FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Roetzheim, RG
   Freund, KM
   Corle, DK
   Murray, DM
   Snyder, FR
   Kronman, AC
   Jean-Pierre, P
   Raich, PC
   Holden, AEC
   Darnell, JS
   Warren-Mears, V
   Patierno, S
AF Roetzheim, Richard G.
   Freund, Karen M.
   Corle, Don K.
   Murray, David M.
   Snyder, Frederick R.
   Kronman, Andrea C.
   Jean-Pierre, Pascal
   Raich, Peter C.
   Holden, Alan E. C.
   Darnell, Julie S.
   Warren-Mears, Victoria
   Patierno, Steven
CA PNRP Design Anal Comm Patient Nav
TI Analysis of combined data from heterogeneous study designs: an applied
   example from the patient navigation research program
SO CLINICAL TRIALS
LA English
DT Article
ID BASE-LINE CHARACTERISTICS; PROSPECTIVE METAANALYSIS; RANDOMIZED-TRIALS;
   CLINICAL-TRIALS; CHOLESTEROL; COLLABORATION; INTERVENTION; METHODOLOGY;
   PREVENTION; RATIONALE
AB Background The Patient Navigation Research Program (PNRP) is a cooperative effort of nine research projects, with similar clinical criteria but with different study designs. To evaluate projects such as PNRP, it is desirable to perform a pooled analysis to increase power relative to the individual projects. There is no agreed-upon prospective methodology, however, for analyzing combined data arising from different study designs. Expert opinions were thus solicited from the members of the PNRP Design and Analysis Committee.
   Purpose To review possible methodologies for analyzing combined data arising from heterogeneous study designs.
   Methods The Design and Analysis Committee critically reviewed the pros and cons of five potential methods for analyzing combined PNRP project data. The conclusions were based on simple consensus. The five approaches reviewed included the following: (1) analyzing and reporting each project separately, (2) combining data from all projects and performing an individual-level analysis, (3) pooling data from projects having similar study designs, (4) analyzing pooled data using a prospective meta-analytic technique, and (5) analyzing pooled data utilizing a novel simulated group-randomized design.
   Results Methodologies varied in their ability to incorporate data from all PNRP projects, to appropriately account for differing study designs, and to accommodate differing project sample sizes.
   Limitations The conclusions reached were based on expert opinion and not derived from actual analyses performed.
C1 [Roetzheim, Richard G.] Univ S Florida, Dept Family Med, Tampa, FL 33612 USA.
   [Roetzheim, Richard G.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
   [Freund, Karen M.; Kronman, Andrea C.] Boston Univ, Sch Med, Dept Med, Womens Hlth Unit, Boston, MA 02118 USA.
   [Corle, Don K.] NCI, Rockville, MD USA.
   [Murray, David M.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
   [Snyder, Frederick R.] NOVA Res Co, Bethesda, MD USA.
   [Jean-Pierre, Pascal] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
   [Jean-Pierre, Pascal] Sylvester Comprehens Canc Ctr, Miami, FL USA.
   [Raich, Peter C.] Denver Hlth & Hosp Author, Div Hematol Oncol, Denver, CO USA.
   [Holden, Alan E. C.] Univ Texas Hlth Sci Ctr San Antonio, Inst Hlth Promot Res, San Antonio, TX 78229 USA.
   [Darnell, Julie S.] Univ Illinois, Sch Publ Hlth, Div Hlth Policy & Adm, Chicago, IL USA.
   [Warren-Mears, Victoria] NW Portland Area Indian Hlth Board, NW Tribal Epidemiol Ctr, Portland, OR USA.
   [Patierno, Steven] George Washington Univ, Med Ctr, George Washington Canc Inst, Washington, DC 20037 USA.
RP Roetzheim, RG (reprint author), Univ S Florida, Dept Family Med, 12901 Bruce B Downs Blvd,MDC 13, Tampa, FL 33612 USA.
EM rroetzhe@health.usf.edu
RI Roetzheim, Richard/J-4696-2012; 
OI Freund, Karen/0000-0002-9049-5574
FU NIH [U01 CA116892, U01 CA 117281, U01CA116903, U01CA116937, U01CA116924,
   U01CA116885, U01CA116875, U01CA116925]; American Cancer Society
   [SIRSG-05-253-01]
FX The Patient Navigation Research Program is supported by NIH Grants U01
   CA116892, U01 CA 117281, U01CA116903, U01CA116937, U01CA116924,
   U01CA116885, U01CA116875, U01CA116925, and American Cancer Society No.
   SIRSG-05-253-01. The contents are solely the responsibility of the
   authors and do not necessarily represent the official views of the
   Center to Reduce Cancer Health Disparities, NCI/NIH, or the American
   Cancer Society.
NR 37
TC 7
Z9 7
U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD APR
PY 2012
VL 9
IS 2
BP 176
EP 187
DI 10.1177/1740774511433284
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 923RN
UT WOS:000302636500004
PM 22273587
ER

PT J
AU Schwartz, RH
AF Schwartz, Ronald H.
TI Historical Overview of Immunological Tolerance
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; FC-GAMMA-RIIB;
   PLASMACYTOID DENDRITIC CELLS; TRANSCRIPTION FACTOR FOXP3; AUTOREACTIVE
   B-CELLS; E3 UBIQUITIN LIGASE; TOLL-LIKE RECEPTORS; AUTOIMMUNE-DISEASE;
   IMMUNE-RESPONSES
AB A fundamental property of the immune system is its ability to mediate self-defense with a minimal amount of collateral damage to the host. The system uses several different mechanisms to achieve this goal, which is collectively referred to as the "process of immunological tolerance." This article provides an introductory historical overview to these various mechanisms, which are discussed in greater detail throughout this collection, and then briefly describes what happens when this process fails, a state referred to as "autoimmunity."
C1 NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Schwartz, RH (reprint author), NIAID, Lab Cellular & Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rs34r@nih.gov
FU NIAID, NIH
FX I thank Dr. Nevil Singh and Dr. Pascal Chappert for constructive
   suggestions that helped to improve the manuscript. This work was
   supported by the Intramural Research Program of NIAID, NIH.
NR 178
TC 5
Z9 5
U1 0
U2 4
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 APR
PY 2012
VL 4
IS 4
AR a006908
DI 10.1101/cshperspect.a006908
PG 14
WC Cell Biology
SC Cell Biology
GA 922ND
UT WOS:000302553400005
PM 22395097
ER

PT J
AU Saha, TD
   Compton, WM
   Chou, SP
   Smith, S
   Ruan, WJ
   Huang, B
   Pickering, RP
   Grant, BF
AF Saha, Tulshi D.
   Compton, Wilson M.
   Chou, S. Patricia
   Smith, Sharon
   Ruan, W. June
   Huang, Boji
   Pickering, Roger P.
   Grant, Bridget F.
TI Analyses related to the development of DSM-5 criteria for substance use
   related disorders 1. Toward amphetamine, cocaine and prescription drug
   use disorder continua using Item Response Theory
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Amphetamine use disorder; Cocaine use disorder; Prescription drug use
   disorder; DSM-5; Item Response Theory
ID ALCOHOL-USE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; MARGINAL
   MAXIMUM-LIKELIHOOD; INTERVIEW SCHEDULE AUDADIS; EM ALGORITHM;
   DEPENDENCE; RELIABILITY; CANNABIS; MODULES; ABUSE
AB Background: Prior research has demonstrated the dimensionality of alcohol, nicotine and cannabis use disorders criteria. The purpose of this study was to examine the unidimensionality of DSM-IV cocaine, amphetamine and prescription drug abuse and dependence criteria and to determine the impact of elimination of the legal problems criterion on the information value of the aggregate criteria.
   Methods: Factor analyses and Item Response Theory (IRT) analyses were used to explore the unidimensionality and psychometric properties of the illicit drug use criteria using a large representative sample of the U.S. population.
   Results: All illicit drug abuse and dependence criteria formed unidimensional latent traits. For amphetamines, cocaine, sedatives, tranquilizers and opioids, IRT models fit better for models without legal problems criterion than models with legal problems criterion and there were no differences in the information value of the IRT models with and without the legal problems criterion, supporting the elimination of that criterion.
   Conclusion: Consistent with findings for alcohol, nicotine and cannabis, amphetamine, cocaine, sedative, tranquilizer and opioid abuse and dependence criteria reflect underlying unitary dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the American Psychiatric Association's DSM-5 Substance and Related Disorders Workgroup. Published by Elsevier Ireland Ltd.
C1 [Saha, Tulshi D.; Chou, S. Patricia; Smith, Sharon; Ruan, W. June; Huang, Boji; Pickering, Roger P.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
   [Compton, Wilson M.] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA.
RP Saha, TD (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3083, Bethesda, MD 20892 USA.
EM sahatd@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
   Institute on Drug Abuse (NIDA)
FX The National Institute on Alcohol Abuse and Alcoholism (NIAAA) funded
   the National Epidemiologic Survey on Alcohol and Related Conditions
   (NESARC) with supplemental funding from the National Institute on Drug
   Abuse (NIDA).
NR 40
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U1 5
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD APR 1
PY 2012
VL 122
IS 1-2
BP 38
EP 46
DI 10.1016/j.drugalcdep.2011.09.004
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 925CW
UT WOS:000302739300006
PM 21963414
ER

PT J
AU MacDonald, C
   Buchkovich, NJ
   Stringer, DK
   Emr, SD
   Piper, RC
AF MacDonald, Chris
   Buchkovich, Nicholas J.
   Stringer, Daniel K.
   Emr, Scott D.
   Piper, Robert C.
TI Cargo ubiquitination is essential for multivesicular body intralumenal
   vesicle formation
SO EMBO REPORTS
LA English
DT Article
DE ubiquitin; lysosome; multivesicular body; endosome; vacuole
ID SACCHAROMYCES-CEREVISIAE; MECHANISMS; COOPERATE; ENDOSOME; PROTEINS;
   BINDING; DOMAINS
AB The efficient formation of a variety of transport vesicles is influenced by the presence of cargo, suggesting that cargo itself might have a defining role in vesicle biogenesis. However, definitive in vivo experiments supporting this concept are lacking, as it is difficult to eliminate endogenous cargo. The Endosomal Sorting Complexes Required for Transport (ESCRT) apparatus sorts ubiquitinated membrane proteins into endosomal intralumenal vesicles (ILVs) that accumulate within multivesicular bodies. Here we show that cargo ubiquitination is required for effective recruitment of the ESCRT machinery onto endosomal membranes and for the subsequent formation of ILVs.
C1 [Buchkovich, Nicholas J.; Emr, Scott D.] Cornell Univ, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA.
   [MacDonald, Chris; Stringer, Daniel K.; Piper, Robert C.] Univ Iowa, Iowa City, IA 52246 USA.
RP Emr, SD (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
EM sde26@cornell.edu; robert-piper@uiowa.edu
OI MacDonald, Chris/0000-0002-7450-600X
FU NIH [R01GM58202]; American Hearth Association
FX We thank J. Ross, J. Shao (University of Iowa Central Microscopy
   Facility), B. Judson and J. Sun for technical assistance, as well as
   members of the Emr and Piper labs for helpful discussion. This work was
   supported in part by an American Hearth Association predoctoral
   fellowship (DKS) and NIH R01GM58202 (RCP).
NR 19
TC 30
Z9 30
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD APR
PY 2012
VL 13
IS 4
BP 331
EP 338
DI 10.1038/embor.2012.18
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 922QI
UT WOS:000302562500016
PM 22370727
ER

