill
TI A Molecular Phylogeny of Living Primates
SO PLOS GENETICS
LA English
DT Article
ID NEW-WORLD MONKEYS; EVOLUTIONARY HISTORY; DNA-SEQUENCES; LEAF MONKEYS;
BRANISELLA-BOLIVIANA; PLACENTAL MAMMALS; DIVERGENCE TIMES; FOSSIL
EVIDENCE; PLATYRRHINE; BIOGEOGRAPHY
AB Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (similar to 8 Mb) from 186 primates representing 61 (similar to 90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.
C1 [Kessing, Bailey; Pontius, Joan; Roelke, Melody] Natl Canc Inst, Lab Genom Divers, SAIC Frederick, Frederick, MD USA.
[Roos, Christian] German Primate Ctr, Gene Bank Primates, Gottingen, Germany.
[Roos, Christian] German Primate Ctr, Primate Genet Lab, Gottingen, Germany.
[Seuanez, Hector N.; Moreira, Miguel A. M.] Univ Fed Rio de Janeiro, Div Genet, Inst Nacl Canc, Rio De Janeiro, Brazil.
[Seuanez, Hector N.; Moreira, Miguel A. M.] Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil.
[Horvath, Julie E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC USA.
[Horvath, Julie E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA.
[Rumpler, Yves] Univ Strasbourg, Fac Med, Strasbourg, France.
[Schneider, Maria Paula C.; Silva, Artur] Fed Univ Para, BR-66059 Belem, Para, Brazil.
RP Perelman, P (reprint author), Inst Chem Biol & Fundamental Med, Lab Cytogenet Animals, Novosibirsk, Russia.
EM slatterJ@mail.nih.gov
RI Inca, Inct/K-2204-2013; Silva, Artur/E-1474-2014; Perelman,
Polina/N-8088-2015; Johnson, Warren/D-4149-2016
OI Perelman, Polina/0000-0002-0982-5100; Johnson,
Warren/0000-0002-5954-186X
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
NIH, NCI, Center for Cancer Research; Duke Primate Genomics Initiative;
Institute for Genome Sciences and Policy at Duke University; CNPq
[303583/2007-0, 304403/2008-3]
FX This project has supported with federal funds from the National Cancer
Institute, National Institutes of Health, under contract N01-CO-12400.
This research has been supported (in part) by the Intramural Research
Program of the NIH, NCI, Center for Cancer Research, the Duke Primate
Genomics Initiative, and Institute for Genome Sciences and Policy at
Duke University. In Brazil, support included CNPq grant 303583/2007-0
(HNS) and CNPq grant 304403/2008-3 (MAMM). The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does its mention of trade
names, commercial products, or organizations imply endorsement by the U.
S. Government. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of manuscript.
NR 85
TC 389
Z9 395
U1 13
U2 137
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2011
VL 7
IS 3
AR e1001342
DI 10.1371/journal.pgen.1001342
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 743DD
UT WOS:000288996600024
PM 21436896
ER
PT J
AU Speliotes, EK
Yerges-Armstrong, LM
Wu, J
Hernaez, R
Kim, LJ
Palmer, CD
Gudnason, V
Eiriksdottir, G
Garcia, ME
Launer, LJ
Nalls, MA
Clark, JM
Mitchell, BD
Shuldiner, AR
Butler, JL
Tomas, M
Hoffmann, U
Hwang, SJ
Massaro, JM
O'Donnell, CJ
Sahani, DV
Salomaa, V
Schadt, EE
Schwartz, SM
Siscovick, DS
Voight, BF
Carr, JJ
Feitosa, MF
Harris, TB
Fox, CS
Smith, AV
Kao, WHL
Hirschhorn, JN
Borecki, IB
AF Speliotes, Elizabeth K.
Yerges-Armstrong, Laura M.
Wu, Jun
Hernaez, Ruben
Kim, Lauren J.
Palmer, Cameron D.
Gudnason, Vilmundur
Eiriksdottir, Gudny
Garcia, Melissa E.
Launer, Lenore J.
Nalls, Michael A.
Clark, Jeanne M.
Mitchell, Braxton D.
Shuldiner, Alan R.
Butler, Johannah L.
Tomas, Marta
Hoffmann, Udo
Hwang, Shih-Jen
Massaro, Joseph M.
O'Donnell, Christopher J.
Sahani, Dushyant V.
Salomaa, Veikko
Schadt, Eric E.
Schwartz, Stephen M.
Siscovick, David S.
Voight, Benjamin F.
Carr, J. Jeffrey
Feitosa, Mary F.
Harris, Tamara B.
Fox, Caroline S.
Smith, Albert V.
Kao, W. H. Linda
Hirschhorn, Joel N.
Borecki, Ingrid B.
CA NASH CRN
GIANT Consortium
MAGIC Investigators
GOLD Consortium
TI Genome-Wide Association Analysis Identifies Variants Associated with
Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic
Traits
SO PLOS GENETICS
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; TRIGLYCERIDE LEVELS; LOCI; HEART; RISK; DESIGN;
ADULTS; STEATOHEPATITIS; PNPLA3; SUSCEPTIBILITY
AB Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (similar to 26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and similar to 2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<56 10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.
C1 [Speliotes, Elizabeth K.; Butler, Johannah L.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.; Butler, Johannah L.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Speliotes, Elizabeth K.; Voight, Benjamin F.; Hirschhorn, Joel N.] Broad Inst, Cambridge, MA USA.
[Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD USA.
[Wu, Jun; Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[Hernaez, Ruben; Clark, Jeanne M.; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hernaez, Ruben; Clark, Jeanne M.] Johns Hopkins Univ Hosp, Div Gen Internal Med, Baltimore, MD 21287 USA.
[Hernaez, Ruben] Washington Hosp Ctr, Dept Internal Med, Washington, DC USA.
[Kim, Lauren J.; Garcia, Melissa E.; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Palmer, Cameron D.; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Palmer, Cameron D.; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Palmer, Cameron D.; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Gudnason, Vilmundur; Eiriksdottir, Gudny; Smith, Albert V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Nalls, Michael A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Clark, Jeanne M.; Kao, W. H. Linda] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, GRECC, Baltimore, MD 21218 USA.
[Tomas, Marta] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
[Tomas, Marta] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hoffmann, Udo; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hwang, Shih-Jen; Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Massaro, Joseph M.] Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Salomaa, Veikko] Natl Publ Hlth Inst, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
[Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA USA.
[Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Carr, J. Jeffrey] Wake Forest Univ Sch Med, Dept Radiol Sci, Winston Salem, NC USA.
[Carr, J. Jeffrey] Wake Forest Univ Sch Med, Dept Internal Med Cardiol, Winston Salem, NC USA.
[Carr, J. Jeffrey] Wake Forest Univ Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Speliotes, EK (reprint author), Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
EM espeliot@med.umich.edu; iborecki@wustl.edu
RI Feitosa, Mary/K-8044-2012; Ripatti, Samuli/H-9446-2014; Polasek,
Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Prokopenko,
Inga/H-3241-2014; Macciardi, Fabio/N-3768-2014; Aben, Katja/G-9686-2016;
Carr, John/A-1938-2012; Smith, Albert/K-5150-2015; kinnunen,
leena/B-7059-2012; Bochud, Murielle/A-3981-2010; Visvikis-Siest,
Sophie/H-2324-2014; Schwarz, Peter/B-5127-2013; Naitza,
Silvia/D-5620-2017; Singleton, Andrew/C-3010-2009; Voight,
Benjamin/F-1775-2011; Palmer, Lyle/K-3196-2014; Witte,
Daniel/C-1722-2008; Brunner, Eric/H-2114-2011; Ridderstrale,
Martin/F-7678-2012; Gudnason, Vilmundur/K-6885-2015; Elliott,
Amanda/G-5120-2012; Rudan, Igor/I-1467-2012; Colaus,
PsyColaus/K-6607-2013; Hernaez, Ruben/C-4039-2014; Kiemeney,
Lambertus/D-3357-2009
OI Marmot, Michael/0000-0002-2431-6419; Mitchell,
Braxton/0000-0003-4920-4744; Ouwehand, Willem/0000-0002-7744-1790;
Lawlor, Debbie A/0000-0002-6793-2262; Johansson,
Asa/0000-0002-2915-4498; de Geus, Eco/0000-0001-6022-2666; Zgaga,
Lina/0000-0003-4089-9703; Zeggini, Eleftheria/0000-0003-4238-659X;
Luben, Robert/0000-0002-5088-6343; Scherag, Andre/0000-0002-9406-4704;
Melzer, David/0000-0002-0170-3838; Forouhi, Nita/0000-0002-5041-248X;
John, Ulrich/0000-0003-0587-5298; Jorgensen, Torben/0000-0001-9453-2830;
Watkins, Hugh/0000-0002-5287-9016; Visscher, Peter/0000-0002-2143-8760;
Feitosa, Mary/0000-0002-0933-2410; Seedorf, Udo/0000-0003-4652-5358;
Massaro, Joseph/0000-0002-2682-4812; Thiering,
Elisabeth/0000-0002-5429-9584; Lango Allen, Hana/0000-0002-7803-8688;
Willems van Dijk, Ko/0000-0002-2172-7394; Esko,
Tonu/0000-0003-1982-6569; Pichler, Irene/0000-0001-8251-0757; Magi,
Reedik/0000-0002-2964-6011; Kivimaki, Mika/0000-0002-4699-5627; Ripatti,
Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862;
Prokopenko, Inga/0000-0003-1624-7457; Macciardi,
Fabio/0000-0003-0537-4266; Aben, Katja/0000-0002-0214-2147; Carr,
John/0000-0002-4398-8237; Smith, Albert/0000-0003-1942-5845; kinnunen,
leena/0000-0001-8739-4812; Bochud, Murielle/0000-0002-5727-0218;
Visvikis-Siest, Sophie/0000-0001-8104-8425; Schwarz,
Peter/0000-0001-6317-7880; Palmer, Lyle/0000-0002-1628-3055; Witte,
Daniel/0000-0002-0769-2922; Gudnason, Vilmundur/0000-0001-5696-0084;
Rudan, Igor/0000-0001-6993-6884; Hernaez, Ruben/0000-0002-1518-4020;
Kiemeney, Lambertus/0000-0002-2368-1326
FU NIH [T32 DK07191-32, F32 DK079466-01, NIH K23DK080145-01, R01DK075787,
N01-AG-12100, K01 DK067207, R01 AG18728, R01HL088119, U01 HL72515, U01
HL084756, T32AG000262, F32AR059469]; Icelandic Heart Association;
Althingi (the Icelandic Parliament); Diabetes Research and Training
Center of Maryland [P60 DK079637]; Nutrition and Obesity Research Center
of Maryland [P30DK072488]; American Diabetes Association [7-07-MN-08];
NIDDK [R01DK075681]; NHLBI [R01HL087700]; National Heart, Lung, and
Blood Institute [N01-HC-25195]; Affymetrix for genotyping services
[N02-HL-6-4278]; National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) [U01DK061718, U01DK061728, U01DK061731, U01DK061732,
U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713];
General Clinical Research Centers or Clinical and Translational Science
[UL1RR024989, M01RR000750, M01RR00188, ULRR02413101, M01RR000827,
UL1RR02501401, M01RR000065, M01RR020359]; US National Institutes of
Health (NIH); National Heart, Lung, and Blood Institute; Generalitat de
Catalunya [2007BP-B100068]; Red HERACLES, ISCIII [RD06/0009]
FX This work was partially supported by NIH grants T32 DK07191-32 to Daniel
Podolsky (for EKS), F32 DK079466-01 to EKS, NIH K23DK080145-01 to EKS,
and R01DK075787 to JNH. The AGES-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). The Old Order Amish Study was supported by NIH research
grants K01 DK067207, R01 AG18728, R01HL088119, U01 HL72515, and U01
HL084756. Partial funding was also provided by the Diabetes Research and
Training Center of Maryland (P60 DK079637) and the Nutrition and Obesity
Research Center of Maryland (P30DK072488). LMY-A was supported by NIH
training grants T32AG000262 and F32AR059469. RH was supported by the
American Diabetes Association Mentor-Based Postdoctoral Fellowship
Program (7-07-MN-08). The NHLBI Family Heart Study was supported by
NIDDK R01DK075681 (to IBB) and NHLBI R01HL087700. 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. This work was partially supported
by the National Heart, Lung, and Blood Institute's Framingham Heart
Study (Contract No. N01-HC-25195) and its contract with Affymetrix for
genotyping services (Contract No. N02-HL-6-4278). The Nonalcoholic
Steatohepatitis Clinical Research Network (NASH CRN) is supported by the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734,
U01DK061737, U01DK061738, U01DK061730, U01DK061713). Several clinical
centers use support from General Clinical Research Centers or Clinical
and Translational Science Awards in conduct of NASH CRN Studies (grants
UL1RR024989, M01RR000750, M01RR00188, ULRR02413101, M01RR000827,
UL1RR02501401, M01RR000065, M01RR020359). The MIGen study was funded by
the US National Institutes of Health (NIH) and National Heart, Lung, and
Blood Institute's STAMPEED genomics research program. MT was supported
by the Beatriu de Pinos postdoctoral fellowship, Generalitat de
Catalunya (2007BP-B100068, MT), and Red HERACLES, ISCIII (RD06/0009).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 50
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U1 2
U2 49
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 MAR
PY 2011
VL 7
IS 3
AR e1001324
DI 10.1371/journal.pgen.1001324
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 743DD
UT WOS:000288996600006
PM 21423719
ER
PT J
AU Costa, CHN
Peters, NC
Maruyama, SR
de Brito, EC
Santos, IKFD
AF Nery Costa, Carlos Henrique
Peters, Nathan C.
Maruyama, Sandra Regina
de Brito, Eldo Cardoso, Jr.
Ferreira de Miranda Santos, Isabel Kinney
CA Working Grp Res Priorities Dev Lei
TI Vaccines for the Leishmaniases: Proposals for a Research Agenda
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CUTANEOUS LEISHMANIASIS; SAND FLIES; VISCERAL LEISHMANIASIS; VACCINATION
STRATEGIES; BORNE DISEASES; LIVE VACCINE; C57BL/6 MICE; RESISTANCE;
INFECTION; PARASITES
C1 [Nery Costa, Carlos Henrique; de Brito, Eldo Cardoso, Jr.] Univ Fed Piaui, Natan Portella Inst Trop Dis, Teresina, Brazil.
[Maruyama, Sandra Regina; Ferreira de Miranda Santos, Isabel Kinney] Univ Sao Paulo, Ribeirao Preto Sch Med, Lab Immunoparasitol, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, Brazil.
[Peters, Nathan C.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ferreira de Miranda Santos, Isabel Kinney] Brazilian Enterprise Agr Res, Natl Ctr Genet Resources & Biotechnol, Brasilia, DF, Brazil.
RP Costa, CHN (reprint author), Univ Fed Piaui, Natan Portella Inst Trop Dis, Teresina, Brazil.
EM imsantos@fmrp.usp.br
RI Maruyama, Sandra/G-1171-2012; de Miranda Santos, Isabel/B-7597-2012;
Goto, Hiro/B-5745-2009; de Miranda Santos, Isabel/D-5261-2016; Fujiwara,
Ricardo/J-7579-2012;
OI de Miranda Santos, Isabel/0000-0002-0438-4430; Goto,
Hiro/0000-0001-7048-562X; Fujiwara, Ricardo/0000-0002-4713-575X;
Santos-Gomes, Gabriela /0000-0001-9264-3887; Maruyama,
Sandra/0000-0001-6807-1452
NR 41
TC 39
Z9 39
U1 3
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAR
PY 2011
VL 5
IS 3
AR e943
DI 10.1371/journal.pntd.0000943
PG 9
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 742KI
UT WOS:000288940800003
ER
PT J
AU Colantonio, AD
Bimber, BN
Neidermyer, WJ
Reeves, RK
Alter, G
Altfeld, M
Johnson, RP
Carrington, M
O'Connor, DH
Evans, DT
AF Colantonio, Arnaud D.
Bimber, Benjamin N.
Neidermyer, William J., Jr.
Reeves, R. Keith
Alter, Galit
Altfeld, Marcus
Johnson, R. Paul
Carrington, Mary
O'Connor, David H.
Evans, David T.
TI KIR Polymorphisms Modulate Peptide-Dependent Binding to an MHC Class I
Ligand with a Bw6 Motif
SO PLOS PATHOGENS
LA English
DT Article
ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; SIMIAN
IMMUNODEFICIENCY VIRUS; SELECTIVE DOWN-REGULATION; HLA-B; INHIBITORY
RECEPTORS; RHESUS MACAQUES; CRYSTAL-STRUCTURE; CUTTING EDGE; HEPATITIS-C
AB Molecular interactions between killer immunoglobulin-like receptors (KIRs) and their MHC class I ligands play a central role in the regulation of natural killer (NK) cell responses to viral pathogens and tumors. Here we identify Mamu-A1*00201 (Mamu-A*02), a common MHC class I molecule in the rhesus macaque with a canonical Bw6 motif, as a ligand for Mamu-KIR3DL05. Mamu-A1*00201 tetramers folded with certain SIV peptides, but not others, directly stained primary NK cells and Jurkat cells expressing multiple allotypes of Mamu-KIR3DL05. Differences in binding avidity were associated with polymorphisms in the D0 and D1 domains of Mamu-KIR3DL05, whereas differences in peptide-selectivity mapped to the D1 domain. The reciprocal exchange of the third predicted MHC class I-contact loop of the D1 domain switched the specificity of two Mamu-KIR3DL05 allotypes for different Mamu-A1*00201-peptide complexes. Consistent with the function of an inhibitory KIR, incubation of lymphocytes from Mamu-KIR3DL05(+) macaques with target cells expressing Mamu-A1*00201 suppressed the degranulation of tetramer-positive NK cells. These observations reveal a previously unappreciated role for D1 polymorphisms in determining the selectivity of KIRs for MHC class I-bound peptides, and identify the first functional KIR-MHC class I interaction in the rhesus macaque. The modulation of KIR-MHC class I interactions by viral peptides has important implications to pathogenesis, since it suggests that the immunodeficiency viruses, and potentially other types of viruses and tumors, may acquire changes in epitopes that increase the affinity of certain MHC class I ligands for inhibitory KIRs to prevent the activation of specific NK cell subsets.
C1 [Colantonio, Arnaud D.; Neidermyer, William J., Jr.; Evans, David T.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA.
[Bimber, Benjamin N.; O'Connor, David H.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Dept Pathol & Lab Med, Madison, WI USA.
[Reeves, R. Keith; Johnson, R. Paul] New England Primate Res Ctr, Div Immunol, Southborough, MA USA.
[Alter, Galit; Altfeld, Marcus; Johnson, R. Paul; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Alter, Galit; Altfeld, Marcus; Johnson, R. Paul; Carrington, Mary] Harvard Univ, Boston, MA 02115 USA.
[Carrington, Mary] NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
RP Colantonio, AD (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA.
EM devans@hms.harvard.edu
OI o'connor, david/0000-0003-2139-470X
FU Public Health Service [AI063993, AI071306, RR000168]; Elizabeth Glaser
Pediatric AIDS Foundation; NIH [HHSN261200800001E]
FX This work was supported by Public Health Service grants AI063993,
AI071306 and RR000168. DTE is an Elizabeth Glaser Scientist supported by
the Elizabeth Glaser Pediatric AIDS Foundation. This project was also
supported in part by intramural NIH funding to the NCI under contract
number HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the DHHS, nor does mention
of trade names, commercial products, or organizations imply endorsement
by the U.S. Government. The funders had no role in the study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 64
TC 24
Z9 25
U1 1
U2 5
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 MAR
PY 2011
VL 7
IS 3
AR e1001316
DI 10.1371/journal.ppat.1001316
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 743CQ
UT WOS:000288994900010
PM 21423672
ER
PT J
AU Meerbrey, KL
Hu, GA
Kessler, JD
Roarty, K
Li, MZ
Fang, JE
Herschkowitz, JI
Burrows, AE
Ciccia, A
Sun, TT
Schmitt, EM
Bernardi, RJ
Fu, XY
Bland, CS
Cooper, TA
Schiff, R
Rosen, JM
Westbrook, TF
Elledge, SJ
AF Meerbrey, Kristen L.
Hu, Guang
Kessler, Jessica D.
Roarty, Kevin
Li, Mamie Z.
Fang, Justin E.
Herschkowitz, Jason I.
Burrows, Anna E.
Ciccia, Alberto
Sun, Tingting
Schmitt, Earlene M.
Bernardi, Ronald J.
Fu, Xiaoyong
Bland, Christopher S.
Cooper, Thomas A.
Schiff, Rachel
Rosen, Jeffrey M.
Westbrook, Thomas F.
Elledge, Stephen J.
TI The pINDUCER lentiviral toolkit for inducible RNA interference in vitro
and in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE lentivirus; vector
ID MAMMALIAN-CELLS; CANCER-CELLS; SCREEN; TRANSFORMATION; EXPRESSION;
TRANSGENE; GENOME; MOUSE; GENE
AB The discovery of RNAi has revolutionized loss-of-function genetic studies in mammalian systems. However, significant challenges still remain to fully exploit RNAi for mammalian genetics. For instance, genetic screens and in vivo studies could be broadly improved by methods that allow inducible and uniform gene expression control. To achieve this, we built the lentiviral pINDUCER series of expression vehicles for inducible RNAi in vivo. Using a multicistronic design, pINDUCER vehicles enable tracking of viral transduction and shRNA or cDNA induction in a broad spectrum of mammalian cell types in vivo. They achieve this uniform temporal, dose-dependent, and reversible control of gene expression across heterogenous cell populations via fluorescence-based quantification of reverse tet-transactivator expression. This feature allows isolation of cell populations that exhibit a potent, inducible target knockdown in vitro and in vivo that can be used in human xenotransplantation models to examine cancer drug targets.
C1 [Hu, Guang] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Meerbrey, Kristen L.; Kessler, Jessica D.; Fang, Justin E.; Sun, Tingting; Schmitt, Earlene M.; Westbrook, Thomas F.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Meerbrey, Kristen L.; Kessler, Jessica D.; Fang, Justin E.; Schmitt, Earlene M.; Westbrook, Thomas F.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Bernardi, Ronald J.; Westbrook, Thomas F.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Fu, Xiaoyong; Schiff, Rachel] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Bland, Christopher S.; Cooper, Thomas A.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[Roarty, Kevin; Herschkowitz, Jason I.; Fu, Xiaoyong; Schiff, Rachel; Rosen, Jeffrey M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Fu, Xiaoyong; Schiff, Rachel] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Li, Mamie Z.; Burrows, Anna E.; Ciccia, Alberto; Elledge, Stephen J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Li, Mamie Z.; Burrows, Anna E.; Ciccia, Alberto; Elledge, Stephen J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Hu, GA (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
EM hug4@niehs.nih.gov; thomasw@bcm.edu; selledge@genetics.med.harvard.edu
RI Hu, Guang/E-7474-2016
OI Hu, Guang/0000-0003-0437-4723
FU Susan G. Komen for the Cure Career Catalyst Award [KG090355];
Specialized Program of Research Excellence Developmental Grant [P50
CA058183]; Department of Defense [BC094077]; National Institutes of
Health (NIH) [R01GM076493, R37 CA16303]; National Institute of
Environmental Health Sciences [Z01ES102745]; US Army [W81XWH0410197]
FX T. F. W. is a scholar of The V Foundation and Mary Kay Ash Foundation
for Cancer Research. This work was supported by Susan G. Komen for the
Cure Career Catalyst Award KG090355 (to T. F. W.) and Specialized
Program of Research Excellence Developmental Grant P50 CA058183 (to T.
F. W. and R. S.), Department of Defense Breast Cancer Research Program
Predoctoral Fellowship BC094077 (to K. L. M.), National Institutes of
Health (NIH) Grant R01GM076493 (to T. A. C.), NIH Grant R37 CA16303 (to
J.M.R.), NIH and National Institute of Environmental Health Sciences
Intramural Research Program Z01ES102745 (to G. H.), and US Army
Innovator Award W81XWH0410197 (to S.J.E.). S.J.E. is an Investigator
with the Howard Hughes Medical Institute.
NR 21
TC 160
Z9 160
U1 1
U2 18
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 1
PY 2011
VL 108
IS 9
BP 3665
EP 3670
DI 10.1073/pnas.1019736108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 728AD
UT WOS:000287844400044
PM 21307310
ER
PT J
AU Punkosdy, GA
Blain, M
Glass, DD
Lozano, MM
O'Mara, L
Dudley, JP
Ahmed, R
Shevach, EM
AF Punkosdy, George A.
Blain, Melissa
Glass, Deborah D.
Lozano, Mary M.
O'Mara, Leigh
Dudley, Jaquelin P.
Ahmed, Rafi
Shevach, Ethan M.
TI Regulatory T-cell expansion during chronic viral infection is dependent
on endogenous retroviral superantigens
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID TUMOR VIRUS SUPERANTIGENS; IMMUNE-RESPONSES; CLONAL DELETION; MICE
LACKING; EXPRESSION; FOXP3; CD4; REPERTOIRES; ENTEROPATHY; MOLECULES
AB Regulatory T cells (Treg) play critical roles in the modulation of immune responses to infectious agents. Further understanding of the factors that control Treg activation and expansion in response to pathogens is needed to manipulate Treg function in acute and chronic infections. Here we show that chronic, but not acute, infection of mice with lymphocytic choriomeningitis virus results in a marked expansion of Foxp3(+) Treg that is dependent on retroviral superantigen (sag) genes encoded in the mouse genome. Sag-dependent Treg expansion was MHC class II dependent, CD4 independent, and required dendritic cells. Thus, one unique mechanism by which certain infectious agents evade host immune responses may be mediated by endogenous Sag-dependent activation and expansion of Treg.
C1 [O'Mara, Leigh; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[O'Mara, Leigh; Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Punkosdy, George A.; Blain, Melissa; Glass, Deborah D.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Lozano, Mary M.; Dudley, Jaquelin P.] Univ Texas Austin, Sect Mol Genet & Microbiol, Austin, TX 78712 USA.
[Lozano, Mary M.; Dudley, Jaquelin P.] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM rahmed@emory.edu; eshevach@niaid.nih.gov
FU National Institutes of Health (NIH), NIAID; Bill and Melinda Gates
Foundation; NIH [R01-CA116813]
FX We thank Y. Belkaid [National Institute of Allergy and Infectious
Diseases (NIAID)] for critical reading of the manuscript. This work was
supported by the Intramural Research Program of the National Institutes
of Health (NIH), NIAID, the Bill and Melinda Gates Foundation, and NIH
Grant R01-CA116813.
NR 40
TC 49
Z9 51
U1 1
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 1
PY 2011
VL 108
IS 9
BP 3677
EP 3682
DI 10.1073/pnas.1100213108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 728AD
UT WOS:000287844400046
PM 21321220
ER
PT J
AU Kryndushkin, D
Wickner, RB
Shewmaker, F
AF Kryndushkin, Dmitry
Wickner, Reed B.
Shewmaker, Frank
TI FUS/TLS forms cytoplasmic aggregates, inhibits cell growth and interacts
with TDP-43 in a yeast model of amyotrophic lateral sclerosis
SO PROTEIN & CELL
LA English
DT Article
DE amyotrophic lateral sclerosis (ALS); fused in sarcoma (FUS); TLS;
proteinopathy; yeast
ID RNA-BINDING PROTEIN; STRESS GRANULES; SACCHAROMYCES-CEREVISIAE; SUP35
PROTEIN; P-BODIES; PRION; FUS; MUTATIONS; TOXICITY; HUNTINGTIN
AB Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the premature loss of motor neurons. While the underlying cellular mechanisms of neuron degeneration are unknown, the cytoplasmic aggregation of several proteins is associated with sporadic and familial forms of the disease. Both wild-type and mutant forms of the RNA-binding proteins FUS and TDP-43 accumulate in cytoplasmic inclusions in the neurons of ALS patients. It is not known if these so-called proteinopathies are due to a loss of function or a gain of toxicity resulting from the formation of cytoplasmic aggregates. Here we present a model of FUS toxicity using the yeast Saccharomyces cerevisiae in which toxicity is associated with greater expression and accumulation of FUS in cytoplasmic aggregates. We find that FUS and TDP-43 have a high propensity for co-aggregation, unlike the aggregation patterns of several other aggregation-prone proteins. Moreover, the biophysical properties of FUS aggregates in yeast are distinctly different from many amyloidogenic proteins, suggesting they are not composed of amyloid.
C1 [Kryndushkin, Dmitry; Shewmaker, Frank] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
[Kryndushkin, Dmitry; Wickner, Reed B.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Shewmaker, F (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM frank.shewmaker@gmail.com
FU Uniformed Services University of the Health Sciences; Intramural
Research Program of the National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases
FX We thank Herman Edskes (NIH) for providing plasmids and for his
thoughtful suggestions, Tetsade Piermartiri for her assistance with
western blotting, Susan Liebman (University of Illinois Chicago) for
providing yeast strains, Kevin O'Connell (NIH) for expert assistance
with confocal microscopy, Judith Frydman (Stanford University) and
Michael Sherman (Boston University) for plasmids. This research was
supported by Uniformed Services University of the Health Sciences and
the Intramural Research Program of the National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 54
TC 30
Z9 30
U1 0
U2 4
PU HIGHER EDUCATION PRESS
PI BEIJING
PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA
SN 1674-800X
J9 PROTEIN CELL
JI Protein Cell
PD MAR
PY 2011
VL 2
IS 3
BP 223
EP 236
DI 10.1007/s13238-011-1525-0
PG 14
WC Cell Biology
SC Cell Biology
GA 029TV
UT WOS:000310519700007
PM 21452073
ER
PT J
AU Park, JH
Dias, CAO
Lee, SB
Valentini, SR
Sokabe, M
Fraser, CS
Park, MH
AF Park, Jong Hwan
Dias, Camila A. O.
Lee, Seung Bum
Valentini, Sandro R.
Sokabe, Masaaki
Fraser, Christopher S.
Park, Myung Hee
TI Production of active recombinant eIF5A: reconstitution in E.coli of
eukaryotic hypusine modification of eIF5A by its coexpression with
modifying enzymes
SO PROTEIN ENGINEERING DESIGN & SELECTION
LA English
DT Article
DE eIF5A; hypusine; polyamine; polycistronic vector; post-translational
modification
ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; 40S
RIBOSOMAL-SUBUNIT; ELONGATION-FACTOR-P; TRANSLATION INITIATION;
DEOXYHYPUSINE SYNTHASE; ESCHERICHIA-COLI; AMINO-ACID; PROTEIN-SYNTHESIS;
CELL VIABILITY
AB Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the polyamine-modified lysine, hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. Hypusine occurs only in eukaryotes and certain archaea, but not in eubacteria. It is formed post-translationally by two consecutive enzymatic reactions catalyzed by deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). Hypusine modification is essential for the activity of eIF5A and for eukaryotic cell proliferation. eIF5A binds to the ribosome and stimulates translation in a hypusine-dependent manner, but its mode of action in translation is not well understood. Since quantities of highly pure hypusine-modified eIF5A is desired for structural studies as well as for determination of its binding sites on the ribosome, we have used a polycistronic vector, pST39, to express eIF5A alone, or to co-express human eIF5A-1 with DHS or with both DHS and DOHH in Escherichia coli cells, to engineer recombinant proteins, unmodified eIF5A, deoxyhypusine- or hypusine-modified eIF5A. We have accomplished production of three different forms of recombinant eIF5A in high quantity and purity. The recombinant hypusine-modified eIF5A was as active in methionyl-puromycin synthesis as the native, eIF5A (hypusine form) purified from mammalian tissue. The recombinant eIF5A proteins will be useful tools in future structure/function and the mechanism studies in translation.
C1 [Park, Jong Hwan; Lee, Seung Bum; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Dias, Camila A. O.; Valentini, Sandro R.] Univ Estadual Paulista UNESP, Dept Biol Sci, Sch Pharmaceut Sci, Araraquara, SP, Brazil.
[Sokabe, Masaaki] Univ Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USA.
[Fraser, Christopher S.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
RP Park, MH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM mhpark@nih.gov
RI Valentini, Sandro/C-4353-2012; Dias, Camila/G-3494-2012; Fraser,
Christopher/H-9186-2013; Inov Farmaceutica, Inct/K-2313-2013
FU National Institute of Dental and Craniofacial Research (NIDCR); NIH [R01
GM092927]; Human Frontier Science Program fellowship [LT00575/2007-L]
FX The research was supported in part by the Intramural Research Program of
National Institute of Dental and Craniofacial Research (NIDCR), NIH, NIH
extramural Grant R01 GM092927 ( to C.S.F.) and by the Human Frontier
Science Program fellowship LT00575/2007-L ( to M.S.).
NR 47
TC 10
Z9 10
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1741-0126
J9 PROTEIN ENG DES SEL
JI Protein Eng. Des. Sel.
PD MAR
PY 2011
VL 24
IS 3
BP 301
EP 309
DI 10.1093/protein/gzq110
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 723DM
UT WOS:000287486500008
PM 21131325
ER
PT J
AU Fitzkee, NC
Torchia, DA
Bax, A
AF Fitzkee, Nicholas C.
Torchia, Dennis A.
Bax, Ad
TI Measuring rapid hydrogen exchange in the homodimeric 36 kDa HIV-1
integrase catalytic core domain
SO PROTEIN SCIENCE
LA English
DT Article
DE NMR; protein stability; dynamics; HX; retroviral integration; active
site dynamics
ID INTRINSICALLY UNSTRUCTURED PROTEINS; PROTON-EXCHANGE; ACTIVE-SITE;
MASS-SPECTROMETRY; NMR-SPECTROSCOPY; IMPROVED SENSITIVITY;
AQUEOUS-SOLUTIONS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; VIRUS INTEGRASE
AB Measurements of rapid hydrogen exchange (HX) of water with protein amide sites contain valuable information on protein structure and function, but current NMR methods for measuring HX rates are limited in their applicability to large protein systems. An alternate method for measuring rapid HX is presented that is well-suited for larger proteins, and we apply the method to the deuterated, homodimeric 36 kDa HIV-1 integrase catalytic core domain (CCD). Using long mixing times for water-amide magnetization exchange at multiple pH values, HX rates spanning more than four orders of magnitude were measured, as well as NOE cross-relaxation rates to nearby exchangeable protons. HX protection factors for the CCD are found to be large (> 10(4)) for residues along the dimer interface, but much smaller in many other regions. Notably, the catalytic helix (residues 152-167) exhibits low HX protection at both ends, indicative of fraying at both termini as opposed to just the N-terminal end, as originally thought. Residues in the LEDGF/p75 binding pocket also show marginal stability, with protection factors in the 10-100 range (similar to 1.4-2.7 kcal/mol). Additionally, elevated NOE cross-relaxation rates are identified and, as expected, correspond to proximity of the amide proton to a rapidly exchanging proton, typically from an OH side chain. Indirect NOE transfer between H(2)O and the amide proton of I141, a residue in the partially disordered active site of the enzyme, suggests its proximity to the side chain of S147, an interaction seen in the DNA-bound form for a homologous integrase.
C1 [Fitzkee, Nicholas C.; Torchia, Dennis A.; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA.
EM bax@nih.gov
FU NIDDK, NIH; Office of the Director, NIH; Intramural AIDS Research
Postdoctoral Fellowship
FX The authors are indebted to Nick Fawzi and Justin Lorieau for helpful
discussions. This work was supported by the Intramural Research Program
of the NIDDK, NIH, and by the Intramural AIDS-Targeted Antiviral Program
of the Office of the Director, NIH. NCF is the recipient of an
Intramural AIDS Research Postdoctoral Fellowship.
NR 65
TC 20
Z9 20
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD MAR
PY 2011
VL 20
IS 3
BP 500
EP 512
DI 10.1002/pro.582
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 731VG
UT WOS:000288136900004
PM 21213249
ER
PT J
AU Tai, CH
Sam, V
Gibrat, JF
Garnier, J
Munson, PJ
Lee, B
AF Tai, Chin-Hsien
Sam, Vichetra
Gibrat, Jean-Francois
Garnier, Jean
Munson, Peter J.
Lee, Byungkook
TI Protein domain assignment from the recurrence of locally similar
structures
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE domain parsing; structure comparisons; clustering; LSSP; secondary
structures; symmetric matrix factorization; singular value
decomposition; pairwise correlation method
ID FOLD SPACE; CLASSIFICATION; IDENTIFICATION; EVOLUTION; DATABASE; PARSER;
CASP6
AB Domains are basic units of protein structure and essential for exploring protein fold space and structure evolution. With the structural genomics initiative, the number of protein structures in the Protein Databank (PDB) is increasing dramatically and domain assignments need to be done automatically. Most existing structural domain assignment programs define domains using the compactness of the domains and/or the number and strength of intra-domain versus inter-domain contacts. Here we present a different approach based on the recurrence of locally similar structural pieces (LSSPs) found by one-against-all structure comparisons with a dataset of 6373 protein chains from the PDB. Residues of the query protein are clustered using LSSPs via three different procedures to define domains. This approach gives results that arc comparable to several existing programs that use geometrical and other structural information explicitly. Remarkably, most of the proteins that contribute the LSSPs defining a domain do not themselves contain the domain of interest. This study shows that domains can be defined by a collection of relatively small locally similar structural pieces containing, on average, tor secondary structure elements. In addition it indicates that domains are indeed made of recurrent small structural pieces that are used to build protein structures of many different folds as suggested by recent studies.
C1 [Tai, Chin-Hsien; Lee, Byungkook] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Sam, Vichetra; Garnier, Jean; Munson, Peter J.] Ctr Informat Technol, Math & Stat Comp Lab, NIH, Bethesda, MD 20892 USA.
[Gibrat, Jean-Francois; Garnier, Jean] INRA, Unite Math Informat & Genome UR1077, Jouy En Josas, France.
RP Lee, B (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM BKLee@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; NIH, Center
for Information Technology; National Institute for Agricultural Research
(INRA), France, Mathematique, Informatique et Genome laboratory
FX Grant sponsor: Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research; Grant sponsor: Intramural
Research Program of the NIH, Center for Information Technology; Grant
sponsor: National Institute for Agricultural Research (INRA), France,
Mathematique, Informatique et Genome laboratory
NR 40
TC 6
Z9 7
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD MAR
PY 2011
VL 79
IS 3
BP 853
EP 866
DI 10.1002/prot.22923
PG 14
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 727FU
UT WOS:000287784000013
PM 21287617
ER
PT J
AU Keyes, KM
Krueger, RF
Grant, BF
Hasin, DS
AF Keyes, K. M.
Krueger, R. F.
Grant, B. F.
Hasin, D. S.
TI Alcohol craving and the dimensionality of alcohol disorders
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Alcohol craving; alcohol use disorders; diagnostic criteria; item
response theory; DSM-V
ID DSM-IV ALCOHOL; ITEM RESPONSE THEORY; INTERVIEW SCHEDULE AUDADIS;
NATIONAL EPIDEMIOLOGIC SURVEY; GENERAL-POPULATION SAMPLE; SUBSTANCE USE
DISORDERS; UNITED-STATES; DRUG MODULES; 12-MONTH PREVALENCE;
DIAGNOSTIC-CRITERIA
AB Background. ICD-10 includes a craving criterion for alcohol dependence while DSM-IV does not. Little is known about whether craving fits with or improves the DSM-IV criteria set for alcohol-use disorders.
Method. Data were derived from current drinkers (n=18352) in the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES), a nationally representative survey of US adults >17 years of age. The Alcohol Use Disorder and Associated Disabilities Interview Schedule was used to assess the eleven DSM-IV dependence and abuse criteria, and alcohol craving. Exploratory factor, item response theory, and regression analyses were used to evaluate the psychometric properties and concurrent validity of DSM-based alcohol disorder criteria with the addition of alcohol craving.
Results. The past 12-month prevalence of craving was 1.3%. Craving formed part of a unidimensional latent variable that included existing DSM-IV criteria. Craving demonstrated high severity on the alcohol-use disorder continuum, resulting in an improved dimensional model with greater discriminatory ability compared with current DSM-IV criteria. Correlates of the diagnosis did not change with the addition of craving, and past 12-month craving was associated with prior alcohol dependence, depression, and earlier age of alcohol disorder onset among those with current DSM-IV alcohol dependence.
Conclusions. The addition of craving to the existing DSM-IV criteria yields a continuous measure that better differentiates individuals with and without alcohol problems along the alcohol-use disorder continuum. Few individuals are newly diagnosed with alcohol dependence given the addition of craving, indicating construct validity but redundancy with existing criteria.
C1 [Keyes, K. M.; Hasin, D. S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Keyes, K. M.; Hasin, D. S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Krueger, R. F.] Washington Univ, Dept Psychiat & Psychol, St Louis, MO USA.
[Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
[Hasin, D. S.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA.
RP Hasin, DS (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,123, New York, NY 10032 USA.
EM dsh2@columbia.edu
FU National Institute on Alcoholism and Alcohol Abuse [K05AA014223];
National Institute on Drug Abuse [RO1DA018652]; National Institute of
Drug Abuse [F31 DA026689]; New York State Psychiatric Institute
FX This research was supported in part by grants from the National
Institute on Alcoholism and Alcohol Abuse (no. K05AA014223 to D.S.H.),
the National Institute on Drug Abuse (no. RO1DA018652 to D.S.H.), a
fellowship from the National Institute of Drug Abuse (no. F31 DA026689
to K.M.K.), and support from the New York State Psychiatric Institute.
The authors wish to thank Timothy Geier for assistance with manuscript
preparation, and Sarah Braunstein, Matthew Lamb and Ann Madsen for
helpful comments on previous drafts of this paper.
NR 55
TC 47
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U1 4
U2 14
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD MAR
PY 2011
VL 41
IS 3
BP 629
EP 640
DI 10.1017/S003329171000053X
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 725CF
UT WOS:000287622100018
PM 20459881
ER
PT J
AU Enoch, MA
AF Enoch, Mary-Anne
TI The role of early life stress as a predictor for alcohol and drug
dependence
SO PSYCHOPHARMACOLOGY
LA English
DT Review
DE Abuse; Addiction; Alcohol; Corticotropin; Dopamine; Gene expression;
Glucocorticoid; HPA axis; Stress; VTA
ID CHILDHOOD SEXUAL-ABUSE; SUBSTANCE USE DISORDERS; COMORBIDITY SURVEY
REPLICATION; ADULT PSYCHIATRIC-DISORDERS; VENTRAL TEGMENTAL AREA;
NATIONAL EPIDEMIOLOGIC SURVEY; LINKED POLYMORPHIC REGION;
NATIVE-AMERICAN TRIBES; LONG-TERM CONSEQUENCES; DSM-IV-DISORDERS
AB Genetic and environmental influences on the development of alcohol and drug dependence are equally important. Exposure to early life stress, that is unfortunately common in the general population, has been shown to predict a wide range of psychopathology, including addiction.
This review will look at the characteristics of early life stress that may be specific predictors for adolescent and adult alcohol and drug dependence and will focus on studies in humans, non-human primates and rodents.
Experiencing maltreatment and cumulative stressful life events prior to puberty and particularly in the first few years of life is associated with early onset of problem drinking in adolescence and alcohol and drug dependence in early adulthood. Early life stress can result in permanent neurohormonal and hypothalamic-pituitary-adrenal axis changes, morphological changes in the brain, and gene expression changes in the mesolimbic dopamine reward pathway, all of which are implicated in the development of addiction. However, a large proportion of children who have experienced even severe early life stress do not develop psychopathology indicating that mediating factors such as gene-environment interactions and family and peer relationships are important for resilience.
There appears to be a direct pathway from chronic stress exposure in pre-pubertal children via adolescent problem drinking to alcohol and drug dependence in early adulthood. However, this route can be moderated by genetic and environmental factors. The role that gene-environment interactions play in the risk-resilience balance is being increasingly recognized.
C1 NIAAA, NIH, DICBR, LNG, Bethesda, MD 20892 USA.
RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA.
EM maenoch@niaaa.nih.gov
RI Price, Katie/H-1931-2012
FU National Institute on Alcohol Abuse and Alcoholism, NIH
FX This research was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, NIH.
NR 187
TC 137
Z9 143
U1 12
U2 87
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAR
PY 2011
VL 214
IS 1
BP 17
EP 31
DI 10.1007/s00213-010-1916-6
PG 15
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 726XD
UT WOS:000287759300003
PM 20596857
ER
PT J
AU Panlilio, LV
Yasar, S
Thorndike, EB
Goldberg, SR
Schindler, CW
AF Panlilio, Leigh V.
Yasar, Sevil
Thorndike, Eric B.
Goldberg, Steven R.
Schindler, Charles W.
TI Automatic recording of mediating behavior in delayed matching- and
nonmatching-to-position procedures in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Delayed spatial matching; Mediating response; Working memory; Rehearsal;
Scopolamine; THC
ID SHORT-TERM-MEMORY; WORKING-MEMORY; SAMPLE PERFORMANCE; CHOLINERGIC
DRUGS; SCOPOLAMINE; LESIONS; NUCLEUS; FORNIX; TASK
AB Delayed matching-to-position and nonmatching-to-position procedures are widely used to model working memory in rodents. Mediating behavior-which enhances performance but is not explicitly required by the task-is generally considered an obstacle to the measurement of memory, but often occurs despite attempts to prevent it. The ubiquitous nature of mediating behavior suggests it might be analogous to rehearsal, an important component of learning and memory in humans.
The aim was to study an easily recordable, rehearsal-like mediating response in rats under baseline conditions and after treatment with amnestic drugs [scopolamine (0.1-0.3 mg/kg) and delta-9-tetrahydrocannabinol (THC; 1-5.6 mg/kg)].
Lighted nosepoke holes were used to present position cues and record delayed matching or nonmatching responses. Performance of a distractor task was required to prevent simply waiting at the correct choice, but the nosepoke holes were left accessible during the delay.
Each rat trained with the nonmatching task exhibited one of two mediating "strategies" that increased the odds of a correct choice: responding in the to-be-correct hole during the delay or responding in the opposite hole during the delay. Rats trained with the matching task all showed the former strategy. Treatment with scopolamine disrupted performance of the mediating response. Scopolamine and THC both decreased the effectiveness of the mediating response, increasing errors even on trials when the "appropriate" mediating behavior did occur.
The procedures and data analysis approach used here provide an objective, automated means of measuring mediating behavior, which might be useful as an animal model of memory rehearsal.
C1 [Panlilio, Leigh V.; Thorndike, Eric B.; Goldberg, Steven R.; Schindler, Charles W.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Yasar, Sevil] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA.
RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM lpanlili@intra.nida.nih.gov
FU NIH, National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Drug Abuse. Thanks to Mark Good for comments
on the manuscript.
NR 24
TC 6
Z9 6
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAR
PY 2011
VL 214
IS 2
BP 495
EP 504
DI 10.1007/s00213-010-2057-7
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 726XE
UT WOS:000287759500011
PM 21086118
ER
PT J
AU Kranick, SM
Gorrindo, T
Hallett, M
AF Kranick, Sarah M.
Gorrindo, Tristan
Hallett, Mark
TI Psychogenic Movement Disorders and Motor Conversion: A Roadmap for
Collaboration Between Neurology and Psychiatry
SO PSYCHOSOMATICS
LA English
DT Article
ID COGNITIVE-BEHAVIORAL THERAPY; CLINICAL-FEATURES; DISSOCIATIVE DISORDER;
SYMPTOMS; TREMOR; TRIAL; PHENOMENOLOGY; PARKINSONISM; MANAGEMENT;
PROGNOSIS
AB Background: There are a host of vague terms to describe psychologically-mediated symptoms that mimic neurological disease, such as "functional," "non-organic," "psychogenic," or "medically unexplained." None of these terms has a direct translation in psychiatric classification, and psychiatrists are often fixed with patients who do not believe in a psychological origin for their symptoms. Objective: Within the framework of psychogenic movement disorders, we discuss the roadblocks to effective collaboration and treatment in these patients and the current state of the literature regarding diagnosis and treatment. Results: We describe the approach to these patients from the perspective of neurology and psychiatry illustrating the differences in terminology and categorization. Conclusion: Psychogenic movement disorders represent a unique opportunity for these fields to collaborate in the care of a potentially curable but significantly disabling disorder. (Psychosomatics 2011: 52:109-116)
C1 [Kranick, Sarah M.; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Gorrindo, Tristan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Kranick, SM (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10-7D42,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
EM sarah.kranick@nih.gov
FU NINDS
FX This research was supported in part by the NINDS Intramural Program.
NR 51
TC 13
Z9 13
U1 1
U2 8
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD MAR-APR
PY 2011
VL 52
IS 2
BP 109
EP 116
PG 8
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 741RF
UT WOS:000288881100002
PM 21397102
ER
PT J
AU Widdowson, MA
Bulens, SN
Beard, RS
Lane, KM
Monroe, SS
Lance, S
Bresee, JS
Glass, RI
AF Widdowson, Marc-Alain
Bulens, Sandra N.
Beard, R. Suzanne
Lane, Kimberley M.
Monroe, Stephen S.
Lance, Susan
Bresee, Joseph S.
Glass, Roger I.
TI Enhanced Surveillance of Norovirus Outbreaks of Gastroenteritis in
Georgia
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID NORWALK-LIKE VIRUSES; ROUND-STRUCTURED VIRUSES; UNITED-STATES; VIRAL
GASTROENTERITIS; FOODBORNE DISEASE; IDENTIFICATION; EPIDEMIOLOGY;
TRANSMISSION; ILLNESS; TRENDS
AB Objectives. The role of noroviruses in both foodborne and person-to-person outbreaks of acute gastroenteritis (AGE) has been difficult to determine in the U.S. because of lack of routine norovirus testing and of national reporting of person-to-person outbreaks. We conducted a prospective study in one state in which enhanced testing for noroviruses was performed to better understand the relative contribution of all gastroenteric pathogens.
Methods. During the two-year period, 2000-2001, we took all fecal specimens from AGE outbreaks reported in Georgia that were negative for bacteria and tested these for norovirus.
Results. We investigated 78 AGE outbreaks, from which suitable fecal samples were collected from 57 of them. Norovirus was identified in 25 (44%) outbreaks, bacteria in 20 (35%) outbreaks, and parasites in one (2%) outbreak. Forty-three (75%) of the outbreaks tested were foodborne, of which 17 (40%) were attributable to norovirus and 18 (42%) were attributable to bacteria. Adjusting for incomplete testing, we estimated that 53% of all AGE outbreaks were attributable to norovirus. A total of 2,674 people were reported ill in the 57 outbreaks, and norovirus infections accounted for 1,735 (65%) of these cases. Norovirus outbreaks tended to be larger than bacterial outbreaks, with a median number of 30 vs. 16 cases per outbreak, respectively (p=0.057).
Conclusions. This study provides further evidence that noroviruses are, overall, the most common cause of AGE outbreaks in the U.S. Improved specimen collection, reporting person-to-person outbreaks, and access to molecular assays are needed to further understand the role of these viruses and methods for their prevention.
C1 [Widdowson, Marc-Alain] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30338 USA.
[Bulens, Sandra N.; Glass, Roger I.] Atlanta Res & Educ Fdn, Atlanta, GA USA.
[Lane, Kimberley M.] Georgia Dept Human Resources, Notifiable Dis Epidemiol Sect, Atlanta, GA USA.
[Beard, R. Suzanne; Monroe, Stephen S.; Lance, Susan] Purdue Univ, W Lafayette, IN 47907 USA.
[Monroe, Stephen S.] Ctr Dis Control & Prevent, Natl Ctr Zoonot Vectorborne & Enter Dis, Atlanta, GA 30338 USA.
[Glass, Roger I.] NIH, Fogarty Ctr, Bethesda, MD 20892 USA.
RP Widdowson, MA (reprint author), Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Rd NE,MS-A34, Atlanta, GA 30338 USA.
EM mwiddowson@cdc.gov
OI Monroe, Stephan/0000-0002-5424-716X
NR 27
TC 1
Z9 1
U1 0
U2 2
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD MAR-APR
PY 2011
VL 126
IS 2
BP 251
EP 258
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 723ZX
UT WOS:000287547000016
PM 21387955
ER
PT J
AU Choyke, PL
AF Choyke, Peter L.
TI Science to Practice: Angiogenic Marker Expression during Tumor
Growth-Can Targeted US Microbubbles Help Monitor Molecular Changes in
the Microvasculature?
SO RADIOLOGY
LA English
DT Editorial Material
AB In the study of Deshpande et al (1), ultrasonographic (US) microbubbles targeted with one of several antibodies-anti-integrin, anti-endoglin, or anti-vascular endothelial growth factor receptor 2-were injected into mice with implanted breast, ovarian, or pancreatic tumors. Changes in the relative uptake of each targeted microbubble were observed as the tumors grew, reflecting changes in the angiogenic mechanisms the tumor invoked at different stages of growth. This opens the possibility of in vivo molecular profiling of tumor angiogenesis as a diagnostic tool.
C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, 900 Rockville Pike,Bldg 10,Room B3B69F, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
NR 5
TC 2
Z9 2
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAR
PY 2011
VL 258
IS 3
BP 655
EP 656
DI 10.1148/radiol.102314
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 724JX
UT WOS:000287573100001
PM 21339343
ER
PT J
AU Chaiworapongsa, T
Romero, R
Savasan, ZA
Ogge, G
Soto, E
Dong, Z
Hassan, SS
AF Chaiworapongsa, Tinnakorn
Romero, Roberto
Savasan, Zeynep Alpay
Ogge, Giovanna
Soto, Eleazar
Dong, Zhong
Hassan, Sonia S.
TI Maternal Plasma Concentrations of Angiogenic/Anti-Angiogenic Factors Are
of Prognostic Value in Patients Suspected To Have Preeclampsia
Presenting to the Obstetrical Triage
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Chaiworapongsa, Tinnakorn; Romero, Roberto; Savasan, Zeynep Alpay; Ogge, Giovanna; Soto, Eleazar; Dong, Zhong; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Chaiworapongsa, Tinnakorn; Romero, Roberto; Savasan, Zeynep Alpay; Soto, Eleazar; Hassan, Sonia S.] Wayne State Univ, Dept OB GYN, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T004
BP 73A
EP 73A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700009
ER
PT J
AU Heuser, CC
AF Heuser, Cara C.
TI Complement and Complement Regulatory Gene Polymorphisms with Severe
Preeclampsia
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Heuser, Cara C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T014
BP 76A
EP 76A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700019
ER
PT J
AU Soto, E
Romero, R
Ogge, G
Yeo, L
Hassan, SS
Kim, CJ
Chaiworapongsa, T
AF Soto, Eleazar
Romero, Roberto
Ogge, Giovanna
Yeo, Lami
Hassan, Sonia S.
Kim, Chong Jai
Chaiworapongsa, Tinnakorn
TI An Anti-Angiogenic State in Late-Onset Preeclampsia Is Associated with
Evidence of 'Maternal Underperfusion' of the Placenta
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Soto, Eleazar; Romero, Roberto; Ogge, Giovanna; Yeo, Lami; Hassan, Sonia S.; Kim, Chong Jai; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Soto, Eleazar; Romero, Roberto; Ogge, Giovanna; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
RI Ogge, Giovanna/G-6109-2011
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T023
BP 78A
EP 79A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700028
ER
PT J
AU Catherino, WH
Britten, J
Malik, M
Gilden, M
Toukhi, H
AF Catherino, William H.
Britten, Joy
Malik, Minnie
Gilden, Melissa
Toukhi, Heba
TI Retinoic Acid Increases the Smooth Muscle Characteristics of the
Leiomyoma Transcriptome
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Catherino, William H.; Britten, Joy; Malik, Minnie; Gilden, Melissa; Toukhi, Heba] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Catherino, William H.] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T075
BP 94A
EP 94A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700080
ER
PT J
AU Hill, MJ
DeCherney, AH
Linehan, M
Levy, G
Venkatesan, A
Armstrong, AY
AF Hill, Micah J.
DeCherney, Alan H.
Linehan, Marston
Levy, Gary
Venkatesan, Aradhana
Armstrong, Alicia Y.
TI Use of MRI Mapping, Core Biopsies and Excisional Biopsies in a Patient
with Hereditary Leiomyoma Renal Cell Cancer (HLRCC)
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Hill, Micah J.; DeCherney, Alan H.; Levy, Gary; Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Linehan, Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Venkatesan, Aradhana] NIH, Dept Radiol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T079
BP 95A
EP 95A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700084
ER
PT J
AU Levy, G
Avila, N
Armstrong, AY
Nieman, L
AF Levy, Gary
Avila, Nilo
Armstrong, Alicia Y.
Nieman, Lynnette
TI Does the Selective Progesterone Receptor Modulator Ulipristal Normalize
the Uterine Cavity in Women with Leiomyoma
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Levy, Gary; Armstrong, Alicia Y.; Nieman, Lynnette] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Avila, Nilo] NIH, Dept Radiol, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T081
BP 95A
EP 95A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700086
ER
PT J
AU Pulanic, TK
Khachikyan, I
Venkatesan, A
Segars, J
Gates, S
Fischer, J
Zurawin, R
Muthupillai, R
Dees, D
Stratton, P
AF Pulanic, T. Klepac
Khachikyan, I.
Venkatesan, A.
Segars, J.
Gates, S.
Fischer, J.
Zurawin, R.
Muthupillai, R.
Dees, D.
Stratton, P.
TI Rapid Accrual for Pilot Study of MR-Guided High Intensity Focused
Ultrasound (MRgHIFU) Ablation of Uterine Fibroids
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Pulanic, T. Klepac; Khachikyan, I.; Segars, J.; Stratton, P.] NICHD, PRAE, NIH, Bethesda, MD USA.
[Venkatesan, A.] NIH, Dept Diagnost Radiol, CC, Bethesda, MD 20892 USA.
[Gates, S.] NCI, SAIC, Frederick, MD 21701 USA.
[Fischer, J.; Muthupillai, R.; Dees, D.] St Lukes Episcopal Hosp, Dept Radiol, Houston, TX 77030 USA.
[Zurawin, R.] Baylor Coll Med, Dept Ob Gyn, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T080
BP 95A
EP 95A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700085
ER
PT J
AU Pang, ALY
Alford, CE
Segars, JH
DeCherney, AH
Rennert, OM
AF Pang, Alan L. Y.
Alford, Connie E.
Segars, James H.
DeCherney, Alan H.
Rennert, Owen M.
TI Identification of the Regulatory Elements That Are Involved in
Translational Repression of the Ard1b Gene
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Pang, Alan L. Y.; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin & Dev Genom, NIH, Bethesda, MD USA.
[Alford, Connie E.; Segars, James H.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult Reprod Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T-112
BP 103A
EP 103A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700115
ER
PT J
AU Moon, KS
Levens, ED
Richter, KS
DeCherney, AH
Chang, FE
AF Moon, Kimberly S.
Levens, Eric D.
Richter, Kevin S.
DeCherney, Alan H.
Chang, Frank E.
TI hCG Salvage after Failed GnRH Agonist Trigger for Final Oocyte
Maturation in IVF Cycles
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Moon, Kimberly S.; Levens, Eric D.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Levens, Eric D.; Richter, Kevin S.; Chang, Frank E.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T163
BP 117A
EP 117A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700166
ER
PT J
AU Skafar, DF
Imudia, AN
Terleckey, L
Kilburn, BA
Simon, J
Armant, DR
AF Skafar, Debra F.
Imudia, Anthony N.
Terleckey, Laura
Kilburn, Brian A.
Simon, Joe
Armant, D. Randall
TI Estradiol Stimulates Cell Death and Reduces Proliferation of the
Cytotrophoblast Cell Line HTR-8/SVneo
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Imudia, Anthony N.; Kilburn, Brian A.; Simon, Joe; Armant, D. Randall] Wayne State Univ, Detroit, MI USA.
[Skafar, Debra F.; Terleckey, Laura] Wayne State Univ Sch Med, Detroit, MI USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T176
BP 121A
EP 121A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700179
ER
PT J
AU Ogge, G
Chaiworapongsa, T
Kusanovic, JP
Yeo, L
Kim, CJ
Hassan, SS
Romero, R
AF Ogge, Giovanna
Chaiworapongsa, Tinnakorn
Kusanovic, Juan Pedro
Yeo, Lami
Kim, Chong Jai
Hassan, Sonia S.
Romero, Roberto
TI Evidence that Placental Lesions Are More Frequent in Early-Onset Than in
Late-Onset Preeclampsia
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Ogge, Giovanna; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Yeo, Lami; Kim, Chong Jai; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
RI Ogge, Giovanna/G-6109-2011
NR 0
TC 1
Z9 1
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T188
BP 124A
EP 124A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700191
ER
PT J
AU Bahado-Singh, RO
AF Bahado-Singh, Ray O.
TI The Relationship between Fetal Gender and the Effects of Treatment of
Mild Gestational Diabetes
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Bahado-Singh, Ray O.] NICHHD, Maternal Fetal Med Units Network, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T239
BP 138A
EP 139A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700241
ER
PT J
AU Ma, KK
AF Ma, Kimberly K.
TI The Obstetrical and Neonatal Implications of a Low Value on the Glucose
Screening Test
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Ma, Kimberly K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T250
BP 142A
EP 142A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700252
ER
PT J
AU Maguire, M
Koziol, D
Vanderhoof, V
DeCherney, A
Troendle, J
Nelson, L
AF Maguire, Marcy
Koziol, Deloris
Vanderhoof, Vien
DeCherney, Alan
Troendle, James
Nelson, Lawrence
TI Association between Organ-Specific Autoantibody Status and Pregnancy
Wastage in Women with Primary Ovarian Insuffi ciency (POI)
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Maguire, Marcy; Vanderhoof, Vien; DeCherney, Alan; Nelson, Lawrence] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Koziol, Deloris] NIH, Biostat & Clin Epidemiol Serv, Bethesda, MD USA.
[Troendle, James] NHLBI, Off Biostat Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T281
BP 150A
EP 150A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700283
ER
PT J
AU Malik, M
Britten, J
Segars, J
Catherino, W
AF Malik, Minnie
Britten, Joy
Segars, James
Catherino, William
TI Validation of 3-Dimensional Leiomyoma Cultures: Growing Fibroids in the
Laboratory
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Malik, Minnie; Britten, Joy; Catherino, William] Uniformed Serv Univ Hlth Sci, OBG, Bethesda, MD 20814 USA.
[Segars, James] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA O-024
BP 163A
EP 163A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700327
ER
PT J
AU Chu, TJ
Mouillet, JF
Sadovsky, Y
AF Chu, Tianjiao
Mouillet, Jean-Francois
Sadovsky, Yoel
TI Gestational Age, but Not Labor, Influences the Fetal Blood microRNA
Landscape.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Sadovsky, Yoel] NICHD Genom & Prote Network Preterm Birth Res, Bethesda, MD USA.
[Chu, Tianjiao; Mouillet, Jean-Francois; Sadovsky, Yoel] Univ Pittsburgh, Magee Womens Res Inst, Dept OBGYN Reprod Sci, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F051
BP 188A
EP 188A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700414
ER
PT J
AU Khachikyan, I
Sinaii, N
Shah, J
Ortiz, R
Segars, J
Stratton, P
AF Khachikyan, Izabella
Sinaii, Ninet
Shah, James
Ortiz, Robin
Segars, Jay
Stratton, Pamela
TI CNS Sensitization and Myofascial Dysfunction in Patients with
Endometriosis and Chronic Pelvic Pain
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Khachikyan, Izabella; Segars, Jay; Stratton, Pamela] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Sinaii, Ninet] Biostat & Clin Epidemiol Serv, Bethesda, MD USA.
[Shah, James; Ortiz, Robin] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F068
BP 192A
EP 193A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700430
ER
PT J
AU Khachikyan, I
Ortiz, R
Sinaii, N
Shah, J
Segars, J
Stratton, P
AF Khachikyan, Izabella
Ortiz, Robin
Sinaii, Ninet
Shah, Jay
Segars, James
Stratton, Pamela
TI All Chronic Pelvic Pain Is Not the Same: Quality of Life Symptoms in
Women with Endometriosis-Associated Pain Differs from Symptoms in
Chronic Pelvic Pain Due to Other Causes
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Khachikyan, Izabella; Segars, James; Stratton, Pamela] NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, CC, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F069
BP 193A
EP 193A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700431
ER
PT J
AU Olson, G
AF Olson, Gayle
TI Among Infants Born Preterm, Is Weight at 2 Years of Age Influenced by
Birth Weight
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Olson, Gayle] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F152
BP 217A
EP 217A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701079
ER
PT J
AU Yu, B
Uchida, N
Beall, S
Tisdale, J
Segars, J
Wolff, E
AF Yu, Bo
Uchida, Naoya
Beall, Stephanie
Tisdale, John
Segars, James
Wolff, Erin
TI Generation of a Novel Cell Line for Use as a Model System To Study
Uterine Disease from a Patient with an HRPT2 Gene Mutation
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Yu, Bo; Uchida, Naoya; Beall, Stephanie; Tisdale, John; Segars, James; Wolff, Erin] NICHD, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F207
BP 232A
EP 232A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701134
ER
PT J
AU Swamy, GK
AF Swamy, Geeta K.
TI Phase II Study To Assess the Safety and Immunogenicity of Two Dose
Levels of 2009 H1N1 Influenza Vaccine in Pregnant Women
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Swamy, Geeta K.] Duke Univ, NIAID VTEU Investigators Protocol 09 0072, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F216
BP 235A
EP 235A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701143
ER
PT J
AU Savasan, ZA
Chaiworapongsa, T
Kusanovic, JP
Dong, Z
Kim, CJ
Hassan, SS
Romero, R
AF Savasan, Zeynep Alpay
Chaiworapongsa, Tinnakorn
Kusanovic, Juan Pedro
Dong, Zhong
Kim, Chong Jai
Hassan, Sonia S.
Romero, Roberto
TI IL-19 in Fetal Systemic Inflammation
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Dong, Zhong; Kim, Chong Jai; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
[Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F220
BP 236A
EP 236A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701147
ER
PT J
AU Madan, I
Chaiworapongsa, T
Ogge, G
Tarca, AL
Bhatti, G
Draghici, S
Hassan, SS
Romero, R
AF Madan, Ichchha
Chaiworapongsa, Tinnakorn
Ogge, Giovanna
Tarca, Adi L.
Bhatti, Gaurav
Draghici, Sorin
Hassan, Sonia S.
Romero, Roberto
TI The Peripheral Whole Blood Transcriptome of Acute Systemic Infection in
Human Pregnancy
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Madan, Ichchha; Chaiworapongsa, Tinnakorn; Ogge, Giovanna; Tarca, Adi L.; Bhatti, Gaurav; Draghici, Sorin; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Madan, Ichchha; Chaiworapongsa, Tinnakorn; Ogge, Giovanna; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Tarca, Adi L.; Bhatti, Gaurav; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA.
RI Draghici, Sorin/B-3074-2013
OI Draghici, Sorin/0000-0002-0786-8377
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F241
BP 242A
EP 242A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701168
ER
PT J
AU Romero, R
Chaiworapongsa, T
Savasan, ZA
Madan, I
Dong, Z
Kusanovic, JP
Kim, CJ
Hassan, SS
AF Romero, Roberto
Chaiworapongsa, Tinnakorn
Savasan, Zeynep Alpay
Madan, Ichchha
Dong, Zhong
Kusanovic, Juan Pedro
Kim, Chong Jai
Hassan, Sonia S.
TI An Alarmin, HMGB1, and One of Its Receptors, sRAGE, Participate in
Clinical Chorioamnionitis at Term
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Madan, Ichchha; Dong, Zhong; Kusanovic, Juan Pedro; Kim, Chong Jai; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Madan, Ichchha; Kusanovic, Juan Pedro; Hassan, Sonia S.] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F249
BP 244A
EP 245A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701176
ER
PT J
AU Romero, R
Chaiworapongsa, T
Savasan, ZA
Madan, I
Dong, Z
Kusanovic, JP
Kim, CJ
Hassan, SS
AF Romero, Roberto
Chaiworapongsa, Tinnakorn
Savasan, Zeynep Alpay
Madan, Ichchha
Dong, Zhong
Kusanovic, Juan Pedro
Kim, Chong Jai
Hassan, Sonia S.
TI HMGB1, a Late Mediator of Sepsis and Death, Is Involved in the Host
Response to Intra-Amniotic Infection/Inflammation in Preterm Gestation
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Madan, Ichchha; Dong, Zhong; Kusanovic, Juan Pedro; Kim, Chong Jai; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Madan, Ichchha; Kusanovic, Juan Pedro; Kim, Chong Jai; Hassan, Sonia S.] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F250
BP 245A
EP 245A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701177
ER
PT J
AU Wolff, E
Uchida, N
Stratton, P
Hsieh, M
Tisdale, J
AF Wolff, Erin
Uchida, Naoya
Stratton, Pamela
Hsieh, Matthew
Tisdale, John
TI Characterization of Endometrial Stem Cells in a Chimeric Bone Marrow
Model in Both Humans and Macaques
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Wolff, Erin; Stratton, Pamela] NICHD, NIH, Bethesda, MD USA.
[Uchida, Naoya; Hsieh, Matthew; Tisdale, John] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA F-306
BP 262A
EP 262A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701233
ER
PT J
AU Savasan, ZA
Chaiworapongsa, T
Kusanovic, JP
Dong, Z
Kim, CJ
Hassan, SS
Romero, R
AF Savasan, Zeynep Alpay
Chaiworapongsa, Tinnakorn
Kusanovic, Juan Pedro
Dong, Zhong
Kim, Chong Jai
Hassan, Sonia S.
Romero, Roberto
TI Studies of the Novel Cytokine, Interleukin-19, in Pregnancy, Parturition
(Term and Preterm) and Intra-Amniotic Infection/Infl ammation
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Dong, Zhong; Kim, Chong Jai; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Savasan, Zeynep Alpay; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA O-065
BP 264A
EP 264A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701240
ER
PT J
AU Edwards, DRV
Baird, DD
Hasan, R
Savitz, DA
Hartmann, KE
AF Edwards, Digna R. Velez
Baird, Donna D.
Hasan, Reem
Savitz, David A.
Hartmann, Katherine E.
TI Vaginal Bleeding during the First-Trimester Independently Associated
with Preterm Birth Risk
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Edwards, Digna R. Velez; Hartmann, Katherine E.] Vanderbilt Univ, Dept Obstet & Gynecol, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Nashville, TN USA.
[Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Hasan, Reem] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Savitz, David A.] Dept Community Hlth & Obstet & Gynecol, Providence, RI USA.
RI Velez Edwards, Digna/C-1090-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA O076
BP 267A
EP 267A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701251
ER
PT J
AU Chason, RJ
Chen, Z
Louis, GMB
Segars, JH
Pyper, C
AF Chason, Rebecca J.
Chen, Zhen
Louis, Germaine M. Buck
Segars, James H.
Pyper, Cecilia
TI Basal Salivary Stress Biomarkers, Lifestyle and Pregnancy Loss
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Chason, Rebecca J.; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Pyper, Cecilia] Univ Oxford, Natl Perinatal Epidemiol Unit, Oxford, England.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA O078
BP 268A
EP 268A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701253
ER
PT J
AU Wolff, E
Alford, C
Remaley, A
Sinaii, N
Childs, R
Stratton, P
AF Wolff, Erin
Alford, Connie
Remaley, Alan
Sinaii, Ninet
Childs, Richard
Stratton, Pamela
TI Hormonal Ovarian Reserve in Patients Undergoing Fertility-Sparing
Peripheral Blood Stem Cell Transplant
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Wolff, Erin; Alford, Connie; Stratton, Pamela] NICHD, NIH, Bethesda, MD USA.
[Remaley, Alan] NIH, DLM, Bethesda, MD USA.
[Sinaii, Ninet] NIH, BCES, Bethesda, MD USA.
[Childs, Richard] NHLBI, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA O-119
BP 280A
EP 280A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701294
ER
PT J
AU Jessmon, P
Jiang, XY
Kilburn, B
Swaminathan, A
Armant, DR
AF Jessmon, Philip
Jiang, Xiaoyu
Kilburn, Brian
Swaminathan, Ashok
Armant, David R.
TI Integrin-Switching Regulated by HBEGF in Human Cytotrophoblast Cells
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Jessmon, Philip; Jiang, Xiaoyu; Kilburn, Brian; Swaminathan, Ashok; Armant, David R.] Wayne State Univ, Detroit, MI USA.
[Jessmon, Philip; Armant, David R.] NICHD, Program Reprod & Adult Endocrinol, NIH, US Dept HHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA O158
BP 291A
EP 291A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701332
ER
PT J
AU Manuck, T
AF Manuck, Tracy
TI The Contribution of Genetic Variation on Chromosome 7 to Spontaneous
Preterm Birth (SPTB) in African-American (AA) Women
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Manuck, Tracy] NICHD, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA S050
BP 309A
EP 309A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701392
ER
PT J
AU Chaiworapongsa, T
Whitten, A
Tarca, AL
Draghici, S
Kim, CJ
Hassan, SS
Romero, R
AF Chaiworapongsa, Tinnakorn
Whitten, Amy
Tarca, Adi L.
Draghici, Sorin
Kim, Chong-Jai
Hassan, Sonia S.
Romero, Roberto
TI Differences and Similarities in the Transcriptional Profile of
Peripheral Whole Blood in Early- and Late-Onset Preeclampsia: Insights
into the Molecular Basis of the Phenotype of Preeclampsia
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Chaiworapongsa, Tinnakorn; Whitten, Amy; Tarca, Adi L.; Kim, Chong-Jai; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Chaiworapongsa, Tinnakorn; Whitten, Amy; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Dept Ob Gyn, Detroit, MI USA.
[Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI USA.
[Kim, Chong-Jai] Wayne State Univ, Dept Pathol, Detroit, MI USA.
RI Draghici, Sorin/B-3074-2013
OI Draghici, Sorin/0000-0002-0786-8377
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA S193
BP 350A
EP 350A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701533
ER
PT J
AU Hill, LD
York, TP
Srinivas, S
Kusanovic, JP
Gomez, R
Elovitz, MA
Romero, R
Strauss, JF
AF Hill, Lori D.
York, Timothy P.
Srinivas, Sindhu
Kusanovic, Juan P.
Gomez, Ricardo
Elovitz, Michal A.
Romero, Roberto
Strauss, Jerome F., III
TI ERAP2 and Preeclampsia: Racial/Ethinic-Specific Associations
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Hill, Lori D.; York, Timothy P.; Strauss, Jerome F., III] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA.
[Srinivas, Sindhu; Elovitz, Michal A.] Univ Penn, Sch Med, Dept OBGYN, Maternal & Child Hlth Res Program, Philadelphia, PA 19104 USA.
[Kusanovic, Juan P.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Kusanovic, Juan P.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Kusanovic, Juan P.; Gomez, Ricardo] Hosp Dr Sotero del Rio, Santiago, Chile.
[Kusanovic, Juan P.; Gomez, Ricardo] Pontificia Univ Catolica Chile, Santiago, Chile.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA S209
BP 355A
EP 355A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701549
ER
PT J
AU Hill, LD
York, TP
Kusanovic, JP
Gomez, R
Eaves, LJ
Romero, R
Strauss, JF
AF Hill, Lori D.
York, Timothy P.
Kusanovic, Juan P.
Gomez, Ricardo
Eaves, Lindon J.
Romero, Roberto
Strauss, Jerome F., III
TI Epistasis between COMT and MTHFR in Maternal-Fetal Dyads Is Associated
with Increased Risk for Preeclampsia
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [York, Timothy P.; Eaves, Lindon J.] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Kusanovic, Juan P.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Kusanovic, Juan P.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Kusanovic, Juan P.; Gomez, Ricardo] Hosp Dr Sotero del Rio, Santiago, Chile.
[Kusanovic, Juan P.; Gomez, Ricardo] Pontificia Univ Catolica Chile, Santiago, Chile.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA S208
BP 355A
EP 355A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701548
ER
PT J
AU Mousa, AA
Archer, KJ
Cappello, R
Estrada-Gutierrez, G
Isaacs, C
Romero, R
Strauss, JF
Walsh, SW
AF Mousa, Ahmad A.
Archer, Kellie J.
Cappello, Renato
Estrada-Gutierrez, Guaddalupe
Isaacs, Christine
Romero, Roberto
Strauss, Jerome F., III
Walsh, Scott W.
TI Epigenetic Alterations in Omental Artery Genes in Women with
Preeclampsia
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Mousa, Ahmad A.; Archer, Kellie J.; Cappello, Renato; Estrada-Gutierrez, Guaddalupe; Isaacs, Christine; Strauss, Jerome F., III; Walsh, Scott W.] Virginia Commonwealth Univ, Richmond, VA USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto] Wayne State Univ, Detroit, MI USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA S213
BP 356A
EP 356A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701553
ER
PT J
AU Weissgerber, T
Gandley, R
AF Weissgerber, Tracey
Gandley, Robin
TI Risk of Types of Pregnancy Associated Hypertension According to
Haptoglobin Phenotype
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Weissgerber, Tracey; Gandley, Robin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
RI Weissgerber, Tracey/D-2324-2014
OI Weissgerber, Tracey/0000-0002-7490-2600
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA S233
BP 362A
EP 362A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701573
ER
PT J
AU Castellanos, FX
Acosta, MT
AF Xavier Castellanos, F.
Teresa Acosta, M.
TI Towards an understanding of the molecular mechanisms underlying the
pharmacological treatments of attention deficit hyperactivity disorder
SO REVISTA DE NEUROLOGIA
LA Spanish
DT Article
DE Alpha-2a noradrenergic receptors; Amphetamines; Atomoxetine; D-1
dopaminergic receptors; Guanfacine; Methylphenidate; Signal to noise
ratio
ID D2R DNA TRANSFER; DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER;
PREFRONTAL CORTEX; HUMAN BRAIN; STIMULANT MEDICATION; REWARD
ANTICIPATION; DOUBLE-BLIND; METHYLPHENIDATE; RECEPTORS
AB Methylphenidate and the amphetamines are the most frequently used medications for treating attention-deficit/hyperactivity disorder (ADHD). These medications modulate both norepinephrine as well as dopamine. Methylphenidate is a pure blocker of the norepinephrine and dopamine transporters. The amphetamines also block reuptake of both catecholamines, but they also release all three monoamines, norepinephrine, dopamine, and serotonin, from presynaptic vesicles. Amphetamines are the most robust agents in increasing synaptic dopamine levels, since they do so regardless of the endogenous level of the relevant neurons. Stimulant-evoked synaptic increases of dopamine have been demonstrated in the striatum in humans, but pharmacologic effects are likely relevant to therapeutic action in other regions, particularly the prefrontal cortex. Blockade of noradrenergic reuptake in the prefrontal cortex may also indirectly increase prefrontal dopamine levels, but there is also evidence that noradrenergic effects are mediated by alpha-2a noradrenergic receptors. A recent study in non-human primates found that methylphenidate and atomoxetine both increased the efficiency of prefrontal pyramidal neurons, but via distinct mechanisms. Methylphenidate decreased non-specific signals, i.e., neuronal noise, via D-1 receptors. By contrast, atomoxetine increased the strength of specific signals via activation of alpha-2 receptors. These findings, although in non-human primates, suggest that combinations of agents working on these complementary systems (D-1, and alpha-2a) may be worth considering and evaluating rigorously in patients with ADHD with sub-optimal responses to mono-therapy.
C1 [Xavier Castellanos, F.] NYU Langone Med Ctr, Child Study Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, Nueva York, NY USA.
[Xavier Castellanos, F.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA.
[Teresa Acosta, M.] Childrens Natl Med Ctr, Serv Neurol, Washington, DC 20010 USA.
[Teresa Acosta, M.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Castellanos, FX (reprint author), NYU Child Study Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, 215 Lexington Ave,14th Floor, New York, NY 10016 USA.
EM francisco.castellanos@nyumc.org
NR 54
TC 3
Z9 3
U1 2
U2 3
PU REVISTA DE NEUROLOGIA
PI BARCELONA
PA C/O CESAR VIGUERA, EDITOR, APDO 94121, 08080 BARCELONA, SPAIN
SN 0210-0010
J9 REV NEUROLOGIA
JI Rev. Neurologia
PD MAR
PY 2011
VL 52
SU 1
BP S155
EP 160
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 972EV
UT WOS:000306260900021
PM 21365598
ER
PT J
AU Takacs, JE
Neary, TB
Ingolia, NT
Saini, AK
Martin-Marcos, P
Pelletier, J
Hinnebusch, AG
Lorsch, JR
AF Takacs, Julie E.
Neary, Timothy B.
Ingolia, Nicholas T.
Saini, Adesh K.
Martin-Marcos, Pilar
Pelletier, Jerry
Hinnebusch, Alan G.
Lorsch, Jon R.
TI Identification of compounds that decrease the fidelity of start codon
recognition by the eukaryotic translational machinery
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE translation initiation; start codon; compound screen; ribosome; yeast
ID SELECTION IN-VIVO; NON-AUG CODONS; SACCHAROMYCES-CEREVISIAE;
TRANSFER-RNA; MESSENGER-RNAS; RIBOSOMAL-SUBUNIT; INITIATOR REGION;
SEQUENCE CONTEXT; SITE SELECTION; PROTEIN-KINASE
AB Translation initiation in eukaryotes involves more than a dozen protein factors. Alterations in six factors have been found to reduce the fidelity of start codon recognition by the ribosomal preinitiation complex in yeast, a phenotype referred to as Sui(-). No small molecules are known that affect the fidelity of start codon recognition. Such compounds would be useful tools for probing the molecular mechanics of translation initiation and its regulation. To find compounds with this effect, we set up a high-throughput screen using a dual luciferase assay in S. cerevisiae. Screening of over 55,000 compounds revealed two structurally related molecules that decrease the fidelity of start codon selection by approximately twofold in the dual luciferase assay. This effect was confirmed using additional in vivo assays that monitor translation from non-AUG start codons. Both compounds increase translation of a natural upstream open reading frame previously shown to initiate translation at a UUG. The compounds were also found to exacerbate increased use of UUG as a start codon (Sui(-) phenotype) conferred by haploinsufficiency of wild-type eukaryotic initiation factor (eIF) 1, or by mutation in eIF1. Furthermore, the effects of the compounds are suppressed by overexpressing eIF1, which is known to restore the fidelity of start codon selection in strains harboring Sui(-) mutations in various other initiation factors. Together, these data strongly suggest that the compounds affect the translational machinery itself to reduce the accuracy of selecting AUG as the start codon.
C1 [Takacs, Julie E.; Neary, Timothy B.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Ingolia, Nicholas T.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Ingolia, Nicholas T.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
[Ingolia, Nicholas T.] Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
[Ingolia, Nicholas T.] Carnegie Inst, Dept Embryol, Baltimore, MD 21218 USA.
[Saini, Adesh K.; Martin-Marcos, Pilar; Hinnebusch, Alan G.] Eunice Kennedy Shriver Inst Child Hlth & Human De, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Pelletier, Jerry] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.
[Pelletier, Jerry] McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada.
RP Lorsch, JR (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
EM jlorsch@jhmi.edu
OI Lorsch, Jon/0000-0002-4521-4999
FU National Institutes of Health [DK078633]
FX We thank Silke Dorner and Jeff Corden for advice on developing the
luciferase assay, Miranda Darby, Kip Bitok, and Kamau Fahie for
technical assistance, and the members of the Lorsch and Hinnebusch labs
for helpful discussions and comments on the manuscript. We are also
grateful to Kristian Baker for the upf1 Delta mutant, Karl Kuchler for
strain YRP1, Jun O. Liu for the Phase I compound library, Scott Strobel
and Marina Santiago for the microbial extract library, and Jonathan S.
Weissman for reagents. This work was supported by National Institutes of
Health grant DK078633 (J.R.L.) and by the Intramural Research Program of
the National Institutes of Health (A.G.H.).
NR 48
TC 10
Z9 12
U1 0
U2 3
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 MAR
PY 2011
VL 17
IS 3
BP 439
EP 452
DI 10.1261/rna.2475211
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719HU
UT WOS:000287195900007
PM 21220547
ER
PT J
AU Malagon, F
Jensen, TH
AF Malagon, Francisco
Jensen, Torben Heick
TI T-body formation precedes virus-like particle maturation in S-cerevisiae
SO RNA BIOLOGY
LA English
DT Article
DE T-body; Ty1; Gag; transposition; VLP
ID YEAST RETROTRANSPOSON TY1; ACTIN MESSENGER-RNA; REVERSE-TRANSCRIPTASE;
ESCHERICHIA-COLI; GENOMIC RNA; GAG; PROTEIN; TRANSPOSITION;
LOCALIZATION; HOST
AB T-bodies are localized S. cerevisiae RNPs containing Ty1 retroviral components and speculated to play a role in the assembly of virus-like particles (VLPs). Mapping requirements for T-body formation, we demonstrate that ectopic expression of immature TyA1/Gag (Gag-p49), a structural component of the Ty1 capsid, is sufficient for T-body formation both under normal conditions as well as in a strain background devoid of endogenous Gag. Moreover, T-bodies are readily formed when Ty1 transposition is blocked. Thus, T-bodies represent an early stage in the Ty1 life cycle, preceding VLP maturation.
C1 [Malagon, Francisco; Jensen, Torben Heick] Aarhus Univ, Dept Mol Biol, Ctr mRNP Biogenesis & Metab, Cf Aarhus C, Denmark.
RP Malagon, F (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM fm@mb.au.dk; thj@mb.au.dk
RI Malagon, Francisco/A-7059-2013
FU Danish National Research-Foundation; Benzon-Foundation; Novo
Nordisk-Foundation
FX We thank Antonin Morillon, Alison Rattray, Soren Lykke-Andersen and
Christian Damgaard for critical comments. This work was supported by the
Danish National Research-, the Benzon- and the Novo Nordisk-Foundations.
NR 29
TC 8
Z9 8
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1547-6286
J9 RNA BIOL
JI RNA Biol.
PD MAR-APR
PY 2011
VL 8
IS 2
SI SI
BP 184
EP 189
DI 10.4161/rna.8.2.14822
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 755MA
UT WOS:000289934300002
PM 21358276
ER
PT J
AU Yedavalli, VSRK
Jeang, KT
AF Yedavalli, Venkat S. R. K.
Jeang, Kuan-Teh
TI Rev-ing up post-transcriptional HIV-1 RNA expression
SO RNA BIOLOGY
LA English
DT Editorial Material
DE PIMT; TGS1; HIV-1; Rev; CRM1; RNA export
ID CONSTITUTIVE TRANSPORT ELEMENT; POTENTIAL ANTIVIRAL AGENTS; U-SNRNA
EXPORT; MESSENGER-RNA; NUCLEAR EXPORT; GENE-EXPRESSION; PROTEIN; CAP;
TRANSLATION; TYPE-1
C1 [Yedavalli, Venkat S. R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kj7e@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU Intramural NIH HHS
NR 65
TC 9
Z9 9
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1547-6286
EI 1555-8584
J9 RNA BIOL
JI RNA Biol.
PD MAR-APR
PY 2011
VL 8
IS 2
SI SI
BP 195
EP 199
DI 10.4161/rna.8.2.14803
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 755MA
UT WOS:000289934300004
PM 21358275
ER
PT J
AU Miller, R
Richards, T
Germain, G
Tossell, JW
Mattai, AA
Gochman, P
Greenstein, DK
Gogtay, N
Rapoport, J
AF Miller, Rachel
Richards, T.
Germain, G.
Tossell, J. W.
Mattai, A. A.
Gochman, P.
Greenstein, D. K.
Gogtay, N.
Rapoport, Judith
TI DIAGNOSTIC OUTCOMES OF CASES REFERRED AS CHILDHOOD-ONSET SCHIZOPHRENIA
AFTER INPATIENT EVALUATION AND MEDICATION WASHOUT: A LONGITUDINAL
FOLLOW-UP.
SO SCHIZOPHRENIA BULLETIN
LA English
DT Meeting Abstract
CT 13th International Congress on Schizophrenia Research (ICSR)
CY APR 02-06, 2011
CL Colorado Springs, CO
C1 [Miller, Rachel; Richards, T.; Germain, G.; Tossell, J. W.; Mattai, A. A.; Gochman, P.; Greenstein, D. K.; Gogtay, N.; Rapoport, Judith] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RI Gogtay, Nitin/A-3035-2008
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD MAR
PY 2011
VL 37
SU 1
BP 6
EP 6
PG 1
WC Psychiatry
SC Psychiatry
GA 726SI
UT WOS:000287746000018
ER
PT J
AU Rapoport, J
Gogtay, N
AF Rapoport, Judith
Gogtay, N.
TI BRAIN DEVELOPMENT IN HEALTHY SIBLINGS OF CHILDHOOD ONSET SCHIZOPHRENIA
PATIENTS
SO SCHIZOPHRENIA BULLETIN
LA English
DT Meeting Abstract
CT 13th International Congress on Schizophrenia Research (ICSR)
CY APR 02-06, 2011
CL Colorado Springs, CO
C1 [Rapoport, Judith; Gogtay, N.] NIMH, Bethesda, MD 20892 USA.
RI Gogtay, Nitin/A-3035-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD MAR
PY 2011
VL 37
SU 1
BP 173
EP 174
PG 2
WC Psychiatry
SC Psychiatry
GA 726SI
UT WOS:000287746000492
ER
PT J
AU Law, AJ
AF Law, Amanda J.
TI COMMON GENETIC VARIATION IN NEUREGULIN 3 (NRG3) REGULATES NRG3
EXPRESSION AND INFLUENCES RISK FOR SCHIZOPHRENIA
SO SCHIZOPHRENIA BULLETIN
LA English
DT Meeting Abstract
CT 13th International Congress on Schizophrenia Research (ICSR)
CY APR 02-06, 2011
CL Colorado Springs, CO
C1 [Law, Amanda J.] NIMH, Clin Brain Disorders, NIH, Bethesda, MD 20892 USA.
RI Law, Amanda/G-6372-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD MAR
PY 2011
VL 37
SU 1
BP 192
EP 193
PG 2
WC Psychiatry
SC Psychiatry
GA 726SI
UT WOS:000287746000542
ER
PT J
AU Cole, V
Apud, JA
Weinberger, DR
Dickinson, D
AF Cole, Veronica
Apud, J. A.
Weinberger, D. R.
Dickinson, D.
TI SUBTYPING SCHIZOPHRENIA PATIENTS BASED ON DEVELOPMENTAL TRAJECTORY:
RELATIONSHIP TO MEASURES OF COGNITION, SYMPTOMS AND FUNCTIONING AFTER
ILLNESS ONSET
SO SCHIZOPHRENIA BULLETIN
LA English
DT Meeting Abstract
CT 13th International Congress on Schizophrenia Research (ICSR)
CY APR 02-06, 2011
CL Colorado Springs, CO
C1 [Cole, Veronica; Apud, J. A.; Weinberger, D. R.; Dickinson, D.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD MAR
PY 2011
VL 37
SU 1
BP 262
EP 262
PG 1
WC Psychiatry
SC Psychiatry
GA 726SI
UT WOS:000287746000743
ER
PT J
AU Hong, LE
Schroeder, M
Ross, TJ
Buchholz, B
Salmeron, BJ
Wonodi, I
Thaker, GK
Stein, EA
AF Hong, L. Elliot
Schroeder, Matthew
Ross, Thomas J.
Buchholz, Brittany
Salmeron, Betty Jo
Wonodi, Ikwunga
Thaker, Gunvant K.
Stein, Elliot A.
TI Nicotine Enhances but Does Not Normalize Visual Sustained Attention and
the Associated Brain Network in Schizophrenia
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE cognition; smoking; cigarette; fMRI; self-medication; RVIP
ID INFORMATION-PROCESSING PERFORMANCE; CIGARETTE-SMOKING; WORKING-MEMORY;
COGNITIVE FUNCTION; NASAL SPRAY; TRANSDERMAL NICOTINE; BASAL FOREBRAIN;
MECHANISMS; SYSTEM; MOOD
AB Sustained attention abnormality in schizophrenia is usually refractory to available treatment. Nicotine can transiently improve sustained attention in schizophrenia patients, although its neural mechanisms are unknown. Understanding the neural basis of this effect may lead to new treatment strategies for this cognitive deficit. Twenty schizophrenia patients and 24 healthy comparison smokers participated in a double-blind, placebo-controlled, crossover, randomized functional magnetic resonance imaging study comparing nicotine vs placebo patch on sustained attention, using the rapid visual information-processing task. Schizophrenia patients had impaired visual sustained attention accuracy and processing speed (all P's <.001) and showed significantly reduced activation in the frontal-parietal-cingulate-thalamic attention network compared with healthy comparison subjects. Nicotine administration enhanced accuracy and processing speed compared with placebo (all P's <.006), with no drug x diagnosis interactions. However, schizophrenia patients' task performance remained impaired during the nicotine condition, even when compared with healthy comparison subjects in the placebo condition (all P's <.01). Nicotine exerted no significant reversal of the impaired attention network associated with schizophrenia. Activations in brain regions associated with nicotine-induced behavioral improvement were not significantly different between patients and comparison subjects. Thus, nicotine transiently enhanced sustained attention similarly in schizophrenia patients and in healthy comparison smokers. The neural mechanisms for this nicotinic effect in schizophrenia appear similar to those for healthy comparison subjects. However, nicotine, at least in a single sustained dose, does not normalize impaired sustained attention and its associated brain network in schizophrenia. These findings provide guidance for developing new treatment strategies for the sustained attention deficit in schizophrenia.
C1 [Hong, L. Elliot; Buchholz, Brittany; Wonodi, Ikwunga; Thaker, Gunvant K.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA.
[Schroeder, Matthew; Ross, Thomas J.; Salmeron, Betty Jo; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD USA.
RP Hong, LE (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, POB 21247, Baltimore, MD 21228 USA.
EM ehong@mprc.umaryland.edu
RI Ross, Thomas/B-7469-2008; Salmeron, Betty Jo/M-1793-2016;
OI Ross, Thomas/0000-0002-7745-3572; Salmeron, Betty
Jo/0000-0003-1699-9333; Schroeder, Matthew/0000-0003-3942-9835
FU National Institute on Health [MH70644, 79172, 49826, 77852, 68580,
N01-DA-5-9909]; National Institute on Drug Abuse; Neurophysiology Core
of the University of Maryland General Clinical Research Center
[M01-RR16500]; Maryland Cigarette Restitution Fund Program
FX National Institute on Health (MH70644, 79172, 49826, 77852, 68580,
N01-DA-5-9909); the National Institute on Drug Abuse Intramural Research
Program; Neurophysiology Core of the University of Maryland General
Clinical Research Center (M01-RR16500); the Maryland Cigarette
Restitution Fund Program-Other Tobacco-Related Diseases Research Grant.
NR 47
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U1 2
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD MAR
PY 2011
VL 37
IS 2
BP 416
EP 425
DI 10.1093/schbul/sbp089
PG 10
WC Psychiatry
SC Psychiatry
GA 726SB
UT WOS:000287745300026
PM 19713300
ER
PT J
AU Kern, RS
Gold, JM
Dickinson, D
Green, MF
Nuechterlein, KH
Baade, LE
Keefe, RSE
Mesholam-Gately, RI
Seidman, LJ
Lee, C
Sugar, CA
Marder, SR
AF Kern, Robert S.
Gold, James M.
Dickinson, Dwight
Green, Michael F.
Nuechterlein, Keith H.
Baade, Lyle E.
Keefe, Richard S. E.
Mesholam-Gately, Raquelle I.
Seidman, Larry J.
Lee, Cathy
Sugar, Catherine A.
Marder, Stephen R.
TI The MCCB impairment profile for schizophrenia outpatients: Results from
the MATRICS psychometric and standardization study
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE MCCB; Cognition; Schizophrenia; Profile
ID CONSENSUS COGNITIVE BATTERY; WORK PERFORMANCE; MEMORY; REHABILITATION;
NEUROCOGNITION; IDENTIFICATION; METAANALYSIS; 1ST-EPISODE; PREDICTORS
AB The MATRICS Psychometric and Standardization Study was conducted as a final stage in the development of the MATRICS Consensus Cognitive Battery (MCCB). The study included 176 persons with schizophrenia or schizoaffective disorder and 300 community residents. Data were analyzed to examine the cognitive profile of clinically stable schizophrenia patients on the MCCB. Secondarily, the data were analyzed to identify which combination of cognitive domains and corresponding cut-off scores best discriminated patients from community residents, and patients competitively employed vs. those not. Raw scores on the ten MCCB tests were entered into the MCCB scoring program which provided age- and gender-corrected T-scores on seven cognitive domains. To test for between-group differences, we conducted a 2 (group) x 7 (cognitive domain) MANOVA with follow-up independent t-tests on the individual domains. Classification and regression trees (CART) were used for the discrimination analyses. Examination of patient T-scores across the seven cognitive domains revealed a relatively compact profile with T-scores ranging from 33.4 for speed of processing to 39.3 for reasoning and problem-solving. Speed of processing and social cognition best distinguished individuals with schizophrenia from community residents: speed of processing along with visual leaming and attention/vigilance optimally distinguished patients competitively employed from those who were not. The cognitive profile findings provide a standard to which future studies can compare results from other schizophrenia samples and related disorders; the classification results point to specific areas and levels of cognitive impairment that may advance work rehabilitation efforts. Published by Elsevier B.V.
C1 [Kern, Robert S.; Green, Michael F.; Nuechterlein, Keith H.; Sugar, Catherine A.; Marder, Stephen R.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Kern, Robert S.; Green, Michael F.; Marder, Stephen R.] VISN 22 Mental Illness Res, Dept Vet Affairs, Los Angeles, CA USA.
[Kern, Robert S.; Green, Michael F.; Marder, Stephen R.] Ctr Clin, Los Angeles, CA USA.
[Gold, James M.] Univ Maryland Baltimore, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD USA.
[Dickinson, Dwight] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Baade, Lyle E.] Univ Kansas, Sch Med, Wichita, KS 67214 USA.
[Keefe, Richard S. E.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA.
[Mesholam-Gately, Raquelle I.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat,Publ Psychiat Div, Beth Israel Deaconess Med Ctr,Massachusetts Menta, Boston, MA 02115 USA.
[Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lee, Cathy; Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Ctr, MIRECC 210 A,Bldg 210,Room 116,11301 Wilshire Blv, Los Angeles, CA 90073 USA.
EM rkern@ucla.edu
FU National Institute for Mental Health [N01MH22006]
FX Funding for the MATRICS Initiative was provided through Contract
N01MH22006 from the National Institute for Mental Health to the
University of California, Los Angeles (Dr. Marder, PI; Dr. Green, Co-PI;
Dr. Fenton, Project Officer). Funding for this study came from an Option
(Dr. Green, PI; Dr. Nuechterlein, Co-PI) to the NIMH MATRICS Initiative.
The NIMH 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 29
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U1 5
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAR
PY 2011
VL 126
IS 1-3
BP 124
EP 131
DI 10.1016/j.schres.2010.11.008
PG 8
WC Psychiatry
SC Psychiatry
GA 743NS
UT WOS:000289025700018
PM 21159492
ER
PT J
AU Wisner, KM
Elvevag, B
Gold, JM
Weinberger, DR
Dickinson, D
AF Wisner, Krista M.
Elvevag, Brita
Gold, James M.
Weinberger, Daniel R.
Dickinson, Dwight
TI A closer look at siblings of patients with schizophrenia: The
association of depression history and sex with cognitive phenotypes
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Cognitive phenotypes; Siblings; Psychiatric history;
Depression; Sex
ID NEUROPSYCHOLOGICAL RISK INDICATORS; CATECHOL-O-METHYLTRANSFERASE;
GENDER-DIFFERENCES; MAJOR DEPRESSION; 1ST-DEGREE RELATIVES;
AFFECTIVE-DISORDERS; WORKING-MEMORY; DEFICITS; PERFORMANCE; DISCORDANT
AB Background: Siblings of patients with schizophrenia show impaired cognition and an increased prevalence of depression history. Although sex has been shown to moderate cognition in patients, this effect has not been examined in siblings. Here we elucidate how a history of depression and sex influences cognition in siblings unaffected by schizophrenia.
Methods: Unaffected siblings of patients with schizophrenia and unrelated healthy controls were evaluated neuropsychologically and completed structured clinical interviews. Participants with a depression history or no psychiatric history were selected for the sample. Cognitive performance of siblings (n = 366) and controls (n = 680) was first examined. Second, cognition of participants with a depression history and those without a psychiatric history was compared while additionally investigating the role of schizophrenia risk and sex.
Results: Relative to controls, siblings, with and without a psychiatric history, demonstrated significant (p <.05) cognitive deficits. Depression history impaired cognition in siblings, but not in controls: whereas sex affected cognition in both siblings and controls. In siblings alone, sex significantly interacted with depression history to influence cognition. This interaction revealed that in male - but not female - siblings a history of depression was associated with greater cognitive impairments.
Conclusion: A history of depression impairs cognition in siblings, but not in controls. Moreover, depression history interacts with sex and demonstrates that only cognition in male siblings is significantly and additionally compromised by a history of depression. This interaction may be an important consideration for future phenotype and genetic association studies. Published by Elsevier B.V.
C1 [Wisner, Krista M.; Elvevag, Brita; Weinberger, Daniel R.; Dickinson, Dwight] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Gold, James M.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
RP Dickinson, D (reprint author), NIMH, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 7SE-5335, Bethesda, MD 20892 USA.
EM Dwight.Dickinson@nih.gov
FU National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 44
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAR
PY 2011
VL 126
IS 1-3
BP 164
EP 173
DI 10.1016/j.schres.2010.09.011
PG 10
WC Psychiatry
SC Psychiatry
GA 743NS
UT WOS:000289025700023
PM 21030214
ER
PT J
AU Pesce, JE
Kpaduwa, CS
Danis, M
AF Pesce, Julianna E.
Kpaduwa, Chinwe S.
Danis, Marion
TI Deliberation to enhance awareness of and prioritize socioeconomic
interventions for health
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE USA; Public participation; Interventions; Health priorities; Health
status disparities; Public assistance; Poverty; Resource allocation
ID INCOME; DETERMINANTS; CARE; DISPARITIES; INSECURITY; COUNTRIES; PUBLICS;
DESIGN
AB Health disparities are, to a large extent, the result of socio-economic factors that cannot be entirely mitigated through the health care system. While an array of social services are thought to be necessary to address the social determinants of health, budget constraints, particularly in difficult economic times, limit the availability of such services. It is therefore necessary to prioritize interventions through some fair process. While it might be appropriate to engage in public deliberation to set priorities, doing so requires that the public accept such a deliberative process and appreciate the social determinants of health. We therefore analyzed the results of a study in which groups deliberated to prioritize socio-economic interventions to examine whether these two requirements can possibly be met and to explore the basis for their priorities. A total of 431 residents of Washington, D.C. with incomes under 200% of the federal poverty threshold participated in 43 groups to engage in a hypothetical exercise to prioritize interventions designed to ameliorate the social determinants of health within the constraints of a limited budget. Findings from pre- and post-exercise questionnaires demonstrate that the priority setting exercise was perceived as a fair deliberative process, and that following the deliberation, participants became more likely to agree that a broad number of determinants contribute to their health. Qualitative analysis of the group discussions indicate that participants prioritized interventions that would provide for basic necessities and improve community conditions, while at the same time addressing more macro-structural factors such as homelessness and unemployment. We conclude that engaging small groups in deliberation about ways to address the social determinants of health can both change participant attitudes and yield informed priorities that might guide public policy aimed at most affordably reducing health disparities. Published by Elsevier Ltd.
C1 [Pesce, Julianna E.; Kpaduwa, Chinwe S.; Danis, Marion] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA.
RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118,10 Ctr Dr,MSC 1156, Bethesda, MD 20892 USA.
EM jpesce@mednet.ucla.edu; kpaduwa@post.harvard.edu; mdanis@nih.gov
FU National Center for Minority Health and Health Disparities; Dept. of
Bioethics at the National Institutes of Health
FX The study was funded by the National Center for Minority Health and
Health Disparities and the Dept. of Bioethics at the National Institutes
of Health. We thank our colleagues who collaborated in conducting the
"Choosing Healthful Interventions Study": Namrata Kotwani, Pamela
Carter-Nolan, Ph,D, John Davies-Cole, Ph.D., and Ivonne Rivera, MPH. We
also thank Joanne Garrett, Ph.D for assistance with the statistical
analysis: Sara Hull, Ph.D. for guidance wilt the qualitative analysis
and thoughtful review of the manuscript; and Bob Goodin, D.Phil for
thoughtful review of the manuscript.
NR 45
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U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD MAR
PY 2011
VL 72
IS 5
BP 789
EP 797
DI 10.1016/j.socscimed.2011.01.002
PG 9
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 755FC
UT WOS:000289911600020
PM 21316832
ER
PT J
AU McIntyre, L
Rondeau, K
Kirkpatrick, S
Hatfield, J
Islam, KS
Huda, SN
AF McIntyre, Lynn
Rondeau, Krista
Kirkpatrick, Sharon
Hatfield, Jennifer
Islam, Khaled Shamsul
Huda, Syed Nazmul
TI Food provisioning experiences of ultra poor female heads of household
living in Bangladesh
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE Bangladesh; Food provisioning; Food insecurity; Women; Head of
household; Ultra poor; Millennium development goals; Whole person
development; Poverty
ID QUALITATIVE CONTENT-ANALYSIS; RURAL BANGLADESH; INSECURITY; STRATEGIES;
IMPACT
AB Ultra poor women in Bangladesh are especially vulnerable to poverty and food insecurity, and they have generally been excluded from recent improvements in hunger and poverty rates in the country. An examination of the food provisioning narratives of 43 ultra poor female heads of household in Bangladesh was conducted in order to deepen understanding of this obstacle to the country's achievement of the First Millennium Development Goal. All participants were the household's sole income provider, had dependent children, and earned less than $1 USD per day. Women were purposively selected based on occupational group, context, and personal characteristics. Ethnographic interviews were conducted in January and February, 2008. Analysis of women's accounts of their daily food routine revealed chronic and pervasive food insecurity punctuated by acute episodes of absolute food deprivation that resulted from seasonal fluctuations in earnings, rising food prices, illness disrupting work, and healthcare costs. Women's accounts of their daily food provisioning experiences suggested compromises in, and trade-offs between, multiple basic needs as a result of inadequate income. Women were further constrained by social norms and gender roles that influenced their ability to work outside the home. Our method of inquiry led us to construct an organizing framework that extends knowledge of ultra poor women in Bangladesh's complex and multi-sphered experience of poverty and food insecurity. Based on these findings, we propose a strategy called whole person development (WPD), which seeks small adjustments to services, programs, and policies based on leverage points identified through in-depth narratives. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [McIntyre, Lynn; Rondeau, Krista; Hatfield, Jennifer] Univ Calgary, Fac Med, Dept Community Hlth Sci, Calgary, AB, Canada.
[Kirkpatrick, Sharon] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Islam, Khaled Shamsul] Bangladesh Secretariat, Minist Hlth & Family Welf, Dhaka, Bangladesh.
[Huda, Syed Nazmul] Univ Dhaka, Inst Nutr & Food Sci, Dhaka 1000, Bangladesh.
RP McIntyre, L (reprint author), Univ Calgary, Fac Med, Dept Community Hlth Sci, 3E43 TRW Bldg,3280 Hosp Dr NW, Calgary, AB, Canada.
EM lmcintyr@ucalgary.ca
OI Kirkpatrick, Sharon/0000-0001-9896-5975
FU Canadian Institutes of Health Research (CIHR)
FX We would like to acknowledge Sanjeeb Drong, Kaosar Afsana (BRAC), Jenny
Munro, Barbara Parker, Tahera Yasmin, the transcriptionists and
translators, the women, and others too many to mention who assisted in
the project. Funding for this study was provided by the Canadian
Institutes of Health Research (CIHR) Seed Grant in Globalization and
Health and the CIHR Global Health and Knowledge Exchange Planning,
Dissemination and Meetings Grant.
NR 52
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD MAR
PY 2011
VL 72
IS 6
BP 969
EP 976
DI 10.1016/j.socscimed.2011.01.011
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 757JA
UT WOS:000290080100020
PM 21345564
ER
PT J
AU Shoreibah, MG
Jackson, CL
Price, PW
Meagher, R
Godwin, AK
Cai, Q
Gildersleeve, JC
AF Shoreibah, Mohamed G.
Jackson, Crystal L.
Price, Paul W.
Meagher, Richard
Godwin, Andrew K.
Cai, Qi
Gildersleeve, Jeffrey C.
TI Anti-Human Embryonic Stem Cell Monoclonal Antibody Hesca-2 Binds to a
Glycan Epitope Commonly Found on Carcinomas
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID LACTO-N-HEXAOSE; HUMAN-MILK; SERUM ANTIBODIES; CANCER; GALECTIN-1;
EXPRESSION; OLIGOSACCHARIDES; DIFFERENTIATION; MICROARRAYS; MARKER
AB Hesca-2, a monoclonal antibody (mAb) IgM raised to the human embryonic stem cell (hESC) line BG-01v, binds with high affinity (nM) to the disaccharide epitope (Gal beta 1-3GlcNAc) on a glycan microarray. This epitope was expressed on pluripotent progenitor hESCs in culture, but not in various differentiated cells derived from hESC based on immunofluorescence microscopy. Hesca-2 stains a limited subset of cells in adult human tissues (eg, esophagus and breast). This mAb also crossreacts in immunofluorescence microscopy studies with several human ovarian cancer cell lines and is cytotoxic to them based on the release of cytosolic enzyme lactate dehydrogenase into the media. Hesca-2 immunohistochemically stained tissue from a number of human tumors, including ovary, breast, colon, and esophageal cancer. These data suggest that Hesca-2 recognizes a surface marker found both in stem cells and certain cancer cells.
C1 [Shoreibah, Mohamed G.; Jackson, Crystal L.; Price, Paul W.] Abeome Corp, Athens, GA USA.
[Meagher, Richard] Univ Georgia, Dept Genet, Athens, GA 30602 USA.
[Godwin, Andrew K.; Cai, Qi] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Gildersleeve, Jeffrey C.] NCI, Frederick, MD 21701 USA.
RP Shoreibah, MG (reprint author), Abeome Corp, 111 Riverbend Rd, Athens, GA USA.
EM mohamed.shoreibah@abeomecorp.com
RI Gildersleeve, Jeffrey/N-3392-2014
FU NIH, NCI
FX This research was supported in part by the Intramural Research Program
of the NIH, NCI. The authors would like to thank Dr. Thomas Schulz of
ViaCyte for his assistance in developing and characterizing Hesca-2.
NR 58
TC 3
Z9 3
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1547-3287
J9 STEM CELLS DEV
JI Stem Cells Dev.
PD MAR
PY 2011
VL 20
IS 3
BP 515
EP 525
DI 10.1089/scd.2010.0172
PG 11
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA 727KP
UT WOS:000287798300014
PM 20887211
ER
PT J
AU Toth, ZE
Leker, RR
Shahar, T
Bratincsak, A
Szalayova, I
Key, S
Miklos, P
Cassiani-Ingoni, R
Mezey, E
AF Toth, Zsuzsanna E.
Leker, Ronen R.
Shahar, Tal
Bratincsak, Andras
Szalayova, Ildiko
Key, Sharon
Miklos Palkovits
Cassiani-Ingoni, Riccardo
Mezey, Eva
TI Bone Marrow-Derived Nonreactive Astrocytes in the Mouse Brain After
Permanent Middle Cerebral Artery Occlusion
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID GROWTH-FACTOR-ALPHA; TYRAMIDE SIGNAL AMPLIFICATION; REDUCES INFARCT
VOLUME; CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; STROMAL CELLS; ADULT
MICE; NEUROLOGICAL DISEASES; THERAPEUTIC BENEFIT; IN-VIVO
AB We studied the effect of permanent unilateral middle cerebral artery occlusion (PMCAO) on the generation of bone marrow (BM)-derived astrocytes in female mice previously transplanted with enchanced green fluorescent protein-expressing BM from male donors. In addition to an untreated PMCAO group, one group of mice also received intracerebral infusion of transforming growth factor-alpha, resulting in a decrease in the size of the infarct. Two months after PMCAO, we found a specific type of astrocyte of BM origin in the side of the injury, near the lesion. These astrocytes did not express glial fibrillary acidic protein (GFAP) by conventional fluorescence immunostaining; however, GFAP was easily detectable by tyramide signal amplification. These cells also expressed S100 beta, confirming their astrocytic character. Unlike the endogenous reactive astrocytes, these BM-derived astrocytes did not proliferate during the first week of ischemia and did not contribute to the glial scar formation. Transforming growth factor-alpha infusion increased the number of BM-derived astrocytes, without affecting their distribution. Interestingly, exclusively by tyramide signal amplification staining, we found that endogenous astrocytes displaying an identical morphology were also present in control mouse and human brains. Our data demonstrate that a subpopulation of nonreactive astrocytes expressing low levels of GFAP can originate from transplanted BM in the ischemic brain. We believe that these cells represent a subpopulation of astrocytes earlier considered to be GFAP negative. The high number of astrocytes with identical morphology and chemical character in control brains suggest that these type of astrocytes may have important functional role in the central nervous system that calls for further studies.
C1 [Toth, Zsuzsanna E.; Szalayova, Ildiko; Key, Sharon; Mezey, Eva] NIMH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA.
[Toth, Zsuzsanna E.; Miklos Palkovits] Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, H-1085 Budapest, Hungary.
[Toth, Zsuzsanna E.; Miklos Palkovits] Hungarian Acad Sci, Budapest, Hungary.
[Leker, Ronen R.; Shahar, Tal; Cassiani-Ingoni, Riccardo] NINDS, Bethesda, MD 20892 USA.
RP Mezey, E (reprint author), NIMH, Natl Inst Dent & Craniofacial Res, Bldg 49,Convent Dr, Bethesda, MD 20892 USA.
EM mezeye@mail.nih.gov
OI Palkovits, Miklos/0000-0003-0578-0387
FU NIDCR; ETT [495/09]; European Grant FP6 BNEII [LSHM-CT-2004-503039];
Bolyai fellowship
FX The research was supported by the Division of Intramural Research
Program of NIDCR (E. Mezey), ETT 495/09 (Z.E. Toth), and by European
Grant FP6 BNEII No. LSHM-CT-2004-503039 (M. Palkovits). Z.E. Toth is
supported by the Bolyai fellowship.
NR 50
TC 2
Z9 2
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1547-3287
J9 STEM CELLS DEV
JI Stem Cells Dev.
PD MAR
PY 2011
VL 20
IS 3
BP 539
EP 546
DI 10.1089/scd.2010.0237
PG 8
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA 727KP
UT WOS:000287798300016
PM 20604679
ER
PT J
AU Sefcik, LS
Aronin, CEP
Awojoodu, AO
Shin, SJ
Mac Gabhann, F
MacDonald, TL
Wamhoff, BR
Lynch, KR
Peirce, SM
Botchwey, EA
AF Sefcik, Lauren S.
Aronin, Caren E. Petrie
Awojoodu, Anthony O.
Shin, Soo J.
Mac Gabhann, Feilim
MacDonald, Timothy L.
Wamhoff, Brian R.
Lynch, Kevin R.
Peirce, Shayn M.
Botchwey, Edward A.
TI Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3
Promotes Local Microvascular Network Growth
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID MUSCLE-CELL DIFFERENTIATION; G-PROTEIN; SPHINGOSINE-1-PHOSPHATE
RECEPTORS; MOLECULAR REGULATION; ENDOTHELIAL-CELLS; FTY720;
ANGIOGENESIS; MIGRATION; CAPILLARY; EDG-1
AB Proper spatial and temporal regulation of microvascular remodeling is critical to the formation of functional vascular networks, spanning the various arterial, venous, capillary, and collateral vessel systems. Recently, our group has demonstrated that sustained release of sphingosine 1-phosphate (S1P) from biodegradable polymers promotes microvascular network growth and arteriolar expansion. In this study, we employed S1P receptor-specific compounds to activate and antagonize different combinations of S1P receptors to elucidate those receptors most critical for promotion of pharmacologically induced microvascular network growth. We show that S1P(1) and S1P(3) receptors act synergistically to enhance functional network formation via increased functional length density, arteriolar diameter expansion, and increased vascular branching in the dorsal skinfold window chamber model. FTY720, a potent activator of S1P(1) and S1P(3), promoted a 107% and 153% increase in length density 3 and 7 days after implantation, respectively. It also increased arteriolar diameters by 60% and 85% 3 and 7 days after implantation. FTY720-stimulated branching in venules significantly more than unloaded poly(D, L-lactic-co-glycolic acid). When implanted on the mouse spinotrapezius muscle, FTY720 stimulated an arteriogenic response characterized by increased tortuosity and collateralization of branching microvascular networks. Our results demonstrate the effectiveness of S1P(1) and S1P(3) receptor-selective agonists (such as FTY720) in promoting microvascular growth for tissue engineering applications.
C1 [Awojoodu, Anthony O.; Shin, Soo J.; Peirce, Shayn M.; Botchwey, Edward A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA.
[Sefcik, Lauren S.] Lafayette Coll, Dept Chem & Biomol Engn, Easton, PA 18042 USA.
[Aronin, Caren E. Petrie] NIAID, NIH, Bethesda, MD 20892 USA.
[Mac Gabhann, Feilim] Johns Hopkins Univ, Inst Computat Med, Baltimore, MD USA.
[Mac Gabhann, Feilim] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.
[MacDonald, Timothy L.] Univ Virginia, Dept Chem, Charlottesville, VA 22908 USA.
[Wamhoff, Brian R.] Univ Virginia, Dept Cardiovasc Med, Charlottesville, VA 22908 USA.
[Wamhoff, Brian R.] Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA USA.
[Lynch, Kevin R.] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA.
[Botchwey, Edward A.] Univ Virginia, Dept Orthopaed Surg, Charlottesville, VA 22908 USA.
[Botchwey, Edward A.] Univ Virginia, Ctr Immun Inflammat & Regenerat Med, Charlottesville, VA 22908 USA.
RP Botchwey, EA (reprint author), Univ Virginia, Dept Biomed Engn, POB 800759, Charlottesville, VA 22908 USA.
EM botchwey@virginia.edu
RI Mac Gabhann, Feilim/A-3436-2010
OI Mac Gabhann, Feilim/0000-0003-3481-7740
FU National Institutes of Health [K01AR052352-01A1, R01AR056445-01A2,
R01DE019935-01, R01GM067958, T32GM008715]; National Science Foundation;
American Heart Association Mid-Atlantic Affiliate [0815211E]
FX Sources of support for this study include the National Institutes of
Health grants K01AR052352-01A1, R01AR056445-01A2, R01DE019935-01, and
R01GM067958 to Dr. Botchwey. Dr. Lauren Sefcik was supported by
predoctoral fellowships from the National Science Foundation and
American Heart Association Mid-Atlantic Affiliate 0815211E. Anthony
Awojoodu is supported by the National Institutes of Health Biotechnology
Training Program Training Grant T32GM008715.
NR 43
TC 24
Z9 24
U1 2
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD MAR
PY 2011
VL 17
IS 5-6
BP 617
EP 629
DI 10.1089/ten.tea.2010.0404
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 727LO
UT WOS:000287801600004
PM 20874260
ER
PT J
AU Hakkinen, KM
Harunaga, JS
Doyle, AD
Yamada, KM
AF Hakkinen, Kirsi M.
Harunaga, Jill S.
Doyle, Andrew D.
Yamada, Kenneth M.
TI Direct Comparisons of the Morphology, Migration, Cell Adhesions, and
Actin Cytoskeleton of Fibroblasts in Four Different Three-Dimensional
Extracellular Matrices
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; BASEMENT-MEMBRANES; COLLAGEN-MATRIX; FIBRONECTIN
FIBRILLOGENESIS; HUMAN KERATINOCYTES; FORCE GENERATION; GENE-EXPRESSION;
TUMOR-CELLS; IN-VIVO; 3D
AB Interactions between cells and the extracellular matrix are at the core of tissue engineering and biology. However, most studies of these interactions have used traditional two-dimensional (2D) tissue culture, which is less physiological than three-dimensional (3D) tissue culture. In this study, we compared cell behavior in four types of commonly used extracellular matrix under 2D and 3D conditions. Specifically, we quantified parameters of cell adhesion and migration by human foreskin fibroblasts in cell-derived matrix or hydrogels of collagen type I, fibrin, or basement membrane extract (BME). Fibroblasts in 3D were more spindle shaped with fewer lateral protrusions and substantially reduced actin stress fibers than on 2D matrices; cells failed to spread in 3D BME. Cell-matrix adhesion structures were detected in all matrices. Although the shapes of these cell adhesions differed, the total area per cell occupied by cell-matrix adhesions in 2D and 3D was nearly identical. Fibroblasts migrated most rapidly in cell-derived 3D matrix and collagen and migrated minimally in BME, with highest migration directionality in cell-derived matrix. This identification of quantitative differences in cellular responses to different matrix composition and dimensionality should help guide the development of customized 3D tissue culture and matrix scaffolds for tissue engineering.
C1 [Hakkinen, Kirsi M.; Harunaga, Jill S.; Doyle, Andrew D.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bldg 30,Room 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM kenneth.yamada@nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
FU HHMI-NIH; National Institute of Dental and Craniofacial Research,
National Institutes of Health
FX Dr. Marinilce Santos provided valuable advice and assistance with
time-lapse microscopy and collagen matrix production. The authors thank
Dr. Allison Berrier for numerous helpful discussions, Dr. Angelo Green
for generously providing the labeled beta1 integrin antibody,
and Kazue Matsumoto for support with the CDM and in many other aspects.
This work was supported by the HHMI-NIH Research Scholars Program and
the Intramural Research Program of the National Institute of Dental and
Craniofacial Research, National Institutes of Health.
NR 78
TC 110
Z9 111
U1 4
U2 30
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD MAR
PY 2011
VL 17
IS 5-6
BP 713
EP 724
DI 10.1089/ten.tea.2010.0273
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 727LO
UT WOS:000287801600012
PM 20929283
ER
PT J
AU Mahairaki, V
Lim, SH
Christopherson, GT
Xu, LY
Nasonkin, I
Yu, C
Mao, HQ
Koliatsos, VE
AF Mahairaki, Vasiliki
Lim, Shawn H.
Christopherson, Gregory T.
Xu, Leyan
Nasonkin, Igor
Yu, Christopher
Mao, Hai-Quan
Koliatsos, Vassilis E.
TI Nanofiber Matrices Promote the Neuronal Differentiation of Human
Embryonic Stem Cell-Derived Neural Precursors In Vitro
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID ELECTROSPUN NANOFIBERS; SPINAL-CORD; POLYMER NANOFIBERS; FIBER DIAMETER;
MOTOR-NEURONS; SCAFFOLDS; GUIDANCE; PROLIFERATION; MIGRATION; ALIGNMENT
AB The potential of human embryonic stem (ES) cells as experimental therapies for neuronal replacement has recently received considerable attention. In view of the organization of the mature nervous system into distinct neural circuits, key challenges of such therapies are the directed differentiation of human ES cell-derived neural precursors (NPs) into specific neuronal types and the directional growth of axons along specified trajectories. In the present study, we cultured human NPs derived from the NIH-approved ES line BGO1 on polycaprolactone fiber matrices of different diameter (i.e., nanofibers and microfibers) and orientation (i.e., aligned and random); fibers were coated with poly-L-ornithine/ laminin to mimic the extracellular matrix and support the adhesion, viability, and differentiation of NPs. On aligned fibrous meshes, human NPs adopt polarized cell morphology with processes extending along the axis of the fiber, whereas NPs on plain tissue culture surfaces or randomfiber substrates form nonpolarized neurite networks. Under differentiation conditions, human NPs cultured on aligned fibrous substrates show a higher rate of neuronal differentiation than other matrices; 62% and 86% of NPs become TUJ1 (+) early neurons on aligned micro-and nanofibers, respectively, whereas only 32% and 27% of NPs acquire the same fate on random micro-and nanofibers. Metabolic cell activity/viability studies reveal that fiber alignment and diameter also have an effect on NP viability, but only in the presence of mitogens. Our findings demonstrate that fibrous substrates serve as an artificial extracellular matrix and provide a microenviroment that influences key aspects of the neuronal differentiation of ES-derived NPs.
C1 [Mahairaki, Vasiliki; Xu, Leyan; Nasonkin, Igor; Koliatsos, Vassilis E.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA.
[Lim, Shawn H.; Yu, Christopher; Mao, Hai-Quan] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA.
[Christopherson, Gregory T.; Mao, Hai-Quan] Johns Hopkins Univ, Whitaker Biomed Engn Inst, Dept Mat Sci & Engn, Baltimore, MD 21205 USA.
[Nasonkin, Igor] NEI, NIH, N NRL, Bethesda, MD 20892 USA.
[Koliatsos, Vassilis E.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Koliatsos, Vassilis E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
RP Mahairaki, V (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, 720 Rutland Ave, Baltimore, MD 21205 USA.
EM vmachai1@jhmi.edu
FU National Institutes of Health [NS45140]; Muscular Dystrophy Association;
Maryland Stem Cell Research Fund Postdoctoral Fellowship
FX This work was supported by grants from the National Institutes of Health
(NS45140, V. E. K.) and the Muscular Dystrophy Association (V. E. K.).
V. M. is a recipient of the Maryland Stem Cell Research Fund
Postdoctoral Fellowship.
NR 50
TC 38
Z9 40
U1 1
U2 15
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD MAR
PY 2011
VL 17
IS 5-6
BP 855
EP 863
DI 10.1089/ten.tea.2010.0377
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 727LO
UT WOS:000287801600024
PM 20973749
ER
PT J
AU Hannas, BR
Furr, J
Lambright, CS
Wilson, VS
Foster, PMD
Gray, LE
AF Hannas, Bethany R.
Furr, Johnathan
Lambright, Christy S.
Wilson, Vickie S.
Foster, Paul M. D.
Gray, L. Earl, Jr.
TI Dipentyl Phthalate Dosing during Sexual Differentiation Disrupts Fetal
Testis Function and Postnatal Development of the Male Sprague-Dawley Rat
with Greater Relative Potency than Other Phthalates
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE antiandrogen; risk assessment; fetal male rat endocrine; dipentyl
phthalate
ID IN-UTERO EXPOSURE; N-BUTYL PHTHALATE; MALE REPRODUCTIVE DEVELOPMENT;
DOSE-DEPENDENT ALTERATIONS; NORMAL-PENTYL PHTHALATE; DI(N-BUTYL)
PHTHALATE; GENE-EXPRESSION; DIETHYLHEXYL PHTHALATE; BENZYL PHTHALATE;
TESTOSTERONE SYNTHESIS
AB Phthalate esters (PEs) constitute a large class of plasticizer compounds that are widely used for many consumer product applications. Ten or more members of the PE class of compounds are known to induce male fetal endocrine toxicity and postnatal reproductive malformations by disrupting androgen production during the sexual differentiation period of development. An early study conducted in the rat pubertal model suggested that dipentyl phthalate (DPeP) may be a more potent testicular toxicant than some more extensively studied phthalates. Regulatory agencies require dose-response and potency data to facilitate risk assessment; however, very little data are currently available for DPeP. The goal of this study was to establish a more comprehensive data set for DPeP, focusing on dose-response and potency information for fetal and postnatal male reproductive endpoints. We dosed pregnant rats on gestational day (GD) 17 or GD 14-18 and subsequently evaluated fetal testicular testosterone (T) production on GD 17.5 and GD 18, respectively. We also dosed pregnant rats on GD 8-18 and evaluated early postnatal endpoints in male offspring. Comparison of these data to data previously obtained under similar conditions for di (2-ethylhexyl) phthalate indicates that DPeP is approximately eightfold more potent in reducing fetal T production and two- to threefold more potent in inducing development of early postnatal male reproductive malformations. Additionally, fetal testicular T production was more sensitive to inhibitory effects of DPeP exposure than was gene expression of target genes involved in male reproductive development, supporting the use of this endpoint as a critical effect in the risk assessment process.
C1 [Hannas, Bethany R.] US EPA, Natl Res Council Fellowship Program, Res Triangle Pk, NC 27711 USA.
[Furr, Johnathan; Lambright, Christy S.; Wilson, Vickie S.; Gray, L. Earl, Jr.] US EPA, Reprod Toxicol Branch, Toxicol Assessment Div, Natl Hlth & Environm Effects Lab,Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Foster, Paul M. D.] NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Gray, LE (reprint author), US EPA, Natl Hlth & Environm Effects Lab, Reprod Toxicol Div, MD-72, Res Triangle Pk, NC 27711 USA.
EM gray.earl@epa.gov
OI Wilson, Vickie/0000-0003-1661-8481
FU National Institute of Environmental Health Sciences; U.S. Environmental
Protection Agency [RW-75-92285501-1]; National Research Council at the
U.S. Environmental Protection Agency National Health and Environmental
Effects Laboratory; National Institute of Environmental Health Sciences,
National Institutes of Health
FX National Toxicology Program at the National Institute of Environmental
Health Sciences Interagency Agreement with the U.S. Environmental
Protection Agency, Cooperative Agreement (#RW-75-92285501-1); National
Research Council Research Associateship Award at the U.S. Environmental
Protection Agency National Health and Environmental Effects Laboratory
to B.R.H.; The research described in this article has been reviewed by
the U.S. EPA and approved for publication. Approval does not signify
that the contents necessarily reflect the views and policies of the
Agency nor does mention of trade names or commercial products constitute
endorsement or recommendation for use. This research was supported in
part by the Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health. This
article may be the work product of an employee or group of employees of
the National Institute of Environmental Health Sciences (NIEHS) and
National Institutes of Health (NIH); however, the statements, opinions,
or conclusions contained therein do not necessarily represent the
statements, opinions, or conclusions of NIEHS, NIH, or the U.S.
government.
NR 40
TC 26
Z9 26
U1 1
U2 20
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAR
PY 2011
VL 120
IS 1
BP 184
EP 193
DI 10.1093/toxsci/kfq386
PG 10
WC Toxicology
SC Toxicology
GA 726SZ
UT WOS:000287747800017
PM 21177253
ER
PT J
AU Afshari, CA
Hamadeh, HK
Bushel, PR
AF Afshari, Cynthia A.
Hamadeh, Hisham K.
Bushel, Pierre R.
TI The Evolution of Bioinformatics in Toxicology: Advancing Toxicogenomics
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE toxicogenomics; informatics; genome; microarray; biomarker
ID GENE-EXPRESSION PROFILES; INDUCED LIVER-INJURY; BIOLOGICAL-SYSTEMS;
RAT-LIVER; NONGENOTOXIC CARCINOGENS; CDNA MICROARRAYS; NATIONAL-CENTER;
TIME-COURSE; TOXICITY; IDENTIFICATION
AB As one reflects back through the past 50 years of scientific research, a significant accomplishment was the advance into the genomic era. Basic research scientists have uncovered the genetic code and the foundation of the most fundamental building blocks for the molecular activity that supports biological structure and function. Accompanying these structural and functional discoveries is the advance of techniques and technologies to probe molecular events, in time, across environmental and chemical exposures, within individuals, and across species. The field of toxicology has kept pace with advances in molecular study, and the past 50 years recognizes significant growth and explosive understanding of the impact of the compounds and environment to basic cellular and molecular machinery. The advancement of molecular techniques applied in a whole-genomic capacity to the study of toxicant effects, toxicogenomics, is no doubt a significant milestone for toxicological research. Toxicogenomics has also provided an avenue for advancing a joining of multidisciplinary sciences including engineering and informatics in traditional toxicological research. This review will cover the evolution of the field of toxicogenomics in the context of informatics integration its current promise, and limitations.
C1 [Afshari, Cynthia A.; Hamadeh, Hisham K.] Amgen Inc, Dept Comparat Biol & Safety Sci, Thousand Oaks, CA 91320 USA.
[Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Afshari, CA (reprint author), Amgen Inc, Dept Comparat Biol & Safety Sci, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA.
EM cafshari@amgen.com
FU National Institutes of Health; National Institute of Environmental
Health Sciences [Z01 ES102345-04]
FX Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences (Z01 ES102345-04).
NR 77
TC 48
Z9 51
U1 1
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAR
PY 2011
VL 120
SU 1
BP S225
EP S237
DI 10.1093/toxsci/kfq373
PG 13
WC Toxicology
SC Toxicology
GA 726TF
UT WOS:000287748400013
PM 21177775
ER
PT J
AU Tokar, EJ
Qu, W
Waalkes, MP
AF Tokar, Erik J.
Qu, Wei
Waalkes, Michael P.
TI Arsenic, Stem Cells, and the Developmental Basis of Adult Cancer
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE arsenic; cancer; development; epigenetics; stem cells
ID INDUCED MALIGNANT-TRANSFORMATION; ACUTE MYELOID-LEUKEMIA;
DRINKING-WATER; IN-UTERO; DIMETHYLARSINIC ACID; DNA METHYLATION;
SKIN-CANCER; POSTNATAL DIETHYLSTILBESTROL; GESTATIONAL EXPOSURE;
PROSTATE-CANCER
AB That chemical insults or nutritive changes during in utero and/or postnatal life can emerge as diseases much later in life are now being accepted as a recurring phenomenon. In this regard, inorganic arsenic is a multisite human carcinogen found at high levels in the drinking water of millions of people, although it has been difficult until recently to produce tumors in rodents with this metalloid. A mouse transplacental model has been developed where maternal exposure to inorganic arsenic either acts as a complete carcinogen or enhances carcinogenic response to other agents given subsequently in the offspring, producing tumors during adulthood. Similarly, human data now have emerged showing that arsenic exposure during the in utero period and/or in early life is associated with cancer in adulthood. The mouse arsenic transplacental model produces tumors or enhances response to other agents in multiple strains and tissues, including sites concordant with human targets of arsenic carcinogenesis. It is now believed that cancer often is a stem cell (SC)-based disease, and there is no reason to think cancer induced by developmental chemical exposure is any different. Indeed, arsenic impacts human SC population dynamics in vitro by blocking exit into differentiation pathways and whereby creating more key targets for transformation. In fact, during in vitro malignant transformation, arsenic causes a remarkable survival selection of SCs, creating a marked overabundance of cancer SCs (CSCs) compared with other carcinogens once a cancer phenotype is obtained. In addition, skin cancers produced following in utero arsenic exposure in mice are highly enriched in CSCs. Thus, arsenic impacts key, long-lived SC populations as critical targets to cause or facilitate later oncogenic events in adulthood as a possible mechanism of developmental basis of adult disease.
C1 [Waalkes, Michael P.] NIEHS, NTP, Natl Toxicol Program Labs, Res Triangle Pk, NC 27709 USA.
RP Waalkes, MP (reprint author), NIEHS, NTP, Natl Toxicol Program Labs, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU National Institute of Environmental Health Sciences
FX National Toxicology Program, National Institute of Environmental Health
Sciences.
NR 95
TC 42
Z9 44
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAR
PY 2011
VL 120
SU 1
BP S192
EP S203
DI 10.1093/toxsci/kfq342
PG 12
WC Toxicology
SC Toxicology
GA 726TF
UT WOS:000287748400011
PM 21071725
ER
PT J
AU Ruthel, G
Burnett, JC
Nuss, JE
Wanner, LM
Tressler, LE
Torres-Melendez, E
Sandwick, SJ
Retterer, CJ
Bavari, S
AF Ruthel, Gordon
Burnett, James C.
Nuss, Jonathan E.
Wanner, Laura M.
Tressler, Lyal E.
Torres-Melendez, Edna
Sandwick, Sarah J.
Retterer, Cary J.
Bavari, Sina
TI Post-Intoxication Inhibition of Botulinum Neurotoxin Serotype A within
Neurons by Small-Molecule, Non-Peptidic Inhibitors
SO TOXINS
LA English
DT Article
DE botulinum neurotoxin; small molecule non-peptidic inhibitor;
neutralizing antibody; Bafilomycin A1
ID TOXIN; IDENTIFICATION; EXOCYTOSIS
AB Botulinum neurotoxins (BoNTs) comprise seven distinct serotypes that inhibit the release of neurotransmitter across neuromuscular junctions, resulting in potentially fatal flaccid paralysis. BoNT serotype A (BoNT/A), which targets synaptosomal-associated protein of 25kDa (SNAP-25), is particularly long-lived within neurons and requires a longer time for recovery of neuromuscular function. There are currently no treatments available to counteract BoNT/A after it has entered the neuronal cytosol. In this study, we examined the ability of small molecule non-peptidic inhibitors (SMNPIs) to prevent SNAP-25 cleavage post-intoxication of neurons. The progressive cleavage of SNAP-25 observed over 5 h following 1 h BoNT/A intoxication was prevented by addition of SMNPIs. In contrast, anti-BoNT/A neutralizing antibodies that strongly inhibited SNAP-25 cleavage when added during intoxication were completely ineffective when added post-intoxication. Although Bafilomycin A1, which blocks entry of BoNT/A into the cytosol by preventing endosomal acidification, inhibited SNAP-25 cleavage post-intoxication, the degree of inhibition was significantly reduced versus addition both during and after intoxication. Post-intoxication application of SMNPIs, on the other hand, was nearly as effective as application both during and after intoxication. Taken together, the results indicate that competitive SMNPIs of BoNT/A light chain can be effective within neurons post-intoxication.
C1 [Ruthel, Gordon; Nuss, Jonathan E.; Wanner, Laura M.; Tressler, Lyal E.; Torres-Melendez, Edna; Sandwick, Sarah J.; Retterer, Cary J.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Burnett, James C.] NCI, SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA.
RP Ruthel, G (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Frederick, MD 21702 USA.
EM gordon.ruthel@amedd.army.mil; burnettjames@mail.nih.gov;
jonathan.nuss@amedd.army.mil; laura.wanner@amedd.army.mil;
lyal.tressler@amedd.army.mil; edna.torres-melendez@amedd.army.mil;
sarah.sandwick@uni-wuerzburg.de; cary.retterer@amedd.army.mil;
sina.bavari@amedd.army.mil
FU Joint Science and Technology Office, Defense Threat Reduction Agency
[3.10084_09_RD_B]; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This research was funded by the Joint Science and Technology Office,
Defense Threat Reduction Agency (Project 3.10084_09_RD_B). Opinions,
interpretations, conclusions, and recommendations are those of the
authors and are not necessarily endorsed by the U.S. Army. Furthermore,
for JCB, in compliance with SAIC-Frederick, Inc. contractual
requirements: this project has been funded 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 or
the U.S. Army.
NR 17
TC 14
Z9 14
U1 0
U2 2
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD MAR
PY 2011
VL 3
IS 3
BP 207
EP 217
DI 10.3390/toxins3030207
PG 11
WC Toxicology
SC Toxicology
GA 994ZP
UT WOS:000307975400005
PM 22069707
ER
PT J
AU Tang, SX
Zhao, JQ
Viswanath, R
Nyambi, PN
Redd, AD
Dastyar, A
Spacek, LA
Quinn, TC
Wang, X
Wood, O
Gaddam, D
Devadas, K
Hewlett, IK
AF Tang, Shixing
Zhao, Jiangqin
Viswanath, Ragupathy
Nyambi, Phillipe N.
Redd, Andrew D.
Dastyar, Armeta
Spacek, Lisa A.
Quinn, Thomas C.
Wang, Xue
Wood, Owen
Gaddam, Durga
Devadas, Krishnakumar
Hewlett, Indira K.
TI Absence of detectable xenotropic murine leukemia virus-related virus in
plasma or peripheral blood mononuclear cells of human immunodeficiency
virus Type 1-infected blood donors or individuals in Africa
SO TRANSFUSION
LA English
DT Article
ID CHRONIC-FATIGUE-SYNDROME; HUMAN RETROVIRUS XMRV; PROSTATE-CANCER
AB BACKGROUND: Since the identification of xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer patients in 2006 and in chronic fatigue syndrome patients in 2009, conflicting findings have been reported regarding its etiologic role in human diseases and prevalence in general populations. In this study, we screened both plasma and peripheral blood mononuclear cells (PBMNCs) collected in Africa from blood donors and human immunodeficiency virus Type 1 (HIV-1)-infected individuals to gain evidence of XMRV infection in this geographic region.
STUDY DESIGN AND METHODS: A total of 199 plasma samples, 19 PBMNC samples, and 50 culture supernatants from PBMNCs of blood donors from Cameroon found to be infected with HIV-1 and HIV-1 patients from Uganda were screened for XMRV infection using a sensitive nested polymerase chain reaction (PCR) or reverse transcription (RT)-PCR assay.
RESULTS: Using highly sensitive nested PCR or RT-PCR and real-time PCR assays capable of detecting at least 10 copies of XMRV plasmid DNA per reaction, none of the 268 samples tested were found to be XMRV DNA or RNA positive.
CONCLUSIONS: Our results failed to demonstrate the presence of XMRV infection in African blood donors or individuals infected with HIV-1. More studies are needed to understand the prevalence, epidemiology, and geographic distribution of XMRV infection worldwide.
C1 US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
NYU, Sch Med, Dept Pathol, New York, NY USA.
Johns Hopkins Univ, Sch Med, Div Intramural Res, NIAID,NIH, Baltimore, MD USA.
RP Tang, SX (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20892 USA.
EM shixing.tang@fda.hhs.gov; indira.hewlett@fda.hhs.gov
FU Division of Intramural Research, NIAID, NIH
FX This work was supported in part by Division of Intramural Research,
NIAID, NIH.
NR 22
TC 21
Z9 21
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2011
VL 51
IS 3
BP 463
EP 468
DI 10.1111/j.1537-2995.2010.02932.x
PG 6
WC Hematology
SC Hematology
GA 732DZ
UT WOS:000288166200005
PM 21077909
ER
PT J
AU Quillen, K
Medrano, C
Adams, S
Peterson, B
Hackett, J
Leitman, SF
Klein, HG
Stroncek, DF
AF Quillen, Karen
Medrano, Consuelito
Adams, Sharon
Peterson, Brett
Hackett, Julia
Leitman, Susan F.
Klein, Harvey G.
Stroncek, David F.
TI Screening plateletpheresis donors for HLA antibodies on two
high-throughput platforms and correlation with recipient outcome
SO TRANSFUSION
LA English
DT Article
ID ACUTE LUNG INJURY; LEUKOCYTE ANTIGEN ANTIBODIES; TRANSFUSION REACTIONS;
BLOOD-DONORS; PLASMA; ALLOIMMUNIZATION; ALLOANTIBODIES; COMPONENTS;
PREGNANCY; STRATEGY
AB BACKGROUND: To determine the prevalence and impact of transfusing plasma containing white blood cell antibodies, we compared two high-throughput HLA antibody screening assays and prospectively examined the medical records of all platelet (PLT) recipients to detect subtle manifestations of transfusion-related acute lung injury and other transfusion reactions.
STUDY DESIGN AND METHODS: Serum samples from 136 plateletpheresis donors were tested for HLA Class I and II antibodies using microbead (LABScreen PRA, One Lambda) and microchip (Dynachip, Invitrogen) assays. Electronic medical records of all recipients were reviewed for vital signs and nursing documentation before and after transfusion.
RESULTS: In the microchip assay with a cutoff value of 0.25, 2.9% of samples were positive for Class I and 8.9% for Class II antibodies; with a cutoff value of 0.1, the results were 14.9 and 21.6%, respectively. In the microbead assay (normalized background ratio, 1.5), 15% were positive for Class I and 21% for Class II antibodies. The prevalence of HLA antibodies was 17% in donors without pregnancy or transfusion history and 47% in donors with such history. The PLTs were transfused in 265 episodes to 67 patients. There were no reported reactions; however, symptoms or vital sign changes were noted in seven transfusion episodes. The incidence of reactions was 2.7% (2/75) for antibody-positive units and 2.6% (5/190) for antibody-negative units.
CONCLUSIONS: Microbead and microchip assays yielded similar results. The prevalence of HLA antibodies was greater in donors with a history of pregnancy or transfusion, but no increase in the incidence of transfusion reactions was noted in recipients of components from donors with HLA antibodies.
C1 [Quillen, Karen; Medrano, Consuelito; Adams, Sharon; Peterson, Brett; Hackett, Julia; Leitman, Susan F.; Klein, Harvey G.; Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Quillen, K (reprint author), Boston Univ, Med Ctr, 88 E Newton St,H-3600, Boston, MA 02118 USA.
EM kq@bu.edu
OI Quillen, Karen/0000-0002-4243-0864
FU Intramural NIH HHS [ZIA CL002119-02]
NR 24
TC 9
Z9 12
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2011
VL 51
IS 3
BP 504
EP 510
DI 10.1111/j.1537-2995.2010.02874.x
PG 7
WC Hematology
SC Hematology
GA 732DZ
UT WOS:000288166200011
PM 20849407
ER
PT J
AU Cable, RG
Glynn, SA
Kiss, JE
Mast, AE
Steele, WR
Murphy, EL
Wright, DJ
Sacher, RA
Gottschall, JL
Vij, V
Simon, TL
AF Cable, Ritchard G.
Glynn, Simone A.
Kiss, Joseph E.
Mast, Alan E.
Steele, Whitney R.
Murphy, Edward L.
Wright, David J.
Sacher, Ronald A.
Gottschall, Jerry L.
Vij, Vibha
Simon, Toby L.
CA NHLBI Retrovirus Epidemiology Dono
TI Iron deficiency in blood donors: analysis of enrollment data from the
REDS-II Donor Iron Status Evaluation (RISE) study
SO TRANSFUSION
LA English
DT Article
ID SERUM TRANSFERRIN RECEPTOR; HEMOGLOBIN; FERRITIN; ANEMIA; DONATION;
STORES; HEMOCHROMATOSIS
AB BACKGROUND: Regular blood donors are at risk of iron deficiency, but characteristics that predispose to this condition are poorly defined.
STUDY DESIGN AND METHODS: A total of 2425 red blood cell donors, either first-time (FT) or reactivated donors (no donations for 2 years) or frequent donors, were recruited for follow-up. At enrollment, ferritin, soluble transferrin receptor (sTfR), and hemoglobin were determined. Donor variables included demographics, smoking, dietary intake, use of iron supplements, and menstrual and/or pregnancy history. Models to predict two measures of iron deficiency were developed: Absent iron stores (AIS) were indicated by a ferritin level of less than 12 ng/mL and iron-deficient erythropoiesis (IDE) by a log(sTfR/ferritin) value of 2.07 or greater.
RESULTS: A total of 15.0% of donors had AIS and 41.7% IDE. In frequent donors, 16.4 and 48.7% of males had AIS and IDE, respectively, with corresponding proportions of 27.1 and 66.1% for females. Donation intensity was most closely associated with AIS and/or IDE (odds ratios from 5.3 to 52.2 for different donation intensity compared to FT donors). Being female, younger, and/or menstruating also increased the likelihood of having AIS and/or IDE, as did having a lower weight. Marginally significant variables for AIS and/or IDE were being a nonsmoker, previous pregnancy, and not taking iron supplements. Dietary variables were in general unrelated to AIS and/or IDE, as was race and/or ethnicity.
CONCLUSION: A large proportion of both female and male frequent blood donors have iron depletion. Donation intensity, sex and/or menstrual status, weight, and age are important independent predictors of AIS and/or IDE. Reducing the frequency of blood donation is likely to reduce the prevalence of iron deficiency among blood donors, as might implementing routine iron supplementation.
C1 [Cable, Ritchard G.] Amer Red Cross Blood Serv, Farmington, CT 06032 USA.
NHLBI, Bethesda, MD 20892 USA.
Inst Transfus Med, Pittsburgh, PA USA.
Blood Ctr SE Wisconsin Inc, Milwaukee, WI 53233 USA.
Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA.
WESTAT Corp, Rockville, MD 20850 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Blood Syst Res Inst, San Francisco, CA USA.
Univ Cincinnati, Hoxworth Blood Ctr, Acad Hlth Ctr, Cincinnati, OH USA.
CSL Plasma, Boca Raton, FL USA.
RP Cable, RG (reprint author), Amer Red Cross Blood Serv, 209 Farmington Ave, Farmington, CT 06032 USA.
EM cabler@usa.redcross.org
FU NHLBI [N01-HB-47168, N01-HB-47169, N01-HB-47171, N01-HB-47172,
N01-HB-47174, N01-HB-47175]
FX This work was supported by NHLBI contracts N01-HB-47168, -47169, -47171,
-47172, -47174, and -47175.
NR 26
TC 70
Z9 74
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2011
VL 51
IS 3
BP 511
EP 522
DI 10.1111/j.1537-2995.2010.02865.x
PG 12
WC Hematology
SC Hematology
GA 732DZ
UT WOS:000288166200012
PM 20804527
ER
PT J
AU Simmons, G
Glynn, SA
Holmberg, JA
Coffin, JM
Hewlett, IK
Lo, SC
Mikovits, JA
Switzer, WM
Linnen, JM
Busch, MP
AF Simmons, Graham
Glynn, Simone A.
Holmberg, Jerry A.
Coffin, John M.
Hewlett, Indira K.
Lo, Shyh-Ching
Mikovits, Judy A.
Switzer, William M.
Linnen, Jeffrey M.
Busch, Michael P.
CA Blood XMRV Sci Res Working Grp
TI The Blood Xenotropic Murine Leukemia Virus-Related Virus Scientific
Research Working Group: mission, progress, and plans
SO TRANSFUSION
LA English
DT Editorial Material
ID CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER; INFECTIOUS RETROVIRUS; MOUSE
DNA; XMRV; DISEASE; CONTAMINATION; CELLS; RISK; SEQUENCES
C1 [Simmons, Graham] Blood Syst Res Inst, San Francisco, CA 94118 USA.
[Simmons, Graham] Univ Calif San Francisco, San Francisco, CA 94118 USA.
[Glynn, Simone A.] NHLBI, Transfus Med & Cellular Therapeut Branch, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
Dept Hlth & Human Serv, Washington, DC USA.
NCI, Bethesda, MD 20892 USA.
Tufts Univ, Sch Med, Boston, MA 02111 USA.
US FDA, Off Blood Res & Review, Silver Spring, MD USA.
US FDA, Div Cellular & Gene Therapies Review, Silver Spring, MD USA.
Univ Nevada, Reno, NV 89557 USA.
Whittemore Peterson Inst, Reno, NV USA.
Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
Gen Probe Inc, San Diego, CA USA.
RP Simmons, G (reprint author), Blood Syst Res Inst, 270 Mason Ave, San Francisco, CA 94118 USA.
EM gsimmons@bloodsystems.org; glynnsa@nhlbi.nih.gov
RI Simmons, Graham/G-3523-2012
OI Simmons, Graham/0000-0002-9615-7023
FU NHLBI NIH HHS [N01HB-57181, N01HB57181, HHSN268200517181C]; PHS HHS
[HHSN268200517181C]
NR 40
TC 21
Z9 21
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2011
VL 51
IS 3
BP 643
EP 653
DI 10.1111/j.1537-2995.2011.03063.x
PG 11
WC Hematology
SC Hematology
GA 732DZ
UT WOS:000288166200028
PM 21366602
ER
PT J
AU Klein, HG
Dodd, RY
Hollinger, FB
Katz, LM
Kleinman, S
McCleary, KK
Silverman, RH
Stramer, SL
AF Klein, Harvey G.
Dodd, Roger Y.
Hollinger, F. Blaine
Katz, Louis M.
Kleinman, Steven
McCleary, K. Kimberly
Silverman, Robert H.
Stramer, Susan L.
CA AABB Interorg Task Force XMRV
TI Xenotropic murine leukemia virus-related virus (XMRV) and blood
transfusion: report of the AABB interorganizational XMRV task force
SO TRANSFUSION
LA English
DT Editorial Material
ID CHRONIC-FATIGUE-SYNDROME; HUMAN RETROVIRUS XMRV; PROSTATE-CANCER; NO
EVIDENCE; DEFINITION
C1 [Klein, Harvey G.] NIH, Dept Transfus Med, Clin Ctr RM 1C 711, Bethesda, MD 20892 USA.
RP Klein, HG (reprint author), NIH, Dept Transfus Med, Clin Ctr RM 1C 711, Bldg 10, Bethesda, MD 20892 USA.
EM HKlein@dtm.cc.nih.gov
NR 35
TC 10
Z9 10
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2011
VL 51
IS 3
BP 654
EP 661
DI 10.1111/j.1537-2995.2010.03012.x
PG 8
WC Hematology
SC Hematology
GA 732DZ
UT WOS:000288166200029
PM 21235597
ER
PT J
AU Bruner, DW
Hanisch, LJ
Reeve, BB
Trotti, AM
Schrag, D
Sit, L
Mendoza, TR
Minasian, L
O'Mara, A
Denicoff, AM
Rowland, JH
Montello, M
Geoghegan, C
Abernethy, AP
Clauser, SB
Castro, K
Mitchell, SA
Burke, L
Trentacosti, AM
Basch, EM
AF Bruner, Deborah Watkins
Hanisch, Laura J.
Reeve, Bryce B.
Trotti, Andy M.
Schrag, Deborah
Sit, Laura
Mendoza, Tito R.
Minasian, Lori
O'Mara, Ann
Denicoff, Andrea M.
Rowland, Julia H.
Montello, Michael
Geoghegan, Cindy
Abernethy, Amy P.
Clauser, Steven B.
Castro, Kathleen
Mitchell, Sandra A.
Burke, Laurie
Trentacosti, Ann Marie
Basch, Ethan M.
TI Stakeholder perspectives on implementing the National Cancer Institute's
patient-reported outcomes version of the Common Terminology Criteria for
Adverse Events (PRO-CTCAE)
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Patient-reported outcomes; Symptoms; adverse events; Oncology; Cancer;
Clinical trials; Toxicity; safety; Tolerability; Comparative
effectiveness research; Cooperative groups; National Cancer Institute
AB The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty-eight percent felt that patients in clinical trials would be willing to self-report adverse symptoms at clinic visits via computer, and 68% felt patients would self-report weekly from home via the internet or an automated telephone system. Lack of computers and limited space and personnel were seen as potential barriers to in-clinic self-reporting, but these were judged to be surmountable with adequate funding. The PRO-CTCAE items and software are viewed by a majority of survey respondents as a means to improve adverse event data quality and comprehensiveness, enhance clinical decision-making, and foster patient-clinician communication. Research is ongoing to assess the measurement properties and feasibility of implementing this measure in cancer clinical trials.
C1 [Bruner, Deborah Watkins] Univ Penn, Abramson Canc Ctr, Sch Nursing, Philadelphia, PA 19104 USA.
[Hanisch, Laura J.] Univ Penn, Abramson Canc Ctr, Canc Control & Outcomes Program, Philadelphia, PA 19104 USA.
[Reeve, Bryce B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Lineberger Comprehens Canc Ctr, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA.
[Trotti, Andy M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Schrag, Deborah] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA.
[Sit, Laura; Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Grp, New York, NY 10065 USA.
[Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA.
[Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[O'Mara, Ann] NCI, Palliat Care Res Community Oncol & Prevent Trial, Canc Prevent Div, Bethesda, MD 20892 USA.
[Denicoff, Andrea M.] NCI, Clin Invest Branch, CTEP, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD 20892 USA.
[Montello, Michael] NCI, Clin Trials Technol, Bethesda, MD 20892 USA.
[Geoghegan, Cindy] Breast Canc Network Strength, Chicago, IL 60603 USA.
[Abernethy, Amy P.] Duke Univ, Med Ctr, Sch Med, Dept Med, Durham, NC 27710 USA.
[Clauser, Steven B.; Castro, Kathleen; Mitchell, Sandra A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Burke, Laurie; Trentacosti, Ann Marie] US FDA, Study Endpoints & Label Dev, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Basch, EM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Grp, 307 E 63rd St,2nd Floor, New York, NY 10065 USA.
EM basche@mskcc.org
OI Abernethy, Amy/0000-0001-6930-8722
FU National Cancer Institute [HHSN261200800043C]
FX This work was supported by the National Cancer Institute under contract
HHSN261200800043C awarded to Dr. Ethan Basch, PI.
NR 26
TC 16
Z9 17
U1 0
U2 2
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD MAR
PY 2011
VL 1
IS 1
BP 110
EP 122
DI 10.1007/s13142-011-0025-3
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V39LG
UT WOS:000209411900019
PM 24073038
ER
PT J
AU Bonifacino, JS
Hierro, A
AF Bonifacino, Juan S.
Hierro, Aitor
TI Transport according to GARP: receiving retrograde cargo at the
trans-Golgi network
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID MOTOR-NEURON DISEASE; AMYOTROPHIC-LATERAL-SCLEROSIS; VESICLE TETHERING
COMPLEXES; SACCHAROMYCES-CEREVISIAE; STRUCTURAL BASIS; EARLY ENDOSOME;
SNARE TLG1P; BINDING-PROTEIN; MEMBRANE-FUSION; GENOMIC SCREEN
AB Tethering factors are large protein complexes that capture transport vesicles and enable their fusion with acceptor organelles at different stages of the endomembrane system. Recent studies have shed new light on the structure and function of a heterotetrameric tethering factor named Golgi-associated retrograde protein (GARP), which promotes fusion of endosome-derived, retrograde transport carriers to the trans-Golgi network (TGN). X-ray crystallography of the Vps53 and Vps54 subunits of GARP has revealed that this complex is structurally related to other tethering factors such as the exocyst, the conserved oligomeric Golgi (COG) and Dsl1 (dependence on SLY1-20) complexes, indicating that they all might work by a similar mechanism. Loss of GARP function compromises the growth, fertility and/or viability of the defective organisms, emphasizing the essential nature of GARP-mediated retrograde transport.
C1 [Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Hierro, Aitor] Ctr Cooperat Res Biosci CIC bioGUNE, Struct Biol Unit, Derio 48160, Spain.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov; ahierro@cicbiogune.es
RI Hierro, Aitor/F-9998-2011; Castilla, Joaquin/E-6952-2012
OI Bonifacino, Juan S./0000-0002-5673-6370; Hierro,
Aitor/0000-0002-7721-1581;
FU US National Institute of Child Health and Human Development; Carlos III
Health Institute [PI081739]; Ministry of Science and Innovation of Spain
FX We thank the members of the Bonifacino and Hierro laboratories for their
contributions to the work discussed here. Work in the Bonifacino
laboratory was funded by the Intramural Program of the US National
Institute of Child Health and Human Development, and in the Hierro
laboratory by the Carlos III Health Institute (PI081739) and the Ramon y
Cajal program of the Ministry of Science and Innovation of Spain. The
authors declare no conflicts of interest.
NR 87
TC 48
Z9 49
U1 1
U2 13
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD MAR
PY 2011
VL 21
IS 3
BP 159
EP 167
DI 10.1016/j.tcb.2010.11.003
PG 9
WC Cell Biology
SC Cell Biology
GA 739PQ
UT WOS:000288730600004
PM 21183348
ER
PT J
AU Makareeva, E
Aviles, NA
Leikin, S
AF Makareeva, Elena
Aviles, Nydea A.
Leikin, Sergey
TI Chaperoning osteogenesis: new protein-folding disease paradigms
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID COLLAGEN TRIPLE-HELIX; ENDOPLASMIC-RETICULUM STRESS; ALPHA-LYTIC
PROTEASE; I COLLAGEN; MOLECULAR CHAPERONE; BONE-FORMATION;
CYCLOPHILIN-B; ER STRESS; PROLYL 3-HYDROXYLATION; DANLOS-SYNDROME
AB Recent discoveries of severe bone disorders in patients with deficiencies in several endoplasmic reticulum chaperones are reshaping the discussion of type I collagen folding and related diseases. Type I collagen is the most abundant protein in all vertebrates and a crucial structural molecule for bone and other connective tissues. Its misfolding causes bone fragility, skeletal deformity and other tissue failures. Studies of newly discovered bone disorders indicate that collagen folding, chaperones involved in the folding process, cellular responses to misfolding and related bone pathologies might not follow conventional protein folding paradigms. In this review, we examine the features that distinguish collagen folding from that of other proteins and describe the findings that are beginning to reveal how cells manage collagen folding and misfolding. We discuss implications of these studies for general protein folding paradigms, unfolded protein response in cells and protein folding diseases.
C1 [Makareeva, Elena; Aviles, Nydea A.; Leikin, Sergey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Leikin, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM leikins@mail.nih.gov
RI Makareeva, Elena/F-5183-2011; Leikin, Sergey/A-5518-2008
OI Leikin, Sergey/0000-0001-7095-0739
FU NICHD, NIH
FX This work was funded by the Intramural Research Program, NICHD, NIH. We
thank Lynn S. Felts for critical reading of the manuscript.
NR 84
TC 26
Z9 26
U1 2
U2 11
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD MAR
PY 2011
VL 21
IS 3
BP 168
EP 176
DI 10.1016/j.tcb.2010.11.007
PG 9
WC Cell Biology
SC Cell Biology
GA 739PQ
UT WOS:000288730600005
PM 21183349
ER
PT J
AU McDonald, SM
Patton, JT
AF McDonald, Sarah M.
Patton, John T.
TI Assortment and packaging of the segmented rotavirus genome
SO TRENDS IN MICROBIOLOGY
LA English
DT Review
ID DOUBLE-STRANDED-RNA; NONSTRUCTURAL PROTEIN NSP2; INFLUENZA-A VIRUS;
MESSENGER-RNA; BACTERIOPHAGE PHI-6; INFECTED-CELLS; CRYOELECTRON
MICROSCOPY; 3-DIMENSIONAL STRUCTURE; REPLICASE PARTICLE; REVERSE
GENETICS
AB The rotavirus (RV) genome comprises 11 segments of double-stranded RNA (dsRNA) and is contained within a non-enveloped, icosahedral particle. During assembly, a highly coordinated selective packaging mechanism ensures that progeny RV virions contain one of each genome segment. Cis-acting signals thought to mediate assortment and packaging are associated with putative panhandle structures formed by base-pairing of the ends of RV plus-strand RNAs (+RNAs). Viral polymerases within assembling core particles convert the 11 distinct +RNAs to dsRNA genome segments. It remains unclear whether RV +RNAs are assorted before or during encapsidation, and the functions of viral proteins during these processes are not resolved. However, as reviewed here, recent insights gained from the study of RV and two other segmented RNA viruses, influenza A virus and bacteriophage Phi 6, reveal potential mechanisms of RV assortment and packaging.
C1 [McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014
FU NIH National Institute of Allergy and Infectious Diseases
FX We would like to thank Michelle Arnold, Kristen Ogden, Aitor Navarro,
and Shane Trask for editorial advice and critical reading of the
manuscript. SMM and JTP are supported by the Intramural Research Program
of the NIH National Institute of Allergy and Infectious Diseases.
NR 89
TC 31
Z9 34
U1 0
U2 16
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0966-842X
J9 TRENDS MICROBIOL
JI Trends Microbiol.
PD MAR
PY 2011
VL 19
IS 3
BP 136
EP 144
DI 10.1016/j.tim.2010.12.002
PG 9
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 738KL
UT WOS:000288638600005
PM 21195621
ER
PT J
AU Patterson, LJ
Daltabuit-Test, M
Xiao, P
Zhao, J
Hu, WL
Wille-Reece, U
Brocca-Cofano, E
Kalyanaraman, VS
Kalisz, I
Whitney, S
Lee, EM
Pal, R
Montefiori, DC
Dandekar, S
Seder, R
Roederer, M
Wiseman, RW
Hirsch, V
Robert-Guroff, M
AF Patterson, L. Jean
Daltabuit-Test, Mara
Xiao, Peng
Zhao, Jun
Hu, William
Wille-Reece, Ulrike
Brocca-Cofano, Egidio
Kalyanaraman, V. S.
Kalisz, Irene
Whitney, Stephen
Lee, Eun Mi
Pal, Ranajit
Montefiori, David C.
Dandekar, Satya
Seder, Robert
Roederer, Mario
Wiseman, Roger W.
Hirsch, Vanessa
Robert-Guroff, Marjorie
TI Rapid SIV Env-specific mucosal and serum antibody induction augments
cellular immunity in protecting immunized, elite-controller macaques
against high dose heterologous SIV challenge
SO VIROLOGY
LA English
DT Article
DE SIV; Elite-control; Virus sequestration; Multifaceted immunity; Vaccine;
Memory
ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; RHESUS MACAQUES;
ANTIRETROVIRAL THERAPY; SHIV89.6P CHALLENGE; DISEASE PROGRESSION;
NONHUMAN-PRIMATES; VACCINE DESIGN; INFECTION; REPLICATION
AB Three Indian rhesus macaques. Ad-Sly primed/protein boosted and exposed twice to high-dose mucosal SIV(mac251) challenges, exhibited elite control of viremia over 6.5 years. They were negative for host factors associated with control of SIV infection. After a third intrarectal challenge with SIV(smE660). all controlled viremia, with one (macaque #5) maintaining undetectable viremia in blood. Acquisition was not blocked, but virus was contained in the jejunum and draining lymph nodes. Polyfunctional memory T cell responses and high-titered neutralizing and non-neutralizing serum and mucosal antibodies were present before and maintained post-challenge. The level of protection seen for animal #5 was predicted from analyses of gene transcription in jejunum 2 weeks post-challenge. Macaques #7 and #9, exhibiting lower pre-challenge cellular and humoral immunity, partially controlled the SIV(smE660) challenge. Initial vaccine-induced control by macaque #5 extended to the SIV(smE660) challenge due to multiple immune mechanisms that were boosted and augmented by cryptic SIV exposure. Published by Elsevier Inc.
C1 [Patterson, L. Jean; Daltabuit-Test, Mara; Xiao, Peng; Zhao, Jun; Brocca-Cofano, Egidio; Robert-Guroff, Marjorie] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA.
[Hu, William; Dandekar, Satya] Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
[Wille-Reece, Ulrike; Seder, Robert; Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Kalyanaraman, V. S.; Kalisz, Irene; Whitney, Stephen; Lee, Eun Mi; Pal, Ranajit] Adv Biosci Labs Inc, Kensington, MD 20895 USA.
[Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Wiseman, Roger W.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53711 USA.
[Hirsch, Vanessa] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
RP Robert-Guroff, M (reprint author), NCI, NIH, Vaccine Branch, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU NIH/NCRR [RR00168]; National Institutes of Health, National Cancer
Institute
FX We gratefully acknowledge the animal caretakers at Advanced BioScience
Laboratories and Bioqual, Inc. for their expertise in caring for our
macaques and collection of serial samples, and Steve Perfetto at the
VRC. NIAID, for help in troubleshooting the 11-color flow panel and
useful discussion. We thank Julian Bess and Jeffrey D. Lifson for the
aldrithiol-inactivated SIV and control microvesicles; George Shaw for
the HIV-2 proviral clone, pJK7312A; Wendy Yeh for SIV plasmid standards;
and Wendy Yeh and Sam Sankaran for consultation on the real time PCR
assay. The following reagents were obtained from the AIDS Research and
Reference Reagent Program, Division of AIDS, NIAID, NIH:
CEM-NKR cells from Dr. Peter Cresswell; complete sets of
SIVmac239 Env peptides and SIVmac239 Gag peptides.
We thank Welkin Johnson, C. Audin, L Hall, J. Morgan and the NEPRC
Genetics Core, funded by NIH/NCRR grant RR00168, for TRIM5 alpha
genotyping. This work was supported by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute.
NR 54
TC 16
Z9 16
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 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 1
PY 2011
VL 411
IS 1
BP 87
EP 102
DI 10.1016/j.virol.2010.12.033
PG 16
WC Virology
SC Virology
GA 725FI
UT WOS:000287630200010
PM 21237474
ER
PT J
AU Feagins, AR
Cordoba, L
Sanford, BJ
Dryman, BA
Huang, YW
LeRoith, T
Emerson, SU
Meng, XJ
AF Feagins, Alicia R.
Cordoba, Laura
Sanford, Brent J.
Dryman, Barbara A.
Huang, Yao-Wei
LeRoith, Tanya
Emerson, Suzanne U.
Meng, Xiang-Jin
TI Intergenotypic chimeric hepatitis E viruses (HEVs) with the genotype 4
human HEV capsid gene in the backbone of genotype 3 swine HEV are
infectious in pigs
SO VIRUS RESEARCH
LA English
DT Article
DE Hepatitis E virus (HEV); Chimeric viruses; Cross-species infection;
Pigs; Host range
ID CROSS-SPECIES INFECTION; CIS-REACTIVE ELEMENT; ORF3 PROTEIN;
RECEPTOR-BINDING; VIRAL-RNA; IN-VITRO; CELLS; REPLICATION; HEPATOMA;
RELEASE
AB Genotypes 1 and 2 hepatitis E virus (HEV) infect only humans whereas genotypes 3 and 4 HEV infect both humans and pigs. To evaluate the mechanism of cross-species HEV infection between humans and swine, in this study we constructed five intergenotypic chimeric viruses and tested for their infectivity in vitro and in pigs. We demonstrated that chimeric viruses containing the ORF2 capsid gene either alone or in combination with its adjacent 5' junction region OR) and 3' noncoding region (NCR) from a genotype 4 human HEV in the backbone of a genotype 3 swine HEV are replication-competent in Huh7 cells and infectious in HepG2/C3A cells and in pigs, and thus supporting the hypothesis that genotypes 3 and 4 human HEV are of swine origin. However, chimeric viruses containing the JR+ ORF2 + 3' NCR of genotypes :3 or 4 HEV in the backbone of genotype 1 human HEV failed to infect pigs, suggesting that other genomic regions such as 5' NCR and ORF1 may also be involved in HEV cross-species infection. The results from :his study provide the first experimental evidence of the exchangeability of the capsid gene between genotype 3 swine HEV and genotype 4 human HEV, and have important implications for understanding the mechanism of HEV cross-species infection. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Feagins, Alicia R.; Cordoba, Laura; Sanford, Brent J.; Dryman, Barbara A.; Huang, Yao-Wei; LeRoith, Tanya; Meng, Xiang-Jin] Virginia Polytech Inst & State Univ, Coll Vet Med, Dept Biomed Sci & Pathobiol, Ctr Mol Med & Infect Dis, Blacksburg, VA 24061 USA.
[Emerson, Suzanne U.] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Meng, XJ (reprint author), Virginia Polytech Inst & State Univ, Coll Vet Med, Dept Biomed Sci & Pathobiol, Ctr Mol Med & Infect Dis, 1981 Kraft Dr, Blacksburg, VA 24061 USA.
EM xjmeng@vt.edu
RI Huang, Yaowei/B-1468-2009; Meng, X.J./B-8769-2009;
OI Huang, Yaowei/0000-0001-9755-8411; Meng, X.J./0000-0002-2739-1334;
LeRoith, Tanya/0000-0002-1196-6949
FU National Institutes of Health [R01AI050611, R01AI074667]
FX We thank Pete Jobst, Dustin Lucas, and Shannon Viers for the animal
care. This study is supported by grants from the National Institutes of
Health (R01AI050611, and R01AI074667).
NR 34
TC 10
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD MAR
PY 2011
VL 156
IS 1-2
BP 141
EP 146
DI 10.1016/j.virusres.2010.12.011
PG 6
WC Virology
SC Virology
GA 738KI
UT WOS:000288638300018
PM 21195119
ER
PT J
AU Sung, MH
McNally, JG
AF Sung, Myong-Hee
McNally, James G.
TI Live cell imaging and systems biology
SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE
LA English
DT Review
ID FLUORESCENCE CORRELATION SPECTROSCOPY; RESONANCE ENERGY-TRANSFER; SINGLE
LIVING CELLS; GENE-EXPRESSION; DYNAMIC PROTEOMICS; FEEDBACK LOOP;
IN-VIVO; PROTEIN; MICROSCOPY; CYCLE
AB Much of the experimental data used to construct mathematical models of molecular networks are derived from in vitro measurements. However, there is increasing evidence that in vitro measurements fail to capture both the complexity and the individuality found in single, living cells. These limitations can be overcome by live cell microscopy which is evolving to enable in vivo biochemistry. Here, we survey the current capabilities of live cell microscopy and illustrate how a number of different imaging approaches could be applied to analyze a specific molecular network. We argue that incorporation of such quantitative live-cell imaging methods is critical for the progress of systems biology. (C) 2010 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3 167-182 DOI: 10.1002/wsbm.108
C1 [Sung, Myong-Hee; McNally, James G.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Sung, MH (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM sungm@mail.nih.gov; mcnallyj@exchange.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 83
TC 13
Z9 13
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5094
EI 1939-005X
J9 WIRES SYST BIOL MED
JI Wiley Interdiscip. Rev.-Syst. Biol
PD MAR-APR
PY 2011
VL 3
IS 2
BP 167
EP 182
DI 10.1002/wsbm.108
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 728SS
UT WOS:000287895400005
PM 20730797
ER
PT J
AU Kim, TH
Jiang, HH
Park, CW
Youn, YS
Lee, S
Chen, XY
Lee, KC
AF Kim, Tae Hyung
Jiang, Hai Hua
Park, Chan Woong
Youn, Yu Seok
Lee, Seulki
Chen, Xiaoyuan
Lee, Kang Choon
TI PEGylated TNF-related apoptosis-inducing ligand (TRAIL)-loaded sustained
release PLGA microspheres for enhanced stability and antitumor activity
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE TRAIL; PEGylation; PICA microspheres; Stability; Sustain release;
Antitumor
ID BIODEGRADABLE MICROSPHERES; POLYMERIC MICROSPHERES; PROTEIN STABILITY;
DELIVERY SYSTEMS; DECOY RECEPTORS; IN-VIVO; DEATH; APO2L/TRAIL; GROWTH;
TRAIL
AB The purpose of this work was to develop an effective PEGylated INF-related apoptosis-inducing ligand (PEG-TRAIL) delivery system for antitumor therapy based on local injection to tumor sites that has a sustained effect without protein aggregation or an initial release burst. The authors designed poly (lactic-co-glycolic) acid (PLGA) microspheres that deliver PEG-TRAIL locally and continuously at tumor sites with sustained biological activity and compared its performance with that of TRAIL microspheres. TRAIL or PEG-TRAIL was microencapsulated into PLGA microspheres using a double-emulsion solvent extraction method. Prepared TRAIL and PEG-TRAIL microspheres showed entirely spherical, smooth surfaces. However. PEG-TRAIL microspheres exhibited a 2.07-fold higher encapsulation efficiency than TRAIL microspheres, and exhibited a tri-phasic in vitro release profile with a lower initial burst (15.8%) than TRAIL microspheres (42.7%). Furthermore, released PEG-TRAIL showed a continued ability to induce apoptosis over 14 days. In vivo pharmacokinetic studies also demonstrated that PEG-TRAIL microspheres had a sustained release profile (18 days), and that the steady-state concentration of PEG-TRAIL in rat plasma was reached at day 3 and maintained until day 15; its steady-state concentration in rat plasma changed from 1444.3 +/- 338.4 to 2697.7 +/- 419.7 pg/ml. However, TRAIL microspheres were released out within 2 days after administration. Finally, in vivo antitumor tests revealed that tumor growths were significantly more inhibited by a single dose of PEG-TRAIL microspheres than TRAIL microspheres when delivered at 300 mu g of TRAIL/mouse. Tumors taken from mouse treated with PEG-TRAIL microspheres showed 783% tumor suppression at 24 days, and this was 3.02-fold higher than that observed for TRAIL microspheres (25.9% tumor inhibition). Furthermore, these improved pharmaceutical characteristics of PEG-TRAIL microspheres resulted in superior therapeutic effects without detectable side effects. These findings strongly suggest that PEG-TRAIL microspheres offer a new therapeutic strategy for the treatment of cancers. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Lee, Kang Choon] SungKyunKwan Univ, Coll Pharm, Drug Targeting Lab, Suwon 440746, South Korea.
[Youn, Yu Seok] Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea.
[Park, Chan Woong; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Lee, KC (reprint author), SungKyunKwan Univ, Coll Pharm, Drug Targeting Lab, 300 Chonchon Dong, Suwon 440746, South Korea.
EM kclee@skku.edu
FU Ministry of Education, Science and Technology of Korea [2009K001604]
FX This study was supported by the Ministry of Education, Science and
Technology of Korea [Grant 2009K001604].
NR 30
TC 28
Z9 30
U1 0
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD FEB 28
PY 2011
VL 150
IS 1
BP 63
EP 69
DI 10.1016/j.jconrel.2010.10.037
PG 7
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 738LQ
UT WOS:000288641700009
PM 21062635
ER
PT J
AU Ganesh, SK
Joo, J
Skelding, K
Mehta, L
Zheng, G
O'Neill, K
Billings, EM
Helgadottir, A
Andersen, K
Thorgeirsson, G
Gudnason, T
Geller, NL
Simari, RD
Holmes, DR
O'Neill, WW
Nabel, EG
AF Ganesh, Santhi K.
Joo, Jungnam
Skelding, Kimberly
Mehta, Laxmi
Zheng, Gang
O'Neill, Kathleen
Billings, Eric M.
Helgadottir, Anna
Andersen, Karl
Thorgeirsson, Gudmundur
Gudnason, Thorarinn
Geller, Nancy L.
Simari, Robert D.
Holmes, David R.
O'Neill, William W.
Nabel, Elizabeth G.
TI Time course analysis of gene expression identifies multiple genes with
differential expression in patients with in-stent restenosis
SO BMC MEDICAL GENOMICS
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; EXCISION-REPAIR GENES; NEURAL-TUBE DEFECTS;
MOLECULAR RESPONSES; CANCER RISK; EGR-1; ATHEROSCLEROSIS; PROLIFERATION;
POLYMORPHISMS; COREPRESSOR
AB Background: The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling of the artery after injury by coronary stent implantation. We hypothesized that the analysis of gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences in transcript expression between individuals who develop ISR and those who do not.
Methods and Results: We determined and investigated PBMC gene expression of 358 patients undergoing an index procedure to treat in de novo coronary artery lesions with bare metallic stents, using a novel time-varying intercept model to optimally assess the time course of gene expression across a time course of blood samples. Validation analyses were conducted in an independent sample of 97 patients with similar time-course blood sampling and gene expression data. We identified 47 probesets with differential expression, of which 36 were validated upon independent replication testing. The genes identified have varied functions, including some related to cellular growth and metabolism, such as the NAB2 and LAMP genes.
Conclusions: In a study of patients undergoing bare metallic stent implantation, we have identified and replicated differential gene expression in peripheral blood mononuclear cells, studied across a time series of blood samples. The genes identified suggest alterations in cellular growth and metabolism pathways, and these results provide the basis for further specific functional hypothesis generation and testing of the mechanisms of ISR.
C1 [Ganesh, Santhi K.; O'Neill, Kathleen; Billings, Eric M.; Nabel, Elizabeth G.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Joo, Jungnam; Zheng, Gang; Geller, Nancy L.] NHLBI, Off Biostat Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Skelding, Kimberly] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA.
[Mehta, Laxmi] Ohio State Univ, Med Ctr, Div Cardiovasc Med, Columbus, OH 43210 USA.
[Helgadottir, Anna] Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford, England.
[Andersen, Karl; Thorgeirsson, Gudmundur; Gudnason, Thorarinn] Landspitali Univ Hosp, Cardiovasc Res Ctr, Reykjavik, Iceland.
[Andersen, Karl; Thorgeirsson, Gudmundur] Univ Iceland, Reykjavik, Iceland.
[Simari, Robert D.; Holmes, David R.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[O'Neill, William W.] Univ Miami, Miller Sch Med, Dept Internal Med, Div Cardiol, Miami, FL 33136 USA.
RP Nabel, EG (reprint author), NHLBI, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
EM enabel@partners.org
RI Mehta, Laxmi/E-3654-2011
FU Division of Intramural Research of the National Heart, Lung and Blood
Institute, National Institutes of Health
FX This work was supported by the Division of Intramural Research of the
National Heart, Lung and Blood Institute, National Institutes of Health.
NR 52
TC 4
Z9 4
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD FEB 28
PY 2011
VL 4
AR 20
DI 10.1186/1755-8794-4-20
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 732SI
UT WOS:000288209500001
PM 21356094
ER
PT J
AU Glasgow, RE
AF Glasgow, Russell E.
TI A Model Program for a Devastating Disease Important Content and Methods
Issues in Translating Research Into Practice
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID INTERVENTIONS
C1 NCI, Dept Disseminat & Implementat Sci, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
RP Glasgow, RE (reprint author), NCI, Dept Disseminat & Implementat Sci, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6144, Rockville, MD 20852 USA.
EM glasgowre@mail.nih.gov
NR 9
TC 1
Z9 1
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD FEB 28
PY 2011
VL 171
IS 4
BP 360
EP 361
DI 10.1001/archinternmed.2011.11
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 728FD
UT WOS:000287858900018
PM 21357813
ER
PT J
AU Ambatipudi, S
Gerstung, M
Gowda, R
Pai, P
Borges, AM
Schaffer, AA
Beerenwinkel, N
Mahimkar, MB
AF Ambatipudi, Srikant
Gerstung, Moritz
Gowda, Ravindra
Pai, Prathamesh
Borges, Anita M.
Schaeffer, Alejandro A.
Beerenwinkel, Niko
Mahimkar, Manoj B.
TI Genomic Profiling of Advanced-Stage Oral Cancers Reveals Chromosome 11q
Alterations as Markers of Poor Clinical Outcome
SO PLOS ONE
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; COPY NUMBER;
NECK-CANCER; HEAD; AMPLICON; ARRAY; AMPLIFICATION; EXPRESSION; DISTAL
AB Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1-q22.2 and losses of 17p13.3 and 11q23-q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers.
C1 [Ambatipudi, Srikant; Gowda, Ravindra; Mahimkar, Manoj B.] Adv Ctr Treatment Res & Educ Canc, Tata Mem Ctr, Canc Res Inst, Navi Mumbai, India.
[Gerstung, Moritz; Beerenwinkel, Niko] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
[Gerstung, Moritz; Beerenwinkel, Niko] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Pai, Prathamesh] Tata Mem Hosp, Tata Mem Ctr, Head & Neck Unit, Mumbai 400012, Maharashtra, India.
[Borges, Anita M.] SL Raheja Hosp, Dept Pathol & Lab Med, Mumbai, Maharashtra, India.
[Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA.
RP Ambatipudi, S (reprint author), Adv Ctr Treatment Res & Educ Canc, Tata Mem Ctr, Canc Res Inst, Navi Mumbai, India.
EM mmahimkar@actrec.gov.in
RI Schaffer, Alejandro/F-2902-2012; Ambatipudi, Srikant/J-4648-2012;
OI Gerstung, Moritz/0000-0001-6709-963X; AMBATIPUDI,
SRIKANT/0000-0003-3102-3603
FU Council of Scientific and Industrial Research [CSIR]
[27(0207)/09/EMR-II]; Tata Memorial Center; SystemsX.ch, Swiss
initiative in systems biology [2009/024]; National Institutes of Health,
NLM
FX The authors are thankful to the Council of Scientific and Industrial
Research [CSIR Grant No: 27(0207)/09/EMR-II]; Tata Memorial Center -
Intramural Research Grant for funding the project. MG and NB have been
funded by SystemsX.ch, the Swiss initiative in systems biology, under
grant No. 2009/024, evaluated by the Swiss National Science Foundation.