PT J
AU Starks, SE
   Hoppin, JA
   Kamel, F
   Lynch, CF
   Jones, MP
   Alavanja, MC
   Sandler, DP
   Gerr, F
AF Starks, Sarah E.
   Hoppin, Jane A.
   Kamel, Freya
   Lynch, Charles F.
   Jones, Michael P.
   Alavanja, Michael C.
   Sandler, Dale P.
   Gerr, Fred
TI Peripheral Nervous System Function and Organophosphate Pesticide Use
   among Licensed Pesticide Applicators in the Agricultural Health Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE agricultural workers; neurological testing; occupational exposure;
   organophosphates; pesticide exposure
ID RELIABILITY; EXPOSURES; NEUROTOXICITY
AB BACKGROUND: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function.
   OBJECTIVE: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS).
   METHODS: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates.
   RESULTS: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold.
   CONCLUSIONS: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators.
C1 [Starks, Sarah E.; Gerr, Fred] Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA 52242 USA.
   [Hoppin, Jane A.; Kamel, Freya; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA.
   [Jones, Michael P.] Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA.
   [Alavanja, Michael C.] NCI, NIH, US Dept HHS, Rockville, MD USA.
RP Gerr, F (reprint author), Univ Iowa, Dept Occupat & Environm Hlth, Univ Iowa Res Pk,140 IREH, Iowa City, IA 52242 USA.
EM fred-gerr@uiowa.edu
OI Sandler, Dale/0000-0002-6776-0018
FU National Institute of Environmental Health Sciences (NIEHS)
   [R01-ES013067-03]; National Institutes of Health, NIEHS [Z01ES04903];
   National Cancer Institute [Z01CP010119]
FX This work was supported by National Institute of Environmental Health
   Sciences (NIEHS) grant R01-ES013067-03, the Intramural Research Program
   of the National Institutes of Health, NIEHS grant Z01ES04903, and
   National Cancer Institute grant Z01CP010119.
NR 18
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Z9 16
U1 1
U2 6
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD APR
PY 2012
VL 120
IS 4
BP 515
EP 520
DI 10.1289/ehp.1103944
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 921KJ
UT WOS:000302476200019
PM 22262687
ER

PT J
AU Walker, VR
   Jefferson, WN
   Couse, JF
   Korach, KS
AF Walker, Vickie R.
   Jefferson, Wendy N.
   Couse, John F.
   Korach, Kenneth S.
TI Estrogen Receptor-alpha Mediates Diethylstilbestrol-Induced Feminization
   of the Seminal Vesicle in Male Mice
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE development; endocrine disruptor; reproductive tract
ID REPRODUCTIVE-TRACT; PRENATAL EXPOSURE; DEVELOPMENTAL EXPOSURE; ANDROGEN
   RECEPTOR; GENE-EXPRESSION; KNOCKOUT MICE; NULL MICE; PROSTATE; BETA;
   CARCINOGENICITY
AB BACKGROUND: Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV).
   OBJECTIVES: The present study was designed to evaluate the role of the estrogen receptor (ER) in this action by using ER-knockout (ERKO) mice.
   METHODS: Wild-type (WT), ER alpha-null (alpha ERKO), and ER beta-null (beta ERKO) male mice were treated with either vehicle or DES (2 mu g/day) on neonatal days 1-5. These mice were divided into two groups: In the first group, intact mice were sacrificed at 10 weeks of age; in the second group, mice were castrated at 10 weeks of age, allowed to recover for 10 days, treated with dihydrotestosterone (DHT) or placebo, and sacrificed 2 weeks later. Body weights and SV weights were recorded, and mRNA expression levels of Ltf(lactoferrin), Svs4, and androgen receptor (Ar) were assessed.
   RESULTS: In DES-treated intact mice, SV weights were reduced in WT and beta ERKO mice but not in alpha ERKO mice. DES-treated WT and beta ERKO males, but not alpha ERKO males, exhibited ectopic expression of LF in the SV. DES treatment resulted in decreased SVS IV protein and mRNA expression in WT males, but no effect was seen in alpha ERKO mice. In addition, DES-treated beta ERKO mice exhibited reduced Svs4 mRNA expression but maintained control levels of SVS IV protein. In DES-treated castrated mice, DHT implants restored SV weights to normal levels in alpha ERKO mice but not in WT mice, suggesting full androgen responsiveness in alpha ERKO mice.
   CONCLUSIONS: These data suggest that DES-induced SV toxicity and feminization are primarily mediated by ER alpha; however, some aspects of androgen response may require the action of ER beta.
C1 [Walker, Vickie R.; Couse, John F.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   [Jefferson, Wendy N.] NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   [Couse, John F.] Taconic Inc, Germantown, NY USA.
RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH,Dept Hlth & Human Serv, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health, National Institute of Environmental
   Health Sciences [Z01ES70065]
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Institute of Environmental
   Health Sciences (Z01ES70065).
NR 41
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U1 2
U2 10
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD APR
PY 2012
VL 120
IS 4
BP 560
EP 565
DI 10.1289/ehp.1103678
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 921KJ
UT WOS:000302476200027
PM 22275727
ER

PT J
AU Schecter, A
   Malik-Bass, N
   Calafat, AM
   Kato, K
   Colacino, JA
   Gent, TL
   Hynan, LS
   Harris, TR
   Malla, S
   Birnbaum, L
AF Schecter, Arnold
   Malik-Bass, Noor
   Calafat, Antonia M.
   Kato, Kayoko
   Colacino, Justin A.
   Gent, Tyra L.
   Hynan, Linda S.
   Harris, T. Robert
   Malla, Sunitha
   Birnbaum, Linda
TI Polyfluoroalkyl Compounds in Texas Children from Birth through 12 Years
   of Age
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE blood; children; infants; PFC; PFOA; PFOS; polyfluoroalkyl compounds;
   United States
ID PERFLUOROOCTANOIC ACID PFOA; PERFLUORINATED COMPOUNDS; NATIONAL-HEALTH;
   SERUM CONCENTRATIONS; NHANES 1999-2000; SULFONATE PFOS; BLOOD-SAMPLES;
   US POPULATION; HUMAN-MILK; CHEMICALS
AB BACKGROUND: For > 50 years, polyfluoroalkyl compounds (PFCs) have been used worldwide, mainly as surfactants and emulsifiers, and human exposure to some PFCs is widespread.
   OBJECTIVES: Our goal was to report PFC serum concentrations from a convenience sample of Dallas, Texas, children from birth to < 13 years of age, and to examine age and sex differences in PFC concentrations.
   METHODS: We analyzed 300 serum samples collected in 2009 for eight PFCs by online solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry.
   RESULTS: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in > 92% of participants; the other PFCs measured were detected less frequently. Overall median concentrations of PFOS (4.1 ng/mL) were higher than those for PFOA (2.85 ng/mL), PFNA (1.2 ng/mL), and PFHxS (1.2 ng/mL). For PFOS, PFOA, PFNA, and PFHxS, we found no significant differences (p < 0.05) by sex, significantly increasing concentrations for all four chemicals by age, and significantly positive correlations between all four compounds.
   CONCLUSIONS: We found no significant differences in the serum concentrations of PFOS, PFOA, PFNA, and PFHxS by sex, but increasing concentrations with age. Our results suggest that these 300 Texas children from birth through 12 years of age continued to be exposed to several PFCs in late 2009, years after changes in production of some PFCs in the United States.
C1 [Schecter, Arnold; Malik-Bass, Noor; Gent, Tyra L.; Harris, T. Robert; Malla, Sunitha] Univ Texas Sch Publ Hlth, Dallas, TX 75390 USA.
   [Calafat, Antonia M.; Kato, Kayoko] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA.
   [Colacino, Justin A.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
   [Hynan, Linda S.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci Biostat, Dallas, TX 75390 USA.
   [Hynan, Linda S.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
   [Birnbaum, Linda] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
RP Schecter, A (reprint author), Univ Texas Sch Publ Hlth, 6011 Harry Hines Blvd,V8-112, Dallas, TX 75390 USA.
EM arnold.schecter@utsouthwestern.edu
OI Hynan, Linda/0000-0002-4642-7769
FU CDC; National Institute of Environmental Health Sciences (NIEHS), NIH
   [T32 ES007062]
FX This study was supported primarily by the CDC and involved the CDC, CMC
   Dallas, the University of Texas Southwestern Medical Center, the
   University of Texas School of Public Health, Dallas Campus, and the
   National Institutes of Health (NIH). Support for J. Colacino was
   provided by an Institutional Training Grant from the National Institute
   of Environmental Health Sciences (NIEHS), NIH (T32 ES007062).
NR 46
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U1 3
U2 37
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD APR
PY 2012
VL 120
IS 4
BP 590
EP 594
DI 10.1289/ehp.1104325
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 921KJ
UT WOS:000302476200032
PM 22182702
ER

PT J
AU Jusko, TA
   Sonneborn, D
   Palkovicova, L
   Kocan, A
   Drobna, B
   Trnovec, T
   Hertz-Picciotto, I
AF Jusko, Todd A.
   Sonneborn, Dean
   Palkovicova, Lubica
   Kocan, Anton
   Drobna, Beata
   Trnovec, Tomas
   Hertz-Picciotto, Irva
TI Pre- and Postnatal Polychlorinated Biphenyl Concentrations and
   Longitudinal Measures of Thymus Volume in Infants
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE atrophy; cohort; epidemiology; immune; Roma; T cell
ID RECEPTOR-DEFICIENT MICE; ORGANOCHLORINE PESTICIDES; SONOGRAPHIC
   MEASUREMENT; EASTERN SLOVAKIA; PCB EXPOSURE; HUMAN SERUM; SIZE;
   2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; DIOXINS; BIRTH
AB BACKGROUND: Previously, we reported an association between higher maternal polychlorinated biphenyl (PCB) concentrations and smaller thymus volume in newborns in a birth cohort residing in eastern Slovakia.
   OBJECTIVE: In the present report we address whether thymus volume at later ages is influenced by prenatal and early postnatal PCB exposure.
   METHODS: At the time of delivery, 1,134 mother-infant pairs were enrolled. Maternal and 6- and 16-month infant blood samples were collected and analyzed for 15 PCB congeners. Thymus volume was measured in infants shortly after birth and at ages 6 and 16 months using ultrasonography.
   RESULTS: Higher maternal PCB concentration was associated with reduced thymus volume at birth [a 0.21 SD reduction in thymus volume for an increase in total maternal PCB concentration from the 10th to the 90th percentile; 95% confidence interval (CI): -0.37, -0.05], whereas maternal PCB concentration was not predictive of 6- and 16-month thymus volume. Six-month infant PCB concentration was associated with a 0.40 SD decrease in 6-month thymus volume (95% CI: -0.76, -0.04). There was also some suggestion that thymus volume at 16 months was positively associated with concurrent infant PCB concentration.
   CONCLUSIONS: The potential adverse effects of in utero PCB exposure on thymic development may extend beyond the neonatal period. Results from this highly exposed cohort provide suggestive evidence that postnatal PCB concentrations may be influential, but a smaller set of 6-month PCB measurements limited statistical power at that time point. Implications regarding impaired immunologic maturation or long-term clinical implications remain to be determined.
C1 [Jusko, Todd A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
   [Sonneborn, Dean; Hertz-Picciotto, Irva] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA.
   [Palkovicova, Lubica; Trnovec, Tomas] Slovak Med Univ, Dept Environm Med, Bratislava, Slovakia.
   [Kocan, Anton; Drobna, Beata] Slovak Med Univ, Dept Tox Organ Pollutants, Bratislava, Slovakia.
RP Jusko, TA (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr,Rall Bldg, Durham, NC 27709 USA.
EM todd.jusko@nih.gov
FU National Institutes of Health [U01-ES016127, R01-CA096525, R03-TW007152,
   R01-ES015359]; National Institutes of Health, National Institute of
   Environmental Health Sciences; ENVIRISK of the European Commission
   [SSPI044232]; U.S. State Department
FX This research received support from National Institutes of Health grants
   U01-ES016127, R01-CA096525, R03-TW007152, and R01-ES015359 and from the
   Intramural Research Program of the National Institutes of Health,
   National Institute of Environmental Health Sciences. Funding was also
   provided by ENVIRISK grant SSPI044232 of the European Commission and by
   a Fulbright Grant from the U.S. State Department.
NR 38
TC 17
Z9 17
U1 1
U2 7
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD APR
PY 2012
VL 120
IS 4
BP 595
EP 600
DI 10.1289/ehp.1104229
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 921KJ
UT WOS:000302476200033
PM 22275729
ER

PT J
AU Birnbaum, LS
AF Birnbaum, Linda S.
TI Environmental Chemicals: Evaluating Low-Dose Effects
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
ID HEALTH; EXPOSURE
C1 [Birnbaum, Linda S.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   [Birnbaum, Linda S.] NIH, NTP, US Dept HHS, Res Triangle Pk, NC USA.
RP Birnbaum, LS (reprint author), NIEHS, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM birnbaumls@niehs.nih.gov
NR 14
TC 36
Z9 38
U1 0
U2 5
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD APR
PY 2012
VL 120
IS 4
BP A143
EP A144
DI 10.1289/ehp.1205179
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 921KJ
UT WOS:000302476200002
PM 22470049
ER

PT J
AU Moriwaki, S
   Takigawa, M
   Igarashi, N
   Nagai, Y
   Amano, H
   Ishikawa, O
   Khan, SG
   Kraemer, KH
AF Moriwaki, Shinichi
   Takigawa, Masahiro
   Igarashi, Naoya
   Nagai, Yayoi
   Amano, Hiroo
   Ishikawa, Osamu
   Khan, Sikandar G.
   Kraemer, Kenneth H.
TI Xeroderma pigmentosum complementation group G patient with a novel
   homozygous missense mutation and no neurological abnormalities
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE DNA repair; mutation; skin cancer; ultraviolet; xeroderma pigmentosum
   group G
ID COCKAYNE-SYNDROME; DNA-REPAIR; MALIGNANT-MELANOMA; SKIN-CANCER; JAPAN;
   GENOTYPE; XPG
AB We describe an unusual xeroderma pigmentosum (XP) patient with a mutation in XP complementation group G, representing only the third reported Japanese XP-G patient. A 40-year-old men (XP3HM), born from consanguineous parents experienced sun sensitivity and pigmentary changes of sun-exposed skin since childhood. He developed a squamous cell carcinoma on his lower lip at the age of 40. He has neither neurological abnormalities nor Cockayne syndrome. The primary fibroblasts of the patient were hypersensitive to killing by UV (D0 = 0.6 J/m2) and the post-UV unscheduled DNA synthesis was 8% of normal. Host cell reactivation complementation analysis implicated XP complementation group G. We identified a novel homozygous mutation (c.194T>C) in a conserved portion of the XPG(ERCC5) gene, resulting in a predicted amino acid change; p.L65P. We confirmed that this genetic change reduced DNA repair thus linking this mutation to increased skin cancer.
C1 [Moriwaki, Shinichi] Osaka Med Coll, Dept Dermatol, Takatsuki, Osaka 5698686, Japan.
   [Takigawa, Masahiro] Hamamatsu Univ Sch Med, Dept Dermatol, Hamamatsu, Shizuoka 4313192, Japan.
   [Igarashi, Naoya; Nagai, Yayoi; Amano, Hiroo; Ishikawa, Osamu] Gunma Univ, Grad Sch Med Maebashi, Dept Dermatol, Gunma, Japan.
   [Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Bethesda, MD 20892 USA.
RP Moriwaki, S (reprint author), Osaka Med Coll, Dept Dermatol, 2-7 Daigaku Machi, Takatsuki, Osaka 5698686, Japan.
EM der002@poh.osaka-med.ac.jp
OI Ishikawa, Osamu/0000-0002-7655-0610
FU Intramural NIH HHS [ZIA BC004517-35]
NR 23
TC 13
Z9 14
U1 4
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0906-6705
EI 1600-0625
J9 EXP DERMATOL
JI Exp. Dermatol.
PD APR
PY 2012
VL 21
IS 4
BP 304
EP 307
DI 10.1111/j.1600-0625.2012.01446.x
PG 4
WC Dermatology
SC Dermatology
GA 908ZW
UT WOS:000301532600013
PM 22417308
ER

PT J
AU Barrioluengo, V
   Wang, Y
   Le Grice, SFJ
   Menendez-Arias, L
AF Barrioluengo, Veronica
   Wang, Yi
   Le Grice, Stuart F. J.
   Menendez-Arias, Luis
TI Intrinsic DNA synthesis fidelity of xenotropic murine leukemia
   virus-related virus reverse transcriptase
SO FEBS JOURNAL
LA English
DT Article
DE DNA polymerase; fidelity; retroviruses; reverse transcriptase; XMRV
ID MISPAIR EXTENSION FREQUENCIES; CHRONIC-FATIGUE-SYNDROME; RETROVIRUS
   XMRV; MUTATION-RATE; MOUSE DNA; IN-VITRO; HIV-1; TYPE-1; CONTAMINATION;
   RESISTANCE
AB Although recent reports have provided strong evidence to suggest that xenotropic murine leukemia virus-related virus (XMRV) is unlikely to be the causative agent of prostate cancer and chronic fatigue syndrome, this recombinant retrovirus can nonetheless infect human cells in vitro and induce a chronic infection in macaques. In the present study, we determined the accuracy of DNA synthesis of the reverse transcriptases (RTs) of XMRV and Moloney murine leukemia virus (MoMLV) using a combination of pre-steady-state kinetics of nucleotide incorporation and an M13mp2-based forward mutation assay. The results obtained were compared with those previously reported for the HIV type 1 BH10 strain (HIV-1BH10) RT. MoMLV and XMRV RTs were 13.9 and 110 times less efficient [as determined by the catalytic rate constant of the nucleotide incorporation reaction (kpol)/equilibrium constant (Kd)] than the HIV-1BH10 RT in incorporating correct nucleotides. Misinsertion and mispair extension kinetic studies demonstrated that MoMLV RT was more accurate than the HIV-1BH10 RT. In comparison with the MoMLV RT, the XMRV RT showed decreased mispair extension fidelity and was less faithful when misincorporating C or A opposite A. However, the XMRV RT showed stronger selectivity against G in misinsertion fidelity assays. Forward mutation assays revealed that XMRV and MoMLV RTs had similar accuracy of DNA-dependent DNA synthesis, but were > 13 times more faithful than the HIV-1BH10 enzyme. The mutational spectra of XMRV and MoMLV RTs were similar in having a relatively higher proportion of frameshifts and transversions compared with the HIV-1BH10 RT. However, the XMRV polymerase was less prone to introduce large deletions and one-nucleotide insertions.
C1 [Barrioluengo, Veronica; Menendez-Arias, Luis] CSIC UAM, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain.
   [Wang, Yi; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Menendez-Arias, L (reprint author), CSIC UAM, Ctr Biol Mol Severo Ochoa, C Nicolas Cabrera 1,Campus Cantoblanco, Madrid 28049, Spain.
EM lmenendez@cbm.uam.es
RI Menendez Arias, Luis /G-2436-2016; Menendez Arias, Luis/N-7447-2016
OI Menendez Arias, Luis/0000-0002-1251-6640
FU Ministery of Science and Innovation of Spain [BIO2010/15532]; Fondo de
   Investigacion Sanitaria through the 'Red Tematica de Investigacion
   Cooperativa en SIDA' [RD06/0006]; Fundacion Ramon Areces; National
   Cancer Institute, National Institutes of Health
FX This work was supported, in part, by grants of the Ministery of Science
   and Innovation of Spain (BIO2010/15532), Fondo de Investigacion
   Sanitaria (through the 'Red Tematica de Investigacion Cooperativa en
   SIDA' RD06/0006), and an institutional grant from the Fundacion Ramon
   Areces. S.F.J. Le G. and Y.W. are supported by the Intramural Research
   Program of the National Cancer Institute, National Institutes of Health.
NR 42
TC 5
Z9 5
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD APR
PY 2012
VL 279
IS 8
BP 1433
EP 1444
DI 10.1111/j.1742-4658.2012.08532.x
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 920IJ
UT WOS:000302397200011
PM 22340433
ER

PT J
AU Senac, JS
   Chandler, RJ
   Sysol, JR
   Li, L
   Venditti, CP
AF Senac, J. S.
   Chandler, R. J.
   Sysol, J. R.
   Li, L.
   Venditti, C. P.
TI Gene therapy in a murine model of methylmalonic acidemia using
   rAAV9-mediated gene delivery
SO GENE THERAPY
LA English
DT Article
DE AAV9; MMA; methylmalonic acidemia; stable isotope; renal disease
ID LIVER-KIDNEY TRANSPLANTATION; SKELETAL-MUSCLE TRANSDUCTION;
   OF-THE-LITERATURE; SYSTEMIC INJECTION; MICE; VECTORS; EXPRESSION;
   MANAGEMENT; SEROTYPE-9; ACIDURIA
AB Methylmalonic acidemia (MMA), an inherited metabolic disorder caused by deficient activity of methylmalonyl-CoA mutase, carries a poor prognosis for long-term survival. While administration of a recombinant adeno-associated virus serotype 8 vector (rAAV8) can rescue Mut(-/-) mice from neonatal lethality and provide sustained phenotypic correction, translation of gene therapy to human subjects will likely require multiple rounds of systemic administration and, ideally, the use of a vector that transduces the kidney. To examine the effectiveness of alternative rAAVs in the treatment of MMA, a serotype 9 rAAV expressing the Mut cDNA was constructed and delivered to newborn Mut(-/-) mice (n=11). rAAV9 gene therapy directed hepatic transgene expression within 24 h and effectively rescued the Mut(-/-) mice from lethality, conferred long-term survival, markedly improved metabolism and resulted in striking preservation of renal function and histology. Systemic readministration of the vector at a dose similar to that used in human clinical trials (2.5 x 10(9) GC of rAAV9 per gram) to older, treated Mut(-/-) mice (n=5) lowered circulating metabolites, increased in vivo propionate oxidative capacity and produced transgene expression in the kidney and liver. Our data support the use of an rAAV9 vector in the acute and chronic treatment of MMA, and highlight the renal tropism afforded by this novel serotype. Gene Therapy (2012) 19, 385-391; doi: 10.1038/gt.2011.108; published online 21 July 2011
C1 [Senac, J. S.; Chandler, R. J.; Sysol, J. R.; Venditti, C. P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Chandler, R. J.] George Washington Univ, Inst Biomed Sci, Washington, DC USA.
   [Li, L.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD USA.
RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bldg 49 Room 4A18, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health;
   National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health; Angels for Alyssa MMA Research Foundation
FX JSS, RJC, JRS and CPV were supported, in part, by the Intramural
   Research Program of the National Human Genome Research Institute,
   National Institutes of Health. LL was supported, in part, by the
   Intramural Research Program of the National Institute of Diabetes and
   Digestive and Kidney Diseases, National Institutes of Health. JRS also
   received support from the Angels for Alyssa MMA Research Foundation.
NR 43
TC 6
Z9 6
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
J9 GENE THER
JI Gene Ther.
PD APR
PY 2012
VL 19
IS 4
BP 385
EP 391
DI 10.1038/gt.2011.108
PG 7
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity; Research & Experimental Medicine
GA 925OD
UT WOS:000302769800004
PM 21776024
ER

PT J
AU Simons-Morton, B
   Abraido-Lanza, AF
   Bernhardt, JM
   Schoenthaler, A
   Schnitzer, A
   Allegrante, JP
AF Simons-Morton, B.
   Abraido-Lanza, A. F.
   Bernhardt, J. M.
   Schoenthaler, A.
   Schnitzer, A.
   Allegrante, J. P.
TI Demystifying peer review (vol 39, pg 3, 2012)
SO HEALTH EDUCATION & BEHAVIOR
LA English
DT Correction
AB Simons-Morton, B., Abraido-Lanza, A. F., Bernhardt, J. M., Schoenthaler, A., Schnitzer, A., & Allegrante, J. P. (2012). Demystifying peer review. Health Education & Behavior, 39(1), 3-7. (Original DOI: 10.1177/1090198111433309).
C1 [Allegrante, J. P.] NIH, Bethesda, MD 20892 USA.
   [Allegrante, J. P.] Columbia Univ, New York, NY USA.
NR 1
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 1090-1981
J9 HEALTH EDUC BEHAV
JI Health Educ. Behav.
PD APR
PY 2012
VL 39
IS 2
BP 244
EP 244
DI 10.1177/1090198112442149
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 918XL
UT WOS:000302284700014
ER