This research was supported in part by the Intramural research Program
of the National Institutes of Health, NLM. The authors thank CSIR for
providing a fellowship to SA during his tenure as a PhD student. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 49
TC 25
Z9 25
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 28
PY 2011
VL 6
IS 2
AR e17250
DI 10.1371/journal.pone.0017250
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729EM
UT WOS:000287931400043
PM 21386901
ER
PT J
AU Lu, HX
Khurana, S
Verma, N
Manischewitz, J
King, L
Beigel, JH
Golding, H
AF Lu, Hanxin
Khurana, Surender
Verma, Nitin
Manischewitz, Jody
King, Lisa
Beigel, John H.
Golding, Hana
TI A Rapid Flp-In System for Expression of Secreted H5N1 Influenza
Hemagglutinin Vaccine Immunogen in Mammalian Cells
SO PLOS ONE
LA English
DT Article
ID EFFICACY; SAFETY; PURIFICATION; ANTIBODIES; ADULTS; VIRUS; DUCKS
AB Background: Continuing transmissions of highly pathogenic H5N1 viruses in poultry and humans underscores the need for a rapid response to potential pandemic in the form of vaccine. Recombinant technologies for production of immunogenic hemagglutinin (HA) could provide an advantage over the traditional inactivated vaccine manufacturing process. Generation of stably transfected mammalian cells secreting properly folded HA proteins is important for scalable controlled manufacturing.
Methodology/Principal Findings: We have developed a Flp-In based 293 stable cell lines through targeted site-specific recombination for expression of secreted hemagglutinin (HA) proteins and evaluated their immunogenicity. H5N1 globular domain HA1(1-330) and HA0(1-500) proteins were purified from the supernatants of 293 Flp-In stable cell lines. Both proteins were properly folded as confirmed by binding to H5N1-neutralizing conformation-dependent human monoclonal antibodies. The HA0 (with unmodified cleavage site) was monomeric, while the HA1 contained oligomeric forms. Upon rabbit immunization, both HA proteins elicited neutralizing antibodies against the homologous virus (A/Vietnam/1203/2004, clade 1) as well as cross-neutralizing antibodies against heterologous H5N1 clade 2 strains, including A/Indonesia/5/2005. These results exceeded the human antibody responses against the inactivated sub-virion H5N1 vaccine.
Conclusions/Significance: Our data suggest that the 293 Flp-In system could serve as a platform for rapid expression of HA immunogens in mammalian cells from emerging influenza strains.
C1 [Lu, Hanxin; Khurana, Surender; Verma, Nitin; Manischewitz, Jody; King, Lisa; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Beigel, John H.] NIAID, Immunoregulat Lab, Div Intramural Res, SAIC Frederick,NCI Frederick, Frederick, MD USA.
RP Lu, HX (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM hana.golding@fda.hhs.gov
OI Tripp, Ralph/0000-0002-2924-9956
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases, National Institutes of Health
FX This project was funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under contract no.
HHSN261200800001E and in part by the National Institute of Allergy and
Infectious Diseases, National Institutes of Health. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 23
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U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 28
PY 2011
VL 6
IS 2
AR e17297
DI 10.1371/journal.pone.0017297
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729EM
UT WOS:000287931400050
PM 21386997
ER
PT J
AU Tikkanen, R
Auvinen-Lintunen, L
Ducci, F
Sjoberg, RL
Goldman, D
Tiihonen, J
Ojansuu, I
Virkkunen, M
AF Tikkanen, Roope
Auvinen-Lintunen, Laura
Ducci, Francesca
Sjoberg, Rickard L.
Goldman, David
Tiihonen, Jari
Ojansuu, Ilkka
Virkkunen, Matti
TI Psychopathy, PCL-R, and MAOA genotype as predictors of violent
reconvictions
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Monoamine oxidase; Psychopathology; Antisocial personality disorder;
Borderline personality disorder; Personality inventory; Violent crimes;
Alcoholism
ID MONOAMINE-OXIDASE-A; FUNCTIONAL POLYMORPHISM; PSYCHIATRIC-PATIENTS;
RISK-ASSESSMENT; GENE PROMOTER; BEHAVIOR; AGGRESSION; DRINKING;
IMPULSIVITY; CHECKLIST
AB The Revised Psychopathy Checklist (PCL-R) has shown a moderate association with violence. The efficacy of PCL-R in varying monoamine oxidase A (MAOA) genotypes is, however, unexamined. The aim of this study was to investigate the effect of PCL-R and psychopathy on the risk for violent reconvictions among 167 MAOA genotyped alcoholic offenders. Violent reconvictions and PCL-R scores among violent offenders were assessed after a 7-year non-incarcerated follow-up. Regression analysis was used to evaluate the alcohol exposure and age-adjusted effect of PCL-R score and psychopathy on the risk for reconvictions among differing MAOA genotypes. Results suggest that the PCL-R total score predicts impulsive reconvictions among high-activity MAOA offenders (6.8% risk increase for every one-point increase in PCL-R total score. P=0.015), but not among low-activity MAOA offenders, whereas antisocial behavior and attitudes predicted reconvictions in both genotypes (17% risk increase among high-activity MAOA offenders and 12.8% increase among low-activity MAOA offenders for every one-point increase in factor 2 score). Both narcissistic self-image with related interpersonal style (factor 1 score) and psychopathy (PCL-R >= 30) failed to predict future violence. Results suggest that the efficacy of PCL-R is altered by MAOA genotype, alcohol exposure, and age, which seems important to note when PCL-R is used for risk assessments that will have legal or costly preventive work consequences. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Tikkanen, Roope; Auvinen-Lintunen, Laura; Ojansuu, Ilkka; Virkkunen, Matti] Univ Helsinki, Inst Clin Med, Dept Psychiat, FIN-00029 Huch, Finland.
[Ducci, Francesca] Div Psychol SGDP Ctr, Inst Psychiat, London, England.
[Sjoberg, Rickard L.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Sjoberg, Rickard L.] Uppsala Univ, Clin Res Ctr, Uppsala, Sweden.
[Sjoberg, Rickard L.] Umea Univ Hosp, Dept Neurosurg, S-90185 Umea, Sweden.
[Tiihonen, Jari] Univ Kuopio, Niuvaniemi Hosp, Dept Forens Psychiat & Clin Physiol, FIN-70211 Kuopio, Finland.
[Tiihonen, Jari] Kuopio Univ Hosp, Dept Clin Physiol, SF-70210 Kuopio, Finland.
[Tiihonen, Jari] Natl Inst Hlth & Welf, Helsinki, Finland.
[Virkkunen, Matti] Kellokoski Psychiat Hosp, Kellokoski, Finland.
RP Tikkanen, R (reprint author), Univ Helsinki, Inst Clin Med, Dept Psychiat, POB 590, FIN-00029 Huch, Finland.
EM roope.tikkanen@helsinki.fi
RI Sjoberg, Rickard/B-9337-2008; Tiihonen, Jari/G-3078-2012; Sjoberg,
Rickard/M-4690-2014; Goldman, David/F-9772-2010
OI Tiihonen, Jari/0000-0002-0400-6798; Goldman, David/0000-0002-1724-5405
FU National Institute on Alcohol Abuse and Alcoholism, NIH
FX This research was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, NIH. We thank the
Legal Register Centre for contribution of register data. No financial
support was received from anyone benefiting from these results. Ms. Aija
Rasanen is to be thanked for diligent secretarial assistance.
NR 32
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U1 1
U2 18
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD FEB 28
PY 2011
VL 185
IS 3
BP 382
EP 386
DI 10.1016/j.psychres.2010.08.026
PG 5
WC Psychiatry
SC Psychiatry
GA 722WY
UT WOS:000287467200014
PM 20850185
ER
PT J
AU Onyamboko, MA
Meshnick, SR
Fleckenstein, L
Koch, MA
Atibu, J
Lokomba, V
Douoguih, M
Hemingway-Foday, J
Wesche, D
Ryder, RW
Bose, C
Wright, LL
Tshefu, AK
Capparelli, EV
AF Onyamboko, Marie A.
Meshnick, Steven R.
Fleckenstein, Lawrence
Koch, Matthew A.
Atibu, Joseph
Lokomba, Victor
Douoguih, Macaya
Hemingway-Foday, Jennifer
Wesche, David
Ryder, Robert W.
Bose, Carl
Wright, Linda L.
Tshefu, Antoinette K.
Capparelli, Edmund V.
TI Pharmacokinetics and pharmacodynamics of artesunate and
dihydroartemisinin following oral treatment in pregnant women with
asymptomatic Plasmodium falciparum infections in Kinshasa DRC
SO MALARIA JOURNAL
LA English
DT Article
ID SULFADOXINE-PYRIMETHAMINE; MALARIA; DISPOSITION; CONGO; BIOAVAILABILITY;
VOLUNTEERS; RESISTANCE; CHILDREN; BURDEN; ANEMIA
AB Background: In many malaria-endemic countries, increasing resistance may soon compromise the efficacy of sulphadoxine-pyrimethamine (SP) for intermittent preventative treatment (IPT) of malaria in pregnancy. Artemisinin-based IPT regimens represent a promising potential alternative to SP. Pharmacokinetic and safety data supporting the use of artemisinin derivatives in pregnancy are urgently needed.
Methods: Subjects included pregnant women with asymptomatic falciparum parasitaemia between 22-26 weeks (n = 13) or 32-36 weeks gestation (n = 13), the same women at three months postpartum, and 25 non-pregnant parasitaemic controls. All subjects received 200 mg orally administered AS. Plasma total and free levels of AS and its active metabolite DHA were determined using a validated LC-MS method. Non-compartmental pharmacokinetic analysis was performed using standard methods.
Results: All pregnant women delivered live babies. The median birth weight was 3025 grams [range 2130, 3620]; 2 of 26 babies had birth weights less than 2500 grams. Rates of parasite clearance by 12 hours post-dose were high and comparable among the groups. Rapid elimination of AS was observed in all three groups. The 90% CI for the pregnancy: postpartum ratio of geometric means for total and free AUC fell within the pre-specified 0.66 - 1.50 therapeutic equivalence interval. However, more pronounced pharmacokinetic differences were observed between the pregnancy and control subjects, with the 90% CI for the pregnancy: control ratio of geometric means for both total 0.68 (90% CI 0.57-0.81) and free AUC 0.78 (90% CI 0.63-0.95) not fully contained within the 0.66 - 1.50 interval. All subjects cleared parasites rapidly, and there was no difference in the percentage of women who were parasitaemic 12 hours after dosing.
Conclusions: A single dose of orally administered AS was found to be both effective and without adverse effects in this study of second and third trimester pregnant women in the DRC. Although DHA AUC during pregnancy and postpartum were similar, the AUC for the pregnant group was less than the non-pregnant controls. The findings of this study suggest that additional studies on the pharmacokinetics of AS in pregnant women are needed.
C1 [Meshnick, Steven R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Onyamboko, Marie A.; Atibu, Joseph; Lokomba, Victor; Tshefu, Antoinette K.] Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
[Fleckenstein, Lawrence] Univ Iowa, Iowa City, IA USA.
[Koch, Matthew A.; Hemingway-Foday, Jennifer] RTI Int, Res Triangle Pk, NC USA.
[Douoguih, Macaya] Crucell Holland BV, Leiden, Netherlands.
[Wesche, David] David Wesche Consulting LLC, Ann Arbor, MI USA.
[Ryder, Robert W.; Capparelli, Edmund V.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Bose, Carl] Univ N Carolina, Chapel Hill, NC USA.
[Wright, Linda L.] NICHHD, NIH, Rockville, MD USA.
RP Meshnick, SR (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, 3301 MHRC, Chapel Hill, NC 27599 USA.
EM meshnick@unc.edu
OI Fleckenstein, Lawrence/0000-0001-5320-4531
FU NICHD
FX A Global Network Study supported by grants from NICHD
NR 32
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Z9 16
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD FEB 28
PY 2011
VL 10
AR 49
DI 10.1186/1475-2875-10-49
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 740SI
UT WOS:000288814300002
PM 21352601
ER
PT J
AU Kojima, H
Sata, F
Takeuchi, S
Sueyoshi, T
Nagai, T
AF Kojima, Hiroyuki
Sata, Fumihiro
Takeuchi, Shinji
Sueyoshi, Tatsuya
Nagai, Tadanori
TI Comparative study of human and mouse pregnane X receptor agonistic
activity in 200 pesticides using in vitro reporter gene assays
SO TOXICOLOGY
LA English
DT Article
DE Pregnane X receptor; Pesticide; Human; Mouse; Reporter gene assay
ID ORPHAN NUCLEAR RECEPTOR; ENDOCRINE-DISRUPTING CHEMICALS; XENOBIOTIC
RECEPTOR; CYP3A4 GENE; MEDIATED TRANSCRIPTION; ANDROGEN RECEPTOR; PXR;
INDUCTION; ESTROGEN; METABOLISM
AB The nuclear receptor, pregnane X receptor (PXR), is a ligand-dependent transcription factor that regulates genes involved in xenobiotic metabolism. Recent studies have shown that PXR activation may affect energy metabolism as well as the endocrine and immune systems. In this study, we characterized and compared the agonistic activities of a variety of pesticides against human PXR (hPXR) and mouse PXR (mPXR). We tested the hPXR and mPXR agonistic activity of 200 pesticides (29 organochlorines, 11 diphenyl ethers, 56 organophosphorus pesticides, 12 pyrethroids, 22 carbamates, 12 acid amides, 7 triazines, 7 ureas, and 44 others) by reporter gene assays using COS-7 simian kidney cells. Of the 200 pesticides tested, 106 and 93 activated hPXR and mPXR, respectively, and a total of 111 had hPXR and/or mPXR agonistic activity with greater or lesser inter-species differences. Although all of the pyrethroids and most of the organochlorines and acid amides acted as PXR agonists, a wide range of pesticides with diverse structures also showed hPXR and/or mPXR agonistic activity. Among the 200 pesticides, pyributicarb, pretilachlor, piperophos and butamifos for hPXR, and phosalone, prochloraz, pendimethalin, and butamifos for mPXR, acted as particularly potent activators at low concentrations in the order of 10(-8)-10(-7) M. In addition, we found that several organophosphorus oxon- and pyributicarb oxon-metabolites decreased PXR activation potency compared to their parent compounds. These results suggest that a large number of structurally diverse pesticides and their metabolites possess PXR-mediated transcriptional activity, and their ability to do so varies in a species-dependent manner in humans and mice. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Kojima, Hiroyuki; Takeuchi, Shinji; Nagai, Tadanori] Hokkaido Inst Publ Hlth, Kita Ku, Sapporo, Hokkaido 0600819, Japan.
[Sata, Fumihiro] Natl Inst Publ Hlth, Wako, Saitama 3510197, Japan.
[Sueyoshi, Tatsuya] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
RP Kojima, H (reprint author), Hokkaido Inst Publ Hlth, Kita Ku, Kita 19,Nishi 12, Sapporo, Hokkaido 0600819, Japan.
EM kojima@iph.pref.hokkaido.jp
FU Japan Society for the Promotion of Science (JSPS) [19590610, 20659104]
FX This study was supported by Grants-in-Aid for Scientific Research (C)
(19590610) and Challenging Exploratory Research (20659104) from the
Japan Society for the Promotion of Science (JSPS).
NR 39
TC 28
Z9 30
U1 1
U2 20
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-483X
J9 TOXICOLOGY
JI Toxicology
PD FEB 27
PY 2011
VL 280
IS 3
BP 77
EP 87
DI 10.1016/j.tox.2010.11.008
PG 11
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 722MJ
UT WOS:000287436100002
PM 21115097
ER
PT J
AU Wurtz, RH
Joiner, WM
Berman, RA
AF Wurtz, Robert H.
Joiner, Wilsaan M.
Berman, Rebecca A.
TI Neuronal mechanisms for visual stability: progress and problems
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE corollary discharge; efference copy; visual stability; superior
colliculus; medial dorsal nucleus; frontal eye field
ID SACCADIC EYE-MOVEMENTS; LATERAL INTRAPARIETAL AREA; MONKEY SUPERIOR
COLLICULUS; INDUCED STIMULUS MOVEMENT; HUMAN PARIETAL CORTEX; OLD-WORLD
MONKEYS; BRAIN-STEM TELLS; INFERIOR PULVINAR; FRONTAL-CORTEX; COROLLARY
DISCHARGE
AB How our vision remains stable in spite of the interruptions produced by saccadic eye movements has been a repeatedly revisited perceptual puzzle. The major hypothesis is that a corollary discharge (CD) or efference copy signal provides information that the eye has moved, and this information is used to compensate for the motion. There has been progress in the search for neuronal correlates of such a CD in the monkey brain, the best animal model of the human visual system. In this article, we briefly summarize the evidence for a CD pathway to frontal cortex, and then consider four questions on the relation of neuronal mechanisms in the monkey brain to stable visual perception. First, how can we determine whether the neuronal activity is related to stable visual perception? Second, is the activity a possible neuronal correlate of the proposed transsaccadic memory hypothesis of visual stability? Third, are the neuronal mechanisms modified by visual attention and does our perceived visual stability actually result from neuronal mechanisms related primarily to the central visual field? Fourth, does the pathway from superior colliculus through the pulvinar nucleus to visual cortex contribute to visual stability through suppression of the visual blur produced by saccades?
C1 [Wurtz, Robert H.; Joiner, Wilsaan M.; Berman, Rebecca A.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
EM bob@lsr.nei.nih.gov
NR 68
TC 54
Z9 54
U1 3
U2 19
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD FEB 27
PY 2011
VL 366
IS 1564
BP 492
EP 503
DI 10.1098/rstb.2010.0186
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 707YQ
UT WOS:000286327900003
PM 21242138
ER
PT J
AU Liu, Y
Kawai, K
Khashabi, S
Deng, CX
Liu, YH
Yiu, S
AF Liu, Ying
Kawai, Kirio
Khashabi, Shabnam
Deng, Chuxia
Liu, Yi-Hsin
Yiu, Samuel
TI Inactivation of Smad4 leads to impaired ocular development and cataract
formation (vol 400, pg 476, 2010)
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Correction
C1 [Liu, Ying; Kawai, Kirio; Khashabi, Shabnam; Liu, Yi-Hsin; Yiu, Samuel] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
[Liu, Ying; Kawai, Kirio; Khashabi, Shabnam; Liu, Yi-Hsin; Yiu, Samuel] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA.
[Liu, Ying] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Ophthalm Lab, Guangzhou 510060, Guangdong, Peoples R China.
[Deng, Chuxia] NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA.
RP Yiu, S (reprint author), Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA.
EM syiu@doheny.org
NR 1
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD FEB 25
PY 2011
VL 405
IS 4
BP 706
EP 706
DI 10.1016/j.bbrc.2011.01.097
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 731ZJ
UT WOS:000288149500035
ER
PT J
AU Zanotti-Fregonara, P
Liow, JS
Fujita, M
Dusch, E
Zoghbi, SS
Luong, E
Boellaard, R
Pike, VW
Comtat, C
Innis, RB
AF Zanotti-Fregonara, Paolo
Liow, Jeih-San
Fujita, Masahiro
Dusch, Elodie
Zoghbi, Sami S.
Luong, Elise
Boellaard, Ronald
Pike, Victor W.
Comtat, Claude
Innis, Robert B.
TI Image-Derived Input Function for Human Brain Using High Resolution PET
Imaging with [C-11](R)-rolipram and [C-11]PBR28
SO PLOS ONE
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; INDEPENDENT COMPONENT ANALYSIS; CEREBRAL
METABOLIC-RATE; NONINVASIVE QUANTIFICATION; DYNAMIC PET; RADIOLIGAND;
RECEPTORS; QUANTITATION; VALIDATION
AB Background: The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods.
Methods: All seven methods were tested on twelve scans with [C-11](R)-rolipram, which has a low radiometabolite fraction, and on nineteen scans with [C-11]PBR28 (high radiometabolite fraction). Logan V-T values for both blood and image inputs were calculated using the metabolite-corrected input functions. The agreement of image-derived Logan V-T values with the reference blood-derived Logan V-T values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.
Results: For both radioligands the highest scores were obtained with two blood-based methods, while the blood-free methods generally performed poorly. All methods gave higher scores with [C-11](R)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.
Conclusion: Our study shows that: 1) Image input methods that are validated for a specific tracer and a specific machine may not perform equally well in a different setting; 2) despite the use of high resolution PET images, blood samples are still necessary to obtain a reliable image input function; 3) the accuracy of image input may also vary between radioligands depending on the magnitude of the radiometabolite fraction: the higher the metabolite fraction of a given tracer (e. g., [C-11]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling.
C1 [Zanotti-Fregonara, Paolo; Liow, Jeih-San; Fujita, Masahiro; Zoghbi, Sami S.; Luong, Elise; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Dusch, Elodie; Comtat, Claude] CEA SHFJ, Orsay, France.
[Boellaard, Ronald] Vrije Univ Amsterdam Med Ctr, Dept Nucl Med, Amsterdam, Netherlands.
RP Zanotti-Fregonara, P (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
EM innisr@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services (IRP-NIMH-NIH)
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services (IRP-NIMH-NIH) (PZ-F, J-SL, MF,
SSZ, EL, VWP, RBI). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 38
TC 22
Z9 22
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 25
PY 2011
VL 6
IS 2
AR e17056
DI 10.1371/journal.pone.0017056
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 726YS
UT WOS:000287764100024
PM 21364880
ER
PT J
AU Ramamurthi, KS
AF Ramamurthi, Kumaran S.
TI mRNA Delivers the Goods
SO SCIENCE
LA English
DT Editorial Material
ID PROTEINS; MEMBRANES
C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ramamurthi, KS (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM ramamurthiks@mail.nih.gov
RI Ramamurthi, Kumaran/P-3516-2015
FU Intramural NIH HHS
NR 9
TC 1
Z9 1
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD FEB 25
PY 2011
VL 331
IS 6020
BP 1021
EP 1022
DI 10.1126/science.1201001
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 726DM
UT WOS:000287699000042
PM 21350158
ER
PT J
AU Chi, YH
Semmes, OJ
Jeang, KT
AF Chi, Ya-Hui
Semmes, Oliver John
Jeang, Kuan-Teh
TI A proteomic study of TAR-RNA binding protein (TRBP)-associated factors
SO CELL AND BIOSCIENCE
LA English
DT Article
ID HIV-1 REPLICATION; KINASE PKR; TRBP; DICER; EXPRESSION; MICRORNAS;
INTERFERENCE; SUPPRESSION; VIRUSES; MIRNAS
AB Background: The human TAR RNA-binding protein, TRBP, was first identified and cloned based on its high affinity binding to the small hairpin trans-activation responsive (TAR) RNA of HIV-1. TRBP has more recently been found to be a constituent of the RNA-induced silencing complex (RISC) serving as a Dicer co-factor in the processing of the similar to 70 nucleotide pre-microRNAs(miRNAs) to 21-25 nucleotide mature miRNAs.
Findings: Using co-immunoprecipitation and protein-identification by mass spectrometry, we characterized intracellular proteins that complex with TRBP. These interacting proteins include those that have been described to act in protein synthesis, RNA modifications and processing, DNA transcription, and cell proliferation.
Conclusions: Our findings provide a proteome of factors that may cooperate with TRBP in activities such as miRNA processing and in RNA interference by the RISC complex.
C1 [Chi, Ya-Hui; Jeang, Kuan-Teh] NIAID, NIH, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Chi, Ya-Hui] Natl Hlth Res Inst, Inst Cellular & Syst Med, Zhunan, Taiwan.
[Semmes, Oliver John] Eastern Virginia Med Sch, Leroy T Canoles Jr Canc Res Ctr, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA.
RP Jeang, KT (reprint author), NIAID, NIH, Mol Virol Sect, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kjcang@niaid.nih.gov
RI Chi, Ya-Hui/B-1080-2010
FU NIAID/NIH intramural funds; Intramural AIDS Targeted Anti-viral Program
(IATAP)
FX Work in the KTJ laboratory was supported in part by NIAID/NIH intramural
funds and by the Intramural AIDS Targeted Anti-viral Program (IATAP).
NR 28
TC 14
Z9 14
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD FEB 25
PY 2011
VL 1
AR 9
DI 10.1186/2045-3701-1-9
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982NS
UT WOS:000307052800003
PM 21711701
ER
PT J
AU Sato, Y
Heimeier, RA
Li, CL
Deng, CX
Shi, YB
AF Sato, Yukiyasu
Heimeier, Rachel A.
Li, Cuiling
Deng, Chuxia
Shi, Yun-Bo
TI Extracellular domain of CD98hc is required for early murine development
SO CELL AND BIOSCIENCE
LA English
DT Article
ID THYROID-HORMONE RECEPTORS; AMINO-ACID TRANSPORTER; LETHALITY; INTEGRINS;
MICE; 4F2
AB Background: The multifunctional protein CD98 heavy chain (CD98hc, Slc3a2) associates with integrin beta 1 through its cytoplasmic and transmembrane domains and the CD98hc-mediated integrin signaling is required for maintenance of ES cell proliferation. CD98hc-null mice exhibit early post-implantation lethality similar to integrin beta 1-null mice, supporting the importance of its interaction with integrin beta 1. On the other hand, the extracellular domain of CD98hc interacts with L-type amino acid transporters (LATs) and is essential for appropriate cell surface distribution of LATs. LATs mediate the transport of amino acids and other molecules such as thyroid hormone. In this respect, CD98hc may also affect development via these transporters.
Results: In this study, mice were generated from embryonic stem (ES) cell line (PST080) harboring a mutant CD98hc allele (CD98hc(Delta/+)). Expression of the CD98hc mutant allele results in Delta CD98hc-beta geo fusion protein where extracellular C-terminal 102 amino acids of CD98hc are replaced with beta geo. Analyses of PST080 ES cells as well as reconstituted frog oocytes demonstrated that Delta CD98hc-beta geo fusion protein preserved its ability to interact with integrin beta 1 although this mutant protein was hardly localized on the cell surface. These findings suggest that Delta CD98hc-beta geo protein can mediate integrin signaling but cannot support amino acid transport through LATs. CD98hc(Delta/+) mice were normal. Although some of the implantation sites lacked embryonic component at E9.5, all the implantation sites contained embryonic component at E7.5. Thus, CD98hc(Delta/Delta) embryos are likely to die between E7.5 and E9.5.
Conclusions: Considering that CD98hc complete knockout (CD98hc(-/-)) embryos are reported to die shortly after implantation, our findings suggest potential stage-specific roles of CD98hc in murine embryonic development. CD98hc may be essential for early post-implantation development by regulating integrin-dependent signaling, while the other function of CD98hc as a component of amino acid transporters may be required for embryonic development at later stages.
C1 [Sato, Yukiyasu; Heimeier, Rachel A.; Shi, Yun-Bo] NICHD, NIH, Sect Mol Morphogenesis, Lab Gene Regulat & Dev,Program Cellular Regulat &, Bethesda, MD 20892 USA.
[Sato, Yukiyasu] Kyoto Univ, Grad Sch Med, Dept Gynecol & Obstet, Sakyo Ku, Kyoto 6068507, Japan.
[Heimeier, Rachel A.] Karolinska Inst, Inst Environm Med IMM, S-17177 Stockholm, Sweden.
[Li, Cuiling; Deng, Chuxia] NIDDK, NIH, Mammalian Genet Sect, GDDB, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NICHD, NIH, Sect Mol Morphogenesis, Lab Gene Regulat & Dev,Program Cellular Regulat &, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
FU Intramural Research Programs of NICHD; NIDDK, NIH
FX This research was supported in part by the Intramural Research Programs
of NICHD and NIDDK, NIH.
NR 16
TC 6
Z9 6
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD FEB 25
PY 2011
VL 1
AR 7
DI 10.1186/2045-3701-1-7
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982NS
UT WOS:000307052800001
PM 21711689
ER
PT J
AU Fugmann, SD
AF Fugmann, Sebastian D.
TI RAG-2 Unleashed: Lymphocytes Beware
SO IMMUNITY
LA English
DT Editorial Material
ID DNA-REPAIR
AB The programmed degradation of the RAG-2 enzyme upon entry to S phase restricts V(D)J recombination to the G0-G1 phase of the cell cycle. In this issue of Immunity, Zhang et al. (2011) show that this is critical to prevent lymphoma formation.
C1 NIA, Lab Mol Biol & Immunol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Fugmann, SD (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 6C218, Baltimore, MD 21224 USA.
EM fugmanns@grc.nia.nih.gov
FU Intramural NIH HHS [ZIA AG000388-04]
NR 8
TC 1
Z9 1
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD FEB 25
PY 2011
VL 34
IS 2
BP 137
EP 139
DI 10.1016/j.immuni.2011.02.007
PG 3
WC Immunology
SC Immunology
GA 729YD
UT WOS:000287989500001
PM 21349423
ER
PT J
AU Lee, JW
Chen, H
Pullikotil, P
Quon, MJ
AF Lee, Ji-Won
Chen, Hui
Pullikotil, Philomena
Quon, Michael J.
TI Protein Kinase A-alpha Directly Phosphorylates FoxO1 in Vascular
Endothelial Cells to Regulate Expression of Vascular Cellular Adhesion
Molecule-1 mRNA
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; FORKHEAD TRANSCRIPTION FACTORS; STIMULATES
PHOSPHORYLATION; CAMP; PKA; ANGIOGENESIS; INVOLVEMENT; METABOLISM;
ACTIVATION; MECHANISMS
AB FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase alpha (PKA-alpha). Therefore, we hypothesized that FoxO1 is a novel direct substrate for PKA-alpha. Using an immune complex kinase assay with [gamma-P-32] ATP, purified PKA-alpha directly phosphorylated wildtype FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). Phosphorylation of wild-type FoxO1 (but not FoxO1-AAA) was detectable using phospho-specific antibodies. Similar results were obtained using purified GST-FoxO1 protein as the substrate. Thus, FoxO1 is a direct substrate for PKA-alpha in vitro. In bovine aortic endothelial cells, interaction between endogenous PKA-alpha and endogenous FoxO1 was detected by co-immunoprecipitation. In human aortic endothelial cells (HAEC), pretreatment with H89 (PKA inhibitor) or siRNA knockdown of PKA-alpha decreased forskolin-or prostaglandin E-2-stimulated phosphorylation of FoxO1. In HAEC transfected with a FoxO-promoter luciferase reporter, co-expression of the catalytic domain of PKA-alpha, catalytically inactive mutant PKA-alpha, or siRNA against PKA-alpha caused corresponding increases or decreases in trans-activation of the FoxO promoter. Expression of vascular cellular adhesion molecule-1 mRNA, up-regulated by FoxO1 in endothelial cells, was enhanced by siRNA knockdown of PKA-alpha or treatment of HAEC with the PKA inhibitor H89. Adhesion of monocytes to endothelial cells was enhanced by H89 treatment or overexpression of FoxO1-AAA, similar to effects of TNF-alpha treatment. We conclude that FoxO1 is a novel physiological substrate for PKA-alpha in vascular endothelial cells.
C1 [Lee, Ji-Won; Chen, Hui; Pullikotil, Philomena; Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Quon, MJ (reprint author), Univ Maryland, Div Endocrinol Diabet & Nutr, 660 W Redwood St,HH 495, Baltimore, MD 21201 USA.
EM quonm@medicine.umaryland.edu
OI Quon, Michael/0000-0002-9601-9915
FU National Center for Complementary and Alternative Medicine, National
Institutes of Health
FX This work was supported in part by funds from the Intramural Research
Program, National Center for Complementary and Alternative Medicine,
National Institutes of Health (to M. J. Q.).
NR 32
TC 23
Z9 25
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 25
PY 2011
VL 286
IS 8
BP 6423
EP 6432
DI 10.1074/jbc.M110.180661
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 723AB
UT WOS:000287476400053
PM 21177856
ER
PT J
AU Keefer, MC
Frey, SE
Elizaga, M
Metch, B
De Rosa, SC
Barroso, PF
Tomaras, G
Cardinali, M
Goepfert, P
Kalichman, A
Philippon, V
McElrath, MJ
Jin, X
Ferrari, G
Defawe, OD
Mazzara, GP
Montefiori, D
Pensiero, M
Panicali, DL
Corey, L
AF Keefer, Michael C.
Frey, Sharon E.
Elizaga, Marnie
Metch, Barbara
De Rosa, Stephen C.
Barroso, Paulo F.
Tomaras, Georgia
Cardinali, Massimo
Goepfert, Paul
Kalichman, Artur
Philippon, Valerie
McElrath, M. Juliana
Jin, Xia
Ferrari, Guido
Defawe, Olivier D.
Mazzara, Gail P.
Montefiori, David
Pensiero, Michael
Panicali, Dennis L.
Corey, Lawrence
CA NIAID HIV Vaccine Trials Network
TI A phase I trial of preventive HIV vaccination with heterologous
poxviral-vectors containing matching HIV-1 inserts in healthy
HIV-uninfected subjects
SO VACCINE
LA English
DT Article
DE Preventive HIV vaccine; MVA and Fowlpox vectors; Phase I clinical trial
ID MALARIA ENDEMIC AREA; T-CELL RESPONSES; IMMUNOGENICITY; DNA;
IMMUNIZATION; SAFETY; PRIME; BOOST; VOLUNTEERS; CANDIDATE
AB We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 and 7 in 150 healthy HIV-negative vaccinia-naive participants. FPV-HIV alone was poorly immunogenic, while the high dose (10(9) pfu/2 ml) of MVA-HIV alone elicited maximal responses after two injections: CD4+ and CD8+ T-cell responses in 26/55 (47.3%) and 5/60(8.3%) of participants, respectively, and IFN-gamma ELISpot responses in 28/62(45.2%). The infrequent CD8+ T-cell responses following MVA-HIV priming were boosted only by the heterologous (FPV-HIV) construct in 14/27 (51.9%) of participants post 4th vaccination. Alternatively, HIV envelope-specific binding antibodies were demonstrated in approximately two-thirds of recipients of the homologous boosting regimen, but in less than 20% of subjects after the heterologous vector boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Keefer, Michael C.] Univ Rochester, Sch Med & Dent, Dept Med, Div Infect Dis, Rochester, NY 14642 USA.
[Frey, Sharon E.] St Louis Univ, Sch Med, St Louis, MO USA.
[Elizaga, Marnie; Metch, Barbara; De Rosa, Stephen C.; McElrath, M. Juliana; Defawe, Olivier D.; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Barroso, Paulo F.] Univ Fed Rio de Janeiro, Sch Med HUCFF, Rio De Janeiro, Brazil.
[Tomaras, Georgia; Ferrari, Guido; Montefiori, David] Duke Univ, Sch Med, Durham, NC USA.
[Cardinali, Massimo] NIAID, Henry M Jackson Fdn, Div Aids, NIH, Bethesda, MD 20892 USA.
[Goepfert, Paul] Univ Alabama, Med Sch Birmingham, Birmingham, AL USA.
[Kalichman, Artur] Ctr Referencia & Treinamento DST AIDS, Sao Paulo, Brazil.
[Philippon, Valerie; Mazzara, Gail P.; Panicali, Dennis L.] Therion Biol Inc, Cambridge, MA USA.
RP Keefer, MC (reprint author), Univ Rochester, Sch Med & Dent, Dept Med, Div Infect Dis, Box 689,601 Elmwood Ave, Rochester, NY 14642 USA.
EM Michael_Keefer@urmc.rochester.edu
RI Ferrari, Guido/A-6088-2015; Tomaras, Georgia/J-5041-2016
FU Division of AIDS, National Institutes of Allergy and Infectious
Diseases, National Institutes of Health [1U01 AI046747, 1U01 AI068614,
1U01 AI046703, 1U01 AI068635, 1U01 AI046725, 1U01 AI068618, 1U01
AI46725, 1U01 AI AI047980, 1U01 AI069511, 1U01 AI047996, 1U01 AI069452,
1U01 AI048021, 1U01 AI 068614, 1U01 AI069414, 1U01 AI069420, AI026507];
National Center for Research Resources (NCRR), National Institutes of
Health (NIH) [UL1 RR 024160]; NIH Roadmap for Medical Research
FX Division of AIDS, National Institutes of Allergy and Infectious
Diseases, National Institutes of Health (grants 1U01 AI046747, 1U01
AI068614, 1U01 AI046703, 1U01 AI068635, 1U01 AI046725, 1U01 AI068618,
1U01 AI46725, 1U01 AI AI047980, 1U01 AI069511, 1U01 AI047996: 1U01
AI069452, 1U01 AI048021, 1U01 AI046747, 1U01 AI 068614, 1U01 AI069414,
1U01 AI069420, AI026507). This publication was also made possible by
Grant Number UL1 RR 024160 from the National Center for Research
Resources (NCRR), a component of the National Institutes of Health
(NIH), and NIH Roadmap for Medical Research.
NR 15
TC 34
Z9 35
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD FEB 24
PY 2011
VL 29
IS 10
BP 1948
EP 1958
DI 10.1016/j.vaccine.2010.12.104
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 739PP
UT WOS:000288730500014
PM 21216311
ER
PT J
AU Petrashevskaya, NN
Ishii, M
D'Souza, K
Koch, SE
Fuller-Bicer, GA
Schwartz, A
AF Petrashevskaya, Natalia N.
Ishii, Masakazu
D'Souza, Karen
Koch, Sheryl E.
Fuller-Bicer, Geraldine A.
Schwartz, Arnold
TI Presynaptic stimulus-release and postsynaptic compensatory changes in
mice lacking the N-type calcium channel alpha(1B)-subunit
SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
LA English
DT Article
DE N-type calcium channel; Sympathetic nervous system;
alpha(1)-adrenoreceptors; beta(1)-adrenoreceptors
ID CA-V 2.2; SYMPATHETIC NEUROTRANSMISSION; BLOCKER CILNIDIPINE;
HUMAN-HEART; EXPRESSION; RECEPTORS; SUBTYPES; SYSTEM; MOUSE; RATS
AB N-type (Ca(v)2.2) voltage-dependent calcium channels (VDCC) play an important role in presynaptic neurotransmitter release in the autonomic nervous system and may be clinically relevant in the treatment of cardiovascular diseases. The physiological impact of N-type VDCC ablation on cardiac function, stimulus-release coupling and cardiac autonomic regulation was studied using mice deficient in the alpha(1B) subunit of the N-type channel (N-type-/-). The positive inotropic effect (increase in + dP/dt) secondary to high frequency field stimulation (HFFS), mediated by the sympathetic nervous system, was decreased by 33 +/- 12.6% in N-type-/- versus 89 +/- 11.4% in Wild-Type (WT)(P < 0.01), whereas the negative inotropic response (decrease in + dP/dt) following HFFS in the presence of propranolol, mediated by the parasympathetic nervous system, was similar to that in Wild-type (WT) animals 34 +/- 5.0% and 35 +/- 5.4%, respectively. There were no changes in the postsynaptic beta-adrenergic responsiveness, beta-adrenoreceptor density or adenylyl cyclase activity. N-type-/- hearts demonstrated an increased contractile response to alpha(1)-adrenoreceptor (alpha(1)-ADR) stimulation with 10(-5) M phenylephrine in the presence of the beta-blocker propranolol, which might be attributed to an increased expression of pLC beta 1. Protein abundance of other signal transducers for alpha(1) ADR transduction protein was not changed in the N-type-/- hearts.
These results suggest that selective impairment of sympathetic inflow does not modulate postsynaptic beta-adrenergic responsiveness, but causes increased functional response to alpha(1)-adrenergic stimulation. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Petrashevskaya, Natalia N.; Ishii, Masakazu; D'Souza, Karen; Koch, Sheryl E.; Fuller-Bicer, Geraldine A.; Schwartz, Arnold] Univ Cincinnati, Coll Med, Dept Surg, Inst Mol Pharmacol & Biophys, Cincinnati, OH 45267 USA.
RP Petrashevskaya, NN (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM petrashevskayn@mail.nih.gov
FU National Heart, Lung and Blood Institute [NIH PO1 HL00219, NIH T32
HL07382]
FX This work was supported by the National Heart, Lung and Blood Institute
grants NIH PO1 HL00219 (A.S.) and NIH T32 HL07382 (A.S., supported
N.N.P., G.A.F-B., S.E.K.). We would like to thank Elizabeth E. Hartman
for genotyping animals and J Mialet-Perez for CAMP and
beta-adrenoreceptor density measurements.
NR 26
TC 1
Z9 1
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1566-0702
J9 AUTON NEUROSCI-BASIC
JI Auton. Neurosci-Basic Clin.
PD FEB 24
PY 2011
VL 160
IS 1-2
BP 9
EP 15
DI 10.1016/j.autneu.2010.09.007
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 729XZ
UT WOS:000287989000002
PM 20937570
ER
PT J
AU Major, JM
Klonoff-Cohen, HS
Pierce, JP
Slymen, DJ
Saltzstein, SL
Macera, CA
Mercola, D
Kattan, MW
AF Major, Jacqueline M.
Klonoff-Cohen, Hillary S.
Pierce, John P.
Slymen, Donald J.
Saltzstein, Sidney L.
Macera, Caroline A.
Mercola, Dan
Kattan, Michael W.
TI Prostate Cancer Postoperative Nomogram Scores and Obesity
SO PLOS ONE
LA English
DT Article
ID BODY-MASS INDEX; RADICAL PROSTATECTOMY; YOUNG MEN; RECURRENCE; DISEASE;
COHORT; SMOKING; TRENDS; RATES; GRADE
AB Purpose: Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity.
Methods: We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs).
Results: In the present study, aggressive prostate cancer (Gleason >= 7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28-0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01-1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11-1.90).
Conclusion: Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making.
C1 [Major, Jacqueline M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Major, Jacqueline M.; Klonoff-Cohen, Hillary S.; Pierce, John P.] Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Klonoff-Cohen, Hillary S.; Pierce, John P.; Saltzstein, Sidney L.] UCSD Moores Canc Ctr, La Jolla, CA USA.
[Slymen, Donald J.; Macera, Caroline A.] San Diego State Univ, Grad Sch Publ Hlth, Dept Epidemiol & Biostat, San Diego, CA 92182 USA.
[Mercola, Dan] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA USA.
[Kattan, Michael W.] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
RP Major, JM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM jacqueline.major@nih.gov
OI , dan/0000-0002-0281-9840
FU UCI Strategic Partners for the Evaluation of Cancer Signatures for
Prostate Cancer study [NCI U01CA114810]
FX This work was supported in part by the UCI Strategic Partners for the
Evaluation of Cancer Signatures for Prostate Cancer study (NCI
U01CA114810). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript. No
additional external funding was received for this study.
NR 27
TC 3
Z9 3
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 24
PY 2011
VL 6
IS 2
AR e17382
DI 10.1371/journal.pone.0017382
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 726XY
UT WOS:000287761700050
PM 21390220
ER
PT J
AU Acharya, SS
Kaplan, RN
Macdonald, D
Fabiyi, OT
DiMichele, D
Lyden, D
AF Acharya, Suchitra S. l
Kaplan, Rosandra N.
Macdonald, Dan
Fabiyi, Oluwa T.
DiMichele, Donna
Lyden, David
TI Neoangiogenesis contributes to the development of hemophilic synovitis
SO BLOOD
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INDUCED JOINT DAMAGE; RHEUMATOID-ARTHRITIS;
PROGENITOR CELLS; PRECURSOR CELLS; IN-VITRO; ANGIOGENESIS; MIGRATION;
MODEL; OVEREXPRESSION
AB Joint arthropathy secondary to recurrent hemarthroses remains a debilitating complication of hemophilia despite the use of prophylactic factor concentrates. Increased vascularity and neoangiogenesis have been implicated in the progression of musculoskeletal disorders and tumor growth. We hypothesized that de novo blood vessel formation could play a major role in the pathogenesis of hemophilic joint disease (HJD). We observed a 4-fold elevation in proangiogenic factors (vascular endothelial growth factor-A [VEGF-A], stromal cell-derived factor-1, and matrix metalloprotease-9) and proangiogenic macrophage/monocyte cells (VEGF(+)/CD68(+) and VEGFR1(+)/CD11b(+)) in the synovium and peripheral blood of HJD subjects along with significantly increased numbers of VEGFR2(+)/AC133(+) endothelial progenitor cells and CD34(+)/VEGFR1(+) hematopoietic progenitor cells. Sera from HJD subjects induced an angiogenic response in endothelial cells that was abrogated by blocking VEGF, whereas peripheral blood mononuclear cells from HJD subjects stimulated synovial cell proliferation, which was blocked by a humanized anti-VEGF antibody (bevacizumab). Human synovial cells, when incubated with HJD sera, could elicit up-regulation of HIF-1 alpha mRNA with HIF-1 alpha expression in the synovium of HJD subjects, implicating hypoxia in the neoangiogenesis process. Our results provide evidence of local and systemic angiogenic response in hemophilic subjects with recurrent hemarthroses suggesting a potential to develop surrogate biologic markers to identify the onset and progression of hemophilic synovitis. (Blood. 2011;117(8):2484-2493)
C1 [Acharya, Suchitra S. l; Kaplan, Rosandra N.; Macdonald, Dan; Fabiyi, Oluwa T.; DiMichele, Donna; Lyden, David] NIH, Dept Pediat Hematol Oncol, Bethesda, MD 20892 USA.
[Kaplan, Rosandra N.; Macdonald, Dan; Fabiyi, Oluwa T.; Lyden, David] Weill Cornell Med Coll, New York, NY USA.
[Kaplan, Rosandra N.; Lyden, David] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
[Kaplan, Rosandra N.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[DiMichele, Donna] NHLBI, NIH, Bethesda, MD 20892 USA.
[Acharya, Suchitra S. l] Cohen Childrens Med Ctr New York, Pediat Hematol Oncol BMT, New York, NY USA.
RP Acharya, SS (reprint author), Cohen Childrens Med Ctr New York, Pediat Hematol Oncol BMT, 269-01 76th Ave,Suite 255, New Hyde Pk, NY 11040 USA.
EM sacharya@nshs.edu
FU Hemophilia of Georgia Foundation; Doris Duke Charitable Foundation; Hope
Street Kids; ASCO; Butler Foundation; Michael Cuccione Foundation;
National Foundation for Cancer Research; Hartwell Foundation; Malcolm
Hewitt Wiener Foundation; Nancy C. and Daniel P. Paduano Foundation;
American Hellenic Educational Progressive Foundation; Charles and Meryl
Witmer Family Foundation; Stavros S. Niarchos Foundation; Champalimaud
Foundation; Susan G. Komen for the Cure; Children's Cancer and Blood
Foundation Laboratories; A. P. Alexander Family donation for hemophilia
research
FX This work was supported by Hemophilia of Georgia Foundation (S.S.A.),
Doris Duke Charitable Foundation, Hope Street Kids, ASCO, Butler
Foundation, Michael Cuccione Foundation (R.N.K.); National Foundation
for Cancer Research, Hartwell Foundation, Malcolm Hewitt Wiener
Foundation, Nancy C. and Daniel P. Paduano Foundation, American Hellenic
Educational Progressive Foundation, Charles and Meryl Witmer Family
Foundation, Stavros S. Niarchos Foundation, and Champalimaud Foundation
(D.L.); and Susan G. Komen for the Cure (R.N.K., D.L.), Children's
Cancer and Blood Foundation Laboratories, and the A. P. Alexander Family
donation for hemophilia research.
NR 39
TC 31
Z9 31
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 24
PY 2011
VL 117
IS 8
BP 2484
EP 2493
DI 10.1182/blood-2010-05-284653
PG 10
WC Hematology
SC Hematology
GA 726DK
UT WOS:000287698800030
PM 21163925
ER
PT J
AU Wickner, RB
AF Wickner, Reed B.
TI PRION DISEASES Infectivity versus toxicity
SO NATURE
LA English
DT Editorial Material
ID SCRAPIE; PROTEIN
C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
NR 7
TC 9
Z9 9
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 24
PY 2011
VL 470
IS 7335
BP 470
EP 471
DI 10.1038/470470a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725NT
UT WOS:000287652900025
PM 21350474
ER
PT J
AU de Gonzalez, AB
Hartge, P
Thun, MJ
AF de Gonzalez, Amy Berrington
Hartge, Patricia
Thun, Michael J.
TI Body-Mass Index and Mortality among White Adults REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [de Gonzalez, Amy Berrington; Hartge, Patricia] NCI, Bethesda, MD 20892 USA.
[Thun, Michael J.] Amer Canc Soc, Atlanta, GA 30329 USA.
RP de Gonzalez, AB (reprint author), NCI, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 24
PY 2011
VL 364
IS 8
BP 782
EP 783
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 725NP
UT WOS:000287652500029
ER
PT J
AU Ricci, A
Marinello, J
Bortolus, M
Sanchez, A
Grandas, A
Pedroso, E
Pommier, Y
Capranico, G
Maniero, AL
Zagotto, G
AF Ricci, Antonio
Marinello, Jessica
Bortolus, Marco
Sanchez, Albert
Grandas, Anna
Pedroso, Enrique
Pommier, Yves
Capranico, Giovanni
Maniero, Anna Lisa
Zagotto, Giuseppe
TI Electron Paramagnetic Resonance (EPR) Study of Spin-Labeled Camptothecin
Derivatives: A Different Look of the Ternary Complex
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DNA TOPOISOMERASE-I; ANTITUMOR-ACTIVITY; MECHANISM; SITE; SPECTROSCOPY;
INHIBITOR; MOTION; DYNAMICS; CLEAVAGE; SEQUENCE
AB Camptothecin (CPT) derivatives are clinically effective poisons of DNA topoisomerase I (Top 1) able to form a ternary complex with the Top1 DNA complex. The aim of this investigation was to examine the dynamic aspects of the ternary complex formation by means of site-directed spin labeling electron paramagnetic resonance (SDSL-EPR). Two semisynthetic CPT derivatives bearing the paramagnetic moiety were synthesized, and their biological activity was tested. A 22-mer DNA oligonucleotide sequence with high affinity cleavage site for Top1 was also synthesized. EPR experiments were carried out on modified CPT in the presence of DNA, of Top1, or of both. In the last case, a slow motion component in the EPR signal appeared, indicating the formation of the ternary complex. Deconvolution of the EPR spectrum allowed to obtain the relative drug amounts in the complex. It was also possible to demonstrate that the residence time of CPT "trapped" in the ternary complex is longer than hundreds of microseconds.
C1 [Bortolus, Marco; Maniero, Anna Lisa] Univ Padua, Dept Chem, I-30039 Padua, Italy.
[Ricci, Antonio; Zagotto, Giuseppe] Univ Padua, Dept Pharmaceut Sci, I-30039 Padua, Italy.
[Marinello, Jessica; Capranico, Giovanni] Univ Bologna, Dept Biochem G Moruzzi, I-40126 Bologna, Italy.
[Sanchez, Albert; Grandas, Anna; Pedroso, Enrique] Univ Barcelona, Dept Organ Chem, E-08028 Barcelona, Spain.
[Sanchez, Albert; Grandas, Anna; Pedroso, Enrique] Univ Barcelona, IBUB, E-08028 Barcelona, Spain.
[Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Maniero, AL (reprint author), Univ Padua, Dept Chem, Via Marzolo 1, I-30039 Padua, Italy.
EM annalisa.maniero@unipd.it; giuseppe.zagotto@unipd.it
RI Capranico, Giovanni/K-1678-2014; Grandas, Anna/K-6419-2014; Pedroso,
Enrique/L-2360-2014;
OI Capranico, Giovanni/0000-0002-8708-6454; Grandas,
Anna/0000-0001-6517-4018; Pedroso, Enrique/0000-0001-8171-3608;
Bortolus, Marco/0000-0002-6033-6521
FU "Associazione Italiana Ricerca sul Cancro", Milan [IG 4494]; University
of Bologna, Bologna, Italy; NIH Intramural Program, Center for Cancer
Research, National Cancer Institute; Ministerio de Ciencia e Innovacion,
Spain [CTQ2007-68014-C02-01]; Generalitat de Catalunya [2009SGR-208]
FX This work was supported by the "Associazione Italiana Ricerca sul
Cancro", Milan (IG 4494 to G. C.), and the University of Bologna,
Bologna, Italy (to G.C.). We wish to acknowledge support from the NIH
Intramural Program, Center for Cancer Research, National Cancer
Institute (to Y.P.), and from the grants CTQ2007-68014-C02-01
(Ministerio de Ciencia e Innovacion, Spain) and 2009SGR-208 (Generalitat
de Catalunya).
NR 41
TC 5
Z9 5
U1 0
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 24
PY 2011
VL 54
IS 4
BP 1003
EP 1009
DI 10.1021/jm101232t
PG 7
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 721FE
UT WOS:000287338200009
PM 21254781
ER
PT J
AU Annunziata, CM
Hernandez, L
Davis, RE
Zingone, A
Lamy, L
Lam, LT
Hurt, EM
Shaffer, AL
Kuehl, WM
Staudt, LM
AF Annunziata, Christina M.
Hernandez, Lidia
Davis, R. Eric
Zingone, Adriana
Lamy, Laurence
Lam, Lloyd T.
Hurt, Elaine M.
Shaffer, Arthur L.
Kuehl, W. Michael
Staudt, Louis M.
TI A mechanistic rationale for MEK inhibitor therapy in myeloma based on
blockade of MAF oncogene expression
SO BLOOD
LA English
DT Article
ID CELL LUNG-CANCER; MULTIPLE-MYELOMA; IN-VITRO; SIGNALING CASCADE;
PATHWAYS; KINASE; TRANSPLANTATION; OVEREXPRESSION; CLASSIFICATION;
ACTIVATION
AB Modulating aberrant transcription of oncogenes is a relatively unexplored opportunity in cancer therapeutics. In approximately 10% of multiple myelomas, the initiating oncogenic event is translocation of musculoaponeurotic fibrosarcoma oncogene homolog (MAF), a transcriptional activator of key target genes, including cyclinD2. Our prior work showed that MAF is up-regulated in an additional 30% of multiple myeloma cases. The present study describes a common mechanism inducing MAF transcription in both instances. The second mode of MAF transcription occurred in myelomas with multiple myeloma SET domain (MMSET) translocation. MMSET knockdown decreased MAF transcription and cell viability. A small-molecule screen found an inhibitor of mitogen-activated protein kinase kinase (MEK), which activates extracellular signal-regulated kinase (ERK)MAP kinases, reduced MAF mRNA in cells representing MMSET or MAF subgroups. ERK activates transcription of FOS, part of the AP-1 transcription factor. By chromatin immunoprecipitation, FOS bound the MAF promoter, and MEK inhibition decreased this interaction. MEK inhibition selectively induced apoptosis in MAF-expressing myelomas, and FOS inactivation was similarly toxic. Reexpression of MAF rescued cells from death induced by MMSET depletion, MEK inhibition, or FOS inactivation. The data presented herein demonstrate that the MEK-ERK pathway regulates MAF transcription, providing molecular rationale for clinical evaluation of MEK inhibitors in MAF-expressing myeloma. (Blood. 2011;117(8):2396-2404)
C1 [Annunziata, Christina M.; Davis, R. Eric; Lamy, Laurence; Lam, Lloyd T.; Hurt, Elaine M.; Shaffer, Arthur L.; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Annunziata, Christina M.; Hernandez, Lidia; Zingone, Adriana] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Staudt, LM (reprint author), Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (L.M.S., C.M.A.).
NR 33
TC 31
Z9 32
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 24
PY 2011
VL 117
IS 8
BP 2396
EP 2404
DI 10.1182/blood-2010-04-278788
PG 9
WC Hematology
SC Hematology
GA 726DK
UT WOS:000287698800020
PM 21163924
ER
PT J
AU Mazan-Mamczarz, K
Hagner, PR
Zhang, YQ
Dai, BJ
Lehrmann, E
Becker, KG
Keene, JD
Gorospe, M
Liu, ZQ
Gartenhaus, RB
AF Mazan-Mamczarz, Krystyna
Hagner, Patrick R.
Zhang, Yongqing
Dai, Bojie
Lehrmann, Elin
Becker, Kevin G.
Keene, Jack D.
Gorospe, Myriam
Liu, Zhenqui
Gartenhaus, Ronald B.
TI ATM regulates a DNA damage response posttranscriptional RNA operon in
lymphocytes
SO BLOOD
LA English
DT Article
ID DOUBLE-STRAND BREAKS; BINDING PROTEIN HUR; STABILIZING FACTOR HUR; P21
MESSENGER-RNA; ATAXIA-TELANGIECTASIA; P53-INDEPENDENT PATHWAY;
CHECKPOINT PATHWAY; EXPRESSION; CHK2; PHOSPHORYLATION
AB Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell-cycle checkpoints and DNA repair after DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression posttranscriptionally. Dysregulation of this DNA damage response RNA operon is probably relevant to lymphoma development in ataxiatelangiectasia persons. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis. (Blood. 2011;117(8):2441-2450)
C1 [Mazan-Mamczarz, Krystyna; Hagner, Patrick R.; Dai, Bojie; Liu, Zhenqui; Gartenhaus, Ronald B.] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
[Keene, Jack D.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA.
[Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA.
[Gartenhaus, Ronald B.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
[Gartenhaus, Ronald B.] Vet Adm Med Ctr, Baltimore, MD 21218 USA.
RP Gartenhaus, RB (reprint author), Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
EM rgartenhaus@som.umaryland.edu
OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656
FU American Cancer Society; Department of Veterans Affairs; National
Institutes of Health [R01AA017972]; National Institute on Aging,
National Institutes of Health
FX This work was supported in part by the American Cancer Society
(Institutional Research Grant; K.M.-M), the Department of Veterans
Affairs (Merit Review Award; R.B.G.), and the National Institutes of
Health (R01AA017972; R.B.G.). K.G.B. and M.G. were supported by the
National Institute on Aging-Intramural Research Program, National
Institutes of Health.
NR 58
TC 22
Z9 22
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 24
PY 2011
VL 117
IS 8
BP 2441
EP 2450
DI 10.1182/blood-2010-09-310987
PG 10
WC Hematology
SC Hematology
GA 726DK
UT WOS:000287698800025
PM 21209379
ER
PT J
AU Yap, DB
Chu, J
Berg, T
Schapira, M
Cheng, SWG
Moradian, A
Morin, RD
Mungall, AJ
Meissner, B
Boyle, M
Marquez, VE
Marra, MA
Gascoyne, RD
Humphries, RK
Arrowsmith, CH
Morin, GB
Aparicio, SAJR
AF Yap, Damian B.
Chu, Justin
Berg, Tobias
Schapira, Matthieu
Cheng, S. -W. Grace
Moradian, Annie
Morin, Ryan D.
Mungall, Andrew J.
Meissner, Barbara
Boyle, Merrill
Marquez, Victor E.
Marra, Marco A.
Gascoyne, Randy D.
Humphries, R. Keith
Arrowsmith, Cheryl H.
Morin, Gregg B.
Aparicio, Samuel A. J. R.
TI Somatic mutations at EZH2 Y641 act dominantly through a mechanism of
selectively altered PRC2 catalytic activity, to increase H3K27
trimethylation
SO BLOOD
LA English
DT Article
ID HISTONE LYSINE METHYLTRANSFERASES; ACUTE MYELOID-LEUKEMIA; PRODUCT
SPECIFICITY; DNA METHYLATION; FUSION GENE; SET DOMAIN; CANCER; CELLS;
H3; PROTEIN
AB Next-generation sequencing of follicular lymphoma and diffuse-large B-cell lymphoma has revealed frequent somatic, heterozygous Y641 mutations in the histone methyltransferase EZH2. Heterozygosity and the presence of equal quantities of both mutant and wild-type mRNA and expressed protein suggest a dominant mode of action. Surprisingly, B-cell lymphoma cell lines and lymphoma samples harboring heterozygous EZH2(Y641) mutations have increased levels of histone H3 Lys-27-specific trimethylation (H3K27me3). Expression of EZH2(Y641F/N) mutants in cells with EZH2(WT) resulted in an increase of H3K27me3 levels in vivo. Structural modeling of EZH2(Y641) mutants suggests a "Tyr/Phe switch" model whereby structurally neutral, nontyrosine residues at position 641 would decrease affinity for unmethylated and monomethylated H3K27 substrates and potentially favor trimethylation. We demonstrate, using in vitro enzyme assays of reconstituted PRC2 complexes, that Y641 mutations result in a decrease in monomethylation and an increase in trimethylation activity of the enzyme relative to the wild-type enzyme. This represents the first example of a disease-associated gain-of-function mutation in a histone methyltransferase, whereby somatic EZH2 Y641 mutations in lymphoma act dominantly to increase, rather than decrease, histone methylation. The dominant mode of action suggests that allele-specific EZH2 inhibitors should be a future therapeutic strategy for this disease. (Blood. 2011;117(8):2451-2459)
C1 [Yap, Damian B.; Chu, Justin; Aparicio, Samuel A. J. R.] British Columbia Canc Agcy, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada.
[Yap, Damian B.; Gascoyne, Randy D.; Aparicio, Samuel A. J. R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Berg, Tobias; Humphries, R. Keith] British Columbia Canc Agcy, Terry Fox Labs, Vancouver, BC V5Z 1L3, Canada.
[Schapira, Matthieu; Arrowsmith, Cheryl H.] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
[Cheng, S. -W. Grace; Moradian, Annie; Morin, Ryan D.; Mungall, Andrew J.; Marra, Marco A.; Morin, Gregg B.] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Meissner, Barbara; Boyle, Merrill; Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada.
[Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Humphries, R. Keith] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
[Arrowsmith, Cheryl H.] Univ Toronto, Ontario Canc Inst, Toronto, ON, Canada.
[Arrowsmith, Cheryl H.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Morin, Gregg B.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
RP Aparicio, SAJR (reprint author), British Columbia Canc Agcy, Dept Mol Oncol, 675 W 10th, Vancouver, BC V5Z 1L3, Canada.
EM saparicio@bccrc.ca
RI Morin, Gregg/E-9123-2012; Tang, Macy/B-9798-2014; Marra,
Marco/B-5987-2008;
OI Morin, Gregg/0000-0001-8949-4374; Yap, Damian/0000-0002-5370-4592;
Humphries, Richard/0000-0003-0540-7005
FU Canada Research Chair in Molecular Oncology; Leukemia Lymphoma Society
of Canada; Terry Fox Foundation; Deutsche Forschungsgemeinschaft (Bonn,
Germany) [BE4198/1-1]; Leukemia and Lymphoma Society; BC Cancer
Foundation; Pfizer Worldwide Research and Development (San Diego, CA);
Canadian Institutes of Health Research; Canadian Foundation for
Innovation; Genome Canada through the Ontario Genomics Institute;
GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg
Foundation; Ontario Innovation Trust; Ontario Ministry for Research and
Innovation; Merck Co, Inc; Novartis Research Foundation; Swedish Agency
for Innovation Systems; Swedish Foundation for Strategic Research;
Wellcome Trust
FX S.A.J.R.A. was supported by a Canada Research Chair in Molecular
Oncology. R.K.H. was supported by the Leukemia Lymphoma Society of
Canada and the Terry Fox Foundation. T.B. was supported by the Deutsche
Forschungsgemeinschaft (Bonn, Germany; grant no. BE4198/1-1). A.J.M. was
supported by the Leukemia and Lymphoma Society (Career Development
Program Fellowship). This work was supported by the BC Cancer Foundation
and Pfizer Worldwide Research and Development (San Diego, CA). The
Structural Genomics Consortium is a registered charity (no. 1097737)
that receives funds from the Canadian Institutes of Health Research, the
Canadian Foundation for Innovation, Genome Canada through the Ontario
Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and
Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario
Ministry for Research and Innovation, Merck & Co, Inc, the Novartis
Research Foundation, the Swedish Agency for Innovation Systems, the
Swedish Foundation for Strategic Research, and the Wellcome Trust.
NR 37
TC 234
Z9 238
U1 9
U2 25
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 24
PY 2011
VL 117
IS 8
BP 2451
EP 2459
DI 10.1182/blood-2010-11-321208
PG 9
WC Hematology
SC Hematology
GA 726DK
UT WOS:000287698800026
PM 21190999
ER
PT J
AU Cheng, KJ
Lee, YS
Rothman, RB
Dersch, CM
Bittman, RW
Jacobson, AE
Rice, KC
AF Cheng, Kejun
Lee, Yong Sok
Rothman, Richard B.
Dersch, Christina M.
Bittman, Ross W.
Jacobson, Arthur E.
Rice, Kenner C.
TI Probes for Narcotic Receptor Mediated Phenomena. 41. Unusual Inverse
mu-Agonists and Potent mu-Opioid Antagonists by Modification of the
N-Substituent in Enantiomeric 5-(3-Hydroxyphenyl)morphans
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID AFFINITY; ANALOGS
AB Conformational restraint in the N-substituent of enantiomeric 5-(3-hydroxyphenyl)morphans was conferred by the addition of a cyclopropane ring or a double bond. All of the possible enantiomers and isomers of the N-substituted compounds were synthesized. Opioid receptor binding assays indicated that some of them had about 20-fold higher mu-affinity than the compound with an N-phenylpropyl substituent (K(i) = 2-450 nM for the examined compounds with various N-substituents). Most of the compounds acted unusually as inverse agonists in the [(35)S]GTP-gamma-S functional binding assay using nondependent cells that stably express the cloned human mu-opioid receptor. Two of the N-substituted compounds with a cyclopropane ring were very potent mu-opioid antagonists ((+)-29, K(e) = 0.17 and (-)-30, K(e) = 0.3) in the [(35)S]GTP-gamma-S functional binding assay. By comparison of the geometry-optimized structures of the newly synthesized compounds, an attempt was made to rationalize their mu-opioid receptor affinity in terms of the spatial position of N-substituents.
C1 [Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Lee, Yong Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, CIT,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Rothman, Richard B.; Dersch, Christina M.; Bittman, Ross W.] NIDA, Clin Psychopharmacol Sect, Chem Biol Res Branch, Addict Res Ctr,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Rice, KC (reprint author), NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, 5625 Fishers Lane,Room 4N03, Bethesda, MD 20892 USA.
EM kr21f@nih.gov
OI Bittman, Ross/0000-0002-1047-0060
FU National Institute on Drug Abuse (NIDA); National Institute of Alcohol
Abuse and Alcoholism; Clinical Psychopharmacology Section, CBRB, NIDA;
NIH
FX The work of the Drug Design and Synthesis Section, CBRB, NIDA, and
NIAAA, was supported by the NIH Intramural Research Programs of the
National Institute on Drug Abuse (NIDA) and the National Institute of
Alcohol Abuse and Alcoholism, and the Clinical Psychopharmacology
Section, CBRB, NIDA, was supported by the NIH Intramural Research
Program of the National Institute on Drug Abuse (NIDA). We also thank
Dr. Klaus Gawrisch and Dr. Walter Teague (Laboratory of Membrane
Biochemistry and Biophysics, NIAAA, for NMR spectral data. The authors
also express their thanks to Noel Whittaker and Wesley White, Laboratory
of Analytical Chemistry, NIDDK, for mass spectral data and 1H
NMR spectral data. The quantum chemical study utilized PC/LINUX clusters
at the Center for Molecular Modeling of the NIH (http://cit. nih.gov),
and this research was supported by the NIH Intramural Research Program
through the Center for Information Technology.
NR 19
TC 11
Z9 11
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 24
PY 2011
VL 54
IS 4
BP 957
EP 969
DI 10.1021/jm1011676
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 721FE
UT WOS:000287338200005
PM 21247164
ER
PT J
AU Marugan, JJ
Zheng, W
Motabar, O
Southall, N
Goldin, E
Westbroek, W
Stubblefield, BK
Sidransky, E
Aungst, RA
Lea, WA
Simeonov, A
Leister, W
Austin, CP
AF Marugan, Juan J.
Zheng, Wei
Motabar, Omid
Southall, Noel
Goldin, Ehud
Westbroek, Wendy
Stubblefield, Barbara K.
Sidransky, Ellen
Aungst, Ronald A.
Lea, Wendy A.
Simeonov, Anton
Leister, William
Austin, Christopher P.
TI Evaluation of Quinazoline Analogues as Glucocerebrosidase Inhibitors
with Chaperone Activity
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID LYSOSOMAL STORAGE DISORDERS; GAUCHER-DISEASE; PHARMACOLOGICAL
CHAPERONES; BETA-GLUCOSIDASE; CHEMICAL CHAPERONES; HIGHLY POTENT;
ENZYME; FIBROBLASTS; STRATEGIES; INCREASE
AB Gaucher disease is a lysosomal storage disorder (LSD) caused by deficiency in the enzyme glucocerebrosidase (GC). Small molecule chaperones of protein folding and translocation have been proposed as a promising therapeutic approach to this LSD. Most small molecule chaperones described in the literature contain an iminosugar scaffold. Here we present the discovery and evaluation of a new series of GC inhibitors with a quinazoline core. We demonstrate that this series can improve the translocation of GC to the lysosome in patient-derived cells. To optimize this chemical series, systematic synthetic modifications were performed and the SAR was evaluated and compared using three different readouts of compound activity: enzymatic inhibition, enzyme thermostabilization, and lysosomal translocation of GC.
C1 [Marugan, Juan J.; Zheng, Wei; Motabar, Omid; Southall, Noel; Lea, Wendy A.; Simeonov, Anton; Leister, William; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD USA.
[Motabar, Omid; Goldin, Ehud; Westbroek, Wendy; Stubblefield, Barbara K.; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Aungst, Ronald A.] Albany Mol Res Inst, Albany, NY 12203 USA.
RP Marugan, JJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr, Rockville, MD USA.
EM maruganj@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research;
National Human Genome Research Institute, National Institutes of Health
FX This research was supported by the Molecular Libraries Initiative of the
NIH Roadmap for Medical Research and the Intramural Research Program of
the National Human Genome Research Institute, National Institutes of
Health.
NR 36
TC 36
Z9 36
U1 0
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 24
PY 2011
VL 54
IS 4
BP 1033
EP 1058
DI 10.1021/jm1008902
PG 26
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 721FE
UT WOS:000287338200012
PM 21250698
ER
PT J
AU Volkow, ND
Baler, RD
Goldstein, RZ
AF Volkow, Nora D.
Baler, Ruben D.
Goldstein, Rita Z.
TI Addiction: Pulling at the Neural Threads of Social Behaviors
SO NEURON
LA English
DT Editorial Material
ID PREFRONTAL CORTEX; DRUG-ABUSE
AB Addiction coopts the brain's neuronal circuits necessary for insight, reward, motivation, and social behaviors. This functional overlap results in addicted individuals making poor choices despite awareness of the negative consequences; it explains why previously rewarding life situations and the threat of judicial punishment cannot stop drug taking and why a medical rather than a criminal approach is more effective in curtailing addiction.
C1 [Volkow, Nora D.; Baler, Ruben D.] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA.
[Goldstein, Rita Z.] Brookhaven Natl Lab, Ctr Translat Neuroimaging, Dept Med Res, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 19
TC 67
Z9 69
U1 2
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD FEB 24
PY 2011
VL 69
IS 4
BP 599
EP 602
DI 10.1016/j.neuron.2011.01.027
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 735KO
UT WOS:000288413200005
PM 21338873
ER
PT J
AU Lindstrom, S
Schumacher, F
Siddiq, A
Travis, RC
Campa, D
Berndt, SI
Diver, WR
Severi, G
Allen, N
Andriole, G
Bueno-de-Mesquita, B
Chanock, SJ
Crawford, D
Gaziano, JM
Giles, GG
Giovannucci, E
Guo, C
Haiman, CA
Hayes, RB
Halkjaer, J
Hunter, DJ
Johansson, M
Kaaks, R
Kolonel, LN
Navarro, C
Riboli, E
Sacerdote, C
Stampfer, M
Stram, DO
Thun, MJ
Trichopoulos, D
Virtamo, J
Weinstein, SJ
Yeager, M
Henderson, B
Ma, J
Le Marchand, L
Albanes, D
Kraft, P
AF Lindstrom, Sara
Schumacher, Fredrick
Siddiq, Afshan
Travis, Ruth C.
Campa, Daniele
Berndt, Sonja I.
Diver, W. Ryan
Severi, Gianluca
Allen, Naomi
Andriole, Gerald
Bueno-de-Mesquita, Bas
Chanock, Stephen J.
Crawford, David
Gaziano, J. Michael
Giles, Graham G.
Giovannucci, Edward
Guo, Carolyn
Haiman, Christopher A.
Hayes, Richard B.
Halkjaer, Jytte
Hunter, David J.
Johansson, Mattias
Kaaks, Rudolf
Kolonel, Laurence N.
Navarro, Carmen
Riboli, Elio
Sacerdote, Carlotta
Stampfer, Meir
Stram, Daniel O.
Thun, Michael J.
Trichopoulos, Dimitrios
Virtamo, Jarmo
Weinstein, Stephanie J.
Yeager, Meredith
Henderson, Brian
Ma, Jing
Le Marchand, Loic
Albanes, Demetrius
Kraft, Peter
TI Characterizing Associations and SNP-Environment Interactions for
GWAS-Identified Prostate Cancer Risk Markers-Results from BPC3
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GROWTH-FACTOR-I; SUSCEPTIBILITY LOCI; SEQUENCE
VARIANTS; BINDING PROTEIN-3; PSA LEVELS; GENES; 8Q24; METAANALYSIS;
MULTIPLE
AB Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade) and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10(-28)). Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test), where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade,8) tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined.
C1 [Lindstrom, Sara; Guo, Carolyn; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Lindstrom, Sara; Guo, Carolyn; Stampfer, Meir; Trichopoulos, Dimitrios; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Schumacher, Fredrick; Haiman, Christopher A.; Stram, Daniel O.; Henderson, Brian] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
[Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Travis, Ruth C.; Allen, Naomi] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.; Weinstein, Stephanie J.; Yeager, Meredith; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA.
[Severi, Gianluca; Giles, Graham G.] Univ Melbourne, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic, Australia.
[Severi, Gianluca; Giles, Graham G.] Univ Melbourne, Ctr Mol Genet Environm & Analyt Epidemiol, Melbourne, Vic, Australia.
[Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Crawford, David] Univ Colorado, Denver Hlth Sci Ctr, Denver, CO 80202 USA.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, GRECC, Boston, MA USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02115 USA.
[Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Giovannucci, Edward; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hayes, Richard B.] NYU Langone Med Ctr, Div Epidemiol, New York, NY USA.
[Halkjaer, Jytte] Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark.
[Hunter, David J.; Stampfer, Meir; Ma, Jing] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hunter, David J.; Stampfer, Meir; Ma, Jing] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Canc Res Ctr, Honolulu, HI 96822 USA.
[Navarro, Carmen] Reg Hlth Author, Dept Epidemiol, Murcia, Spain.
[Navarro, Carmen] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Sacerdote, Carlotta] CPO Piemonte Torino, Turin, Italy.
[Sacerdote, Carlotta] Human Genet Fdn, Turin, Italy.
[Trichopoulos, Dimitrios] Ctr Food & Nutr Policies, Athens, Greece.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Lindstrom, S (reprint author), Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA.
EM pkraft@hsph.harvard.edu
RI Albanes, Demetrius/B-9749-2015; Campa, Daniele/K-1617-2016;
OI Campa, Daniele/0000-0003-3220-9944; Sacerdote,
Carlotta/0000-0002-8008-5096; Giles, Graham/0000-0003-4946-9099; Hayes,
Richard/0000-0002-0918-661X
FU US National Institutes of Health, National Cancer Institute
[U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07];
NIH/National Cancer Institute, Division of Cancer Epidemiology and
Genetics
FX This work was supported by the US National Institutes of Health,
National Cancer Institute [cooperative agreements U01-CA98233-07 to
David J. Hunter, U01-CA98710-06 to Michael J. Thun, U01-CA98216-06 to
Elio Riboli and Rudolf Kaaks, and U01-CA98758-07 to Brian E. Henderson,
and Intramural Research Program of NIH/National Cancer Institute,
Division of Cancer Epidemiology and Genetics]. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 43
TC 40
Z9 42
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 24
PY 2011
VL 6
IS 2
AR e17142
DI 10.1371/journal.pone.0017142
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 726XY
UT WOS:000287761700031
PM 21390317
ER
PT J
AU Olnes, MJ
Sloand, EM
AF Olnes, Matthew J.
Sloand, Elaine M.
TI Targeting Immune Dysregulation in Myelodysplastic Syndromes
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; ANTITHYMOCYTE GLOBULIN; BONE-MARROW;
APLASTIC-ANEMIA; INTERFERON-GAMMA; SCORING SYSTEM; CYCLOSPORINE-A;
UNITED-STATES; SYNDROME MDS; PHASE-III
AB Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders characterized by ineffective hematopoiesis and a tendency to develop leukemia. In some patients, laboratory and clinical evidence supports a role for the immune system in the pathogenesis of early MDS. Many younger patients who respond to immunosuppressive therapy with drugs such as antithymocyte globulin and cyclosporine have clonal expansions of cytotoxic CD8(+) T cells that suppress normal hematopoiesis, as well as expansion of CD4(+) helper T-cell subsets that promote and sustain autoimmunity. Immunosuppressive therapy can produce hematologic responses in some patients and may improve survival and halt leukemic progression. In this report, we describe a 56-year-old woman who presented with fatigue and easy bruising, eventually became pancytopenic, and was diagnosed with MDS. After treatment with a clinical protocol using alemtuzumab, an anti-CD52 antibody, her blood cell counts returned to normal and she has remained in complete remission for more than 2 years of follow-up. In this article, we review the pathobiology of immune dysregulation in MDS and summarize the role of immunosuppressive therapy in MDS. JAMA. 2011; 305(8): 814-819
C1 [Olnes, Matthew J.; Sloand, Elaine M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Olnes, Matthew J.] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
RP Olnes, MJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-1341, Bethesda, MD 20892 USA.
EM olnesmj@nhlbi.nih.gov
FU Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI);
Center for Human Immunology, Autoimmunity, and Inflammation; National
Institutes of Health; NHLBI
FX Dr Olnes is supported by Intramural funding from the Hematology Branch,
National Heart, Lung, and Blood Institute (NHLBI); and the Center for
Human Immunology, Autoimmunity, and Inflammation; National Institutes of
Health. Dr Sloand was supported by the Intramural NHLBI.
NR 50
TC 27
Z9 28
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 23
PY 2011
VL 305
IS 8
BP 814
EP 819
DI 10.1001/jama.2011.194
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 724RQ
UT WOS:000287594300025
PM 21343581
ER
PT J
AU Samuel, AS
Subbiah, M
Shive, H
Collins, PL
Samal, SK
AF Samuel, Arthur S.
Subbiah, Madhuri
Shive, Heather
Collins, Peter L.
Samal, Siba K.
TI Experimental infection of hamsters with avian paramyxovirus serotypes 1
to 9
SO VETERINARY RESEARCH
LA English
DT Article
ID NEWCASTLE-DISEASE VIRUS; COMPLETE GENOME SEQUENCE; COMPLETE
NUCLEOTIDE-SEQUENCE; RESPIRATORY-DISEASE; COMMERCIAL POULTRY; MODEL;
YUCAIPA; PROTEIN; VIRULENCE; CHICKENS
AB Avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds throughout the world and are separated into nine serotypes (APMV-1 to -9). Only in the case of APMV-1, the infection of non-avian species has been investigated. The APMVs presently are being considered as human vaccine vectors. In this study, we evaluated the replication and pathogenicity of all nine APMV serotypes in hamsters. The hamsters were inoculated intranasally with each virus and monitored for clinical disease, pathology, histopathology, virus replication, and seroconversion. On the basis of one or more of these criteria, each of the APMV serotypes was found to replicate in hamsters. The APMVs produced mild or inapparent clinical signs in hamsters except for APMV-9, which produced moderate disease. Gross lesions were observed over the pulmonary surface of hamsters infected with APMV-2 & -3, which showed petechial and ecchymotic hemorrhages, respectively. Replication of all of the APMVs except APMV-5 was confirmed in the nasal turbinates and lungs, indicating a tropism for the respiratory tract. Histologically, the infection resulted in lung lesions consistent with bronchointerstitial pneumonia of varying severity and nasal turbinates with blunting or loss of cilia of the epithelium lining the nasal septa. The majority of APMV-infected hamsters exhibited transient histological lesions that self resolved by 14 days post infection (dpi). All of the hamsters infected with the APMVs produced serotype-specific HI or neutralizing antibodies, confirming virus replication. Taken together, these results demonstrate that all nine known APMV serotypes are capable of replicating in hamsters with minimal disease and pathology.
C1 [Samuel, Arthur S.; Subbiah, Madhuri; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Shive, Heather] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU NIAID [N01A060009]; NIAID, NIH
FX We thank Daniel Rockemann, Flavia Dias and all our laboratory members
for their excellent technical assistance and help. "This research was
supported by NIAID contract no. N01A060009 (85% support) and NIAID, NIH
Intramural Research Program (15% support). The views expressed herein do
not necessarily reflect the official policies of the Department of
Health and Human Services; nor does mention of trade names, commercial
practices, or organizations imply endorsement by the U.S. Government."
NR 55
TC 5
Z9 6
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 0928-4249
J9 VET RES
JI Vet. Res.
PD FEB 23
PY 2011
VL 42
AR 38
DI 10.1186/1297-9716-42-38
PG 12
WC Veterinary Sciences
SC Veterinary Sciences
GA 764VD
UT WOS:000290661600002
PM 21345199
ER
PT J
AU Hein, N
Jiang, K
Cornelissen, C
Luscher, B
AF Hein, Nadine
Jiang, Kan
Cornelissen, Christian
Luescher, Bernhard
TI TGF beta 1 enhances MAD1 expression and stimulates promoter-bound Pol II
phosphorylation: basic functions of C/EBP, SP and SMAD3 transcription
factors
SO BMC MOLECULAR BIOLOGY
LA English
DT Article
ID HISTONE DEACETYLASE ACTIVITY; MYC ANTAGONIST MAD1; CASEIN KINASE-II;
TGF-BETA; C-MYC; MYC/MAX/MAD NETWORK; GENE-EXPRESSION; CELL-GROWTH;
DIFFERENTIATION; REPRESSION
AB Background: The MAD1 protein, a member of the MYC/MAX/MAD network of transcriptional regulators, controls cell proliferation, differentiation and apoptosis. MAD1 functions as a transcriptional repressor, one direct target gene being the tumor suppressor PTEN. Repression of this gene is critical to mediate the anti-apoptotic function of MAD1. Under certain conditions it also antagonizes the functions of the oncoprotein MYC. Previous studies have demonstrated that MAD1 expression is controlled by different cytokines and growth factors. Moreover we have recently demonstrated that the MAD1 promoter is controlled by the cytokine granulocyte colony-stimulating factor (G-CSF) through the activation of STAT3, MAP kinases and C/EBP transcription factors.
Results: We observed that in addition to G-CSF, the cytokine transforming growth factor beta (TGF beta 1) rapidly induced the expression of MAD1 mRNA and protein in promyelocytic tumor cells. Moreover we found that C/EBP and SP transcription factors cooperated in regulating the expression of MAD1. This cooperativity was dependent on the respective binding sites in the proximal promoter, with the CCAAT boxes being bound by C/EBP alpha/beta heterodimers. Both C/EBP and SP transcription factors bound constitutively to DNA without obvious changes in response to TGF beta 1. In addition SMAD3 stimulated the MAD1 reporter, cooperated with C/EBP alpha and was bound to the core promoter region. Thus SMAD3 appears to be a potential link between TGF beta 1 signaling and C/EBP regulated promoter activity. Moreover TGF beta 1 stimulated the phosphorylation of polymerase II at serine 2 and its progression into the gene body, consistent with enhanced processivity.
Conclusions: Our findings suggest that C/EBP and SP factors provide a platform of transcription factors near the core promoter of the MAD1 gene that participate in mediating signal transduction events emanating from different cytokine receptors. SMAD3, a target of TGF beta 1 signaling, appears to be functionally relevant. We suggest that a key event induced by TGF beta 1 at the MAD1 promoter is the recruitment or activation of cofactors, possibly in complex with C/EBP, SP, and SMAD3 transcriptional regulators, that control polymerase activity.
C1 [Hein, Nadine; Jiang, Kan; Cornelissen, Christian; Luescher, Bernhard] Rhein Westfal TH Aachen, Sch Med, Inst Biochem & Mol Biol, D-52057 Aachen, Germany.
[Hein, Nadine] Peter MacCallum Canc Ctr, Growth Control & Differentiat Program, Lab Growth Control, Melbourne, Vic, Australia.
[Jiang, Kan] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Luscher, B (reprint author), Rhein Westfal TH Aachen, Sch Med, Inst Biochem & Mol Biol, D-52057 Aachen, Germany.
EM luescher@rwth-aachen.de
FU Deutsche Forschungsgemeinschaft [SFB 542, B8, C11]
FX We thank R. Bernards, A. Friedman, H. Rotheneder, and G. Suske for
providing reagents, K. Eckert, J. Luscher-Firzlaff, and L.-G. Larsson
for helpful discussions. This work was supported by the Deutsche
Forschungsgemeinschaft Grant SFB 542 projects B8 and C11 to BL.
NR 42
TC 4
Z9 5
U1 3
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2199
J9 BMC MOL BIOL
JI BMC Mol. Biol.
PD FEB 23
PY 2011
VL 12
AR 9
DI 10.1186/1471-2199-12-9
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 734JA
UT WOS:000288329200001
PM 21345218
ER
PT J
AU Lussier, MP
Nasu-Nishimura, Y
Roche, KW
AF Lussier, Marc P.
Nasu-Nishimura, Yukiko
Roche, Katherine W.
TI Activity-Dependent Ubiquitination of the AMPA Receptor Subunit GluA2
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SYNAPTIC PLASTICITY; GLUTAMATE RECEPTORS; RECYCLING ENDOSOMES;
ENDOCYTOSIS; DEGRADATION; DYNAMIN; POLYUBIQUITINATION; INTERNALIZATION;
TRAFFICKING; INHIBITION
AB AMPA receptors (AMPARs) are postsynaptic glutamate-gated ion channels that mediate fast excitatory neurotransmission in the mammalian brain. Synaptic activity modulates the density of synaptic AMPARs, thereby affecting synaptic function, learning, and memory. Consequently, there is intense interest in defining the molecular mechanisms regulating AMPAR trafficking. Protein expression in the postsynaptic density of excitatory synapses is tightly regulated by ubiquitination, a posttranslational modification that dynamically regulates protein trafficking and degradation in response to synaptic activity. In this study, we demonstrate that increasing synaptic activity, via treatment with the GABA(A) receptor antagonist bicuculline, rapidly and robustly induces ubiquitination of the GluA2 AMPAR subunit. Similarly, treatment with AMPAR agonists results in GluA2 ubiquitination, which suggests that ligand binding plays a critical role. Finally, we find that clathrin-and dynamin-dependent endocytosis of AMPARs is required for activity-dependent GluA2 ubiquitination. Our finding that GluA2 undergoes activity-dependent ubiquitination expands our understanding of how ubiquitination regulates synaptic plasticity.
C1 [Lussier, Marc P.; Nasu-Nishimura, Yukiko; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Roche, KW (reprint author), NINDS, Receptor Biol Sect, NIH, Bldg 35,Room 2C-903,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rochek@ninds.nih.gov
OI Roche, Katherine/0000-0001-7282-6539
FU National Institute of Neurological Disorders and Stroke; Le Fond de la
Recherche en Sante du Quebec
FX The National Institute of Neurological Disorders and Stroke Intramural
Research Program (K. W. R.) supported this research and M. P. L. is the
recipient of a postdoctoral fellowship from Le Fond de la Recherche en
Sante du Quebec. We thank John D. Badger II for technical assistance.
NR 29
TC 40
Z9 40
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 23
PY 2011
VL 31
IS 8
BP 3077
EP 3081
DI 10.1523/JNEUROSCI.5944-10.2011
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 725TX
UT WOS:000287670100035
PM 21414928
ER
PT J
AU Xue, JM
Gochuico, BR
Alawad, AS
Feghali-Bostwick, CA
Noth, I
Nathan, SD
Rosen, GD
Rosas, IO
Dacic, S
Ocak, I
Fuhrman, CR
Cuenco, KT
Smith, MA
Jacobs, SS
Zeevi, A
Morel, PA
Pilewski, JM
Valentine, VG
Gibson, KF
Kaminski, N
Sciurba, FC
Zhang, YZ
Duncan, SR
AF Xue, Jianmin
Gochuico, Bernadette R.
Alawad, Ahmad Samer
Feghali-Bostwick, Carol A.
Noth, Imre
Nathan, Steven D.
Rosen, Glenn D.
Rosas, Ivan O.
Dacic, Sanja
Ocak, Iclal
Fuhrman, Carl R.
Cuenco, Karen T.
Smith, Mary A.
Jacobs, Susan S.
Zeevi, Adriana
Morel, Penelope A.
Pilewski, Joseph M.
Valentine, Vincent G.
Gibson, Kevin F.
Kaminski, Naftali
Sciurba, Frank C.
Zhang, Yingze
Duncan, Steven R.
TI The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with
Idiopathic Pulmonary Fibrosis
SO PLOS ONE
LA English
DT Article
ID INTERSTITIAL LUNG-DISEASE; HIGH-RESOLUTION; T-CELLS; HAPLOTYPE;
ALVEOLITIS; ASSOCIATION; IMPAIRMENT; PREVALENCE; SCLEROSIS; INFECTION
AB Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients.
Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U. S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95% CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DL(CO)) compared to the 184 disease subjects who lacked this allele (37.8 +/- 1.7% vs. 42.8 +/- 1.4%, p = 0.036).
Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease.
C1 [Xue, Jianmin; Alawad, Ahmad Samer; Feghali-Bostwick, Carol A.; Pilewski, Joseph M.; Gibson, Kevin F.; Kaminski, Naftali; Sciurba, Frank C.; Zhang, Yingze; Duncan, Steven R.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
[Gochuico, Bernadette R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Noth, Imre] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA.
[Nathan, Steven D.; Smith, Mary A.] Inova Fairfax Hosp, Adv Lung Dis Program, Falls Church, VA USA.
[Rosen, Glenn D.; Jacobs, Susan S.] Stanford Univ, Med Ctr, Dept Med, Stanford, CA 94305 USA.
[Rosas, Ivan O.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA.
[Dacic, Sanja; Zeevi, Adriana] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
[Ocak, Iclal; Fuhrman, Carl R.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA.
[Cuenco, Karen T.] Univ Pittsburgh, Dept Oral Biol Dent Med & Human Genet, Pittsburgh, PA USA.
[Morel, Penelope A.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA.
[Valentine, Vincent G.] Univ Texas Med Branch, Dept Med, Galveston, TX USA.
RP Xue, JM (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
EM duncsr@upmc.edu
OI Morel, Penelope/0000-0002-1743-3676
FU United States National Institutes of Health [1RO1HL073241, 1P50
HL084932, 1 P50 HL084948, 5T32 HL007563]; National Human Genome Research
Institute
FX This research was supported in part by the United States National
Institutes of Health grants 1RO1HL073241, 1P50 HL084932, 1 P50 HL084948,
5T32 HL007563, and the Intramural Research 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 24
Z9 25
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 23
PY 2011
VL 6
IS 2
AR e14715
DI 10.1371/journal.pone.0014715
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725PJ
UT WOS:000287657500003
PM 21373184
ER
PT J
AU Volkow, ND
Tomasi, D
Wang, GJ
Vaska, P
Fowler, JS
Telang, F
Alexoff, D
Logan, J
Wong, C
AF Volkow, Nora D.