PT J
AU Everson, GT
   Shiffman, ML
   Hoefs, JC
   Morgan, TR
   Sterling, RK
   Wagner, DA
   Lauriski, S
   Curto, TM
   Stoddard, A
   Wright, EC
AF Everson, Gregory T.
   Shiffman, Mitchell L.
   Hoefs, John C.
   Morgan, Timothy R.
   Sterling, Richard K.
   Wagner, David A.
   Lauriski, Shannon
   Curto, Teresa M.
   Stoddard, Anne
   Wright, Elizabeth C.
CA HALT-C Trial Grp
TI Quantitative liver function tests improve the prediction of clinical
   outcomes in chronic hepatitis C: Results from the hepatitis C antiviral
   long-term treatment against cirrhosis trial
SO HEPATOLOGY
LA English
DT Article
ID CHRONIC HCV INFECTION; PROGNOSTIC VALUE; UNITED-STATES; BIOPSY; DISEASE;
   FIBROSIS; COMPLICATIONS; MODEL; STAGE; THERAPY
AB Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred and twenty-seven participants in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (kelim), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, perfused hepatic mass (PHM), and liver and spleen volumes (by single-photon emission computed tomography) were measured. Baseline QLFTs were significantly worse (P = 0.0017 to P < 0.0001) and spleen volumes were larger (P < 0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as low and high risk for clinical outcome yielded hazard ratios ranging from 2.21 (95% confidence interval [CI]: 1.29-3.78) for GEC to 6.52 (95% CI: 3.63-11.71) for CA clearance after oral administration (Cloral). QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with high-risk results for CA Cloral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with low risk QLFTs experienced a clinical outcome. Conclusion: QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance the noninvasive monitoring, counseling, and management of patients with chronic HCV. (HEPATOLOGY 2012)
C1 [Everson, Gregory T.; Lauriski, Shannon] Univ Colorado Denver, Div Gastroenterol & Hepatol, Sect Hepatol, Aurora, CO 80045 USA.
   [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA.
   [Hoefs, John C.; Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
   [Hoefs, John C.; Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
   [Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA.
   [Wagner, David A.] Metab Solut Inc, Nashua, NH USA.
   [Curto, Teresa M.; Stoddard, Anne] New England Res Inst, Watertown, MA 02172 USA.
   [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Everson, GT (reprint author), Univ Colorado Denver, Div Gastroenterol & Hepatol, Sect Hepatol, 1635 N Aurora Court,B-154, Aurora, CO 80045 USA.
EM greg.everson@ucdenver.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
   [N01-DK-9-2327, M01RR-00051, N01-DK-9-2320, M01RR-00827, N01-DK-9-2322,
   M01RR-00065, N01-DK-9-2328]; National Institute of Allergy and
   Infectious Diseases; National Cancer Institute; National Center for
   Minority Health and Health Disparities; General Clinical Research Center
   from the National Center for Research Resources, National Institutes of
   Health; Metabolic Solutions, Inc.; Hoffmann-La Roche, Inc. through
   National Institutes of Health
FX This study was supported by the National Institute of Diabetes and
   Digestive and Kidney Diseases (Contract N01-DK-9-2327, Grant
   M01RR-00051; Contract N01-DK-9-2320, Grant M01RR-00827; Contract
   N01-DK-9-2322, Grant M01RR-00065; Contract N01-DK-9-2328), the National
   Institute of Allergy and Infectious Diseases, the National Cancer
   Institute, the National Center for Minority Health and Health
   Disparities, and by General Clinical Research Center grants from the
   National Center for Research Resources, National Institutes of Health.
   Additional funding was supplied by Metabolic Solutions, Inc. and by
   Hoffmann-La Roche, Inc., through Cooperative Research and Development
   Agreements with the National Institutes of Health.
NR 53
TC 23
Z9 23
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD APR
PY 2012
VL 55
IS 4
BP 1019
EP 1029
DI 10.1002/hep.24752
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 916AW
UT WOS:000302069900005
PM 22030902
ER

PT J
AU Ishikawa, T
   Factor, VM
   Marquardt, JU
   Raggi, C
   Seo, D
   Kitade, M
   Conner, EA
   Thorgeirsson, SS
AF Ishikawa, Tsuyoshi
   Factor, Valentina M.
   Marquardt, Jens U.
   Raggi, Chiara
   Seo, Daekwan
   Kitade, Mitsuteru
   Conner, Elizabeth A.
   Thorgeirsson, Snorri S.
TI Hepatocyte growth factor/c-met signaling is required for
   stem-cell-mediated liver regeneration in mice
SO HEPATOLOGY
LA English
DT Article
ID OVAL CELLS; MATRIX METALLOPROTEINASES; PROGENITOR CELLS; MOUSE-LIVER;
   RAT-LIVER; PROLIFERATION; FIBROSIS; INJURY; DIFFERENTIATION; MACROPHAGES
AB Hepatocyte growth factor (HGF)/c-Met supports a pleiotrophic signal transduction pathway that controls stem cell homeostasis. Here, we directly addressed the role of c-Met in stem-cellmediated liver regeneration by utilizing mice harboring c-met floxed alleles and Alb-Cre or Mx1-Cre transgenes. To activate oval cells, the hepatic stem cell (HSC) progeny, we used a model of liver injury induced by diet containing the porphyrinogenic agent, 3,5-diethocarbonyl-1,4-dihydrocollidine (DDC). Deletion of c-met in oval cells was confirmed in both models by polymerase chain reaction analysis of fluorescence-activated cell-sorted epithelial cell adhesion molecule (EpCam)-positive cells. Loss of c-Met receptor decreased the sphere-forming capacity of oval cells in vitro as well as reduced oval cell pool, impaired migration, and decreased hepatocytic differentiation in vivo, as demonstrated by double immunofluorescence using oval- (A6 and EpCam) and hepatocyte-specific (i.e. hepatocyte nuclear factor 4-alpha) antibodies. Furthermore, lack of c-Met had a profound effect on tissue remodeling and overall composition of HSC niche, which was associated with greatly reduced matrix metalloproteinase (MMP)9 activity and decreased expression of stromal-cellderived factor 1. Using a combination of double immunofluorescence of cell-typespecific markers with MMP9 and gelatin zymography on the isolated cell populations, we identified macrophages as a major source of MMP9 in DDC-treated livers. The Mx1-Cre-driven c-met deletion caused the greatest phenotypic impact on HSCs response, as compared to the selective inactivation in the epithelial cell lineages achieved in c-Metfl/fl; Alb-Cre+/- mice. However, in both models, genetic loss of c-met triggered a similar cascade of events, leading to the failure of HSC mobilization and death of the mice. Conclusion: These results establish a direct contribution of c-Met in the regulation of HSC response and support a unique role for HGF/c-Met as an essential growth-factorsignaling pathway for regeneration of diseased liver. (HEPATOLOGY 2012)
C1 [Ishikawa, Tsuyoshi; Factor, Valentina M.; Marquardt, Jens U.; Raggi, Chiara; Seo, Daekwan; Kitade, Mitsuteru; Conner, Elizabeth A.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 4146A,37 Convent Dr, Bethesda, MD 20892 USA.
EM Snorri_thorgeirsson@nih.gov
OI RAGGI, Chiara/0000-0003-2473-3535
FU National Institutes of Health, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Cancer Institute.
NR 53
TC 58
Z9 62
U1 1
U2 34
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD APR
PY 2012
VL 55
IS 4
BP 1215
EP 1226
DI 10.1002/hep.24796
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 916AW
UT WOS:000302069900025
PM 22095660
ER

PT J
AU Chen, F
   Du, SY
   Bian, JH
   You, ZB
   Wu, Y
AF Chen, Fang
   Du, Shouyang
   Bian, Jianghui
   You, Zhi-Bing
   Wu, Yan
TI Chronic hypoxia exposure during pregnancy is associated with a decreased
   active nursing activity in mother and an abnormal birth weight and
   postnatal growth in offspring of rats
SO HORMONES AND BEHAVIOR
LA English
DT Article
DE Corticosterone; Gestational hypoxia; Maternal behavior; Offspring
   development; Rat
ID PITUITARY-ADRENAL AXIS; PRENATAL STRESS; MATERNAL-BEHAVIOR; GESTATIONAL
   STRESS; NORWAY RATS; CARE; CORTICOSTERONE; INSULIN; MICE; HIPPOCAMPUS
AB Stress during pregnancy is known to have a significant impact on animal's behavior and offspring development. The effects of gestational hypoxia on maternal behavior have not been studied. In the present study, we investigated the effects of gestational hypoxia exposure on dam's maternal behavior, offspring's growth and plasma corticosterone levels after parturition in rats. Altitude hypoxia (3 and 5 km) was simulated in the hypobaric chambers during the last week of pregnancy and the effects were compared to those found in controls exposed at sea level. We found that gestational hypoxia significantly decreased dam's arched-back nursing activity across the lactation period. The effect was more profound in 5 km group. Gestational hypoxia also altered other maternal behaviors such as blanket and passive nursing. Hypoxia exposure was associated with abnormal birth weight and postnatal growth in pups, with a significantly higher and lower birth weight than control found in 3 and 5 km groups, respectively, and accelerated growth in both stressed groups. Gestational hypoxia exposure significantly elevated plasma corticosterone levels in dams at the time of weaning and in pups across the measurement days. Taken together, the present results indicate that hypoxia, particularly severe hypoxia during the late phase of pregnancy has a significantly adverse impact on animal's behavior, endocrine function and offspring development The higher birth weight found in the offspring of 3 km group suggests a compensatory system counteracting with the inhibitory effects of hypoxia on fetus growth at this altitude. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Chen, Fang; Du, Shouyang; Wu, Yan] Hangzhou Normal Univ, Xiasha High Educ Area, Coll Life & Environm Sci, Hangzhou 310036, Zhejiang, Peoples R China.
   [Bian, Jianghui] Chinese Acad Sci, NW Plateau Inst Biol, Xining 810008, Qinghai, Peoples R China.
   [You, Zhi-Bing] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wu, Y (reprint author), Hangzhou Normal Univ, Xiasha High Educ Area, Coll Life & Environm Sci, 16 Xuelin St, Hangzhou 310036, Zhejiang, Peoples R China.
EM wuyanqh@163.com
FU National Natural Science Foundation of China [30570294, 31170394];
   Hangzhou Key Laboratory of Animal Adaptation and Evolution
FX This study was supported by the National Natural Science Foundation of
   China (30570294, 31170394) and Hangzhou Key Laboratory of Animal
   Adaptation and Evolution. We thank Dr. Stephan Steidl, at Behavioral
   Neuroscience Branch, NIDA-IRP, for his critical reading and editing the
   manuscript.
NR 60
TC 5
Z9 7
U1 2
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0018-506X
J9 HORM BEHAV
JI Horm. Behav.
PD APR
PY 2012
VL 61
IS 4
BP 504
EP 511
DI 10.1016/j.yhbeh.2012.01.009
PG 8
WC Behavioral Sciences; Endocrinology & Metabolism
SC Behavioral Sciences; Endocrinology & Metabolism
GA 925LW
UT WOS:000302763700006
PM 22285933
ER

PT J
AU Chen, XJ
   Udupa, JK
   Bagci, U
   Ying, ZG
   Yao, JH
AF Chen, Xinjian
   Udupa, Jayaram K.
   Bagci, Ulas
   Ying Zhuge
   Yao, Jianhua
TI Medical Image Segmentation by Combining Graph Cuts and Oriented Active
   Appearance Models
SO IEEE TRANSACTIONS ON IMAGE PROCESSING
LA English
DT Article
DE Active appearance model (AAM); graph cut (GC); live wire (LW); object
   segmentation
ID SHAPE MODELS; ENERGY MINIMIZATION; FUZZY CONNECTEDNESS; LIVER
   SEGMENTATION; OBJECT DEFINITION; CARDIAC MR; CT IMAGES; ALGORITHMS;
   ATLAS; CONSTRUCTION
AB In this paper, we propose a novel method based on a strategic combination of the active appearance model (AAM), live wire (LW), and graph cuts (GCs) for abdominal 3-D organ segmentation. The proposed method consists of three main parts: model building, object recognition, and delineation. In the model building part, we construct the AAM and train the LW cost function and GC parameters. In the recognition part, a novel algorithm is proposed for improving the conventional AAM matching method, which effectively combines the AAM and LW methods, resulting in the oriented AAM (OAAM). A multiobject strategy is utilized to help in object initialization. We employ a pseudo-3-D initialization strategy and segment the organs slice by slice via a multiobject OAAM method. For the object delineation part, a 3-D shape-constrained GC method is proposed. The object shape generated from the initialization step is integrated into the GC cost computation, and an iterative GC-OAAM method is used for object delineation. The proposed method was tested in segmenting the liver, kidneys, and spleen on a clinical CT data set and also on the MICCAI 2007 Grand Challenge liver data set. The results show the following: 1) The overall segmentation accuracy of true positive volume fraction TPVF > 94.3% and false positive volume fraction FPVF < 0.2% can be achieved; 2) the initialization performance can be improved by combining the AAM and LW; 3) the multiobject strategy greatly facilitates initialization; 4) compared with the traditional 3-D AAM method, the pseudo-3-D OAAM method achieves comparable performance while running 12 times faster; and 5) the performance of the proposed method is comparable to state-of-the-art liver segmentation algorithm. The executable version of the 3-D shape-constrained GC method with a user interface can be downloaded from http://xinjianchen.wordpress.com/research/.
C1 [Chen, Xinjian; Bagci, Ulas; Yao, Jianhua] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA.
   [Udupa, Jayaram K.] Univ Penn, Dept Radiol, Med Image Proc Grp, Philadelphia, PA 19104 USA.
   [Ying Zhuge] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20814 USA.
RP Chen, XJ (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20814 USA.
EM myfuturejian@gmail.com; jay@mail.med.upenn.edu; bagciu@mail.nih.gov;
   zhugey@mail.nih.gov; jyao@mail.nih.gov
RI Bagci, Ulas/A-4225-2012; Chen, Xinjian/E-8592-2016; 
OI Bagci, Ulas/0000-0001-7379-6829
FU Clinical Center, NIH
FX Manuscript received December 27, 2010; revised May 10, 2011, October 03,
   2011, and January 04, 2012; accepted January 09, 2012. Date of
   publication January 31, 2012; date of current version March 21, 2012.
   This work was supported in part by the Intramural Research Program of
   the Clinical Center, NIH. The associate editor coordinating the review
   of this manuscript and approving it for publication was Prof. Margaret
   Cheney.
NR 49
TC 55
Z9 67
U1 5
U2 30
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1057-7149
J9 IEEE T IMAGE PROCESS
JI IEEE Trans. Image Process.
PD APR
PY 2012
VL 21
IS 4
BP 2035
EP 2046
DI 10.1109/TIP.2012.2186306
PG 12
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
   Electronic
SC Computer Science; Engineering
GA 917MP
UT WOS:000302181800048
PM 22311862
ER

PT J
AU Paulson, ML
   Olivier, KN
   Holland, SM
AF Paulson, M. L.
   Olivier, K. N.
   Holland, S. M.
TI Pulmonary non-tuberculous mycobacterial infection in congenital
   contractural arachnodactyly
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE atypical mycobacterial; Mycobacterium avium complex; human fibrillin 2
   (congenital contracrural arachnodactyly) protein; fibrillin
ID EXTRACELLULAR MICROFIBRILS; MARFAN-SYNDROME; DISEASE; MUTATIONS
AB Congenital contractural arachnodactyly (CCA) is caused by mutations within the fibrillin-2 gene (FBN2), which is crucial for microfibril structure. Affected individuals may have contractures, chest wall deformities, scoliosis, abnormal ear folding and elongated limbs. We describe a novel FBN2 mutation in a woman with CCA who also had pulmonary non-tuberculous mycobacteria (NTM) infection. The population with pulmonary NTM infections shares phenotypic features with CCA, such as elongated body habitus, scoliosis and pectus deformities. While it is unlikely that FBN2 defects account for susceptibility to NTM infection in the majority of cases, the overlap between these two diseases suggests some shared pathophysiology.
C1 [Paulson, M. L.] NCI, Lab Clin Infect Dis, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA.
RP Paulson, ML (reprint author), NCI, Lab Clin Infect Dis, SAIC Frederick Inc, NIH, 9000 Rockville Pike,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM paulsonm@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health; National Cancer
   Institute, National Institutes of Health [HHSN261200800001E]
FX This research was supported [in part] by the Division of Intramural
   Research, National Institute of Allergy and Infectious Diseases,
   National Institutes of Health, and funded in part with federal funds
   from the National Cancer Institute, National Institutes of Health, under
   Contract No. HHSN261200800001E.
NR 10
TC 11
Z9 11
U1 0
U2 1
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD APR
PY 2012
VL 16
IS 4
BP 561
EP 563
DI 10.5588/ijtld.11.0301
PG 3
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA 919OA
UT WOS:000302336300025
PM 22325249
ER

PT J
AU Cabral-Marques, O
   Schimke, LF
   Pereira, PVS
   Falcai, A
   de Oliveira, JB
   Hackett, MJ
   Errante, PR
   Weber, CW
   Ferreira, JF
   Kuntze, G
   Rosario, NA
   Ochs, HD
   Torgerson, TR
   Carvalho, BTC
   Condino-Neto, A
AF Cabral-Marques, Otavio
   Schimke, Lena-Friederike
   Soeiro Pereira, Paulo Vitor
   Falcai, Angela
   de Oliveira, Joao Bosco
   Hackett, Mary J.
   Errante, Paolo Ruggero
   Weber, Cristina Worm
   Ferreira, Janaira Fernandes
   Kuntze, Gisele
   Rosario-Filho, Nelson Augusto
   Ochs, Hans D.
   Torgerson, Troy R.
   Costa Carvalho, Beatriz Tavares
   Condino-Neto, Antonio
TI Expanding the Clinical and Genetic Spectrum of Human CD40L Deficiency:
   The Occurrence of Paracoccidioidomycosis and Other Unusual Infections in
   Brazilian Patients
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE Paracoccidioides brasiliensis; CD40 ligand; primary immunodeficiency;
   X-linked hyper-IgM syndrome
ID HYPER-IGM SYNDROME; CHRONIC MUCOCUTANEOUS CANDIDIASIS;
   HUMAN-IMMUNODEFICIENCY-VIRUS; FUNGAL-INFECTIONS; ENDEMIC AREA; LIGAND
   GENE; T-CELLS; MUTATIONS; DISEASE; SERIES
AB CD40 ligand (CD40L) deficiency or X-linked hyper-IgM syndrome (X-HIGM) is a well-described primary immunodeficiency in which Pneumocystis jiroveci pneumonia is a common clinical feature. We have identified an unusual high incidence of fungal infections and other not yet described infections in a cohort of 11 X-HIGM patients from nine unrelated Brazilian families. Among these, we describe the first case of paracoccidioidomycosis (PCM) in X-HIGM. The molecular genetic analysis of CD40L was performed by gene sequencing and evaluation of CD40L protein expression. Nine of these 11 patients (82%) had fungal infections. These included fungal species common to CD40L deficiency (P. jiroveci and Candida albicans) as well as Paracoccidioides brasiliensis. One patient presented with PCM at age 11 years and is now doing well at 18 years of age. Additionally, one patient presented with a simultaneous infection with Klebsiella and Acinetobacter, and one with condyloma caused by human papilloma virus. Molecular analysis revealed four previously described CD40L mutations, two novel missense mutations (c.433 T>G and c.476 G>C) resulting in the absence of CD40L protein expression by activated CD4(+) cells and one novel insertion (c.484_485insAA) within the TNFH domain leading to a frame shift and premature stop codon. These observations demonstrated that the susceptibility to fungal infections in X-HIGM extends beyond those typically associated with X-HIGM (P. jiroveci and C. albicans) and that these patients need to be monitored for those pathogens.
C1 [Cabral-Marques, Otavio; Schimke, Lena-Friederike; Soeiro Pereira, Paulo Vitor; Falcai, Angela; Errante, Paolo Ruggero; Condino-Neto, Antonio] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, BR-05508000 Sao Paulo, Brazil.
   [Hackett, Mary J.; Ochs, Hans D.; Torgerson, Troy R.] Univ Washington, Dept Pediat, Sch Med & Seattle, Childrens Hosp, Seattle, WA 98195 USA.
   [de Oliveira, Joao Bosco] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
   [Weber, Cristina Worm] Pediat Allergy & Immunol Clin, Caxias Do Sul, RS, Brazil.
   [Ferreira, Janaira Fernandes] Albert Sabin Hosp, Fortaleza, Ceara, Brazil.
   [Kuntze, Gisele] Pequeno Principe Hosp, Curitiba, Parana, Brazil.
   [Rosario-Filho, Nelson Augusto] Univ Fed Parana, Dept Pediat, Sch Med, BR-80060000 Curitiba, Parana, Brazil.
   [Costa Carvalho, Beatriz Tavares] Univ Fed Sao Paulo, Div Allergy & Clin Immunol & Rheumatol, Dept Pediat, Sch Med, Sao Paulo, Brazil.
RP Condino-Neto, A (reprint author), Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, 1730 Lineu Prestes Ave, BR-05508000 Sao Paulo, Brazil.
EM condino@icb.usp.br
OI Oliveira, Joao/0000-0001-9388-8173
FU FAPESP [2008/06635-0, 2008/55700-9]; CNPq; Jeffrey Modell Foundation
FX The authors thank FAPESP (grant 2008/06635-0 to OCM and grant
   2008/55700-9 to ACN), CNPq, and Jeffrey Modell Foundation for financial
   support and the patients and their families for their participation in
   this study.
NR 55
TC 15
Z9 16
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 212
EP 220
DI 10.1007/s10875-011-9623-6
PG 9
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200002
PM 22193914
ER

PT J
AU Ding, L
   Mo, A
   Jutivorakool, K
   Pancholi, M
   Holland, SM
   Browne, SK
AF Ding, Li
   Mo, Allen
   Jutivorakool, Kamonwan
   Pancholi, Minjal
   Holland, Steven M.
   Browne, Sarah K.
TI Determination of Human Anticytokine Autoantibody Profiles Using a
   Particle-Based Approach
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE Interferon gamma; luminex; thymoma; pulmonary alveolar proteinosis;
   immunodeficiency
ID PEMPHIGUS-VULGARIS; RITUXIMAB; DISEASE; ASSAY; IGG
AB Background Anticytokine autoantibodies cause numerous human diseases, ranging from pure red cell aplasia to acquired immunodeficiencies. Rapid, simple, and affordable detection and monitoring of these antibodies is essential. We sought to develop a standardizable assay that is rapid, sensitive, and specific and able to simultaneously detect multiple anticytokine autoantibodies in small volumes (<10 mu l).
   Methods We conjugated purified human cytokines to commercially available fluorescently labeled microspheres and tested them against sera from well-characterized subjects with at least one high-titer, disease-associated anticytokine autoantibody.
   Results Cytokine-conjugated microspheres efficiently and rapidly determined plasma concentration and IgG subclass of anticytokine autoantibodies in single or multiplex formats.
   Conclusion This particle-based multiplex assay can reproducibly characterize anticytokine autoantibodies. This efficient and inexpensive approach to diagnosing and monitoring anticytokine autoantibodies has clinical applications.
C1 [Ding, Li; Mo, Allen; Jutivorakool, Kamonwan; Pancholi, Minjal; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
   [Mo, Allen] Colgate Univ, Hamilton, NY 13346 USA.
RP Browne, SK (reprint author), NIAID, Lab Clin Infect Dis, 9000 Rockville Pike,MSC 1684,Bldg 10-CRC,Rm B3-42, Bethesda, MD 20892 USA.
EM brownesa@niaid.nih.gov
FU Division of Intramural Research at the National Institute of Allergy and
   Infectious Diseases; Colgate University
FX This work was supported by the Division of Intramural Research at the
   National Institute of Allergy and Infectious Diseases and Colgate
   University.
NR 17
TC 18
Z9 18
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 238
EP 245
DI 10.1007/s10875-011-9621-8
PG 8
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200005
PM 22170314
ER

PT J
AU Cunha, LAO
   Figueiredo, BCG
   Silva, ML
   Nunes, JBS
   Cunha, JM
   Oliveira, JB
   Pinto, JA
AF Cunha, L. A. O.
   Figueiredo, B. C. G.
   Silva, M. L.
   Nunes, J. B. S.
   Cunha, J. M.
   Oliveira, Joao Bosco
   Pinto, J. A.
TI Could Maternal T Cell Engraftment Be Good to a SCID Patient?
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Cunha, L. A. O.; Figueiredo, B. C. G.; Silva, M. L.; Nunes, J. B. S.; Pinto, J. A.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
   [Cunha, J. M.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
   [Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 358
EP 359
PG 2
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200038
ER