Tomasi, Dardo
Wang, Gene-Jack
Vaska, Paul
Fowler, Joanna S.
Telang, Frank
Alexoff, Dave
Logan, Jean
Wong, Christopher
TI Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose
Metabolism
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CEREBRAL-BLOOD-FLOW; MOBILE PHONES; ELECTROMAGNETIC-FIELDS; MAGNETIC
STIMULATION; TELEPHONE USE; PET; ACTIVATION; RADIATION; HUMANS; CORTEX
AB Context The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear.
Objective To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity.
Design, Setting, and Participants Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with ((18)F) fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes ("on" condition) and once with both cell phones deactivated ("off" condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm(3)) and P<.05 (corrected for multiple comparisons) were considered significant.
Main Outcome Measure Brain glucose metabolism computed as absolute metabolism (mu mol/100 g per minute) and as normalized metabolism (region/whole brain).
Results Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 mu mol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67-4.2]; P=.004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R=0.95, P<.001) and normalized metabolism (R=0.89; P<.001).
Conclusions In healthy participants and compared with no exposure, 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance. JAMA. 2011; 305(8): 808-814
C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Volkow, Nora D.; Tomasi, Dardo; Telang, Frank; Wong, Christopher] NIAAA, Bethesda, MD USA.
[Wang, Gene-Jack; Vaska, Paul; Fowler, Joanna S.; Alexoff, Dave; Logan, Jean] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Health (NIH)
FX This study was carried out at Brookhaven National Laboratory (BNL) and
was supported by the Intramural Research Program of the National
Institutes of Health (NIH) and by infrastructure support from the
Department of Energy.
NR 36
TC 84
Z9 92
U1 4
U2 36
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 23
PY 2011
VL 305
IS 8
BP 808
EP 813
DI 10.1001/jama.2011.186
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 724RQ
UT WOS:000287594300024
PM 21343580
ER
PT J
AU Miller, MJ
Walz, AJ
Zhu, H
Wu, CR
Moraski, G
Mollmann, U
Tristani, EM
Crumbliss, AL
Ferdig, MT
Checkley, L
Edwards, RL
Boshoff, HI
AF Miller, Marvin J.
Walz, Andrew J.
Zhu, Helen
Wu, Chunrui
Moraski, Garrett
Moellmann, Ute
Tristani, Esther M.
Crumbliss, Alvin L.
Ferdig, Michael T.
Checkley, Lisa
Edwards, Rachel L.
Boshoff, Helena I.
TI Design, Synthesis, and Study of a Mycobactin-Artemisinin Conjugate That
Has Selective and Potent Activity against Tuberculosis and Malaria
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID DRUG-RESISTANT TUBERCULOSIS; IRON CHELATORS; DELIVERY AGENTS;
SIDEROPHORES; MECHANISM; ANALOGS; CANCER
AB Although the antimalarial agent artemisinin itself is not active against tuberculosis, conjugation to a mycobacterial-specific siderophore (microbial iron chelator) analogue induces significant and selective anti-tuberculosis activity, including activity against multi-and extensively drug-resistant strains of Mycobacterium tuberculosis. The conjugate also retains potent antimalarial activity. Physicochemical and whole-cell studies indicated that ferric-to-ferrous reduction of the iron complex of the conjugate initiates the expected bactericidal Fenton-type radical chemistry on the artemisinin component. Thus, this "Trojan horse" approach demonstrates that new pathogen-selective therapeutic agents in which the iron component of the delivery vehicle also participates in triggering the antibiotic activity can be generated. The result is that one appropriate conjugate has potent and selective activity against two of the most deadly diseases in the world.
C1 [Miller, Marvin J.; Walz, Andrew J.; Zhu, Helen; Wu, Chunrui; Moraski, Garrett] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.
[Moellmann, Ute] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany.
[Tristani, Esther M.; Crumbliss, Alvin L.] Duke Univ, Dept Chem, French Family Sci Ctr, Durham, NC 27708 USA.
[Ferdig, Michael T.; Checkley, Lisa] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Edwards, Rachel L.; Boshoff, Helena I.] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA.
RP Miller, MJ (reprint author), Univ Notre Dame, Dept Chem & Biochem, 251 Nieuwland Sci Hall, Notre Dame, IN 46556 USA.
EM mmiller1@nd.edu
RI Ferdig, Michael/C-6627-2016;
OI Moraski, Garrett/0000-0002-6992-5584; Edwards,
Rachel/0000-0002-7928-7440
FU U.S. National Institutes of Health [R01 AI054193, AI055035]; NSF [CHE
0809466]; NIH, NIAID
FX M.J.M. and M.T.F. gratefully acknowledge support from the U.S. National
Institutes of Health (Grants R01 AI054193 and AI055035). A.L.C. thanks
the NSF (CHE 0809466) for financial support. This research was supported
in part by the Intramural Research Program of the NIH, NIAID.
NR 29
TC 45
Z9 46
U1 2
U2 33
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD FEB 23
PY 2011
VL 133
IS 7
BP 2076
EP 2079
DI 10.1021/ja109665t
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 728YA
UT WOS:000287909200019
PM 21275374
ER
PT J
AU Volkow, ND
Tomasi, D
Wang, GJ
Fowler, JS
Telang, F
Goldstein, RZ
Alia-Klein, N
Wong, C
AF Volkow, Nora D.
Tomasi, Dardo
Wang, Gene-Jack
Fowler, Joanna S.
Telang, Frank
Goldstein, Rita Z.
Alia-Klein, Nelly
Wong, Christopher
TI Reduced Metabolism in Brain "Control Networks" following Cocaine-Cues
Exposure in Female Cocaine Abusers
SO PLOS ONE
LA English
DT Article
ID GENDER-DIFFERENCES; DEPENDENT PATIENTS; TREATMENT-SEEKING;
SUBSTANCE-ABUSE; SMOKED COCAINE; WOMEN; MEN; PROGESTERONE; ADDICTION;
STRESS
AB Objective: Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.
Method: To test this we compared brain metabolism (using PET and (18)FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video.
Results: Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6%+/- 10) whereas males tended to increase it (+5.5% +/- 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus).
Conclusions: Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.
C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA.
[Volkow, Nora D.; Tomasi, Dardo; Telang, Frank] NIAAA, Bethesda, MD USA.
[Wang, Gene-Jack; Fowler, Joanna S.; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Bethesda, MD USA.
EM nvolkow@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015
FU NIH (NIAAA); DOE [DE-AC01-76CH00016]; Medical Directions, Inc.; Federal
Judicial Center; Gruter Institute for Law and Behavioral Research
FX This research was supported by NIH's Intramural Research Program
(NIAAA), and by DOE (DE-AC01-76CH00016). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.; Dr. Volkow reports no competing
interests; Dr. Tomasi reports no competing interests; Dr. Wang reports
no competing interests; Dr. Fowler reports no competing interests; Dr.
Telang reports no competing interests; Dr. Goldstein received
consultation fee from Medical Directions, Inc. and honoraria fee from
Federal Judicial Center and the Gruter Institute for Law and Behavioral
Research; Dr. Klein reports no competing interests; Mr. Wong reports no
competing interests. This does not alter the authors' adherence to all
the PLoS ONE policies on sharing data and materials.
NR 47
TC 31
Z9 31
U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 23
PY 2011
VL 6
IS 2
AR e16573
DI 10.1371/journal.pone.0016573
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725PJ
UT WOS:000287657500011
PM 21373180
ER
PT J
AU Quiel, J
Caucheteux, S
Laurence, A
Singh, NJ
Bocharov, G
Ben-Sasson, SZ
Grossman, Z
Paul, WE
AF Quiel, Juan
Caucheteux, Stephane
Laurence, Arian
Singh, Nevil J.
Bocharov, Gennady
Ben-Sasson, Shlomo Z.
Grossman, Zvi
Paul, William E.
TI Antigen-stimulated CD4 T-cell expansion is inversely and log-linearly
related to precursor number
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cytokine; T-cell cluster
ID BETA-CHAIN GENES; IN-VIVO; DENDRITIC CELLS; ACTIVATION; MEMORY;
FREQUENCY; RECEPTOR; LIGAND; REPERTOIRE; NAIVE
AB Antigen-driven expansion of specific CD4 T cells diminishes, on a per cell basis, as infused cell number increases. There is a linear relation between log precursor number and log factor of expansion (FE), with a slope of similar to-0.5 over a range from 3 to 30,000 precursors. Cell number dependence of FE is observed at low precursor number, implying that the underlying process physiologically regulates antigen-driven T-cell expansion. FE of small numbers of transgenic precursors is not significantly affected by concomitant responses of large numbers of cells specific for different antigens. Increasing antigen amount or exogenous IL-2, IL-7, or IL-15 does not significantly affect FE, nor does FE depend on Fas, TNF-alpha receptor, cytotoxic T-lymphocyte antigen-4, IL-2, or IFN-gamma. Small numbers of Foxp3-deficient T-cell receptor transgenic cells expand to a greater extent than do large numbers, implying that this effect is not mediated by regulatory T cells. Increasing dendritic cell number does result in larger FE, but the quantitative relation between FE and precursor number is not abrogated. Although not excluding competition for peptide/MHC complexes as an explanation, fall in FE with increasing precursor number could be explained by a negative feedback in which increasing numbers of responding cells in a cluster inhibit the expansion of cells of the same specificity within that cluster.
C1 [Quiel, Juan; Caucheteux, Stephane; Ben-Sasson, Shlomo Z.; Grossman, Zvi; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Singh, Nevil J.] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Laurence, Arian] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Bocharov, Gennady] Russian Acad Sci, Inst Numer Math, Moscow 119333, Russia.
RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM wpaul@niaid.nih.gov
RI Laurence, Arian/A-8770-2009
OI Laurence, Arian/0000-0003-0942-8292
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health; US Civilian Research and Development Foundation
[RUX1-2710-MO-06]; Russian Foundation for Basic Research [08-01-00141a];
Russian Academy of Sciences "Basic Research for Medicine"
FX We thank Julie Edwards for her advice on cell sorting strategies and for
excellent operation of our cell sorter and Shirley Starnes for excellent
editorial assistance. This research was supported by the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health. G.B. was supported by the US
Civilian Research and Development Foundation (Award RUX1-2710-MO-06); in
part, by the Russian Foundation for Basic Research (Grant 08-01-00141a);
and, in part, by the program of the Russian Academy of Sciences "Basic
Research for Medicine."
NR 39
TC 16
Z9 16
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 22
PY 2011
VL 108
IS 8
BP 3312
EP 3317
DI 10.1073/pnas.1018525108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 724ML
UT WOS:000287580400046
PM 21292989
ER
PT J
AU Bocharov, G
Quiel, J
Luzyanina, T
Alon, H
Chiglintsev, E
Chereshnev, V
Meier-Schellersheim, M
Paul, WE
Grossman, Z
AF Bocharov, Gennady
Quiel, Juan
Luzyanina, Tatyana
Alon, Hagit
Chiglintsev, Egor
Chereshnev, Valery
Meier-Schellersheim, Martin
Paul, William E.
Grossman, Zvi
TI Feedback regulation of proliferation vs. differentiation rates explains
the dependence of CD4 T-cell expansion on precursor number
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE time delay; parameter estimation
ID MATHEMATICAL-MODEL; MEMORY; ANTIGEN; TOLERANCE; DYNAMICS; NAIVE; SELF;
RECOGNITION; UNCERTAINTY; SENSITIVITY
AB The mechanisms regulating clonal expansion and contraction of T cells in response to immunization remain to be identified. A recent study established that there was a log-linear relation between CD4 T-cell precursor number (PN) and factor of expansion (FE), with a slope of similar to-0.5 over a range of 3-30,000 precursors per mouse. The results suggested inhibition of precursor expansion either by competition for specific antigen-presenting cells or by the action of other antigen-specific cells in the same microenvironment as the most likely explanation. Several molecular mechanisms potentially accounting for such inhibition were examined and rejected. Here we adopt a previously proposed concept, "feedback-regulated balance of growth and differentiation," and show that it can explain the observed findings. We assume that the most differentiated effectors (or memory cells) limit the growth of less differentiated effectors, locally, by increasing the rate of differentiation of the latter cells in a dose-dependent manner. Consequently, expansion is blocked and reversed after a delay that depends on initial PN, accounting for the dependence of the peak of the response on that number. We present a parsimonious mathematical model capable of reproducing immunization response kinetics. Model definition is achieved in part by requiring consistency with available BrdU-labeling and carboxyfluorescein diacetate succinimidyl ester (CFSE)-dilution data. The calibrated model correctly predicts FE as a function of PN. We conclude that feedback-regulated balance of growth and differentiation, although awaiting definite experimental characterization of the hypothetical cells and molecules involved in regulation, can explain the kinetics of CD4 T-cell responses to antigenic stimulation.
C1 [Bocharov, Gennady] Russian Acad Sci, Inst Numer Math, Moscow 119333, Russia.
[Quiel, Juan; Meier-Schellersheim, Martin; Paul, William E.; Grossman, Zvi] NIAID, NIH, Bethesda, MD 20892 USA.
[Luzyanina, Tatyana] Russian Acad Sci, Inst Math Problems Biol, Pushchino 142290, Russia.
[Alon, Hagit; Grossman, Zvi] Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel.
[Chiglintsev, Egor] Novosibirsk State Univ, Novosibirsk 630090, Russia.
[Chereshnev, Valery] Russian Acad Sci, Ural Branch, Inst Immunol & Physiol, Ekaterinburg 620219, Russia.
RP Bocharov, G (reprint author), Russian Acad Sci, Inst Numer Math, Moscow 119333, Russia.
EM bocharov@inm.ras.ru; wpaul@niaid.nih.gov; lcgross@post.tau.ac.il
RI Luzyanina, Tatyana/N-7698-2013; Barley, Kamal/F-9579-2011; Chereshnev,
Valeriy/Q-1730-2015
OI Luzyanina, Tatyana/0000-0002-3586-6563; Barley,
Kamal/0000-0003-1874-9813;
FU US Civilian Research and Development Foundation [RUX1-2710-MO-06];
Tauber Family Foundation (United States); Russian Academy of Sciences
Program "Basic Research for Medicine"; Russian Foundation for Basic
Research; National Institute of Allergy and Infectious Diseases of the
National Institutes of Health
FX This work was supported by the US Civilian Research and Development
Foundation (Award RUX1-2710-MO-06), by the Tauber Family Foundation
(United States), by the Russian Academy of Sciences Program "Basic
Research for Medicine" and the Russian Foundation for Basic Research,
and by the Intramural Research Program of the National Institute of
Allergy and Infectious Diseases of the National Institutes of Health.
NR 33
TC 16
Z9 16
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 22
PY 2011
VL 108
IS 8
BP 3318
EP 3323
DI 10.1073/pnas.1019706108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 724ML
UT WOS:000287580400047
PM 21292990
ER
PT J
AU Dehghan, A
Dupuis, J
Barbalic, M
Bis, JC
Eiriksdottir, G
Lu, C
Pellikka, N
Wallaschofski, H
Kettunen, J
Henneman, P
Baumert, J
Strachan, DP
Fuchsberger, C
Vitart, V
Wilson, JF
Pare, G
Naitza, S
Rudock, ME
Surakka, I
de Geus, EJC
Alizadeh, BZ
Guralnik, J
Shuldiner, A
Tanaka, T
Zee, RYL
Schnabel, RB
Nambi, V
Kavousi, M
Ripatti, S
Nauck, M
Smith, NL
Smith, AV
Sundvall, J
Scheet, P
Liu, YM
Ruokonen, A
Rose, LM
Larson, MG
Hoogeveen, RC
Freimer, NB
Teumer, A
Tracy, RP
Launer, LJ
Buring, JE
Yamamoto, JF
Folsom, AR
Sijbrands, EJG
Pankow, J
Elliott, P
Keaney, JF
Sun, W
Sarin, AP
Fontes, JD
Badola, S
Astor, BC
Hofman, A
Pouta, A
Werdan, K
Greiser, KH
Kuss, O
Schwabedissen, HEMZ
Thiery, J
Jamshidi, Y
Nolte, IM
Soranzo, N
Spector, TD
Volzke, H
Parker, AN
Aspelund, T
Bates, D
Young, L
Tsui, K
Siscovick, DS
Guo, XQ
Rotter, JI
Uda, M
Schlessinger, D
Rudan, I
Hicks, AA
Penninx, BW
Thorand, B
Gieger, C
Coresh, J
Willemsen, G
Harris, TB
Uitterlinden, AG
Jarvelin, MR
Rice, K
Radke, D
Salomaa, V
van Dijk, KW
Boerwinkle, E
Vasan, RS
Ferrucci, L
Gibson, QD
Bandinelli, S
Snieder, H
Boomsma, DI
Xiao, XJ
Campbell, H
Hayward, C
Pramstaller, PP
van Duijn, CM
Peltonen, L
Psaty, BM
Gudnason, V
Ridker, PM
Homuth, G
Koenig, W
Ballantyne, CM
Witteman, JCM
Benjamin, EJ
Perola, M
Chasman, DI
AF Dehghan, Abbas
Dupuis, Josee
Barbalic, Maja
Bis, Joshua C.
Eiriksdottir, Gudny
Lu, Chen
Pellikka, Niina
Wallaschofski, Henri
Kettunen, Johannes
Henneman, Peter
Baumert, Jens
Strachan, David P.
Fuchsberger, Christian
Vitart, Veronique
Wilson, James F.
Pare, Guillaume
Naitza, Silvia
Rudock, Megan E.
Surakka, Ida
de Geus, Eco J. C.
Alizadeh, Behrooz Z.
Guralnik, Jack
Shuldiner, Alan
Tanaka, Toshiko
Zee, Robert Y. L.
Schnabel, Renate B.
Nambi, Vijay
Kavousi, Maryam
Ripatti, Samuli
Nauck, Matthias
Smith, Nicholas L.
Smith, Albert V.
Sundvall, Jouko
Scheet, Paul
Liu, Yongmei
Ruokonen, Aimo
Rose, Lynda M.
Larson, Martin G.
Hoogeveen, Ron C.
Freimer, Nelson B.
Teumer, Alexander
Tracy, Russell P.
Launer, Lenore J.
Buring, Julie E.
Yamamoto, Jennifer F.
Folsom, Aaron R.
Sijbrands, Eric J. G.
Pankow, James
Elliott, Paul
Keaney, John F.
Sun, Wei
Sarin, Antti-Pekka
Fontes, Joao D.
Badola, Sunita
Astor, Brad C.
Hofman, Albert
Pouta, Anneli
Werdan, Karl
Greiser, Karin H.
Kuss, Oliver
Schwabedissen, Henriette E. Meyer Zu
Thiery, Joachim
Jamshidi, Yalda
Nolte, Ilja M.
Soranzo, Nicole
Spector, Timothy D.
Voelzke, Henry
Parker, Alexander N.
Aspelund, Thor
Bates, David
Young, Lauren
Tsui, Kim
Siscovick, David S.
Guo, Xiuqing
Rotter, Jerome I.
Uda, Manuela
Schlessinger, David
Rudan, Igor
Hicks, Andrew A.
Penninx, Brenda W.
Thorand, Barbara
Gieger, Christian
Coresh, Joe
Willemsen, Gonneke
Harris, Tamara B.
Uitterlinden, Andre G.
Jaervelin, Marjo-Riitta
Rice, Kenneth
Radke, Doerte
Salomaa, Veikko
van Dijk, Ko Willems
Boerwinkle, Eric
Vasan, Ramachandran S.
Ferrucci, Luigi
Gibson, Quince D.
Bandinelli, Stefania
Snieder, Harold
Boomsma, Dorret I.
Xiao, Xiangjun
Campbell, Harry
Hayward, Caroline
Pramstaller, Peter P.
van Duijn, Cornelia M.
Peltonen, Leena
Psaty, Bruce M.
Gudnason, Vilmundur
Ridker, Paul M.
Homuth, Georg
Koenig, Wolfgang
Ballantyne, Christie M.
Witteman, Jacqueline C. M.
Benjamin, Emelia J.
Perola, Markus
Chasman, Daniel I.
TI Meta-Analysis of Genome-Wide Association Studies in > 80 000 Subjects
Identifies Multiple Loci for C-Reactive Protein Levels
SO CIRCULATION
LA English
DT Article
DE genetics; inflammation; meta-analysis; myocardial infarction;
genome-wide association study
ID CORONARY-HEART-DISEASE; GENETICALLY ISOLATED POPULATION; NETHERLANDS
TWIN REGISTER; EPIDEMIOLOGIC APPLICATIONS; COMMON VARIANTS; ALPHA-GENE;
CRP GENE; DESIGN; INFLAMMATION; FRAMINGHAM
AB Background-C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels.
Methods and Results-We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P < 2.9 x 10(-6)). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained approximate to 5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease.
Conclusions-We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation. (Circulation. 2011; 123: 731-738.)
C1 [Dehghan, Abbas; Kavousi, Maryam; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
[Dupuis, Josee; Lu, Chen] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, Josee; Larson, Martin G.; Yamamoto, Jennifer F.; Keaney, John F.; Fontes, Joao D.; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Dupuis, Josee; Larson, Martin G.; Yamamoto, Jennifer F.; Keaney, John F.; Fontes, Joao D.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA.
[Eiriksdottir, Gudny; Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Pellikka, Niina; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Genom, Helsinki, Finland.
[Wallaschofski, Henri; Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Kettunen, Johannes; Peltonen, Leena] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England.
[Henneman, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Baumert, Jens; Thorand, Barbara; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Strachan, David P.] St Georges Univ London, Div Community Hlth Sci, London, England.
[Fuchsberger, Christian; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy.
[Fuchsberger, Christian; Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
[Vitart, Veronique; Hayward, Caroline] Western Gen Hosp, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Wilson, James F.; Rudan, Igor; Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Pare, Guillaume; Freimer, Nelson B.] Harvard Univ, Sch Med, Ctr Cardiovasc Dis Prevent, Boston, MA USA.
[Naitza, Silvia; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Rudock, Megan E.; Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Wake Forest, NC USA.
[Surakka, Ida; Ripatti, Samuli; Sarin, Antti-Pekka] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Alizadeh, Behrooz Z.; Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands.
[Guralnik, Jack; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Shuldiner, Alan; Gibson, Quince D.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA.
[Zee, Robert Y. L.; Rose, Lynda M.; Buring, Julie E.; Bates, David; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
[Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med, Mainz, Germany.
[Nambi, Vijay; Hoogeveen, Ron C.; Astor, Brad C.; Coresh, Joe; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Nambi, Vijay; Hoogeveen, Ron C.; Astor, Brad C.; Coresh, Joe; Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Prevent, Houston, TX USA.
[Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA.
[Sundvall, Jouko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Dis Risk, Helsinki, Finland.
[Scheet, Paul; Xiao, Xiangjun] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, Oulu, Finland.
[Teumer, Alexander; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Tracy, Russell P.] Colchester Res Facil, Dept Pathol, Colchester, VT USA.
[Tracy, Russell P.] Colchester Res Facil, Dept Biochem, Colchester, VT USA.
[Folsom, Aaron R.; Pankow, James] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Sijbrands, Eric J. G.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Elliott, Paul; Jaervelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Med Res Council Hlth Protect Agcy Ctr Environm &, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Sun, Wei] Univ N Carolina, Dept Genet, Dept Biostat, Chapel Hill, NC USA.
[Parker, Alexander N.; Young, Lauren; Tsui, Kim] Amgen Inc, Cambridge, MA USA.
[Pouta, Anneli; Jaervelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Life Course & Serv, Helsinki, Finland.
[Werdan, Karl] Univ Halle Wittenberg, Dept Med 3, Halle, Germany.
[Greiser, Karin H.; Kuss, Oliver] Univ Halle Wittenberg, Inst Med Epidemiol Biostat & Informat, Halle, Germany.
[Greiser, Karin H.] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany.
[Schwabedissen, Henriette E. Meyer Zu] Ernst Moritz Arndt Univ Greifswald, Dept Pharmacol, Greifswald, Germany.
[Thiery, Joachim] Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany.
[Jamshidi, Yalda] St Georges Univ London, Div Clin Dev Sci, London, England.
[Jamshidi, Yalda] Kings Coll London, St Thomas Hosp, Dept Twin Res, London WC2R 2LS, England.
[Jamshidi, Yalda] Kings Coll London, St Thomas Hosp, Genet Epidemiol Unit, London WC2R 2LS, England.
[Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England.
[Spector, Timothy D.] Kings Coll London, Dept Twin Res, London WC2R 2LS, England.
[Spector, Timothy D.] Kings Coll London, Genet Epidemiol Unit, London WC2R 2LS, England.
[Voelzke, Henry; Radke, Doerte] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
[Guo, Xiuqing; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Rudan, Igor] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
[Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, EMGO Inst, Amsterdam, Netherlands.
[Jaervelin, Marjo-Riitta] Univ Oulu, Fac Med, Inst Hlth Sci, Oulu, Finland.
[Jaervelin, Marjo-Riitta] Univ Oulu, Fac Med, Bioctr Oulu, Oulu, Finland.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland.
[van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands.
[van Dijk, Ko Willems] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.
RP Witteman, JCM (reprint author), Erasmus MC, Dept Epidemiol, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM j.witteman@erasmusmc.nl; dchasman@rics.bwh.harvard.edu
RI Guo, XQ/G-4621-2010; Fuchsberger, Christian/C-9646-2010; Gudnason,
Vilmundur/K-6885-2015; Aspelund, Thor/F-4826-2011; Willems van Dijk,
Ko/A-1798-2008; Aspelund, Thor/C-5983-2008; Rudan, Igor/I-1467-2012;
Rice, Kenneth/A-4150-2013; xiao, xiangjun/B-1722-2013; Schnabel,
Renate/F-6527-2014; Pramstaller, Peter/C-2357-2008; Thorand,
Barbara/B-5349-2014; Lu, Chen/D-8514-2015; Ripatti, Samuli/H-9446-2014;
Wilson, James F/A-5704-2009; de Geus, Eco/M-9318-2015; Smith,
Albert/K-5150-2015; Hayward, Caroline/M-8818-2016; Naitza,
Silvia/D-5620-2017; Hicks, Andrew/E-9518-2017;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Willems van Dijk,
Ko/0000-0002-2172-7394; Aspelund, Thor/0000-0002-7998-5433; Rudan,
Igor/0000-0001-6993-6884; Rice, Kenneth/0000-0001-5779-4495; Thorand,
Barbara/0000-0002-8416-6440; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; de Geus, Eco/0000-0001-6022-2666;
Smith, Albert/0000-0003-1942-5845; Hayward,
Caroline/0000-0002-9405-9550; Hicks, Andrew/0000-0001-6320-0411; Larson,
Martin/0000-0002-9631-1254; Fuchsberger, Christian/0000-0002-5918-8947;
Soranzo, Nicole/0000-0003-1095-3852; Sijbrands,
Eric/0000-0001-8857-7389; Kuss, Oliver/0000-0003-3301-5869;
Ramachandran, Vasan/0000-0001-7357-5970; Dupuis,
Josee/0000-0003-2871-3603; Jamshidi, Yalda/0000-0003-0151-6482;
Benjamin, Emelia/0000-0003-4076-2336; Gieger,
Christian/0000-0001-6986-9554; Ziad Alizadeh,
Behrooz/0000-0002-1415-8007; Jarvelin, Marjo-Riitta/0000-0002-2149-0630;
Pankow, James/0000-0001-7076-483X; Dehghan, Abbas/0000-0001-6403-016X
FU Roche; AstraZeneca; Amgen
FX Dr Ridker has received research grant support from Roche, AstraZeneca,
and Amgen and is listed as a coinventor on patents held by the Brigham
and Women's Hospital that relate to the use of inflammatory biomarkers
in cardiovascular disease and diabetes mellitus.
NR 77
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U1 2
U2 27
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 22
PY 2011
VL 123
IS 7
BP 731
EP U151
DI 10.1161/CIRCULATIONAHA.110.948570
PG 91
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 724PF
UT WOS:000287588000012
PM 21300955
ER
PT J
AU Mewton, N
Liu, CY
Croisille, P
Bluemke, D
Lima, JAC
AF Mewton, Nathan
Liu, Chia Ying
Croisille, Pierre
Bluemke, David
Lima, Joao A. C.
TI Assessment of Myocardial Fibrosis With Cardiovascular Magnetic Resonance
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Review
DE cardiac magnetic resonance; late gadolinium enhancement; myocardial
fibrosis; T1 mapping
ID LATE GADOLINIUM ENHANCEMENT; IDIOPATHIC DILATED CARDIOMYOPATHY;
LEFT-VENTRICULAR HYPERTROPHY; CORONARY-ARTERY-DISEASE; AORTIC-VALVE
DISEASE; INVERSION-RECOVERY MOLLI; CHRONIC HEART-FAILURE;
DELAYED-ENHANCEMENT; NONISCHEMIC CARDIOMYOPATHY; CONTRAST ENHANCEMENT
AB Diffuse interstitial or replacement myocardial fibrosis is a common feature of a broad variety of cardiomyopathies. Myocardial fibrosis leads to impaired cardiac diastolic and systolic function and is related to adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) may uniquely characterize the extent of replacement fibrosis and may have prognostic value in various cardiomyopathies. Myocardial longitudinal relaxation time mapping is an emerging technique that could improve CMR's diagnostic accuracy, especially for interstitial diffuse myocardial fibrosis. As such, CMR could be integrated in the monitoring and therapeutic management of a large number of patients. This review summarizes the advantages and limitations of CMR for the assessment of myocardial fibrosis. (J Am Coll Cardiol 2011; 57: 891-903) (C) 2011 by the American College of Cardiology Foundation
C1 [Lima, Joao A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD 21287 USA.
[Mewton, Nathan; Croisille, Pierre] Hosp Civils Lyon, Hop Cardiovasc Louis Pradel, Dept Radiol, Lyon, France.
[Bluemke, David] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ, Dept Med, Div Cardiol, 600 N Wolfe St Blalock 524, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Croisille, Pierre/H-4928-2014; 刘, 李陆/H-8469-2015;
OI Croisille, Pierre/0000-0003-4019-3460; Bluemke,
David/0000-0002-8323-8086
FU French Federation of Cardiology; National Institutes of Health
[P20HL101397]
FX Dr. Mewton was supported by a post-doctoral research grant from the
French Federation of Cardiology. This project was also part of a
research effort funded by a National Institutes of Health grant no.
P20HL101397 to Dr. Lima. All other authors have reported that they have
no relationships to disclose. Deborah Kwan, MD, served as Guest Editor
for this paper.
NR 105
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U1 2
U2 30
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 22
PY 2011
VL 57
IS 8
BP 891
EP 903
DI 10.1016/j.jacc.2010.11.013
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 725NB
UT WOS:000287650900003
PM 21329834
ER
PT J
AU McDermott, MM
Liu, KA
Ferrucci, L
Tian, L
Guralnik, JM
Liao, YH
Criqui, MH
AF McDermott, Mary M.
Liu, Kiang
Ferrucci, Luigi
Tian, Lu
Guralnik, Jack M.
Liao, Yihua
Criqui, Michael H.
TI Decline in Functional Performance Predicts Later Increased Mobility Loss
and Mortality in Peripheral Arterial Disease
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE mortality; peripheral vascular disease; physical functioning
ID ANKLE BRACHIAL INDEX; LOWER-EXTREMITY FUNCTION; PHYSICAL-ACTIVITY; LEG
SYMPTOMS; DAILY-LIFE; RISK; ASSOCIATION; DISABILITY; CLASSIFICATION;
OSTEOARTHRITIS
AB Objectives We hypothesized that a greater 2-year decline in office-based functional performance measures would be associated with greater mobility loss and mortality in people with peripheral arterial disease (PAD).
Background Associations of decline in functional performance with clinically important outcomes in patients with PAD are unknown.
Methods A total of 440 men and women with PAD completed the 6-min walk test and measures of walking velocity at baseline and annually for 2 years. Participants were categorized into tertiles according to their functional decline between baseline and 2-year follow-up and were followed annually after the functional change assessment. Cox proportional hazard models were used to assess relations between the 2-year change in functional performance with later mortality and mobility loss, with adjustments for age, sex, race, ankle brachial index, comorbidities, and other confounders.
Results A total of 102 participants (23.2%) died during a median follow-up of 44.5 months after functional change was assessed. Of 319 participants without baseline mobility disability, 60 (18.8%) developed mobility loss after functional change was assessed. Participants in the tertile with the greatest 6-min walk decline had the highest subsequent mobility loss (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.56 to 7.85; p = 0.002), all-cause mortality (HR: 2.16; 95% CI: 1.28 to 3.64; p = 0.004), and cardiovascular disease mortality (HR: 2.45; 95% CI: 1.08 to 5.54; p = 0.031), compared with those with the smallest 6-min walk decline. Greater declines in fastest-paced 4-m walking velocity were associated with higher mobility loss (p trend = 0.018), all-cause mortality (p trend = 0.01), and cardiovascular mortality (p trend = 0.004).
Conclusions Participants with PAD with declining functional performance are at increased risk for later mobility loss and mortality. (J Am Coll Cardiol 2011;57:962-70) (C) 2011 by the American College of Cardiology Foundation
C1 [McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[McDermott, Mary M.; Liu, Kiang; Liao, Yihua] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
RP McDermott, MM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU NHLBI NIH HHS [R01 HL064739, R01 HL058099, R01 HL058099-03, R01
HL058099-04, R01 HL064739-01A1, R01 HL064739-02, R01 HL064739-03, R01
HL064739-04, R01 HL071223, R01 HL071223-01, R01 HL071223-02, R01
HL071223-03, R01 HL071223-04, R01 HL076298, R01 HL076298-01A1, R01
HL076298-02, R01 HL076298-03, R01 HL076298-04]
NR 22
TC 30
Z9 30
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 22
PY 2011
VL 57
IS 8
BP 962
EP 970
DI 10.1016/j.jacc.2010.09.053
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 725NB
UT WOS:000287650900012
PM 21329843
ER
PT J
AU Hensley, SE
Das, SR
Gibbs, JS
Bailey, AL
Schmidt, LM
Bennink, JR
Yewdell, JW
AF Hensley, Scott E.
Das, Suman R.
Gibbs, James S.
Bailey, Adam L.
Schmidt, Loren M.
Bennink, Jack R.
Yewdell, Jonathan W.
TI Influenza A Virus Hemagglutinin Antibody Escape Promotes Neuraminidase
Antigenic Variation and Drug Resistance
SO PLOS ONE
LA English
DT Article
ID IN-VITRO; 4-GUANIDINO-NEU5AC2EN; MUTATIONS; VARIANTS; SENSITIVITY;
GENERATION; ZANAMIVIR
AB Drugs inhibiting the influenza A virus (IAV) neuraminidase (NA) are the cornerstone of anti-IAV chemotherapy and prophylaxis in man. Drug-resistant mutations in NA arise frequently in human isolates, limiting the therapeutic application of NA inhibitors. Here, we show that antibody-driven antigenic variation in one domain of the H1 hemagglutinin Sa site leads to compensatory mutations in NA, resulting in NA antigenic variation and acquisition of drug resistance. These findings indicate that influenza A virus resistance to NA inhibitors can potentially arise from antibody driven HA escape, confounding analysis of influenza NA evolution in nature.
C1 [Hensley, Scott E.; Das, Suman R.; Gibbs, James S.; Bailey, Adam L.; Schmidt, Loren M.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Hensley, SE (reprint author), Wistar Inst Anat & Biol, Philadelphia, PA USA.
EM jyewdell@niaid.nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012; Das, Suman/C-8760-2009
FU National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 21
TC 33
Z9 35
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2011
VL 6
IS 2
AR e15190
DI 10.1371/journal.pone.0015190
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725PA
UT WOS:000287656600003
PM 21364978
ER
PT J
AU Mizuno, N
Baxa, U
Steven, AC
AF Mizuno, Naoko
Baxa, Ulrich
Steven, Alasdair C.
TI Structural dependence of HET-s amyloid fibril infectivity assessed by
cryoelectron microscopy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE assembly nucleation; cryoelectron microscopy; protein template;
polymorphism; three-dimensional image reconstruction
ID SACCHAROMYCES-CEREVISIAE; ELECTRON-MICROSCOPY; PODOSPORA-ANSERINA; PRION
PROTEIN; HET-S(218-289) PRION; YEAST; PROPAGATION; HSP104; MECHANISM;
MODEL
AB HET-s is a prion protein of the fungus Podospora anserina which, in the prion state, is active in a self/nonself recognition process called heterokaryon incompatibility. Its prionogenic properties reside in the C-terminal "prion domain." The HET-s prion domain polymerizes in vitro into amyloid fibrils whose properties depend on the pH of assembly; above pH 3, infectious singlet fibrils are produced, and below pH 3, noninfectious triplet fibrils. To investigate the correlation between structure and infectivity, we performed cryo-EM analyses. Singlet fibrils have a helical pitch of approximately 410 angstrom and a left-handed twist. Triplet fibrils have three protofibrils whose lateral dimensions (36 x 25 angstrom) and axial packing (one subunit per 9.4 angstrom) match those of singlets but differ in their supercoiling. At 8.5-angstrom resolution, the cross-section of the singlet fibril reconstruction is largely consistent with that of a beta-solenoid model previously determined by solid-state NMR. Reconstructions of the triplet fibrils show three protofibrils coiling around a common axis and packed less tightly at pH 3 than at pH 2, eventually peeling off. Taken together with the earlier observation that fragmentation of triplet fibrils by sonication does not increase infectivity, these observations suggest a novel mechanism for self-propagation, whereby daughter fibrils nucleate on the lateral surface of singlet fibrils. In triplets, this surface is occluded, blocking nucleation and thereby explaining their lack of infectivity.
C1 [Mizuno, Naoko; Baxa, Ulrich; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
FU National Institute of Arthritis, Musculoskeletal, and Skin Diseases
FX We thank Dr. D.L.D. Caspar for insightful discussions and many
suggestions; Dr. S. Saupe for advice on sample preparation, Drs. C.
Biertumpfel and G. Cardone for helpful discussions; and Drs. B. Heymann
and D. Winkler for support with computational and microscopy resources,
respectively. This work was supported by the Intramural Research Program
of the National Institute of Arthritis, Musculoskeletal, and Skin
Diseases.
NR 42
TC 38
Z9 39
U1 1
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 22
PY 2011
VL 108
IS 8
BP 3252
EP 3257
DI 10.1073/pnas.1011342108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 724ML
UT WOS:000287580400036
PM 21300906
ER
PT J
AU Kveraga, K
Ghuman, AS
Kassam, KS
Aminoff, EA
Hamalainen, MS
Chaumon, M
Bar, M
AF Kveraga, Kestutis
Ghuman, Avniel Singh
Kassam, Karim S.
Aminoff, Elissa A.
Haemaelaeinen, Matti S.
Chaumon, Maximilien
Bar, Moshe
TI Early onset of neural synchronization in the contextual associations
network
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE phase locking; oscillations; beta; visual cognition
ID PARAHIPPOCAMPAL PLACE AREA; MEDIAL TEMPORAL-LOBES; VISUAL OBJECT
RECOGNITION; TOP-DOWN FACILITATION; RETROSPLENIAL CORTEX; MEMORY
RETRIEVAL; SCENE PERCEPTION; PHASE SYNCHRONIZATION; ORBITOFRONTAL
CORTEX; CORTICAL NETWORKS
AB Objects are more easily recognized in their typical context. However, is contextual information activated early enough to facilitate the perception of individual objects, or is contextual facilitation caused by postperceptual mechanisms? To elucidate this issue, we first need to study the temporal dynamics and neural interactions associated with contextual processing. Studies have shown that the contextual network consists of the parahippocampal, retrosplenial, and medial prefrontal cortices. We used functional MRI, magnetoencephalography, and phase synchrony analyses to compare the neural response to stimuli with strong or weak contextual associations. The context network was activated in functional MRI and preferentially synchronized in magnetoencephalography (MEG) for stimuli with strong contextual associations. Phase synchrony increased early (150-250 ms) only when it involved the parahippocampal cortex, whereas retrosplenial-medial prefrontal cortices synchrony was enhanced later (300-400 ms). These results describe the neural dynamics of context processing and suggest that context is activated early during object perception.
C1 [Kveraga, Kestutis; Haemaelaeinen, Matti S.; Chaumon, Maximilien; Bar, Moshe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Kveraga, Kestutis; Haemaelaeinen, Matti S.; Bar, Moshe] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Ghuman, Avniel Singh] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Kassam, Karim S.] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA.
[Aminoff, Elissa A.] Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA.
[Chaumon, Maximilien] Boston Coll, Dept Psychol, Chestnut Hill, MA 02459 USA.
[Bar, Moshe] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Kveraga, K (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM kestas@nmr.mgh.harvard.edu
RI Hamalainen, Matti/C-8507-2013;
OI Aminoff, Elissa/0000-0002-6455-8930; Ghuman, Avniel/0000-0003-1746-4656
FU National Institute of Mental Health [K01-MH084011]; National Institutes
of Health [NS50615, EY019477]; National Science Foundation [0842947]
FX This research was supported by National Institute of Mental Health Grant
K01-MH084011 (to K.K.), National Institutes of Health Grants NS50615 and
EY019477 (to M.B.), and National Science Foundation Grant 0842947 (to
M.B.).
NR 84
TC 49
Z9 55
U1 5
U2 21
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 22
PY 2011
VL 108
IS 8
BP 3389
EP 3394
DI 10.1073/pnas.1013760108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 724ML
UT WOS:000287580400059
PM 21300869
ER
PT J
AU Yonamine, I
Bamba, T
Nirala, NK
Jesmin, N
Kosakowska-Cholody, T
Nagashima, K
Fukusaki, E
Acharya, JK
Acharya, U
AF Yonamine, Ikuko
Bamba, Takeshi
Nirala, Niraj K.
Jesmin, Nahid
Kosakowska-Cholody, Teresa
Nagashima, Kunio
Fukusaki, Eiichiro
Acharya, Jairaj K.
Acharya, Usha
TI Sphingosine kinases and their metabolites modulate endolysosomal
trafficking in photoreceptors
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID DROSOPHILA-MELANOGASTER; MOLECULAR-CLONING; FUNCTIONAL-CHARACTERIZATION;
SACCHAROMYCES-CEREVISIAE; SPHINGOLIPID METABOLISM; RETINAL DEGENERATION;
MEMBRANE TRAFFICKING; PROTEIN-TRANSPORT; CELL-SURVIVAL; DEEP-ORANGE
AB Internalized membrane proteins are either transported to late endosomes and lysosomes for degradation or recycled to the plasma membrane. Although proteins involved in trafficking and sorting have been well studied, far less is known about the lipid molecules that regulate the intracellular trafficking of membrane proteins. We studied the function of sphingosine kinases and their metabolites in endosomal trafficking using Drosophila melanogaster photoreceptors as a model system. Gain- and loss-of-function analyses show that sphingosine kinases affect trafficking of the G protein-coupled receptor Rhodopsin and the light-sensitive transient receptor potential (TRP) channel by modulating the levels of dihydrosphingosine 1 phosphate (DHS1P) and sphingosine 1 phosphate (S1P). An increase in DHS1P levels relative to S1P leads to the enhanced lysosomal degradation of Rhodopsin and TRP and retinal degeneration in wild-type photoreceptors. Our results suggest that sphingosine kinases and their metabolites modulate photoreceptor homeostasis by influencing endolysosomal trafficking of Rhodopsin and TRP.
C1 [Yonamine, Ikuko; Nirala, Niraj K.; Jesmin, Nahid; Acharya, Usha] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
[Yonamine, Ikuko; Nirala, Niraj K.; Jesmin, Nahid; Acharya, Usha] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
[Bamba, Takeshi; Fukusaki, Eiichiro] Osaka Univ, Dept Biotechnol, Grad Sch Engn, Suita, Osaka 5650871, Japan.
[Kosakowska-Cholody, Teresa; Acharya, Jairaj K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
[Nagashima, Kunio] Sci Applicat Int Corp, Electron Microscopy Facil, Frederick, MD 21702 USA.
[Nagashima, Kunio] Sci Applicat Int Corp, Image Anal Lab, Frederick, MD 21702 USA.
RP Acharya, U (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM usha.acharya@umassmed.edu
FU National Institutes of Health [RO1EY16469]; intramural division of the
National Cancer Institute
FX This work is supported by a National Institutes of Health grant
(RO1EY16469) to U. Acharya and by the intramural division of the
National Cancer Institute to J.K. Acharya.
NR 58
TC 13
Z9 13
U1 1
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD FEB 21
PY 2011
VL 192
IS 4
BP 557
EP 567
DI 10.1083/jcb.201004098
PG 11
WC Cell Biology
SC Cell Biology
GA 731HM
UT WOS:000288096900004
PM 21321100
ER
PT J
AU Bernad, R
Sanchez, P
Rivera, T
Rodriguez-Corsino, M
Boyarchuk, E
Vassias, I
Ray-Gallet, D
Arnaoutov, A
Dasso, M
Almouzni, G
Losada, A
AF Bernad, Rafael
Sanchez, Patricia
Rivera, Teresa
Rodriguez-Corsino, Miriam
Boyarchuk, Ekaterina
Vassias, Isabelle
Ray-Gallet, Dominique
Arnaoutov, Alexei
Dasso, Mary
Almouzni, Genevieve
Losada, Ana
TI Xenopus HJURP and condensin II are required for CENP-A assembly
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID HISTONE H3 VARIANT; MITOTIC CHROMOSOME ARCHITECTURE; CENTROMERIC
CHROMATIN REQUIRES; FISSION YEAST SCM3; BUDDING YEAST; DNA-SYNTHESIS;
EGG EXTRACTS; HUMAN-CELLS; IN-VITRO; NUCLEOSOME
AB Centromeric protein A (CENP-A) is the epigenetic mark of centromeres. CENP-A replenishment is necessary in each cell cycle to compensate for the dilution associated to DNA replication, but how this is achieved mechanistically is largely unknown. We have developed an assay using Xenopus egg extracts that can recapitulate the spatial and temporal specificity of CENP-A deposition observed in human cells, providing us with a robust in vitro system amenable to molecular dissection. Here we show that this deposition depends on Xenopus Holliday junction-recognizing protein (xHJURP), a member of the HJURP/Scm3 family recently identified in yeast and human cells, further supporting the essential role of these chaperones in CENP-A loading. Despite little sequence homology, human HJURP can substitute for xHJURP. We also report that condensin II, but not condensin I, is required for CENP-A assembly and contributes to retention of centromeric CENP-A nucleosomes both in mitosis and interphase. We propose that the chromatin structure imposed by condensin II at centromeres enables CENP-A incorporation initiated by xHJURP.
C1 [Bernad, Rafael; Sanchez, Patricia; Rivera, Teresa; Rodriguez-Corsino, Miriam; Losada, Ana] Spanish Natl Canc Res Ctr CNIO, Chromosome Dynam Grp, Mol Oncol Programme, Madrid 28029, Spain.
[Boyarchuk, Ekaterina; Vassias, Isabelle; Ray-Gallet, Dominique; Almouzni, Genevieve] Inst Curie, Lab Nucl Dynam & Genome Plast, UMR218, CNRS, F-75248 Paris 05, France.
[Arnaoutov, Alexei; Dasso, Mary] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Losada, A (reprint author), Spanish Natl Canc Res Ctr CNIO, Chromosome Dynam Grp, Mol Oncol Programme, Madrid 28029, Spain.
EM alosada@cnio.es
RI Losada, Ana/H-5917-2015;
OI Losada, Ana/0000-0001-5251-3383; Dasso, Mary/0000-0002-5410-1371
FU Spanish Ministry of Science and Innovation [BFU2007-66627]; European
Commission Epigenome Network of Excellence [LSHG-CT-2004-503433,
MIRG-31126, ALTF 77-2007]; La Ligue Nationale contre le Cancer (Equipe
labelisee Ligue); PIC Programs ("Retinoblastome" and "Replication,
Instabilite chromosomique et cancer"); European Commission [ITN
FP7-PEOPLE-2007, FP7-PEOPLE-2008]; Breast cancer and Epigenetics
[ACI-2007-Canceropole IdF]; ANR "FaRC" [PCV06_142302]; ANR "ECenS"
[ANR-09-BLAN-0257-01]; INCa "GepiG"
FX This research has been supported by the Spanish Ministry of Science and
Innovation (grants BFU2007-66627 and CSD-Inesgen to A. Losada, a Juan de
la Cierva contract for R. Bernad, and FPI fellowships to P. Sanchez and
T. Rivera); the European Commission Epigenome Network of Excellence
(LSHG-CT-2004-503433) to G. Almouzni and A. Losada; MIRG-31126 to A.
Losada; and EMBO fellowship ALTF 77-2007 for R. Bernad. Further support
for the group of G. Almouzni comes from La Ligue Nationale contre le
Cancer (Equipe labelisee Ligue 2010); PIC Programs ("Retinoblastome" and
"Replication, Instabilite chromosomique et cancer"); European Commission
ITN FP7-PEOPLE-2007 "Image DDR" and FP7-PEOPLE-2008 "Nucleosome 4D";
ACI-2007-Canceropole IdF "Breast cancer and Epigenetics"; ANR "FaRC"
PCV06_142302 and ANR "ECenS" ANR-09-BLAN-0257-01; and INCa "GepiG".
NR 67
TC 53
Z9 53
U1 0
U2 5
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD FEB 21
PY 2011
VL 192
IS 4
BP 569
EP 582
DI 10.1083/jcb.201005136
PG 14
WC Cell Biology
SC Cell Biology
GA 731HM
UT WOS:000288096900005
PM 21321101
ER
PT J
AU Brochet, DXP
Xie, WJ
Yang, DM
Cheng, HP
Lederer, WJ
AF Brochet, Didier X. P.
Xie, Wenjun
Yang, Dongmei
Cheng, Heping
Lederer, W. Jonathan
TI Quarky Calcium Release in the Heart
SO CIRCULATION RESEARCH
LA English
DT Article
DE quarky Ca2+ release; Ca2+ spark; Ca2+ blink; ryanodine receptor; Ca2+
leak
ID RYANODINE RECEPTOR CLUSTERS; PIG CARDIAC MYOCYTES; CA2+ SPARKS;
SARCOPLASMIC-RETICULUM; SR CA2+; RAT; TERMINATION; DIFFUSION; EVENTS;
MUSCLE
AB Rationale: In cardiac myocytes, "Ca2+ sparks" represent the stereotyped elemental unit of Ca2+ release arising from activation of large arrays of ryanodine receptors (RyRs), whereas "Ca2+ blinks" represent the reciprocal Ca2+ depletion signal produced in the terminal cisterns of the junctional sarcoplasmic reticulum. Emerging evidence, however, suggests possible substructures in local Ca2+ release events.
Objective: With improved detection ability and sensitivity provided by simultaneous spark-blink pair measurements, we investigated possible release events that are smaller than sparks and their interplay with regular sparks.
Methods and Results: We directly visualized small solitary release events amid noise: spontaneous Ca2+ quark-like or "quarky" Ca2+ release (QCR) events in rabbit ventricular myocytes. Because the frequency of QCR events in paced myocytes is much higher than the frequency of Ca2+ sparks, the total Ca2+ leak attributable to the small QCR events is approximately equal to that of the spontaneous Ca2+ sparks. Furthermore, the Ca2+ release underlying a spark consists of an initial high-flux stereotypical release component and a low-flux highly variable QCR component. The QCR part of the spark, but not the initial release, is sensitive to cytosolic Ca2+ buffering by EGTA, suggesting that the QCR component is attributable to a Ca2+-induced Ca2+ release mechanism. Experimental evidence, together with modeling, suggests that QCR events may depend on the opening of rogue RyR2s (or small cluster of RyR2s).
Conclusions: QCR events play an important role in shaping elemental Ca2+ release characteristics and the nonspark QCR events contribute to "invisible" Ca2+ leak in health and disease. (Circ Res. 2011;108:210-218.)
C1 [Xie, Wenjun; Cheng, Heping] Peking Univ, Inst Mol Med, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China.
[Brochet, Didier X. P.; Lederer, W. Jonathan] Univ Maryland, Ctr Biomed Engn & Technol BioMET, Baltimore, MD 21201 USA.
[Yang, Dongmei] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
RP Cheng, HP (reprint author), Peking Univ, Inst Mol Med, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China.
EM dbrochet@umaryland.edu; chengp@pku.edu.cn
RI cheng, heping/A-7299-2011; Xie, Wenjun/G-3869-2015
OI Xie, Wenjun/0000-0003-0493-062X
FU NIH, National Institute on Aging; National Heart, Lung, and Blood
Institute [P01 HL67849, R01-HL36974]; Leducq North American-European
Atrial Fibrillation Research Alliance, European Union by European
Community [FP7/2007-2013, HEALTH-F2-2009-241526]; Maryland Stem Cell
Commissio; Chinese Natural Science Foundation [30630021]; Major State
Basic Science Development Program [2007CB512100, 2011CB809100]
FX This work was supported in part by the Intramural Research Program of
the NIH, National Institute on Aging (to D.Y.); National Heart, Lung,
and Blood Institute grants (grants P01 HL67849 and R01-HL36974), Leducq
North American-European Atrial Fibrillation Research Alliance, European
Union Seventh Framework Program (FP7) "Identification and therapeutic
targeting of common arrhythmia trigger mechanisms" by European
Community's Seventh Framework Programme FP7/2007-2013 under grant
agreement HEALTH-F2-2009-241526, EUTrigTreat and support from the
Maryland Stem Cell Commission (to W.J.L.); and the Chinese Natural
Science Foundation (30630021) and the Major State Basic Science
Development Program (2007CB512100, 2011CB809100) (to H.C.).
NR 27
TC 36
Z9 37
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD FEB 21
PY 2011
VL 108
IS 2
BP 210
EP 218
DI 10.1161/CIRCRESAHA.110.231258
PG 9
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 709DX
UT WOS:000286418700010
PM 21148431
ER
PT J
AU Berezhkovskii, AM
AF Berezhkovskii, A. M.
TI Renewal theory for single-molecule systems with multiple reaction
channels
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID MOTORS
AB Some single-molecule systems share a common feature: the system performs different cycles returning after each cycle to the same state. In such systems we deal with renewal processes. Examples include (1) single-molecule enzymatic reactions, (2) membrane transport through single-occupancy channels, (3) single-molecule fluorescence spectroscopy, and (4) motion of molecular motors. The paper is focused on the analysis of such systems by means of the renewal theory. To be more specific, the theory of renewal processes is used to study multivariate distribution functions of the numbers of different events in a given observation time. Our main results are simple formulas derived for the Laplace transforms of the distribution functions. General results are illustrated by consideration of several examples. [doi:10.1063/1.3551506]
C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
EM berezh@mail.nih.gov
FU National Institutes of Health (NIH), Center for Information Technology
FX The author is grateful to Sergey Bezrukov, Irina Gopich, Stas
Shvartsman, Attila Szabo, and George Weiss for numerous enlightening
discussions of different aspects of the problem and related questions.
This study was supported by the Intramural Research Program of the
National Institutes of Health (NIH), Center for Information Technology.
NR 15
TC 2
Z9 2
U1 1
U2 4
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD FEB 21
PY 2011
VL 134
IS 7
AR 074114
DI 10.1063/1.3551506
PG 8
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 723KS
UT WOS:000287506000015
PM 21341835
ER
PT J
AU Min, CK
Son, YJ
Kim, CK
Park, SJ
Lee, JW
AF Min, Cheol-Ki
Son, Young-Jin
Kim, Chang-Kyu
Park, Sang-Joong
Lee, Jin-Won
TI Increased expression, folding and enzyme reaction rate of recombinant
human insulin by selecting appropriate leader peptide
SO JOURNAL OF BIOTECHNOLOGY
LA English
DT Article
DE Leader peptide; Sulfitolysis; S-sulfonated preproinsulin (SSPPI);
Proinsulin; Enzymatic conversion
ID ESCHERICHIA-COLI; HUMAN PROINSULIN; FUSION PROTEIN; C-PEPTIDE;
CARBOXYPEPTIDASE-B; IN-VITRO; CONVERSION; TRYPSIN; PURIFICATION;
DEGRADATION
AB Five new expression vectors for recombinant human insulin production (pPT-B5Kpi, pPT-T10Rpi, pPT-T13Rpi, pPT-H27Rpi, pPT-B5Rpi), which have different sizes and leader peptide structure, were constructed and compared based on their expression level, yields of S-sulfonated preproinsulin (SSPPI) and folded proinsulin and enzymatic conversion rate. The ranking of expression level of the five fused proinsulins was H27R >> T10R > B5K > T13Ru approximate to B5R. In particular, the expression level of H27R was more than double (60-70%) the level of the other fused proinsulins, and this high expression level led to large amounts of SSPPI, folded proinsulin and insulin. Changes to the leader peptide structure affected not only protein expression level, but also refolding yield because the leader peptide affects protein conformation and hydrophobicity. The refolding yield of H27R was 85% at 500 L pilot scale. This high refolding yield was caused by the hydrophilic character of H27R. However, the beta-mercaptoethanol concentration needed for refolding and the pH required to precipitate impurities after refolding had to be changed for high refolding yield. To avoid using CNBr, which is used to cleave fusion proteins, we used lysine and arginine linkers to connect the fusion protein and proinsulin. This fusion protein could be simultaneously cleaved by trypsin during enzymatic conversion to eliminate the C-peptide. The length and kind of leader peptide did not affect the enzyme reaction rate. Only the leader peptide linker connecting the B-chain influenced enzyme reaction rate. By testing several leader peptides, we constructed a new strain with 30% increased productivity based on expression level, refolding yield and enzyme reaction. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Min, Cheol-Ki; Lee, Jin-Won] Sogang Univ, Dept Integrated Biotechnol, Seoul 121742, South Korea.
[Son, Young-Jin] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Kim, Chang-Kyu] Konkuk Univ, Dept Anim Biotechnol, Coll Anim Biosci & Technol, Seoul 143701, South Korea.
[Park, Sang-Joong] Res Inst Chong Kun Dang Corp, Lab Bioengn, Cheonan Chungam Si, South Korea.
RP Lee, JW (reprint author), Sogang Univ, Dept Integrated Biotechnol, Seoul 121742, South Korea.
EM jinwonlee@sogang.ac.kr
FU Korea Ministry of Knowledge Economy
FX This work was supported by interdisciplinary program of integrated
biotechnology funded by the Korea Ministry of Knowledge Economy.
NR 34
TC 8
Z9 8
U1 1
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1656
J9 J BIOTECHNOL
JI J. Biotechnol.
PD FEB 20
PY 2011
VL 151
IS 4
BP 350
EP 356
DI 10.1016/j.jbiotec.2010.12.023
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 730TO
UT WOS:000288057600008
PM 21219941
ER
PT J
AU English, BC
Price, DK
Figg, WD
AF English, Bevin C.
Price, Douglas K.
Figg, William D.
TI Disclosing the Cancer Diagnosis: The Myth and the Truth Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [English, Bevin C.; Price, Douglas K.; Figg, William D.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP English, BC (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 2
TC 0
Z9 0
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 FEB 20
PY 2011
VL 29
IS 6
BP E147
EP E147
DI 10.1200/JCO.2010.32.4244
PG 1
WC Oncology
SC Oncology
GA 722OP
UT WOS:000287444000009
ER
PT J
AU Luo, XH
Huang, CY
AF Luo, Xianghua
Huang, Chiung-Yu
TI Analysis of recurrent gap time data using the weighted risk-set method
and the modified within-cluster resampling method
SO STATISTICS IN MEDICINE
LA English
DT Article
DE clustered survival data; Cox proportional hazards model; Kaplan-Meier
estimator; log-rank test; multiple outputation; multivariate survival
times
ID CENSORED SURVIVAL-DATA; LONG-TERM COURSE; NONPARAMETRIC-ESTIMATION;
MARGINAL REGRESSION; TRANSFORMATION MODELS; COUNTING-PROCESSES; HAZARDS
MODEL; EVENT DATA; SCHIZOPHRENIA; HOSPITALIZATION
AB The gap times between recurrent events are often of primary interest in medical and epidemiology studies. The observed gap times cannot be naively treated as clustered survival data in analysis because of the sequential structure of recurrent events. This paper introduces two important building blocks, the averaged counting process and the averaged at-risk process, for the development of the weighted risk-set (WRS) estimation methods. We demonstrate that with the use of these two empirical processes, existing risk-set based methods for univariate survival time data can be easily extended to analyze recurrent gap times. Additionally, we propose a modified within-cluster resampling (MWCR) method that can be easily implemented in standard software. We show that the MWCR estimators are asymptotically equivalent to the WRS estimators. An analysis of hospitalization data from the Danish Psychiatric Central Register is presented to illustrate the proposed methods. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Luo, XH (reprint author), Univ Minnesota, Sch Publ Hlth, Div Biostat, 420 Delaware St SE,MMC 303, Minneapolis, MN 55455 USA.
EM luox0054@umn.edu
NR 40
TC 9
Z9 9
U1 4
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD FEB 20
PY 2011
VL 30
IS 4
BP 301
EP 311
DI 10.1002/sim.4074
PG 11
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 718FJ
UT WOS:000287106200001
PM 20963733
ER
PT J
AU Franquelim, HG
Chiantia, S
Veiga, AS
Santos, NC
Schwille, P
Castanho, MARB
AF Franquelim, Henri G.
Chiantia, Salvatore
Veiga, Ana Salome
Santos, Nuno C.
Schwille, Petra
Castanho, Miguel A. R. B.
TI Anti-HIV-1 antibodies 2F5 and 4E10 interact differently with lipids to
bind their epitopes
SO AIDS
LA English
DT Article
DE 2F5; 4E10; gp41; HIV-1; membrane proximal external region; microscopy;
supported lipid bilayers
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; BROADLY
NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; HIV-1 GP41;
PHOSPHATIDYLINOSITOL PHOSPHATE; ENVELOPE GLYCOPROTEIN; SIMULTANEOUSLY
BIND; MEMBRANE-FUSION; VIRAL MEMBRANE
AB Objectives: 2F5 and 4E10 are two broadly neutralizing monoclonal antibodies (mAbs) targeting the membrane proximal external region (MPER) of HIV-1 gp41 envelope protein. This region, which contacts the viral membrane, is highly conserved and has been regarded as a promising target for vaccine development. We aimed to clarify the basis of 2F5 and 4E10 molecular interactions with epitope cores in MPER and lipid bilayers.
Design: Microscopy-based approaches were used to infer and quantify the effects of both mAbs on membranes, in the presence and absence of the epitope cores. Supported lipid bilayers (SLBs), with and without phase separation, were used as membrane models. Fluorescent-labeled and nonlabeled MPER-derived peptides containing both 2F5 and 4E10 epitopes were used.
Methods: mAbs 2F5 and 4E10 membrane interactions, in the presence or absence of MPER-derived peptides, were evaluated by combined atomic force and confocal microscopies.
Results: Both mAbs form lipid-segregated aggregates on SLBs and do not induce other significant membrane perturbations. Furthermore, the affinity of MPER toward membranes is differently affected by both mAbs and correlates with the mAbs-epitope core lipid interactions. 2F5 is able to dock the MPER peptide on the membrane, whereas 4E10 extracts the MPER from the lipid bilayer.
Conclusion: The results reveal the molecular details underneath 2F5/4E10 membrane-epitope binding and a model is proposed to explain the differential mAbs neutralization efficacies, which relates to the exposure of the epitopes in the lipid bilayers and the role of the lipids in mAb-epitope binding. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Franquelim, Henri G.; Veiga, Ana Salome; Santos, Nuno C.; Castanho, Miguel A. R. B.] Univ Lisbon, Inst Mol Med, Fac Med, P-1649028 Lisbon, Portugal.
[Chiantia, Salvatore; Schwille, Petra] Tech Univ Dresden, Biotechnol Zentrum, Dresden, Germany.
[Veiga, Ana Salome] NCI, Biol Chem Lab, Frederick, MD 21701 USA.
RP Castanho, MARB (reprint author), Univ Lisbon, Inst Mol Med, Fac Med, Ed Egas Moniz,Av Prof Egas Moniz, P-1649028 Lisbon, Portugal.
EM macastanho@fm.ul.pt
RI Santos, Nuno/N-7248-2013;
OI Santos, Nuno/0000-0002-0580-0475; Veiga, Ana Salome/0000-0002-9892-2243;
Chiantia, Salvatore/0000-0003-0791-967X; Castanho,
Miguel/0000-0001-7891-7562
FU Max Planck Gesellschaft (Germany); Fundacao para a Ciencia e Tecnologia
- Ministerio da Ciencia, Tecnologia e Ensino Superior (Portugal)
[SFRH/BD/39039/2007, PTDC/QUI-BIQ/104787/2008, PTDC/QUI/69937/2006,
REEQ/140/BIO/2005]
FX The authors are grateful for the support from the Max Planck
Gesellschaft (Germany). Fundacao para a Ciencia e Tecnologia -
Ministerio da Ciencia, Tecnologia e Ensino Superior (Portugal) is
acknowledged for funding (SFRH/BD/39039/2007 grant to H.G.F. and
projects PTDC/QUI-BIQ/104787/2008, PTDC/QUI/69937/2006 and
REEQ/140/BIO/2005).
NR 54
TC 18
Z9 18
U1 0
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD FEB 20
PY 2011
VL 25
IS 4
BP 419
EP 428
DI 10.1097/QAD.0b013e328342ff11
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 716LN
UT WOS:000286970300003
PM 21245727
ER
PT J
AU Reynolds, SJ
Makumbi, F
Nakigozi, G
Kagaayi, J
Gray, RH
Wawer, M
Quinn, TC
Serwadda, D
AF Reynolds, Steven J.
Makumbi, Frederick
Nakigozi, Gertrude
Kagaayi, Joseph
Gray, Ronald H.
Wawer, Maria
Quinn, Thomas C.
Serwadda, David
TI HIV-1 transmission among HIV-1 discordant couples before and after the
introduction of antiretroviral therapy
SO AIDS
LA English
DT Article
DE antiretroviral; discordant couples; HIV transmission; HIV-1
ID HETEROSEXUAL TRANSMISSION
AB Objective: To evaluate the impact of antiretroviral therapy (ART) on HIV-1 transmission rates among HIV-1 discordant couples in Rakai, Uganda.
Design: Observational cohort study.
Methods: HIV-1 discordant couples were retrospectively identified between 2004 and 2009. Study participants underwent annual screening for HIV-1 and were interviewed to evaluate risk behaviors. Participants were offered voluntary counseling and testing and provided with risk reduction counseling. Free ART was offered to participants with a CD4 cell count of 250 cells/mu l or less or WHO stage IV disease. HIV-1 incidence and sexual risk behaviors were compared before and after the HIV-1-positive index partners started ART.
Results: Two hundred and fifty HIV-1 discordant couples were followed between 2004 and 2009 and 32 HIV-1-positive partners initiated ART. Forty-two HIV-1 transmissions occurred over 459.4 person-years prior to ART initiation, incidence 9.2/100 person-years [95% confidence interval (CI) 6.59-12.36]. In 32 couples in which the HIV-1 index partners started ART, no HIV-1 transmissions occurred during 53.6 person-years. The 95% CI for the incidence rate difference was -11.91 to -6.38 (P = 0.0097). Couples reported more consistent condom use during ART use, but there was no significant difference in the number of sexual partners or other risk behaviors. Viral load was markedly reduced in persons on ART.
Conclusion: HIV-1 transmission may be reduced among HIV-1 discordant couples after initiation of ART due to reductions in HIV-1 viral load and increased consistent condom use. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Reynolds, Steven J.; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Makumbi, Frederick; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Nakigozi, Gertrude; Kagaayi, Joseph] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Gray, Ronald H.; Wawer, Maria] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Reynolds, SJ (reprint author), 2190 Kampala Pl, Dulles, VA 20189 USA.
EM sjr@jhmi.edu
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; Eunice Kennedy Shriver National Institute of Child
Health and Human Development [R01 HD 050180]
FX The authors would like to thank the Rakai Health Sciences Program (RHSP)
clients and study staff. This study was supported in part by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases and in part by grant number R01 HD 050180 from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development. Its contents are solely the responsibility of the authors
and do not necessarily represent the official views of the NIAID or
NICHD. All authors contributed to study design and manuscript writing.
S.J.R., F.M., G.K., J.K., and D.S. contributed to study implementation
and data collection. F.M. performed statistical analyses.
NR 6
TC 108
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U1 4
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD FEB 20
PY 2011
VL 25
IS 4
BP 473
EP 477
DI 10.1097/QAD.0b013e3283437c2b
PG 5
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 716LN
UT WOS:000286970300009
PM 21160416
ER
PT J
AU Korn, EL
Freidlin, B
AF Korn, Edward L.
Freidlin, Boris
TI Outcome-Adaptive Randomization: Is It Useful?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BAYESIAN CLINICAL-TRIALS; ACUTE MYELOID-LEUKEMIA; DESIGN ISSUES;
PHASE-II; ALLOCATION; CYTARABINE; ASSIGNMENT; OLDER; RULE
AB Outcome-adaptive randomization is one of the possible elements of an adaptive trial design in which the ratio of patients randomly assigned to the experimental treatment arm versus the control treatment arm changes from 1: 1 over time to randomly assigning a higher proportion of patients to the arm that is doing better. Outcome-adaptive randomization has intuitive appeal in that, on average, a higher proportion of patients will be treated on the better treatment arm (if there is one). In both the randomized phase II and phase III settings with a short-term binary outcome, we compare outcome-adaptive randomization with designs that use 1: 1 and 2: 1 fixed-ratio randomizations (in the latter, twice as many patients are randomly assigned to the experimental treatment arm). The comparisons are done in terms of required sample sizes, the numbers and proportions of patients having an inferior outcome, and we restrict attention to the situation in which one treatment arm is a control treatment (rather than the less common situation of two experimental treatments without a control treatment). With no differential patient accrual rates because of the trial design, we find no benefits to outcome-adaptive randomization over 1: 1 randomization, and we recommend the latter. If it is thought that the patient accrual rates will be substantially higher because of the possibility of a higher proportion of patients being randomly assigned to the experimental treatment (because the trial will be more attractive to patients and clinicians), we recommend using a fixed 2: 1 randomization instead of an outcome-adaptive randomization.
C1 [Korn, Edward L.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN-8129, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 24
TC 67
Z9 67
U1 0
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2011
VL 29
IS 6
BP 771
EP 776
DI 10.1200/JCO.2010.31.1423
PG 6
WC Oncology
SC Oncology
GA 722OP
UT WOS:000287444000038
PM 21172882
ER
PT J
AU Nalls, MA
Plagnol, V
Hernandez, DG
Sharma, M
Sheerin, UM
Saad, M
Simon-Sanchez, J
Schulte, C
Lesage, S
Sveinbjornsdottir, S
Arepalli, S
Barker, R
Ben-Shlomo, Y
Berendse, HW
Berg, D
Bhatia, K
de Bie, RMA
Biffi, A
Bloem, B
Bochdanovits, Z
Bonin, M
Bras, JM
Brockmann, K
Brooks, J
Burn, DJ
Charlesworth, G
Chen, HL
Chinnery, PF
Chong, S
Clarke, CE
Cookson, MR
Cooper, JM
Corvol, JC
Counsell, C
Damier, P
Dartigues, JF
Deloukas, P
Deuschl, G
Dexter, DT
van Dijk, KD
Dillman, A
Durif, F
Durr, A
Edkins, S
Evans, JR
Foltynie, T
Gao, JJ
Gardner, M
Gibbs, JR
Goate, A
Gray, E
Guerreiro, R
Gustafsson, O
Harris, C
van Hilten, JJ
Hofman, A
Hollenbeck, A
Holton, J
Hu, M
Huang, XM
Huber, H
Hudson, G
Hunt, SE
Huttenlocher, J
Illig, T
Jonsson, PV
Lambert, JC
Langford, C
Lees, A
Lichtner, P
Limousin, P
Lopez, G
Lorenz, D
McNeill, A
Moorby, C
Moore, M
Morris, HR
Morrison, KE
Mudanohwo, E
O'Sullivan, SS
Pearson, J
Perlmutter, JS
Petursson, H
Pollak, P
Post, B
Potter, S
Ravina, B
Revesz, T
Riess, O
Rivadeneira, F
Rizzu, P
Ryten, M
Sawcer, S
Schapira, A
Scheffer, H
Shaw, K
Shoulson, I
Sidransky, E
Smith, C
Spencer, CCA
Stefansson, H
Stockton, JD
Strange, A
Talbot, K
Tanner, CM
Tashakkori-Ghanbaria, A
Tison, F
Trabzuni, D
Traynor, BJ
Uitterlinden, AG
Velseboer, D
Vidailhet, M
Walker, R
van de Warrenburg, B
Wickremaratchi, M
Williams, N
Williams-Gray, CH
Winder-Rhodes, S
Stefansson, K
Martinez, M
Hardy, J
Heutink, P
Brice, A
Gasser, T
Singleton, AB
Wood, NW
AF Nalls, Michael A.
Plagnol, Vincent
Hernandez, Dena G.
Sharma, Manu
Sheerin, Una-Marie
Saad, Mohamad
Simon-Sanchez, Javier
Schulte, Claudia
Lesage, Suzanne
Sveinbjornsdottir, Sigurlaug
Arepalli, Sampath
Barker, Roger
Ben-Shlomo, Yoav
Berendse, Henk W.
Berg, Daniela
Bhatia, Kailash
de Bie, Rob M. A.
Biffi, Alessandro
Bloem, Bas
Bochdanovits, Zoltan
Bonin, Michael
Bras, Jose M.
Brockmann, Kathrin
Brooks, Janet
Burn, David J.
Charlesworth, Gavin
Chen, Honglei
Chinnery, Patrick F.
Chong, Sean
Clarke, Carl E.
Cookson, Mark R.
Cooper, J. Mark
Corvol, Jean Christophe
Counsell, Carl
Damier, Philippe
Dartigues, Jean-Francois
Deloukas, Panos
Deuschl, Guenther
Dexter, David T.
van Dijk, Karin D.
Dillman, Allissa
Durif, Frank
Duerr, Alexandra
Edkins, Sarah
Evans, Jonathan R.
Foltynie, Thomas
Gao, Jianjun
Gardner, Michelle
Gibbs, J. Raphael
Goate, Alison
Gray, Emma
Guerreiro, Rita
Gustafsson, Omar
Harris, Clare
van Hilten, Jacobus J.
Hofman, Albert
Hollenbeck, Albert
Holton, Janice
Hu, Michele
Huang, Xuemei
Huber, Heiko
Hudson, Gavin
Hunt, Sarah E.
Huttenlocher, Johanna
Illig, Thomas
Jonsson, Palmi V.
Lambert, Jean-Charles
Langford, Cordelia
Lees, Andrew
Lichtner, Peter
Limousin, Patricia
Lopez, Grisel
Lorenz, Delia
McNeill, Alisdair
Moorby, Catriona
Moore, Matthew
Morris, Huw R.
Morrison, Karen E.
Mudanohwo, Ese
O'Sullivan, Sean S.
Pearson, Justin
Perlmutter, Joel S.
Petursson, Hjoervar
Pollak, Pierre
Post, Bart
Potter, Simon
Ravina, Bernard
Revesz, Tamas
Riess, Olaf
Rivadeneira, Fernando
Rizzu, Patrizia
Ryten, Mina
Sawcer, Stephen
Schapira, Anthony
Scheffer, Hans
Shaw, Karen
Shoulson, Ira
Sidransky, Ellen
Smith, Colin
Spencer, Chris C. A.
Stefansson, Hreinn
Stockton, Joanna D.
Strange, Amy
Talbot, Kevin
Tanner, Carlie M.
Tashakkori-Ghanbaria, Avazeh
Tison, Francois
Trabzuni, Daniah
Traynor, Bryan J.
Uitterlinden, Andre G.
Velseboer, Daan
Vidailhet, Marie
Walker, Robert
van de Warrenburg, Bart
Wickremaratchi, Mirdhu
Williams, Nigel
Williams-Gray, Caroline H.
Winder-Rhodes, Sophie
Stefansson, Kari
Martinez, Maria
Hardy, John
Heutink, Peter
Brice, Alexis
Gasser, Thomas
Singleton, Andrew B.
Wood, Nicholas W.
CA Int Parkinson Dis Genomics Consort
Wellcome Trust Case-Control Consor
TI Imputation of sequence variants for identification of genetic risks for
Parkinson's disease: a meta-analysis of genome-wide association studies
SO LANCET
LA English
DT Article
ID SYNAPTOTAGMIN-XI; COMMON; LOCI; SUSCEPTIBILITY; MUTATIONS; SUGGESTS;
REGION; STK39; SNCA
AB Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease.
Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated.
Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk.
Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.
C1 [Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20837 USA.
[Plagnol, Vincent; Wood, Nicholas W.] UCL Genet Inst, London, England.
[Hernandez, Dena G.; Sheerin, Una-Marie; Bhatia, Kailash; Bras, Jose M.; Charlesworth, Gavin; Gardner, Michelle; Gibbs, J. Raphael; Guerreiro, Rita; Ryten, Mina; Trabzuni, Daniah; Hardy, John; Wood, Nicholas W.] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Sharma, Manu] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Sharma, Manu] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany.
[Saad, Mohamad] CPTP, INSERM, U563, Toulouse, France.
[Saad, Mohamad; Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France.
[Simon-Sanchez, Javier; Bochdanovits, Zoltan; Rizzu, Patrizia; Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands.
[Lesage, Suzanne; Corvol, Jean Christophe; Duerr, Alexandra] INSERM, UMR S975, Paris, France.
[Lesage, Suzanne] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Paris, France.
[Lesage, Suzanne; Corvol, Jean Christophe; Duerr, Alexandra] CNRS, Paris, France.
[Sveinbjornsdottir, Sigurlaug] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland.
[Sveinbjornsdottir, Sigurlaug] MEHT Broomfield Hosp, Dept Neurol, Chelmsford, Essex, England.
[Sveinbjornsdottir, Sigurlaug] Univ London, Queen Mary Coll, London, England.
[Barker, Roger] Univ Cambridge, Addenbrookes Hosp, Dept Neurol, Cambridge CB2 2QQ, England.
[Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol BS8 1TH, Avon, England.
[Berendse, Henk W.; van Dijk, Karin D.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands.
[Berendse, Henk W.; van Dijk, Karin D.] Vrije Univ Amsterdam Med Ctr, Alzheimers Ctr, Amsterdam, Netherlands.
[de Bie, Rob M. A.; Velseboer, Daan] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands.
[Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Biffi, Alessandro] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Bloem, Bas; Post, Bart; van de Warrenburg, Bart] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6525 ED Nijmegen, Netherlands.
[Bonin, Michael; Petursson, Hjoervar; Riess, Olaf] Univ Tubingen, Inst Human Genet, Dept Med Genet, Tubingen, Germany.
[Burn, David J.] Newcastle Univ, Clin Ageing Res Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Chen, Honglei] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC USA.
[Chinnery, Patrick F.; Hudson, Gavin] Newcastle Univ, Sch Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Clarke, Carl E.; Moorby, Catriona; Morrison, Karen E.] Univ Birmingham, Sch Clin & Expt Med, Birmingham, W Midlands, England.
[Clarke, Carl E.] Sandwell & W Birmingham Hosp NHS Trust, City Hosp, Dept Neurol, Birmingham, W Midlands, England.
[Cooper, J. Mark; McNeill, Alisdair; Schapira, Anthony] UCL Inst Neurol, Dept Clin Neurosci, London, England.
[Corvol, Jean Christophe] Hop La Pitie Salpetriere, INSERM, CIC 9503, Paris, France.
[Counsell, Carl] Univ Aberdeen, Div Appl Hlth Sci, Populat Hlth Sect, Aberdeen, Scotland.
[Damier, Philippe] CHU Nantes, CIC0004, Serv Neurol, F-44035 Nantes 01, France.
[Dartigues, Jean-Francois] Univ Victor Segalen, INSERM, U897, Bordeaux, France.
[Deloukas, Panos; Edkins, Sarah; Gray, Emma; Hunt, Sarah E.; Potter, Simon; Tashakkori-Ghanbaria, Avazeh] Wellcome Trust Sanger Inst, Cambridge, England.
[Deuschl, Guenther] Univ Kiel, Univ Klinikum Schleswig Holstein, Neurol Klin, Kiel, Germany.
[Dexter, David T.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Parkinsons Dis Res Grp, London, England.
[Durif, Frank] Hop Gabriel Montpied, Serv Neurol, Clermont Ferrand, France.
[Duerr, Alexandra] Hop La Pitie Salpetriere, AP HP, Paris, France.
[Evans, Jonathan R.; Langford, Cordelia] Cambridge Ctr Brain Repair, Cambridge, England.
[Gustafsson, Omar] Oslo Univ Hosp, deCODE Genet, N-0407 Oslo, Norway.
[Gustafsson, Omar] Oslo Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway.
[van Hilten, Jacobus J.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Hollenbeck, Albert] AARP, Washington, DC USA.
[Holton, Janice] UCL Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England.
[Hu, Michele] John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Bioengn, Hershey, PA 17033 USA.
[Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Jonsson, Palmi V.] Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland.
[Lambert, Jean-Charles] INSERM, U744, F-59045 Lille, France.
[Lambert, Jean-Charles] Univ Lille Nord, Inst Pasteur Lille, Lille, France.
[Lichtner, Peter] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Limousin, Patricia] Inst Neurol, Sobell Dept, Unit Funct Neurosurg, London WC1N 3BG, England.
[Lopez, Grisel] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD USA.
[Morris, Huw R.] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales.
[Morrison, Karen E.] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Dept Neurosci, Birmingham, W Midlands, England.
[Mudanohwo, Ese] UCL Inst Neurol, Neurogenet Unit, London, England.
[Perlmutter, Joel S.] Washington Univ, Dept Neurol Radiol & Neurobiol, St Louis, MO 63130 USA.
[Pollak, Pierre] CHU Grenoble, Serv Neurol, F-38043 Grenoble, France.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Sawcer, Stephen] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
[Scheffer, Hans] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Shoulson, Ira] Univ Rochester, Dept Neurol, Rochester, NY USA.
[Smith, Colin; Walker, Robert] Univ Edinburgh, Dept Pathol, Edinburgh, Midlothian, Scotland.
[Spencer, Chris C. A.; Strange, Amy] Wellcome Trust Ctr Human Genet, Oxford, England.
[Talbot, Kevin] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England.
[Tanner, Carlie M.] Parkinsons Inst & Clin Ctr, Dept Clin Res, Sunnyvale, CA USA.
[Tison, Francois] Hop Haut Leveque, Serv Neurol, Pessac, France.
[Vidailhet, Marie] Univ Paris 06, INSERM, UMR S975, CNRS,UMR 7225, F-75252 Paris 05, France.
[Wickremaratchi, Mirdhu] Cardiff Univ, Dept Neurol, Cardiff, S Glam, Wales.
[Williams-Gray, Caroline H.] Addenbrookes Hosp, Dept Neurol, Cambridge, England.
[Winder-Rhodes, Sophie] Univ Cambridge, Dept Psychiat, Cambridge CB2 1TN, England.
[Winder-Rhodes, Sophie] Univ Cambridge, MRC, Cambridge CB2 1TN, England.
[Winder-Rhodes, Sophie] Univ Cambridge, Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 1TN, England.
[Martinez, Maria] INSERM, U563, F-75654 Paris 13, France.
[Brice, Alexis] Univ Paris 06, Pitie Salpetriere Hosp, AP HP, CNRS,UMR 7225,INSERM,UMR S975, F-75252 Paris 05, France.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20837 USA.
EM singleta@mail.nih.gov
RI Traynor, Bryan/G-5690-2010; Deloukas, Panos/B-2922-2013; Bras,
Jose/A-1428-2011; Cooper, J Mark/D-5826-2013; Deuschl,
Gunther/A-7986-2010; lambert, jean-charles/F-8787-2013; Wood,
Nicholas/C-2505-2009; LICEND, CEMND/F-1296-2015; Bloem,
B.R./H-8013-2014; Trabzuni, Daniah/C-4034-2012; Rivadeneira,
Fernando/O-5385-2015; van de Warrenburg, Bart/D-1935-2010; Lambert,
jean-charles/A-9553-2014; Scheffer, Hans/E-4644-2012; Bloem,
Bastiaan/E-3812-2010; Guerreiro, Rita/A-1327-2011; Morris,
Huw/B-8527-2008; Charlesworth, Gavin/B-5895-2011; Singleton,
Andrew/C-3010-2009; turton, miranda/F-4682-2011; Holton,
Janice/F-6831-2011; Talbot, Kevin /F-7361-2011; Plagnol,
Vincent/A-5667-2011; mcneill, alisdair/B-1267-2012; O'Sullivan,
Sean/C-9333-2012; Hardy, John/C-2451-2009; Lees, Andrew/A-6605-2009;
Martinez, Maria/B-3111-2013; corvol, jean-christophe/I-6387-2012;
Revesz, Tamas/A-8732-2010; Hudson, Gavin/E-7117-2017;
OI Deloukas, Panos/0000-0001-9251-070X; Cooper, J Mark/0000-0002-3007-3054;
Wood, Nicholas/0000-0002-9500-3348; Trabzuni,
Daniah/0000-0003-4826-9570; Rivadeneira, Fernando/0000-0001-9435-9441;
Lambert, jean-charles/0000-0003-0829-7817; Scheffer,
Hans/0000-0002-2986-0915; Morris, Huw/0000-0002-5473-3774; Holton,
Janice/0000-0002-3882-5249; O'Sullivan, Sean/0000-0002-0583-7956;
Martinez, Maria/0000-0003-2180-4537; corvol,
jean-christophe/0000-0001-7325-0199; Revesz, Tamas/0000-0003-2501-0259;
Walker, Robert/0000-0001-7383-7846; Bras, Jose/0000-0001-8186-0333;
Schulte, Claudia/0000-0003-4006-1265; Plagnol,
Vincent/0000-0002-5597-9215; Stefansson, Hreinn/0000-0002-9331-6666;
Bhatia, Kailash/0000-0001-8185-286X; Chen, Honglei/0000-0003-3446-7779
FU deCODE; Eisai; Merck-Serono; Cephalon; Novartis; National Institute on
Aging, National Institute of Neurological Disorders and Stroke, National
Institute of Environmental Health Sciences; National Human Genome
Research Institute of the National Institutes of Health, Department of
Health and Human Services [Z01-AG000949-02, Z01-ES101986]; US Department
of Defense [W81XWH-09-2-0128]; National Institutes of Health [NS057105,
RA024992]; American Parkinson disease Association (APDA); Barnes Jewish
Hospital Foundation; Greater St Louis Chapter of the APDA;
Hersenstichting Nederland; Neuroscience Campus Amsterdam; section of
medical genomics; Prinses Beatrix Fonds; Forschungszentrum fur Umwelt
und Gesundheit; German National Genome Network (German Ministry for
Education and Research) [01GS08134]; German Federal Ministry of
Education and Research [NGFN 01GR0468]; Helmholtz Alliance Mental Health
in an Ageing Society [HA-215]; Helmholtz Association; French National
Agency of Research [ANR-08-MNP-012]; Landspitali University Hospital;
Icelandic Research Council; European Community [PIAP-GA-2008-230596];
Wellcome Trust [083948/Z/07/Z]; Medical Research Council; Wellcome Trust
disease centre [WT089698/Z/09/Z]; Parkinson's UK [8047, J-0804]; Medical
Research Council [G0700943]; Department of Health's National Institute
for Health Research Biomedical Research Centres; Wellcome Trust/Medical
Research Council [WT089698]; Parkinson's Disease Consortium (UKPDC)
FX KSt has received grants from deCODE. JH has received consulting fees or
honoraria from Eisai and his institute has received consulting fees or
honoraria from Merck-Serono. TG has received consultancy fees from
Cephalon and Merck-Serono; grants from Novartis; payments for lectures
including service on speakers' bureaus from Boehringer Ingelheim,
Merck-Serono, UCB, and Valeant; and holds patents NGFN2 and KASPP. MAN,
VP, DGH, MSh, U-MS, MSa, JS-S, CS, SL, SS, KS, MM, PH, ABr, ABS, and NWW
declare that they have no conflicts of interest.; This work was
supported by the Intramural Research Programs of the National Institute
on Aging, National Institute of Neurological Disorders and Stroke,
National Institute of Environmental Health Sciences, and National Human
Genome Research Institute of the National Institutes of Health,
Department of Health and Human Services (project numbers Z01-AG000949-02
and Z01-ES101986). This work was also supported by the US Department of
Defense (award number W81XWH-09-2-0128); National Institutes of Health
(grants NS057105 and RA024992); American Parkinson disease Association
(APDA); Barnes Jewish Hospital Foundation; Greater St Louis Chapter of
the APDA; Hersenstichting Nederland; Neuroscience Campus Amsterdam; and
the section of medical genomics, the Prinses Beatrix Fonds. The KORA
(Cooperative Research in the Region of Augsburg) research platform was
started and financed by the Forschungszentrum fur Umwelt und Gesundheit,
which is funded by the German Federal Ministry of Education, Science,
Research, and Technology and by the State of Bavaria. This study was
also funded by the German National Genome Network (NGENplus number
01GS08134, German Ministry for Education and Research); by the German
Federal Ministry of Education and Research (NGFN 01GR0468, PopGen); and
01EW0908 in the frame of ERA-NET NEURON and Helmholtz Alliance Mental
Health in an Ageing Society (HA-215), which was funded by the Initiative
and Networking Fund of the Helmholtz Association. The French GWAS work
was supported by the French National Agency of Research
(ANR-08-MNP-012). This study was also sponsored by the Landspitali
University Hospital Research Fund (grant to SSv); Icelandic Research
Council (grant to SSv); and European Community Framework Programme 7,
People Programme, and IAPP on novel genetic and phenotypic markers of
Parkinson's disease and Essential Tremor (MarkMD), contract number
PIAP-GA-2008-230596 MarkMD (to HP and JHu). We used the Biowulf Linux
cluster at the National Institutes of Health, Bethesda, MD, USA, and DNA
panels, samples, and clinical data from the National Institute of
Neurological Disorders and Stroke Human Genetics Resource Center DNA and
Cell Line Repository. People who contributed samples are acknowledged in
descriptions of every panel on the repository website. We thank The
French Parkinson's Disease Genetics Study Group: Y Agid, M Anheim, A-M
Bonnet, M Borg, A Brice, E Broussolle, J-C Corvol, P Damier, A Destee, A
Darr, F Durif, S Klebe, E Lohmann, M Martinez, P Pollak, O Rascol, F
Tison, C Tranchant, M Venn, F Viallet, and M Vidailhet. We also thank
the members of the French 3C Consortium: Annick Alperovitch, Claudine
Berr, Christophe Tzourio, and Philippe Amouyel for allowing us souse
part of the 3C cohort; and D Zelenika for support in generating the
genome-wide molecular data. We used genome-wide association data
generated by the Wellcome Trust Case-Control Consortium 2 (WTCCC2) from
UK patients with Parkinson's disease and UK control individuals from the
1958 Birth Cohort and National Blood Service. Genotyping of UK
replication cases on ImmunoChip was part of the WTCCC2 project, which
was funded by the Wellcome Trust (083948/Z/07/Z). UK population control
data was made available through WTCCC1. This study was supported by the
Medical Research Council and Wellcome Trust disease centre (grant
WT089698/Z/09/Z to NW, J Ha, and ASc). This study was also supported by
Parkinson's UK (grants 8047 and J-0804) and the Medical Research Council
(G0700943). We thank Jeffrey Barrett for assistance with the design of
the ImmunoChip.; DNA extration work that was done in the UK was
undertaken at University College London Hospitals, University College
London, who received a proportion of funding from the Department of
Health's National Institute for Health Research Biomedical Research
Centres funding. This study was supported in part by the Wellcome
Trust/Medical Research Council Joint Call in Neurodegeneration award
(WT089698) to the Parkinson's Disease Consortium (UKPDC), whose members
are from the UCL Institute of Neurology, University of Sheffield, and
the Medical Research Council Protein Phosphorylation Unit at the
University of Dundee.