PT J
AU Albert, MH
   Aydin, S
   Alsum, Z
   Chatila, T
   Su, HL
   Heinz, V
   Al-Herz, W
   Keles, S
   Picard, C
   Kilic, S
   Gathmann, B
   Honig, M
   Almousa, H
   Sawalle-Belohradsky, J
   Gennery, A
   Geha, RS
   Renner, E
   Grimbacher, B
   Freeman, AF
   Engelhardt, KR
AF Albert, Michael H.
   Aydin, Susanne
   Alsum, Zobaida
   Chatila, Talal
   Su, Helen
   Heinz, Valerie
   Al-Herz, Waleed
   Keles, Sevgi
   Picard, Capucine
   Kilic, Sara
   Gathmann, Benjamin
   Hoenig, Manfred
   Almousa, Hamoud
   Sawalle-Belohradsky, Julie
   Gennery, Andrew
   Geha, Raif S.
   Renner, Ellen
   Grimbacher, Bodo
   Freeman, Alexandra F.
   Engelhardt, Karin R.
TI Clinical Presentation, Long-Term Outcome and Therapeutic Management of
   DOCK8 Deficiency-an International Survey of 125 Patients
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Albert, Michael H.; Aydin, Susanne; Heinz, Valerie; Sawalle-Belohradsky, Julie; Renner, Ellen] Univ Munich, Dr Von Haunerschen Kinderspital, D-80337 Munich, Germany.
   [Alsum, Zobaida; Almousa, Hamoud] King Faisal Specialist Hosp & Res Ctr, Ryadh, Saudi Arabia.
   [Chatila, Talal] Univ Calif Los Angeles, Los Angeles, CA USA.
   [Chatila, Talal] Childrens Hosp, Boston, MA 02115 USA.
   [Su, Helen; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Kuwait, Kuwait.
   [Keles, Sevgi] Konya Univ, Meram Med Fac, Konya, Turkey.
   [Picard, Capucine] Univ Paris 05, Hop Necker Enfants Malad, Paris, France.
   [Kilic, Sara] Uludag Univ, Fac Med, Bursa, Turkey.
   [Gathmann, Benjamin; Grimbacher, Bodo; Engelhardt, Karin R.] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany.
   [Hoenig, Manfred] Univ Kinderklin, Ulm, Germany.
   [Gennery, Andrew] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Geha, Raif S.] Harvard Univ, Sch Med, Childrenns Hosp, Div Immunol, Boston, MA USA.
   [Grimbacher, Bodo; Engelhardt, Karin R.] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England.
   [Grimbacher, Bodo; Engelhardt, Karin R.] UCL, London, England.
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 359
EP 359
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200039
ER

PT J
AU Engelhardt, KR
   Gertz, EM
   Keles, S
   Schaffer, AA
   Ceja, R
   Sassi, A
   Graham, L
   Massaad, MJ
   Bejaoui, M
   Barbouche, MR
   Geha, RS
   Chatila, TA
   Grimbacher, B
AF Engelhardt, Karin R.
   Gertz, E. Michael
   Keles, Sevgi
   Schaeffer, Alejandro A.
   Ceja, Ruben
   Sassi, Atfa
   Graham, Laura
   Massaad, Michel J.
   Bejaoui, Mohamed
   Barbouche, Mohamed-Ridha
   Geha, Raif S.
   Chatila, Talal A.
   Grimbacher, Bodo
CA 38 Referring Phys
TI DOCK8 Deficiency and Diagnostic Guidelines for Hyper-IgE Syndromes
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Engelhardt, Karin R.; Graham, Laura] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England.
   [Engelhardt, Karin R.; Graham, Laura] UCL, London, England.
   [Engelhardt, Karin R.; 38 Referring Phys] Univ Med Ctr Freiburg, CCI, Freiburg, Germany.
   [Gertz, E. Michael; Schaeffer, Alejandro A.] NIH, Dept Hlth & Human Serv, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
   [Keles, Sevgi; Ceja, Ruben] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Immunol Allergy & Rheumatol, Los Angeles, CA 90095 USA.
   [Keles, Sevgi] Selcuk Univ, Div Pediat Allergy & Immunol, Konya, Turkey.
   [Sassi, Atfa] Inst Pasteur, Lab Immunopathol Vaccinol & Mol Genet, Tunis, Tunisia.
   [Bejaoui, Mohamed] Bone Marrow Transplantat Cener, Dept Pediat, Tunis, Tunisia.
   [Barbouche, Mohamed-Ridha] Inst Pasteur, Dept Immunol, Tunis, Tunisia.
   [Geha, Raif S.] Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA.
   [Ceja, Ruben; Massaad, Michel J.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
RI Schaffer, Alejandro/F-2902-2012; Sassi, Atfa/A-5676-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 361
EP 361
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200045
ER

PT J
AU Sanchez, LA
   Cuellar-Rodriguez, J
   Zerbe, CS
   Hsu, AP
   Hickstein, DD
   Freeman, AF
   Holland, SM
AF Sanchez, Lauren A.
   Cuellar-Rodriguez, Jennifer
   Zerbe, Christa S.
   Hsu, Amy P.
   Hickstein, Dennis D.
   Freeman, Alexandra F.
   Holland, Steven M.
TI Thrombotic Complications in GATA2 Deficiency
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Sanchez, Lauren A.; Cuellar-Rodriguez, Jennifer; Zerbe, Christa S.; Hsu, Amy P.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Hickstein, Dennis D.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 362
EP 362
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200048
ER

PT J
AU Lopez-Herrera, G
   Tampella, G
   Baronio, M
   Vitali, M
   Lougaris, V
   Plebani, A
   Pan-Hammarstrom, Q
   Hammarstrom, L
   Du, LK
   Hultenby, K
   Trujillo-Vargas, CM
   Phadwal, K
   Simon, AK
   Moutschen, M
   Etzioni, A
   Srugo, AMI
   Melamed, D
   Liu, CH
   Philippet, P
   Dideberg, V
   Aghamohammadi, A
   Rezai, N
   Enright, V
   Stauss, H
   Herholz, P
   Salzer, U
   Eibel, H
   Pfeifer, D
   Velkeen, H
   Gertz, EM
   Schaffer, AA
   Grimbacher, B
AF Lopez-Herrera, Gabriela
   Tampella, Giacomo
   Baronio, Manuela
   Vitali, Massimilaino
   Lougaris, Vassilious
   Plebani, Alessandro
   Pan-Hammarstroem, Qiang
   Hammarstroem, Lennart
   Du, Likun
   Hultenby, Kjell
   Trujillo-Vargas, Claudia M.
   Phadwal, Kanchan
   Simon, Anna Katharina
   Moutschen, Michel
   Etzioni, Amos
   Srugo, Adi Mory Izhak
   Melamed, Doron
   Liu, Chonghai
   Philippet, Pierre
   Dideberg, Vinciane
   Aghamohammadi, Asghar
   Rezai, Nima
   Enright, Victoria
   Stauss, Hans
   Herholz, Peer
   Salzer, Ulrich
   Eibel, Hermann
   Pfeifer, Dietmar
   Velkeen, Hendrik
   Gertz, E. Michael
   Schaeffer, Alejandro A.
   Grimbacher, Bodo
TI Mutations in LRBA are Associated with a Syndrome of Immune Deficiency
   and Autoimmunity
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Lopez-Herrera, Gabriela; Trujillo-Vargas, Claudia M.; Stauss, Hans; Grimbacher, Bodo] UCL, Dept Immunol, Div Infect & Immun, Royal Free Hosp, London, England.
   [Lopez-Herrera, Gabriela] Immunodeficiency Res Unit, Mexico City, DF, Mexico.
   [Lopez-Herrera, Gabriela] Natl Inst Pediat, Mexico City, DF, Mexico.
   [Plebani, Alessandro] Univ Brescia, Dept Pediat, Brescia, Italy.
   [Plebani, Alessandro] Univ Brescia, Inst Mol Med A Novicelli, Brescia, Italy.
   [Hultenby, Kjell; Liu, Chonghai] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
   [Trujillo-Vargas, Claudia M.] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia.
   [Phadwal, Kanchan; Simon, Anna Katharina] Univ Oxford, BRC Translat Immunol Lab, NIHR, Nuffield Dept Med,John Radcliffe Hosp, Oxford OX3 9DS, England.
   [Simon, Anna Katharina] Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England.
   [Moutschen, Michel] Univ Liege Ctr Immunol CIL, Lab Immunoendocrinol, Inst Pathol, Liege, Belgium.
   [Melamed, Doron] Technion Israel Inst Technol, Meyers Children Hosp, Rambam Hlth Care Campus & Rappaport Fac Med, Haifa, Israel.
   [Liu, Chonghai] Affiliated Hosp, N Sichuan Med Coll, Dept Pediat, Nanchong 637000, Sichuan, Peoples R China.
   [Philippet, Pierre] CHC Esperance, Dept Pediat, Montegnee, Belgium.
   [Dideberg, Vinciane] Univ Liege, Ctr Human Genet, Liege, Belgium.
   [Aghamohammadi, Asghar] Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Childrens Med Ctr, Pediat Ctr Excellence, Tehran, Iran.
   [Rezai, Nima] Univ Tehran Med Sci, Sch Med, Mol Immunol Res Ctr, Tehran, Iran.
   [Rezai, Nima] Univ Tehran Med Sci, Sch Med, Dept Immunol, Tehran, Iran.
   [Eibel, Hermann] Univ Med Ctr Freiburg, CCI, Freiburg, Germany.
   [Pfeifer, Dietmar] Univ Freiburg, Dept Hematol & Oncol, D-79106 Freiburg, Germany.
   [Velkeen, Hendrik] Leiden Univ, Med Ctr, Dept Hematol, Leiden, Netherlands.
   [Gertz, E. Michael; Schaeffer, Alejandro A.] NIH, Department Hlth & Human Serv, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
RI Schaffer, Alejandro/F-2902-2012
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 363
EP 364
PG 2
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200053
ER

PT J
AU Myles, IA
   Gaidamakova, EK
   McDaniel, DP
   Fowler, CJ
   Valdez, PA
   Gayen, M
   Gupta, P
   Sharma, A
   Glass, P
   Maheshwari, RK
   Daly, MJ
   Datta, SK
AF Myles, Ian A.
   Gaidamakova, Elena K.
   McDaniel, Dennis P.
   Fowler, Cedar J.
   Valdez, Patricia A.
   Gayen, Manoshi
   Gupta, Paridhi
   Sharma, Anuj
   Glass, Pamela
   Maheshwari, Radha K.
   Daly, Michael J.
   Datta, Sandip K.
TI Sterility Without Loss of Immunogenicity with Irradiated Vaccine
   Preparations of Viruses and Staphylococcus Aureus
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Myles, Ian A.; Fowler, Cedar J.; Valdez, Patricia A.; Datta, Sandip K.] NIAID, NIH, Bethesda, MD 20892 USA.
   [Gaidamakova, Elena K.; McDaniel, Dennis P.; Daly, Michael J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   [Gayen, Manoshi; Gupta, Paridhi; Sharma, Anuj; Glass, Pamela; Maheshwari, Radha K.] Birla Inst Technol & Sci, Pilani, Rajasthan, India.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 365
EP 365
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200057
ER

PT J
AU Browne, SK
   Rosen, LB
   Rader, C
   Holland, SM
AF Browne, Sarah K.
   Rosen, Lindsey B.
   Rader, Christoph
   Holland, Steven M.
TI Titer, and Not Avidity Determines Degree of Pathogenicity of Anti-IFN
   gamma Autoantibodies in Mediating Immunodeficiency
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Browne, Sarah K.; Rosen, Lindsey B.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 371
EP 372
PG 2
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200077
ER

PT J
AU Jutivorakool, K
   Ding, L
   Hsu, AP
   Holland, SM
   Browne, SK
AF Jutivorakool, Kamonwan
   Ding, Li
   Hsu, Amy P.
   Holland, Steven M.
   Browne, Sarah K.
TI Epitope Mapping, Isotype and IgG Subclass of Anti-Interferon Gamma
   Autoantibodies
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Jutivorakool, Kamonwan; Ding, Li; Hsu, Amy P.; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Jutivorakool, Kamonwan] Chulalongkorn Univ, Dept Med, Fac Med, Bangkok, Thailand.
   [Jutivorakool, Kamonwan] King Chulalongkorn Mem Hosp, Thai Red Cross Soc, Bangkok, Thailand.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 371
EP 371
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200075
ER

PT J
AU Freeman, AF
   Renner, E
   Olivier, KN
   Henderson, C
   Langenbeck, A
   Kwong, KF
   Holland, SM
AF Freeman, Alexandra F.
   Renner, Ellen
   Olivier, Kenneth N.
   Henderson, Carolyn
   Langenbeck, Anne
   Kwong, King F.
   Holland, Steven M.
TI Lung Surgery Outcomes in Stat3 Mutated Hyper IgE Syndrome
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Freeman, Alexandra F.; Olivier, Kenneth N.; Henderson, Carolyn; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Renner, Ellen] Dr von Haunersches Kinderspital, Munich, Germany.
   [Kwong, King F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 372
EP 372
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200079
ER