NR 35
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Z9 384
U1 10
U2 78
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD FEB 19
PY 2011
VL 377
IS 9766
BP 641
EP 649
DI 10.1016/S0140-6736(10)62345-8
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 727DB
UT WOS:000287776600033
ER
PT J
AU Garcia, MC
Williams, J
Johnson, K
Olden, K
Roberts, JD
AF Garcia, Melissa C.
Williams, Jason
Johnson, Katina
Olden, Kenneth
Roberts, John D.
TI Arachidonic acid stimulates formation of a novel complex containing
nucleolin and RhoA
SO FEBS LETTERS
LA English
DT Article
DE Nucleolin; RhoA; Rho kinase; Arachidonic acid; Cell adhesion
ID CARCINOMA CELL-LINE; PROTEIN-KINASE-C; COLLAGEN TYPE-IV; FATTY-ACIDS;
ADHESION; CANCER; PHOSPHOPROTEIN; CYTOSKELETON; PATHWAY; ROLES
AB Arachidonic acid (AA) stimulates cell adhesion through a p38 mitogen activated protein kinase-mediated RhoA signaling pathway. Here we report that a proteomic screen following AA-treatment identified nucleolin, a multifunctional nucleolar protein, in a complex with the GTPase, RhoA, that also included the Rho kinase, ROCK. AA-stimulated cell adhesion was inhibited by expression of nucleolin-targeted shRNA and formation of the multiprotein complex was blocked by expression of dominant-negative RhoA. AA-treatment also induced ROCK-dependent serine phosphorylation of nucleolin and translocation of nucleolin from the nucleus to the cytoplasm, where it appeared to co-localize with RhoA. These data suggest the existence of a new signaling pathway through which the location and post-translational state of nucleolin are modulated.
Structured summary:
Nucleolin physically interacts with RHOA by anti bait coimmunoprecipitation (View Interaction 1, 2)
Nucleolin and RHOA colocalize by fluorescence microscopy (View interaction)
ROCK physically interacts with RHOA by pull down (View interaction)
ROCK physically interacts with HSP 90-beta, HSP70, Nucleolin, Nebulin and RHOA by pull down (View interaction)
Nucleolin physically interacts with ROCK2 by anti bait coimmunoprecipitation (View interaction)
ROCK physically interacts with Nucleolin and RHOA by pull down (View interaction) (C) 2011 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
C1 [Garcia, Melissa C.; Olden, Kenneth; Roberts, John D.] NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Williams, Jason; Johnson, Katina] NIEHS, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Roberts, JD (reprint author), NIEHS, NIH, Mol Carcinogenesis Lab, Mail Drop D2-05,POB 12233, Res Triangle Pk, NC 27709 USA.
EM roberts1@niehs.nih.gov
OI Garcia-Sherman, Melissa/0000-0003-1409-4397
FU National Institutes of Health through the National Institute of
Environmental Health Sciences
FX We thank Drs. Paul Wade, David Armstrong, and Steven Akiyama for a
careful reading of the manuscript. This research was supported by the
Intramural Research Program of the National Institutes of Health through
the National Institute of Environmental Health Sciences.
NR 24
TC 8
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U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD FEB 18
PY 2011
VL 585
IS 4
BP 618
EP 622
DI 10.1016/j.febslet.2011.01.035
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 719UR
UT WOS:000287237100006
PM 21281639
ER
PT J
AU Hewitt, SC
Korach, KS
AF Hewitt, Sylvia C.
Korach, Kenneth S.
TI A Hand to Support the Implantation Window
SO SCIENCE
LA English
DT Editorial Material
ID EMBRYO IMPLANTATION; MOUSE MODELS; RESPONSES; PROLIFERATION; ALPHA
C1 [Hewitt, Sylvia C.; Korach, Kenneth S.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
RP Hewitt, SC (reprint author), Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU Intramural NIH HHS [ZIA ES070065-35]
NR 13
TC 6
Z9 6
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD FEB 18
PY 2011
VL 331
IS 6019
BP 863
EP 864
DI 10.1126/science.1202372
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722SO
UT WOS:000287455100032
PM 21330520
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Thought Exercises on Accountability and Performance Measures at the
National Heart, Lung, and Blood Institute (NHLBI): An Invited Commentary
for Circulation Research
SO CIRCULATION RESEARCH
LA English
DT Article
C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 17
TC 18
Z9 18
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD FEB 18
PY 2011
VL 108
IS 4
BP 405
EP 409
DI 10.1161/RES.0b013e3182125662
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 723CQ
UT WOS:000287484200006
PM 21335430
ER
PT J
AU Kim, HK
Choi, IJ
Kim, CG
Kim, HS
Oshima, A
Michalowski, A
Green, JE
AF Kim, Hark Kyun
Choi, Il Ju
Kim, Chan Gyoo
Kim, Hee Sung
Oshima, Akira
Michalowski, Aleksandra
Green, Jeffrey E.
TI A Gene Expression Signature of Acquired Chemoresistance to Cisplatin and
Fluorouracil Combination Chemotherapy in Gastric Cancer Patients
SO PLOS ONE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; C-MYC; BREAST-CANCER; RESISTANCE; SENSITIVITY;
DNA; CARCINOMAS; THERAPY; ADENOCARCINOMA; 5-FU/CISPLATIN
AB Background: We initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives.
Methodology/Principal Findings: A prospective, high-throughput transcriptional profiling study was performed using endoscopic biopsy samples from 123 metastatic gastric cancer patients prior to cisplatin and fluorouracil (CF) combination chemotherapy. 22 patients who initially responded to CF were re-biopsied after they developed resistance to CF. An acquired chemotherapy resistance signature was identified by analyzing the gene expression profiles from the matched pre-and post-CF treated samples. The acquired resistance signature was able to segregate a separate cohort of 101 newly-diagnosed gastric cancer patients according to the time to progression after CF. Hierarchical clustering using a 633-gene acquired resistance signature (feature selection at P<0.01) separated the 101 pretreatment patient samples into two groups with significantly different times to progression (2.5 vs. 4.7 months). This 633-gene signature included the upregulation of AKT1, EIF4B, and RPS6 (mTOR pathway), DNA repair and drug metabolism genes, and was enriched for genes overexpressed in embryonic stem cell signatures. A 72-gene acquired resistance signature (a subset of the 633 gene signature also identified in ES cell-related gene sets) was an independent predictor for time to progression (adjusted P = 0.011) and survival (adjusted P = 0.034) of these 101 patients.
Conclusion/Significance: This signature may offer new insights into identifying new targets and therapies required to overcome the acquired resistance of gastric cancer to CF.
C1 [Kim, Hark Kyun; Oshima, Akira; Michalowski, Aleksandra; 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, South Korea.
RP Kim, HK (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM jegreen@nih.gov
OI Kim, Chan Gyoo/0000-0002-1651-2559
FU National Institutes of Health, Center for Cancer Research, National
Cancer Institute; Korean National Cancer Center through the Ministry of
Education, Science and Technology [0910570]; Ministry of Education,
Science and Technology [2010K001121]
FX Funding: This work was supported in part by the National Institutes of
Health Intramural Program, Center for Cancer Research, National Cancer
Institute; by the Korean National Cancer Center Grant 0910570 and by the
Converging Research Center Program through the Ministry of Education,
Science and Technology (2010K001121). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 47
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U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 18
PY 2011
VL 6
IS 2
AR e16694
DI 10.1371/journal.pone.0016694
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 723CC
UT WOS:000287482800012
PM 21364753
ER
PT J
AU Sims, JK
Wade, PA
AF Sims, Jennifer K.
Wade, Paul A.
TI SnapShot: Chromatin Remodeling: CHD
SO CELL
LA English
DT Editorial Material
ID COMPLEXES; MI-2/NURD; CELLS
C1 [Sims, Jennifer K.; Wade, Paul A.] Lab Mol Carcinogenesis, NIEHS, Res Triangle Pk, NC 27709 USA.
FU Intramural Research Program of the National Institute of Environmental
Health Science, NIH [Z01ES101965]
FX This work was supported by the Intramural Research Program of the
National Institute of Environmental Health Science, NIH (project number
Z01ES101965 to PAW). We gratefully acknowledge helpful suggestions from
S. Khorasanizadeh, T. Kutateladze, S. Venkatachalam, J. Wysocka, and
members of the Wade laboratory.
NR 8
TC 15
Z9 15
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 18
PY 2011
VL 144
IS 4
BP 626
EP 627
DI 10.1016/j.cell.2011.02.019
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 722ZC
UT WOS:000287473100016
PM 21335242
ER
PT J
AU Kohr, MJ
Sun, JH
Aponte, A
Wang, GH
Gucek, M
Murphy, E
Steenbergen, C
AF Kohr, Mark J.
Sun, Junhui
Aponte, Angel
Wang, Guanghui
Gucek, Marjan
Murphy, Elizabeth
Steenbergen, Charles
TI Simultaneous Measurement of Protein Oxidation and S-Nitrosylation During
Preconditioning and Ischemia/Reperfusion Injury With Resin-Assisted
Capture
SO CIRCULATION RESEARCH
LA English
DT Article
DE ischemic preconditioning; S-nitrosothiol; reactive oxygen species
ID NITRIC-OXIDE; MASS-SPECTROMETRY; CARDIOPROTECTION; REPERFUSION;
NITROSATION; CARDIOMYOCYTES; ISCHEMIA; STRESS; THIOLS; SIGNAL
AB Rationale: Redox modifications play an important role in many cellular processes, including cell death. Ischemic preconditioning (IPC) has been shown to involve redox signaling. Protein S-nitrosylation (SNO) is increased following myocardial IPC, and SNO is thought to provide cardioprotection, in part, by reducing cysteine oxidation during ischemia/reperfusion (IR) injury.
Objective: To test the hypothesis that SNO provides cardioprotection, in part, by shielding against cysteine oxidation following IR injury.
Methods and Results: We developed a new method to measure protein oxidation using resin-assisted capture (Ox-RAC), which is similar to the SNO-RAC method used in the quantification of SNO. Langendorff-perfused hearts were subjected to various perfusion protocols (control, IPC, IR, IPC-IR, IPC/reperfusion) and homogenized. Each sample was divided into 2 equal aliquots, and the SNO-RAC/Ox-RAC procedure was performed to simultaneously analyze SNO and oxidation. We identified 31 different SNO proteins with IPC, 27 of which showed increased SNO compared to baseline. Of the proteins that showed significantly increased SNO with IPC, 76% showed decreased oxidation or no oxidation following ischemia and early reperfusion (IPC-IR) at the same site when compared to IR alone; for non-SNO proteins, oxidation was reduced by only 50%. We further demonstrated that IPC-induced protein SNO is quickly reversible.
Conclusions: These results support the hypothesis that IPC-induced protein SNO provides cardioprotection by shielding cysteine residues from reactive oxygen species-induced oxidation during IR injury. Therefore, the level of protein SNO plays a critical role in IR injury, where ROS production is increased. (Circ Res. 2011;108:418-426.)
C1 [Kohr, Mark J.; Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21257 USA.
[Kohr, Mark J.; Sun, Junhui; Murphy, Elizabeth] NHLBI, NIH, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Aponte, Angel; Wang, Guanghui; Gucek, Marjan] NHLBI, NIH, Prote Core Facil, Bethesda, MD 20892 USA.
RP Steenbergen, C (reprint author), Johns Hopkins Med Inst, Dept Pathol, 632 N Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21257 USA.
EM csteenb1@jhmi.edu
RI Sun, Junhui/C-3499-2011;
OI Kohr, Mark/0000-0002-6034-5962
FU NIH [1F32HL096142, 5R01HL039752]; National Heart, Lung, and Blood
Institute/NIH
FX This work was supported by NIH grants 1F32HL096142 (to M. K.) and
5R01HL039752 (to C. S.) and the National Heart, Lung, and Blood
Institute/NIH Intramural Program (to A. A., E. M., G. W., J.S., and M.
G.).
NR 31
TC 84
Z9 85
U1 1
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD FEB 18
PY 2011
VL 108
IS 4
BP 418
EP U50
DI 10.1161/CIRCRESAHA.110.232173
PG 16
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 723CQ
UT WOS:000287484200008
PM 21193739
ER
PT J
AU Yung, SC
Parenti, D
Murphy, PM
AF Yung, Sunny C.
Parenti, David
Murphy, Philip M.
TI Host Chemokines Bind to Staphylococcus aureus and Stimulate Protein A
Release
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; SURFACE-PROTEINS; UNITED-STATES; CUTTING
EDGE; CELL-WALL; ANTIMICROBIAL ACTIVITY; COMPLEMENT ACTIVATION;
CUTANEOUS INFECTION; GAMMA-INTERFERON; AUGUST 2009
AB There are few examples of host signals that are beneficial to bacteria during infection. Here we found that 31 out of 42 host immunoregulatory chemokines were able to induce release of the virulence factor protein A (SPA) from a strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Detailed study of chemokine CXCL9 revealed that SPA release occurred through a post-translational mechanism and was inversely proportional to bacterial density. CXCL9 bound specifically to the cell membrane of CA-MRSA, and the related SPA-releasing chemokine CXCL10 bound to both cell wall and cell membrane. Clinical samples from patients infected with S. aureus and samples from a mouse model of CA-MRSA skin abscess all contained extracellular SPA. Further, SPA-releasing chemokines were present in mouse skin lesions infected with CA-MRSA. Our data identify a potential new mode of immune evasion, in which the pathogen exploits a host defense factor to release a virulence factor; moreover, chemokine binding may serve a scavenging function in immune evasion by S. aureus.
C1 [Yung, Sunny C.; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Parenti, David] George Washington Univ, Dept Med, Med Ctr, Washington, DC 20037 USA.
RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bldg 10,Rm 11N113, Bethesda, MD 20892 USA.
EM pmm@nih.gov
FU Division of Intramural Research of the NIAID, National Institutes of
Health
FX This work was supported by the Division of Intramural Research of the
NIAID, National Institutes of Health.
NR 54
TC 14
Z9 14
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 18
PY 2011
VL 286
IS 7
BP 5069
EP 5077
DI 10.1074/jbc.M110.195180
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719SY
UT WOS:000287230600014
PM 21138841
ER
PT J
AU Balla, A
Erdelyi, LS
Soltesz-Katona, E
Balla, T
Varnai, P
Hunyady, L
AF Balla, Andras
Erdelyi, Laszlo Sandor
Soltesz-Katona, Eszter
Balla, Tamas
Varnai, Peter
Hunyady, Laszlo
TI Demonstration of Angiotensin II-induced Ras Activation in the
trans-Golgi Network and Endoplasmic Reticulum Using Bioluminescence
Resonance Energy Transfer-based Biosensors
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; COUPLED RECEPTOR ENDOCYTOSIS; GTP-BINDING
PROTEINS; SMOOTH-MUSCLE-CELLS; SIGNAL-TRANSDUCTION; LIVING CELLS; LIVE
CELLS; H-RAS; K-RAS; PLASMA-MEMBRANE
AB Previous studies have demonstrated that molecules of the Ras signaling pathway are present in intracellular compartments, including early endosomes, the endoplasmic reticulum (ER), and the Golgi, and suggested that mitogens can regulate Ras activity in these endomembranes. In this study, we investigated the effect of angiotensin II (AngII) on intracellular Ras activity in living HEK293 cells expressing angiotensin type 1 receptors (AT(1)-Rs) using newly developed bioluminescence resonance energy transfer biosensors. To investigate the subcellular localization of AngII-induced Ras activation, we targeted our probes to various intracellular compartments, such as the trans-Golgi network (TGN), the ER, and early endosomes. Using these biosensors, we detected AngII-induced Ras activation in the TGN and ER, but not in early endosomes. In cells expressing a cytoplasmic tail deletion AT(1)-R mutant, the AngII-induced response was enhanced, suggesting that receptor internalization and beta-arrestin binding are not required for AngII-induced Ras activation in endomembranes. Although we were able to demonstrate EGF-induced Ras activation in the plasma membrane and TGN, but not in other endomembranes, AG1478, an EGF receptor inhibitor, did not affect the AngII-induced response, suggesting that the latter is independent of EGF receptor transactivation. AngII was unable to stimulate Ras activity in the studied compartments in cells expressing a G protein coupling-deficient AT(1)R mutant ((125)DRY(127) to (125)AAY(127)). These data suggest that AngII can stimulate Ras activity in the TGN and ER with a G protein-dependent mechanism, which does not require beta-arrestin-mediated signaling, receptor internalization, and EGF receptor transactivation.
C1 [Balla, Andras; Erdelyi, Laszlo Sandor; Soltesz-Katona, Eszter; Varnai, Peter; Hunyady, Laszlo] Semmelweis Univ, Dept Physiol, Fac Med, H-1444 Budapest, Hungary.
[Balla, Tamas] Eunice Kennedy Shriver NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Hunyady, Laszlo] Semmelweis Univ, Lab Neurobiochem & Mol Physiol, H-1444 Budapest, Hungary.
[Hunyady, Laszlo] Hungarian Acad Sci, H-1444 Budapest, Hungary.
RP Hunyady, L (reprint author), Semmelweis Univ, Dept Physiol, Fac Med, POB 259, H-1444 Budapest, Hungary.
EM hunyady@eok.sote.hu
OI Balla, Andras/0000-0002-6450-2793; Balla, Tamas/0000-0002-9077-3335
FU Hungarian Scientific Research Fund OTKA [NK72661]; Hungarian Ministry of
Public Health (ETT) [337/2009]; National Development Agency of Hungary
(NFU TAMOP) [4.2.2-08/1/KMR]
FX This work was supported in part by Hungarian Scientific Research Fund
(OTKA) Grant NK72661, Hungarian Ministry of Public Health (ETT) Grant
337/2009, and National Development Agency of Hungary (NFU TAMOP) Grant
4.2.2-08/1/KMR.
NR 46
TC 4
Z9 4
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 18
PY 2011
VL 286
IS 7
BP 5319
EP 5327
DI 10.1074/jbc.M110.176933
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719SY
UT WOS:000287230600040
PM 21062747
ER
PT J
AU Friis, S
Godiksen, S
Bornholdt, J
Selzer-Plon, J
Rasmussen, HB
Bugge, TH
Lin, CY
Vogel, LK
AF Friis, Stine
Godiksen, Sine
Bornholdt, Jette
Selzer-Plon, Joanna
Rasmussen, Hanne Borger
Bugge, Thomas H.
Lin, Chen-Yong
Vogel, Lotte K.
TI Transport via the Transcytotic Pathway Makes Prostasin Available as a
Substrate for Matriptase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FACTOR ACTIVATOR INHIBITOR-1; EPIDERMAL BARRIER FUNCTION; PROTEOLYTIC
CASCADE; SODIUM-CHANNEL; HUMAN-MILK; PROTEASE; DIFFERENTIATION;
LOCALIZATION; PURIFICATION; EXPRESSION
AB The matriptase-prostasin proteolytic cascade is essential for epidermal tight junction formation and terminal epidermal differentiation. This proteolytic pathway may also be operative in a variety of other epithelia, as both matriptase and prostasin are involved in tight junction formation in epithelial monolayers. However, in polarized epithelial cells matriptase is mainly located on the basolateral plasma membrane whereas prostasin is mainly located on the apical plasma membrane. To determine how matriptase and prostasin interact, we mapped the subcellular itinerary of matriptase and prostasin in polarized colonic epithelial cells. We show that zymogen matriptase is activated on the basolateral plasma membrane where it is able to cleave relevant substrates. After activation, matriptase forms a complex with the cognate matriptase inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1 and is efficiently endocytosed. The majority of prostasin is located on the apical plasma membrane albeit a minor fraction of prostasin is present on the basolateral plasma membrane. Basolateral prostasin is endocytosed and transcytosed to the apical plasma membrane where a long retention time causes an accumulation of prostasin. Furthermore, we show that prostasin on the basolateral membrane is activated before it is transcytosed. This study shows that matriptase and prostasin co-localize for a brief period of time at the basolateral plasma membrane after which prostasin is transported to the apical membrane as an active protease. This study suggests a possible explanation for how matriptase or other basolateral serine proteases activate prostasin on its way to its apical destination.
C1 [Vogel, Lotte K.] Univ Copenhagen, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark.
[Godiksen, Sine] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
[Rasmussen, Hanne Borger] Univ Copenhagen, Dept Biomed Sci, DK-2200 Copenhagen, Denmark.
[Bugge, Thomas H.] NIDCR, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA.
[Lin, Chen-Yong] Univ Maryland, Dept Biochem & Mol Biol, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Vogel, LK (reprint author), Blegdamsvej 3,Bldg 6-4, DK-2200 Copenhagen N, Denmark.
EM vogel@sund.ku.dk
RI Rasmussen, Hanne /N-9652-2016
OI Rasmussen, Hanne /0000-0002-2218-5646
FU NIDCR; National Institutes of Health [R01-CA-123223]; Harboe Foundation;
Augustinus Foundation; Brothers Hartmanns Foundation; A.P. Mollers
Foundation for the Advancement of Medical Science; University of
Copenhagen; Lundbeck Foundation
FX This work was supported, in whole or in part, by the NIDCR Intramural
Research Program and by National Institutes of Health Grant
R01-CA-123223. This work was also supported by The Harboe Foundation,
The Augustinus Foundation, The Brothers Hartmanns Foundation, The A.P.
Mollers Foundation for the Advancement of Medical Science, The Cluster
of Cell Biology at the University of Copenhagen, and the Lundbeck
Foundation.
NR 34
TC 19
Z9 19
U1 2
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 18
PY 2011
VL 286
IS 7
BP 5793
EP 5802
DI 10.1074/jbc.M110.186874
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719SY
UT WOS:000287230600088
PM 21148558
ER
PT J
AU Moreno, E
Hoffmann, H
Gonzalez-Sepulveda, M
Navarro, G
Casado, V
Cortes, A
Mallol, J
Vignes, M
McCormick, PJ
Canela, EI
Lluis, C
Moratalla, R
Ferre, S
Ortiz, J
Franco, R
AF Moreno, Estefana
Hoffmann, Hanne
Gonzalez-Sepulveda, Marta
Navarro, Gemma
Casado, Vicent
Cortes, Antoni
Mallol, Josefa
Vignes, Michel
McCormick, Peter J.
Canela, Enric I.
Lluis, Carme
Moratalla, Rosario
Ferre, Sergi
Ortiz, Jordi
Franco, Rafael
TI Dopamine D-1-histamine H-3 Receptor Heteromers Provide a Selective Link
to MAPK Signaling in GABAergic Neurons of the Direct Striatal Pathway
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MEDIUM SPINY NEURONS; HISTAMINE H-3; RAT-BRAIN; INHIBITION; AGONIST;
D-1; H3; NEUROTRANSMITTER; PHARMACOLOGY; HALOPERIDOL
AB Previously, using artificial cell systems, we identified receptor heteromers between the dopamine D-1 or D-2 receptors and the histamine H-3 receptor. In addition, we demonstrated two biochemical characteristics of the dopamine D-1 receptor-histamine H-3 receptor heteromer. We have now extended this work to show the dopamine D-1 receptor-histamine H-3 receptor heteromer exists in the brain and serves to provide a novel link between the MAPK pathway and the GABAergic neurons in the direct striatal efferent pathway. Using the biochemical characteristics identified previously, we found that the ability of H-3 receptor activation to stimulate p44 and p42 extracellular signal-regulated MAPK (ERK 1/2) phosphorylation was only observed in striatal slices of mice expressing D-1 receptors but not in D-1 receptor-deficient mice. On the other hand, the ability of both D-1 and H-3 receptor antagonists to block MAPK activation induced by either D-1 or H-3 receptor agonists was also found in striatal slices. Taken together, these data indicate the occurrence of D-1-H-3 receptor complexes in the striatum and, more importantly, that H-3 receptor agonist-induced ERK 1/2 phosphorylation in striatal slices is mediated by D-1-H-3 receptor heteromers. Moreover, H-3 receptor-mediated phospho-ERK 1/2 labeling co-distributed with D-1 receptor-containing but not with D-2 receptor-containing striatal neurons. These results indicate that D-1-H-3 receptor heteromers work as processors integrating dopamine-and histamine-related signals involved in controlling the function of striatal neurons of the direct striatal pathway.
C1 [Franco, Rafael] Univ Navarra, Ctr Invest Med Aplicada, Pamplona 31008, Spain.
[Moreno, Estefana; Navarro, Gemma; Casado, Vicent; Cortes, Antoni; Mallol, Josefa; McCormick, Peter J.; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Fac Biol, E-08028 Barcelona, Spain.
[Moreno, Estefana; Navarro, Gemma; Casado, Vicent; Cortes, Antoni; Mallol, Josefa; McCormick, Peter J.; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
[Hoffmann, Hanne; Gonzalez-Sepulveda, Marta; Ortiz, Jordi] Univ Autonoma Barcelona, Fac Med, Inst Neurosci, Bellaterra 08193, Spain.
[Hoffmann, Hanne; Gonzalez-Sepulveda, Marta; Ortiz, Jordi] Univ Autonoma Barcelona, Fac Med, Dept Biochem & Mol Biol, Bellaterra 08193, Spain.
[Vignes, Michel] Univ Montpellier 2, Univ Montpellier 1&2, Max Mousseron Biomol Inst, CNRS,UMR 5247, F-34095 Montpellier, France.
[Ferre, Sergi] Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Moratalla, Rosario] CSIC, Inst Cajal, E-28002 Madrid, Spain.
RP Franco, R (reprint author), Univ Navarra, Ctr Invest Med Aplicada, Pio 12,5, I-31008 Pamplona, Italy.
EM rfranco@unav.es
RI Ortiz, Jordi/E-9018-2011; Canela, Enric I./M-8726-2013; McCormick,
Peter/E-7387-2012; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015;
Moratalla, Rosario/H-9280-2015; Casado, Vicent/K-1660-2014;
OI Moreno, Estefania/0000-0002-2491-5753; Ortiz, Jordi/0000-0002-9748-2290;
Canela, Enric I./0000-0003-4992-7440; McCormick,
Peter/0000-0002-2225-5181; Ferre, Sergi/0000-0002-1747-1779; Franco,
Rafael/0000-0003-2549-4919; Moratalla, Rosario/0000-0002-7623-8010;
Gonzalez Sepulveda, Marta/0000-0002-5627-847X; Casado,
Vicent/0000-0002-1764-3825
FU Spanish Ministerio de Ciencia y Tecnologia [SAF2008-00146,
SAF2008-03229-E, SAF2009-07276, SAF2006-08240, SAF2009-12510]; Centre
National de la Recherche Scintifique; French Ministry of Research and
Higher Education; Red de Transtornos Adictivos [RD06/0001/0015];
Fundacio La Marato de TV3 [060110]; National Institute on Drug Abuse
FX This study was supported by Grants SAF2008-00146, SAF2008-03229-E,
SAF2009-07276, SAF2006-08240, and SAF2009-12510 from the Spanish
Ministerio de Ciencia y Tecnologia, the Centre National de la Recherche
Scintifique, the French Ministry of Research and Higher Education, Red
de Transtornos Adictivos RD06/0001/0015, Grant 060110 from Fundacio La
Marato de TV3 and the Intramural Funds of the National Institute on Drug
Abuse.
NR 32
TC 48
Z9 48
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 18
PY 2011
VL 286
IS 7
BP 5846
EP 5854
DI 10.1074/jbc.M110.161489
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719SY
UT WOS:000287230600093
PM 21173143
ER
PT J
AU Datta, SAK
Heinrich, F
Raghunandan, S
Krueger, S
Curtis, JE
Rein, A
Nanda, H
AF Datta, Siddhartha A. K.
Heinrich, Frank
Raghunandan, Sindhu
Krueger, Susan
Curtis, Joseph E.
Rein, Alan
Nanda, Hirsh
TI HIV-1 Gag Extension: Conformational Changes Require Simultaneous
Interaction with Membrane and Nucleic Acid
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE retroviral assembly; neutron reflectivity; SANS; disordered proteins;
tethered membranes
ID BILAYER-LIPID MEMBRANES; IN-VITRO; NUCLEOCAPSID PROTEIN; MATRIX PROTEIN;
DOMAIN; BINDING; POLYPROTEIN; PARTICLES; RNA; IDENTIFICATION
AB The retroviral Gag polyprotein mediates viral assembly. The Gag protein has been shown to interact with other Gag proteins, with the viral RNA, and with the cell membrane during the assembly process. Intrinsically disordered regions linking ordered domains make characterization of the protein structure difficult. Through small-angle scattering and molecular modeling, we have previously shown that monomeric human immunodeficiency virus type 1 (HIV-1) Gag protein in solution adopts compact conformations. However, cryo-electron microscopic analysis of immature virions shows that in these particles, HIV-1 Gag protein molecules are rod shaped. These differing results imply that large changes in Gag conformation are possible and may be required for viral formation. By recapitulating key interactions in the assembly process and characterizing the Gag protein using neutron scattering, we have identified interactions capable of reversibly extending the Gag protein. In addition, we demonstrate advanced applications of neutron reflectivity in resolving Gag conformations on a membrane. Several kinds of evidence show that basic residues found on the distal N- and C-terminal domains enable both ends of Gag to bind to either membranes or nucleic acid. These results, together with other published observations, suggest that simultaneous interactions of an HIV-1 Gag molecule with all three components (protein, nucleic acid, and membrane) are required for full extension of the protein. Published by Elsevier Ltd.
C1 [Raghunandan, Sindhu; Krueger, Susan; Curtis, Joseph E.; Nanda, Hirsh] NIST, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA.
[Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Heinrich, Frank] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
RP Nanda, H (reprint author), NIST, NIST Ctr Neutron Res, 100 Bur Dr,Stop 6103, Gaithersburg, MD 20899 USA.
EM hirsh.nanda@nist.gov
RI Heinrich, Frank/A-5339-2010;
OI Heinrich, Frank/0000-0002-8579-553X; Datta,
Siddhartha/0000-0002-4098-7490
FU National Science Foundation [DMR-0454672]; National Institutes of
Health, National Cancer Institute, Center for Cancer Research
FX This work utilized facilities supported in part by the National Science
Foundation under Agreement No. DMR-0454672. This research was supported
in part by the Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Center for Cancer Research.
NR 35
TC 52
Z9 52
U1 1
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD FEB 18
PY 2011
VL 406
IS 2
BP 205
EP 214
DI 10.1016/j.jmb.2010.11.051
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 762SJ
UT WOS:000290501100001
PM 21134384
ER
PT J
AU McFarland, AP
Savan, R
Wagage, S
Addison, A
Ramakrishnan, K
Karwan, M
Tri, D
Young, HA
AF McFarland, Adelle P.
Savan, Ram
Wagage, Sagie
Addison, Augustina
Ramakrishnan, Karthika
Karwan, Megan
Tri Duong
Young, Howard A.
TI Localized Delivery of Interferon-beta by Lactobacillus Exacerbates
Experimental Colitis
SO PLOS ONE
LA English
DT Article
ID ACTIVE ULCERATIVE-COLITIS; DENDRITIC CELLS; MULTIPLE-SCLEROSIS; T-CELLS;
IN-VITRO; IFN-BETA; FUNCTIONAL SPECIALIZATION; GENE-EXPRESSION;
MECHANISM; RECEPTOR
AB Background: There have been conflicting reports of the role of Type I interferons (IFN) in inflammatory bowel disease (IBD). Clinical trials have shown potent efficacy of systemic interferon-beta (IFN-beta) in inducing remission of ulcerative colitis. Likewise, IFNAR1(-/-) mice display an increased sensitivity to dextran sulfate sodium (DSS)-induced colitis, suggesting Type I IFN play a protective role during inflammation of the gut. Curiously, however, there have also been reports detailing the spontaneous development of IBD in patients receiving systemic IFN-beta therapy for multiple sclerosis or hepatitis.
Methodology/Principal Findings: To investigate the effects of local administration of IFN-beta on a murine model of colitis, we developed a transgenic Lactobacillus acidophilus strain that constitutively expresses IFN-beta (La-IFN-beta). While pretreatment of mice with control Lactobacillus (La-EV) provided slight protective benefits, La-IFN-beta increased sensitivity to DSS. Analysis showed colitic mice pretreated with L alpha-IFN-beta had increased production of TNF-alpha, IFN-gamma, IL-17A and IL-13 by intestinal tissues and decreased regulatory T cells (Tregs) in their small intestine. Examination of CD103(+) dendritic cells (DCs) in the Peyer's patches revealed that IFNAR1 expression was dramatically reduced by La-IFN-beta. Similarly, bone marrow-derived DCs matured with La-IFN-beta experienced a 3-fold reduction of IFNAR1 and were impaired in their ability to induce Tregs.
Conclusions/Significance: Our IFNAR1 expression data identifies a correlation between the loss/downregulation of IFNAR1 on DCs and exacerbation of colitis. Our data show that Lactobacillus secreting IFN-b has an immunological effect that in our model results in the exacerbation of colitis. This study underscores that the selection of therapeutics delivered by a bacterial vehicle must take into consideration the simultaneous effects of the vehicle itself.
C1 [McFarland, Adelle P.; Savan, Ram; Wagage, Sagie; Addison, Augustina; Ramakrishnan, Karthika; Karwan, Megan; Young, Howard A.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Tri Duong] N Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27695 USA.
RP McFarland, AP (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM YoungHow@mail.nih.gov
RI Duong, Tri/B-5594-2012
OI Duong, Tri/0000-0002-4803-8564
FU Office of Dietary Supplements, National Institutes of Health (NIH);
National Cancer Institute (NCI), NIH [HHSN261200800001E]; NIH, NCI,
Center for Cancer Research
FX Funding: This project has been funded in whole or in part with federal
funds from the Office of Dietary Supplements, National Institutes of
Health (NIH) and the National Cancer Institute (NCI), NIH, under the
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the United States
government. This research was supported 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 70
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Z9 18
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 18
PY 2011
VL 6
IS 2
AR e16967
DI 10.1371/journal.pone.0016967
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 723CC
UT WOS:000287482800024
PM 21365015
ER
PT J
AU Wiese, C
Nikolova, T
Zahanich, I
Sulzbacher, S
Fuchs, J
Yamanaka, S
Graf, E
Ravens, U
Boheler, KR
Wobus, AM
AF Wiese, Cornelia
Nikolova, Teodora
Zahanich, Ihor
Sulzbacher, Sabine
Fuchs, Joerg
Yamanaka, Satoshi
Graf, Eva
Ravens, Ursula
Boheler, Kenneth R.
Wobus, Anna M.
TI Differentiation induction of mouse embryonic stem cells into sinus
node-like cells by suramin
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Embryonic stem cells; Mouse; Cardiac differentiation; Suramin;
Brachyury; Sinus node-like cells
ID BONE MORPHOGENETIC PROTEINS; FIBROBLAST-GROWTH-FACTOR; FACTOR
RECEPTOR-BINDING; IN-VITRO; CONDUCTION SYSTEM; MUSCLE-CELLS; VENTRICULAR
CARDIOMYOCYTES; CARDIAC DIFFERENTIATION; FUNCTIONAL-PROPERTIES;
EXPRESSION PATTERN
AB Background: Embryonic stem (ES) cells differentiate into cardiac phenotypes representing early pacemaker-, atrial-, ventricular-, and sinus node-like cells, however, ES-derived specification into sinus nodal cells is not yet known. By using the naphthylamine derivative of urea, suramin, we were able to follow the process of cardiac specialization into sinus node-like cells.
Methods: Differentiating mouse ES cells were treated with suramin (500 mu M) from day 5 to 7 of embryoid body formation, and cells were analysed for their differentiation potential via morphological analysis, flow cytometry, RT-PCR, immunohistochemistry and patch clamp analysis.
Results: Application of suramin resulted in an increased number of cardiac cells, but inhibition of neuronal, skeletal muscle and definitive endoderm differentiation. Immediately after suramin treatment, a decreased mesendoderm differentiation was found. Brachyury, FGF10, Wnt8 and Wnt3a transcript levels were significantly down-regulated, followed by a decrease in mesoderm-and cardiac progenitor-specific markers BMP2, GATA4/5, Wnt11, Isl1, Nkx2.5 and Tbx5 immediately after removal of the substance. With continued differentiation, a significant up-regulation of Brachyury, FGF10 and GATA5 transcript levels was observed, whereas Nkx2.5, Isl1, Tbx5, BMP2 and Wnt11 levels were normalized to control levels. At advanced differentiation stages, sinus node-specific HCN4, Tbx2 and Tbx3 transcript levels were significantly up-regulated. Immunofluorescence and patch-clamp analysis confirmed the increased number of sinus node-like cells, and electrophysiological analysis revealed a lower number of atrial-and ventricular-like cardiomyocytes following suramin treatment.
Conclusion: We conclude that the interference of suramin with the cardiac differentiation process modified mesoderm-and cardiac-specific gene expression resulting in enhanced formation of sinus node-like cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Wiese, Cornelia; Nikolova, Teodora; Sulzbacher, Sabine; Wobus, Anna M.] Leibniz Inst Plant Genet & Crop Plant Res IPK, In Vitro Differentiat Grp, D-06466 Gatersleben, Germany.
[Fuchs, Joerg] Leibniz Inst Plant Genet & Crop Plant Res IPK, Dept Cytogenet, D-06466 Gatersleben, Germany.
[Yamanaka, Satoshi; Boheler, Kenneth R.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Zahanich, Ihor; Graf, Eva; Ravens, Ursula] Tech Univ Dresden, Dept Pharmacol & Toxicol, D-01307 Dresden, Germany.
RP Wobus, AM (reprint author), Leibniz Inst Plant Genet & Crop Plant Res IPK, In Vitro Differentiat Grp, Corrensstr 3, D-06466 Gatersleben, Germany.
EM wobusam@ipk-gatersleben.de
FU EU [LSHB-CT-2004-502988]; University Clinics Grosshadern of the
Ludwigs-Maximilians University Munich; Aventis Foundation
FX This work was supported by the EU grant "SC&CR" (LSHB-CT-2004-502988) to
A.M.W., an Institutional Grant of the University Clinics Grosshadern of
the Ludwigs-Maximilians University Munich (Prof. Reichart) and the
Aventis Foundation to C.W.
NR 84
TC 17
Z9 19
U1 0
U2 25
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD FEB 17
PY 2011
VL 147
IS 1
BP 95
EP 111
DI 10.1016/j.ijcard.2009.08.021
PG 17
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 722OM
UT WOS:000287443300022
PM 19775764
ER
PT J
AU Geiger, TR
Song, JY
Rosado, A
Peeper, DS
AF Geiger, Thomas R.
Song, Ji-Ying
Rosado, Aranzazu
Peeper, Daniel S.
TI Functional Characterization of Human Cancer-Derived TRKB Mutations
SO PLOS ONE
LA English
DT Article
ID NEUROTROPHIC RECEPTOR TRKB; HER2-POSITIVE BREAST-CANCER; ETV6-NTRK3 GENE
FUSION; TYROSINE KINASE; CELL-LINES; ADJUVANT CHEMOTHERAPY; ANOIKIS
RESISTANCE; COLORECTAL CANCERS; SOMATIC MUTATIONS; LUNG-CANCER
AB Cancer originates from cells that have acquired mutations in genes critical for controlling cell proliferation, survival and differentiation. Often, tumors continue to depend on these so-called driver mutations, providing the rationale for targeted anticancer therapies. To date, large-scale sequencing analyses have revealed hundreds of mutations in human tumors. However, without their functional validation it remains unclear which mutations correspond to driver, or rather bystander, mutations and, therefore, whether the mutated gene represents a target for therapeutic intervention. In human colorectal tumors, the neurotrophic receptor TRKB has been found mutated on two different sites in its kinase domain (TRKB(T695I) and TRKB(D751N)). Another site, in the extracellular part of TRKB, is mutated in a human lung adenocarcinoma cell line (TRKB(L138F)). Lastly, our own analysis has identified one additional TRKB point mutation proximal to the kinase domain (TRKB(P507L)) in a human melanoma cell line. The functional consequences of all these point mutations, however, have so far remained elusive. Previously, we have shown that TRKB is a potent suppressor of anoikis and that TRKB-expressing cells form highly invasive and metastatic tumors in nude mice. To assess the functional consequences of these four TRKB mutations, we determined their potential to suppress anoikis and to form tumors in nude mice. Unexpectedly, both colon cancer-derived mutants, TRKB(T695I) and TRKB(D751N), displayed reduced activity compared to that of wild-type TRKB. Consistently, upon stimulation with the TRKB ligand BDNF, these mutants were impaired in activating TRKB and its downstream effectors AKT and ERK. The two mutants derived from human tumor cell lines (TRKB(L138F) and TRKB(P507L)) were functionally indistinguishable from wild-type TRKB in both in-vitro and in-vivo assays. In conclusion, we fail to detect any gain-of-function of four cancer-derived TRKB point mutations.
C1 [Geiger, Thomas R.; Rosado, Aranzazu; Peeper, Daniel S.] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands.
[Song, Ji-Ying] Netherlands Canc Inst, Dept Expt Anim Pathol, NL-1066 CX Amsterdam, Netherlands.
RP Geiger, TR (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM d.peeper@nki.nl
FU European Union
FX This work was supported by a European Union FP6 grant to T. R. G., A. R.
and D. S. P. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 50
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Z9 14
U1 3
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 17
PY 2011
VL 6
IS 2
AR e16871
DI 10.1371/journal.pone.0016871
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 723BX
UT WOS:000287482300023
PM 21379385
ER
PT J
AU Yu, SY
Cui, KR
Jothi, R
Zhao, DM
Jing, XF
Zhao, K
Xue, HH
AF Yu, Shuyang
Cui, Kairong
Jothi, Raja
Zhao, Dong-Mei
Jing, Xuefang
Zhao, Keji
Xue, Hai-Hui
TI GABP controls a critical transcription regulatory module that is
essential for maintenance and differentiation of hematopoietic
stem/progenitor cells
SO BLOOD
LA English
DT Article
ID STEM-CELLS; SELF-RENEWAL; BINDING-PROTEIN; LYMPHOCYTE DEVELOPMENT;
IN-VIVO; DNA METHYLTRANSFERASE; CHROMATIN OCCUPANCY; OXIDATIVE STRESS;
PROGENITOR CELLS; GENE-EXPRESSION
AB Maintaining a steady pool of self-renewing hematopoietic stem cells (HSCs) is critical for sustained production of multiple blood lineages. Many transcription factors and molecules involved in chromatin and epigenetic modifications have been found to be critical for HSC self-renewal and differentiation; however, their interplay is less understood. The transcription factorGAbinding protein (GABP), consisting of DNA-binding subunit GABP alpha and transactivating subunit GABP beta, is essential for lymphopoiesis as shown in our previous studies. Here we demonstrate cell-intrinsic, absolute dependence on GABP alpha for maintenance and differentiation of hematopoietic stem/progenitor cells. Through genome-wide mapping of GABP alpha binding and transcriptomic analysis of GABP alpha-deficient HSCs, we identified Zfx and Etv6 transcription factors and prosurvival Bcl-2 family members including Bcl-2, Bcl-X(L), and Mcl-1 as direct GABP target genes, underlying its pivotal role in HSC survival. GABP also directly regulates Foxo3 and Pten and hence sustains HSC quiescence. Furthermore, GABP activates transcription of DNA methyltransferases and histone acetylases including p300, contributing to regulation of HSC self-renewal and differentiation. These systematic analyses revealed a GABP-controlled gene regulatory module that programs multiple aspects of HSC biology. Our studies thus constitute a critical first step in decoding how transcription factors are orchestrated to regulate maintenance and multipotency of HSCs. (Blood. 2011; 117(7):2166-2178)
C1 [Yu, Shuyang; Zhao, Dong-Mei; Jing, Xuefang; Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA.
[Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Jothi, Raja] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC USA.
[Zhao, Dong-Mei] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA.
[Xue, Hai-Hui] Univ Iowa, Interdisciplinary Immunol Grad Program, Carver Coll Med, Iowa City, IA 52242 USA.
RP Xue, HH (reprint author), 51 Newton Rd,BSB 3-710, Iowa City, IA 52246 USA.
EM hai-hui-xue@uiowa.edu
RI cheng, yong/I-4270-2012; Jothi, Raja/G-3780-2015
FU NIH [AI042767, HL095540]; National Heart, Lung and Blood Institute, NIH;
National Institute of Environmental Health Sciences [1ZIAES102625-01]
FX This study is supported by NIH grants AI042767 and HL095540 (H-H.X.),
the intramural research program of the National Heart, Lung and Blood
Institute, NIH (K.Z.), and the National Institute of Environmental
Health Sciences (1ZIAES102625-01; R.J.).
NR 54
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Z9 41
U1 1
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 17
PY 2011
VL 117
IS 7
BP 2166
EP 2178
DI 10.1182/blood-2010-09-306563
PG 13
WC Hematology
SC Hematology
GA 722OB
UT WOS:000287440900018
PM 21139080
ER
PT J
AU Hall, FS
Schwarzbaum, JM
Perona, MTG
Templin, JS
Caron, MG
Lesch, KP
Murphy, DL
Uhl, GR
AF Hall, F. S.
Schwarzbaum, J. M.
Perona, M. T. G.
Templin, J. S.
Caron, M. G.
Lesch, K. -P.
Murphy, D. L.
Uhl, G. R.
TI A GREATER ROLE FOR THE NOREPINEPHRINE TRANSPORTER THAN THE SEROTONIN
TRANSPORTER IN MURINE NOCICEPTION
SO NEUROSCIENCE
LA English
DT Article
DE knockout mice; serotonin transporter; norepinephrine transporter;
analgesia; nociception; amitriptyline
ID CENTRAL NERVOUS-SYSTEM; RAT FORMALIN TEST; MORPHINE-INDUCED
ANTINOCICEPTION; MONOAMINE REUPTAKE INHIBITORS; TRICYCLIC
ANTI-DEPRESSANTS; NUCLEUS RAPHE MAGNUS; SOLE ANALGESIC AGENT;
PERIAQUEDUCTAL GRAY; NEUROPATHIC PAIN; INTRATHECAL CLONIDINE
AB Norepinephrine and serotonin involvement in nociceptive functions is supported by observations of analgesic effects of norepinephrine transporter (NET) and serotonin transporter (SERT) inhibitors such as amitriptyline. However, the relative contribution of NET and SERT to baseline nociception, as well as amitriptyline analgesia, is unclear. Amitriptyline and morphine analgesia in wild-type (WT) mice and littermates with gene knockout (KO) of SERT, NET or both transporters was conducted using the hotplate and tail-flick tests. Hypoalgesia was observed in NET KO mice, and to a lesser extent in SERT KO mice. The magnitude of this hypoalgesia in NET KO mice was so profound that it limited the assessment of drug-induced analgesia. Nonetheless, the necessary exclusion of these subjects because of profound baseline hypoalgesia strongly supports the role of norepinephrine and NET in basal nociceptive behavior while indicating a much smaller role for serotonin and SERT. To further clarify the role of NET and SERT in basal nociceptive sensitivity further experiments were conducted in SERT KO and NET KO mice across a range of temperatures. NET KO mice were again found to have pronounced thermal hypoalgesia compared to WT mice in both the hotplate and tail-flick tests, while only limited effects were observed in SERT KO mice. Furthermore, in the acetic acid writhing test of visceral nociception pronounced hypoalgesia was again found in NET KO mice, but no change in SERT KO mice. As some of these effects may have resulted from developmental consequences of NET KO, the effects of the selective NET blocker nisoxetine and the selective SERT blocker fluoxetine were also examined in WT mice: only nisoxetine produced analgesia in these mice. Collectively these data suggest that NET has a far greater role in determining baseline analgesia, and perhaps other analgesic effects, than SERT in mice. Published by Elsevier Ltd on behalf of IBRO.
C1 [Hall, F. S.; Schwarzbaum, J. M.; Perona, M. T. G.; Templin, J. S.; Uhl, G. R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Caron, M. G.] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA.
[Caron, M. G.] Duke Univ, Dept Med, Durham, NC 27710 USA.
[Lesch, K. -P.] Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany.
[Murphy, D. L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA.
RP Hall, FS (reprint author), NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
EM shall@intra.nida.nih.gov
RI Lesch, Klaus-Peter/J-4906-2013; Hall, Frank/C-3036-2013
OI Lesch, Klaus-Peter/0000-0001-8348-153X; Hall, Frank/0000-0002-0822-4063
FU National Institute on Drug Abuse (USA)
FX This work was supported by funding from the Intramural Research Program
of the National Institute on Drug Abuse (USA). We gratefully acknowledge
animal care support from the Charles River/Triad animal care support
section, especially our breeder/geneticist Kriss Knestaut. Experiments
were conducted under protocols approved by the NIDA Intramural Animal
Care and Use Committee.
NR 95
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U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD FEB 17
PY 2011
VL 175
BP 315
EP 327
DI 10.1016/j.neuroscience.2010.11.057
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 718FK
UT WOS:000287106300030
PM 21129446
ER
PT J
AU Stanescu, HC
Arcos-Burgos, M
Medlar, A
Bockenhauer, D
Kottgen, A
Dragomirescu, L
Voinescu, C
Patel, N
Pearce, K
Hubank, M
Stephens, HAF
Laundy, V
Padmanabhan, S
Zawadzka, A
Hofstra, JM
Coenen, MJH
den Heijer, M
Kiemeney, LALM
Bacq-Daian, D
Stengel, B
Powis, SH
Brenchley, P
Feehally, J
Rees, AJ
Debiec, H
Wetzels, JFM
Ronco, P
Mathieson, PW
Kleta, R
AF Stanescu, Horia C.
Arcos-Burgos, Mauricio
Medlar, Alan
Bockenhauer, Detlef
Kottgen, Anna
Dragomirescu, Liviu
Voinescu, Catalin
Patel, Naina
Pearce, Kerra
Hubank, Mike
Stephens, Henry A. F.
Laundy, Valerie
Padmanabhan, Sandosh
Zawadzka, Anna
Hofstra, Julia M.
Coenen, Marieke J. H.
den Heijer, Martin
Kiemeney, Lambertus A. L. M.
Bacq-Daian, Delphine
Stengel, Benedicte
Powis, Stephen H.
Brenchley, Paul
Feehally, John
Rees, Andrew J.
Debiec, Hanna
Wetzels, Jack F. M.
Ronco, Pierre
Mathieson, Peter W.
Kleta, Robert
TI Risk HLA-DQA1 and PLA(sub 2)R1 Alleles in Idiopathic Membranous
Nephropathy.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MANNOSE RECEPTOR FAMILY; CLASS-II GENES; GLOMERULONEPHRITIS;
SUSCEPTIBILITY; ANTIGEN; ASSOCIATION; DETERMINANTS; AUTOIMMUNITY; LOCI
AB Background: Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population.
Methods: We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients). The patients were compared with racially matched control subjects; population stratification and quality controls were carried out according to standard criteria. Associations were calculated by means of a chi-square basic allele test; the threshold for significance was adjusted for multiple comparisons (with the Bonferroni method).
Results: In a joint analysis of data from the 556 patients studied (398 men), we identified significant alleles at two genomic loci associated with idiopathic membranous nephropathy. Chromosome 2q24 contains the gene encoding M-type phospholipase A(sub 2) receptor (PLA(sub 2)R1) (SNP rs4664308, P=8.6 x 10(sup -29)), previously shown to be the target of an autoimmune response. Chromosome 6p21 contains the gene encoding HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1) (SNP rs2187668, P=8.0 x 10(sup -93)). The association with HLA-DQA1 was significant in all three populations (P=1.8 x 10(sup -9), P=5.6 x 10(sup -27), and P=5.2 x 10(sup -36) in the French, Dutch, and British groups, respectively). The odds ratio for idiopathic membranous nephropathy with homozygosity for both risk alleles was 78.5 (95% confidence interval, 34.6 to 178.2).
Conclusions: An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. Our findings suggest a basis for understanding this disease and illuminate how adaptive immunity is regulated by HLA.
N Engl J Med 2011;364:616-26.
C1 [Stanescu, Horia C.; Medlar, Alan; Bockenhauer, Detlef; Voinescu, Catalin; Patel, Naina; Stephens, Henry A. F.; Powis, Stephen H.; Kleta, Robert] UCL, Royal Free Hosp, Ctr Nephrol, London NW3 2PF, England.
[Stanescu, Horia C.; Bockenhauer, Detlef; Patel, Naina; Pearce, Kerra; Hubank, Mike; Kleta, Robert] UCL, Inst Child Hlth, London NW3 2PF, England.
[Kleta, Robert] UCL, Dept Physiol, London NW3 2PF, England.
[Kleta, Robert] UCL, Genet Inst, London NW3 2PF, England.
[Bockenhauer, Detlef; Kleta, Robert] Great Ormond St Hosp Sick Children, London, England.
[Stephens, Henry A. F.] Anthony Nolan Trust, London, England.
[Laundy, Valerie; Mathieson, Peter W.] Univ Bristol, Acad Renal Unit, Bristol, Avon, England.
[Padmanabhan, Sandosh] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Zawadzka, Anna] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Brenchley, Paul] Univ Manchester, Sch Biomed, Manchester, Lancs, England.
[Feehally, John] Univ Leicester, John Walls Renal Unit, Leicester, Leics, England.
[Feehally, John] Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England.
[Arcos-Burgos, Mauricio] NHGRI, NIH, Bethesda, MD 20892 USA.
[Kottgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany.
[Kottgen, Anna] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Dragomirescu, Liviu] Univ Bucharest, Dept Syst Ecol, Bucharest, Romania.
[Hofstra, Julia M.; Wetzels, Jack F. M.] Radboud Univ Nijmegen, Med Ctr, Dept Nephrol, NL-6525 ED Nijmegen, Netherlands.
[Coenen, Marieke J. H.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Hubank, Mike; Kiemeney, Lambertus A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands.
[Kiemeney, Lambertus A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands.
[Kiemeney, Lambertus A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Bacq-Daian, Delphine] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France.
[Stengel, Benedicte] Univ Paris Sud, INSERM, UMR S 1018, Villejuif, France.
[Debiec, Hanna; Ronco, Pierre] Univ Paris 06, Tenon Hosp, AP HP, INSERM,UMR S 702, Paris, France.
[Rees, Andrew J.] Med Univ Vienna, Clin Inst Pathol, Vienna, Austria.
RP Kleta, R (reprint author), UCL, Royal Free Hosp, Ctr Nephrol, Rowland Hill St, London NW3 2PF, England.
EM r.kleta@ucl.ac.uk
RI Bockenhauer, Detlef/C-5951-2008; Coenen, Marieke/A-2159-2010; Kottgen,
Anna/D-2920-2012; Hubank, Michael/C-1837-2008; Wetzels,
Jack/A-1720-2014; Kiemeney, Lambertus/D-3357-2009; Hofstra,
Julia/A-4171-2015; Stengel, Benedicte/G-5730-2015; Padmanabhan,
Sandosh/S-3963-2016;
OI Bockenhauer, Detlef/0000-0001-5878-941X; Hubank,
Michael/0000-0002-2901-0742; Kiemeney, Lambertus/0000-0002-2368-1326;
Brenchley, Paul/0000-0003-1290-9919; Padmanabhan,
Sandosh/0000-0003-3869-5808
FU David and Elaine Potter Charitable Foundation; St Peter's Trust for
Kidney, Bladder and Prostate Research; Special Trustees of Great Ormond
Street Hospital; Kids Kidney Research UK; Medical Research Council (MRC)
at the Centre for Integrated Genomic Medical Research, University of
Manchester; MRC [G0000934]; Wellcome Trust [068545/Z/02]; National
Institute for Health Research Manchester Biomedical Research Centre;
Kidney Research UK; Dutch Kidney Foundation; French Ministry of Health
[PHRC AOM 00022]; Ministry of Environment [EN00D08]; Ministry of
Research [01P0513]; Biomedecine Agency; Agence Nationale pour la
Recherche [ANR-07-Physio-016-01]; European Community
[HEALTH-F2-2007-201590]; Fondation pour la Recherche Medicale;
Association pour l'Utilisation du Rein Artificiel; Assistance
Publique-Hopitaux de Paris
FX Supported by grants from the David and Elaine Potter Charitable
Foundation (to Drs. Powis and Kleta), St Peter's Trust for Kidney,
Bladder and Prostate Research (to Drs. Bockenhauer, Powis, and Kleta),
the Special Trustees of Great Ormond Street Hospital (to Dr.
Bockenhauer), Kids Kidney Research UK (to Drs. Bockenhauer and Kleta),
Medical Research Council (MRC) at the Centre for Integrated Genomic
Medical Research, University of Manchester; grants from the MRC
(G0000934) and the Wellcome Trust (068545/Z/02); the National Institute
for Health Research Manchester Biomedical Research Centre (to Dr.
Brenchley); and the MRC and Kidney Research UK, as part of the
MRC/Kidney Research UK National DNA Bank for Glomerulonephritis, for the
collection of the British idiopathic membranous nephropathy DNA samples;
grants from the Dutch Kidney Foundation (Nierstichting Nederland OW 08,
to Drs. Wetzels and Hofstra); grants from the French Ministry of Health
(PHRC AOM 00022), the Ministry of Environment (Decision d'aide EN00D08),
the Ministry of Research (Decision d'aide 01P0513), and the Biomedecine
Agency (AO Recherche et Greffes 2005); grants from the Agence Nationale
pour la Recherche (ANR-07-Physio-016-01), Coordination Theme 1 (Health)
of the European Community's 7th Framework Program
(HEALTH-F2-2007-201590), Fondation pour la Recherche Medicale, and
Association pour l'Utilisation du Rein Artificiel (to Drs. Ronco and
Debiec), and a Contrat d'Interface from Assistance Publique-Hopitaux de
Paris (to Dr. Debiec).
NR 40
TC 169
Z9 188
U1 1
U2 37
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 17
PY 2011
VL 364
IS 7
BP 616
EP 626
DI 10.1056/NEJMoa1009742
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 722BW
UT WOS:000287406000007
PM 21323541
ER
PT J
AU Aragon, R
AF Aragon, Richard
TI Thinking Outside the Box: Fostering Innovation and Non-Hypothesis-Driven
Research at NIH
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID EXTRACTION
AB The National Institutes of Health (NIH) has long been known as an institution that supports biomedical advances through hypothesis-driven research. Another aspect of NIH, however, has received comparatively little attention and may be critical to advancing translational science beyond its current limitations. Specifically, this aspect of NIH focuses on supporting innovation through the development of high-risk technologies that have the potential to empower research.
C1 NCI, Off Biorepositories & Biospecimen Res, Ctr Strateg Sci Initiat, Off Director, Bethesda, MD 20892 USA.
RP Aragon, R (reprint author), NCI, Off Biorepositories & Biospecimen Res, Ctr Strateg Sci Initiat, Off Director, Bethesda, MD 20892 USA.
EM Richard.Aragon@hhs.gov
NR 10
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 16
PY 2011
VL 3
IS 70
AR 70cm5
DI 10.1126/scitranslmed.3001742
PG 5
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795JW
UT WOS:000292971500001
PM 21325614
ER
PT J
AU Bookman, EB
Langehorne, AA
Eckfeldt, JH
Glass, KC
Jarvik, GP
Klag, M
Koski, G
Motulsky, A
Wilfond, B
Manolio, TA
Fabsitz, RR
Luepker, RV
AF Bookman, Ebony B.
Langehorne, Aleisha A.
Eckfeldt, John H.
Glass, Kathleen C.
Jarvik, Gail P.
Klag, Michael
Koski, Greg
Motulsky, Arno
Wilfond, Benjamin
Manolio, Teri A.
Fabsitz, Richard R.
Luepker, Russell V.
TI Comment on "Multidimensional Results Reporting to Participants in
Genomic Studies: Getting It Right"
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Letter
ID WORKING GROUP
C1 [Bookman, Ebony B.; Manolio, Teri A.; Fabsitz, Richard R.] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Langehorne, Aleisha A.] NHLBI, Biomed Res Training Program Underrepresented, Bethesda, MD 20892 USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Glass, Kathleen C.] McGill Univ, Dept Human Genet & Pediat, Montreal, PQ H3G 1Y6, Canada.
[Klag, Michael] Johns Hopkins Univ, Dept Internal Med, Baltimore, MD 21205 USA.
[Koski, Greg] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA.
[Jarvik, Gail P.] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA.
[Motulsky, Arno] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Wilfond, Benjamin] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Luepker, Russell V.] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA.
RP Bookman, EB (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
EM ebony.bookman@nih.gov
RI Jarvik, Gail/N-6476-2014
OI Jarvik, Gail/0000-0002-6710-8708
NR 3
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 16
PY 2011
VL 3
IS 70
AR 70le1
DI 10.1126/scitranslmed.3001516
PG 1
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795JW
UT WOS:000292971500005
PM 21325615
ER
PT J
AU Votteler, J
Neumann, L
Hahn, S
Hahn, F
Rauch, P
Schmidt, K
Studtrucker, N
Solbak, SMO
Fossen, T
Henklein, P
Ott, DE
Holland, G
Bannert, N
Schubert, U
AF Votteler, Joerg
Neumann, Liane
Hahn, Sabine
Hahn, Friedrich
Rauch, Pia
Schmidt, Kerstin
Studtrucker, Nicole
Solbak, Sara M. O.
Fossen, Torgils
Henklein, Peter
Ott, David E.
Holland, Gudrun
Bannert, Norbert
Schubert, Ulrich
TI Highly conserved serine residue 40 in HIV-1 p6 regulates capsid
processing and virus core assembly
SO RETROVIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; LATE DOMAINS; P6(GAG) PROTEIN; GAG
POLYPROTEIN; EBOLA-VIRUS; TYPE-1 P6; TSG101; CELL; UBIQUITIN; RETROVIRUS
AB Background: The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L-) domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX), is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6.
Results: Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA) and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site.
Conclusions: Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively affects CA maturation and virus core formation, and consequently the infectivity of released virions.
C1 [Votteler, Joerg; Neumann, Liane; Hahn, Sabine; Hahn, Friedrich; Rauch, Pia; Schmidt, Kerstin; Studtrucker, Nicole; Schubert, Ulrich] Univ Erlangen Nurnberg, Inst Virol, Erlangen, Germany.
[Solbak, Sara M. O.; Fossen, Torgils] Univ Bergen, Ctr Pharm, Bergen, Norway.
[Henklein, Peter] Humboldt Univ, Inst Biochem, Berlin, Germany.
[Ott, David E.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Holland, Gudrun; Bannert, Norbert] Robert Koch Inst, D-1000 Berlin, Germany.
RP Schubert, U (reprint author), Univ Erlangen Nurnberg, Inst Virol, Erlangen, Germany.
EM Ulrich.Schubert@viro.med.uni-erlangen.de
FU German Human Genome Research Project [IE-S08T06]; German Research
Council [SFB 643-A1, SCHU1125/3, SCHU 1125/5]
FX We thank Dr. Henning Heumann and the surgical staff of the Olgahospital,
Stuttgart, for generous assistance in obtaining post-tonsillectomy
samples, Raymond Sowder for HPLC purification, and Victor Wray for
critical reading of the manuscript. This work was supported by a grant
IE-S08T06 from the German Human Genome Research Project, by grants SFB
643-A1, SCHU1125/3, and SCHU 1125/5, from the German Research Council to
US.
NR 58
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Z9 11
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD FEB 16
PY 2011
VL 8
AR 11
DI 10.1186/1742-4690-8-11
PG 16
WC Virology
SC Virology
GA 758ZR
UT WOS:000290208800001
PM 21324168
ER
PT J
AU Umhau, JC
AF Umhau, John C.
TI Docosahexaenoic Acid Supplementation and Alzheimer Disease
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
RP Umhau, JC (reprint author), NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
EM umhau@jhu.edu
NR 5
TC 5
Z9 5
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 16
PY 2011
VL 305
IS 7
BP 672
EP 672
DI 10.1001/jama.2011.140
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 721NH
UT WOS:000287361100014
PM 21325181
ER
PT J
AU Picchioni, D
Horovitz, SG
Fukunaga, M
Carr, WS
Meltzer, JA
Balkin, TJ
Duyn, JH
Braun, AR
AF Picchioni, Dante
Horovitz, Silvina G.
Fukunaga, Masaki
Carr, Walter S.
Meltzer, Jed A.
Balkin, Thomas J.
Duyn, Jeff H.
Braun, Allen R.
TI Infraslow EEG oscillations organize large-scale cortical-subcortical
interactions during sleep: A combined EEG/fMRI study
SO BRAIN RESEARCH
LA English
DT Article
DE Biological rhythms and sleep; Cortical oscillations; EEG; fMRI; Systems
consolidation
ID SLOW-WAVE SLEEP; RESTING HUMAN BRAIN; FUNCTIONAL CONNECTIVITY; DEFAULT
MODE; ALPHA-RHYTHM; SPINDLE ACTIVITY; POWER-DENSITY; FMRI; NETWORK; MRI
AB Infraslow (<0.1 Hz) oscillations of brain activity, measured by EEG and other methods, have become a subject of increasing interest. While their prominence during sleep has been established, the functional significance of these oscillations for sleep physiology is unknown. To clarify this role, we examined correlations between infraslow EEG oscillations and BOLD fMRI during the course of natural sleep in healthy volunteers. Infraslow EEG oscillations appear to organize a broad dissociation of activity in cortical and subcortical regions: in general, correlations between power in the infraslow EEG band and BOLD were positive in subcortical regions and negative in the cortex. Robust negative correlations were found principally in paramedian heteromodal cortices whereas positive correlations were seen in cerebellum, thalamus, basal ganglia, lateral neocortices and hippocampus. This pattern of correlations suggests a mechanism by which infraslow oscillations may organize sleep-dependent neuroplastic processes including consolidation of episodic memory. Published by Elsevier B.V.
C1 [Picchioni, Dante] Walter Reed Army Inst Res, Dept Behav Biol, Div Psychiat & Neurosci, Silver Spring, MD 20910 USA.
[Horovitz, Silvina G.; Fukunaga, Masaki; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Carr, Walter S.; Meltzer, Jed A.; Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
RP Picchioni, D (reprint author), Walter Reed Army Inst Res, Dept Behav Biol, Div Psychiat & Neurosci, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
EM dante.picchioni@amedd.army.mil
RI Fukunaga, Masaki/F-6441-2013;
OI Fukunaga, Masaki/0000-0003-1010-2644; Meltzer, Jed/0000-0002-4301-1901
FU Intramural NIH HHS [Z99 DC999999]
NR 49
TC 20
Z9 21
U1 1
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD FEB 16
PY 2011
VL 1374
BP 63
EP 72
DI 10.1016/j.brainres.2010.12.035
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 725DA
UT WOS:000287624200008
PM 21168395
ER
PT J
AU Suhasini, AN
Rawtani, NA
Wu, YL
Sommers, JA
Sharma, S
Mosedale, G
North, PS
Cantor, SB
Hickson, ID
Brosh, RM
AF Suhasini, Avvaru N.
Rawtani, Nina A.
Wu, Yuliang
Sommers, Joshua A.
Sharma, Sudha
Mosedale, Georgina
North, Phillip S.
Cantor, Sharon B.
Hickson, Ian D.
Brosh, Robert M., Jr.
TI Interaction between the helicases genetically linked to Fanconi anemia
group J and Bloom's syndrome
SO EMBO JOURNAL
LA English
DT Article
DE BLM; Bloom's syndrome; FANCJ; Fanconi anemia; helicase
ID TOPOISOMERASE III-ALPHA; REPLICATION PROTEIN-A; DNA-DAMAGE RESPONSE;
GENOMIC STABILITY; BREAST-CANCER; S-PHASE; HOMOLOGOUS RECOMBINATION;
ESSENTIAL COMPONENT; HOLLIDAY JUNCTIONS; CRYSTAL-STRUCTURE
AB Bloom's syndrome (BS) and Fanconi anemia (FA) are autosomal recessive disorders characterized by cancer and chromosomal instability. BS and FA group J arise from mutations in the BLM and FANCJ genes, respectively, which encode DNA helicases. In this work, FANCJ and BLM were found to interact physically and functionally in human cells and co-localize to nuclear foci in response to replication stress. The cellular level of BLM is strongly dependent upon FANCJ, and BLM is degraded by a proteasome-mediated pathway when FANCJ is depleted. FANCJ-deficient cells display increased sister chromatid exchange and sensitivity to replication stress. Expression of a FANCJ C-terminal fragment that interacts with BLM exerted a dominant negative effect on hydroxyurea resistance by interfering with the FANCJ-BLM interaction. FANCJ and BLM synergistically unwound a DNA duplex substrate with sugar phosphate backbone discontinuity, but not an 'undamaged' duplex. Collectively, the results suggest that FANCJ catalytic activity and its effect on BLM protein stability contribute to preservation of genomic stability and a normal response to replication stress. The EMBO Journal (2011) 30, 692-705. doi:10.1038/emboj.2010.362; Published online 14 January 2011
C1 [Suhasini, Avvaru N.; Rawtani, Nina A.; Wu, Yuliang; Sommers, Joshua A.; Sharma, Sudha; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA.
[Mosedale, Georgina; North, Phillip S.; Hickson, Ian D.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
[Cantor, Sharon B.] Univ Massachusetts, Sch Med, Dept Canc Biol, Womens Canc Program,UMASS Mem Canc Ctr, Worcester, MA USA.
[Hickson, Ian D.] Univ Copenhagen, Dept Cellular & Mol Med, Ctr Hlth Aging, Copenhagen, Denmark.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
OI Sharma, Sudha/0000-0003-2765-2482
FU NIH; National Institute on Aging; Cancer Research UK; Fanconi Anemia
Research Fund
FX We thank the Fanconi Anemia Research Fund for the FA-A and FA-D2 null
and corrected cell lines. We acknowledge Dr Fred Indig (NIA-NIH) and Mr
Al May (NIA-NIH) for their assistance with confocal imaging. This
research was supported by the Intramural Research program of the NIH,
National Institute on Aging, Cancer Research UK, and the Fanconi Anemia
Research Fund (RMB).
NR 60
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U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD FEB 16
PY 2011
VL 30
IS 4
BP 692
EP 705
DI 10.1038/emboj.2010.362
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 721YV
UT WOS:000287395300008
PM 21240188
ER
PT J
AU Carlson, BR
Lloyd, KE
Kruszewski, A
Kim, IH
Rodriguiz, RM
Heindel, C
Faytell, M
Dudek, SM
Wetsel, WC
Soderling, SH
AF Carlson, Benjamin R.
Lloyd, Krissey E.
Kruszewski, Allison
Kim, Il-Hwan
Rodriguiz, Ramona M.
Heindel, Clifford
Faytell, Marika
Dudek, Serena M.
Wetsel, William C.
Soderling, Scott H.
TI WRP/srGAP3 Facilitates the Initiation of Spine Development by an Inverse
F-BAR Domain, and Its Loss Impairs Long-Term Memory
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ACTIN-BASED PLASTICITY; DENDRITIC SPINES; MENTAL-RETARDATION; MEMBRANE
INVAGINATION; SYNAPTIC PLASTICITY; TRANSGENIC MICE; AMPA RECEPTORS;
SMALL GTPASES; IN-VIVO; RHO
AB The WAVE-associated Rac GAP, WRP, is thought to regulate key aspects of synapse development and function and may be linked to mental retardation in humans. WRP contains a newly described inverse F-BAR (IF-BAR) domain of unknown function. Our studies show that this domain senses/facilitates outward protrusions analogous to filopodia and that the molecular basis for this is likely explained by a convex lipid-binding surface on the WRP IF-BAR domain. In dendrites the IF-BAR domain of WRP forms a bud on the shaft from which precursors to spines emerge. Loss of WRP in vivo and in vitro results in reduced density of spines. In vivo this is primarily a loss of mushroom-shaped spines. Developmentally, WRP function is critical at the onset of spinogenesis, when dendritic filopodia are prevalent. Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated. Results from these studies confirm that loss of WRP is linked to impaired learning and memory.
C1 [Carlson, Benjamin R.; Lloyd, Krissey E.; Kruszewski, Allison; Kim, Il-Hwan; Heindel, Clifford; Wetsel, William C.; Soderling, Scott H.] Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA.
[Wetsel, William C.; Soderling, Scott H.] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA.
[Rodriguiz, Ramona M.; Faytell, Marika; Wetsel, William C.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
[Soderling, Scott H.] Duke Univ, Sch Med, Neonatal Perinatal Res Inst, Durham, NC 27710 USA.
[Rodriguiz, Ramona M.; Faytell, Marika; Wetsel, William C.] Duke Univ, Sch Med, Mouse Behav & Neuroendocrine Anal Core Facil, Durham, NC 27710 USA.
[Dudek, Serena M.] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Soderling, SH (reprint author), Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA.
EM s.soderling@cellbio.duke.edu
OI Dudek, Serena M./0000-0003-4094-8368
FU National Institutes of Health [R01-NS059957]; March of Dimes Grant Basil
O'Connor Starter Scholar Research Grant [5-FY07-671]; Dana Foundation;
National Institute of Environmental Health Sciences [1ZIAES100221-08]
FX This work was supported by National Institutes of Health Grant
R01-NS059957 (S. H. S.), March of Dimes Grant Basil O'Connor Starter
Scholar Research Grant 5-FY07-671 (S. H. S.), Dana Foundation Grant (S.
H. S.), and Intramural Research Program of the National Institute of
Environmental Health Sciences Grant 1ZIAES100221-08 (S. M. D.). We thank
Thomas McIntosh and Jihong Tong for their help with the liposome
experiments, Tim Oliver for microscopy assistance, Hal Mekeel (Cell and
Developmental Biology, University of North Carolina, Chapel Hill, NC)
for assistance with SEM, the Duke Transgenic Mouse Facility of the Duke
Comprehensive Cancer Center for embryonic stem cell selection and
chimeric mouse production, and Guoping Feng for the Thy-1 GFP-O and
SLICKV lines of mice. We also thank Jiechun Zhou, Matt Pease, and
Caroline J. Kim for their assistance in the behavioral testing and Amar
Doshi for assisting with histology.
NR 61
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U1 1
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 16
PY 2011
VL 31
IS 7
BP 2447
EP 2460
DI 10.1523/JNEUROSCI.4433-10.2011
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 721XZ
UT WOS:000287392400013
PM 21325512
ER
PT J
AU Mercier, E
Droit, A
Li, LP
Robertson, G
Zhang, XK
Gottardo, R
AF Mercier, Eloi
Droit, Arnaud
Li, Leping
Robertson, Gordon
Zhang, Xuekui
Gottardo, Raphael
TI An Integrated Pipeline for the Genome-Wide Analysis of Transcription
Factor Binding Sites from ChIP-Seq
SO PLOS ONE
LA English
DT Article
ID LEUKEMIA INHIBITORY FACTOR; BREAST-CANCER; EM ALGORITHM; DNA; MOTIFS;
DISCOVERY; SEQUENCES; ALIGNMENT; IDENTIFICATION; ASSOCIATION
AB ChIP-Seq has become the standard method for genome-wide profiling DNA association of transcription factors. To simplify analyzing and interpreting ChIP-Seq data, which typically involves using multiple applications, we describe an integrated, open source, R-based analysis pipeline. The pipeline addresses data input, peak detection, sequence and motif analysis, visualization, and data export, and can readily be extended via other R and Bioconductor packages. Using a standard multicore computer, it can be used with datasets consisting of tens of thousands of enriched regions. We demonstrate its effectiveness on published human ChIP-Seq datasets for FOXA1, ER, CTCF and STAT1, where it detected co-occurring motifs that were consistent with the literature but not detected by other methods. Our pipeline provides the first complete set of Bioconductor tools for sequence and motif analysis of ChIP-Seq and ChIP-chip data.
C1 [Mercier, Eloi; Droit, Arnaud] Inst Rech Clin Montreal, Computat Biol Unit, Montreal, PQ H2W 1R7, Canada.
[Droit, Arnaud] Univ Laval, Dept Mol Med, Fac Med Endocrinol & Genom, Ctr Rech,CHUQ CRCHUQ, Quebec City, PQ, Canada.
[Li, Leping] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Robertson, Gordon] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada.
[Zhang, Xuekui] Univ British Columbia, Dept Stat, Vancouver, BC V6T 1W5, Canada.
[Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
RP Mercier, E (reprint author), Inst Rech Clin Montreal, Computat Biol Unit, Montreal, PQ H2W 1R7, Canada.
EM rgottard@fhcrc.org
RI zhang, xuekui/C-5105-2015
FU National Institutes of Health (NIH) [R01-HG005692]; NIH, National
Institute of Environmental Health Sciences [ES101765-05]; Network of
Applied Genetic Medicine (RMGA); Genome Canada; Genome British Columbia;
Heart and Stroke Foundation of BC/Yukon; British Columbia Knowledge
Development Fund; Juvenile Diabetes Research Foundation; Vancouver
Foundation; BC Cancer Foundation; Michael Smith Foundation for Health
Research
FX Raphael Gottardo was supported by National Institutes of Health (NIH)
grant no. R01-HG005692; Leping Li was supported in part by Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences (ES101765-05); Arnaud Droit was supported by The Network of
Applied Genetic Medicine (RMGA); and Gordon Robertson was supported by
the MORGEN (Dissecting Gene Expression Networks in Mammalian
Organogenesis) project, which was funded by Genome Canada, Genome
British Columbia, the Heart and Stroke Foundation of BC/Yukon, the
British Columbia Knowledge Development Fund, the Juvenile Diabetes
Research Foundation, the Vancouver Foundation, the BC Cancer Foundation,
and the Michael Smith Foundation for Health Research. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 70
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 16
PY 2011
VL 6
IS 2
AR e16432
DI 10.1371/journal.pone.0016432
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721YC
UT WOS:000287392700019
PM 21358819
ER
PT J
AU Wuchty, S
Arjona, D
Li, AG
Kotliarov, Y
Walling, J
Ahn, S
Zhang, A
Maric, D
Anolik, R
Zenklusen, JC
Fine, HA
AF Wuchty, Stefan
Arjona, Dolores
Li, Aiguo
Kotliarov, Yuri
Walling, Jennifer
Ahn, Susie
Zhang, Alice
Maric, Dragan
Anolik, Rachel
Zenklusen, Jean Claude
Fine, Howard A.
TI Prediction of Associations between microRNAs and Gene Expression in
Glioma Biology
SO PLOS ONE
LA English
DT Article
ID STEM-CELL DIVISION; TARGET PREDICTIONS; ASTROCYTIC GLIOMAS;
MESSENGER-RNAS; AKT PATHWAY; GLIOBLASTOMA; REVEALS; TUMORS;
AMPLIFICATION; PROFILES
AB Despite progress in the determination of miR interactions, their regulatory role in cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that the mere knowledge of physical interactions between specific mRNAs and miRs can be used to determine associated regulatory interactions, allowing us to identify 626 associated interactions, involving 128 miRs that putatively modulate the expression of 246 mRNAs. Experimentally determining the expression of miRs, we found an over-representation of over(under)-expressed miRs with various predicted mRNA target sequences. Such significantly associated miRs that putatively bind over-expressed genes strongly tend to have binding sites nearby the 3'UTR of the corresponding mRNAs, suggesting that the presence of the miRs near the translation stop site may be a factor in their regulatory ability. Our analysis predicted a significant association between miR-128 and the protein kinase WEE1, which we subsequently validated experimentally by showing that the over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells.
C1 [Wuchty, Stefan] NINDS, Neurooncol Branch, NCI, Natl Ctr Biotechnol Informat,NIH, Bethesda, MD 20892 USA.
RP Wuchty, S (reprint author), NINDS, Neurooncol Branch, NCI, Natl Ctr Biotechnol Informat,NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
RI Kotliarov, Yuri/B-6938-2017
FU National Institutes of Health, National Cancer Institute
FX Funding was provided by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 53
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 16
PY 2011
VL 6
IS 2
AR e14681
DI 10.1371/journal.pone.0014681
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721YC
UT WOS:000287392700003
PM 21358821
ER
PT J
AU Guevara-Aguirre, J
Balasubramanian, P
Guevara-Aguirre, M
Wei, M
Madia, F
Cheng, CW
Hwang, D
Martin-Montalvo, A
Saavedra, J
Ingles, S
de Cabo, R
Cohen, P
Longo, VD
AF Guevara-Aguirre, Jaime
Balasubramanian, Priya
Guevara-Aguirre, Marco
Wei, Min
Madia, Federica
Cheng, Chia-Wei
Hwang, David
Martin-Montalvo, Alejandro
Saavedra, Jannette
Ingles, Sue
de Cabo, Rafael
Cohen, Pinchas
Longo, Valter D.
TI Growth Hormone Receptor Deficiency Is Associated with a Major Reduction
in Pro-Aging Signaling, Cancer, and Diabetes in Humans
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID FORKHEAD TRANSCRIPTION FACTOR; INCREASED INSULIN SENSITIVITY; FATAL
NEOPLASTIC DISEASES; PROTEIN-KINASE B; AMES DWARF MICE; LIFE-SPAN;
SACCHAROMYCES-CEREVISIAE; FAMILY-MEMBER; CAENORHABDITIS-ELEGANS;
SUPEROXIDE-DISMUTASE
AB Mutations in growth signaling pathways extend life span, as well as protect against age-dependent DNA damage in yeast and decrease insulin resistance and cancer in mice. To test their effect in humans, we monitored for 22 years Ecuadorian individuals who carry mutations in the growth hormone receptor (GHR) gene that lead to severe GHR and IGF-1 (insulin-like growth factor-1) deficiencies. We combined this information with surveys to identify the cause and age of death for individuals in this community who died before this period. The individuals with GHR deficiency exhibited only one nonlethal malignancy and no cases of diabetes, in contrast to a prevalence of 17% for cancer and 5% for diabetes in control subjects. A possible explanation for the very low incidence of cancer was suggested by in vitro studies: Serum from subjects with GHR deficiency reduced DNA breaks but increased apoptosis in human mammary epithelial cells treated with hydrogen peroxide. Serum from GHR-deficient subjects also caused reduced expression of RAS, PKA (protein kinase A), and TOR (target of rapamycin) and up-regulation of SOD2 (superoxide dismutase 2) in treated cells, changes that promote cellular protection and life-span extension in model organisms. We also observed reduced insulin concentrations (1.4 mu U/ml versus 4.4 mu U/ml in unaffected relatives) and a very low HOMA-IR (homeostatic model assessment-insulin resistance) index (0.34 versus 0.96 in unaffected relatives) in individuals with GHR deficiency, indicating higher insulin sensitivity, which could explain the absence of diabetes in these subjects. These results provide evidence for a role of evolutionarily conserved pathways in the control of aging and disease burden in humans.
C1 [Guevara-Aguirre, Jaime; Guevara-Aguirre, Marco; Saavedra, Jannette] Inst Endocrinol Metab & Reprod, Quito, Ecuador.
[Balasubramanian, Priya; Longo, Valter D.] Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA 90089 USA.
[Balasubramanian, Priya; Wei, Min; Madia, Federica; Cheng, Chia-Wei; Longo, Valter D.] Univ So Calif, Andrus Gerontol Ctr, Los Angeles, CA 90089 USA.
[Hwang, David; Cohen, Pinchas] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Endocrinol, Los Angeles, CA 90095 USA.
[Martin-Montalvo, Alejandro; de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Martin-Montalvo, Alejandro] Univ Pablo Olavide Consejo Super Invest Cient, Ctr Andaluz Biol Desarrollo, E-41013 Seville, Spain.
[Martin-Montalvo, Alejandro] Ctr Biomed Res Rare Dis, ISCIII, E-41013 Seville, Spain.
[Ingles, Sue] Univ So Calif, Keck Sch Med, Div Epidemiol, Los Angeles, CA 90089 USA.
[Longo, Valter D.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA 90089 USA.
RP Guevara-Aguirre, J (reprint author), Inst Endocrinol Metab & Reprod, Quito, Ecuador.
EM jguevara@iemyr-ecuador.org; vlongo@usc.edu
RI de Cabo, Rafael/J-5230-2016; Martin-Montalvo, Alejandro/C-2031-2017
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693; Wei,
Min/0000-0002-2649-9271; Martin-Montalvo, Alejandro/0000-0002-3886-5355
FU NIH-National Institute on Aging (NIA) [AG20642, AG025135]; Ted Bakewell
(The Bakewell Foundation); V Foundation for Cancer Research; University
of Southern California Center for Excellence in Genomic Science [1P30
DK063491]; Institute of Endocrinology, Metabolism and Reproduction,
Ecuador
FX This study was funded in part by NIH-National Institute on Aging (NIA)
grants AG20642 and AG025135 to V. D. L.; Ted Bakewell (The Bakewell
Foundation), the V Foundation for Cancer Research, and a University of
Southern California Center for Excellence in Genomic Science pilot grant
to V. D. L.; grant 1P30 DK063491 to P. C.; the Institute of
Endocrinology, Metabolism and Reproduction, Ecuador; and the Intramural
Research Program of the NIH-NIA.
NR 72
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U1 3
U2 44
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 16
PY 2011
VL 3
IS 70
AR 70ra13
DI 10.1126/scitranslmed.3001845
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795JW
UT WOS:000292971500003
PM 21325617
ER
PT J
AU Song, G
Hsu, CH
Riemer, C
Miller, W
AF Song, Giltae
Hsu, Chih-Hao
Riemer, Cathy
Miller, Webb
TI Evaluation of methods for detecting conversion events in gene clusters
SO BMC BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT 9th Asia Pacific Bioinformatics Conference (APBC)
CY JAN 11-14, 2011
CL Incheon, SOUTH KOREA
ID COALESCENT SIMULATION; RECOMBINATION DETECTION; NUCLEOTIDE-SEQUENCES;
HUMAN GENOME; EVOLUTION; MODEL; DNA; ALIGNMENTS; ALGORITHM; SELECTION
AB Background: Gene clusters are genetically important, but their analysis poses significant computational challenges. One of the major reasons for these difficulties is gene conversion among the duplicated regions of the cluster, which can obscure their true relationships. Many computational methods for detecting gene conversion events have been released, but their performance has not been assessed for wide deployment in evolutionary history studies due to a lack of accurate evaluation methods.
Results: We designed a new method that simulates gene cluster evolution, including large-scale events of duplication, deletion, and conversion as well as small mutations. We used this simulation data to evaluate several different programs for detecting gene conversion events.
Conclusions: Our evaluation identifies strengths and weaknesses of several methods for detecting gene conversion, which can contribute to more accurate analysis of gene cluster evolution.
C1 [Song, Giltae; Riemer, Cathy; Miller, Webb] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
[Hsu, Chih-Hao] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Song, G (reprint author), Penn State Univ, Ctr Comparat Genom & Bioinformat, 506 Wartik Lab, University Pk, PA 16802 USA.
EM gsong@bx.psu.edu
OI Song, Giltae/0000-0001-8796-4678
FU NHGRI [HG02238]
FX This study was supported by grant HG02238 from NHGRI. The authors thank
Benjamin Dickins and Darren Martin for helpful suggestions.
NR 45
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Z9 3
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 15
PY 2011
VL 12
SU 1
AR S45
DI 10.1186/1471-2105-12-S1-S45
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 759DN
UT WOS:000290221000046
PM 21342577
ER
PT J
AU Szakal, C
Narayan, K
Fu, J
Lefman, J
Subramaniam, S
AF Szakal, Christopher
Narayan, Kedar
Fu, Jing
Lefman, Jonathan
Subramaniam, Sriram
TI Compositional Mapping of the Surface and Interior of Mammalian Cells at
Submicrometer Resolution
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID ION MASS-SPECTROMETRY; TOF-SIMS; SINGLE CELLS; SPATIAL-RESOLUTION;
MICROSCOPY; LOCALIZATION; CHOLESTEROL; FIXATION; BORON; METHODOLOGY
AB We present progress toward imaging of chemical species within intact mammalian cells using secondary ion mass spectrometry, including the simultaneous mapping of subcellular elemental and molecular species along with intrinsic membrane-specific cellular Markers. Results from imaging both the cell surface and cell interior exposed by site-specific focused ion beam milling demonstrate that in-plane resolutions of approximately 400-500 nm can be achieved. The results from mapping cell surface phosphatidylcholine and several other molecular ions present in the cells establish that spatially resolved chemical signatures of individual cells can be derived from novel multivariate analysis and classification of the molecular images obtained at different m/z ratios. The methods we present here for specimen preparation and chemical imaging of cell interiors provide the foundation for obtaining 3D molecular maps of unstained mammalian cells, with particular relevance for probing the subcellular distributions of small molecules, such as drugs and metabolites.
C1 [Szakal, Christopher; Lefman, Jonathan] Natl Inst Stand & Technol, Surface & Microanal Sci Div, Gaithersburg, MD 20899 USA.
[Narayan, Kedar; Fu, Jing; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Szakal, C (reprint author), Natl Inst Stand & Technol, Surface & Microanal Sci Div, 100 Bur Dr, Gaithersburg, MD 20899 USA.
EM cszakal@nist.gov
RI Sanders, Susan/G-1957-2011; Fu, Jing/D-8512-2012;
OI Fu, Jing/0000-0002-7752-5417
FU Chemical Science and Technology Laboratory (CSTL) at NIST, Gaithersburg,
MD; National Cancer Institute, NIH, Bethesda, MD; NIST and NIH
FX This work was supported by the Chemical Science and Technology
Laboratory (CSTL) at NIST, Gaithersburg, MD, and by the intramural
program of the National Cancer Institute, NIH, Bethesda, MD. This
research was performed while Jonathan Lefman held a National Research
Council Research Associateship Award at NIST and NIH. The authors thank
Dr. Keana Scott from NIST for her assistance in FIB milling and her
valuable insights into the single cell imaging project, Dr. Andrew
Konicek from NIST for additional algorithm development and manuscript
editing, and Donald Bliss from the National Library of Medicine, NIH for
creation of Figure 1f, which was also used as the table of content and
abstract graphics.
NR 48
TC 29
Z9 30
U1 3
U2 33
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD FEB 15
PY 2011
VL 83
IS 4
BP 1207
EP 1213
DI 10.1021/ac1030607
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 719CK
UT WOS:000287176900010
PM 21268648
ER
PT J
AU Neta, G
Goldman, LR
Barr, D
Apelberg, BJ
Witter, FR
Halden, RU
AF Neta, Gila
Goldman, Lynn R.
Barr, Dana
Apelberg, Benjamin J.
Witter, Frank R.
Halden, Rolf U.
TI Fetal Exposure to Chlordane and Permethrin Mixtures in Relation to
Inflammatory Cytokines and Birth Outcomes
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID POLYBROMINATED DIPHENYL ETHERS; NON-HODGKIN-LYMPHOMA;
POLYCHLORINATED-BIPHENYLS; AGRICULTURAL HEALTH; HUMAN SERUM; IN-UTERO;
LYMPHOCYTES; PESTICIDES; INSECTICIDES; ASTHMA
AB We sought to characterize the relationships between cord serum concentrations of chlordane and permethrin pesticides, inflammatory cytokines, gestational age, and size at birth. Umbilical cord serum levels of trans-nonachlor, oxychlordane, cis- and trans-permethrin, piperonyl butoxide, and cytokines (TNF-alpha, IFN-gamma, IL-1 beta, IL-2, IL-6, IL-8, IL-10, IL-12p70, GMCSF) were quantified in 300 newborns at the Johns Hopkins Hospital in Baltimore, MD (2004-2005). Principal component analyses were used to quantitate chlordane and permethrin mixtures and to identify independent cytokine components. Five cytokine components described 87% of the variance in cord serum cytokine levels; these (and predominant loadings) were as follows: (1) all 9 cytokines; (2) acute phase (IL-1 beta, IL-6); (3) anti-inflammatory (IL-10); (4) TNF-alpha; and (5) IL-1 beta. Of these, the TNF-alpha component was significantly associated with a 2-day decrease in gestational age. Chlordane was associated with lower levels of the pro-inflammatory IL-1 beta [beta: -0.11 (-0.20, -0.02)]. Permethrin was negatively associated with the anti-inflammatory cytokine IL-10 [beta: -0.14 (-0.22, -0.05)]. Neither pesticides nor cytokines were significantly associated with birthweight, length, or head circumference, and pesticides were not associated with gestational age. Our findings suggest that chlordane and permethrin concentrations in cord blood may be associated with levels of inflammatory cytokines in the fetus.
C1 [Neta, Gila; Halden, Rolf U.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Neta, Gila; Goldman, Lynn R.; Apelberg, Benjamin J.; Halden, Rolf U.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Barr, Dana] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Witter, Frank R.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA.
[Halden, Rolf U.] Arizona State Univ, Sch Sustainable Engn & Built Environm, Tempe, AZ 85287 USA.
RP Neta, G (reprint author), 6120 Execut Blvd, Rockville, MD 20852 USA.
EM netagil@mail.nih.gov
RI Goldman, Lynn/D-5372-2012; Halden, Rolf/F-9562-2010
OI Halden, Rolf/0000-0001-5232-7361
FU Center for a Livable Future; National Cancer Institute; Maryland
Cigarette Restitution Program; Maryland Mothers and Babies Study;
National Institute of Environmental Health Sciences [R01ES015445]
FX We would like to acknowledge the financial support Gila Neta received
from the Center for a Livable Future and the Intramural Research Program
of the National Cancer Institute. This research was supported by the
Maryland Cigarette Restitution Program Research Grant, Maryland Mothers
and Babies Study, and by award number R01ES015445 from the National
Institute of Environmental Health Sciences. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Environmental Health
Sciences or the National Institutes of Health. We would like to
acknowledge Neal Fedarko at the Bayview General Clinical Research
Center.
NR 38
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U1 0
U2 12
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 FEB 15
PY 2011
VL 45
IS 4
BP 1680
EP 1687
DI 10.1021/es103417j
PG 8
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA 718LI
UT WOS:000287122400074
PM 21235202
ER
PT J
AU Stolzenberg-Solomon, R
Weinstein, SJ
Helzlsouer, K
AF Stolzenberg-Solomon, Rachael
Weinstein, Stephanie J.
Helzlsouer, Kathy
TI RE: "CIRCULATING 25-HYDROXYVITAMIN D AND RISK OF PANCREATIC CANCER"
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
C1 [Stolzenberg-Solomon, Rachael; Weinstein, Stephanie J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20854 USA.
[Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD 21231 USA.
RP Stolzenberg-Solomon, R (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20854 USA.
EM rs221z@nih.gov
NR 12
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD FEB 15
PY 2011
VL 173
IS 4
BP 477
EP 477
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 716QV
UT WOS:000286989500015
ER
PT J
AU Lin, Q
Fang, D
Hou, XW
Le, YY
Fang, JH
Wen, F
Gong, WH
Chen, KQ
Wang, JM
Su, SB
AF Lin, Qing
Fang, Dan
Hou, Xinwei
Le, Yingying
Fang, Jiazhu
Wen, Feng
Gong, Wanghua
Chen, Keqiang
Wang, Ji Ming
Su, Shao Bo
TI HCV Peptide (C5A), an Amphipathic alpha-Helical Peptide of Hepatitis
Virus C, Is an Activator of N-Formyl Peptide Receptor in Human
Phagocytes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NS5A PROTEIN; CHEMOKINES; CELLS; LIVER;
EXPRESSION; FORMYLPEPTIDE; INFECTION; FPR; INFLAMMATION
AB The hepatitis C virus (HCV) nonstructural 5A, a phosphorylated zinc metalloprotein, is an essential component of the HCV replication complex. An amphipathic alpha-helical peptide (HCV peptide [C5A]) derived from nonstructural 5A membrane anchor domain possesses potent anti-HCV and anti-HIV activity in vitro. In this study, we aimed to investigate the potential of HCV peptide (C5A) to regulate host immune responses. The capacity of HCV peptide (C5A) in vitro to induce migration and calcium mobilization of human phagocytes and chemoattractant receptor-transfected cells was investigated. The recruitment of phagocytes in vivo induced by HCV peptide (C5A) and its adjuvant activity were examined. The results revealed that HCV peptide (C5A) was a chemoattractant and activator of human phagocytic leukocytes by using a G-protein coupled receptor, namely formyl peptide receptor. In mice, HCV peptide (C5A) induced massive phagocyte infiltration after injection in the air pouch or the s.c. region. HCV peptide (C5A) also acted as an immune adjuvant by enhancing specific T cell responses to Ag challenge in mice. Our results suggest that HCV peptide (C5A) derived from HCV regulates innate and adaptive immunity in the host by activating the formyl peptide receptor. The Journal of Immunology, 2011, 186: 2087-2094.
C1 [Lin, Qing; Fang, Dan; Fang, Jiazhu; Wen, Feng; Su, Shao Bo] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Hou, Xinwei; Le, Yingying] Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
[Gong, Wanghua] Sci Applicat Int Corp Frederick, Basic Res Program, Frederick, MD 21702 USA.
[Chen, Keqiang; Wang, Ji Ming] NCI, Ctr Canc Res, Lab Mol Immunoregulat Canc & Inflammat Prog, Frederick, MD 21702 USA.
RP Su, SB (reprint author), Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, 54 S Xianlie Rd, Guangzhou 510275, Guangdong, Peoples R China.
EM shaobo.su@gmail.com
OI Lin, Qing/0000-0002-8890-800X
FU National Basic Research Program of China [2007CB512206]; National
Natural Science Foundation of China [81072483]; National Cancer
Institute, National Institutes of Health [NO1-CO-12400]
FX This work was supported by grants from the National Basic Research
Program of China (2007CB512206) and the National Natural Science
Foundation of China (81072483). W.G., K.C., and J.M.W. were supported by
federal funds from the National Cancer Institute, National Institutes of
Health, under Contract No. NO1-CO-12400, and by the Intramural Research
Program of the National Cancer Institute, National Institutes of Health.
NR 42
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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 FEB 15
PY 2011
VL 186
IS 4
BP 2087
EP 2094
DI 10.4049/jimmunol.1002340
PG 8
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700027
PM 21228351
ER
PT J
AU Kleinman, JE
AF Kleinman, Joel E.
TI Genetic Variation in PCLO Is Associated with Prefrontal Cortex
Expression and Bipolar Disorder
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID HUMAN BRAIN; SCHIZOPHRENIA; RISK; COGNITION
C1 NIMH, Clin Brain Disorders Branch, GCAP,NIH, IRP,Sect Neuropathol,Genes Cognit & Psychosis Pro, Bethesda, MD 20892 USA.
RP Kleinman, JE (reprint author), NIMH, Clin Brain Disorders Branch, GCAP,NIH, IRP,Sect Neuropathol,Genes Cognit & Psychosis Pro, Bldg 10,Room 3C103,10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA.
EM joel.kleinman@mail.nih.gov
FU Intramural NIH HHS
NR 10
TC 1
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U1 0
U2 2
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 FEB 15
PY 2011
VL 69
IS 4
BP 298
EP 298
DI 10.1016/j.biopsych.2010.12.008
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 718JV
UT WOS:000287118300001
PM 21272735
ER
PT J
AU Armant, DR
AF Armant, D. Randall
TI Life and death responses to trophinin-mediated adhesion during
blastocyst implantation
SO CELL CYCLE
LA English
DT News Item
ID EMBRYO IMPLANTATION; CELLS
C1 [Armant, D. Randall] Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
[Armant, D. Randall] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
EM D.Armant@Wayne.edu
OI Armant, D. Randall/0000-0001-5904-9325
FU NICHD NIH HHS [R01 HD045966]
NR 7
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U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD FEB 15
PY 2011
VL 10
IS 4
BP 574
EP 575
DI 10.4161/cc.10.4.14846
PG 2
WC Cell Biology
SC Cell Biology
GA 721KO
UT WOS:000287352500008
PM 21311237
ER
PT J
AU Daou, S
Mashtalir, N
Hammond-Martel, I
Pak, H
Yu, H
Sui, GC
Vogel, JL
Kristie, TM
Affar, E
AF Daou, Salima
Mashtalir, Nazar
Hammond-Martel, Ian
Pak, Helen
Yu, Helen
Sui, Guangchao
Vogel, Jodi L.
Kristie, Thomas M.
Affar, El Bachir
TI Crosstalk between O-GlcNAcylation and proteolytic cleavage regulates the
host cell factor-1 maturation pathway
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE limited proteolysis; transcription; signalling
ID N-ACETYLGLUCOSAMINE; NUCLEAR-PORE; HCF-1; PROTEIN; ASSOCIATION;
COMPLEXES; GLCNAC; DOMAIN; GLYCOSYLATION; GLYCOPROTEINS
AB Host Cell Factor 1 (HCF-1) plays critical roles in regulating gene expression in a plethora of physiological processes. HCF-1 is first synthesized as a precursor, and subsequently specifically proteolytically cleaved within a large middle region termed the proteolytic processing domain (PPD). Although the underlying mechanism remains enigmatic, proteolysis of HCF-1 regulates its transcriptional activity and is important for cell cycle progression. Here we report that HCF-1 proteolysis is a regulated process. We demonstrate that a large proportion of the signaling enzyme O-linked-N-acetylglucosaminyl transferase (OGT) is complexed with HCF-1 and this interaction is essential for HCF-1 cleavage. Moreover, HCF-1 is, in turn, required for stabilizing OGT in the nucleus. We provide evidence indicating that OGT regulates HCF-1 cleavage via interaction with and O-GlcNAcylation of the HCF-1 PPD. In contrast, although OGT also interacts with the basic domain in the HCF-1 amino-terminal subunit, neither the interaction nor the O-GlcNAcylation of this region are required for proteolysis. Moreover, we show that OGT-mediated modulation of HCF-1 impacts the expression of the herpes simplex virus immediate-early genes, targets of HCF-1 during the initiation of viral infection. Together the data indicate that O-GlcNAcylation of HCF-1 is a signal for its proteolytic processing and reveal a unique crosstalk between these posttranslational modifications. Additionally, interactions of OGT with multiple HCF-1 domains may indicate that OGT has several functions in association with HCF-1.
C1 [Daou, Salima; Mashtalir, Nazar; Hammond-Martel, Ian; Pak, Helen; Yu, Helen; Affar, El Bachir] Univ Montreal, Dept Med, Maisonneuve Rosemont Hosp Res Ctr, Montreal, PQ H1T 2M4, Canada.
[Sui, Guangchao] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA.
[Vogel, Jodi L.; Kristie, Thomas M.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Affar, E (reprint author), Univ Montreal, Dept Med, Maisonneuve Rosemont Hosp Res Ctr, Montreal, PQ H1T 2M4, Canada.
EM aelbachir.hmr@ssss.gouv.qc.ca
FU Terry Fox Foundation [018144]; Laboratory of Viral Diseases, Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health (NIH)
FX We thank Winship Herr for his generous gift of HCF-1 constructs and
antibodies and James J.D. Hsieh for his kind gift of MLL1 construct. We
thank Elliot Drobetsky for the critical reading of the manuscript. This
work was supported by grants to E. B. A. from the Terry Fox Foundation
(grant#018144). Work in T.M.K's laboratory was supported by the
Laboratory of Viral Diseases, Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health (NIH). E. B. A. is a scholar of Le Fonds de la Recherche en Sante
du Quebec. S. D. is a PhD Scholar of the Islamic Bank for Development.
N.M. is a PhD Scholar of Le Fonds Quebecois de la Recherche sur la
Nature et les Technologies. H.Y. is a PhD Scholar of the Canadian
Institutes for Health Research.
NR 35
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 15
PY 2011
VL 108
IS 7
BP 2747
EP 2752
DI 10.1073/pnas.1013822108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721TB
UT WOS:000287377000027
PM 21285374
ER
PT J
AU Nishizawa, R
Nishiyama, T
Hisaichi, K
Minamoto, C
Matsunaga, N
Takaoka, Y
Nakai, H
Jenkinson, S
Kazmierski, WM
Tada, H
Sagawa, K
Shibayama, S
Fukushima, D
Maeda, K
Mitsuya, H
AF Nishizawa, Rena
Nishiyama, Toshihiko
Hisaichi, Katsuya
Minamoto, Chiaki
Matsunaga, Naoki
Takaoka, Yoshikazu
Nakai, Hisao
Jenkinson, Stephen
Kazmierski, Wieslaw M.
Tada, Hideaki
Sagawa, Kenji
Shibayama, Shiro
Fukushima, Daikichi
Maeda, Kenji
Mitsuya, Hiroaki
TI Spirodiketopiperazine-based CCR5 antagonist: Discovery of an
antiretroviral drug candidate
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE CCR5; Chemokine; Anti-HIV
ID CHEMOKINE RECEPTOR; HIV-1 INFECTION; VIRAL ENTRY; CORECEPTOR; COFACTOR;
POTENT
AB Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally-available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable pharmaceutical profile for use as a drug candidate. (c) 2010 Elsevier Ltd. All rights reserved.
C1 [Nishizawa, Rena; Nishiyama, Toshihiko; Hisaichi, Katsuya; Minamoto, Chiaki; Matsunaga, Naoki; Takaoka, Yoshikazu; Nakai, Hisao] Ono Pharmaceut Co Ltd, Med Chem Res Lab, Osaka 6188585, Japan.
[Tada, Hideaki; Sagawa, Kenji; Shibayama, Shiro; Fukushima, Daikichi] Ono Pharmaceut Co Ltd, Exploratory Res Lab, Ibaraki 300424, Japan.
[Jenkinson, Stephen; Kazmierski, Wieslaw M.] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC 27709 USA.
[Maeda, Kenji; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 8600811, Japan.
[Maeda, Kenji; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Nishizawa, R (reprint author), Ono Pharmaceut Co Ltd, Med Chem Res Lab, Osaka 6188585, Japan.
EM r.nishizawa@ono.co.jp
NR 22
TC 8
Z9 8
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD FEB 15
PY 2011
VL 21
IS 4
BP 1141
EP 1145
DI 10.1016/j.bmcl.2010.12.109
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 716MF
UT WOS:000286972400012
PM 21256008
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI $1 Billion to the National Heart, Lung, and Blood Institute Economic
Stimulus or Bust? Reply
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Letter
ID DYNAMICS
C1 NHLBI, Off Director, Div Cardiovasc Sci, NIH,Rockledge Ctr 2, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Off Director, Div Cardiovasc Sci, NIH,Rockledge Ctr 2, 6701 Rockledge Dr,Suite 8030,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 8
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 15
PY 2011
VL 57
IS 7
BP 889
EP 889
DI 10.1016/j.jacc.2010.10.020
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 718MK
UT WOS:000287126700023
ER
PT J
AU Ramey, VH
Wang, HW
Nakajima, Y
Wong, A
Liu, JA
Drubin, D
Barnes, G
Nogales, E
AF Ramey, Vincent H.
Wang, Hong-Wei
Nakajima, Yuko
Wong, Amanda
Liu, Jian
Drubin, David
Barnes, Georjana
Nogales, Eva
TI The Dam1 ring binds to the E-hook of tubulin and diffuses along the
microtubule
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID YEAST DASH COMPLEX; CHROMOSOME SEGREGATION; BUDDING YEAST; KINETOCHORE;
DEPOLYMERIZATION; MECHANISM; MOVEMENT; DRIVEN; ARCHITECTURE; ATTACHMENT
AB There has been much effort in recent years aimed at understanding the molecular mechanism by which the Dam1 kinetochore complex is able to couple microtubule depolymerization to poleward movement. Both a biased diffusion and a forced walk model have been proposed, and several key functional aspects of Dam1-microtubule binding are disputed. Here, we investigate the elements involved in tubulin-Dam1 complex interactions and directly visualize Dam1 rings on microtubules in order to infer their dynamic behavior on the microtubule lattice and its likely relevance at the kinetochore. We find that the Dam1 complex has a preference for native tubulin over tubulin that is lacking its acidic C-terminal tail. Statistical mechanical analysis of images of Dam1 rings on microtubules, applied to both the distance between rings and the tilt angle of the rings with respect to the microtubule axis, supports a diffusive ring model. We also present a cryo-EM reconstruction of the Dam1 ring, likely the relevant assembly form of the complex for energy coupling during microtubule depolymerization in budding yeast. The present studies constitute a significant step forward by linking structural and biochemical observations toward a comprehensive understanding of the Dam1 complex.
C1 [Ramey, Vincent H.; Wang, Hong-Wei; Nogales, Eva] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Ramey, Vincent H.] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
[Nakajima, Yuko; Wong, Amanda; Barnes, Georjana; Nogales, Eva] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Wong, Amanda; Nogales, Eva] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
[Liu, Jian] NHLBI, Computat Biol Lab, Bethesda, MD 20824 USA.
RP Nogales, E (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
EM enogales@lbl.gov
RI Liu, Jian/C-6755-2011
FU NIGMS [2PO1GM51487C, R01GM47842]
FX We would like to thank Greg Alushin for help with pelleting assays, Nate
Krefman for his valuable comments on the manuscript, and Daniel Smith
for stimulating discussion about statistical modeling. This work was
funded by NIGMS grants to E.N. (2PO1GM51487C) and G. B. (R01GM47842).
E.N. is a Howard Hughes Medical Institute Investigator.
NR 31
TC 20
Z9 20
U1 0
U2 3
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD FEB 15
PY 2011
VL 22
IS 4
BP 457
EP 466
DI 10.1091/mbc.E10-10-0841
PG 10
WC Cell Biology
SC Cell Biology
GA 720TS
UT WOS:000287305700003
PM 21169562
ER
PT J
AU Kabat, GC
Park, Y
Hollenbeck, AR
Schatzkin, A
Rohan, TE
AF Kabat, Geoffrey C.
Park, Yikyung
Hollenbeck, Albert R.
Schatzkin, Arthur
Rohan, Thomas E.
TI Reproductive factors and exogenous hormone use and risk of adult glioma
in women in the NIH-AARP Diet and Health Study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE glioma; menstrual factors; reproductive factors; hormones
ID BRAIN-TUMORS; ESTROGEN-RECEPTOR; GLIAL-CELLS; 2-METHOXYESTRADIOL;
GLIOBLASTOMA; COHORT; SEX; MENINGIOMA; GROWTH; MODEL
AB Experimental evidence suggests that estrogen and other steroid hormones may protect against glioma. Although epidemiologic studies provide only weak support for a role of exogenous or endogenous hormones in gliogenesis, few cohort studies have addressed this question. The authors, therefore, examined the association between menstrual and reproductive factors, exogenous hormone use, and glioma risk among 225,355 women aged 50-71 years who completed the baseline questionnaire in the NIH-AARP Diet and Health Study. During 7.5 years of follow-up, 174 cases of incident, primary glioma were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for exposures, taking potential confounders into account. Older age at menarche was positively associated with risk: HR 1.67 (95% CI: 1.03, 2.69). Other reproductive factors, including age at first live birth, parity, age at menopause, type of menopause (natural vs. medical) and exogenous hormone use showed no association with glioma risk. The results were similar when the analysis was restricted to cases with glioblastoma (N = 130). The present study provides only limited support for the hypothesis that menstrual/reproductive factors or exogenous hormone use play a role in gliogenesis.
C1 [Kabat, Geoffrey C.; Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Park, Yikyung; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Kabat, GC (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
EM geoffrey.kabat@einstein.yu.edu
OI Park, Yikyung/0000-0002-6281-489X
FU Intramural NIH HHS [ZIA CP010196-05]
NR 32
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U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 15
PY 2011
VL 128
IS 4
BP 944
EP 950
DI 10.1002/ijc.25413
PG 7
WC Oncology
SC Oncology
GA 710ZO
UT WOS:000286555700022
PM 20473903
ER
PT J
AU Barry, KH
Zhang, YW
Lan, Q
Zahm, SH
Holford, TR
Leaderer, B
Boyle, P
Hosgood, HD
Chanock, S
Yeager, M
Rothman, N
Zheng, TZ
AF Barry, Kathryn Hughes
Zhang, Yawei
Lan, Qing
Zahm, Shelia Hoar
Holford, Theodore R.
Leaderer, Brian
Boyle, Peter
Hosgood, H. Dean, III
Chanock, Stephen
Yeager, Meredith
Rothman, Nathaniel
Zheng, Tongzhang
TI Genetic Variation in Metabolic Genes, Occupational Solvent Exposure, and
Risk of Non-Hodgkin Lymphoma
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE genetic predisposition to disease; lymphoma; non-Hodgkin; metabolism;
occupational exposure; polymorphism; single nucleotide; solvents
ID AIRCRAFT MANUFACTURING WORKERS; ORGANIC-SOLVENTS; BENZENE EXPOSURE;
CONNECTICUT WOMEN; CANCER INCIDENCE; DRINKING-WATER; POLYMORPHISMS;
MORTALITY; TRICHLOROETHYLENE; TOXICITY
AB Using 1996-2000 data among Connecticut women, the authors evaluated whether genetic variation in 4 metabolic genes modifies organic solvent associations with non-Hodgkin lymphoma and 5 major histologic subtypes. P-interaction values were determined from cross-product terms between dichotomous (ever/never) solvent variables and genotypes at examined loci in unconditional logistic regression models. The false discovery rate method was used to account for multiple comparisons. Overall associations between the chlorinated solvents dichloromethane (odds ratio (OR) = 1.69, 95% confidence interval (CI): 1.06, 2.69), carbon tetrachloride (OR = 2.33, 95% CI: 1.23, 4.40), and methyl chloride (OR = 1.44, 95% CI: 0.94, 2.20) and total non-Hodgkin lymphoma were increased among women TT for rs2070673 in the cytochrome P4502E1 gene, CYP2E1 (dichloromethane: OR = 4.42, 95% CI: 2.03, 9.62; P-interaction < 0.01; carbon tetrachloride: OR = 5.08, 95% CI: 1.82, 14.15; P-interaction = 0.04; and methyl chloride: OR = 2.37, 95% CI: 1.24, 4.51; P-interaction = 0.03). In contrast, no effects of these solvents were observed among TA/AA women. Similar patterns were observed for diffuse large B-cell lymphoma and follicular lymphoma, as well as marginal zone lymphoma for dichloromethane. The weak, nonsignificant overall association between benzene and diffuse large B-cell lymphoma (OR = 1.29, 95% CI: 0.84, 1.98) was increased among women AA for rs2234922 in the microsomal epoxide hydrolase gene, EPHX1 (OR = 1.77, 95% CI: 1.06, 2.97; P-interaction = 0.06). In contrast, no effect was observed among AG/GG women. Additional studies with larger sample size are needed to replicate these findings.
C1 [Barry, Kathryn Hughes] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Barry, Kathryn Hughes; Zhang, Yawei; Holford, Theodore R.; Leaderer, Brian; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Chanock, Stephen; Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Boyle, Peter] Int Prevent Res Inst, Lyon, France.
RP Barry, KH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8091,MSC 7240, Bethesda, MD 20892 USA.
EM barrykh@mail.nih.gov
RI Boyle, Peter/A-4380-2014; Zahm, Shelia/B-5025-2015
OI Boyle, Peter/0000-0001-6251-0610;
FU National Cancer Institute [CA62006, T32 CA105666]; National Cancer
Institute, National Institutes of Health (NIH); NIH [1D43TW007864-01,
1D43TW008323-01]; National Center for Research Resources (NCRR), NIH
[UL1 RR024139]; NIH Roadmap for Medical Research
FX This work was supported by the National Cancer Institute (CA62006 and
T32 CA105666); the Intramural Research Program of the National Cancer
Institute, National Institutes of Health (NIH); NIH Fogarty training
grants (1D43TW007864-01 and 1D43TW008323-01); Clinical and Translational
Science Award (UL1 RR024139) from the National Center for Research
Resources (NCRR), NIH; and the NIH Roadmap for Medical Research.
NR 59
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U1 1
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD FEB 15
PY 2011
VL 173
IS 4
BP 404
EP 413
DI 10.1093/aje/kwq360
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 716QV
UT WOS:000286989500006
PM 21228414
ER
PT J
AU Smith, BT
Lynch, JW
Fox, CS
Harper, S
Abrahamowicz, M
Almeida, ND
Loucks, EB
AF Smith, Brendan T.
Lynch, John W.
Fox, Caroline S.
Harper, Sam
Abrahamowicz, Michal
Almeida, Nisha D.
Loucks, Eric B.
TI Life-Course Socioeconomic Position and Type 2 Diabetes Mellitus
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE adult; diabetes mellitus; educational status; incidence; occupations;
parents; risk factors; socioeconomic factors
ID CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR
RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; BRITISH WOMENS HEART; 3RD
NATIONAL-HEALTH; OF-THE-LITERATURE; INSULIN-RESISTANCE;
EDUCATIONAL-ATTAINMENT; PHYSICAL-ACTIVITY
AB Evidence is lacking on whether the duration and timing of low socioeconomic position (SEP) across a person's life course may be associated with incidence of type 2 diabetes mellitus (T2D). The authors' objectives were to investigate associations between cumulative SEP and the incidence of T2D in the Framingham Offspring Study (n = 1,893; 52% women; mean baseline age = 34 years). Pooled logistic regression analyses demonstrated that age-adjusted cumulative SEP was associated with T2D in women (for low vs. high cumulative SEP, odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.08, 3.42). Age-adjusted analyses for young-adulthood SEP (7.85 for < 12 vs. > 16 years of education, OR = 2.84, 95% CI: 1.03), active professional life SEP (for laborer vs. professional/executive/supervisory/technical occupations, OR = 2.40, 95% CI: 1.05, 5.47), and social-mobility frameworks (for declining life-course SEP, OR = 2.99, 95% CI: 1.39, 6.44; for stable low vs. stable high life-course SEP, OR = 1.85, 95% CI: 1.02, 3.35) all demonstrated associations between low SEP and T2D incidence in women. No association was observed between childhood SEP and T2D in women for father's education (some high school or less vs. any postsecondary education, OR = 1.26, 95% CI: 0.72, 2.22). In men, there was little evidence of associations between life-course SEP and T2D incidence. These findings suggest that cumulative SEP is inversely associated with incidence of T2D in women, and that this association may be primarily due to the women's educational levels and occupations.
C1 [Smith, Brendan T.] Inst Work & Hlth, Toronto, ON M5G 2E9, Canada.
[Smith, Brendan T.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Lynch, John W.] Univ S Australia, Sansom Inst, Sch Hlth Sci, Adelaide, SA 5001, Australia.
[Lynch, John W.] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Fox, Caroline S.] Boston Univ, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA.
[Harper, Sam; Abrahamowicz, Michal; Almeida, Nisha D.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
[Abrahamowicz, Michal] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada.
[Loucks, Eric B.] Brown Univ, Dept Community Hlth, Epidemiol Sect, Ctr Populat Hlth & Clin Epidemiol, Providence, RI 02912 USA.
RP Smith, BT (reprint author), Inst Work & Hlth, 481 Univ Ave,Suite 800, Toronto, ON M5G 2E9, Canada.
EM bsmith@iwh.on.ca
RI Harper, Sam/A-3406-2008; Lynch, John/A-4797-2008; Loucks,
Eric/I-1272-2014
OI Harper, Sam/0000-0002-2767-1053; Lynch, John/0000-0003-2781-7902;
Loucks, Eric/0000-0002-9962-0386
FU Canadian Institutes of Health Research [MOP81239, HOA80072]; National
Institutes of Health/National Heart, Lung, and Blood Institute
[N01-HC-25195]
FX The work was supported by Canadian Institutes of Health Research
operating grant MOP81239; Canadian Institutes of Health Research
Interdisciplinary Capacity Enhancement grant HOA80072; and a Canadian
Institutes of Health Research New Investigator Award (to E. B. L.). The
Framingham Heart Study is supported by National Institutes of
Health/National Heart, Lung, and Blood Institute contract N01-HC-25195.
NR 57
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U1 0
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD FEB 15
PY 2011
VL 173
IS 4
BP 438
EP 447
DI 10.1093/aje/kwq379
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 716QV
UT WOS:000286989500010
PM 21242301
ER
PT J
AU Mudd, SH
AF Mudd, S. Harvey
TI Hypermethioninemias of Genetic and Non-Genetic Origin: A Review
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Review
DE hypermethioninemia; methionine; S-adenosylmethionine;
adenosyltransferase; homocysteine; homocystinuria; cystathionine
beta-synthase; glycine; methyltransferase; S-adenosylhomocysteine;
hydrolase; citrin; tyrosinemia type I; fumarylacetoacetate; deficiency;
liver; disease; prematurity; low-birth-weight
ID CYSTATHIONINE BETA-SYNTHASE; GLYCINE N-METHYLTRANSFERASE; TYROSINEMIA
TYPE-I; NEONATAL INTRAHEPATIC CHOLESTASIS; METHIONINE
ADENOSYLTRANSFERASE-I/III; S-ADENOSYLMETHIONINE SYNTHETASE;
ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY; ASPARTATE GLUTAMATE CARRIER;
ADENOSYL-L-METHIONINE; PYRIDOXINE-NONRESPONSIVE HOMOCYSTINURIA
AB This review covers briefly the major conditions, genetic and non-genetic, sometimes leading to abnormally elevated methionine, with emphasis on recent developments. A major aim is to assist in the differential diagnosis of hypermethioninemia. The genetic conditions are: (1) Homocystinuria due to cystathionine p-synthase (CBS) deficiency. At least 150 different mutations in the CBS gene have been identified since this deficiency was established in 1964. Hypermethioninemia is due chiefly to remethylation of the accumulated homocysteine. (2) Deficient activity of methionine adenosyltransferases I and III (MAT I/III), the isoenzymes the catalytic subunit of which are encoded by MAT1A. Methionine accumulates because its conversion to S-adenosylmethionine (AdoMet) is impaired. (3) Glycine N-methyltrasferase (GNMT) deficiency. Disruption of a quantitatively major pathway for AdoMet disposal leads to AdoMet accumulation with secondary down-regulation of methionine flux into AdoMet. (4) S-adenosylhomocysteine (AdoHcy) hydrolase (AHCY) deficiency. Not being catabolized normally, AdoHcy accumulates and inhibits many AdoMet-dependent methyltransferases, producing accumulation of AdoMet and, thereby, hypermethioninemia. (5) Citrin deficiency, found chiefly in Asian countries. Lack of this mitochondrial aspartate-glutamate transporter may produce (usually transient) hypermethioninemia, the immediate cause of which remains uncertain. (6) Fumarylacetoacetate hydrolase (FAH) deficiency (tyrosinemia type I) may lead to hypermethioninemia secondary either to liver damage and/or to accumulation of fumarylacetoacetate, an inhibitor of the high K-m MAT. Additional possible genetic causes of hypermethioninemia accompanied by elevations of plasma AdoMet include mitochondrial disorders (the specificity and frequency of which remain to be elucidated). Non-genetic conditions include: (a) Liver disease, which may cause hypermethioninemia, mild, or severe. (b) Low-birth-weight and/or prematurity which may cause transient hypermethioninemia. (c) Ingestion of relatively large amounts of methionine which, even in full-term, normal-birth-weight babies may cause hypermethioninemia. Published 2011 Wiley-Liss, Inc.
C1 [Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Mudd, SH (reprint author), Room 2D46,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM muddh@mail.nih.gov
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U1 3
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4868
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD FEB 15
PY 2011
VL 157C
IS 1
BP 3
EP 32
DI 10.1002/ajmg.c.30293
PG 30
WC Genetics & Heredity
SC Genetics & Heredity
GA 729ZC
UT WOS:000287992200002
PM 21308989
ER
PT J
AU Huang, WY
Yang, PM
Chang, YF
Marquez, VE
Chen, CC
AF Huang, Wen-Yu
Yang, Pei-Ming
Chang, Yu-Fan
Marquez, Victor E.
Chen, Ching-Chow
TI Methotrexate induces apoptosis through p53/p21-dependent pathway and
increases E-cadherin expression through downregulation of HDAC/EZH2
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Methotrexate; p53; p21; HDAC; EZH2
ID CELL LUNG-CANCER; HISTONE DEACETYLASE INHIBITORS; GROUP PROTEIN EZH2;
P53 ACETYLATION; BREAST-CANCER; DNA-DAMAGE; GENE; ACTIVATION;
REPRESSION; P21
AB Methotrexate (MTX) is a dihydrofolate reductase (DHFR) inhibitor widely used as an anticancer drug in different kinds of human cancers. Here we investigated the anti-tumor mechanism of MTX against non-small cell lung cancer (NSCLC) A549 cells. MTX not only inhibited in vitro cell growth via induction of apoptosis, but also inhibited tumor formation in animal xenograft model. RNase protection assay (RPA) and RT-PCR demonstrated its induction of p53 target genes including DR5, p21, Puma and Noxa. Moreover, MTX promoted p53 phosphorylation at Ser15 and acetylaion at Lys373/382, which increase its stability and expression. The apoptosis and inhibition of cell viability induced by MIX were dependent on p53 and, partially, on p21. In addition, MIX also increased E-cadherin expression through inhibition of histone deacetylase (HDAC) activity and downregulation of polycomb group protein enhancer of zeste homologue 2 (EZH2). Therefore, the anticancer mechanism of MIX acts through initiation of p53-dependent apoptosis and restoration of E-cadherin expression by downregulation of HDAC/EZH2. (c) 2010 Elsevier Inc. All rights reserved.
C1 [Huang, Wen-Yu; Yang, Pei-Ming; Chang, Yu-Fan; Chen, Ching-Chow] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10018, Taiwan.
[Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Chen, CC (reprint author), Natl Taiwan Univ, Coll Med, Dept Pharmacol, 1,Jen Ai Rd,Sect 1, Taipei 10018, Taiwan.
EM chingchowchen@ntu.edu.tw
RI Yang, Pei-Ming/G-3763-2014;
OI Yang, Pei-Ming/0000-0002-4004-2518; CHEN, CHING-CHOW/0000-0002-7810-0939
FU National Science Council of Taiwan [NSC 97-2320-B002-033-MY3]
FX This work was supported by a research grant from National Science
Council of Taiwan (NSC 97-2320-B002-033-MY3).
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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 FEB 15
PY 2011
VL 81
IS 4
BP 510
EP 517
DI 10.1016/j.bcp.2010.11.014
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 712YX
UT WOS:000286703300005
PM 21114963
ER
PT J
AU Lever, AML
Jeang, KT
AF Lever, Andrew M. L.
Jeang, Kuan-Teh
TI Insights into Cellular Factors That Regulate HIV-1 Replication in Human
Cells
SO BIOCHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HEPATITIS-B-VIRUS; SINGLE AMINO-ACID;
RNA-BINDING PROTEIN; FUNCTIONAL GENOMIC SCREEN; SMALL INTERFERING RNAS;
LONG TERMINAL REPEAT; NUCLEAR-PORE COMPLEX; RETROVIRUS RESTRICTION;
CYTIDINE DEAMINASE
AB Retroviruses integrate into the host cell's chromosome. Accordingly, many aspects of the life cycle of retroviruses like HIV-1 are intimately linked to the functions of cellular proteins and RNAs. In this review, we discuss in brief recent genomewide screens for the identification of cellular proteins that assist HIV-1 replication in human cells. We also review findings for other cellular moieties that help or restrict the viral life cycle.
C1 [Lever, Andrew M. L.] Univ Cambridge, Addenbrookes Hosp, Cambridge CB2 0QQ, England.
[Jeang, Kuan-Teh] NIAID, NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kjeang@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU Medical Research Council (U.K.) [G0801709, G0800142]; Biomedical
Research Centre [RG52162]; National Institute of Allergy and Infectious
Diseases; office of the Director of the National Institutes of Health
FX A.M.L.L. is supported by grants from the Medical Research Council (U.K.)
(G0801709 and G0800142) and the Biomedical Research Centre (RG52162).
K.-T.J. is supported by intramural funds from the National Institute of
Allergy and Infectious Diseases and by the Intramural Targeted Antiviral
Program (IATAP) from the office of the Director of the National
Institutes of Health.
NR 216
TC 24
Z9 24
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 15
PY 2011
VL 50
IS 6
BP 920
EP 931
DI 10.1021/bi101805f
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 717MB
UT WOS:000287049500002
PM 21218853
ER
PT J
AU Savitz, JB
Nugent, AC
Bogers, W
Roiser, JP
Bain, EE
Neumeister, A
Zarate, CA
Manji, HK
Cannon, DM
Marrett, S
Henn, F
Charney, DS
Drevets, WC
AF Savitz, Jonathan B.
Nugent, Allison C.
Bogers, Wendy
Roiser, Jonathan P.
Bain, Earle E.
Neumeister, Alexander
Zarate, Carlos A., Jr.
Manji, Husseini K.
Cannon, Dara M.
Marrett, Sean
Henn, Fritz
Charney, Dennis S.
Drevets, Wayne C.
TI Habenula Volume in Bipolar Disorder and Major Depressive Disorder: A
High-Resolution Magnetic Resonance Imaging Study
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Bipolar disorder; habenula; high resolution; lithium; magnetic resonance
imaging; major depressive disorder
ID VENTRAL TEGMENTAL AREA; DORSAL RAPHE NUCLEUS; LATERAL HABENULA;
TRYPTOPHAN DEPLETION; LITHIUM TREATMENT; COMPLEX; DOPAMINE; SEROTONIN;
RESPONSES; INCREASE
AB Background: Increased activity of the habenula has been implicated in the etiology of major depressive disorder (MDD), in which reductions in habenula volume are present after death. We conducted the first magnetic resonance imaging analysis of habenula volume in MDD and bipolar disorder (BD).
Methods: High-resolution images (resolution approximately.4mm(3)) were acquired with a 3T scanner, and a pulse sequence was optimized for tissue contrast resolution. The habenula was manually segmented by one rater blind to diagnosis. Seventy-four healthy control subjects (HC) were compared with both medicated (lithium/divalproex, n = 15) and unmedicated, depressed BD (n = 22) patients; unmedicated, depressed MDD patients (n = 28); and unmedicated MDD patients in remission (n = 32).
Results: The unmedicated BD patients displayed significantly smaller absolute (p < .01) and normalized (p < .05) habenula volumes than the HC subjects. In post hoc assessments analyzing men and women separately, the currently-depressed women with MDD had smaller absolute (p < .05) habenula volumes than the HC women. None of the other psychiatric groups differed significantly from the HC group.
Conclusions: We provide further evidence for the involvement of the habenula in affective illness but suggest that a reduction in volume might be more pronounced in unmedicated, depressed BD subjects and female currently depressed MDD subjects. The habenula plays major roles in the long-term modification of monoamine transmission and behavioral responses to stress and in the suppression of dopamine cell activity after the absence of an expected reward. A reduction in habenula volume might thus have functional consequences that contribute to the risk for developing affective disease.
C1 [Savitz, Jonathan B.; Drevets, Wayne C.] Univ Oklahoma, Laureate Inst Brain Res, Coll Med, Tulsa, OK 74136 USA.
[Savitz, Jonathan B.; Drevets, Wayne C.] Univ Oklahoma, Dept Psychiat, Coll Med, Tulsa, OK 74136 USA.
[Savitz, Jonathan B.; Nugent, Allison C.; Bogers, Wendy; Drevets, Wayne C.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Marrett, Sean] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Roiser, Jonathan P.] UCL, Inst Cognit Neurosci, London, England.
[Bain, Earle E.] Abbott Labs, Deerfield, IL USA.
[Neumeister, Alexander; Charney, Dennis S.] Mt Sinai Sch Med, New York, NY USA.
[Henn, Fritz] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
[Cannon, Dara M.] Natl Univ Ireland, Div Psychiat, Galway, Ireland.
RP Savitz, JB (reprint author), Univ Oklahoma, Laureate Inst Brain Res, Coll Med, 6655 S Yale Ave, Tulsa, OK 74136 USA.
EM jonathansavitz@hotmail.com
RI Savitz, Jonathan/C-3088-2009; Roiser, Jonathan/A-1791-2010; Cannon,
Dara/C-1323-2009;
OI Savitz, Jonathan/0000-0001-8143-182X; Cannon, Dara/0000-0001-7378-3411;
Marrett, Sean/0000-0001-8179-6511; Nugent, Allison/0000-0003-2569-2480
FU National Institutes of Health
FX This study was funded by the intramural research program at the National
Institutes of Health. We would like to thank Ghedem Solomon and Niara
Wright for administrative support. Dr. Bain is currently an employee of
Abbott Laboratories. Dr. Manji is currently an employee of Johnson and
Johnson. In 2006 and 2007, DC consulted for AstraZeneca, Bristol-Myers
Squibb Company, Cyberonics, Neurogen, Neuroscience Education Institute,
Novartis Pharmaceuticals Corporation, Orexin, and Unilever, UK Central
Resources, Limited. Dr. Charney has a patent pending for the use of
ketamine in the treatment of depression. Dr. Drevets consulted for
Pfizer Pharmaceuticals. Dr. Zarate is listed as coinventor on a patent
for the use of ketamine in major depression. Dr. Zarate has assigned his
patent rights on ketamine to the US government. All other authors report
no biomedical financial interests or potential conflicts of interest.
NR 28
TC 57
Z9 59
U1 0
U2 9
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 FEB 15
PY 2011
VL 69
IS 4
BP 336
EP 343
DI 10.1016/j.biopsych.2010.09.027
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 718JV
UT WOS:000287118300007
PM 21094939
ER
PT J
AU Machado-Vieira, R
Pivovarova, NB
Stanika, RI
Yuan, PX
Wang, Y
Zhou, RL
Zarate, CA
Drevets, WC
Brantner, CA
Baum, A
Laje, G
McMahon, FJ
Chen, GA
Du, J
Manji, HK
Andrews, SB
AF Machado-Vieira, Rodrigo
Pivovarova, Natalia B.
Stanika, Ruslan I.
Yuan, Peixiong
Wang, Yun
Zhou, Rulun
Zarate, Carlos A., Jr.
Drevets, Wayne C.
Brantner, Christine A.
Baum, Amber
Laje, Gonzalo
McMahon, Francis J.
Chen, Guang
Du, Jing
Manji, Husseini K.
Andrews, S. Brian
TI The Bcl-2 Gene Polymorphism rs956572AA Increases Inositol
1,4,5-Trisphosphate Receptor-Mediated Endoplasmic Reticulum Calcium
Release in Subjects with Bipolar Disorder
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Bcl-2; bipolar disorder; calcium; electron probe micro-analysis;
endoplasmic reticulum; inositol 1;4;5-trisphosphate; mania; mitochondria
ID CELL-DEATH; SYMPATHETIC NEURONS; ALZHEIMERS-DISEASE; CA2+ HOMEOSTASIS;
OXIDATIVE STRESS; MOOD DISORDERS; PROTEIN BCL-2; EXPRESSION; LITHIUM; ER
AB Background: Bipolar disorder (BPD) is characterized by altered intracellular calcium (Ca(2+)) homeostasis. Underlying mechanisms involve dysfunctions in endoplasmic reticulum (ER) and mitochondrial Ca(2+) handling, potentially mediated by B-cell lymphoma 2 (Bcl-2), a key protein that regulates Ca(2+) signaling by interacting directly with these organelles, and which has been implicated in the pathophysiology of BPD. Here, we examined the effects of the Bcl-2 gene single nucleotide polymorphism (SNP) rs956572 on intracellular Ca(2+) dynamics in patients with BPD.
Methods: Live cell fluorescence imaging and electron probe microanalysis were used to measure intracellular and intra-organelle free and total calcium in lymphoblasts from 18 subjects with BPD carrying the AA, AG, or GG variants of the rs956572 SNP. Analyses were carried out under basal conditions and in the presence of agents that affect Ca(2+) dynamics.
Results: Compared with GG homozygotes, variant AA-which expresses significantly reduced Bcl-2 messenger RNA and protein exhibited elevated basal cytosolic Ca(2+) and larger increases in inositol 1,4,5-trisphosphate receptor-mediated cytosolic Ca(2+) elevations, the latter in parallel with enhanced depletion of the ER Ca(2+) pool. The aberrant behavior of AA cells was reversed by chronic lithium treatment and mimicked in variant GG by a Bcl-2 inhibitor. In contrast, no differences between SNP variants were found in ER or mitochondrial total Ca(2+) content or in basal store-operated Ca(2+) entry.
Conclusions: These results demonstrate that, in patients with BPD, abnormal Bcl-2 gene expression in the AA variant contributes to dysfunctional Ca(2+) homeostasis through a specific ER inositol 1,4,5-trisphosphate receptor-dependent mechanism.
C1 [Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
[Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.; Drevets, Wayne C.; Chen, Guang; Du, Jing; Manji, Husseini K.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, Bethesda, MD 20892 USA.
[Yuan, Peixiong; Wang, Yun; Zhou, Rulun] NIMH, Biomarker Lab, Bethesda, MD 20892 USA.
[Baum, Amber; Laje, Gonzalo; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Pivovarova, Natalia B.; Stanika, Ruslan I.; Brantner, Christine A.; Andrews, S. Brian] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
RP Manji, HK (reprint author), Johnson & Johnson Pharmaceut, 1125 Trenton Harbourton Rd,E32000, Titusville, NJ 08560 USA.
EM hmanji@its.jnj.com
RI Du, Jing/A-9023-2012; Laje, Gonzalo/L-2654-2014; MACHADO-VIEIRA,
RODRIGO/D-8293-2012; Chen, Guang/A-2570-2017;
OI Laje, Gonzalo/0000-0003-2763-3329; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190; Brantner, Christine/0000-0001-8172-901X;
McMahon, Francis/0000-0002-9469-305X
FU Intramural NIH HHS [ZIA MH002927-01]; NHGRI NIH HHS [N01HG65403]; NIMH
NIH HHS [R01 MH59545, MH058693, MH52618, R01 MH058693, R01 MH059533, R01
MH059534, R01 MH059535, R01 MH059545, R01 MH059548, R01 MH059553, R01
MH059556, R01 MH059567, R01 MH060068, R01 MH59533, R01 MH59535, R01
MH59567, R01 MH59602, R01 MH60068, R01MH59553, U01 MH46274, U01 MH46280,
U01 MH46282, Z01 MH002810]
NR 46
TC 40
Z9 41
U1 1
U2 3
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 FEB 15
PY 2011
VL 69
IS 4
BP 344
EP 352
DI 10.1016/j.biopsych.2010.10.019
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 718JV
UT WOS:000287118300008
PM 21167476
ER
PT J
AU Choi, KH
Higgs, BW
Wendland, JR
Song, J
McMahon, FJ
Webster, MJ
AF Choi, Kwang H.
Higgs, Brandon W.
Wendland, Jens R.
Song, Jonathan
McMahon, Francis J.
Webster, Maree J.
TI Gene Expression and Genetic Variation Data Implicate PCLO in Bipolar
Disorder
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Allelic expression; expression quantitative trait loci (eQTL); genetic
variants; functional genomics; risk factors
ID GENOME-WIDE ASSOCIATION; MAJOR DEPRESSIVE DISORDER; FALSE DISCOVERY
RATE; MOOD DISORDERS; METAANALYSIS; LOCI; SNPS; INDIVIDUALS; SUPPORTS;
PICCOLO
AB Background: Genetic variation may contribute to differential gene expression in the brain of individuals with psychiatric disorders. To test this hypothesis, we identified genes that were differentially expressed in individuals with bipolar disorder, along with nearby single nucleotide polymorphisms (SNPs) that were associated with expression of the same genes. We then tested these SNPs for association with bipolar disorder in large case-control samples.
Methods: We used the Stanley Genomics Database to extract gene expression and SNP microarray data from individuals with bipolar disorder (n = 40) and unaffected controls (n = 43). We identified 367 genes that were differentially expressed in the prefrontal cortex of cases vs. controls (fold change > 1.3 and FDR q-value < .05) and 45 nearby SNPs that were associated with expression of those same genes (FDR q-value < .05). We tested these SNPs for association with bipolar disorder in a meta-analysis of genome-wide association studies (GWAS) including 4,936 cases and 6,654 healthy controls.
Results: We identified 45 SNPs that were associated with expression of differentially expressed genes, including HBS1L (15 SNPs), HLA-DPB1 (15 SNPs), AMFR (8 SNPs), PCLO (2 SNPs) and WDR41 (2 SNPs). Of these, one SNP (rs13438494), in an intron of the piccolo (PCLO) gene, was significantly associated with bipolar disorder (FDR adjusted p < .05) in the meta-analysis of GWAS.
Conclusions: These results support the previous findings implicating PCLO in mood disorders and demonstrate the utility of combining gene expression and genetic variation data to improve our understanding of the genetic contribution to bipolar disorder.
C1 [Choi, Kwang H.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
[Choi, Kwang H.; Song, Jonathan; Webster, Maree J.] Uniformed Serv Univ Hlth Sci, Stanley Lab Brain Res, Bethesda, MD 20814 USA.
[Wendland, Jens R.; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Higgs, Brandon W.] Elashoff Consulting, Redwood City, CA USA.
RP Choi, KH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
EM kwang.choi@usuhs.mil
RI Wendland, Jens/A-1809-2012;
OI McMahon, Francis/0000-0002-9469-305X; Higgs, Brandon/0000-0002-2951-0245
FU Stanley Medical Research Institute
FX We thank the Stanley Medical Research Institute for supporting this
work, in particular Dr. E Fuller Torrey and Theodore and Vada Stanley.
We thank Drs. Anthony Altar, Sabine Bahn, and Chunyu Liu for
contributing the microarray data for the current study. We thank many
researchers and collaborators for making GWAS data/results available for
the meta-analysis. Complete acknowledgments for the data used in the
meta-analysis are given in the primary publication (4). All authors
report no biomedical financial interests or potential conflicts of
interest.
NR 58
TC 26
Z9 26
U1 0
U2 6
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 FEB 15
PY 2011
VL 69
IS 4
BP 353
EP 359
DI 10.1016/j.biopsych.2010.09.042
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 718JV
UT WOS:000287118300009
PM 21185011
ER
PT J
AU Ye, YP
Zhu, L
Ma, Y
Niu, G
Chen, XY
AF Ye, Yunpeng
Zhu, Lei
Ma, Ying
Niu, Gang
Chen, Xiaoyuan
TI Synthesis and evaluation of new iRGD peptide analogs for tumor optical
imaging
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE iRGD peptide; Integrin receptor; Near-infrared fluorescent probe;
Optical imaging; Tumor targeting
ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN BREAST-CANCER; INTEGRIN
ALPHA(V)BETA(3); RGD PEPTIDE; INTEGRIN-ALPHA(V)BETA(3) EXPRESSION;
IN-VIVO; ANGIOGENESIS; RECEPTOR; NEOVASCULATURE; FLUORESCENCE
AB Recently, a disulfide-based cyclic RGD peptide called iRGD, that is, c(CRGDKGPDC), has been reported to interact with both integrin and neuropilin-1 receptors for cellular and deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy. In this study, two new near-infrared fluorescent iRGD conjugates, that is, Ac-Cys(IRDye (R) 800CW)-iRGD (1), and its dual labeling analog DOTA-Cys( IRDye (R) 800CW)-iRGD (2) were synthesized via the specific mercapto-maleimide reaction for tumor imaging. Both 1 and 2 showed significant tumor localization in optical imaging of MDA-MB-435 tumor-bearing mice. The potential of such iRGD compounds in tumor-targeted imaging and drug delivery deserves further exploration. Published by Elsevier Ltd.
C1 [Ye, Yunpeng; Zhu, Lei; Ma, Ying; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
RI Zhu, Lei/P-9786-2016
OI Zhu, Lei/0000-0002-1820-4795
FU NIBIB/NIH intramural research
FX Research supported by NIBIB/NIH intramural research.
NR 37
TC 16
Z9 19
U1 5
U2 57
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD FEB 15
PY 2011
VL 21
IS 4
BP 1146
EP 1150
DI 10.1016/j.bmcl.2010.12.112
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 716MF
UT WOS:000286972400013
PM 21251820
ER
PT J
AU Mohammed, MZ
Vyjayanti, VN
Laughton, CA
Dekker, LV
Fischer, PM
Wilson, DM
Abbotts, R
Shah, S
Patel, PM
Hickson, ID
Madhusudan, S
AF Mohammed, M. Z.
Vyjayanti, V. N.
Laughton, C. A.
Dekker, L. V.
Fischer, P. M.
Wilson, D. M., III
Abbotts, R.
Shah, S.
Patel, P. M.
Hickson, I. D.
Madhusudan, S.
TI Development and evaluation of human AP endonuclease inhibitors in
melanoma and glioma cell lines
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE melanoma; glioma; DNA repair; human apurinic/apyrimidinic endonuclease 1
(APE1); small molecule inhibitors
ID DNA-REPAIR ENZYME; HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE-1; HUMAN
APURINIC ENDONUCLEASE; ACID SUBSTITUTION VARIANTS; BASE EXCISION-REPAIR;
ABASIC SITES; CANCER; DOCKING; PROTEIN; HAP1
AB AIMS: Modulation of DNA base excision repair (BER) has the potential to enhance response to chemotherapy and improve outcomes in tumours such as melanoma and glioma. APE1, a critical protein in BER that processes potentially cytotoxic abasic sites (AP sites), is a promising new target in cancer. In the current study, we aimed to develop small molecule inhibitors of APE1 for cancer therapy.
METHODS: An industry-standard high throughput virtual screening strategy was adopted. The Sybyl8.0 (Tripos, St Louis, MO, USA) molecular modelling software suite was used to build inhibitor templates. Similarity searching strategies were then applied using ROCS 2.3 (Open Eye Scientific, Santa Fe, NM, USA) to extract pharmacophorically related subsets of compounds from a chemically diverse database of 2.6 million compounds. The compounds in these subsets were subjected to docking against the active site of the APE1 model, using the genetic algorithm-based programme GOLD2.7 (CCDC, Cambridge, UK). Predicted ligand poses were ranked on the basis of several scoring functions. The top virtual hits with promising pharmaceutical properties underwent detailed in vitro analyses using fluorescence-based APE1 cleavage assays and counter screened using endonuclease IV cleavage assays, fluorescence quenching assays and radiolabelled oligonucleotide assays. Biochemical APE1 inhibitors were then subjected to detailed cytotoxicity analyses.
RESULTS: Several specific APE1 inhibitors were isolated by this approach. The IC50 for APE1 inhibition ranged between 30 nM and 50 mu M. We demonstrated that APE1 inhibitors lead to accumulation of AP sites in genomic DNA and potentiated the cytotoxicity of alkylating agents in melanoma and glioma cell lines.
CONCLUSIONS: Our study provides evidence that APE1 is an emerging drug target and could have therapeutic application in patients with melanoma and glioma. British Journal of Cancer (2011) 104, 653-663. doi:10.1038/sj.bjc.6606058 www.bjcancer.com Published online 25 January 2011 (C) 2011 Cancer Research UK
C1 [Mohammed, M. Z.; Abbotts, R.; Shah, S.; Patel, P. M.; Madhusudan, S.] Univ Nottingham, Univ Nottingham Hosp, Sch Mol Med Sci, Acad Unit Oncol,Lab Mol Oncol,Translat DNA Repair, Nottingham, England.
[Vyjayanti, V. N.; Wilson, D. M., III] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Laughton, C. A.; Dekker, L. V.; Fischer, P. M.] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England.
[Laughton, C. A.; Dekker, L. V.; Fischer, P. M.] Univ Nottingham, Ctr Biomol Sci, Nottingham NG7 2RD, England.
[Hickson, I. D.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, CRUK Labs, Oxford OX3 9DU, England.
RP Madhusudan, S (reprint author), Univ Nottingham, Univ Nottingham Hosp, Sch Mol Med Sci, Acad Unit Oncol,Lab Mol Oncol,Translat DNA Repair, Nottingham, England.
EM srinivasan.madhusudan@nottingham.ac.uk
RI Laughton, Charles/E-5667-2010; Dekker, Lodewijk/J-6934-2013; Shah,
Suharsh/N-1514-2015; Fischer, Peter/E-5657-2010;
OI Laughton, Charles/0000-0003-4090-3960; Dekker,
Lodewijk/0000-0001-5247-3297; Fischer, Peter/0000-0002-5866-9271;
Madhusudan, Srinivasan/0000-0002-5354-5480
FU University of Nottingham and the Nottingham University Hospitals
Charity, UK; NIH, National Institute on Aging, USA; Cancer Research UK
FX We thank members of the Laboratory of Molecular Oncology, University of
Nottingham for useful discussions. MZ Mohammed and R Abbotts were
supported by the University of Nottingham and the Nottingham University
Hospitals Charity, UK. VN Vyjayanti and DM Wilson III were supported by
the Intramural Research Program of NIH, National Institute on Aging,
USA. Ian D Hickson is supported by Cancer Research UK.
NR 47
TC 30
Z9 34
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD FEB 15
PY 2011
VL 104
IS 4
BP 653
EP 663
DI 10.1038/sj.bjc.6606058
PG 11
WC Oncology
SC Oncology
GA 728ZY
UT WOS:000287915600016
PM 21266972
ER
PT J
AU Trabert, B
Sigurdson, AJ
Sweeney, AM
Strom, SS
McGlynn, KA
AF Trabert, Britton
Sigurdson, Alice J.
Sweeney, Anne M.
Strom, Sara S.
McGlynn, Katherine A.
TI Marijuana Use and Testicular Germ Cell Tumors
SO CANCER
LA English
DT Article
DE marijuana use; seminomas; nonseminomas; testicular germ cell tumors;
hospital-based case-control
ID CANNABINOID RECEPTOR; INTERNATIONAL TRENDS; RISK-FACTORS; CANCER;
ASSOCIATION; MORTALITY
AB BACKGROUND: Since the early 1970s, the incidence of testicular germ cell tumors (TGCTs) in the United States has been increasing; however, potential environmental exposures accounting for this increase have not been identified. A previous study reported a significant association between frequent and long-term current marijuana users and TGCT risk. The purpose of this study was to evaluate the relation between marijuana use and TGCTs in a hospital-based case-control study. METHODS: TGCT patients diagnosed between January 1990 and October 1996 (n = 187) and male friend controls (n = 148) were enrolled in the study. All participants were between the ages of 18 and 50 at the time of diagnosis and resided in Texas, Louisiana, Arkansas, or Oklahoma. Associations of marijuana use and TGCTs were estimated using unconditional logistic regression, adjusting for age, race, prior cryptorchidism, cigarette smoking, and alcohol intake. RESULTS: Overall, patients with TGCTs were more likely to be frequent marijuana users (daily or greater) compared with controls (odds ratio [OK 2.2; 95% confidence interval [Cl], 1.0-5.1). Histological-specific analyses revealed that patients with nonseminoma were significantly more likely than controls to be frequent users (OR, 3.1; 95% Cl, 1.2-8.2) and long-term (>= 10 years) users (OR, 2.4; 95% Cl, 1.0-6.1). CONCLUSIONS: The finding of an association between frequent marijuana use and TGCTs, particularly among men with nonseminoma, was consistent with the findings of a previous report. Additional studies of marijuana use and TGCTs are warranted, especially studies evaluating the role of endocannabinoid signaling and cannabinoid receptors in TGCTs. Cancer 2011;117:848-53. (C) 2010 American Cancer Society
C1 [Trabert, Britton; McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
[Sweeney, Anne M.] Texas A&M Univ Syst Hlth Sci Ctr, Dept Epidemiol & Biostat, Sch Rural Publ Hlth, College Stn, TX USA.
[Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
RP Trabert, B (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Suite 550,6120 Execut Blvd, Rockville, MD 20852 USA.
EM trabertbl@mail.nih.gov
RI Trabert, Britton/F-8051-2015
FU University of Texas M. D. Anderson Cancer Center (National Cancer
Institute) [R25-CA-57730]; National Cancer Institute
FX Supported by The University of Texas M. D. Anderson Cancer Center
Education Program in Cancer Prevention (National Cancer Institute grant
R25-CA-57730) and the Intramural Research Program of the National Cancer
Institute.
NR 26
TC 22
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U1 1
U2 12
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD FEB 15
PY 2011
VL 117
IS 4
BP 848
EP 853
DI 10.1002/cncr.25499
PG 6
WC Oncology
SC Oncology
GA 716KC
UT WOS:000286966500025
PM 20925043
ER
PT J
AU Rubin, BP
Nishijo, K
Chen, HIH
Yi, XL
Schuetze, DP
Pal, R
Prajapati, SI
Abraham, J
Arenkiel, BR
Chen, QR
Davis, S
McCleish, AT
Capecchi, MR
Michalek, JE
Zarzabal, LA
Khan, J
Yu, ZX
Parham, DM
Barr, FG
Meltzer, PS
Chen, YD
Keller, C
AF Rubin, Brian P.
Nishijo, Koichi
Chen, Hung-I Harry
Yi, Xiaolan
Schuetze, David P.
Pal, Ranadip
Prajapati, Suresh I.
Abraham, Jinu
Arenkiel, Benjamin R.
Chen, Qing-Rong
Davis, Sean
McCleish, Amanda T.
Capecchi, Mario R.
Michalek, Joel E.
Zarzabal, Lee Ann
Khan, Javed
Yu, Zhongxin
Parham, David M.
Barr, Frederic G.
Meltzer, Paul S.
Chen, Yidong
Keller, Charles
TI Evidence for an Unanticipated Relationship between Undifferentiated
Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma
SO CANCER CELL
LA English
DT Article
ID CHILDRENS ONCOLOGY GROUP; MUSCLE SATELLITE CELLS; SOFT-TISSUE SARCOMAS;
MALIGNANT FIBROUS HISTIOCYTOMA; HEDGEHOG SIGNALING PATHWAY; ADULT
SKELETAL-MUSCLE; GENE-EXPRESSION; INTERGROUP RHABDOMYOSARCOMA; ALVEOLAR
RHABDOMYOSARCOMAS; CHILDHOOD RHABDOMYOSARCOMA
AB Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin, we demonstrate that eRMS and undifferentiated pleomorphic sarcoma (UPS) lie in a continuum, with satellite cells predisposed to giving rise to UPS. Conversely, p53 loss in maturing myoblasts gives rise to eRMS, which have the highest myodifferentiation potential. Regardless of origin, Rb1 loss modifies tumor phenotype to mimic UPS. In human sarcomas that lack pathognomic chromosomal translocations, p53 loss of function is prevalent, whereas Shh or Rb1 alterations likely act primarily as modifiers. Thus, sarcoma phenotype is strongly influenced by cell of origin and mutational profile.
C1 [Nishijo, Koichi; Chen, Hung-I Harry; Yi, Xiaolan; Prajapati, Suresh I.; Abraham, Jinu; McCleish, Amanda T.; Chen, Yidong; Keller, Charles] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Rubin, Brian P.; Schuetze, David P.] Cleveland Clin Fdn, Dept Anat Pathol, Taussig Canc Ctr, Cleveland, OH 44195 USA.
[Rubin, Brian P.; Schuetze, David P.] Cleveland Clin Fdn, Dept Mol Genet, Taussig Canc Ctr, Cleveland, OH 44195 USA.
[Rubin, Brian P.; Schuetze, David P.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA.
[Pal, Ranadip] Texas Tech Univ, Lubbock, TX 79409 USA.
[Arenkiel, Benjamin R.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
[Chen, Qing-Rong; Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD 20877 USA.
[Davis, Sean; Meltzer, Paul S.] NCI, Genet Branch, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Capecchi, Mario R.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
[Michalek, Joel E.; Zarzabal, Lee Ann; Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Yu, Zhongxin; Parham, David M.] Univ Oklahoma, Med Ctr, Dept Pathol, Oklahoma City, OK 73104 USA.
[Yu, Zhongxin; Parham, David M.] Univ Oklahoma, Med Ctr, Dept Pediat, Oklahoma City, OK 73104 USA.
[Barr, Frederic G.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Keller, Charles] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA.
[Keller, Charles] Univ Texas Hlth Sci Ctr San Antonio, Dept Cell & Struct Biol, San Antonio, TX 78229 USA.
[Keller, Charles] Oregon Hlth & Sci Univ, Dept Pediat, Pediat Canc Biol Program, Pape Family Pediat Res Inst, Portland, OR 97239 USA.
RP Keller, C (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA.
EM keller@ohsu.edu
RI Khan, Javed/P-9157-2014;
OI Khan, Javed/0000-0002-5858-0488; Keller, Charles/0000-0003-2505-7487;
Davis, Sean/0000-0002-8991-6458
FU Scott Carter Foundation [K99NS064171-02, 5R01CA133229-04]; NICHD
FX Trainee and research support was provided by the Scott Carter Foundation
as well K99NS064171-02 and 5R01CA133229-04. Human tissue samples were
provided by the NCI-supported Cooperative Human Tissue Network. The
NICHD-supported DSHB is maintained by The University of Iowa. Authors
thank Maricela Castillo for technical assistance.
NR 62
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U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD FEB 15
PY 2011
VL 19
IS 2
BP 177
EP 191
DI 10.1016/j.ccr.2010.12.023
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 727BE
UT WOS:000287771500007
PM 21316601
ER
PT J
AU Cai, QY
Wen, WQ
Qu, SMA
Li, GL
Egan, KM
Chen, KX
Deming, SL
Shen, HB
Shen, CY
Gammon, MD
Blot, WJ
Matsuo, K
Haiman, CA
Khoo, US
Iwasaki, M
Santella, RM
Zhang, LN
Fair, AM
Hu, ZB
Wu, PE
Signorello, LB
Titus-Ernstoff, L
Tajima, K
Henderson, BE
Chan, KYK
Kasuga, Y
Newcomb, PA
Zheng, H
Cui, Y
Wang, FR
Shieh, YL
Iwata, H
Le Marchand, L
Chan, SY
Shrubsole, MJ
Trentham-Dietz, A
Tsugane, S
Garcia-Closas, M
Long, JR
Li, C
Shi, JJ
Huang, B
Xiang, YB
Gao, YT
Lu, W
Shu, XO
Zheng, W
AF Cai, Qiuyin
Wen, Wanqing
Qu, Shimian
Li, Guoliang
Egan, Kathleen M.
Chen, Kexin
Deming, Sandra L.
Shen, Hongbing
Shen, Chen-Yang
Gammon, Marilie D.
Blot, William J.
Matsuo, Keitaro
Haiman, Christopher A.
Khoo, Ui Soon
Iwasaki, Motoki
Santella, Regina M.
Zhang, Lina
Fair, Alecia Malin
Hu, Zhibin
Wu, Pei-Ei
Signorello, Lisa B.
Titus-Ernstoff, Linda
Tajima, Kazuo
Henderson, Brian E.
Chan, Kelvin Y. K.
Kasuga, Yoshio
Newcomb, Polly A.
Zheng, Hong
Cui, Yong
Wang, Furu
Shieh, Ya-Lan
Iwata, Hiroji
Le Marchand, Loic
Chan, Sum Yin
Shrubsole, Martha J.
Trentham-Dietz, Amy
Tsugane, Shoichiro
Garcia-Closas, Montserrat
Long, Jirong
Li, Chun
Shi, Jiajun
Huang, Bo
Xiang, Yong-Bing
Gao, Yu-Tang
Lu, Wei
Shu, Xiao-Ou
Zheng, Wei
TI Replication and Functional Genomic Analyses of the Breast Cancer
Susceptibility Locus at 6q25.1 Generalize Its Importance in Women of
Chinese, Japanese, and European Ancestry
SO CANCER RESEARCH
LA English
DT Article
ID WIDE ASSOCIATION; GENETIC-VARIANTS; ER-ALPHA; RISK; POLYMORPHISMS;
COHORT
AB We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 x 10(-30)], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 x 10(-4)], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r(2) = 0.83) populations, but not in Africans (r(2) = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. Cancer Res; 71(4); 1344-55. (C)2011 AACR.
C1 [Cai, Qiuyin; Wen, Wanqing; Qu, Shimian; Li, Guoliang; Deming, Sandra L.; Blot, William J.; Signorello, Lisa B.; Shrubsole, Martha J.; Long, Jirong; Li, Chun; Shi, Jiajun; Huang, Bo; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med,Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Fair, Alecia Malin; Cui, Yong] Meharry Med Coll, Nashville, TN 37208 USA.
[Egan, Kathleen M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control,Med Res Ctr, Tampa, FL 33612 USA.
[Chen, Kexin; Zhang, Lina; Zheng, Hong] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin, Peoples R China.
[Shen, Hongbing; Hu, Zhibin; Wang, Furu] Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Peoples R China.
[Shen, Chen-Yang; Wu, Pei-Ei; Shieh, Ya-Lan] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Matsuo, Keitaro; Tajima, Kazuo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Aichi, Japan.
[Iwata, Hiroji] Aichi Canc Ctr Cent Hosp, Dept Breast Oncol, Nagoya, Aichi, Japan.
[Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Khoo, Ui Soon; Chan, Kelvin Y. K.; Chan, Sum Yin] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Iwasaki, Motoki; Tsugane, Shoichiro] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Div, Tokyo 104, Japan.
[Santella, Regina M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
[Titus-Ernstoff, Linda] Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH USA.
[Titus-Ernstoff, Linda] Hood Ctr Children & Families, Lebanon, NH USA.
[Kasuga, Yoshio] Nagano Matsushiro Gen Hosp, Dept Surg, Nagano, Japan.
[Newcomb, Polly A.; Trentham-Dietz, Amy] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA.
[Trentham-Dietz, Amy] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96822 USA.
[Xiang, Yong-Bing; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Lu, Wei] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China.
RP Cai, QY (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med,Vanderbilt Ingram Canc Ctr, 1161 21st Ave S,MCN B-2104, Nashville, TN 37232 USA.
EM qiuyin.cai@vanderbilt.edu
RI Li, Chun/B-8388-2012; Shen, CY/F-6271-2010; Khoo, Ui Soon/C-1345-2014;
Tsugane, Shocichiro/A-2424-2015; Garcia-Closas, Montserrat /F-3871-2015;
Shrubsole, Martha/K-5052-2015; LI, GUOLIANG/E-7359-2015
OI Matsuo, Keitaro/0000-0003-1761-6314; Khoo, Ui Soon/0000-0003-2200-7505;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Shrubsole,
Martha/0000-0002-5591-7575; LI, GUOLIANG/0000-0001-8493-4684
FU US NIH [R01CA124558]; Vanderbilt-Ingram Cancer Center [P30CA68485];
Shanghai Breast Cancer Study [R01CA64277]; Nashville Breast Health Study
[R01CA100374]; Shanghai Breast Cancer Survival Study [R01CA118229];
Shanghai Endometrial Cancer Study [R01CA92585]; National Natural Science
Foundation of China [30771844]; Nanjing Study, China [IRT0631]; Taiwan
Biobank Stud [DOH97-01]; Hong Kong Study (Research Grant Council, Hong
Kong SAR, China) [HKU 7520/05M, 76730M]; Nagoya study (Ministry of
Education, Culture, Sports, Science, and Technology of Japan)
[17015052]; Ministry of Health, Labor and Welfare of Japan [H20-002];
Multiethnic Cohort Study [CA63464, CA54281, CA132839]; Nagano Breast
Cancer Study (Ministry of Education, Culture, Sports, Science, and
Technology of Japan) [17015049]; Collaborative Breast Cancer Study
including Massachusetts [R01CA47305]; Wisconsin [R01 CA47147]; New
Hampshire centers [R01CA69664]; Long Island Breast Cancer Study Project
[U01CA/ES66572, P30ES009089, P30ES010126]; Southern Community Cohort
Study [R01CA092447]
FX This research was supported by US NIH grant R01CA124558. The genotyping
assays conducted at Vanderbilt University were done at the Survey and
Biospecimen Core, which is supported in part by the Vanderbilt-Ingram
Cancer Center (P30CA68485). Participating studies (Principal
Investigator, grant support) of the consortium are as follows: the
Shanghai Breast Cancer Study (W. Zheng, R01CA64277), the Nashville
Breast Health Study (W. Zheng, R01CA100374), the Shanghai Breast Cancer
Survival Study (X.O. Shu, R01CA118229), the Shanghai Endometrial Cancer
Study (X.O. Shu, R01CA92585, contributed only controls to the
consortium), the Tianjin Study (K. Chen, the National Natural Science
Foundation of China Grant No. 30771844), the Nanjing Study (H. Shen,
IRT0631, China), the Taiwan Biobank Study (C.-Y. Shen, DOH97-01), the
Hong Kong Study (U.S. Khoo, Research Grant Council, Hong Kong SAR,
China, HKU 7520/05M and 76730M), the Nagoya study (K. Tajima,
Grants-in-Aid for Scientific Research on Priority Areas (17015052) from
the Ministry of Education, Culture, Sports, Science, and Technology of
Japan; H. Tanaka, Grants-in-Aid for the Third Term Comprehensive
Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor
and Welfare of Japan, H20-002), the Multiethnic Cohort Study (B. E.
Henderson, CA63464; L. Kolonel, CA54281; and C.A. Haiman, CA132839), the
Nagano Breast Cancer Study [S. Tsugane, Grants-in-Aid for the Third Term
Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of
Health, Labor and Welfare of Japan, and for Scientific Research on
Priority Areas (17015049) from the Ministry of Education, Culture,
Sports, Science, and Technology of Japan], the Collaborative Breast
Cancer Study including Massachusetts (K.M. Egan, R01CA47305), Wisconsin
(P.A. Newcomb, R01 CA47147) and New Hampshire (L. Titus-Ernstoff,
R01CA69664) centers, the Long Island Breast Cancer Study Project (M. D.
Gammon, U01CA/ES66572; R.M. Santella, P30ES009089; J.A. Swenberg,
P30ES010126), and the Southern Community Cohort Study (W.J. Blot,
R01CA092447). The content is solely the responsibility of the authors
and does not necessarily represent the official views of the funding
agencies.
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2011
VL 71
IS 4
BP 1344
EP 1355
DI 10.1158/0008-5472.CAN-10-2733
PG 12
WC Oncology
SC Oncology
GA 721KP
UT WOS:000287352600017
PM 21303983
ER
PT J
AU Mohler, JL
Titus, MA
Bai, SX
Kennerley, BJ
Lih, FB
Tomer, KB
Wilson, EM
AF Mohler, James L.
Titus, Mark A.
Bai, Suxia
Kennerley, Brian J.
Lih, Fred B.
Tomer, Kenneth B.
Wilson, Elizabeth M.
TI Activation of the Androgen Receptor by Intratumoral Bioconversion of
Androstanediol to Dihydrotestosterone in Prostate Cancer
SO CANCER RESEARCH
LA English
DT Article
ID OXIDATIVE 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE; STEROID
5-ALPHA-REDUCTASE; HYDROXYSTEROID DEHYDROGENASES; INCREASED EXPRESSION;
COREGULATOR MAGE-11; DEPRIVATION THERAPY; MASS-SPECTROMETRY; LNCAP
CELLS; IN-VIVO; TESTOSTERONE
AB The androgen receptor (AR) mediates the growth of benign and malignant prostate in response to dihydrotestosterone (DHT). In patients undergoing androgen deprivation therapy for prostate cancer, AR drives prostate cancer growth despite low circulating levels of testicular androgen and normal levels of adrenal androgen. In this report, we demonstrate the extent of AR transactivation in the presence of 5 alpha-androstane-3 alpha,17 beta-diol (androstanediol) in prostate-derived cell lines parallels the bioconversion of androstanediol to DHT. AR transactivation in the presence of androstanediol in prostate cancer cell lines correlated mainly with mRNA and protein levels of 17 beta-hydroxysteroid dehydrogenase 6 (17 beta-HSD6), one of several enzymes required for the interconversion of androstanediol to DHT and the inactive metabolite androsterone. Levels of retinol dehydrogenase 5, and dehydrogenase/reductase short-chain dehydrogenase/reductase family member 9, which also convert androstanediol to DHT, were lower than 17 beta-HSD6 in prostate-derived cell lines and higher in the castration-recurrent human prostate cancer xenograft. Measurements of tissue androstanediol using mass spectrometry demonstrated androstanediol metabolism to DHT and androsterone. Administration of androstanediol dipropionate to castration-recurrent CWR22R tumor-bearing athymic castrated male mice produced a 28-fold increase in intratumoral DHT levels. AR transactivation in prostate cancer cells in the presence of androstanediol resulted from the cell-specific conversion of androstanediol to DHT, and androstanediol increased LAPC-4 cell growth. The ability to convert androstanediol to DHT provides a mechanism for optimal utilization of androgen precursors and catabolites for DHT synthesis. Cancer Res; 71(4); 1486-96. (c) 2011 AACR.
C1 [Mohler, James L.; Bai, Suxia; Wilson, Elizabeth M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Mohler, James L.; Titus, Mark A.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA.
[Mohler, James L.] SUNY Buffalo, Dept Urol, Buffalo, NY 14260 USA.
[Bai, Suxia; Kennerley, Brian J.; Wilson, Elizabeth M.] Univ N Carolina, Labs Reprod Biol, Dept Pediat, Chapel Hill, NC 27599 USA.
[Wilson, Elizabeth M.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Lih, Fred B.; Tomer, Kenneth B.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Wilson, EM (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB7500, Chapel Hill, NC 27599 USA.
EM emw@med.unc.edu
RI Tomer, Kenneth/E-8018-2013
FU National Cancer Institute Center [P01-CA77739]; Cancer Center [CA16156];
University of North Carolina at Chapel Hill Lineberger Cancer Center
[CA34026]; National Institute of Child Health and Human Development
[HD16910]; NIH; National Institute of Environmental Health Sciences [Z01
ES5050167]
FX National Cancer Institute Center grant P01-CA77739 (J.L. Mohler and E.
M. Wilson) and Cancer Center Support Grant to Roswell Park Cancer
Institute CA16156 (J.L. Mohler), University of North Carolina at Chapel
Hill Lineberger Cancer Center CA34026 (J.L. Mohler), and US Public
Health Service grants HD16910 from the National Institute of Child
Health and Human Development (E.M. Wilson) and by the Intramural Program
of the NIH, National Institute of Environmental Health Sciences (Z01
ES5050167; K.B. Tomer).
NR 55
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U1 0
U2 6
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 FEB 15
PY 2011
VL 71
IS 4
BP 1486
EP 1496
DI 10.1158/0008-5472.CAN-10-1343
PG 11
WC Oncology
SC Oncology
GA 721KP
UT WOS:000287352600030
PM 21303972
ER
PT J
AU Ambs, S
Glynn, SA
AF Ambs, Stefan
Glynn, Sharon A.
TI Candidate pathways linking inducible nitric oxide synthase to a
basal-like transcription pattern and tumor progression in human breast
cancer
SO CELL CYCLE
LA English
DT Article
DE nitric oxide; inducible nitric oxide synthase; breast cancer;
basal-like; stem cell; survival
ID ENDOTHELIAL GROWTH-FACTOR; WILD-TYPE P53; GENE-EXPRESSION; IN-VIVO; IL-8
EXPRESSION; CARCINOMA-CELLS; BETA-CATENIN; DNA-DAMAGE; NOS2 GENE; SJL
MICE
AB Inducible nitric oxide synthase (NOS2) is an inflammation responsive enzyme (EC 1.14.13.39) that is induced during acute and chronic inflammation and tissue injury as part of the host defense and wound healing process. NOS2 upregulation leads to increased nitric oxide (NO) production, the means by which this enzyme can initiate NO-dependent signal transduction, influence the redox state of cells and induce modifications of proteins, lipids and DNA. Aberrant expression of NOS2 has been observed in many types of human tumors. In breast cancer, increased NOS2 is associated with markers of poor outcome and decreased survival. Growth factor and cytokine signaling, tissue remodeling, NF kappa B activation and hypoxia are candidate mechanisms that induce NOS2 in tumor epithelial and tumor-infiltrating cells. NOS2 induction will trigger the release of variable amounts of NO into the tumor microenvironment and can activate oncogenic pathways, including the Akt, epidermal growth factor receptor and c-Myc signaling pathways, and stimulate tumor microvascularization. Constitutively increased NO levels may also select for mutant p53 cells to overcome the tumor suppressor function of NO-activated wild-type p53. More recent findings suggest that NO induces stem cell-like tumor characteristics in breast cancer. In this review, we will discuss the effects of NO in tumor biology and disease progression with an emphasis on breast cancer, and will examine the mechanisms that link increased NO to a basal-like transcription pattern in human breast tumors and poor disease outcome.
C1 [Ambs, Stefan] NCI, Lab Human Carcinogenesis, CCR, Bethesda, MD 20892 USA.
[Glynn, Sharon A.] Natl Univ Ireland Galway, Prostate Canc Inst, Galway, Ireland.
RP Ambs, S (reprint author), NCI, Lab Human Carcinogenesis, CCR, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov; sharon.glynn@nuigalway.ie
RI Glynn, Sharon/D-7136-2013
OI Glynn, Sharon/0000-0003-1459-2580
FU NIH, National Cancer Institute, Center for Cancer Research, USA
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, USA.
NR 91
TC 25
Z9 26
U1 0
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD FEB 15
PY 2011
VL 10
IS 4
BP 619
EP 624
DI 10.4161/cc.10.4.14864
PG 6
WC Cell Biology
SC Cell Biology
GA 721KO
UT WOS:000287352500018
PM 21293193
ER
PT J
AU Amaravadi, RK
Lippincott-Schwartz, J
Yin, XM
Weiss, WA
Takebe, N
Timmer, W
DiPaola, RS
Lotze, MT
White, E
AF Amaravadi, Ravi K.
Lippincott-Schwartz, Jennifer
Yin, Xiao-Ming
Weiss, William A.
Takebe, Naoko
Timmer, William
DiPaola, Robert S.
Lotze, Michael T.
White, Eileen
TI Principles and Current Strategies for Targeting Autophagy for Cancer
Treatment
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID ENDOPLASMIC-RETICULUM STRESS; RESISTANT PROSTATE-CANCER; CELL-SURVIVAL;
TRANSLATIONAL CONTROL; RHEUMATOID-ARTHRITIS; DENDRITIC CELLS;
STARVATION; HYDROXYCHLOROQUINE; DEGRADATION; APOPTOSIS
AB Autophagy is an evolutionarily conserved, intracellular self-defense mechanism in which organelles and proteins are sequestered into autophagic vesicles that are subsequently degraded through fusion with lysosomes. Cells, thereby, prevent the toxic accumulation of damaged or unnecessary components, but also recycle these components to sustain metabolic homoeostasis. Heightened autophagy is a mechanism of resistance for cancer cells faced with metabolic and therapeutic stress, revealing opportunities for exploitation as a therapeutic target in cancer. We summarize recent developments in the field of autophagy and cancer and build upon the results presented at the Cancer Therapy Evaluation Program (CTEP) Early Drug Development meeting in March 2010. Herein, we describe our current understanding of the core components of the autophagy machinery and the functional relevance of autophagy within the tumor microenvironment, and we outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy, and immunotherapy. Finally, we describe ongoing clinical trials involving HCQ as a first generation autophagy inhibitor, as well as strategies for the development of novel, more potent, and specific inhibitors of autophagy. Clin Cancer Res; 17(4); 654-66. (C) 2011 AACR.
C1 [DiPaola, Robert S.; White, Eileen] Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Amaravadi, Ravi K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Amaravadi, Ravi K.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Lippincott-Schwartz, Jennifer] NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
[Yin, Xiao-Ming] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA.
[Weiss, William A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Weiss, William A.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Weiss, William A.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
[Weiss, William A.] Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA.
[Weiss, William A.] Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Takebe, Naoko; Timmer, William] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
[DiPaola, Robert S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Med Oncol, Newark, NJ 07103 USA.
[White, Eileen] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08855 USA.
[Lotze, Michael T.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
RP White, E (reprint author), Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08903 USA.
EM Ravi.Amaravadi@uphs.upenn.edu; whiteei@umdnj.edu
OI Weiss, William/0000-0003-2230-9132
FU NIH [P50CA097257]; Burroughs Wellcome Fund; American Brain Tumor
Association; Brain Tumor Society; Accelerate Brain Cancer Cure;
Pediatric Brain Tumor; Samuel G. Waxman Foundations;
[1K23CA120862-01A2]; [W81XWH-09-1-0394]; [W81XWH-09-1-0145]; [U01
CA132194]; [CA83817]; [CA111456]; [R37CA53370]; [RO1CA130893];
[RC1CA147961]
FX Grants supporting this work include: R. K. Amaravadi, 1K23CA120862-01A2;
W. A. Weiss, NIH P50CA097257, Burroughs Wellcome Fund, American Brain
Tumor Association, The Brain Tumor Society, Accelerate Brain Cancer
Cure, Pediatric Brain Tumor, and Samuel G. Waxman Foundations; R. S.
DiPaola, W81XWH-09-1-0394, W81XWH-09-1-0145, and U01 CA132194; X. M.
Yin, CA83817, CA111456; and E. White, R37CA53370, RO1CA130893, and
RC1CA147961.
NR 104
TC 375
Z9 388
U1 15
U2 99
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD FEB 15
PY 2011
VL 17
IS 4
BP 654
EP 666
DI 10.1158/1078-0432.CCR-10-2634
PG 13
WC Oncology
SC Oncology
GA 728ZM
UT WOS:000287913200005
PM 21325294
ER
PT J
AU Stein, WD
Gulley, JL
Schlom, J
Madan, RA
Dahut, W
Figg, WD
Ning, YM
Arlen, PM
Price, D
Bates, SE
Fojo, T
AF Stein, Wilfred D.
Gulley, James L.
Schlom, Jeff
Madan, Ravi A.
Dahut, William
Figg, William D.
Ning, Yang-min
Arlen, Phil M.
Price, Doug
Bates, Susan E.
Fojo, Tito
TI Tumor Regression and Growth Rates Determined in Five Intramural NCI
Prostate Cancer Trials: The Growth Rate Constant as an Indicator of
Therapeutic Efficacy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PHASE-II TRIAL; RADICAL PROSTATECTOMY; PLUS THALIDOMIDE;
CLINICAL-TRIALS; DOUBLING TIME; WORKING GROUP; SURVIVAL; DOCETAXEL;
VACCINE; RECOMMENDATIONS
AB Purpose: In solid tumors such as prostate cancer, novel paradigms are needed to assess therapeutic efficacy. We utilized a method estimating tumor growth and regression rate constants from serial PSA measurements, and assessed its potential in patients with metastatic castration resistant prostate carcinoma (mCRPC).
Experimental Design: Patients were enrolled in five phase II studies, including an experimental vaccine trial, representing the evolution of therapy in mCRPC. PSA measurements obtained before, and during, therapy were used. Data analysis using a two-phase mathematical equation yielded concomitant PSA growth and regression rate constants.
Results: Growth rate constants (g) can be estimated while patients receive therapy and in such patients g is superior to PSA-DT in predicting OS. Incremental reductions in growth rate constants were recorded in successive trials with a 10-fold slower g in the most recent combination therapy trial (log g = 10(-3.17)) relative to single-agent thalidomide (log g = 10(-2.08)) more than a decade earlier. Growth rate constants correlated with survival, except in patients receiving vaccine-based therapy where the evidence demonstrates prolonged survival presumably due to immunity developing subsequent to vaccine administration.
Conclusion: Incremental reductions in tumor growth rate constants suggest increased efficacy in successive chemotherapy trials. The derived growth rate constant correlates with survival, and may be used to assess efficacy. The PSA-TRICOM vaccine appears to have provided marked benefit not apparent during vaccination, but consistent with subsequent development of a beneficial immune response. If validated as a surrogate for survival, growth rate constants would offer an important new efficacy endpoint for clinical trials. Clin Cancer Res; 17(4); 907-17. (C) 2010 AACR.
C1 [Stein, Wilfred D.; Madan, Ravi A.; Dahut, William; Figg, William D.; Price, Doug; Bates, Susan E.; Fojo, Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Gulley, James L.; Schlom, Jeff; Madan, Ravi A.; Arlen, Phil M.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stein, Wilfred D.] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel.
[Ning, Yang-min] US FDA, DDOP OODP CDER, Silver Spring, MD USA.
RP Fojo, T (reprint author), NCI, Med Oncol Branch, NIH, NIH Bldg 10,RM 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tfojo@helix.nih.gov
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 37
TC 115
Z9 115
U1 0
U2 3
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 FEB 15
PY 2011
VL 17
IS 4
BP 907
EP 917
DI 10.1158/1078-0432.CCR-10-1762
PG 11
WC Oncology
SC Oncology
GA 728ZM
UT WOS:000287913200030
PM 21106727
ER
PT J
AU Sissung, TM
Gardner, ER
Piekarz, RL
Howden, R
Chen, XH
Woo, S
Franke, R
Clark, JA
Miller-DeGraff, L
Steinberg, SM
Venzon, D
Liewehr, D
Kleeberger, SR
Bates, SE
Price, DK
Rosing, DR
Cabell, C
Sparreboom, A
Figg, WD
AF Sissung, Tristan M.
Gardner, Erin R.
Piekarz, Richard L.
Howden, Reuben
Chen, Xiaohong
Woo, Sukyung
Franke, Ryan
Clark, James A.
Miller-DeGraff, Laura
Steinberg, Seth M.
Venzon, David
Liewehr, David
Kleeberger, Steven R.
Bates, Susan E.
Price, Douglas K.
Rosing, Douglas R.
Cabell, Christopher
Sparreboom, Alex
Figg, William D.
TI Impact of ABCB1 Allelic Variants on QTc Interval Prolongation
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID T-CELL LYMPHOMA; HUMAN MDR1 GENE; P-GLYCOPROTEIN; DEPSIPEPTIDE FR901228;
HUMAN PLACENTA; HUMAN HEART; EXPRESSION; RESISTANCE; EFFLUX; DISPOSITION
AB Purpose: Although the ABCB1 (P-glycoprotein) drug transporter is a constituent of several blood-tissue barriers (i.e., blood-brain and blood-nerve), its participation in a putative blood-heart barrier has been poorly explored. ABCB1 could decrease the intracardiac concentrations of drugs that cause QT prolongation and cardiotoxicity.
Experimental Design: ABCB1-related romidepsin transport kinetics were explored in LLC-PK1 cells transfected with different ABCB1 genetic variants. ABCB1 plasma and intracardiac concentrations were determined in Abcb1a/1b (-/-) mice and wild-type FVB controls. These same mice were used to evaluate romidepsin-induced heart rate-corrected QT interval (QTc) prolongation over time. Finally, a cohort of 83 individuals with available QTcB and ABCB1 genotyping data were used to compare allelic variation in ABCB1 versus QTc-prolongation phenotype.