PT J
AU Menard, L
   Tangye, S
   Church, J
   Klion, A
   Cunningham-Rundles, C
   Nichols, K
   Meffre, E
AF Menard, Laurence
   Tangye, Stuart
   Church, Joseph
   Klion, Amy
   Cunningham-Rundles, Charlotte
   Nichols, Kim
   Meffre, Eric
TI Slam-Associated Protein (SAP) is Essential for the Establishment of
   Human B Cell Tolerance
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Menard, Laurence; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA.
   [Church, Joseph] Childrens Hosp Los Angeles, Los Angeles, CA USA.
   [Klion, Amy] NIAID, NIH, Bethesda, MD 20892 USA.
   [Cunningham-Rundles, Charlotte] Mt Sinai Med Ctr, New York, NY 10029 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 373
EP 373
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200082
ER

PT J
AU Sowerwine, KJ
   Nicholas, SK
   Holland, SM
   Freeman, AF
AF Sowerwine, Kathryn J.
   Nicholas, Sarah K.
   Holland, Steven M.
   Freeman, Alexandra F.
TI Adverse Reactions After Administration of 23-Valent Pneumococcal
   Polysaccharide Vaccine (PPV-23) in STAT3 Deficient Hyper IgE Syndrome
   (STAT3 HIES)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Sowerwine, Kathryn J.; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Nicholas, Sarah K.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 378
EP 379
PG 2
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200098
ER

PT J
AU Sowerwine, KJ
   Boris, L
   Davis, J
   Welch, P
   Holland, SM
   Freeman, AF
AF Sowerwine, Kathryn J.
   Boris, Lisa
   Davis, Joie
   Welch, Pamela
   Holland, Steven M.
   Freeman, Alexandra F.
TI Clinical and Immunologic Findings in Young Children with Early Diagnosis
   of STAT3 Deficient Hyper IgE Syndrome (STAT3 HIES)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Sowerwine, Kathryn J.; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Boris, Lisa; Davis, Joie; Welch, Pamela] NIAID, DCR, ICMOB, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 378
EP 378
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200097
ER

PT J
AU Siegel, AM
   Lawrence, MG
   Freeman, AF
   Stone, K
   Barber, J
   Jung, MY
   Desai, A
   Olivera, A
   Farber, O
   Gilfillan, AM
   Rivera, J
   Milner, J
AF Siegel, Andrea M.
   Lawrence, Monica G.
   Freeman, Alexandra F.
   Stone, Kelly
   Barber, John
   Jung, Mi-yeon
   Desai, Avanti
   Olivera, Ana
   Farber, Orly
   Gilfillan, Alasdair M.
   Rivera, Juan
   Milner, Joshua
TI Impaired Mast Cell Function Leads to Reduced Allergic Disease in Ad-hies
   Patients
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Barber, John] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA.
   [Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Milner, Joshua] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 379
EP 380
PG 2
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200101
ER

PT J
AU Lawrence, MG
   Barber, J
   Desai, A
   O'Brien, M
   Jones, N
   Garabedian, E
   Sokolic, R
   Candotti, F
   Stone, K
   Milner, J
AF Lawrence, Monica G.
   Barber, John
   Desai, Avanti
   O'Brien, Michelle
   Jones, Nina
   Garabedian, Elizabeth
   Sokolic, Robert
   Candotti, Fabio
   Stone, Kelly
   Milner, Joshua
TI Lymphopenia is Associated with a TH2 Phenotype and Specific Allergen
   Sensitivity in Patients with ADA-SCID
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Lawrence, Monica G.; Barber, John; Desai, Avanti; O'Brien, Michelle; Jones, Nina; Stone, Kelly; Milner, Joshua] NIAID, Bethesda, MD 20892 USA.
   [Sokolic, Robert] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
RI Sokolic, Robert/I-6072-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 383
EP 383
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200112
ER

PT J
AU Barber, J
   Yokomizo, L
   Milner, J
AF Barber, John
   Yokomizo, Lauren
   Milner, Joshua
TI A Novel Approach to Activating CD4 T-Cells and Assessing the Diversity
   of T-Cell Receptors Using Randomized Peptide Pools
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Barber, John; Yokomizo, Lauren; Milner, Joshua] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA.
   [Yokomizo, Lauren] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 384
EP 384
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200116
ER

PT J
AU Dowdell, K
   Lu, LH
   Kuehn, H
   Rao, VK
   Fleisher, TA
   Oliveira, JB
AF Dowdell, Kennichi
   Lu, Lianghao
   Kuehn, Hyesun
   Rao, V. Koneti
   Fleisher, Thomas A.
   Oliveira, Joao Bosco
TI The BH3 Mimetic, Small Molecule, ABT-737, was Effective for the
   Treatment of THE MRL/LPR-/- Mouse Model of Autoimmune
   Lymphoproliferative Syndrome (ALPS)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 385
EP 385
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200120
ER

PT J
AU Uzel, G
   Sampaio, EP
   Lawrence, MG
   Hsu, AP
   Dorsey, M
   Freeman, AF
   Gambinieri, E
   Dat, QT
   Torgerson, TR
   Milner, J
   Holland, SM
AF Uzel, Gulbu
   Sampaio, Elizabeth P.
   Lawrence, Monica G.
   Hsu, Amy P.
   Dorsey, Morna
   Freeman, Alexandra F.
   Gambinieri, Eleonora
   Dat, Q. Tran
   Torgerson, Troy R.
   Milner, Joshua
   Holland, Steven M.
TI Dominant Gain-of-Function Mutations in STAT1 and FOXP3+IPEX-Like Disease
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Uzel, Gulbu; Hsu, Amy P.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
   [Dorsey, Morna] Univ S Florida, Dept Allergy Immunol & Rheumatol, St Petersburg, FL 33701 USA.
   [Gambinieri, Eleonora] Univ Florence, Anna Meyer Childrens Hosp, Haematol Oncol Dept, BMT Unit, Florence, Italy.
   [Torgerson, Troy R.] Univ Washington, Ctr Immun & Immunotherapies, Seattle Childrens Res Inst, Seattle, WA 98195 USA.
   [Milner, Joshua] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 386
EP 386
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200121
ER

PT J
AU Leiding, JW
   Marciano, BE
   DeRavin, SS
   Malech, HL
   Holland, SM
AF Leiding, Jennifer W.
   Marciano, Beatriz E.
   DeRavin, Suk See
   Malech, Harry L.
   Holland, Steven M.
TI Diabetes and Cardiovascular Disease in p47phox-/- Chronic Granulomatous
   Disease
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Leiding, Jennifer W.; Marciano, Beatriz E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [DeRavin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 389
EP 389
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200132
ER

PT J
AU Cunha, LAO
   Oliveira, JB
   Guimaraes, TN
   Figueiredo, BCG
   Silva, ML
   Nunes, JBS
   Miranda, LC
   Pinto, JA
AF Cunha, L. A. O.
   Oliveira, Joao Bosco
   Guimaraes, Tiago Nunes
   Figueiredo, B. C. G.
   Silva, M. L.
   Nunes, J. B. S.
   Miranda, L. C.
   Pinto, J. A.
TI CD3 Delta Deficiency: Finding a Familial Cluster in Minas Gerais, Brazil
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Guimaraes, Tiago Nunes] Univ Fed Minas Gerais, Sch Med, Div Allergy & Immunol, Belo Horizonte, MG, Brazil.
   [Oliveira, Joao Bosco] NIH, Serv Immunol, Dept Lab Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 391
EP 391
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200137
ER

PT J
AU Rosenzweig, SD
   Kuehn, H
   Fleisher, TA
   Oliveira, JB
AF Rosenzweig, Sergio D.
   Kuehn, Hyesun
   Fleisher, Thomas A.
   Oliveira, Joao Bosco
TI Caspase-8 Deficiency Manifesting as Adult-Onset Multi-Organ
   Granulomatous Disorder with Recurrent Infections
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 391
EP 391
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200136
ER

PT J
AU Matharu, K
   Zarember, KA
   Kuhns, DB
   Spalding, C
   Garofalo, M
   Dimaggio, T
   Holland, SM
   Malech, HL
   Gallin, JI
AF Matharu, Kabir
   Zarember, Kol A.
   Kuhns, Douglas B.
   Spalding, Chris
   Garofalo, Mary
   Dimaggio, Thomas
   Holland, Steven M.
   Malech, Harry L.
   Gallin, John I.
TI B-Cell Activating Factor (BAFF/BLYS) in Chronic Granulomatous Disease
   (CGD)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Matharu, Kabir] NIAID, Host Def Lab, Howard Hughes Med Inst, Chevy Chase, MD USA.
   [Matharu, Kabir; Zarember, Kol A.; Garofalo, Mary; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Chevy Chase, MD USA.
   [Kuhns, Douglas B.; Dimaggio, Thomas] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
   [Spalding, Chris; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 392
EP 392
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200141
ER

PT J
AU Falcone, EL
   Greenberg, DE
   Tierce, ML
   de la Morena, MT
   Chase, JM
   Church, J
   Zelazny, AM
   Holland, SM
AF Falcone, Emilia Liana
   Greenberg, David E.
   Tierce, Millard Lucien
   de la Morena, M. Teresa
   Chase, John M.
   Church, Joseph
   Zelazny, Adrian M.
   Holland, Steven M.
TI Methylotrophs: A New Group of Bacteria Affecting Patients with Chronic
   Granulomatous Disease
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Falcone, Emilia Liana; Zelazny, Adrian M.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA.
   [Tierce, Millard Lucien] Childrens Hosp Michigan, Detroit, MI 48201 USA.
   [de la Morena, M. Teresa] UT SW Med Ctr, Dept Pediat, Childrens Med Ctr Dallas, Dallas, TX USA.
   [Chase, John M.; Church, Joseph] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
   [Chase, John M.] Univ So Calif, Div Gen Pediat, Childrens Hosp Los Angeles, Los Angeles, CA USA.
   [Church, Joseph] Univ So Calif, Div Clin Immunol & Allergy, Childrens Hosp Los Angeles, Los Angeles, CA USA.
   [Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 402
EP 403
PG 2
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200173
ER

PT J
AU Pechacek, JJ
   Hsu, AP
   Bax, H
   Dias, DL
   Paulson, M
   Ding, L
   Uzel, G
   Rosen, LB
   Browne, SK
   Datta, S
   Milner, J
   Chandrasekaran, P
   Zerbe, CS
   Wiley, H
   Greenberg, DE
   Hoover, S
   Rosenzweig, SD
   Galgiani, JN
   Holland, SM
   Sampaio, EP
AF Pechacek, Joseph J.
   Hsu, Amy P.
   Bax, Hannalore
   Dias, Dalton L.
   Paulson, Michelle
   Ding, Li
   Uzel, Gulbu
   Rosen, Lindsey B.
   Browne, Sarah K.
   Datta, Shrimati
   Milner, Joshua
   Chandrasekaran, Prabha
   Zerbe, Christa S.
   Wiley, Henry
   Greenberg, David E.
   Hoover, Susan
   Rosenzweig, Sergio D.
   Galgiani, John N.
   Holland, Steven M.
   Sampaio, Elizabeth P.
TI Dominant STAT1 Mutations Leading to Disseminated Fungal Infections
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Pechacek, Joseph J.; Hsu, Amy P.; Ding, Li; Uzel, Gulbu; Browne, Sarah K.; Zerbe, Christa S.; Holland, Steven M.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
   [Bax, Hannalore] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
   [Bax, Hannalore] Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands.
   [Paulson, Michelle] SAIC Frederick, Clin Res Directorate, CMRP, Bethesda, MD USA.
   [Rosen, Lindsey B.] NIAID, LCID, NIH, Bethesda, MD 20892 USA.
   [Milner, Joshua] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA.
   [Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA.
   [Hoover, Susan; Galgiani, John N.] Univ Arizona, Valley Fever Ctr Excellence, Coll Med, Tucson, AZ 85721 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 403
EP 403
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200174
ER