Results: Here, we show that mice lacking the ABCB1-type P-glycoprotein have higher intracardiac concentrations of a model ABCB1 substrate, romidepsin, that correspond to changes in QT prolongation from baseline (Delta QTc) over time. Consistent with this observation, we also show that patients carrying genetic variants that could raise ABCB1 expression in the cardiac endothelium have lower Delta QTc following a single dose of romidepsin.
Conclusions: To our knowledge, this is the first evidence that Abcb1-type P-glycoprotein can limit intracardiac exposure to a drug that mediates QT prolongation and suggests that certain commonly inherited polymorphisms in ABCB1 may serve as markers for QT prolongation following the administration of ABCB1-substrate drugs. Clin Cancer Res; 17(4); 937-46. (C) 2010 AACR.
C1 [Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Sissung, Tristan M.; Chen, Xiaohong; Woo, Sukyung; Figg, William D.] NCI, Clin Pharmacol Program, Frederick, MD 21701 USA.
[Gardner, Erin R.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Howden, Reuben; Clark, James A.; Miller-DeGraff, Laura; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, Durham, NC USA.
[Franke, Ryan; Sparreboom, Alex] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Steinberg, Seth M.; Venzon, David; Liewehr, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Rosing, Douglas R.] Natl Heart Lung & Blood Inst, Cardiovasc Branch, Bethesda, MD USA.
[Cabell, Christopher] Quintiles Transnatl Corp, Res Triangle Pk, NC USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Institutes of Health, National Cancer Institute; National
Institute of Environmental Health Science, Research Triangle Park
[HHSN261200800001E]
FX This study was supported in whole or in part by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
and the National Institute of Environmental Health Science, Research
Triangle Park under contract HHSN261200800001E. (ERG).
NR 48
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 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD FEB 15
PY 2011
VL 17
IS 4
BP 937
EP 946
DI 10.1158/1078-0432.CCR-10-0925
PG 10
WC Oncology
SC Oncology
GA 728ZM
UT WOS:000287913200033
PM 21106724
ER
PT J
AU Fossat, N
Jones, V
Khoo, PL
Bogani, D
Hardy, A
Steiner, K
Mukhopadhyay, M
Westphal, H
Nolan, PM
Arkell, R
Tam, PPL
AF Fossat, Nicolas
Jones, Vanessa
Khoo, Poh-Lynn
Bogani, Debora
Hardy, Andrea
Steiner, Kirsten
Mukhopadhyay, Mahua
Westphal, Heiner
Nolan, Patrick M.
Arkell, Ruth
Tam, Patrick P. L.
TI Stringent requirement of a proper level of canonical WNT signalling
activity for head formation in mouse embryo
SO DEVELOPMENT
LA English
DT Article
DE Dkk1; Lrp6; beta-Catenin; ENU mutant; WNT signalling; Head formation;
Mouse; Gene dosage
ID PROSENCEPHALIC NEURAL PLATE; RECEPTOR-RELATED PROTEIN-6;
WNT/BETA-CATENIN; BETA-CATENIN; FOREBRAIN DEVELOPMENT; LIMB
MORPHOGENESIS; DICKKOPF PROTEINS; PRECHORDAL PLATE; AXIS FORMATION;
GASTRULATION
AB In mouse embryos, loss of Dickkopf-1 (DKK1) activity is associated with an ectopic activation of WNT signalling responses in the precursors of the craniofacial structures and leads to a complete truncation of the head at early organogenesis. Here, we show that ENU-induced mutations of genes coding for two WNT canonical pathway factors, the co-receptor LRP6 and the transcriptional co-activator beta-catenin, also elicit an ectopic signalling response and result in loss of the rostral tissues of the forebrain. Compound mutant embryos harbouring combinations of mutant alleles of Lrp6, Ctnnb1 and Dkk1 recapitulate the partial to complete head truncation phenotype of individual homozygous mutants. The demonstration of a synergistic interaction of Dkk1, Lrp6 and Ctnnb1 provides compelling evidence supporting the concepts that (1) stringent regulation of the level of canonical WNT signalling is necessary for head formation, (2) activity of the canonical pathway is sufficient to account for the phenotypic effects of mutations in three different components of the signal cascade and (3) rostral parts of the brain and the head are differentially more sensitive to canonical WNT signalling and their development is contingent on negative modulation of WNT signalling activity.
C1 [Fossat, Nicolas; Jones, Vanessa; Khoo, Poh-Lynn; Steiner, Kirsten; Tam, Patrick P. L.] Univ Sydney, Embryol Unit, Childrens Med Res Inst, Sydney, NSW 2145, Australia.
[Fossat, Nicolas; Tam, Patrick P. L.] Univ Sydney, Sydney Med Sch, Westmead, NSW 2145, Australia.
[Bogani, Debora; Hardy, Andrea; Nolan, Patrick M.; Arkell, Ruth] MRC, Mammalian Genet Unit, Harwell OX11 0RD, Oxon, England.
[Mukhopadhyay, Mahua; Westphal, Heiner] NIH, Lab Mammalian Genes & Dev, Eunice Kennedy Shriver Inst Child Hlth & Human De, Bethesda, MD 20892 USA.
[Arkell, Ruth] Australian Natl Univ, ARC Special Res Ctr Mol Genet, Dev & Mol Genet & Evolut Grp, Res Sch Biol Sci, Canberra, ACT 2601, Australia.
RP Tam, PPL (reprint author), Univ Sydney, Embryol Unit, Childrens Med Res Inst, 214 Hawkesbury Rd, Sydney, NSW 2145, Australia.
EM ptam@cmri.org.au
OI Nolan, Patrick/0000-0001-5550-0334
FU NHMRC of Australia [372103]; NHMRC [372102]
FX Authors thank Thomas Lamonerie for sending reagents, Guillermo Oliver
for the Tcf4 probe, Rebecca Storen for providing mice and David Loebel
for critical reading of the manuscript. Animal experimentation has been
approved by the CMRI/CHW Animal Care and Ethics Committee. Our work is
supported by the NHMRC of Australia (Grant 372103) and Mr James Fairfax.
N.F. is a University of Sydney Post-Doctoral Fellow and P.P.L.T. is a
NHMRC Senior Principal Research Fellow (Grant 372102).
NR 46
TC 26
Z9 28
U1 1
U2 6
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 FEB 15
PY 2011
VL 138
IS 4
BP 667
EP 676
DI 10.1242/dev.052803
PG 10
WC Developmental Biology
SC Developmental Biology
GA 711KN
UT WOS:000286590400008
PM 21228006
ER
PT J
AU Hong, SK
Jang, MK
Brown, JL
McBride, AA
Feldman, B
AF Hong, Sung-Kook
Jang, Moon Kyoo
Brown, Jamie L.
McBride, Alison A.
Feldman, Benjamin
TI Embryonic mesoderm and endoderm induction requires the actions of
non-embryonic Nodal-related ligands and Mxtx2
SO DEVELOPMENT
LA English
DT Article
DE Mxtx2; Ndr1; Ndr2; Ntla; Mesendoderm; Yolk syncytial layer; Zebrafish
ID YOLK SYNCYTIAL LAYER; ZEBRAFISH EMBRYOGENESIS; MORPHOGENETIC MOVEMENTS;
MOUSE EMBRYO; GENE; PROTEIN; EXPRESSION; GASTRULATION; SIGNALS; AXIS
AB Vertebrate mesoderm and endoderm formation requires signaling by Nodal-related ligands from the TGF. superfamily. The factors that initiate Nodal-related gene transcription are unknown in most species and the relative contributions of Nodal-related ligands from embryonic, extraembryonic and maternal sources remain uncertain. In zebrafish, signals from the yolk syncytial layer (YSL), an extraembryonic domain, are required for mesoderm and endoderm induction, and YSL expression of nodal-related 1 (ndr1) and ndr2 accounts for a portion of this activity. A variable requirement of maternally derived Ndr1 for dorsal and anterior axis formation has also been documented. Here we show that Mxtx2 directly activates expression of ndr2 via binding to its first intron and is required for ndr2 expression in the YSL. Mxtx2 is also required for the Nodal signaling-independent expression component of the no tail a (ntla) gene, which is required for posterior (tail) mesoderm formation. Therefore, Mxtx2 defines a new pathway upstream of Nodal signaling and posterior mesoderm formation. We further show that the co-disruption of extraembryonic Ndr2, extraembryonic Ndr1 and maternal Ndr1 eliminates endoderm and anterior (head and trunk) mesoderm, recapitulating the loss of Nodal signaling phenotype. Therefore, non-embryonic sources of Nodal-related ligands account for the complete spectrum of early Nodal signaling requirements. In summary, the induction of mesoderm and endoderm depends upon the combined actions of Mxtx2 and Nodal-related ligands from non-embryonic sources.
C1 [Hong, Sung-Kook; Brown, Jamie L.; Feldman, Benjamin] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Jang, Moon Kyoo; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Feldman, B (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM bfeldman@mail.nih.gov
OI Feldman, Benjamin/0000-0003-4838-8641; McBride,
Alison/0000-0001-5607-5157
FU National Human Genome Research Institute; National Institute of Allergy
and Infectious Diseases, National Institutes of Health
FX We thank Alexander Schier, Igor Dawid, Karuna Sampath and Jerome
Collignon for helpful suggestions. This research was supported by the
Intramural Research Programs of the National Human Genome Research
Institute and the National Institute of Allergy and Infectious Diseases,
National Institutes of Health. Deposited in PMC for release after 12
months.
NR 52
TC 17
Z9 17
U1 1
U2 7
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 FEB 15
PY 2011
VL 138
IS 4
BP 787
EP 795
DI 10.1242/dev.058974
PG 9
WC Developmental Biology
SC Developmental Biology
GA 711KN
UT WOS:000286590400020
PM 21266414
ER
PT J
AU Gao, B
Song, H
Bishop, K
Elliot, G
Garrett, L
English, MA
Andre, P
Robinson, J
Sood, R
Minami, Y
Economides, AN
Yang, YZ
AF Gao, Bo
Song, Hai
Bishop, Kevin
Elliot, Gene
Garrett, Lisa
English, Milton A.
Andre, Philipp
Robinson, James
Sood, Raman
Minami, Yasuhiro
Economides, Aris N.
Yang, Yingzi
TI Wnt Signaling Gradients Establish Planar Cell Polarity by Inducing
Vangl2 Phosphorylation through Ror2
SO DEVELOPMENTAL CELL
LA English
DT Article
ID RECEPTOR TYROSINE KINASE; NEURAL-TUBE DEFECTS; RECESSIVE
ROBINOW-SYNDROME; BRACHYDACTYLY TYPE-B; I-EPSILON; LOOP-TAIL;
DROSOPHILA; PATHWAY; MUTATIONS; CATENIN
AB It is fundamentally important that signaling gradients provide positional information to govern morphogenesis of multicellular organisms. Morphogen gradients can generate different cell types in specific spatial order at distinct threshold concentrations. However, it is largely unknown whether and how signaling gradients also control cell polarities by acting as global cues. Here, we show that Wnt signaling gradient provides directional information to a field of cells. Vangl2, a core component in planar cell polarity, forms Wnt-induced receptor complex with Ror2 to sense Wnt dosages. Wnts dose-dependently induce Vangl2 phosphorylation of serine/threonine residues and Vangl2 activities depend on its levels of phosphorylation. In the limb bud, Wnt5a signaling gradient controls limb elongation by establishing PCP in chondrocytes along the proximal-distal axis through regulating Vangl2 phosphorylation. Our studies have provided new insight to Robinow syndrome, Brachydactyly Type B1, and spinal bifida which are caused by mutations in human ROR2, WNT5A, or VANGL.
C1 [Gao, Bo; Song, Hai; Bishop, Kevin; Elliot, Gene; Garrett, Lisa; English, Milton A.; Andre, Philipp; Robinson, James; Sood, Raman; Yang, Yingzi] NHGRI, Bethesda, MD 20892 USA.
[Minami, Yasuhiro] Kobe Univ, Fac Med Sci, Dept Physiol & Cell Biol, Chuo Ku, Kobe, Hyogo 6500017, Japan.
[Economides, Aris N.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
RP Yang, YZ (reprint author), NHGRI, Bethesda, MD 20892 USA.
EM yingzi@mail.nih.gov
RI Gao, Bo/F-4688-2013;
OI Economides, Aris/0000-0002-6508-8942
FU National Human Genome Research Institute
FX We thank the Yang lab for stimulating discussion, Drs. J. Rubin and A.
Kimmel for critical reading of the manuscript and S. Wincovitch for
confocal microscopic analysis. We are grateful to Dr. J. Rubin for CKI
cDNA constructs, Dr. M. Kelley for the Vangl2 antibodies, and Dr. R.
Nusse for Ror2 antibodies. This study is supported by the intramural
research program of National Human Genome Research Institute.
NR 59
TC 175
Z9 177
U1 3
U2 28
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD FEB 15
PY 2011
VL 20
IS 2
BP 163
EP 176
DI 10.1016/j.devcel.2011.01.001
PG 14
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 725LS
UT WOS:000287646800006
PM 21316585
ER
PT J
AU Mughal, MR
Baharani, A
Chigurupati, S
Son, TG
Chen, E
Yang, P
Okun, E
Arumugam, T
Chan, SL
Mattson, MP
AF Mughal, Mohamed R.
Baharani, Akanksha
Chigurupati, Srinivasulu
Son, Tae Gen
Chen, Edmund
Yang, Peter
Okun, Eitan
Arumugam, Thiruma
Chan, Sic L.
Mattson, Mark P.
TI Electroconvulsive shock ameliorates disease processes and extends
survival in huntingtin mutant mice
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID NEURONAL INTRANUCLEAR INCLUSIONS; RESISTANT DEPRESSED-PATIENTS;
TRANSGENIC MOUSE MODEL; NEUROTROPHIC FACTOR; RAT-BRAIN; SYNAPTIC
PLASTICITY; SLOWS DISEASE; DIETARY RESTRICTION; STRIATAL NEURONS;
GENE-EXPRESSION
AB Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expanded polyglutamine repeats in the huntingtin (Htt) protein. Mutant Htt may damage and kill striatal neurons by a mechanism involving reduced production of brain-derived neurotrophic factor (BDNF) and increased oxidative and metabolic stress. Because electroconvulsive shock (ECS) can stimulate the production of BDNF and protect neurons against stress, we determined whether ECS treatment would modify the disease process and provide a therapeutic benefit in a mouse model of HD. ECS (50 mA for 0.2 s) or sham treatment was administered once weekly to male N171-82Q Htt mutant mice beginning at 2 months of age. Endpoints measured included motor function, striatal and cortical pathology, and levels of protein chaperones and BDNF. ECS treatment delayed the onset of motor symptoms and body weight loss and extended the survival of HD mice. Striatal neurodegeneration was attenuated and levels of protein chaperones (Hsp70 and Hsp40) and BDNF were elevated in striatal neurons of ECS-treated compared with sham-treated HD mice. Our findings demonstrate that ECS can increase the resistance of neurons to mutant Htt resulting in improved functional outcome and extended survival. The potential of ECS as an intervention in subjects that inherit the mutant Htt gene merits further consideration.
C1 [Baharani, Akanksha; Chigurupati, Srinivasulu; Chan, Sic L.] Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, Orlando, FL 32816 USA.
[Mughal, Mohamed R.; Chigurupati, Srinivasulu; Son, Tae Gen; Chen, Edmund; Yang, Peter; Okun, Eitan; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Arumugam, Thiruma] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Chan, SL (reprint author), Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, 4000 Cent Florida Blvd, Orlando, FL 32816 USA.
EM schan@mail.ucf.edu; mattsonm@grc.nia.nih.gov
RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; okun,
eitan/K-1314-2016
OI okun, eitan/0000-0001-8474-1487
FU National Institute on Aging of the National Institutes of Health; NIH
[1R21NS066265-01]
FX This research was supported by the Intramural Research Program of the
National Institute on Aging of the National Institutes of Health, and by
NIH grant (1R21NS066265-01) to S. L. C.
NR 79
TC 10
Z9 10
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD FEB 15
PY 2011
VL 20
IS 4
BP 659
EP 669
DI 10.1093/hmg/ddq512
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 709VL
UT WOS:000286469400004
PM 21106706
ER
PT J
AU Nayak, TK
Garmestani, K
Baidoo, KE
Milenic, DE
Brechbiel, MW
AF Nayak, Tapan K.
Garmestani, Kayhan
Baidoo, Kwamena E.
Milenic, Diane E.
Brechbiel, Martin W.
TI PET imaging of tumor angiogenesis in mice with VEGF-A-targeted
Y-86-CHX-A ''-DTPA-bevacizumab
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE PET imaging; VEGF-A; angiogenesis; bevacizumab; Y-86
ID RADIOLABELED BEVACIZUMAB; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER;
BIODISTRIBUTION; GROWTH; EXPRESSION; YTTRIUM-86; DOSIMETRY; THERAPY; MRI
AB Bevacizumab is a humanized monoclonal antibody that binds to tumor-secreted vascular endothelial growth factor (VEGF)-A and inhibits tumor angiogenesis. In 2004, the antibody was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal carcinoma in combination with chemotherapy. This report describes the preclinical evaluation of a radioimmunoconjugate, Y-86-CHX-A ''-DTPA-bevacizumab, for potential use in Positron Emission Tomography (PET) imaging of VEGF-A tumor angiogenesis and as a surrogate marker for Y-90-based radioimmunotherapy. Bevacizumab was conjugated to CHX-A ''-DTPA and radiolabeled with Y-86. In vivo biodistribution and PET imaging studies were performed on mice bearing VEGF-A secreting human colorectal (LS-174T), human ovarian (SKOV-3) and VEGF-A negative human mesothelioma (MSTO-211H) xenografts. Biodistribution and PET imaging studies demonstrated highly specific tumor uptake of the radioimmunoconjugate. In mice bearing VEGF-A secreting LS-174T, SKOV-3 and VEGF-A negative MSTO-211H tumors, the tumor uptake at 3 days postinjection was 13.6 +/- 1.5, 17.4 +/- 1.7 and 6.8 +/- 0.7 % ID/g, respectively. The corresponding tumor uptake in mice coinjected with 0.05 mg cold bevacizumab were 5.8 +/- 1.3, 8.9 +/- 1.9 and 7.4 +/- 1.0 % ID/g, respectively at the same time point, demonstrating specific blockage of the target in VEGF-A secreting tumors. The LS-174T and SKOV3 tumors were clearly visualized by PET imaging after injecting 1.8-2.0 MBq Y-86-CHX-A ''-DTPA-bevacizumab. Organ uptake quantified by PET closely correlated (r(2) = 0.87, p = 0.64, n = 18) to values determined by biodistribution studies. This preclinical study demonstrates the potential of the radioimmunoconjugate, Y-86-CHX-A ''-DTPA-bevacizumab, for noninvasive assessment of the VEGF-A tumor angiogenesis status and as a surrogate marker for Y-90-CHX-A ''-DTPA-bevacizumab radioimmunotherapy.
C1 [Nayak, Tapan K.; Garmestani, Kayhan; Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Nayak, TK (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,B3B69, Bethesda, MD 20892 USA.
EM tapann@gmail.com
OI Nayak, Tapan/0000-0002-3706-6092
FU National Institute of Health (NIH); NCI; Center for Cancer Research,
United States Department of Health and Human Services
FX Grant sponsors: National Institute of Health (NIH) (Intramural Research
Program), NCI, Center for Cancer Research, United States Department of
Health and Human Services
NR 29
TC 36
Z9 37
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 15
PY 2011
VL 128
IS 4
BP 920
EP 926
DI 10.1002/ijc.25409
PG 7
WC Oncology
SC Oncology
GA 710ZO
UT WOS:000286555700019
PM 20473899
ER
PT J
AU Castle, PE
AF Castle, Philip E.
TI Do selective estrogen receptor modulators treat cervical precancer and
cancer? time to pool data from relevant trials
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Letter
ID BREAST-CANCER; HUMAN-PAPILLOMAVIRUS; PREVENTION; WOMEN; RISK; TAMOXIFEN;
COHORT
C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd Room 5026,MSC 7234, Bethesda, MD 20892 USA.
EM castlep@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010124-12]
NR 15
TC 7
Z9 7
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 15
PY 2011
VL 128
IS 4
BP 997
EP 998
DI 10.1002/ijc.25393
PG 2
WC Oncology
SC Oncology
GA 710ZO
UT WOS:000286555700028
PM 20473883
ER
PT J
AU Zigler, JS
Zhang, C
Grebe, R
Sehrawat, G
Hackler, L
Adhya, S
Hose, S
McLeod, DS
Bhutto, I
Barbour, W
Parthasarathy, G
Zack, DJ
Sergeev, Y
Lutty, GA
Handa, JT
Sinha, D
AF Zigler, J. Samuel, Jr.
Zhang, Cheng
Grebe, Rhonda
Sehrawat, Gitanjali
Hackler, Laszlo, Jr.
Adhya, Souvonik
Hose, Stacey
McLeod, D. Scott
Bhutto, Imran
Barbour, Walid
Parthasarathy, Geetha
Zack, Donald J.
Sergeev, Yuri
Lutty, Gerard A.
Handa, James T.
Sinha, Debasish
TI Mutation in the beta A3/A1-crystallin gene impairs phagosome degradation
in the retinal pigmented epithelium of the rat
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE beta A3/A1-crystallin; Cathepsin D; Retinal pigmented epithelium ( RPE);
Photoreceptor outer segment discs; Lysosome; Phagocytosis; Autophagy
ID ROD OUTER SEGMENTS; ALPHA-V-BETA-5 INTEGRIN; HUMAN LENSES; CATHEPSIN-D;
RCS RAT; PHAGOCYTOSIS; PROTEIN; CELLS; MATURATION; RENEWAL
AB Phagocytosis of the shed outer segment discs of photoreceptors is a major function of the retinal pigmented epithelium (RPE). We demonstrate for the first time that beta A3/A1-crystallin, a major structural protein of the ocular lens, is expressed in RPE cells. Further, by utilizing the Nuc1 rat, in which the beta A3/A1-crystallin gene is mutated, we show that this protein is required by RPE cells for proper degradation of outer segment discs that have been internalized in phagosomes. We also demonstrate that in wild-type RPE, beta A3/A1-crystallin is localized to the lysosomes. However, in the Nuc1 RPE, beta A3/A1-crystallin fails to translocate to the lysosomes, perhaps because misfolding of the mutant protein masks sorting signals required for proper trafficking. The digestion of phagocytized outer segments requires a high level of lysosomal enzyme activity, and cathepsin D, the major enzyme responsible for proteolysis of the outer segments, is decreased in mutant RPE cells. Interestingly, our results also indicate a defect in the autophagy process in the Nuc1 RPE, which is probably also linked to impaired lysosomal function, because phagocytosis and autophagy might share common mechanisms in degradation of their targets. beta A3/A1-crystallin is a novel lysosomal protein in RPE, essential for degradation of phagocytosed material.
C1 [Zigler, J. Samuel, Jr.; Zhang, Cheng; Grebe, Rhonda; Sehrawat, Gitanjali; Hackler, Laszlo, Jr.; Adhya, Souvonik; Hose, Stacey; McLeod, D. Scott; Bhutto, Imran; Barbour, Walid; Parthasarathy, Geetha; Zack, Donald J.; Lutty, Gerard A.; Handa, James T.; Sinha, Debasish] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Sergeev, Yuri] NEI, NIH, Bethesda, MD 20892 USA.
RP Sinha, D (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM Debasish@jhmi.edu
OI Zack, Don/0000-0002-7966-1973
FU National Institutes of Health [EY018636, EY019037, EY019037-S, EY09357,
EY016151-5, EY14005, EY01765]; National Eye Institute; Helena Rubinstein
Foundation; Research to Prevent Blindness
FX This work was supported by grants from the National Institutes of
Health: EY018636 (D. S.), EY019037 (D. S.), EY019037-S (D. S.), EY09357
(G. A. L.), EY016151-5 (G. A. L.), EY14005 (J.T.H.), EY01765 (Wilmer
Imaging Core), Intramural Research Program, National Eye Institute
(J.S.Z. and Y.S.), Helena Rubinstein Foundation (D. S.) and Research to
Prevent Blindness (an unrestricted grant to The Wilmer Eye Institute).
We thank Robert N. Fariss and Nataliya Goriyenko of the National Eye
Institute for help with the in situ phagocytosis assay and the staff
members at Spring Valley Laboratories, Woodbine, MD, for taking care of
the experimental animals. We thank Noriko Esumi and Morton Goldberg for
critical reading and discussion regarding this manuscript. Deposited in
PMC for release after 12 months.
NR 51
TC 32
Z9 32
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 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD FEB 15
PY 2011
VL 124
IS 4
BP 523
EP 531
DI 10.1242/jcs.078790
PG 9
WC Cell Biology
SC Cell Biology
GA 713HJ
UT WOS:000286726100004
PM 21266465
ER
PT J
AU Castiel, A
Danieli, MM
David, A
Moshkovitz, S
Aplan, PD
Kirsch, IR
Brandeis, M
Kramer, A
Izraeli, S
AF Castiel, Asher
Danieli, Michal Mark
David, Ahuvit
Moshkovitz, Sharon
Aplan, Peter D.
Kirsch, Ilan R.
Brandeis, Michael
Kraemer, Alwin
Izraeli, Shai
TI The Stil protein regulates centrosome integrity and mitosis through
suppression of Chfr
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Centrosome; Chfr; Mitosis; Sil; Stil
ID POLO-LIKE KINASE-1; MITOTIC CHECKPOINT PROTEIN; SIL GENE; CENTRIOLE
DUPLICATION; SPINDLE CHECKPOINT; TUMOR SUPPRESSION; DNA-DAMAGE; ENTRY;
LIGASE; PLK1
AB Stil (Sil, SCL/TAL1 interrupting locus) is a cytosolic and centrosomal protein expressed in proliferating cells that is required for mouse and zebrafish neural development and is mutated in familial microcephaly. Recently the Drosophila melanogaster ortholog of Stil was found to be important for centriole duplication. Consistent with this finding, we report here that mouse embryonic fibroblasts lacking Stil are characterized by slow growth, low mitotic index and absence of clear centrosomes. We hypothesized that Stil regulates mitosis through the tumor suppressor Chfr, an E3 ligase that blocks mitotic entry in response to mitotic stress. Mouse fibroblasts lacking Stil by genomic or RNA interference approaches, as well as E9.5 Stil(-/-) embryos, express high levels of the Chfr protein and reduced levels of the Chfr substrate Plk1. Exogenous expression of Stil, knockdown of Chfr or overexpression of Plk1 reverse the abnormal mitotic phenotypes of fibroblasts lacking Stil. We further demonstrate that Stil increases Chfr auto-ubiquitination and reduces its protein stability. Thus, Stil is required for centrosome organization, entry into mitosis and cell proliferation, and these functions are at least partially mediated by Chfr and its targets. This is the first identification of a negative regulator of the Chfr mitotic checkpoint.
C1 [Castiel, Asher; Danieli, Michal Mark; David, Ahuvit; Moshkovitz, Sharon; Izraeli, Shai] Sheba Canc Res Ctr, IL-52621 Ramat Gan, Israel.
[Castiel, Asher; Danieli, Michal Mark; David, Ahuvit; Moshkovitz, Sharon; Izraeli, Shai] Edmond & Lily Safra Childrens Hosp, Chaim Sheba Med Ctr, IL-52621 Ramat Gan, Israel.
[Castiel, Asher; David, Ahuvit; Izraeli, Shai] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Aplan, Peter D.; Kirsch, Ilan R.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA.
[Brandeis, Michael] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel.
[Kraemer, Alwin] German Canc Res Ctr, Clin Cooperat Unit Mol Hematol Oncol, D-69120 Heidelberg, Germany.
[Kraemer, Alwin] Univ Heidelberg, Dept Internal Med 5, D-69120 Heidelberg, Germany.
RP Izraeli, S (reprint author), Sheba Canc Res Ctr, IL-52621 Ramat Gan, Israel.
EM Shai.Izraeli@sheba.health.gov.il
RI Aplan, Peter/K-9064-2016
FU US-Israel Binational Science Foundation; Israel Cancer Research
Foundation; Israel Science Foundation; DKFZ-MOST; NCI/NIH
FX We thank Hitoshi Nakagama for providing the HA-Chfr and HA-Chfr Delta RF
vectors, Thanos Halazonetis for providing the pIRES-2HA-Chfr vector and
Hannah Tamary for the Myc-ubiquitin vector. We appreciate the advice of
Aharon Ciechanover and the assistance from all members of the Izraeli
laboratory. This research was partially funded by research grants from
the US-Israel Binational Science Foundation (to S. I., P. D. A. and I.
R. K.), the Israel Cancer Research Foundation (M. M. D. and S. I.), the
Israel Science Foundation (S. I. and M. B.), the DKFZ-MOST grant (S. I.
and A. K.) and the intramural funding of the NCI/NIH. This research was
done as partial fulfillment of the requirement for a PhD degree of A. C.
and A. D. at the Sackler Faculty of Medicine, Tel Aviv University. The
authors declare they have no conflicts of interest. Deposited in PMC for
release after 12 months.
NR 44
TC 27
Z9 27
U1 0
U2 7
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 FEB 15
PY 2011
VL 124
IS 4
BP 532
EP 539
DI 10.1242/jcs.079731
PG 8
WC Cell Biology
SC Cell Biology
GA 713HJ
UT WOS:000286726100005
PM 21245198
ER
PT J
AU Kim, JY
Morgan, M
Kim, DG
Lee, JY
Bai, L
Lin, Y
Liu, ZG
Kim, YS
AF Kim, Joo-Young
Morgan, Michael
Kim, Dong-Gun
Lee, Ju-Yeon
Bai, Lang
Lin, Yong
Liu, Zheng-gang
Kim, You-Sun
TI TNF alpha-induced noncanonical NF-kappa B activation is attenuated by
RIP1 through stabilization of TRAF2
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE TNF alpha; TNFR1; RIP1; TRAF2; Noncanonical NF-kappa B
ID NECROSIS-FACTOR RECEPTOR; TOLL-LIKE-RECEPTORS; CELL-DEATH; SIGNALING
COMPLEX; KINASE RIP; DEPENDENT APOPTOSIS; MULTIPLE-MYELOMA; IKK-ALPHA;
PATHWAYS; UBIQUITINATION
AB The current paradigm of noncanonical NF-kappa B signaling suggests that the loss of TRAF2, TRAF3 or cIAP1 and cIAP2 leads to stabilization of NF-kappa B-inducing kinase (NIK) to activate the noncanonical pathway. Although a crucial role of RIP1 in the TNF alpha-induced canonical NF-kappa B pathway has been well established, its involvement in noncanonical activation of NF-kappa B through the TNFR1 receptor, is unknown. Here we show that TNF alpha is capable of activating the noncanonical NF-kappa B pathway, but that activation of this pathway is negatively regulated by RIP1. In the absence of RIP1, TNFR1 stimulation leads to activation of the noncanonical NF-kappa B pathway through TRAF2 degradation, leading to NIK stabilization, IKK alpha phosphorylation and the processing of p100 to generate p52. Thus although RIP1(-/-) mouse embryonic fibroblasts are sensitive at early time points to cell death induced by TNF alpha, probably as a result of lack of canonical NF-kappa B activation, the late activation of the noncanonical NF-kappa B pathway protects the remaining cells from further cell death. The TNFR1-dependent noncanonical NF-kappa B activation in RIP1(-/-) cells suggests that there is functional interplay between the two NF-kappa B pathways during TNFR1 signaling, which might regulate the number and kinds of NF-kappa B transcription factors and thus finely control NF-kappa B-dependent gene transcription.
C1 [Kim, Joo-Young; Kim, Dong-Gun; Lee, Ju-Yeon; Kim, You-Sun] Ajou Univ, Sch Med, Inst Med Sci, Suwon 443749, South Korea.
[Morgan, Michael; Liu, Zheng-gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bai, Lang; Lin, Yong] Lovelace Resp Res Inst, Mol Biol & Lung Canc Program, Albuquerque, NM 87108 USA.
RP Kim, YS (reprint author), Ajou Univ, Sch Med, Inst Med Sci, Suwon 443749, South Korea.
EM yousunkim@ajou.ac.kr
FU Korean Government [2009-0067084]; Ajou University School of Medicine
[3-2008025-0]; Ajou University
FX We thank Wen-Chen Yeh and Tak Wah Mak for TRAF2-/- MEFs;
Michelle Kelliher for RIP1-/- MEFs. This work was supported
by a National Research Foundation of Korea Grant funded by the Korean
Government (2009-0067084). This work was also supported by Research
Grant funded by the Ajou University School of Medicine (3-2008025-0) and
by the grant of 'The Ajou University Excellence Research Program in
2010'.
NR 56
TC 23
Z9 25
U1 0
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD FEB 15
PY 2011
VL 124
IS 4
BP 647
EP 656
DI 10.1242/jcs.075770
PG 10
WC Cell Biology
SC Cell Biology
GA 713HJ
UT WOS:000286726100016
PM 21266470
ER
PT J
AU Fragale, A
Stellacci, E
Ilari, R
Remoli, AL
Lanciotti, A
Perrotti, E
Shytaj, I
Orsatti, R
Lawrence, HR
Lawrence, NJ
Wu, J
Rehli, M
Ozato, K
Battistini, A
AF Fragale, Alessandra
Stellacci, Emilia
Ilari, Ramona
Remoli, Anna Lisa
Lanciotti, Angela
Perrotti, Edvige
Shytaj, Iart
Orsatti, Roberto
Lawrence, Harshani R.
Lawrence, Nicholas J.
Wu, Jerry
Rehli, Michael
Ozato, Keiko
Battistini, Angela
TI Critical Role of IRF-8 in Negative Regulation of TLR3 Expression by Src
Homology 2 Domain-Containing Protein Tyrosine Phosphatase-2 Activity in
Human Myeloid Dendritic Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SEQUENCE-BINDING-PROTEIN; TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA;
IMMUNE-RESPONSE; I INTERFERON; ICSBP; TRANSCRIPTION; ACTIVATION; VIRUS;
MICE
AB Despite extensive studies that unraveled ligands and signal transduction pathways triggered by TLRs, little is known about the regulation of TLR gene expression. TLR3 plays a crucial role in the recognition of viral pathogens and induction of immune responses by myeloid DCs. IFN regulatory factor (IRF)-8, a member of the IRF family, is a transcriptional regulator that plays essential roles in the development and function of myeloid lineage, affecting different subsets of myeloid DCs. In this study, we show that IRF-8 negatively controls TLR3 gene expression by suppressing IRF-1- and/or polyinosinic-polycytidylic acid-stimulated TLR3 expression in primary human monocyte-derived DCs (MDDCs). MDDCs expressed TLR3 increasingly during their differentiation from monocytes to DCs with a peak at day 5, when TLR3 expression was further enhanced upon stimulation with polyinosinic-polycytidylic acid and then was promptly downregulated. We found that both IRF-1 and IRF-8 bind the human TLR3 promoter during MDDC differentiation in vitro and in vivo but with different kinetic and functional effects. We demonstrate that IRF-8-induced repression of TLR3 is specifically mediated by ligand-activated Src homology 2 domain-containing protein tyrosine phosphatase association. Indeed, Src homology 2 domain-containing protein tyrosine phosphatase-dephosphorylated IRF-8 bound to the human TLR3 promoter competing with IRF-1 and quashing its activity by recruitment of histone deacetylase 3. Our findings identify IRF-8 as a key player in the control of intracellular viral dsRNA-induced responses and highlight a new mechanism for negative regulation of TLR3 expression that can be exploited to block excessive TLR activation. The Journal of Immunology, 2011, 186: 1951-1962.
C1 [Fragale, Alessandra; Stellacci, Emilia; Ilari, Ramona; Remoli, Anna Lisa; Lanciotti, Angela; Perrotti, Edvige; Shytaj, Iart; Orsatti, Roberto; Battistini, Angela] Ist Super Sanita, Dipartimento Malattie Infett Parassitarie & Immun, I-00161 Rome, Italy.
[Stellacci, Emilia] Ist Super Sanita, Dipartimento Ematol Oncol & Med Mol, I-00161 Rome, Italy.
[Lanciotti, Angela] Ist Super Sanita, Dipartimento Biol Cellulare & Neurosci, I-00161 Rome, Italy.
[Lawrence, Harshani R.; Lawrence, Nicholas J.; Wu, Jerry] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Rehli, Michael] Univ Hosp, Dept Hematol & Oncol, Regensburg, Germany.
[Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20814 USA.
RP Battistini, A (reprint author), Ist Super Sanita, Dipartimento Malattie Infett Parassitarie & Immun, Viale Regina Elena 299, I-00161 Rome, Italy.
EM angela.battistini@iss.it
RI Rehli, Michael/E-9093-2011; REMOLI, ANNA LISA/C-2961-2016; BATTISTINI,
ANGELA/C-2944-2016; PERROTTI, EDVIGE/C-2956-2016; Lanciotti,
Angela/J-6431-2016; stellacci, emilia/J-2747-2014;
OI Rehli, Michael/0000-0003-3992-932X; Lanciotti,
Angela/0000-0003-1615-1770; Shytaj, Iart Luca/0000-0002-9980-1275
FU Istituto Superiore di Sanita-National Institutes of Health; Italian AIDS
Project; Italian Ministry of Health; Istituto Superiore di
Sanita-Alliance Against Cancer; National Institutes of Health
[P01CA118210]
FX This work was supported in part by grants from the Istituto Superiore di
Sanita-National Institutes of Health Scientific Cooperation agreement
(to A.B.), the Italian AIDS Project (to A.B.), the Italian Ministry of
Health (Special Program in Oncology) (to A.B.), Istituto Superiore di
Sanita-Alliance Against Cancer Program 3 (to A.B.), and in part by
National Institutes of Health Grant P01CA118210 (to J.W.).
NR 42
TC 12
Z9 12
U1 1
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 FEB 15
PY 2011
VL 186
IS 4
BP 1951
EP 1962
DI 10.4049/jimmunol.1000918
PG 12
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700012
PM 21220691
ER
PT J
AU Dolan, BP
Li, L
Veltri, CA
Ireland, CM
Bennink, JR
Yewdell, JW
AF Dolan, Brian P.
Li, Lily
Veltri, Charles A.
Ireland, Chris M.
Bennink, Jack R.
Yewdell, Jonathan W.
TI Distinct Pathways Generate Peptides from Defective Ribosomal Products
for CD8(+) T Cell Immunosurveillance
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID I ANTIGEN PRESENTATION; PROTEIN-DEGRADATION; MAMMALIAN-CELLS; MAJOR
SOURCE; EEYARESTATIN; TRANSLATION; HYPOTHESIS; MOLECULES
AB To understand better the endogenous sources of MHC class I peptide ligands, we generated an antigenic reporter protein whose degradation is rapidly and reversibly controlled with Shield-1, a cell-permeant drug. Using this system, we demonstrate that defective ribosomal products (DRiPs) represent a major and highly efficient source of peptides and are completely resistant to our attempts to stabilize the protein. Although peptides also derive from nascent Shield-1-sensitive proteins and "retirees" created by Shield-1 withdrawal, these are much less efficient sources on a molar basis. We use this system to identify two drugs-each known to inhibit polyubiquitin chain disassembly-that selectively inhibit presentation of Shield-1-resistant DRiPs. These findings provide the initial evidence for distinct biochemical pathways for presentation of DRiPs versus retirees and implicate polyubiquitin chain disassembly or the actions of deubiquitylating enzymes as playing an important role in DRiP presentation. The Journal of Immunology, 2011, 186: 2065-2072.
C1 [Dolan, Brian P.; Li, Lily; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Veltri, Charles A.; Ireland, Chris M.] Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Room 2E13C-1,Bldg 33, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012
FU National Institute of Allergy and Infectious Diseases Division of
Intramural Research; National Institutes of Health [CA 36622]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases Division of Intramural Research and by National
Institutes of Health Grant CA 36622 (to C.M.I.).
NR 27
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U1 0
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 FEB 15
PY 2011
VL 186
IS 4
BP 2065
EP 2072
DI 10.4049/jimmunol.1003096
PG 8
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700024
PM 21228349
ER
PT J
AU Catalfamo, M
Wilhelm, C
Tcheung, L
Proschan, M
Friesen, T
Park, JH
Adelsberger, J
Baseler, M
Maldarelli, F
Davey, R
Roby, G
Rehm, C
Lane, C
AF Catalfamo, Marta
Wilhelm, Christopher
Tcheung, Lueng
Proschan, Michael
Friesen, Travis
Park, Jung-Hyun
Adelsberger, Joseph
Baseler, Michael
Maldarelli, Frank
Davey, Richard
Roby, Gregg
Rehm, Catherine
Lane, Clifford
TI CD4 and CD8 T Cell Immune Activation during Chronic HIV Infection: Roles
of Homeostasis, HIV, Type I IFN, and IL-7
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; PLASMACYTOID DENDRITIC CELLS; EXPRESSION;
INTERFERON; LYMPHOCYTES; RECEPTOR; TURNOVER; IMMUNODEFICIENCY;
PROLIFERATION; REPERTOIRE
AB Immune activation plays an important role in the pathogenesis of HIV disease. Although the causes are not fully understood, the forces that lead to immune dysfunction differ for CD4 and CD8 T cells. In this study, we report that the molecular pathways that drive immune activation during chronic HIV infection are influenced by differences in the homeostatic regulation of the CD4 and CD8 T cell pools. Proliferation of CD4 T cells is controlled more tightly by CD4 T cell numbers than is CD8 T cell proliferation. This difference reflects the importance of maintaining a polyclonal CD4 T cell pool in host surveillance. Both pools of T cells were found to be driven by viral load and its associated state of inflammation. In the setting of HIV-induced lymphopenia, naive CD4 T cells were recruited mainly into the proliferating pool in response to CD4 T cell depletion, whereas naive CD8 T cell proliferation was driven mainly by levels of HIV RNA. RNA analysis revealed increased expression of genes associated with type I IFN and common gamma chain cytokine signaling in CD4 T cell subsets and only type I IFN-associated genes in CD8 T cell subsets. In vitro studies demonstrated enhanced STAT1 phosphorylation in response to IFN-alpha and increased expression of the IFNAR1 transcripts in naive and memory CD4 T cells compared with that observed in CD8 T cells. CD4 T cell subsets also showed enhanced STAT1 phosphorylation in response to exogenous IL-7. The Journal of Immunology, 2011, 186: 2106-2116.
C1 [Catalfamo, Marta; Wilhelm, Christopher; Tcheung, Lueng; Friesen, Travis; Davey, Richard; Roby, Gregg; Rehm, Catherine; Lane, Clifford] NIAID, NIH, Clin & Mol Retrovirol Sect, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Proschan, Michael] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA.
[Park, Jung-Hyun] NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA.
[Adelsberger, Joseph; Baseler, Michael] Sci Applicat Int Corp, AIDS Monitoring Labs, Frederick, MD 21702 USA.
[Maldarelli, Frank] NCI, NIH, Host Virus Interact Branch, Bethesda, MD 20892 USA.
RP Catalfamo, M (reprint author), NIAID, NIH, Clin & Mol Retrovirol Sect, Immunoregulat Lab, Bldg 10,Room 11B01,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM catalfam@mail.nih.gov
RI Park, Jung Hyun /B-5712-2015
OI Park, Jung Hyun /0000-0002-9547-9055
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Science Applications International Corporation
(Frederick, MD); National Cancer Institute, National Institutes of
Health [N01-CO-12400]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health and Science Applications International Corporation
(Frederick, MD). This work was also supported in part by federal funds
from the National Cancer Institute, National Institutes of Health under
Contract N01-CO-12400.
NR 39
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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 FEB 15
PY 2011
VL 186
IS 4
BP 2106
EP 2116
DI 10.4049/jimmunol.1002000
PG 11
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700029
PM 21257970
ER
PT J
AU You, Y
Myers, RC
Freeberg, L
Foote, J
Kearney, JF
Justement, LB
Carter, RH
AF You, Yuying
Myers, Riley C.
Freeberg, Larry
Foote, Jeremy
Kearney, John F.
Justement, Louis B.
Carter, Robert H.
TI Marginal Zone B Cells Regulate Antigen Capture by Marginal Zone
Macrophages
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID STREPTOCOCCUS-PNEUMONIAE; MONOCLONAL-ANTIBODY; SCAVENGER RECEPTORS;
DENDRITIC CELLS; MOUSE SPLEEN; B1B CELLS; IN-VIVO; MICE; RESPONSES;
MARCO
AB The marginal zone (MZ) of the mouse spleen contains macrophages that express receptors that trap pathogens, including the scavenger receptor macrophage receptor with a collagenous structure and the C-type lectin specific intracellular adhesion molecule-grabbing nonintegrin receptor 1 (SIGN-R1). We previously reported that expression of SIGN-R1 was decreased in CD19-deficient mice. In this study, we demonstrate that SIGN-R1 is expressed on a subset of macrophage receptor with a collagenous structure (MARCO)(+) macrophages. This subset is diminished when MZ B cells are absent due to either genetic developmental defects or following transient migration of B cells out of the MZ. When B cells return to the MZ, there is a delay in recovery of SIGN-R1-expressing macrophages. During this period, capture of Ficoll, which for the macrophages requires SIGN-R1, remains defective not only by the macrophages, but also by the B cells. Thus, MZ B cells regulate expression of molecules on macrophages that are important for trapping Ag, which, in turn, is required for Ag capture by the B cells. The Journal of Immunology, 2011, 186: 2172-2181.
C1 [Carter, Robert H.] NIAMSD, Bethesda, MD 20892 USA.
[You, Yuying; Myers, Riley C.; Freeberg, Larry; Foote, Jeremy; Kearney, John F.; Justement, Louis B.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
RP Carter, RH (reprint author), NIAMSD, Bldg 31,Room 4C32,31 Ctr Dr,MSC 2350, Bethesda, MD 20892 USA.
EM carterrob@mail.nih.gov
OI Justement, Louis/0000-0001-7058-867X
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
National Institutes of Health [R01 AI 46225, R01 AI 14782]
FX This work was supported in part by the National Institute of Arthritis
and Musculoskeletal and Skin Diseases and National Institutes of Health
Grants R01 AI 46225 (to L.B.J.) and R01 AI 14782 (to J.F.K.).
NR 33
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U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2011
VL 186
IS 4
BP 2172
EP 2181
DI 10.4049/jimmunol.1002106
PG 10
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700036
PM 21257969
ER
PT J
AU Pene, F
Paun, A
Sonder, SU
Rikhi, N
Wang, HS
Claudio, E
Siebenlist, U
AF Pene, Frederic
Paun, Andrea
Sonder, Soren Ulrik
Rikhi, Nimisha
Wang, Hongshan
Claudio, Estefania
Siebenlist, Ulrich
TI The I kappa B Family Member Bcl-3 Coordinates the Pulmonary Defense
against Klebsiella pneumoniae Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ONCOPROTEIN BCL-3; CELL MALIGNANCIES;
UP-REGULATION; CUTTING EDGE; MURINE MODEL; CYCLIN D1; T-CELLS; ROLES;
TRANSCRIPTION
AB Bcl-3 is an atypical member of the I kappa B family that has the potential to positively or negatively modulate nuclear NF-kappa B activity in a context-dependent manner. Bcl-3's biologic impact is complex and includes roles in tumorigenesis and diverse immune responses, including innate immunity. Bcl-3 may mediate LPS tolerance, suppressing cytokine production, but it also seems to contribute to defense against select systemic bacterial challenges. However, the potential role of Bcl-3 in organ-specific host defense against bacteria has not been addressed. In this study, we investigated the relevance of Bcl-3 in a lung challenge with the Gram-negative pathogen Klebsiella pneumoniae. In contrast to wild-type mice, Bcl-3-deficient mice exhibited significantly increased susceptibility toward K. pneumoniae pneumonia. The mutant mice showed increased lung damage marked by neutrophilic alveolar consolidation, and they failed to clear bacteria in lungs, which correlated with increased bacteremic dissemination. Loss of Bcl-3 incurred a dramatic cytokine imbalance in the lungs, which was characterized by higher levels of IL-10 and a near total absence of IFN-gamma. Moreover, Bcl-3-deficient mice displayed increased lung production of the neutrophil-attracting chemokines CXCL-1 and CXCL-2. Alveolar macrophages and neutrophils are important to antibacterial lung defense. In vitro stimulation of Bcl-3-deficient alveolar macrophages with LPS or heat-killed K. pneumoniae recapitulated the increase in IL-10 production, and Bcl-3-deficient neutrophils were impaired in intracellular bacterial killing. These findings suggest that Bcl-3 is critically involved in lung defense against Gram-negative bacteria, modulating functions of several cells to facilitate efficient clearance of bacteria. The Journal of Immunology, 2011, 186: 2412-2421.
C1 [Pene, Frederic; Paun, Andrea; Sonder, Soren Ulrik; Rikhi, Nimisha; Wang, Hongshan; Claudio, Estefania; Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Siebenlist, U (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B15A, Bethesda, MD 20892 USA.
EM usiebenlist@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 34
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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 FEB 15
PY 2011
VL 186
IS 4
BP 2412
EP 2421
DI 10.4049/jimmunol.1001331
PG 10
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700061
PM 21228348
ER
PT J
AU Jelinek, I
Leonard, JN
Price, GE
Brown, KN
Meyer-Manlapat, A
Goldsmith, PK
Wang, Y
Venzon, D
Epstein, SL
Segal, DM
AF Jelinek, Ivett
Leonard, Joshua N.
Price, Graeme E.
Brown, Kevin N.
Meyer-Manlapat, Anna
Goldsmith, Paul K.
Wang, Yan
Venzon, David
Epstein, Suzanne L.
Segal, David M.
TI TLR3-Specific Double-Stranded RNA Oligonucleotide Adjuvants Induce
Dendritic Cell Cross-Presentation, CTL Responses, and Antiviral
Protection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTOR-3; BONE-MARROW CULTURES; ANTIGEN PRESENTATION; INNATE
IMMUNITY; IN-VIVO; ADAPTIVE IMMUNITY; CUTTING EDGE; RECOGNITION;
ACTIVATION; CD8(+)
AB Maturation of dendritic cells (DC) to competent APC is essential for the generation of acquired immunity and is a major function of adjuvants. dsRNA, a molecular signature of viral infection, drives DC maturation by activating TLR3, but the size of dsRNA required to activate DC and the expression patterns of TLR3 protein in DC subsets have not been established. In this article, we show that cross-priming CD8 alpha(+) and CD103(+) DC subsets express much greater levels of TLR3 than other DC. In resting DC, TLR3 is located in early endosomes and other intracellular compartments but migrates to LAMP1(+) endosomes on stimulation with a TLR3 ligand. Using homogeneous dsRNA oligonucleotides (ONs) ranging in length from 25 to 540 bp, we observed that a minimum length of similar to 90 bp was sufficient to induce CD86, IL-12p40, IFN-beta, TNF-alpha, and IL-6 expression, and to mature DC into APC that cross-presented exogenous Ags to CD8(+) T cells. TLR3 was essential for activation of DC by dsRNA ONs, and the potency of activation increased with dsRNA length and varied between DC subsets. In vivo, dsRNA ONs, in a size-dependent manner, served as adjuvants for the generation of Ag-specific CTL and for inducing protection against lethal challenge with influenza virus when given with influenza nucleoprotein as an immunogen. These results provide the basis for the development of TLR3-specific adjuvants capable of inducing immune responses tailored for viral pathogens. The Journal of Immunology, 2011, 186: 2422-2429.
C1 [Jelinek, Ivett; Leonard, Joshua N.; Brown, Kevin N.; Meyer-Manlapat, Anna; Wang, Yan; Segal, David M.] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Price, Graeme E.; Epstein, Suzanne L.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Goldsmith, Paul K.] NCI, Antibody & Prot Purificat Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Segal, DM (reprint author), NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bldg 10,Room 4B36,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dave_segal@nih.gov
RI Leonard, Joshua/B-7649-2009
FU National Cancer Institute; National Institute of Allergy and Infectious
Diseases
FX This work was supported by the Intramural Research Program of the
National Cancer Institute and by a National Institutes of Health/Food
and Drug Administration Intramural Biodefense Award from the National
Institute of Allergy and Infectious Diseases.
NR 64
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U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2011
VL 186
IS 4
BP 2422
EP 2429
DI 10.4049/jimmunol.1002845
PG 8
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700062
PM 21242525
ER
PT J
AU Fan, JS
Ishmael, FT
Fang, X
Myers, A
Cheadle, C
Huang, SK
Atasoy, U
Gorospe, M
Stellato, C
AF Fan, Jinshui
Ishmael, Faoud T.
Fang, Xi
Myers, Allen
Cheadle, Chris
Huang, Shau-Ku
Atasoy, Ulus
Gorospe, Myriam
Stellato, Cristiana
TI Chemokine Transcripts as Targets of the RNA-Binding Protein HuR in Human
Airway Epithelium
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID AU-RICH ELEMENT; NF-KAPPA-B; KINASE-REGULATED PHOSPHORYLATION; MAMMALIAN
STRESS GRANULES; STABILIZING FACTOR HUR; NITRIC-OXIDE SYNTHASE;
TUMOR-NECROSIS-FACTOR; FACTOR MESSENGER-RNA; T-CELL-ACTIVATION;
ELAV-LIKE PROTEIN
AB HuR is a regulator of mRNA turnover or translation of inflammatory genes through binding to adenylate-uridylate-rich elements and related motifs present in the 3`untranslated region (UTR) of mRNAs. We postulate that HuR critically regulates the epithelial response by associating with multiple ARE-bearing, functionally related inflammatory transcripts. We aimed to identify HuR targets in the human airway epithelial cell line BEAS-2B challenged with TNF-alpha plus IFN-gamma, a strong stimulus for inflammatory epithelial responses. Ribonucleoprotein complexes from resting and cytokine-treated cells were immunoprecipitated using anti-HuR and isotype-control Ab, and eluted mRNAs were reverse-transcribed and hybridized to an inflammatory-focused gene array. The chemokines CCL2, CCL8, CXCL1, and CXCL2 ranked highest among 27 signaling and inflammatory genes significantly enriched in the HuR RNP-IP from stimulated cells over the control immunoprecipitation. Among these, 20 displayed published HuR binding motifs. Association of HuR with the four endogenous chemokine mRNAs was validated by single-gene ribonucleoprotein-immunoprecipitation and shown to be 3`UTR-dependent by biotin pull-down assay. Cytokine treatment increased mRNA stability only for CCL2 and CCL8, and transient silencing and overexpression of HuR affected only CCL2 and CCL8 expression in primary and transformed epithelial cells. Cytokine-induced CCL2 mRNA was predominantly cytoplasmic. Conversely, CXCL1 mRNA remained mostly nuclear and unaffected, as CXCL2, by changes in HuR levels. Increase in cytoplasmic HuR and HuR target expression partially relied on the inhibition of AMP-dependent kinase, a negative regulator of HuR nucleocytoplasmic shuttling. HuR-mediated regulation in airway epithelium appears broader than previously appreciated, coordinating numerous inflammatory genes through multiple posttranscriptional mechanisms. The Journal of Immunology, 2011, 186: 2482-2494.
C1 [Fan, Jinshui; Fang, Xi; Myers, Allen; Cheadle, Chris; Huang, Shau-Ku; Stellato, Cristiana] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Baltimore, MD 21224 USA.
[Ishmael, Faoud T.] Penn State Univ, Coll Med, Dept Med, Hershey, PA 17033 USA.
[Ishmael, Faoud T.] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA.
[Atasoy, Ulus] Univ Missouri, Dept Surg, Columbia, MO 65211 USA.
[Atasoy, Ulus] Univ Missouri, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA.
[Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA.
RP Stellato, C (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle,Room 1A 12A, Baltimore, MD 21224 USA.
EM stellato@jhmi.edu
RI Stellato, Cristiana/P-3001-2015
OI Stellato, Cristiana/0000-0002-1294-8355
FU National Institutes of Health [R01 AI060990-01A1]; American Academy of
Allergy, Asthma and Immunology; National Institute on Aging, National
Institutes of Health
FX This work was supported by National Institutes of Health Grant R01
AI060990-01A1 and by the American Academy of Allergy, Asthma and
Immunology/Aventis Women Physician in Allergy Junior Faculty Development
Award (to C.S.). M.G. is supported by the National Institute on
Aging-Intramural Research Program, National Institutes of Health.
NR 99
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U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2011
VL 186
IS 4
BP 2482
EP 2494
DI 10.4049/jimmunol.0903634
PG 13
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700068
PM 21220697
ER
PT J
AU Garcia, F
Climent, N
Assoumou, L
Gil, C
Gonzalez, N
Alcami, J
Leon, A
Romeu, J
Dalmau, J
Martinez-Picado, J
Lifson, J
Autran, B
Costagliola, D
Clotet, B
Gatell, JM
Plana, M
Gallart, T
AF Garcia, Felipe
Climent, Nuria
Assoumou, Lambert
Gil, Cristina
Gonzalez, Nuria
Alcami, Jose
Leon, Agathe
Romeu, Joan
Dalmau, Judith
Martinez-Picado, Javier
Lifson, Jeff
Autran, Brigitte
Costagliola, Dominique
Clotet, Bonaventura
Gatell, Josep M.
Plana, Montserrat
Gallart, Teresa
CA DCV2 MANON07 AIDS Vaccine Res Obje
TI A Therapeutic Dendritic Cell-Based Vaccine for HIV-1 Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNIZATION; RESPONSES; TRIAL
AB A double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cells (MD-DCs) pulsed with heat inactivated autologous HIV-1 was performed. Therapeutic vaccinations were feasible, safe, and well tolerated. At week 24 after first vaccination (primary end point), a modest significant decrease in plasma viral load was observed in vaccine recipients, compared with control subjects (P = .03). In addition, the change in plasma viral load after vaccination tended to be inversely associated with the increase in HIV-specific T cell responses in vaccinated patients but tended to be directly correlated with HIV-specific T cell responses in control subjects.
C1 [Garcia, Felipe; Climent, Nuria; Gil, Cristina; Leon, Agathe; Gatell, Josep M.; Gallart, Teresa] Univ Barcelona, Hosp Clin Barcelona, HIV Dev Program Catalonia, Infect Dis Dept,Inst Invest Biomed August Pi & Su, E-08036 Barcelona, Spain.
[Martinez-Picado, Javier] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain.
[Gonzalez, Nuria; Alcami, Jose] Inst Salud Carlos III, AIDS Immunopathogenesis Unit, Ctr Nacl Microbiol, Madrid, Spain.
[Romeu, Joan; Clotet, Bonaventura] Hosp Badalona Germans Trias & Pujol, Lluita SIDA Fdn, Badalona, Spain.
[Dalmau, Judith; Martinez-Picado, Javier; Clotet, Bonaventura] IrsiCaixa Fdn, HIV Dev Program Catalonia, Badalona, Spain.
[Assoumou, Lambert; Costagliola, Dominique] INSERM, U943, Paris, France.
[Assoumou, Lambert; Costagliola, Dominique] Univ Paris 06, Unite Mixte Rech Sante 943, Hop La Pitie Salpetriere, Paris, France.
[Autran, Brigitte] Univ Paris 06, Unite Mixte Rech Sante 945, Hop La Pitie Salpetriere, INSERM, Paris, France.
[Lifson, Jeff] Sci Applicat Int Corp, AIDS & Canc Virus Program, Frederick, MD USA.
[Plana, Montserrat] NCI, Frederick, MD 21701 USA.
RP Garcia, F (reprint author), Univ Barcelona, Hosp Clin Barcelona, HIV Dev Program Catalonia, Infect Dis Dept,Inst Invest Biomed August Pi & Su, Villarroel 170, E-08036 Barcelona, Spain.
EM fgarcia@clinic.ub.es
RI Martinez-Picado, Javier/G-5507-2012; Costagliola, Dominique/H-5849-2011;
Dalmau, Judith/I-7065-2016; Garcia, Felipe/F-4242-2014
OI Martinez-Picado, Javier/0000-0002-4916-2129; Costagliola,
Dominique/0000-0003-0765-0869; Dalmau, Judith/0000-0001-7513-3711;
Garcia, Felipe/0000-0001-7658-5832
FU Mutua Madrilena del Automovil, STREP (UE) Life sciences [FIS PS09/01297,
FIPSE 36750/08, SAF2008-04395, SAF 05/05566, FIPSE 36536/05, FIS 040503,
FIS 070291, FIS 03/0072]; IDIBAPS, Barcelona, Spain; Fundacio Privada
Clinic per a la Recerca Biomedica in collaboration with the Spanish
Health Department [FIS 03/0072]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; Spanish Ministry of Health;
Abbott Laboratories; Boehringer Ingelheim; Bristol Myers Squibb;
GlaxoSmithKline; Merck Sharp; Dohme; Roche
FX This study was partially supported by grants: FIS PS09/01297, FIPSE
36750/08, SAF2008-04395, SAF 05/05566, FIPSE 36536/05, FIS 040503, FIS
070291, contract FIS 03/0072, Mutua Madrilena del Automovil, STREP (UE)
Life sciences, genomics and biotechnology for health LSH2005_2.3.0.10,
PROFIT (FIT 090100-2005-9), MARATO TV3, RIS**, ORVACS***.; Dr Felipe
Garcia was recipient of a Research Grant from IDIBAPS****, Barcelona,
Spain.; Dr. M. Plana was supported by contract FIS 03/0072 from the
Fundacio Privada Clinic per a la Recerca Biomedica in collaboration with
the Spanish Health Department; Dr. Lifson is supported with federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E.; *FIPSE is a non-profit Foundation
including: Spanish Ministry of Health, Abbott Laboratories, Boehringer
Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp and Dohme
and Roche).; **Red Tematica Cooperativa de Grupos de Investigacion en
Sida del Fondo de Investigacion Sanitaria (FIS).; ***ORVACS: Objectif
recherche vaccin sida.; ****IDIBAPS: Institut d'Investigacions
Biomadiques August Pi I Sunyer The authors do not have a commercial or
other association that might pose a conflict of interest.
NR 18
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U1 0
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 15
PY 2011
VL 203
IS 4
BP 473
EP 478
DI 10.1093/infdis/jiq077
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 709VE
UT WOS:000286468700006
PM 21233310
ER
PT J
AU Benninger, DH
Berman, BD
Houdayer, E
Pal, N
Luckenbaugh, DA
Schneider, L
Miranda, S
Hallett, M
AF Benninger, D. H.
Berman, B. D.
Houdayer, E.
Pal, N.
Luckenbaugh, D. A.
Schneider, L.
Miranda, S.
Hallett, M.
TI Intermittent theta-burst transcranial magnetic stimulation for treatment
of Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID HUMAN MOTOR CORTEX; LEVODOPA-INDUCED DYSKINESIAS; CORTICAL EXCITABILITY;
PREFRONTAL CORTEX; DOPAMINE RELEASE; PERFORMANCE; PLASTICITY; STROKE;
RTMS
AB Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD).
Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS.
Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures.
Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation.
Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD.
Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD. Neurology (R) 2011; 76: 601-609
C1 [Benninger, D. H.] Univ Basel Hosp, Dept Neurol, CH-4051 Basel, Switzerland.
[Benninger, D. H.; Berman, B. D.; Houdayer, E.; Pal, N.; Schneider, L.; Miranda, S.; Hallett, M.] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA.
[Luckenbaugh, D. A.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Benninger, DH (reprint author), Univ Basel Hosp, Dept Neurol, Petersgraben 4, CH-4051 Basel, Switzerland.
EM benningerd@uhbs.ch
RI Benninger, David/A-8157-2015
OI Benninger, David/0000-0002-1049-9533
FU NIH/NINDS; NIH/NIMH; Fyssen Foundation; Neurotoxin Institute; Ariston
Pharmaceuticals; US Department of Defense (Army); NIH (from Brainsway)
FX Supported by the Intramural Research Program of the NIH/NINDS.; Dr.
Benninger receives research support through the Intramural Research
Program of the NIH/NINDS. Dr. Berman receives research support through
the Intramural Program of the NIH/NIMH. Dr. Houdayer receives research
support from the Fyssen Foundation. Ms. Pal reports no disclosures. Dr.
Luckenbaugh serves as Statistical Consultant for Bipolar Disorders; and
receives research support through the Intramural Program of the
NIH/NIMH. Mr. Schneider and Prof. Miranda report no disclosures. Dr.
Hallett serves as Chair of the Medical Advisory Board for and receives
funding for travel from the Neurotoxin Institute; serves as Chair of the
Medical Advisory Board of the Benign Essential Blepharospasm Foundation;
serves on editorial advisory boards for Clinical Neurophysiology
(Editor-in-Chief), Western Hemisphere, Brain, Acta Neurologica
Scandinavica, Journal of Clinical Neurophysiology, Italian Journal of
Neurological Sciences, Medical Problems of Performing Artists, Annals of
Neurology, Neurology and Clinical Neurophysiology, The Cerebellum,
NeuroRx, Current Trends in Neurology, Faculty of 1000 Biology, European
Neurology, Faculty of 1000 Medicine, Brain Stimulation, Journal of
Movement Disorders (Korea), and World Neurology; may accrue revenue on
patents re: Immunotoxin (MAB-Ricin) for the treatment of focal movement
disorders and Coil for Magnetic Stimulation and methods for using the
same; receives royalties from publishing from Blackwell Publisher,
Cambridge University Press, Springer Verlag, Taylor & Francis Group,
Oxford University Press, John Wiley & Sons, and Elsevier; receives
research support from Ariston Pharmaceuticals, NIH/NINDS (Intramural
Program) and the US Department of Defense (Army); has received license
fee payments from the NIH (from Brainsway) for licensing the patent for
the H-coil; and with his spouse held stock in Agilent Technologies,
Amgen, Amylin Pharmaceuticals, Merck & Co., Monsanto Co New Del,
sanofi-aventis, Coventry Health Care Inc., Sigma Aldrich Corp., Warner
Chilcott Ltd., Pfizer Inc, Genentech, Inc., United Health Group, St.
Jude Medical, and Eli Lilly and Company.
NR 31
TC 43
Z9 52
U1 2
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD FEB 15
PY 2011
VL 76
IS 7
BP 601
EP 609
DI 10.1212/WNL.0b013e31820ce6bb
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 721OH
UT WOS:000287363800006
PM 21321333
ER
PT J
AU MacNeil, LK
Xavier, P
Garvey, MA
Gilbert, DL
Ranta, ME
Denckla, MB
Mostofsky, SH
AF MacNeil, L. K.
Xavier, P.
Garvey, M. A.
Gilbert, D. L.
Ranta, M. E.
Denckla, M. B.
Mostofsky, S. H.
TI Quantifying excessive mirror overflow in children with
attention-deficit/hyperactivity disorder
SO NEUROLOGY
LA English
DT Article
ID MOTOR OVERFLOW; BEHAVIORAL-INHIBITION; RESPONSE-INHIBITION;
FINGER-MOVEMENTS; SUBTLE SIGNS; ADHD; BOYS; AGE; DEFICIT; ADULTS
AB Objectives: Qualitative observations have revealed that children with attention-deficit/hyperactivity disorder (ADHD) show increased overflow movements, a motor sign thought to reflect impaired inhibitory control. The goal of this study was to develop and implement methods for quantifying excessive mirror overflow movements in children with ADHD.
Methods: Fifty right-handed children aged 8.2-13.3 years, 25 with ADHD (12 girls) and 25 typically developing (TD) control children (10 girls), performed a sequential finger-tapping task, completing both left-handed (LHFS) and right-handed finger sequencing (RHFS). Phasic overflow of the index and ring fingers was assessed in 34 children with video recording, and total overflow in 48 children was measured by calculating the total angular displacement of the index and ring fingers with electrogoniometer recordings.
Results: Phasic overflow and total overflow across both hands were greater in children with ADHD than in TD children, particularly during LHFS. Separate gender analyses revealed that boys, but not girls, with ADHD showed significantly more total phasic overflow and total overflow than did their gender-matched control children.
Conclusions: The quantitative overflow measures used in this study support past qualitative findings that motor overflow persists to a greater degree in children with ADHD than in age-matched TD peers. The quantitative findings further suggest that persistence of mirror overflow is more prominent during task execution of the nondominant hand and reveal gender-based differences in developmental neural systems critical to motor control. These quantitative measures will assist future physiologic investigation of the brain basis of motor control in ADHD. Neurology (R) 2011; 76: 622-628
C1 [Mostofsky, S. H.] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Lab Neurocognit & Imaging Res,Ctr Autism & Relate, Baltimore, MD 21205 USA.
[Garvey, M. A.] NIMH, Div Dev Translat Res, NIH, Bethesda, MD 20892 USA.
[Gilbert, D. L.] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH USA.
Univ Cincinnati, Sch Med, Cincinnati, OH USA.
[Denckla, M. B.; Mostofsky, S. H.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Denckla, M. B.; Mostofsky, S. H.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Denckla, M. B.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
RP Mostofsky, SH (reprint author), Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Lab Neurocognit & Imaging Res,Ctr Autism & Relate, 716 N Broadway, Baltimore, MD 21205 USA.
EM mostofsky@kennedykrieger.org
RI Gilbert, Donald/D-6443-2016
OI Gilbert, Donald/0000-0002-9245-6878
FU NIH [R01 MH078160, R01 MH085328, NIMH R01 MH078160, NIMH R01 MH08185,
NINDS NS056276, NINDS R01 NS043480-05, NIMH R01 MH085328, NINDS R01
NS048527, NICHD P50 HD052121]; Johns Hopkins University School of
Medicine Institute for Clinical and Translational Research (NIH/National
Center for Research Resources) [UL1 RR025005]; Cincinnati Children's
Hospital Research Foundation; University of Cincinnati; Tourette
Syndrome Association
FX Supported in part by NIH grants R01 MH078160 and R01 MH085328 and the
Johns Hopkins University School of Medicine Institute for Clinical and
Translational Research (NIH/National Center for Research Resources
Clinical and Translational Science Award program, UL1 RR025005). The
views expressed in this article do not necessarily represent the views
of the NIH.; L. K. MacNeil, P. Xavier, and Dr. Garvey report no
disclosures. Dr. Gilbert has received honoraria from the Tourette
Syndrome Association/Centers for Disease Control and Prevention, the
Movement Disorder Society, the American Academy of Neurology, and the
American Academy of Pediatrics; serves on the medical advisory board for
the Tourette Syndrome Association; writes board review questions for
PREP SA (American Academy of Pediatrics); and has received research
support from the NIH (NIMH R01 MH078160 [coinvestigator], NIMH R01
MH08185 [coinvestigator], and NINDS NS056276 [coinvestigator]), the
Cincinnati Children's Hospital Research Foundation, the University of
Cincinnati, and the Tourette Syndrome Association. M. E. Ranta reports
no disclosures. Dr. Denckla receives royalties from the publication of
Rapid Automatized Naming & Rapid Alternating Stimulus Tests RAN/RAS (Pro
Education, 2005) and has received research support from the NIH (NINDS
R01 NS043480-05 [PI] and NIMH R01 MH078160 [coinvestigator]). Dr.
Mostofsky has served on a scientific advisory for Bristol-Myers Squibb;
serves on the editorial board of Neurocase; and receives research
support from the NIH (NIMH R01 MH085328 [PI], NINDS R01 NS048527 [PI],
NIMH R01 MH078160 [PI], and NICHD P50 HD052121 [coinvestigator]) and
Autism Speaks.
NR 30
TC 27
Z9 27
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD FEB 15
PY 2011
VL 76
IS 7
BP 622
EP 628
DI 10.1212/WNL.0b013e31820c3052
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 721OH
UT WOS:000287363800009
PM 21321336
ER
PT J
AU Bengali, Z
Satheshkumar, PS
Yang, ZL
Weisberg, AS
Paran, N
Moss, B
AF Bengali, Zain
Satheshkumar, P. S.
Yang, Zhilong
Weisberg, Andrea S.
Paran, Nir
Moss, Bernard
TI Drosophila S2 Cells Are Non-Permissive for Vaccinia Virus DNA
Replication Following Entry via Low pH-Dependent Endocytosis and Early
Transcription
SO PLOS ONE
LA English
DT Article
ID INTRACELLULAR MATURE VIRION; SURFACE HEPARAN-SULFATE; MEMBRANE-PROTEIN;
GENE-EXPRESSION; ESSENTIAL COMPONENT; INTERMEDIATE STAGE; FUSION
COMPLEX; A27L PROTEIN; HOST-CELLS; L1 PROTEIN
AB Vaccinia virus (VACV), a member of the chordopox subfamily of the Poxviridae, abortively infects insect cells. We have investigated VACV infection of Drosophila S2 cells, which are useful for protein expression and genome-wide RNAi screening. Biochemical and electron microscopic analyses indicated that VACV entry into Drosophila S2 cells depended on the VACV multiprotein entry-fusion complex but appeared to occur exclusively by a low pH-dependent endocytic mechanism, in contrast to both neutral and low pH entry pathways used in mammalian cells. Deep RNA sequencing revealed that the entire VACV early transcriptome, comprising 118 open reading frames, was robustly expressed but neither intermediate nor late mRNAs were made. Nor was viral late protein synthesis or inhibition of host protein synthesis detected by pulse-labeling with radioactive amino acids. Some reduction in viral early proteins was noted by Western blotting. Nevertheless, synthesis of the multitude of early proteins needed for intermediate gene expression was demonstrated by transfection of a plasmid containing a reporter gene regulated by an intermediate promoter. In addition, expression of a reporter gene with a late promoter was achieved by cotransfection of intermediate genes encoding the late transcription factors. The requirement for transfection of DNA templates for intermediate and late gene expression indicated a defect in viral genome replication in VACV-infected S2 cells, which was confirmed by direct analysis. Furthermore, VACV-infected S2 cells did not support the replication of a transfected plasmid, which occurs in mammalian cells and is dependent on all known viral replication proteins, indicating a primary restriction of DNA synthesis.
C1 [Bengali, Zain; Satheshkumar, P. S.; Yang, Zhilong; Weisberg, Andrea S.; Paran, Nir; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Bengali, Z (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
RI Yang, Zhilong/E-8967-2010
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX The work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 59
TC 14
Z9 14
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 15
PY 2011
VL 6
IS 2
AR e17248
DI 10.1371/journal.pone.0017248
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721QH
UT WOS:000287369200030
PM 21347205
ER
PT J
AU Balagopalan, L
Ashwell, BA
Bernot, KM
Akpan, IO
Quasba, N
Barr, VA
Samelson, LE
AF Balagopalan, Lakshmi
Ashwell, Benjamin A.
Bernot, Kelsie M.
Akpan, Itoro O.
Quasba, Naeha
Barr, Valarie A.
Samelson, Lawrence E.
TI Enhanced T-cell signaling in cells bearing linker for activation of
T-cell (LAT) molecules resistant to ubiquitylation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE endocytosis; protein degradation; ubiquitin
ID RECEPTOR MICROCLUSTERS; ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION;
IMMUNOLOGICAL SYNAPSE; INTERNALIZATION; UBIQUITINATION; DEGRADATION;
RECRUITMENT; CANCER; TRAFFICKING
AB Linker for activation of T cells (LAT) plays a central role in T-cell activation by nucleating signaling complexes that are critical for the propagation of T-cell signals from the plasma membrane to the cellular interior. The role of phosphorylation and palmitoylation in LAT function has been well studied, but not much is known about other strategies by which the cell modulates LAT activity. We have focused on LAT ubiquitylation and have mapped the sites on which LAT is ubiquitylated. To elucidate the biological role of this process, we substituted LAT lysines with arginines. This resulted in a dramatic decrease in overall LAT ubiquitylation. Ubiquitylation-resistant mutants of LAT were internalized at rates comparable to wild-type LAT in a mechanism that required Cbl family proteins. However, these mutants displayed a defect in protein turnover rates. T-cell signaling was elevated in cells reconstituted with LAT mutants resistant to ubiquitylation, indicating that inhibition of LAT ubiquitylation enhances T-cell potency. These results support LAT ubiquitylation as a molecular checkpoint for attenuation of T-cell signaling.
C1 [Balagopalan, Lakshmi; Ashwell, Benjamin A.; Bernot, Kelsie M.; Akpan, Itoro O.; Quasba, Naeha; Barr, Valarie A.; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM samelson@helix.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank D. Bohmann for the HA-ubiquitin construct, B. Taylor for cell
sorting, C. Regan and J. Pinski for technical help, and A. Weissman, S.
Lipkowitz, and R. Kortum for critically reading the manuscript. This
research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 39
TC 27
Z9 28
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 15
PY 2011
VL 108
IS 7
BP 2885
EP 2890
DI 10.1073/pnas.1007098108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721TB
UT WOS:000287377000050
PM 21282648
ER
PT J
AU Ross, JM
Coppotelli, G
Olson, L
AF Ross, Jaime M.
Coppotelli, Giuseppe
Olson, Lars
TI Reply to Quistorff and Grunnet: Dysfunctional mitochondria, brain
lactate, and lactate dehydrogenase isoforms
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
C1 [Ross, Jaime M.; Olson, Lars] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden.
[Ross, Jaime M.] NIDA, NIH, Baltimore, MD 21224 USA.
[Coppotelli, Giuseppe] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
RP Ross, JM (reprint author), Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden.
EM rossja@nida.nih.gov; Lars.Olson@ki.se
RI Ross, Jaime/A-6893-2012
NR 5
TC 1
Z9 1
U1 1
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 15
PY 2011
VL 108
IS 7
BP E22
EP E22
DI 10.1073/pnas.1018791108
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721TB
UT WOS:000287377000003
ER
PT J
AU Joubert, BR
Reif, DM
Edwards, SW
Leiner, KA
Hudgens, EE
Egeghy, P
Gallagher, JE
Hubal, EC
AF Joubert, Bonnie R.
Reif, David M.
Edwards, Stephen W.
Leiner, Kevin A.
Hudgens, Edward E.
Egeghy, Peter
Gallagher, Jane E.
Hubal, Elaine Cohen
TI Evaluation of genetic susceptibility to childhood allergy and asthma in
an African American urban population
SO BMC MEDICAL GENETICS
LA English
DT Article
ID EPSILON-RI-BETA; ETHNICALLY DIVERSE POPULATIONS; CORONARY-HEART-DISEASE;
SERUM IGE LEVELS; ADAM33 GENE; BRONCHIAL HYPERRESPONSIVENESS; HAPLOTYPE
RECONSTRUCTION; PROMOTER POLYMORPHISM; INDIAN POPULATION; LINKAGE
ANALYSES
AB Background: Asthma and allergy represent complex phenotypes, which disproportionately burden ethnic minorities in the United States. Strong evidence for genomic factors predisposing subjects to asthma/allergy is available. However, methods to utilize this information to identify high risk groups are variable and replication of genetic associations in African Americans is warranted.
Methods: We evaluated 41 single nucleotide polymorphisms (SNP) and a deletion corresponding to 11 genes demonstrating association with asthma in the literature, for association with asthma, atopy, testing positive for food allergens, eosinophilia, and total serum IgE among 141 African American children living in Detroit, Michigan. Independent SNP and haplotype associations were investigated for association with each trait, and subsequently assessed in concert using a genetic risk score (GRS).
Results: Statistically significant associations with asthma were observed for SNPs in GSTM1, MS4A2, and GSTP1 genes, after correction for multiple testing. Chromosome 11 haplotype CTACGAGGCC (corresponding to MS4A2 rs574700, rs1441586, rs556917, rs502581, rs502419 and GSTP1 rs6591256, rs17593068, rs1695, rs1871042, rs947895) was associated with a nearly five-fold increase in the odds of asthma (Odds Ratio (OR) = 4.8, p = 0.007). The GRS was significantly associated with a higher odds of asthma (OR = 1.61, 95% Confidence Interval = 1.21, 2.13; p = 0.001).
Conclusions: Variation in genes associated with asthma in predominantly non-African ethnic groups contributed to increased odds of asthma in this African American study population. Evaluating all significant variants in concert helped to identify the highest risk subset of this group.
C1 [Joubert, Bonnie R.; Egeghy, Peter] US EPA, Natl Exposure Res Lab, Durham, NC USA.
[Reif, David M.; Hubal, Elaine Cohen] US EPA, Natl Ctr Computat Toxicol, Durham, NC USA.
[Edwards, Stephen W.; Hudgens, Edward E.; Gallagher, Jane E.] US EPA, Natl Hlth & Environm Effects Res Lab, Durham, NC USA.
[Leiner, Kevin A.] Integrated Syst Lab, Res Triangle Pk, NC USA.
[Joubert, Bonnie R.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Joubert, BR (reprint author), US EPA, Natl Exposure Res Lab, Durham, NC USA.
EM brjoubert@gmail.com
OI Reif, David/0000-0001-7815-6767
NR 73
TC 9
Z9 9
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD FEB 14
PY 2011
VL 12
DI 10.1186/1471-2350-12-25
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 730KP
UT WOS:000288032500002
PM 21320344
ER
PT J
AU Martiniova, L
Lu, J
Chiang, J
Bernardo, M
Lonser, R
Zhuang, ZP
Pacak, K
AF Martiniova, Lucia
Lu, Jie
Chiang, Jeffrey
Bernardo, Marcelino
Lonser, Russell
Zhuang, Zhengping
Pacak, Karel
TI Pharmacologic Modulation of Serine/Threonine Phosphorylation Highly
Sensitizes PHEO in a MPC Cell and Mouse Model to Conventional
Chemotherapy
SO PLOS ONE
LA English
DT Article
ID POLO-LIKE KINASE-1; DNA-DAMAGE; CANCER-CHEMOTHERAPY; PHEOCHROMOCYTOMA;
INHIBITION; CYCLE; PARAGANGLIOMA; TEMOZOLOMIDE; DACARBAZINE;
CYCLOPHOSPHAMIDE
AB Background: The failure of cytotoxic cancer regimens to cure the most drug-resistant, well-differentiated solid tumors has attributed to the heterogeneity of cell types that differ in their capacities for growth, differentiation, and metastases. We investigated the effect of LB1, a small molecule inhibitor of serine/threonine protein phosphatase 2A (PP2A), on its ability to inhibit a low growth fraction and highly drug-resistant solid neuroendocrine tumor, such as metastatic pheochromocytoma (PHEO). Subsequently, we evaluated the increased efficacy of chemotherapy combined with LB1.
Methodology/Principal Findings: The effect of LB1 and temozolomide (TMZ), a standard chemotherapeutic agent that alone only transiently suppressed the growth and regression of metastatic PHEO, was evaluated in vitro on a single PHEO cell line and in vivo on mouse model of metastatic PHEO. In the present study, we show that metastatic PHEO, for which there is currently no cure, can be eliminated by combining LB1, thereby inhibiting PP2A, with TMZ. This new treatment approach resulted in long term, disease-free survival of up to 40% of animals bearing multiple intrahepatic metastases, a disease state that the majority of patients die from. Inhibition of PP2A was associated with prevention of G1/S phase arrest by p53 and of mitotic arrest mediated by polo-like kinase 1 (Plk-1).
Conclusions/Significance: The elimination of DNA damage-induced defense mechanisms, through transient pharmacologic inhibition of PP2A, is proposed as a new approach for enhancing the efficacy of non-specific cancer chemotherapy regimens against a broad spectrum of low growth fraction tumors very commonly resistant to cytotoxic drugs.
C1 [Martiniova, Lucia; Pacak, Karel] NICHHD, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA.
[Lu, Jie; Lonser, Russell; Zhuang, Zhengping] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA.
[Chiang, Jeffrey] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Bernardo, Marcelino] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Bernardo, Marcelino] NCI, Lab Anim Sci Program, SAIC Frederick, Frederick, MD 21701 USA.
[Martiniova, Lucia] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia.
RP Martiniova, L (reprint author), NICHHD, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA.
EM zhuangp@ninds.nih.gov; karel@mail.nih.gov
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development; National Cancer Institute;
National Institute of Neurological Disorders and Stroke (NINDS)
FX This research was supported by the Intramural Research Programs of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Cancer Institute, and
the National Institute of Neurological Disorders and Stroke (NINDS). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 36
TC 18
Z9 21
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 14
PY 2011
VL 6
IS 2
AR e14678
DI 10.1371/journal.pone.0014678
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721PR
UT WOS:000287367600007
PM 21339823
ER
PT J
AU Weibel, S
Raab, V
Yu, YA
Worschech, A
Wang, E
Marincola, FM
Szalay, AA
AF Weibel, Stephanie
Raab, Viktoria
Yu, Yong A.
Worschech, Andrea
Wang, Ena
Marincola, Francesco M.
Szalay, Aladar A.
TI Viral-mediated oncolysis is the most critical factor in the late-phase
of the tumor regression process upon vaccinia virus infection
SO BMC CANCER
LA English
DT Article
ID HERPES-SIMPLEX-VIRUS; INNATE-IMMUNITY; EXPRESSION PATTERNS; RNA
AMPLIFICATION; BREAST-TUMORS; CELL LINES; THERAPY; CANCER;
MICROENVIRONMENT; ANGIOGENESIS
AB Background: In principle, the elimination of malignancies by oncolytic virotherapy could proceed by different mechanisms - e.g. tumor cell specific oncolysis, destruction of the tumor vasculature or an anti-tumoral immunological response. In this study, we analyzed the contribution of these factors to elucidate the responsible mechanism for regression of human breast tumor xenografts upon colonization with an attenuated vaccinia virus (VACV).
Methods: Breast tumor xenografts were analyzed 6 weeks post VACV infection (p.i.; regression phase) by immunohistochemistry and mouse-specific expression arrays. Viral-mediated oncolysis was determined by tumor growth analysis combined with microscopic studies of intratumoral virus distribution. The tumor vasculature was morphologically characterized by diameter and density measurements and vessel functionality was analyzed by lectin perfusion and extravasation studies. Immunological aspects of viral-mediated tumor regression were studied in either immune-deficient mouse strains (T-, B-, NK-cell-deficient) or upon cyclophosphamide-induced immunosuppression (MHCII+-cell depletion) in nude mice.
Results: Late stage VACV-infected breast tumors showed extensive necrosis, which was highly specific to cancer cells. The tumor vasculature in infected tumor areas remained functional and the endothelial cells were not infected. However, viral colonization triggers hyperpermeability and dilatation of the tumor vessels, which resembled the activated endothelium in wounded tissue. Moreover, we demonstrated an increased expression of genes involved in leukocyte-endothelial cell interaction in VACV-infected tumors, which orchestrate perivascular inflammatory cell infiltration. The immunohistochemical analysis of infected tumors displayed intense infiltration of MHCII-positive cells and colocalization of tumor vessels with MHCII+/CD31(+) vascular leukocytes. However, GI-101A tumor growth analysis upon VACV-infection in either immunosuppressed nude mice (MHCII+-cell depleted) or in immune-deficient mouse strains (T-, B-, NK-cell-deficient) revealed that neither MHCII-positive immune cells nor T-, B-, or NK cells contributed significantly to VACV-mediated tumor regression. In contrast, tumors of immunosuppressed mice showed enhanced viral spreading and tumor necrosis.
Conclusions: Taken together, these results indicate that VACV-mediated oncolysis is the primary mechanism of tumor shrinkage in the late regression phase. Neither the destruction of the tumor vasculature nor the massive VACV-mediated intratumoral inflammation was a prerequisite for tumor regression. We propose that approaches to enhance viral replication and spread within the tumor microenvironment should improve therapeutical outcome.
C1 [Weibel, Stephanie; Raab, Viktoria; Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Dept Biochem, Bioctr, D-97074 Wurzburg, Germany.
[Weibel, Stephanie; Raab, Viktoria; Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Res Ctr Expt Biomed, Rudolf Virchow Ctr, D-97078 Wurzburg, Germany.
[Weibel, Stephanie; Raab, Viktoria; Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Inst Mol Infect Biol, D-97078 Wurzburg, Germany.
[Yu, Yong A.; Worschech, Andrea; Szalay, Aladar A.] Genelux Corp, San Diego Sci Ctr, San Diego, CA 92109 USA.
[Worschech, Andrea; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Szalay, AA (reprint author), Univ Wurzburg, Dept Biochem, Bioctr, D-97074 Wurzburg, Germany.
EM aaszalay@genelux.com
RI Worschech, Andrea/I-3919-2012
OI Worschech, Andrea/0000-0002-4303-8653
FU Genelux Corporation (R&D facility in San Diego, CA, USA)
FX This work was supported by a research grant from Genelux Corporation
(R&D facility in San Diego, CA, USA) awarded to the University of
Wuerzburg, Germany.; This work was supported by grants from Genelux
Corporation (R&D facility in San Diego, CA, USA). SW received a
postdoctoral fellowship, VR and AW received a graduate fellowship by
Genelux Corporation awarded to the University of Wuerzburg, Germany. YAY
and AAS are salaried employees of Genelux Corporation and have personal
financial interests in Genelux Corporation.
NR 45
TC 22
Z9 26
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD FEB 14
PY 2011
VL 11
AR 68
DI 10.1186/1471-2407-11-68
PG 17
WC Oncology
SC Oncology
GA 726AA
UT WOS:000287686800001
PM 21320309
ER
PT J
AU Rivera, A
Hohl, TM
Collins, N
Leiner, I
Gallegos, A
Saijo, S
Coward, JW
Iwakura, Y
Pamer, EG
AF Rivera, Amariliz
Hohl, Tobias M.
Collins, Nichole
Leiner, Ingrid
Gallegos, Alena
Saijo, Shinobu
Coward, Jesse W.
Iwakura, Yoichiro
Pamer, Eric G.
TI Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by
inhibiting T helper type 1 CD4 T cell differentiation
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID RESPIRATORY FUNGAL-INFECTION; PATTERN-RECOGNITION RECEPTOR;
TRANSCRIPTION FACTOR GATA-3; BETA-GLUCAN RECEPTOR; TGF-BETA; DENDRITIC
CELLS; IN-VIVO; LINEAGE COMMITMENT; SIGNALING PATHWAYS; ADAPTIVE
IMMUNITY
AB Pulmonary infection of mice with Aspergillus fumigatus induces concurrent T helper type 1 (Th1) and Th17 responses that depend on Toll-like receptor/MyD88 and Dectin-1, respectively. However, the mechanisms balancing Th1 and Th17 CD4 T cell populations during infection remain incompletely defined. In this study, we show that Dectin-1 deficiency disproportionally increases Th1 responses and decreases Th17 differentiation after A. fumigatus infection. Dectin-1 signaling in A. fumigatus-infected wild-type mice reduces IFN-gamma and IL-12p40 expression in the lung, thereby decreasing T-bet expression in responding CD4 T cells and enhancing Th17 responses. Absence of IFN-gamma or IL-12p35 in infected mice or T-bet in responding CD4 T cells enhances Th17 differentiation, independent of Dectin-1 expression, in A. fumigatus-infected mice. Transient deletion of monocyte- derived dendritic cells also reduces Th1 and boosts Th17 differentiation of A. fumigatus-specific CD4 T cells. Our findings indicate that Dectin-1-mediated signals alter CD4 T cell responses to fungal infection by decreasing the production of IL-12 and IFN-gamma in innate cells, thereby decreasing T-bet expression in A. fumigatus-specific CD4 T cells and enabling Th17 differentiation.
C1 [Rivera, Amariliz; Collins, Nichole; Leiner, Ingrid; Coward, Jesse W.; Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
[Pamer, Eric G.] Mem Sloan Kettering Canc Ctr, Infect Dis Serv, New York, NY 10065 USA.
[Gallegos, Alena] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Saijo, Shinobu; Iwakura, Yoichiro] Univ Tokyo, Ctr Expt Med & Syst Biol, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan.
[Hohl, Tobias M.] Fred Hutchinson Canc Res Ctr, Infect Dis Sci Vaccine & Infect Dis Div, Div Clin Res, Seattle, WA 98109 USA.
RP Pamer, EG (reprint author), Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
EM riveraam@umdnj.edu; pamere@mskcc.org
RI Iwakura, Yoichiro/E-5457-2011;
OI Iwakura, Yoichiro/0000-0002-9934-5775; Hohl, Tobias/0000-0002-9097-5412
FU National Cancer Institute [K01CA117914]; National Institute of Allergy
and Infectious Diseases [K08AI071998, R01AI067359, 5P01CA023766]
FX This work was supported by a National Cancer Institute grant to A.
Rivera (K01CA117914) and National Institute of Allergy and Infectious
Diseases grants to T. M. Hohl (K08AI071998) and E. G. Pamer (R01AI067359
and 5P01CA023766).
NR 70
TC 67
Z9 69
U1 0
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD FEB 14
PY 2011
VL 208
IS 2
BP 369
EP 381
DI 10.1084/jem.20100906
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 721PE
UT WOS:000287366300013
PM 21242294
ER
PT J
AU Salvadore, G
Nugent, AC
Lemaitre, H
Luckenbaugh, DA
Tinsley, R
Cannon, DM
Neumeister, A
Zarate, CA
Drevets, WC
AF Salvadore, Giacomo
Nugent, Allison C.
Lemaitre, Herve
Luckenbaugh, David A.
Tinsley, Ruth
Cannon, Dara M.
Neumeister, Alexander
Zarate, Carlos A., Jr.
Drevets, Wayne C.
TI Prefrontal cortical abnormalities in currently depressed versus
currently remitted patients with major depressive disorder
SO NEUROIMAGE
LA English
DT Article
DE Voxel-based morphometry (VBM); Remission; Dorsolateral prefrontal cortex
(DLPFC); Gray matter; Clinical outcome
ID VOXEL-BASED MORPHOMETRY; MOOD DISORDERS; HIPPOCAMPAL VOLUME; CORTEX
ABNORMALITIES; UNIPOLAR DEPRESSION; ANTERIOR CINGULATE; BIPOLAR
DISORDER; SEGMENTATION; REDUCTION; STRESS
AB Previous neuromorphometric investigations of major depressive disorder (MDD) have reported abnormalities in gray matter in several regions, although the results have been inconsistent across studies. Some discrepancies in the results across studies may reflect design limitations such as small sample sizes, whereas others may reflect biological variability that potentially manifests as differences in clinical course. For example, it remains unclear whether the abnormalities found in persistently depressed MDD subjects extend to or persist in patients who experience prolonged remission. The aim of the present study was to investigate gray matter (GM) differences in unmedicated, currently-depressed participants (dMDD) and unmedicated, currently-remitted (rMDD) participants with MDD compared to healthy controls (HC).
The GM density and volume were compared across groups using voxel-based morphometry, a quantitative neuroanatomical technique, and high-resolution MRI images from 107 HC, 58 dMDD and 27 rMDD subjects. Relative to the HC group the dMDD group had reduced GM in the dorsal anterolateral (DALPFC), the dorsomedial (DMPFC) and the ventrolateral prefrontal cortex (VLPFC). Relative to the rMDD group the dMDD group showed reduced GM in the DALPFC, the VLPFC, the anterior cingulate cortex (ACC), the precuneus and the inferior parietal lobule. No regions were identified in which the rMDD group showed significantly lower GM compared to the HC group after p-values were corrected for the number of comparisons performed.
In unmedicated patients in the depressed phase of MOD, we found evidence of morphometric abnormalities in DALPFC and in medial prefrontal cortical regions belonging to the visceromotor network. These findings, along with the absence of GM abnormalities in the remitted sample imply a possible link between greater GM tissue and better clinical outcome. Consistent with other neuroimaging and post-mortem neuropathological studies of MDD, we also found evidence of decreased white matter in patients with dMDD and rMDD. Published by Elsevier Inc.
C1 [Salvadore, Giacomo; Nugent, Allison C.; Luckenbaugh, David A.; Tinsley, Ruth; Zarate, Carlos A., Jr.; Drevets, Wayne C.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Lemaitre, Herve] Fac Med Paris Sud, CEA, INSERM, Res Unit Neuroimaging & Psychiat U1000, Orsay, France.
[Cannon, Dara M.] Natl Univ Ireland Galway, Dept Psychiat, Galway, Ireland.
[Neumeister, Alexander] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Drevets, Wayne C.] Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK USA.
[Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK USA.
RP Salvadore, G (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM salvadoreg@mail.nih.gov
RI Cannon, Dara/C-1323-2009;
OI Cannon, Dara/0000-0001-7378-3411; Lemaitre, Herve/0000-0002-5952-076X;
Nugent, Allison/0000-0003-2569-2480
FU National Institute of Mental Health, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health.
NR 41
TC 69
Z9 77
U1 1
U2 9
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 FEB 14
PY 2011
VL 54
IS 4
BP 2643
EP 2651
DI 10.1016/j.neuroimage.2010.11.011
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 710FH
UT WOS:000286495800010
PM 21073959
ER
PT J
AU Gonzalez-Castillo, J
Roopchansingh, V
Bandettini, PA
Bodurka, J
AF Gonzalez-Castillo, J.
Roopchansingh, V.
Bandettini, P. A.
Bodurka, J.
TI Physiological noise effects on the flip angle selection in BOLD fMRI
SO NEUROIMAGE
LA English
DT Article
DE Physiological noise; Imaging flip angle; Temporal signal-to-noise ratio;
TSNR; fMRI
ID SIGNAL-TO-NOISE; MAGNETIC-RESONANCE; FUNCTIONAL MRI; HUMAN BRAIN; VISUAL
ACTIVATION; VOXEL VOLUME; 3.0 TESLA; REPRODUCIBILITY; OXYGENATION;
INFLOW
AB This work addresses the choice of imaging flip angle in blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). When noise of physiological origin becomes the dominant noise source in fMRI timeseries, it causes a nonlinear dependence of the temporal signal-to-noise ratio (TSNR) versus signal-to-noise ratio (SNR) that can be exploited to perform BOLD fMRI at angles well below the Ernst angle without any detrimental effect on our ability to detect sites of neuronal activation. We show, both experimentally and theoretically, that for situations where available SNR is high and physiological noise dominates over system/thermal noise, although TSNR still reaches it maximum for the Ernst angle, reduction of imaging flip angle well below this angle results in negligible loss in TSNR. Moreover, we provide a way to compute a suggested imaging flip angle, which constitutes a conservative estimate of the minimum flip angle that can be used under given experimental SNR and physiological noise levels. For our experimental conditions, this suggested angle equals 7.63 degrees for the grey matter compartment, while the Ernst angle = 77 degrees. Finally, using data from eight subjects with a combined visual-motor task we show that imaging at angles as low as 9 degrees introduces no significant differences in observed hemodynamic response time-course, contrast-to-noise ratio, voxel-wise effect size or statistical maps of activation as compared to imaging at 75 degrees (an angle close to the Ernst angle). These results suggest that using low flip angles in BOLD fMRI experimentation to obtain benefits such as (1) reduction of RF power, (2) limitation of apparent T(1)-related inflow effects, (3) reduction of through-plane motion artifacts, (4) lower levels of physiological noise, and (5) improved tissue contrast is feasible when physiological noise dominates and SNR is high. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Gonzalez-Castillo, J.; Bandettini, P. A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Roopchansingh, V.; Bandettini, P. A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
[Bodurka, J.] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
RP Gonzalez-Castillo, J (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM javier.gonzalez-castillo@nih.gov
RI Gonzalez-Castillo, Javier/B-6903-2012; Bandettini, Peter/F-5871-2012;
OI Gonzalez-Castillo, Javier/0000-0002-6520-5125
FU Intramural NIH HHS [Z99 MH999999]
NR 37
TC 34
Z9 35
U1 1
U2 6
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 FEB 14
PY 2011
VL 54
IS 4
BP 2764
EP 2778
DI 10.1016/j.neuroimage.2010.11.020
PG 15
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 710FH
UT WOS:000286495800022
PM 21073963
ER
PT J
AU Lee, J
Fukunaga, M
Duyn, JH
AF Lee, Jongho
Fukunaga, Masaki
Duyn, Jeff H.
TI Improving contrast to noise ratio of resonance frequency contrast images
(phase images) using balanced steady-state free precession
SO NEUROIMAGE
LA English
DT Article
DE Ultra high field MRI; MR microscopy; Balanced SSFP and GRE sequence
comparison; 7 Tesla
ID MAGNETIC-FIELD STRENGTHS; WHITE-MATTER CONTRAST; HUMAN BRAIN; IN-VIVO;
GRADIENT-ECHO; SSFP FMRI; IRON CONTENT; IMAGING SWI; 7 TESLA; 7.0 T
AB Recent MRI studies have exploited subtle magnetic susceptibility differences between brain tissues to improve anatomical contrast and resolution. These susceptibility differences lead to resonance frequency shifts which can be visualized by reconstructing the signal phase in conventional gradient echo (GRE) acquisition techniques. In this work, a method is proposed to improve the contrast to noise ratio per unit time (CNR efficiency) of anatomical MRI based on resonance frequency contrast. The method, based on the balanced steady-state free precession (bSSFP) MRI acquisition technique, was evaluated in its ability to generate contrast between gray and white matter in human brain at 3 T and 7 T. The results show substantially improved CNR efficiency of bSSFP phase images (2.85 +/- 0.21 times at 3 T and 1.71 +/- 0.11 times at 7 T) compared to the GRE data in a limited spatial area. This limited spatial coverage is attributed to the sensitivity of bSSFP to macroscopic B(o) inhomogeneities. With this CNR improvement, high resolution bSSFP phase images (resolution = 0.3 x 0.3 x 2 mm(3), acquisition time = 10 min) acquired at 3 T had sufficient CNR to allow the visualization of cortical laminar structures in in vivo human primary visual cortex. Practical application of the proposed method may require improvement of B(o) homogeneity and stability by additional preparatory scans and/or compensation schemes such as respiration and drift compensation. Without these additions, the CNR benefits of the method may be limited to studies at low field or limited regions of interest. Published by Elsevier Inc.
C1 [Lee, Jongho; Fukunaga, Masaki; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
[Fukunaga, Masaki] Osaka Univ, WPI Immunol Frontier Res Ctr, Osaka, Japan.
RP Lee, J (reprint author), 9000 Rockville Pike,Bldg 10,Room B1D723A, Bethesda, MD 20892 USA.
EM jonghoyi@mail.nih.gov
RI Fukunaga, Masaki/F-6441-2013
OI Fukunaga, Masaki/0000-0003-1010-2644
FU NIH, NINDS
FX This research was supported (in part) by the Intramural Research Program
of the NIH, NINDS.
NR 62
TC 6
Z9 6
U1 0
U2 9
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 FEB 14
PY 2011
VL 54
IS 4
BP 2779
EP 2788
DI 10.1016/j.neuroimage.2010.10.071
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 710FH
UT WOS:000286495800023
PM 21040793
ER
PT J
AU Tomasi, D
Volkow, ND
Wang, GJ
Wang, R
Telang, F
Caparelli, EC
Wong, C
Jayne, M
Fowler, JS
AF Tomasi, D.
Volkow, N. D.
Wang, G. J.
Wang, R.
Telang, F.
Caparelli, E. C.
Wong, C.
Jayne, M.
Fowler, J. S.
TI Methylphenidate enhances brain activation and deactivation responses to
visual attention and working memory tasks in healthy controls
SO NEUROIMAGE
LA English
DT Article
DE BOLD-fMRI; Dopamine; Cognition; Brain function; Stimulants; MPH
ID SLEEP-DEPRIVATION; DOPAMINERGIC MODULATION; SELECTIVE ATTENTION;
FUNCTIONAL MRI; YOUNG ADULTS; 4 TESLA; FMRI; NETWORKS; PATTERNS; SPACE
AB Methylphenidate (MPH) is a stimulant drug that amplifies dopamineric and noradrenergic signaling in the brain, which is believed to underlie its cognition enhancing effects. However, the neurobiological effects by which MPH improves cognition are still poorly understood. Here, functional magnetic resonance imaging (fMRI) was used together with working memory (WM) and visual attention (VA) tasks to test the hypothesis that 20 mg oral MPH would increase activation in the dorsal attention network (DAN) and deactivation in the default mode network (DMN) as well as improve performance during cognitive tasks in healthy men. The group of subjects that received MPH (MPH group; N = 16) had higher activation than the group of subjects who received no medication (control group: N = 16) in DAN regions (parietal and prefrontal cortex, regions increasingly activated with increased cognitive load) and had increased deactivation in the insula and posterior cingulate cortex (regions increasingly deactivated with increased cognitive load) and these effects did not differ for the VA and the WM tasks. These findings provide the first evidence that MPH enhances activation of the DAN whereas it alters DMN deactivation. This suggests that MPH (presumably by amplifying dopamine and noradrenergic signaling) modulates cognition in part through its effects on DAN and DMN. Published by Elsevier Inc.
C1 [Tomasi, D.; Wang, G. J.; Wang, R.; Caparelli, E. C.; Fowler, J. S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Tomasi, D.; Volkow, N. D.; Telang, F.; Wong, C.; Jayne, M.] NIAAA, Bethesda, MD USA.
RP Tomasi, D (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 490,30 Bell Ave, Upton, NY 11973 USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institute on Alcohol Abuse and Alcoholism [2RO1AA09481];
National Center for Research Resources [GCRC 5-MO1-RR-10710]
FX The National Institute on Alcohol Abuse and Alcoholism (2RO1AA09481) and
the National Center for Research Resources (GCRC 5-MO1-RR-10710)
supported this work. The authors thank Karen Apelskog-Torres, Barbara
Hubbard, Hai-Dee Lee, and Joan Terry for assistance in various aspects
of these studies.
NR 51
TC 62
Z9 63
U1 1
U2 12
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 FEB 14
PY 2011
VL 54
IS 4
BP 3101
EP 3110
DI 10.1016/j.neuroimage.2010.10.060
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 710FH
UT WOS:000286495800052
PM 21029780
ER
PT J
AU Lane, J
Bertuzzi, S
AF Lane, Julia
Bertuzzi, Stefano
TI Measuring the Results of Science Investments
SO SCIENCE
LA English
DT Editorial Material
C1 [Lane, Julia] Natl Sci Fdn, Arlington, VA 22230 USA.
[Bertuzzi, Stefano] NIH, NIH Off Sci Policy Anal, Bethesda, MD 20892 USA.
RP Lane, J (reprint author), Natl Sci Fdn, 4201 Wilson Blvd, Arlington, VA 22230 USA.
EM jlane@nsf.gov; stefano_bertuzzi@nih.gov
OI Lane, Julia/0000-0002-8139-2960
NR 15
TC 39
Z9 40
U1 0
U2 13
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD FEB 11
PY 2011
VL 331
IS 6018
BP 678
EP 680
DI 10.1126/science.1201865
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 719LH
UT WOS:000287205700031
PM 21310987
ER
PT J
AU Borck, G
Rehman, AU
Lee, K
Pogoda, HM
Kakar, N
von Ameln, S
Grillet, N
Hildebrand, MS
Ahmed, ZM
Nurnberg, G
Ansar, M
Basit, S
Javed, Q
Morell, RJ
Nasreen, N
Shearer, AE
Ahmad, A
Kahrizi, K
Shaikh, RS
Ali, RA
Khan, SN
Goebel, I
Meyer, NC
Kimberling, WJ
Webster, JA
Stephan, DA
Schiller, MR
Bahlo, M
Najmabadi, H
Gillespie, PG
Nurnberg, P
Wollnik, B
Riazuddin, S
Smith, RJH
Ahmad, W
Muller, U
Hammerschmidt, M
Friedman, TB
Riazuddin, S
Leal, SM
Ahmad, J
Kubisch, C
AF Borck, Guntram
Rehman, Atteeq Ur
Lee, Kwanghyuk
Pogoda, Hans-Martin
Kakar, Naseebullah
von Ameln, Simon
Grillet, Nicolas
Hildebrand, Michael S.
Ahmed, Zubair M.
Nuernberg, Gudrun
Ansar, Muhammad
Basit, Sulman
Javed, Qamar
Morell, Robert J.
Nasreen, Nabilah
Shearer, A. Eliot
Ahmad, Adeel
Kahrizi, Kimia
Shaikh, Rehan S.
Ali, Rana A.
Khan, Shaheen N.
Goebel, Ingrid
Meyer, Nicole C.
Kimberling, William J.
Webster, Jennifer A.
Stephan, Dietrich A.
Schiller, Martin R.
Bahlo, Melanie
Najmabadi, Hossein
Gillespie, Peter G.
Nuernberg, Peter
Wollnik, Bernd
Riazuddin, Saima
Smith, Richard J. H.
Ahmad, Wasim
Mueller, Ulrich
Hammerschmidt, Matthias
Friedman, Thomas B.
Riazuddin, Sheikh
Leal, Suzanne M.
Ahmad, Jamil
Kubisch, Christian
TI Loss-of-Function Mutations of ILDR1 Cause Autosomal-Recessive Hearing
Impairment DFNB42
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID STIMULATED LIPOPROTEIN RECEPTOR; LINKAGE ANALYSIS; MOUSE MODELS;
HAIR-CELLS; INNER-EAR; DEAFNESS; ZEBRAFISH; MICE; IDENTIFICATION;
HYPERLIPIDEMIA
AB By using homozygosity mapping in a consanguineous Pakistani family, we detected linkage of nonsyndromic hearing loss to a 7.6 Mb region on chromosome 3q13.31-q21.1 within the previously reported DFNB42 locus. Subsequent candidate gene sequencing identified a homozygous nonsense mutation (c.1135G>T [p.Glu379X]) in ILDR1 as the cause of hearing impairment. By analyzing additional consanguineous families with homozygosity at this locus, we detected ILDR1 mutations in the affected individuals of 10 more families from Pakistan and Iran. The identified ILDR1 variants include missense, nonsense, frameshift, and splice-site mutations as well as a start codon mutation in the family that originally defined the DFNB42 locus. ILDR1 encodes the evolutionarily conserved immunoglobulin-like domain containing receptor 1, a putative transmembrane receptor of unknown function. In situ hybridization detected expression of Ildr1, the murine ortholog, early in development in the vestibule and in hair cells and supporting cells of the cochlea. Expression in hair cell- and supporting cell-containing neurosensory organs is conserved in the zebrafish, in which the ildr1 ortholog is prominently expressed in the developing ear and neuromasts of the lateral line. These data identify loss-of-function mutations of ILDR1, a gene with a conserved expression pattern pointing to a conserved function in hearing in vertebrates, as underlying nonsyndromic prelingual sensorineural hearing impairment.
C1 [Borck, Guntram; von Ameln, Simon; Goebel, Ingrid; Wollnik, Bernd; Kubisch, Christian] Univ Cologne, Inst Human Genet, D-50931 Cologne, Germany.
[Borck, Guntram; von Ameln, Simon; Nuernberg, Gudrun; Goebel, Ingrid; Nuernberg, Peter; Wollnik, Bernd; Hammerschmidt, Matthias; Kubisch, Christian] Univ Cologne, CMMC, D-50931 Cologne, Germany.
[Rehman, Atteeq Ur; Morell, Robert J.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Rockville, MD 20850 USA.
[Rehman, Atteeq Ur; Shaikh, Rehan S.; Ali, Rana A.; Khan, Shaheen N.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 54500, Pakistan.
[Lee, Kwanghyuk; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Pogoda, Hans-Martin; Hammerschmidt, Matthias] Univ Cologne, Inst Dev Biol, D-50674 Cologne, Germany.
[Kakar, Naseebullah; Nasreen, Nabilah; Ahmad, Jamil] BUITEMS, Dept Biotechnol & Informat, Quetta 78300, Pakistan.
[von Ameln, Simon; Goebel, Ingrid; Kubisch, Christian] Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany.
[Grillet, Nicolas; Mueller, Ulrich] Scripps Res Inst, Dorris Neurosci Ctr, La Jolla, CA 92037 USA.
[Grillet, Nicolas; Mueller, Ulrich] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
[Hildebrand, Michael S.; Shearer, A. Eliot; Meyer, Nicole C.; Smith, Richard J. H.] Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA.
[Ahmed, Zubair M.] Univ Cincinnati, Div Pediat Ophthalmol, Cincinnati Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA.
[Ahmed, Zubair M.] Univ Cincinnati, Dept Ophthalmol, Coll Med, Cincinnati, OH 45229 USA.
[Nuernberg, Gudrun; Nuernberg, Peter] Univ Cologne, CCG, D-50931 Cologne, Germany.
[Ansar, Muhammad; Basit, Sulman; Javed, Qamar; Ahmad, Wasim] Quaid I Azam Univ, Dept Biochem, Fac Biol Sci, Islamabad 45320, Pakistan.
[Ahmad, Adeel] King Edward Med Univ, Mayo Hosp, Lahore 54000, Pakistan.
[Kahrizi, Kimia; Najmabadi, Hossein] Univ Social Welf & Rehabil Sci, Genet Res Ctr, Tehran 19834, Iran.
[Shaikh, Rehan S.] Bahauddin Zakariya Univ, Inst Biotechnol, Multan 60800, Pakistan.
[Kimberling, William J.] Boys Town Natl Res Hosp, Dept Genet, Omaha, NE 68131 USA.
[Webster, Jennifer A.] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA.
[Stephan, Dietrich A.] Inst Individualized Hlth IGNITE, Palo Alto, CA 94301 USA.
[Stephan, Dietrich A.] Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA.
[Stephan, Dietrich A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Stephan, Dietrich A.] Fox Chase Canc Ctr, Canc Genome Inst, Philadelphia, PA 19111 USA.
[Schiller, Martin R.] Univ Nevada, Sch Life Sci, Las Vegas, NV 89052 USA.
[Bahlo, Melanie] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3052, Australia.
[Gillespie, Peter G.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA.
[Gillespie, Peter G.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
[Nuernberg, Gudrun; Nuernberg, Peter; Wollnik, Bernd; Hammerschmidt, Matthias; Kubisch, Christian] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany.
[Riazuddin, Saima] Univ Cincinnati, Lab Mol Genet, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA.
[Riazuddin, Saima] Univ Cincinnati, Coll Med, Dept Otolaryngol, Cincinnati, OH 45229 USA.
[Smith, Richard J. H.] Univ Iowa, Interdept Mental PhD Program Genet, Dept Otolaryngol, Iowa City, IA 52242 USA.
[Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Jinnah Hosp Complex, Lahore 54550, Pakistan.
RP Borck, G (reprint author), Univ Cologne, Inst Human Genet, D-50931 Cologne, Germany.
EM guntram.borck@uk-koeln.de
RI Kubisch, Christian/F-1893-2011; Ansar, Muhammad/H-5967-2011; Basit,
Sulman/B-2947-2013; Borck, Guntram/F-1868-2015; Nasim Khan,
Shaheen/F-2135-2015; Ansar, Muhammad/F-4808-2015; Ahmad,
Wasim/E-9713-2015; Basit, Sulman/F-6395-2015;
OI Barr-Gillespie, Peter/0000-0002-9787-5860; Basit,
Sulman/0000-0003-4294-6825; Kubisch, Christian/0000-0003-4220-0978;
Hildebrand, Michael/0000-0003-2739-0515; Ansar,
Muhammad/0000-0001-5891-7063; Najmabadi, Hossein/0000-0002-6084-7778;
Lee, Kwanghyuk/0000-0001-7781-9696; Morell, Robert/0000-0003-1537-7356
FU Deutsche Forschungsgemeinschaft (DFG) [BO2985/3-1]; European Commission
[LSHG-CT-20054-512063]; NIH [RO1 DC002842, DC007704, N01-HG-65403];
NHMRC; Doris Duke Fellowship; Skaggs Institute for Chemical Biology; NIH
from NIDCD [DC000039-14]; Higher Education Commission (HEC), Government
of Pakistan; NIH-NIDCD [DC03594]; ICGEB, Trieste, Italy
FX We wish to thank the family members for their invaluable participation
and cooperation. We thank Dennis Drayna and Changsoo Kang for critically
reading the manuscript. This work was funded by the Deutsche
Forschungsgemeinschaft (DFG; BO2985/3-1; to GB.), the European
Commission FP6 Integrated Project EURO-HEAR, Grant LSHG-CT-20054-512063
(to B.W. and C.K.), NIH RO1 DC002842 (to R.J.H.S), NHMRC Career
Development Award (to M.B.), NHMRC Overseas Biomedical Fellowship (to
M.S.H.), Doris Duke Fellowship (to A.E.S), NIH DC007704 and Skaggs
Institute for Chemical Biology (to U.M.), NIH intramural funds from
NIDCD DC000039-14 (to T.B.F.), Higher Education Commission (HEC),
Government of Pakistan (to W.A.), NIH-NIDCD grant DC03594 (to S.M.L.),
and the ICGEB, Trieste, Italy (to Sheikh R.). J.A. thanks Dost Muhammad
Baloch and Ahmed Farooq Bazai, VC, BUITEMS, for faculty funds.
Genotyping services were partially provided by the Center for Inherited
Disease Research (CIDR). CIDR is fully funded through a federal contract
from the NIH to The Johns Hopkins University, Contract Number
N01-HG-65403 (to S.M.L.).
NR 37
TC 41
Z9 44
U1 0
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 11
PY 2011
VL 88
IS 2
BP 127
EP 137
DI 10.1016/j.ajhg.2010.12.011
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 725YZ
UT WOS:000287684100001
PM 21255762
ER
PT J
AU Opdyke, JA
Fozo, EM
Hemm, MR
Storz, G
AF Opdyke, Jason A.
Fozo, Elizabeth M.
Hemm, Matthew R.
Storz, Gisela
TI RNase III Participates in GadY-Dependent Cleavage of the gadX-gadW mRNA
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE antisense RNA; acid response; ribonuclease; OOP RNA
ID ESCHERICHIA-COLI; ANTISENSE RNA; ACID RESISTANCE; GENE; SYSTEM; PROTEIN;
LAMBDA; IDENTIFICATION; DEGRADATION; CHROMOSOME
AB The adjacent gadX and gadW genes encode transcription regulators that are part of a complex regulatory circuit controlling the Escherichia coli response to acid stress. We previously showed that the small RNA GadY positively regulates gadX mRNA levels. The gadY gene is located directly downstream of the gadX coding sequence on the opposite strand of the chromosome. We now report that gadX is transcribed in an operon with gadW, although this full-length mRNA does not accumulate. Base pairing of the GadY small RNA with the intergenic region of the gadX-gadW mRNA results in directed processing events within the region of complementarity. The resulting two halves of the cleaved mRNA accumulate to much higher levels than the unprocessed mRNA. We examined the ribonucleases required for this processing, and found that multiple enzymes are involved in the GadY-directed cleavage including the double-strand RNA-specific endoribonuclease RNase III. Published by Elsevier Ltd.
C1 [Opdyke, Jason A.; Fozo, Elizabeth M.; Hemm, Matthew R.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
EM storz@helix.nih.gov
OI Storz, Gisela/0000-0001-6698-1241
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Research Council; Life Sciences Foundation
FX We thank M. Thomason and A. Zhang for technical assistance; N. Majdalani
for strains; P. Backlund and A. Yergey for performing the mass
spectrometric analysis; J. Belasco, S. Durand, S. Gottesman, and M.
Thomason for helpful discussions and comments. This research was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, a
Research Associateship from the National Research Council (E.M.F.), and
a postdoctoral fellowship from the Life Sciences Foundation (M.R.H.).
NR 32
TC 46
Z9 48
U1 0
U2 12
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD FEB 11
PY 2011
VL 406
IS 1
BP 29
EP 43
DI 10.1016/j.jmb.2010.12.009
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 720LI
UT WOS:000287281800004
PM 21147125
ER
PT J
AU Chen, Y
Guzik, S
Sumner, JP
Moreland, J
Koretsky, AP
AF Chen, Yun
Guzik, Stephanie
Sumner, James P.
Moreland, John
Koretsky, Alan P.
TI Magnetic manipulation of actin orientation, polymerization, and gliding
on myosin using superparamagnetic iron oxide particles
SO NANOTECHNOLOGY
LA English
DT Article
ID MICROTUBULES; FIELDS; CYTOSKELETON; TRANSPORT; MOTILITY; CELLS
AB The actin cytoskeleton controls cell shape, motility, as well as intracellular molecular trafficking. The ability to remotely manipulate actin is therefore highly desirable as a tool to probe and manipulate biological processes at the molecular level. We demonstrate actin manipulation by labeling actin filaments with superparamagnetic iron oxide particles (IOPs) and applying a uniform magnetic field to affect actin orientation, polymerization and gliding on myosin. We show for the first time magnetic manipulation of magnetizable actin filaments at the molecular level while gliding on a bed of myosin molecules and during polymerization. A model for the magnetic alignment and guiding mechanism is proposed based on the torque from the induced molecular anisotropy due to interactions between neighboring IOPs distributed along magnetically labeled actin molecules.
C1 [Koretsky, Alan P.] NINDS, NIH, LFMI, Bethesda, MD 20892 USA.
[Chen, Yun; Moreland, John; Koretsky, Alan P.] Natl Inst Stand & Technol, Boulder, CO USA.
RP Koretsky, AP (reprint author), NINDS, NIH, LFMI, 10 Ctr Dr,MSC 1065,Bldg 10,Room B1D728, Bethesda, MD 20892 USA.
EM koretskya@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015;
OI Koretsky, Alan/0000-0002-8085-4756; Chen, Yun/0000-0001-6917-7814
FU National Research Council; National Institute of Standards and
Technology; National Institute of Biomedical Imaging and BioEngineering
FX This work is supported by National Research Council, National Institute
of Standards and Technology, and National Institute of Biomedical
Imaging and BioEngineering. We thank Dr James Seller for helpful
discussion and the supply of myosin V. We also thank Dr Ikuko Fujiwara
for the supply of actin and Dr Shumin Wang for helpful discussion. This
paper is a contribution of the National Institute of Standards and
Technology, not subject to copyright.
NR 16
TC 4
Z9 4
U1 0
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
J9 NANOTECHNOLOGY
JI Nanotechnology
PD FEB 11
PY 2011
VL 22
IS 6
AR 065101
DI 10.1088/0957-4484/22/6/065101
PG 7
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA 703RL
UT WOS:000285998900002
PM 21212476
ER
PT J
AU Zeeberg, BR
Liu, HF
Kahn, AB
Ehler, M
Rajapakse, VN
Bonner, RF
Brown, JD
Brooks, BP
Larionov, VL
Reinhold, W
Weinstein, JN
Pommier, YG
AF Zeeberg, Barry R.
Liu, Hongfang
Kahn, Ari B.
Ehler, Martin
Rajapakse, Vinodh N.
Bonner, Robert F.
Brown, Jacob D.
Brooks, Brian P.
Larionov, Vladimir L.
Reinhold, William
Weinstein, John N.
Pommier, Yves G.
TI RedundancyMiner: De-replication of redundant GO categories in microarray
and proteomics analysis
SO BMC BIOINFORMATICS
LA English
DT Article
ID GENE-ONTOLOGY; TOOL; GOMINER; CANCER; GRAPH
AB Background: The Gene Ontology (GO) Consortium organizes genes into hierarchical categories based on biological process, molecular function and subcellular localization. Tools such as GoMiner can leverage GO to perform ontological analysis of microarray and proteomics studies, typically generating a list of significant functional categories. Two or more of the categories are often redundant, in the sense that identical or nearly-identical sets of genes map to the categories. The redundancy might typically inflate the report of significant categories by a factor of three-fold, create an illusion of an overly long list of significant categories, and obscure the relevant biological interpretation.
Results: We now introduce a new resource, RedundancyMiner, that de-replicates the redundant and nearly-redundant GO categories that had been determined by first running GoMiner. The main algorithm of RedundancyMiner, MultiClust, performs a novel form of cluster analysis in which a GO category might belong to several category clusters. Each category cluster follows a "complete linkage" paradigm. The metric is a similarity measure that captures the overlap in gene mapping between pairs of categories.
Conclusions: RedundancyMiner effectively eliminated redundancies from a set of GO categories. For illustration, we have applied it to the clarification of the results arising from two current studies: (1) assessment of the gene expression profiles obtained by laser capture microdissection (LCM) of serial cryosections of the retina at the site of final optic fissure closure in the mouse embryos at specific embryonic stages, and (2) analysis of a conceptual data set obtained by examining a list of genes deemed to be "kinetochore" genes.
C1 [Zeeberg, Barry R.; Reinhold, William; Pommier, Yves G.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Hongfang; Larionov, Vladimir L.] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20007 USA.
[Kahn, Ari B.] SRA Int Inc, Fairfax, VA USA.
[Ehler, Martin; Bonner, Robert F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Med Biophys, Bethesda, MD 20892 USA.
[Rajapakse, Vinodh N.] Univ Maryland, Dept Math, College Pk, MD 20742 USA.
[Brown, Jacob D.; Brooks, Brian P.] NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat, Houston, TX 77030 USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Computat Biol & Syst Biol, Houston, TX 77030 USA.
RP Zeeberg, BR (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Room 5068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA.
EM barry@discover.nci.nih.gov
RI Bonner, Robert/C-6783-2015
FU NIH, National Cancer Institute, Center for Cancer Research; Chapman
Foundation; NIH [R01LM009959A1]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
work by JNW was supported in part by a generous gift from the Chapman
Foundation. HF is supported by the NIH grant R01LM009959A1.
NR 21
TC 9
Z9 9
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 10
PY 2011
VL 12
AR 52
DI 10.1186/1471-2105-12-52
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 729UQ
UT WOS:000287976900001
PM 21310028
ER
PT J
AU Simeon, FG
Wendahl, MT
Pike, VW
AF Simeon, Fabrice G.
Wendahl, Matthew T.
Pike, Victor W.
TI Syntheses of 2-Amino and 2-Halothiazole Derivatives as High-Affinity
Metabotropic Glutamate Receptor Subtype 5 Ligands and Potential
Radioligands for in Vivo Imaging
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; MGLUR5 ANTAGONIST MPEP;
ALZHEIMERS-DISEASE; COCAINE; BRAIN; RELAPSE; SEEKING; MODELS; MICE
AB The structure of the potent selective mGlu(5) ligand, SP203 (1, 3-fluoro-5-[[2-(fluoromethyl)thiazol-4-yl]ethynyl]benzonitrile), was modified by replacing the 2-fluoromethyl substituent with an amino or halo substituent and by variation of substituents in the distal aromatic ring to provide a series of new high-affinity mGlu(5) ligands. In this series, among the most potent ligands obtained, the 2-chlorothiazoles 7a and 7b and the 2-fluorothiazole 10b showed subnanomolar mGlu(5) affinity. 10b also displayed > 10000-fold selectivity over all other metabotropic receptor subtypes plus a wide range of other receptors and binding sites. The 2-fluorothiazoles 10a and 10b were labeled using [F-18]fluoride ion (t(1/2) = 109.7 min) in moderately high radiochemical yield to provide potential radioligands that may resist troublesome radiodefluorination during the imaging of brain mGlu(5) with position emission tomography. The iodo compound 9b has nanomolar affinity for mGlu(5) and may also serve as a lead to a potential I-123-labeled ligand for imaging brain mGlu(5) with single photon emission computed tomography.
C1 [Simeon, Fabrice G.; Wendahl, Matthew T.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Simeon, FG (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM simeonf@mail.nih.gov
FU National Institutes of Health (NIH); National Institute of Mental Health
[NO1MH32004]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH). We are grateful to NIH Clinical
Center PET Department for cyclotron irradiations (Chief: Dr. Peter
Herscovitch). We are also grateful to the National Institute of Mental
Health's Psychoactive Drug Screening Program (PDSP) (contract no.
NO1MH32004) for ligand Ki determinations and receptor
screening. The NIMH PDSP is directed by Dr. Bryan L. Roth MD, Ph.D. at
the University of North Carolina at Chapel Hill and Project Officer
Jamie Driscol at NIMH, Bethesda, MD, USA.
NR 31
TC 6
Z9 6
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 10
PY 2011
VL 54
IS 3
BP 901
EP 908
DI 10.1021/jm101430m
PG 8
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 714HJ
UT WOS:000286798100018
PM 21207959
ER
PT J
AU Dunleavy, K
Bollard, CM
AF Dunleavy, Kieron
Bollard, Catherine M.
TI Sobering realities of surviving Hodgkin Lymphoma
SO BLOOD
LA English
DT Editorial Material
ID CHILDHOOD-CANCER SURVIVOR; NEOPLASMS
C1 [Dunleavy, Kieron] NCI, Bethesda, MD 20892 USA.
Baylor Coll Med, Houston, TX 77030 USA.
RP Dunleavy, K (reprint author), NCI, Bethesda, MD 20892 USA.
FU NCI NIH HHS [P50 CA126752]
NR 7
TC 10
Z9 12
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 10
PY 2011
VL 117
IS 6
BP 1772
EP 1773
DI 10.1182/blood-2010-11-317131
PG 3
WC Hematology
SC Hematology
GA 719HA
UT WOS:000287192300004
PM 21310929
ER
PT J
AU Luke, JM
Carnes, AE
Sun, P
Hodgson, CP
Waugh, DS
Williams, JA
AF Luke, Jeremy M.
Carnes, Aaron E.
Sun, Ping
Hodgson, Clague P.
Waugh, David S.
Williams, James A.
TI Thermostable tag (TST) protein expression system: Engineering
thermotolerant recombinant proteins and vaccines
SO JOURNAL OF BIOTECHNOLOGY
LA English
DT Article
DE Vaccine; Maltodextrin-binding protein; Thermostable; Flagellin;
Hemagglutinin; Affinity tag
ID ESCHERICHIA-COLI; BINDING PROTEINS; FLAGELLIN; ACTIVATION; DOMAIN;
SOLUBILITY; ADJUVANT; PARTNERS; BACTERIA; IMMUNITY
AB Methods to increase temperature stability of vaccines and adjuvants are needed to reduce dependence on cold chain storage. We report herein creation and application of pVEX expression vectors to improve vaccine and adjuvant manufacture and thermostability. Defined media fermentation yields of 6 g/L thermostable toll-like receptor 5 agonist flagellin were obtained using an IPTG inducible pVEX-flagellin expression vector. Alternative pVEX vectors encoding Pyrococcus furiosus maltodextrin-binding protein (pfMBP) as a fusion partner improved Influenza hemagglutinin antigen vaccine solubility and thermostability. A pfMBP hemagglutinin HA2 domain fusion protein was a potent immunogen. Manufacturing processes that combined up to 5 g/L defined media fermentation yields with rapid, selective, thermostable pfMBP fusion protein purification were developed. The pVEX pfMBP-based thermostable tag (TST) platform is a generic protein engineering approach to enable high yield manufacture of thermostable recombinant protein vaccine components. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Williams, James A.] Nat Technol Corp, Res & Dev, Lincoln, NE 68521 USA.
[Sun, Ping; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Williams, JA (reprint author), Nat Technol Corp, Res & Dev, 4701 Innovat Dr, Lincoln, NE 68521 USA.
EM jim@natx.com
NR 32
TC 7
Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1656
J9 J BIOTECHNOL
JI J. Biotechnol.
PD FEB 10
PY 2011
VL 151
IS 3
BP 242
EP 250
DI 10.1016/j.jbiotec.2010.12.011
PG 9
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 722JD
UT WOS:000287427600002
PM 21168452
ER
PT J
AU Fernandez, C
Minton, AP
AF Fernandez, Cristina
Minton, Allen P.
TI Effect of Nonadditive Repulsive Intermolecular Interactions on the Light
Scattering of Concentrated Protein-Osmolyte Mixtures
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID BOVINE SERUM-ALBUMIN; HARD PARTICLE MODEL; SELF-ASSOCIATING PROTEINS;
OSMOTIC-PRESSURE
AB The static light scattering of three globular proteins; bovine serum albumin, ovalbumin, and ovomucoid, and binary mixtures of each protein and trimethylamine oxide (TMAO) containing between 10 and 70% protein, Were measured as a function of total weight per volume concentration up to 100 g/L. The observed dependence of scattering upon concentration may be accounted for quantitatively by an effective hard sphere model incorporating an extension that takes into account the nonadditive nature of the repulsive intermolecular interaction between protein and TMAO.
C1 [Fernandez, Cristina; Minton, Allen P.] NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Minton, AP (reprint author), NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
RI Fernandez, Cristina/G-2269-2015;
OI Fernandez, Cristina/0000-0003-3792-4015; Minton,
Allen/0000-0001-8459-1247
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX The authors thank Dr. Peter McPhie, NIH, for critical review of a
preliminary draft of this report. This research was supported by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 25
TC 13
Z9 13
U1 1
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD FEB 10
PY 2011
VL 115
IS 5
BP 1289
EP 1293
DI 10.1021/jp110285b
PG 5
WC Chemistry, Physical
SC Chemistry
GA 714HF
UT WOS:000286797700061
PM 21175126
ER
PT J
AU Khattar, SK
Kumar, S
Xiao, S
Collins, PL
Samal, SK
AF Khattar, Sunil K.
Kumar, Sachin
Xiao, Sa
Collins, Peter L.
Samal, Siba K.
TI Experimental Infection of Mice with Avian Paramyxovirus Serotypes 1 to 9
SO PLOS ONE
LA English
DT Article
ID NEWCASTLE-DISEASE-VIRUS; HEMAGGLUTININ-NEURAMINIDASE PROTEIN; COMPLETE
GENOME SEQUENCE; COMPLETE NUCLEOTIDE-SEQUENCE; VACCINE VECTOR; COMPLETE
REGRESSION; FUSION PROTEIN; GREAT-BRITAIN; CLEAVAGE SITE; VIRULENCE
AB The nine serotypes of avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds worldwide. APMV-1, also called Newcastle disease virus, was shown to be attenuated in non-avian species and is being developed as a potential vector for human vaccines. In the present study, we extended this evaluation to the other eight serotypes by evaluating infection in BALB/c mice. Mice were inoculated intranasally with a prototype strain of each of the nine serotypes and monitored for clinical disease, gross pathology, histopathology, virus replication and viral antigen distribution, and seroconversion. On the basis of multiple criteria, each of the APMV serotypes except serotype 5 was found to replicate in mice. Five of the serotypes produced clinical disease and significant weight loss in the following order of severity: 1, 2>6, 9>7. However, disease was short-lived. The other serotypes produced no evident clinical disease. Replication of all of the APMVs except APMV-5 in the nasal turbinates and lungs was confirmed by the recovery of infectious virus and by substantial expression of viral antigen in the epithelial lining detected by immunohistochemistry. Trace levels of infectious APMV-4 and -9 were detected in the brain of some animals; otherwise, no virus was detected in the brain, small intestine, kidney, or spleen. Histologically, infection with the APMVs resulted in lung lesions consistent with broncho-interstitial pneumonia of varying severity that were completely resolved at 14 days post infection. All of the mice infected with the APMVs except APMV-5 produced serotype-specific HI serum antibodies, confirming a lack of replication of APMV-5. Taken together, these results demonstrate that all APMV serotypes except APMV-5 are capable of replicating in mice with minimal disease and pathology.
C1 [Khattar, Sunil K.; Kumar, Sachin; Xiao, Sa; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Khattar, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU NIAID [N01A060009]; NIAID, NIH
FX This research was supported by NIAID contract no. N01A060009 (85%
support) and NIAID, NIH Intramural Research Program (15% support). The
views expressed herein do not necessarily reflect the official policies
of the Department of Health and Human Services; nor does mention of
trade names, commercial practices, or organizations imply endorsement by
the U. S. Government. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 59
TC 9
Z9 10
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 10
PY 2011
VL 6
IS 2
AR e16776
DI 10.1371/journal.pone.0016776
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721NZ
UT WOS:000287363000017
PM 21347313
ER
PT J
AU Ragert, P
Nierhaus, T
Cohen, LG
Villringer, A
AF Ragert, Patrick
Nierhaus, Till
Cohen, Leonardo G.
Villringer, Arno
TI Interhemispheric Interactions between the Human Primary Somatosensory
Cortices
SO PLOS ONE
LA English
DT Article
ID POSTERIOR CORPUS-CALLOSUM; MOTOR CORTEX; MEDIAN NERVE; CONNECTIONS;
STIMULATION; INFORMATION; MODULATION; PLASTICITY; FIELDS; INPUT
AB In the somatosensory domain it is still unclear at which processing stage information reaches the opposite hemispheres. Due to dense transcallosal connections, the secondary somatosensory cortex (S2) has been proposed to be the key candidate for interhemispheric information transfer. However, recent animal studies showed that the primary somatosensory cortex (S1) might as well account for interhemispheric information transfer. Using paired median nerve somatosensory evoked potential recordings in humans we tested the hypothesis that interhemispheric inhibitory interactions in the somatosensory system occur already in an early cortical processing stage such as S1. Conditioning right S1 by electrical median nerve (MN) stimulation of the left MN (CS) resulted in a significant reduction of the N20 response in the target (left) S1 relative to a test stimulus (TS) to the right MN alone when the interstimulus interval between CS and TS was between 20 and 25 ms. No such changes were observed for later cortical components such as the N20/P25, N30, P40 and N60 amplitude. Additionally, the subcortically generated P14 response in left S1 was also not affected. These results document the existence of interhemispheric inhibitory interactions between S1 in human subjects in the critical time interval of 20-25 ms after median nerve stimulation.
C1 [Ragert, Patrick; Nierhaus, Till; Villringer, Arno] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Nierhaus, Till; Villringer, Arno] Charite, Dept Neurol, Berlin, Germany.
[Villringer, Arno] Humboldt Univ, Berlin Sch Mind & Brain, Berlin, Germany.
RP Ragert, P (reprint author), Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany.
EM ragert@cbs.mpg.de
RI Winstein, Carolee/A-8375-2008
NR 29
TC 23
Z9 23
U1 2
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 10
PY 2011
VL 6
IS 2
AR e16150
DI 10.1371/journal.pone.0016150
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721NZ
UT WOS:000287363000006
PM 21347308
ER
PT J
AU Jensen, RT
Delle Fave, G
AF Jensen, Robert T.
Delle Fave, Gianfranco
TI Promising Advances in the Treatment of Malignant Pancreatic Endocrine
Tumors.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID NEUROENDOCRINE TUMORS
C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
[Delle Fave, Gianfranco] Univ Roma La Sapienza, Div Digest & Liver Dis, Rome, Italy.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
NR 10
TC 31
Z9 33
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 10
PY 2011
VL 364
IS 6
BP 564
EP 565
DI 10.1056/NEJMe1013903
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 718QH
UT WOS:000287139900013
PM 21306243
ER
PT J
AU Slager, SL
Rabe, KG
Achenbach, SJ
Vachon, CM
Goldin, LR
Strom, SS
Lanasa, MC
Spector, LG
Rassenti, LZ
Leis, JF
Camp, NJ
Glenn, M
Kay, NE
Cunningham, JM
Hanson, CA
Marti, GE
Weinberg, JB
Morrison, VA
Link, BK
Call, TG
Caporaso, NE
Cerhan, JR
AF Slager, Susan L.
Rabe, Kari G.
Achenbach, Sara J.
Vachon, Celine M.
Goldin, Lynn R.
Strom, Sara S.
Lanasa, Mark C.
Spector, Logan G.
Rassenti, Laura Z.
Leis, Jose F.
Camp, Nicola J.
Glenn, Martha
Kay, Neil E.
Cunningham, Julie M.
Hanson, Curtis A.
Marti, Gerald E.
Weinberg, J. Brice
Morrison, Vicki A.
Link, Brian K.
Call, Timothy G.
Caporaso, Neil E.
Cerhan, James R.
TI Genome-wide association study identifies a novel susceptibility locus at
6p21.3 among familial CLL
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; FOLLICULAR LYMPHOMA;
RISK; VARIANTS; GENES
AB Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values <= 3.37 x 10(-8)), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 x 10(-9)). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies. (Blood. 2011;117(6):1911-1916)
C1 [Slager, Susan L.; Rabe, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Leis, Jose F.; Kay, Neil E.; Cunningham, Julie M.; Hanson, Curtis A.; Call, Timothy G.; Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN 55905 USA.
[Goldin, Lynn R.; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Lanasa, Mark C.; Weinberg, J. Brice] Duke Univ, Med Ctr, Durham, NC USA.
[Spector, Logan G.; Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA.
[Rassenti, Laura Z.] Univ Calif San Diego, Med Ctr, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Camp, Nicola J.; Glenn, Martha] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Marti, Gerald E.] US FDA, Bethesda, MD 20014 USA.
[Weinberg, J. Brice] Durham Vet Adm Med Ctr, Durham, NC USA.
[Morrison, Vicki A.] Minneapolis Vet Adm Med Ctr, Minneapolis, MN USA.
[Link, Brian K.] Univ Iowa, Iowa City, IA USA.
RP Slager, SL (reprint author), Mayo Clin, Coll Med, 200 1st St SW, Rochester, MN 55905 USA.
EM slager@mayo.edu
OI Cerhan, James/0000-0002-7482-178X; Spector, Logan/0000-0003-2516-0222
FU National Institutes of Health (NIH) [CA118444, CA92153]; NIH, NCI;
Veterans Affairs Research Service; Chronic Lymphocytic Leukemia Research
Consortium; National Center for Research Resources; NIH Roadmap for
Medical Research [1 UL1 RR024150]; NCI [CA15083, N01-PC-35 141];
University of Utah Huntsman Cancer Institute; Utah State Department of
Health; University of Utah; Leukemia & Lymphoma Society; Bernstein
Family Fund for Leukemia and Lymphoma Research
FX This work was supported by National Institutes of Health (NIH) grants
CA118444 and CA92153; the Intramural Research Program of the NIH, NCI;
the Veterans Affairs Research Service, and the Chronic Lymphocytic
Leukemia Research Consortium. Additional support was provided by the
National Center for Research Resources, a component of NIH and the NIH
Roadmap for Medical Research (1 UL1 RR024150) and by the NCI (CA15083).
Data collection in Utah was made possible by the Utah Population
Database and the Utah Registry. Partial support for all data in the Utah
Population Database was provided by the University of Utah Huntsman
Cancer Institute. The Utah Cancer Registry is funded by contract
N01-PC-35 141 from the NCI Surveillance Epidemiology and End Results
program with additional support from the Utah State Department of Health
and the University of Utah. Sample collection at Duke University was
supported by a Leukemia & Lymphoma Society Career Development Award (to
M.C.L.) and by the Bernstein Family Fund for Leukemia and Lymphoma
Research.
NR 17
TC 61
Z9 64
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 10
PY 2011
VL 117
IS 6
BP 1911
EP 1916
DI 10.1182/blood-2010-09-308205
PG 6
WC Hematology
SC Hematology
GA 719HA
UT WOS:000287192300026
PM 21131588
ER
PT J
AU Ju, W
Zhang, ML
Jiang, JK
Thomas, CJ
Oh, U
Bryant, BR
Chen, J
Sato, N
Tagaya, Y
Morris, JC
Janik, JE
Jacobson, S
Waldmann, TA
AF Ju, Wei
Zhang, Meili
Jiang, Jian-Kang
Thomas, Craig J.
Oh, Unsong
Bryant, Bonita R.
Chen, Jing
Sato, Noriko
Tagaya, Yutaka
Morris, John C.
Janik, John E.
Jacobson, Steven
Waldmann, Thomas A.
TI CP-690,550, a therapeutic agent, inhibits cytokine-mediated Jak3
activation and proliferation of T cells from patients with ATL and
HAM/TSP
SO BLOOD
LA English
DT Article
ID VIRUS TYPE-I; SEVERE COMBINED IMMUNODEFICIENCY; TROPICAL SPASTIC
PARAPARESIS; MICE LACKING JAK3; HTLV-I; ALLOGRAFT-REJECTION;
LEUKEMIA-LYMPHOMA; CELLULAR-TRANSFORMATION; NONHUMAN-PRIMATES;
INTERFERON-ALFA
AB The retrovirus, human T-cell-lymphotrophic virus-1 (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and the neurological disorder HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-I-encoded protein tax constitutively activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems that in turn activate the Jak3 (Janus kinase 3)/STAT5 (signal transducers and activators of transcription 5) pathway, suggesting a therapeutic strategy that involves targeting Jak3. We evaluated the action of the Jak3 inhibitor CP-690,550 on cytokine dependent ex vivo proliferation that is characteristic of peripheral blood mononuclear cells (PBMCs) from select patients with smoldering or chronic subtypes of ATL, or from those with HAM/TSP whose PBMCs are associated with autocrine/paracrine pathways that involve the production of IL-2, IL-9, IL-15, and their receptors. CP-690,550 at 50nM inhibited the 6-day ex vivo spontaneous proliferation of PBMCs from ATL and HAM/TSP patients by 67.1% and 86.4%, respectively. Furthermore, CP-690,550 inhibited STAT5 phosphorylation in isolated ATL T cells ex vivo. Finally, in an in vivo test of biological activity, CP-690,550 treatment of mice with a CD8 T-cell IL-15-transgenic leukemia that manifests an autocrine IL-15/IL-15R alpha pathway prolonged the survival duration of these tumor-bearing mice. These studies support further evaluation of the Jak3 inhibitor CP-690,550 in the treatment of select patients with HTLV-I-associated ATL and HAM/TSP. (Blood. 2011; 117(6): 1938-1946)
C1 [Ju, Wei; Zhang, Meili; Bryant, Bonita R.; Chen, Jing; Sato, Noriko; Tagaya, Yutaka; Morris, John C.; Janik, John E.; Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jiang, Jian-Kang; Thomas, Craig J.] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Oh, Unsong; Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD USA.
RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov
FU Center for Cancer Research, NCI, NIH
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, NCI, NIH.
NR 47
TC 31
Z9 31
U1 3
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 10
PY 2011
VL 117
IS 6
BP 1938
EP 1946
DI 10.1182/blood-2010-09-305425
PG 9
WC Hematology
SC Hematology
GA 719HA
UT WOS:000287192300029
PM 21106989
ER
PT J
AU Li, Q
Haigis, KM
McDaniel, A
Harding-Theobald, E
Kogan, SC
Akagi, K
Wong, JCY
Braun, BS
Wolff, L
Jacks, T
Shannon, K
AF Li, Qing
Haigis, Kevin M.
McDaniel, Andrew
Harding-Theobald, Emily
Kogan, Scott C.
Akagi, Keiko
Wong, Jasmine C. Y.
Braun, Benjamin S.
Wolff, Linda
Jacks, Tyler
Shannon, Kevin
TI Hematopoiesis and leukemogenesis in mice expressing oncogenic Nras(G12D)
from the endogenous locus
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; K-RAS ONCOGENE; SOMATIC ACTIVATION; N-RAS;
MYELOPROLIFERATIVE DISORDER; ERYTHROID-DIFFERENTIATION; CONDITIONAL
EXPRESSION; SIGNAL-TRANSDUCTION; HYPERACTIVE RAS; HUMAN CANCER
AB NRAS is frequently mutated in hematologic malignancies. We generated Mx1-Cre, Lox-STOP-Lox (LSL)-Nras(G12D) mice to comprehensively analyze the phenotypic, cellular, and biochemical consequences of endogenous oncogenic Nras expression in hematopoietic cells. Here we show that Mx1-Cre, LSL-Nras(G12D) mice develop an indolent myeloproliferative disorder but ultimately die of a diverse spectrum of hematologic cancers. Expressing mutant Nras in hematopoietic tissues alters the distribution of hematopoietic stem and progenitor cell populations, and Nras mutant progenitors show distinct responses to cytokine growth factors. Injecting Mx1-Cre, LSL-Nras(G12D) mice with the MOL4070LTR retrovirus causes acute myeloid leukemia that faithfully recapitulates many aspects of human NRAS-associated leukemias, including cooperation with deregulated Evi1 expression. The disease phenotype in Mx1-Cre, LSL-Nras(G12D) mice is attenuated compared with Mx1-Cre, LSL-Kras(G12D) mice, which die of aggressive myeloproliferative disorder by 4 months of age. We found that endogenous Kras(G12D) expression results in markedly elevated Ras protein expression and Ras-GTP levels in Mac1(+) cells, whereas Mx1-Cre, LSL-Nras(G12D) mice show much lower Ras protein and Ras-GTP levels. Together, these studies establish a robust and tractable system for interrogating the differential properties of oncogenic Ras proteins in primary cells, for identifying candidate cooperating genes, and for testing novel therapeutic strategies. (Blood. 2011; 117(6): 2022-2032)
C1 [McDaniel, Andrew; Harding-Theobald, Emily; Wong, Jasmine C. Y.; Braun, Benjamin S.; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
[Li, Qing] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94158 USA.
[Kogan, Scott C.; Shannon, Kevin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
[Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Columbus, OH 43210 USA.
[Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol, Columbus, OH 43210 USA.
[Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Dept Med Genet, Columbus, OH 43210 USA.
[Wolff, Linda] NCI, Cellular Oncol Lab, Frederick, MD 21701 USA.
[Jacks, Tyler] MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
[Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Shannon, K (reprint author), Univ Calif San Francisco, Dept Pediat, Helen Diller Family Canc Res Bldg,1450 3rd St,Rm, San Francisco, CA 94158 USA.
EM shannonk@peds.ucsf.edu
FU National Institutes of Health [U01 CA84221, R37 CA72614, K01 CA118425,
K08 CA134649, K08 CA119105, T32 CA129583]; Leukemia & Lymphoma Society;
Jeffrey and Karen Peterson Family Foundation; Frank A. Campini
Foundation; National Cancer Institute Center for Cancer Research
FX This work was supported by the National Institutes of Health (grants U01
CA84221, R37 CA72614, K01 CA118425, K08 CA134649, K08 CA119105, and T32
CA129583), the Leukemia & Lymphoma Society, the Jeffrey and Karen
Peterson Family Foundation, and the Frank A. Campini Foundation. T.J. is
an Investigator of the Howard Hughes Medical Institute. S.C.K. is a
Leukemia & Lymphoma Society Scholar. The Intramural Research Program of
the National Cancer Institute Center for Cancer Research supports
research in the laboratory of L.W.
NR 46
TC 56
Z9 57
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 10
PY 2011
VL 117
IS 6
BP 2022
EP 2032
DI 10.1182/blood-2010-04-280750
PG 11
WC Hematology
SC Hematology
GA 719HA
UT WOS:000287192300039
PM 21163920
ER
PT J
AU Rajaraman, P
Simpson, J
Neta, G
de Gonzalez, AB
Ansell, P
Linet, MS
Ron, E
Roman, E
AF Rajaraman, Preetha
Simpson, Jill
Neta, Gila
de Gonzalez, Amy Berrington
Ansell, Pat
Linet, Martha S.
Ron, Elaine
Roman, Eve
TI Early life exposure to diagnostic radiation and ultrasound scans and
risk of childhood cancer: case-control study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; IONIZING-RADIATION; MULTIPLE-MYELOMA; OXFORD
SURVEY; X-RAYS; LEUKEMIA; MALIGNANCIES; IRRADIATION; PREGNANCY;
MORTALITY
AB Objective To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days).
Design Case-control study.
Setting England and Wales.
Participants 2690 childhood cancer cases and 4858 age, sex, and region matched controls from the United Kingdom Childhood Cancer Study (UKCCS), born 1976-96.
Main outcome measures Risk of all childhood cancer, leukaemia, lymphoma, and central nervous system tumours, measured by odds ratios.
Results Logistic regression models conditioned on matching factors, with adjustment for maternal age and child's birth weight, showed no evidence of increased risk of childhood cancer with in utero exposure to ultrasound scans. Some indication existed of a slight increase in risk after in utero exposure to x rays for all cancers (odds ratio 1.l4, 95% confidence interval 0.90 to 1.45) and leukaemia (1.36, 0.91 to 2.02), but this was not statistically significant. Exposure to diagnostic x rays in early infancy (0-100 days) was associated with small, non-significant excess risks for all cancers and leukaemia, as well as increased risk of lymphoma (odds ratio 5.14, 1.27 to 20.78) on the basis of small numbers.
Conclusions Although the results for lymphoma need to be replicated, all of the findings indicate possible risks of cancer from radiation at doses lower than those associated with commonly used procedures such as computed tomography scans, suggesting the need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages.
C1 [Rajaraman, Preetha; Neta, Gila; de Gonzalez, Amy Berrington; Linet, Martha S.; Ron, Elaine] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Simpson, Jill; Ansell, Pat; Roman, Eve] Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England.
RP Rajaraman, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM rajarama@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services, USA; Leukaemia and Lymphoma Research
FX This research was supported in part by intramural funds from the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services, USA. 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. The
United Kingdom Childhood Cancer Study (UKCCS) is sponsored and
administered by Leukaemia and Lymphoma Research. The UKCCS was conducted
by 12 teams of investigators (10 clinical and epidemiological and two
biological) based in university departments, research institutes, and
the National Health Service in Scotland. Its work is coordinated by a
management committee. The researchers are independent from the funders.
NR 26
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Z9 44
U1 2
U2 17
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD FEB 10
PY 2011
VL 342
AR d472
DI 10.1136/bmj.d472
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 722BC
UT WOS:000287403200003
PM 21310791
ER
PT J
AU Federico, S
Paoletta, S
Cheong, SL
Pastorin, G
Cacciari, B
Stragliotto, S
Klotz, KN
Siegel, J
Gao, ZG
Jacobson, KA
Moro, S
Spalluto, G
AF Federico, Stephanie
Paoletta, Silvia
Cheong, Siew Lee
Pastorin, Giorgia
Cacciari, Barbara
Stragliotto, Stefano
Klotz, Karl Norbert
Siegel, Jeffrey
Gao, Zhan-Guo
Jacobson, Kenneth A.
Moro, Stefano
Spalluto, Giampiero
TI Synthesis and Biological Evaluation of a New Series of
1,2,4-Triazolo[1,5-a]-1,3,5-triazines as Human A(2A) Adenosine Receptor
Antagonists with Improved Water Solubility
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HUMAN A(3); HIGH-AFFINITY; LIGAND RECOGNITION; PARKINSONS-DISEASE; A(2B)
RECEPTOR; HIGHLY POTENT; DERIVATIVES; PHARMACOLOGY; TRIAZOLOTRIAZINE;
RADIOLIGAND
AB The structure-activity relationship (SAR) of 1,2,4-triazolo[1,5-a]-1,3,5-triazine derivatives related to ZM241385 as antagonists of the A(2A) adenosine receptor (AR) was explored through the synthesis of analogues substituted at the 5 position. The A(2A) AR X-ray structure was used to propose a structural basis for the activity and selectivity of the analogues and to direct the synthetic design strategy to provide access to solvent-exposed regions. Thus, we have identified a point of substitution for the attachment of solubilizing groups to enhance both aqueous solubility and physicochemical properties, maintaining potent interactions with the A(2A) AR and, in some cases, receptor subtype selectivity. Among the most potent and selective novel compounds were a long-chain ether-containing amine congener 20 (K-i 11.5 nM) and its urethane-protected derivative 14 (K-i 17.8 nM). Compounds 20 and 31 (K-i 11.5 and 16.9 nM, respectively) were readily water-soluble up to 10 mM. The analogues were docked in the crystallographic structure of the hA(2A) AR and in a homology model of the hA(3) AR, and the per residue electrostatic and hydrophobic contributions to the binding were assessed and stabilizing factors were proposed.
C1 [Paoletta, Silvia; Stragliotto, Stefano; Moro, Stefano] Univ Padua, Dipartimento Sci Farmaceut, MMS, I-35131 Padua, Italy.
[Federico, Stephanie; Spalluto, Giampiero] Univ Trieste, Dipartimento Sci Farmaceut, I-34127 Trieste, Italy.
[Cheong, Siew Lee; Pastorin, Giorgia] Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore.
[Cacciari, Barbara] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
[Klotz, Karl Norbert] Univ Wurzburg, Inst Pharmakol, D-97078 Wurzburg, Germany.
[Siegel, Jeffrey; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, MRS, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Moro, S (reprint author), Univ Padua, Dipartimento Sci Farmaceut, MMS, Via Marzolo 5, I-35131 Padua, Italy.
EM stefano.moro@unipd.it; spalluto@units.it
RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; Pastorin,
Giorgia/B-5907-2015;
OI Moro, Stefano/0000-0002-7514-3802; Jacobson,
Kenneth/0000-0001-8104-1493; Federico, Stephanie/0000-0003-2800-5287
FU University of Padova, Italy; Italian Ministry for University and
Research (MIUR), Rome, Italy; NIH, National Institute of Diabetes and
Digestive and Kidney Diseases
FX The work coordinated by S.M. was carried out with financial support from
the University of Padova, Italy, and the Italian Ministry for University
and Research (MIUR), Rome, Italy. This research was also supported in
part by the Intramural Research Program of the NIH, National Institute
of Diabetes and Digestive and Kidney Diseases. S.M. is very grateful to
Chemical Computing Group Inc. (Montreal, Quebec, Canada) for the
scientific and technical partnership.
NR 53
TC 21
Z9 21
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 10
PY 2011
VL 54
IS 3
BP 877
EP 889
DI 10.1021/jm101349u
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 714HJ
UT WOS:000286798100016
PM 21214204
ER
PT J
AU Green, ED
Guyer, MS
AF Green, Eric D.
Guyer, Mark S.
CA Natl Human Genome Res Inst
TI Charting a course for genomic medicine from base pairs to bedside
SO NATURE
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; WIDE ASSOCIATION;
BREAST-CANCER; FUNCTIONAL ELEMENTS; GENETICS RESEARCH; AMERICAN SOCIETY;
CROHNS-DISEASE; RECEPTOR GENE; THERAPY
AB There has been much progress in genomics in the ten years since a draft sequence of the human genome was published. Opportunities for understanding health and disease are now unprecedented, as advances in genomics are harnessed to obtain robust foundational knowledge about the structure and function of the human genome and about the genetic contributions to human health and disease. Here we articulate a 2011 vision for the future of genomics research and describe the path towards an era of genomic medicine.
C1 [Green, Eric D.; Guyer, Mark S.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Green, ED (reprint author), NHGRI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM egreen@nhgri.nih.gov
NR 103
TC 384
Z9 392
U1 4
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 204
EP 213
DI 10.1038/nature09764
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200034
PM 21307933
ER
PT J
AU Alberi, L
Liu, SX
Wang, Y
Badie, R
Smith-Hicks, C
Wu, J
Pierfelice, TJ
Abazyan, B
Mattson, MP
Kuhl, D
Pletnikov, M
Worley, PF
Gaiano, N
AF Alberi, Lavinia
Liu, Shuxi
Wang, Yue
Badie, Ramy
Smith-Hicks, Constance
Wu, Jing
Pierfelice, Tarran J.
Abazyan, Bagrat
Mattson, Mark P.
Kuhl, Dietmar
Pletnikov, Mikhail
Worley, Paul F.
Gaiano, Nicholas
TI Activity-Induced Notch Signaling in Neurons Requires Arc/Arg3.1 and Is
Essential for Synaptic Plasticity in Hippocampal Networks
SO NEURON
LA English
DT Article
ID LONG-TERM-MEMORY; IMMEDIATE-EARLY GENE; MOUSE-BRAIN; CELL FATE;
DROSOPHILA; EXPRESSION; RECEPTOR; MICE; ARC; PROTEIN
AB Notch signaling in the nervous system has been most studied in the context of cell fate specification. However, numerous studies have suggested that Notch also regulates neuronal morphology, synaptic plasticity, learning, and memory. Here we show that Notch1 and its ligand Jagged1 are present at the synapse, and that Notch signaling in neurons occurs in response to synaptic activity. In addition, neuronal Notch signaling is positively regulated by Arc/Arg3.1, an activity-induced gene required for synaptic plasticity. In Arc/Arg3.1 mutant neurons, the proteolytic activation of Notch1 is disrupted both in vivo and in vitro. Conditional deletion of Notch1 in the postnatal hippocampus disrupted both long-term potentiation (LTP) and long-term depression (LTD), and led to deficits in learning and short-term memory. Thus, Notch signaling is dynamically regulated in response to neuronal activity, Arc/Arg3.1 is a context-dependent Notch regulator, and Notch1 is required for the synaptic plasticity that contributes to memory formation.
C1 [Alberi, Lavinia; Liu, Shuxi; Badie, Ramy; Pierfelice, Tarran J.; Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD 21205 USA.
[Alberi, Lavinia; Liu, Shuxi; Badie, Ramy; Smith-Hicks, Constance; Pierfelice, Tarran J.; Worley, Paul F.; Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Smith-Hicks, Constance; Wu, Jing; Mattson, Mark P.; Worley, Paul F.; Gaiano, Nicholas] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
[Abazyan, Bagrat; Pletnikov, Mikhail] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Wang, Yue; Mattson, Mark P.] NIA, Neurosci Lab, Baltimore, MD 21224 USA.
[Kuhl, Dietmar] Univ Med Ctr Hamburg Eppendorf, Inst Mol & Cellular Cognit, Ctr Mol Neurobiol ZMNH, D-20251 Hamburg, Germany.
RP Alberi, L (reprint author), Univ Fribourg, Dept Med Anat, Rte Albert Gockel 1, CH-1700 Fribourg, Switzerland.
EM lavinia.alberi@unifr.ch; gaiano@jhmi.edu
RI Mattson, Mark/F-6038-2012;
OI Kuhl, Dietmar/0000-0002-4772-6701
FU Institute for Cell Engineering at Johns Hopkins University; NARSAD;
James S. McDonnell Foundation; National Institute of Mental Health
FX The authors thank Jason Shepherd, Richard Flannery, Marlin Dehoff, Vera
Goh, and Keejung Yoon for technical and intellectual input during the
course of this project. We also thank Ted Dawson and Jay Baraban for
critically reading the manuscript. Funding for this work came from the
Institute for Cell Engineering at Johns Hopkins University (N.G.), a
NARSAD Young Investigator Award (N.G), the James S. McDonnell Foundation
(N.G.), and the National Institute of Mental Health (P.F.W.).
NR 32
TC 77
Z9 81
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD FEB 10
PY 2011
VL 69
IS 3
BP 437
EP 444
DI 10.1016/j.neuron.2011.01.004
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 724XM
UT WOS:000287609700006
PM 21315255
ER
PT J
AU Mentis, GZ
Blivis, D
Liu, WF
Drobac, E
Crowder, ME
Kong, L
Alvarez, FJ
Sumner, CJ
O'Donovan, MJ
AF Mentis, George Z.
Blivis, Dvir
Liu, Wenfang
Drobac, Estelle
Crowder, Melissa E.
Kong, Lingling
Alvarez, Francisco J.
Sumner, Charlotte J.
O'Donovan, Michael J.
TI Early Functional Impairment of Sensory-Motor Connectivity in a Mouse
Model of Spinal Muscular Atrophy
SO NEURON
LA English
DT Article
ID VESICULAR GLUTAMATE TRANSPORTERS; AMYOTROPHIC-LATERAL-SCLEROSIS; PRIMARY
AFFERENT SYNAPSES; ELECTROPHYSIOLOGICAL PROPERTIES;
NEUROMUSCULAR-JUNCTIONS; ALZHEIMERS-DISEASE; PROTEIN EXPRESSION;
SYNAPTIC INPUTS; NEURON PROTEIN; RENSHAW CELLS
AB To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes, illustrating the reversibility of these synaptic defects. Deafferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention.
C1 [Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Crowder, Melissa E.; O'Donovan, Michael J.] NINDS, Sect Dev Biol, NIH, Bethesda, MD 20892 USA.
[Mentis, George Z.; Drobac, Estelle] Columbia Univ, Dept Neurol, New York, NY 10032 USA.
[Mentis, George Z.; Drobac, Estelle] Columbia Univ, Ctr Motor Neuron Biol & Dis, New York, NY 10032 USA.
[Crowder, Melissa E.; Kong, Lingling; Sumner, Charlotte J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA.
[Crowder, Melissa E.; Kong, Lingling; Sumner, Charlotte J.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA.
[Alvarez, Francisco J.] Wright State Univ, Dept Neurosci Cell Biol & Physiol, Dayton, OH 45435 USA.
RP Mentis, GZ (reprint author), NINDS, Sect Dev Biol, NIH, Bethesda, MD 20892 USA.
EM gzmentis@columbia.edu
RI Blivis, Dvir/F-9385-2012; o'donovan, michael/A-2357-2015; Alvarez,
Francisco/H-4929-2011
OI Blivis, Dvir/0000-0001-6203-7325; o'donovan,
michael/0000-0003-2487-7547;
FU NINDS [R01NS062869]; SMA Foundation; Howard Hughes Medical Institute
FX We are grateful to Drs. T.M. Jessell, C.E. Henderson, S. Przedborski, L.
Pellizzoni, N.A. Shneider, and K. Fischbeck for comments on the
manuscript and for the generous support of Dr. K. Fischbeck. The
technical assistance of the late Ms. A.A. Taye (genotyping) and Mrs. J.
Sisco (muscle spindle staining) is also appreciated. Thanks to Dr. D.
Ladle for assistance in muscle dissection. The work was supported by the
NINDS Intramural Program and the SMA Foundation (G.Z.M.). C.J.S. was
supported by an NINDS grant (R01NS062869) and Howard Hughes Medical
Institute Physician Scientist Award.
NR 71
TC 126
Z9 126
U1 3
U2 22
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD FEB 10
PY 2011
VL 69
IS 3
BP 453
EP 467
DI 10.1016/j.neuron.2010.12.032
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 724XM
UT WOS:000287609700008
PM 21315257
ER
PT J
AU Stevens, AJ
Jensen, JJ
Wyller, K
Kilgore, PC
Chatterjee, S
Rohrbaugh, ML
AF Stevens, Ashley J.
Jensen, Jonathan J.
Wyller, Katrine
Kilgore, Patrick C.
Chatterjee, Sabarni
Rohrbaugh, Mark L.
TI The Role of Public-Sector Research in the Discovery of Drugs and
Vaccines.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
AB Background: Historically, public-sector researchers have performed the upstream, basic research that elucidated the underlying mechanisms of disease and identified promising points of intervention, whereas corporate researchers have performed the downstream, applied research resulting in the discovery of drugs for the treatment of diseases and have carried out development activities to bring them to market. However, the boundaries between the roles of the public and private sectors have shifted substantially since the dawn of the biotechnology era, and the public sector now has a much more direct role in the applied-research phase of drug discovery.
Methods: We identified new drugs and vaccines approved by the Food and Drug Administration (FDA) that were discovered by public-sector research institutions (PSRIs) and classified them according to their therapeutic category and potential therapeutic effect.
Results: We found that during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs. These drugs included 93 small-molecule drugs, 36 biologic agents, 15 vaccines, 8 in vivo diagnostic materials, and 1 over-the-counter drug. More than half of these drugs have been used in the treatment or prevention of cancer or infectious diseases. PSRI-discovered drugs are expected to have a disproportionately large therapeutic effect.
Conclusions: Public-sector research has had a more immediate effect on improving public health than was previously realized.
N Engl J Med 2011;364:535-41.
C1 [Stevens, Ashley J.; Jensen, Jonathan J.] Boston Univ, Sch Management, Inst Technol Entrepreneurship & Commercializat, Boston, MA 02215 USA.
[Stevens, Ashley J.; Jensen, Jonathan J.] Boston Univ, Sch Management, Off Technol Dev, Boston, MA 02215 USA.
[Wyller, Katrine] Norwegian Radium Hosp Res Fdn, Oslo, Norway.
[Kilgore, Patrick C.] Boston Univ, Sch Law, Boston, MA 02215 USA.
[Chatterjee, Sabarni; Rohrbaugh, Mark L.] NIH, Off Technol Transfer, Bethesda, MD 20892 USA.
RP Stevens, AJ (reprint author), Boston Univ, Sch Management, Inst Technol Entrepreneurship & Commercializat, 53 Bay State Rd, Boston, MA 02215 USA.
EM astevens@bu.edu
RI Kilgore, Paul/L-1462-2013;
OI Kilgore, Paul/0000-0003-3214-4482; Rohrbaugh, Mark/0000-0002-6136-3337
NR 19
TC 66
Z9 66
U1 0
U2 7
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 10
PY 2011
VL 364
IS 6
BP 535
EP 541
DI 10.1056/NEJMsa1008268
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 718QH
UT WOS:000287139900007
PM 21306239
ER
PT J
AU Kurmangaliyev, YZ
Goland, A
Gelfand, MS
AF Kurmangaliyev, Yerbol Z.
Goland, Alexander
Gelfand, Mikhail S.
TI Evolutionary patterns of phosphorylated serines
SO BIOLOGY DIRECT
LA English
DT Article
ID PROTEIN-PHOSPHORYLATION; POSTTRANSLATIONAL MODIFICATIONS;
PHOSPHOPROTEOME ANALYSIS; LYSINE ACETYLATION; PROTEOMIC ANALYSIS;
MASS-SPECTROMETRY; GLOBAL ANALYSIS; IN-VIVO; SITES; CONSERVATION
AB Posttranslationally modified amino acids are chemically distinct types of amino acids and in terms of evolution they might behave differently from their non-modified counterparts. In order to check this possibility, we reconstructed the evolutionary history of phosphorylated serines in several groups of organisms. Comparisons of substitution vectors have revealed some significant differences in the evolution of modified and corresponding non-modified amino acids. In particular, phosphoserines are more frequently substituted to aspartate and glutamate, compared to non-phosphorylated serines.
C1 [Kurmangaliyev, Yerbol Z.; Goland, Alexander; Gelfand, Mikhail S.] RAS, Inst Informat Transmiss Problems, Kharkevich Inst, Moscow 127994, Russia.
[Kurmangaliyev, Yerbol Z.] Natl Ctr Biotechnol Republ Kazakhstan, Astana 010000, Kazakhstan.
[Gelfand, Mikhail S.] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia.
RP Gelfand, MS (reprint author), RAS, Inst Informat Transmiss Problems, Kharkevich Inst, Bolshoi Karetny Pereulok 19, Moscow 127994, Russia.
EM gelfand@iitp.ru
RI Gelfand, Mikhail/F-3425-2012
FU Russian Foundation of Basic Research [09-04-92745]; Russian Academy of
Sciences; [2.740.11.0101]
FX We are grateful to Dmitry Malko, Ekaterina Ermakova and Anna Lyubetskaya
who shared their programs and data, and to Stefka Tyanova and Jurgen Cox
for useful discussions. This study was partially supported by the state
contract 2.740.11.0101, Russian Foundation of Basic Research
(09-04-92745), and program "Molecular and Cellular Biology" of the
Russian Academy of Sciences.
NR 35
TC 2
Z9 2
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD FEB 9
PY 2011
VL 6
AR 8
DI 10.1186/1745-6150-6-8
PG 7
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 725MH
UT WOS:000287648300001
PM 21306633
ER
PT J
AU Riazuddin, S
Ahmed, ZM
Hegde, RS
Khan, SN
Nasir, I
Shaukat, U
Riazuddin, S
Butman, JA
Griffith, AJ
Friedman, TB
Choi, BY
AF Riazuddin, Saima
Ahmed, Zubair M.
Hegde, Rashmi S.
Khan, Shaheen N.
Nasir, Idrees
Shaukat, Uzma
Riazuddin, Sheikh
Butman, John A.
Griffith, Andrew J.
Friedman, Thomas B.
Choi, Byung Yoon
TI Variable expressivity of FGF3 mutations associated with deafness and
LAMM syndrome
SO BMC MEDICAL GENETICS
LA English
DT Article
ID FIBROBLAST-GROWTH-FACTOR; SENSORINEURAL HEARING-LOSS; INNER-EAR
AGENESIS; STRUCTURAL BASIS; NONSYNDROMIC DEAFNESS; LADD SYNDROME; FACTOR
FAMILY; MICRODONTIA; MICROTIA; SPECIFICITY
AB Background: Recessive mutations of fibroblast growth factor 3 (FGF3) can cause LAMM syndrome (OMIM 610706), characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia.
Methods: We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to FGF3 mutations. Ten affected individuals from three large Pakistani families segregating FGF3 mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations.
Results: Two families segregated reported mutations (p.R104X and p.R95W) and one family segregated a novel mutation (p.R132GfsX26) of FGF3. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced FGF10 as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of FGF3, otitis media, or a consequence of genetic background in these three family members.
Conclusions: We noted a less prominent dental and external ear phenotype in association with the homozygous p.R95W. Therefore, we conclude that the manifestations of recessive FGF3 mutations range from fully penetrant LAMM syndrome to deafness with residual inner ear structures and, by extension, with minimal syndromic features, an observation with implications for cochlear implantation candidacy.
C1 [Riazuddin, Saima] Cincinnati Childrens Hosp Res Fdn, Div Pediat Otolaryngol Head & Neck Surg, Mol Genet Lab, Cincinnati, OH USA.
[Ahmed, Zubair M.] Cincinnati Childrens Hosp Res Fdn, Div Pediat Ophthalmol, Cincinnati, OH USA.
[Hegde, Rashmi S.] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH USA.
[Khan, Shaheen N.; Nasir, Idrees; Shaukat, Uzma] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Griffith, Andrew J.; Choi, Byung Yoon] NIDCD, Otolaryngol Branch, NIH, Rockville, MD USA.
[Friedman, Thomas B.; Choi, Byung Yoon] NIDCD, Mol Genet Lab, NIH, Rockville, MD USA.
[Choi, Byung Yoon] Seoul Natl Univ, Bundang Hosp, Coll Med, Dept Otorhinolaryngol, Songnam, South Korea.
[Riazuddin, Saima; Ahmed, Zubair M.; Hegde, Rashmi S.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
RP Choi, BY (reprint author), NIDCD, Otolaryngol Branch, NIH, Rockville, MD USA.
EM twinwifegirl@empal.com
RI Nasim Khan, Shaheen/F-2135-2015; Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU National Institute on Deafness and Other Communication Disorders
[DC00039-14, DC00060-07]; Higher Education Commission (HEC), Islamabad,
Pakistan; EMRO/WHO-COMSTECH; Ministry of Science and Technology (MoST),
Islamabad, Pakistan; International Center for Genetic Engineering and
Biotechnology, Trieste, Italy [08/009]; NIDCD [R00-DC009287-03]
FX We thank the members of the study families for their participation,
Mayya N. Kawar, Erich Boger, and Barbara P. Zwiesler for technical
assistance, and Meghan Drummond and Steven Raft for critical review of
the manuscript. This study was supported by National Institute on
Deafness and Other Communication Disorders intramural research funds
DC00039-14 and DC00060-07. Part of the work in Pakistan was supported by
the Higher Education Commission (HEC), Islamabad, Pakistan;
EMRO/WHO-COMSTECH and Ministry of Science and Technology (MoST),
Islamabad, Pakistan; the International Center for Genetic Engineering
and Biotechnology, Trieste, Italy under project CRP/PAK08-01 (Contract
no. 08/009). Work at Cincinnati Children's Hospital Research Foundation
is supported by intramural research funds and the NIDCD research grant
(R00-DC009287-03).
NR 38
TC 7
Z9 8
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD FEB 9
PY 2011
VL 12
AR 21
DI 10.1186/1471-2350-12-21
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 724NJ
UT WOS:000287583000001
PM 21306635
ER
PT J
AU McGinnis, EM
Keil, A
AF McGinnis, E. Menton
Keil, Andreas
TI Selective Processing of Multiple Features in the Human Brain: Effects of
Feature Type and Salience
SO PLOS ONE
LA English
DT Article
ID EVENT-RELATED POTENTIALS; FEATURE-BASED ATTENTION;
HEMISPHERIC-DIFFERENCES; VISUAL-ATTENTION; COLOR; CORTEX; CONJUNCTIONS;
MECHANISMS; LOCATION; STIMULI
AB Identifying targets in a stream of items at a given constant spatial location relies on selection of aspects such as color, shape, or texture. Such attended (target) features of a stimulus elicit a negative-going event-related brain potential (ERP), termed Selection Negativity (SN), which has been used as an index of selective feature processing. In two experiments, participants viewed a series of Gabor patches in which targets were defined as a specific combination of color, orientation, and shape. Distracters were composed of different combinations of color, orientation, and shape of the target stimulus. This design allows comparisons of items with and without specific target features. Consistent with previous ERP research, SN deflections extended between 160-300 ms. Data from the subsequent P3 component (300-450 ms post-stimulus) were also examined, and were regarded as an index of target processing. In Experiment A, predominant effects of target color on SN and P3 amplitudes were found, along with smaller ERP differences in response to variations of orientation and shape. Manipulating color to be less salient while enhancing the saliency of the orientation of the Gabor patch (Experiment B) led to delayed color selection and enhanced orientation selection. Topographical analyses suggested that the location of SN on the scalp reliably varies with the nature of the to-be-attended feature. No interference of non-target features on the SN was observed. These results suggest that target feature selection operates by means of electrocortical facilitation of feature-specific sensory processes, and that selective electrocortical facilitation is more effective when stimulus saliency is heightened.
C1 [McGinnis, E. Menton; Keil, Andreas] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA.
RP McGinnis, EM (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA.
EM mmcginnis@ufl.edu
RI Keil, Andreas/F-9427-2011
OI Keil, Andreas/0000-0002-4064-1924
FU National Institute of Mental Health [P50-MH072850, R21 MH082702, R01
MH084392]
FX This research was supported in part by National Institute of Mental
Health grants P50-MH072850 and R21 MH082702 to P.J. Lang, by National
Institute of Mental Health grant R01 MH084392 to A. Keil. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 44
TC 8
Z9 8
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 9
PY 2011
VL 6
IS 2
AR e16824
DI 10.1371/journal.pone.0016824
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721NN
UT WOS:000287361700037
PM 21347379
ER
PT J
AU Prots, I
Skapenko, A
Lipsky, PE
Schulze-Koops, H
AF Prots, Iryna
Skapenko, Alla
Lipsky, Peter E.
Schulze-Koops, Hendrik
TI Analysis of the Transcriptional Program of Developing Induced Regulatory
T Cells
SO PLOS ONE
LA English
DT Article
ID IMMUNOLOGICAL SELF-TOLERANCE; TGF-BETA; FACTOR FOXP3; GENE-EXPRESSION;
RETINOIC-ACID; CUTTING EDGE; PERIPHERAL-BLOOD; INDUCTION;
DIFFERENTIATION; TREG
AB CD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). To gain insight into the mechanisms governing iTreg development, we performed longitudinal transcriptional profiling of CD25+ T cells during their differentiation from uncommitted naive CD4 T cells. Microarray analysis of mRNA from CD25+ iTregs early after stimulation revealed expression of genes involved in cell cycle progression and T cell activation, which largely overlapped with genes expressed in CD25+ effector T cells (Teffs) used as a control. Whereas expression of these genes remained elevated in Teffs, it declined gradually in developing iTregs, resulting in a more quiescent phenotype in mature iTregs. A similar pattern of kinetics was observed for biological processes and for intracellular pathways over-represented within the expressed genes. A maximum dichotomy of transcriptional activity between iTregs and Teffs was reached at late stages of their maturation. Of interest, members of the FoxO and FoxM1 transcription factor family pathways exhibited a reciprocal expression pattern in iTregs and Teffs, suggesting a role of these transcription factors in determining T cell fate.
C1 [Prots, Iryna; Skapenko, Alla; Schulze-Koops, Hendrik] Univ Munich, Med Poliklin, Div Rheumatol, D-8000 Munich, Germany.
[Lipsky, Peter E.] Natl Inst Arthrit & Musculoskeletal & Skin, NIH, Bethesda, MD USA.
RP Prots, I (reprint author), Univ Munich, Med Poliklin, Div Rheumatol, Pettenkoferstr 8A, D-8000 Munich, Germany.
EM alla.skapenko@med.uni-muenchen.de
FU Deutsche Forschungsgemeinschaft [Schu786/8-1, Schu786/2-5, SK59/4-1]
FX This work was supported by the Deutsche Forschungsgemeinschaft
(http://www.dfg.de/index.jsp; Grants Schu786/8-1, Schu786/2-5, and
SK59/4-1). The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 61
TC 6
Z9 7
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 9
PY 2011
VL 6
IS 2
AR e16913
DI 10.1371/journal.pone.0016913
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721NN
UT WOS:000287361700053
PM 21347372
ER
PT J
AU Kwak, JT
Hewitt, SM
Sinha, S
Bhargava, R
AF Kwak, Jin Tae
Hewitt, Stephen M.
Sinha, Saurabh
Bhargava, Rohit
TI Multimodal microscopy for automated histologic analysis of prostate
cancer
SO BMC CANCER
LA English
DT Article
ID FT-IR; INFRARED SPECTROSCOPY; PATHOLOGICAL IMAGES; FEATURE-SELECTION;
DIAGNOSIS; CLASSIFICATION; HISTOPATHOLOGY; IDENTIFICATION; RECOGNITION;
PITFALLS
AB Background: Prostate cancer is the single most prevalent cancer in US men whose gold standard of diagnosis is histologic assessment of biopsies. Manual assessment of stained tissue of all biopsies limits speed and accuracy in clinical practice and research of prostate cancer diagnosis. We sought to develop a fully-automated multimodal microscopy method to distinguish cancerous from non-cancerous tissue samples.
Methods: We recorded chemical data from an unstained tissue microarray (TMA) using Fourier transform infrared (FT-IR) spectroscopic imaging. Using pattern recognition, we identified epithelial cells without user input. We fused the cell type information with the corresponding stained images commonly used in clinical practice. Extracted morphological features, optimized by two-stage feature selection method using a minimum-redundancy-maximalrelevance (mRMR) criterion and sequential floating forward selection (SFFS), were applied to classify tissue samples as cancer or non-cancer.
Results: We achieved high accuracy (area under ROC curve (AUC) > 0.97) in cross-validations on each of two data sets that were stained under different conditions. When the classifier was trained on one data set and tested on the other data set, an AUC value of similar to 0.95 was observed. In the absence of IR data, the performance of the same classification system dropped for both data sets and between data sets.
Conclusions: We were able to achieve very effective fusion of the information from two different images that provide very different types of data with different characteristics. The method is entirely transparent to a user and does not involve any adjustment or decision-making based on spectral data. By combining the IR and optical data, we achieved high accurate classification.
C1 [Kwak, Jin Tae; Sinha, Saurabh] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA.
[Kwak, Jin Tae; Bhargava, Rohit] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA.
[Hewitt, Stephen M.] NCI, Tissue Array Res Program, NIH, Bethesda, MD 20850 USA.
[Bhargava, Rohit] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.
RP Sinha, S (reprint author), Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA.
EM sinhas@illinois.edu; rxb@illinois.edu
OI Hewitt, Stephen/0000-0001-8283-1788; Bhargava, Rohit/0000-0001-7360-994X
FU National Cancer Institute [R01CA138882]; National Institutes of Health;
DoD; computational science and engineering (CSE) fellowship
FX The project described was supported by Award Number R01CA138882 from the
National Cancer Institute. The project is also supported by National
Institutes of Health intramural funding (to S. M. H). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute or the
National Institutes of Health. The project was also supported by a DoD
prostate cancer research program young investigator award (to R. B.) and
a computational science and engineering (CSE) fellowship (to J.T.K).
NR 53
TC 34
Z9 34
U1 0
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD FEB 9
PY 2011
VL 11
AR 62
DI 10.1186/1471-2407-11-62
PG 16
WC Oncology
SC Oncology
GA 730DX
UT WOS:000288014100001
PM 21303560
ER
EF