PT J
AU Sokolic, R
   Muul, L
   Garabedian, E
   Shaw, K
   Hershfield, MS
   Wayne, AS
   Kohn, DB
   Candotti, F
AF Sokolic, Robert
   Muul, Linda
   Garabedian, Elizabeth
   Shaw, Kit
   Hershfield, Michael S.
   Wayne, Alan S.
   Kohn, Donald B.
   Candotti, Fabio
TI Systemic Effects of PEG-ADA Withdrawal with or Without Chemotherapy
   (CHTX) and Cytotherapy (CTX) in Adenosine Deaminase-Deficient Severe
   Combined Immune Deficiency (ADA-SCID)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Sokolic, Robert] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
   [Shaw, Kit; Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA.
   [Hershfield, Michael S.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
   [Wayne, Alan S.] NCI, Bethesda, MD 20892 USA.
RI Sokolic, Robert/I-6072-2012
NR 0
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 404
EP 404
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200176
ER

PT J
AU Falcao, ACAM
   Marques, PTL
   Santos, AR
   Oliveira, JB
AF Augusto Moura Falcao, Ana Carla
   Lyra Marques, Paula Teixeira
   Santos, Andreia Rangel
   Oliveira, Joao Bosco
TI Disseminated Histoplasmosis Caused by IL12RB1 Gene Mutations in Two
   Brazilian Siblings
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Augusto Moura Falcao, Ana Carla; Lyra Marques, Paula Teixeira] Univ Fed Pernambuco, Recife, PE, Brazil.
   [Oliveira, Joao Bosco] NIH, Serv Immunol, Dept Lab Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 405
EP 405
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200180
ER

PT J
AU Punwani, D
   Gonzalez-Espinosa, D
   Dutra, A
   Pak, E
   Puck, J
AF Punwani, Divya
   Gonzalez-Espinosa, Diana
   Dutra, Amalia
   Pak, Evgenia
   Puck, Jennifer
TI A Universal Callibrator for TREC Testing Assists Newborn Screening for
   SCID and Studies of Immunoreconstitution
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Clinical-Immunology-Society (CIS)/North American
   Conference on Primary Immune Deficiency Diseases
CY MAY 17-20, 2012
CL Chicago, IL
SP Clin Immunol Soc (CIS)
C1 [Punwani, Divya; Gonzalez-Espinosa, Diana; Puck, Jennifer] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Dutra, Amalia; Pak, Evgenia] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD APR
PY 2012
VL 32
IS 2
BP 409
EP 409
PG 1
WC Immunology
SC Immunology
GA 923JI
UT WOS:000302615200191
ER

PT J
AU Stojmirovic, A
   Yu, YK
AF Stojmirovic, Aleksandar
   Yu, Yi-Kuo
TI Information Flow in Interaction Networks II: Channels, Path Lengths, and
   Potentials
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE Markov chains; random walks; matrices; proteins; networks; information
   theory; pathways; channels
ID PROTEIN INTERACTION NETWORK; COLLABORATIVE RECOMMENDATION; INTERACTION
   DATABASE; MAP; YEAST; RESOURCE; GRAPH; SUM
AB In our previous publication, a framework for information flow in interaction networks based on random walks with damping was formulated with two fundamental modes: emitting and absorbing. While many other network analysis methods based on random walks or equivalent notions have been developed before and after our earlier work, one can show that they can all be mapped to one of the two modes. In addition to these two fundamental modes, a major strength of our earlier formalism was its accommodation of context-specific directed information flow that yielded plausible and meaningful biological interpretation of protein functions and pathways. However, the directed flow from origins to destinations was induced via a potential function that was heuristic. Here, with a theoretically sound approach called the channel mode, we extend our earlier work for directed information flow. This is achieved by constructing a potential function facilitating a purely probabilistic interpretation of the channel mode. For each network node, the channel mode combines the solutions of emitting and absorbing modes in the same context, producing what we call a channel tensor. The entries of the channel tensor at each node can be interpreted as the amount of flow passing through that node from an origin to a destination. Similarly to our earlier model, the channel mode encompasses damping as a free parameter that controls the locality of information flow. Through examples involving the yeast pheromone response pathway, we illustrate the versatility and stability of our new framework.
C1 [Stojmirovic, Aleksandar; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Yu, YK (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM yyu@ncbi.nlm.nih.gov
OI Stojmirovic, Aleksandar/0000-0003-0957-6893
FU National Library of Medicine at the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Library of Medicine at the National Institutes of Health.
NR 38
TC 8
Z9 8
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD APR
PY 2012
VL 19
IS 4
BP 379
EP 403
DI 10.1089/cmb.2010.0228
PG 25
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 922NH
UT WOS:000302553800004
PM 22409812
ER

PT J
AU Kendra, R
   Bell, KM
   Guimond, JM
AF Kendra, Rachel
   Bell, Kathryn M.
   Guimond, Jennifer M.
TI The Impact of Child Abuse History, PTSD Symptoms, and Anger Arousal on
   Dating Violence Perpetration Among College Women
SO JOURNAL OF FAMILY VIOLENCE
LA English
DT Article
DE Dating violence; Anger; PTSD; Child abuse
ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE;
   FAMILY-OF-ORIGIN; SEXUAL-ABUSE; ADULT VICTIMIZATION; PHYSICAL VIOLENCE;
   TRAUMA; MALTREATMENT; SYMPTOMATOLOGY; RECOGNITION
AB Preliminary research suggests that child abuse is indirectly associated with female-perpetrated intimate partner violence via posttraumatic stress disorder (PTSD) symptoms and anger. To date, however, no known studies have investigated these relationships for physical and psychological dating violence within a female college sample. Therefore, the purpose of the current study was to examine the impact of child abuse history, PTSD symptoms, and anger arousal on female-perpetrated physical and psychological dating violence. Female undergraduates (N = 496) completed measures of child abuse, PTSD symptoms, anger arousal, and dating violence perpetration as part of a larger trauma and violence study. Results indicated that child abuse directly predicted female-perpetrated physical and psychological dating violence and indirectly impacted female-perpetrated physical and psychological dating violence via PTSD symptoms and anger arousal. The direct relationships between PTSD symptoms and female-perpetrated physical and psychological dating violence were nonsignificant after controlling for the effect of anger arousal.
C1 [Bell, Kathryn M.] Capital Univ, Dept Psychol, Columbus, OH 43209 USA.
   [Kendra, Rachel] No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA.
   [Guimond, Jennifer M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, DHHS, Bethesda, MD USA.
RP Bell, KM (reprint author), Capital Univ, Dept Psychol, Columbus, OH 43209 USA.
EM kbell626@capital.edu
OI Guimond, Jennifer/0000-0002-8887-5885
NR 81
TC 14
Z9 14
U1 7
U2 24
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7482
J9 J FAM VIOLENCE
JI J. Fam. Violence
PD APR
PY 2012
VL 27
IS 3
BP 165
EP 175
DI 10.1007/s10896-012-9415-7
PG 11
WC Psychology, Clinical; Family Studies
SC Psychology; Family Studies
GA 923UN
UT WOS:000302645500001
ER

PT J
AU Liu, S
   Chen, ZS
   Zhu, F
   Hu, YL
AF Liu, Shuang
   Chen, Zhisong
   Zhu, Feng
   Hu, Yinling
TI I kappa B Kinase Alpha and Cancer
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Review
ID SQUAMOUS-CELL CARCINOMAS; SKIN TUMOR-DEVELOPMENT; HELIX-LOOP-HELIX;
   IKK-ALPHA; TERMINAL DIFFERENTIATION; EPIDERMAL MORPHOGENESIS; EXPRESSION
   PROMOTES; SIGNALING PATHWAY; SOMATIC MUTATION; GENE-EXPRESSION
AB I kappa B kinase alpha (Ikk-alpha) gene mutations and IKK-alpha downregulation have been detected in various human squamous cell carcinomas (SCCs), which are malignancies derived from squamous epithelial cells. These squamous epithelial cells distribute to many organs in the body; however, the epidermis is the only organ mainly composed of stratified squamous epithelial cells, called keratinocytes. SCC is the second most common type of skin cancer. Reducing IKK-alpha expression promotes tumor initiation, and its loss greatly enhances tumor progression from benign papillomas to malignant carcinomas during chemical skin carcinogenesis in mice. Thus, IKK-alpha has emerged as a tumor suppressor for SCCs. Furthermore, inducible deletion of IKK-alpha in the keratinocytes of adult mice causes spontaneous skin papillomas and carcinomas, indicating that IKK-alpha deletion functions as a tumor initiator as well as a tumor promoter. This article discusses IKK-alpha biological activities and associated molecular events in skin tumor development, which may provide insight into the diagnosis, treatment, and prevention of human squamous cell carcinomas (SCCs) in the future.
C1 [Liu, Shuang; Chen, Zhisong; Zhu, Feng; Hu, Yinling] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
RP Hu, YL (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
EM huy2@mail.nih.gov
FU National Cancer Institute [CA102510, CA117314]
FX Our studies were supported by National Cancer Institute grants CA102510
   and CA117314 (to Y.H) and National Cancer Institute intramural program.
NR 62
TC 4
Z9 4
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD APR
PY 2012
VL 32
IS 4
BP 152
EP 158
DI 10.1089/jir.2011.0107
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 925OT
UT WOS:000302771400002
PM 22149351
ER

PT J
AU Goldstein, DS
AF Goldstein, David S.
TI Cardiac Sympathetic Neuroimaging in Dementia with Lewy Bodies
SO JOURNAL OF NEUROIMAGING
LA English
DT Review
DE Power spectral analysis; heart rate variability; sympathetic;
   parasympathetic; autonomic
ID PARKINSONS-DISEASE
AB J Neuroimaging 2012;22:109-110.
C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC 1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU Division of Intramural Research, NINDS, NIH
FX Division of Intramural Research, NINDS, NIH.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1051-2284
J9 J NEUROIMAGING
JI J. Neuroimaging
PD APR
PY 2012
VL 22
IS 2
BP 109
EP 110
DI 10.1111/j.1552-6569.2010.00526.x
PG 2
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 923PM
UT WOS:000302631200006
PM 20977534
ER

PT J
AU Sancarlo, D
   Pilotto, A
   Panza, F
   Copetti, M
   Longo, MG
   D'Ambrosio, P
   D'Onofrio, G
   Ferrucci, L
   Pilotto, A
AF Sancarlo, Daniele
   Pilotto, Andrea
   Panza, Francesco
   Copetti, Massimiliano
   Longo, Maria Grazia
   D'Ambrosio, Piero
   D'Onofrio, Grazia
   Ferrucci, Luigi
   Pilotto, Alberto
TI A Multidimensional Prognostic Index (MPI) based on a comprehensive
   geriatric assessment predicts short- and long-term all-cause mortality
   in older hospitalized patients with transient ischemic attack
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Transient ischemic attack (TIA); All-cause mortality; Risk factor;
   Multidimensional Prognostic Index (MPI); Aging; Comprehensive geriatric
   assessment (CGA)
ID MAJOR VASCULAR EVENTS; EARLY STROKE RISK; ELDERLY PATIENTS; FOLLOW-UP;
   VALIDATION; SCORE; SURVIVAL; REFINEMENT; DISEASE; DEFICIT
AB A multidimensional impairment may influence the clinical outcome of acute diseases in older patients. The aim of the current study was to evaluate whether a Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment (CGA) predicts short- and long-term all-cause mortality in older patients hospitalized for transient ischemic attack (TIA). In this prospective study with 1-year follow-up, 654 patients aged 65 and older with a diagnosis of TIA according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM 435.x) were enrolled. A standardized CGA that included information on functional (activities of daily living, ADL, and Instrumental ADL), cognitive status (Short Portable Mental Status Questionnaire), nutrition (Mini Nutritional Assessment), risk of pressure sores (Exton-Smith Scale), comorbidities (Cumulative Illness Rating Scale), medications and co-habitation status was used to calculate the MPI for mortality using a previously validated algorithm. Higher MPI values were significantly associated with higher 1-month all-cause mortality (incidence rates: MPI-1 low risk = 0.32%, MPI-2 moderate risk = 5.36%, MPI-3 high risk = 10.42%; p < 0.001), 6-month all-cause mortality (MPI-1 = 1.95%, MPI-2 = 9.77%, MPI-3 = 27.22%; p < 0.001) and 12-month all-cause mortality (MPI-1 = 5.19%, MPI-2 = 16.47%, MPI-3 = 44.32%; p < 0.001). Age- and gender-adjusted Cox regression analyses demonstrated that MPI was a significant predictor of all-cause mortality. MPI showed a significant high discriminatory power with an area under the receiver operating characteristics (ROC) curve of 0.819, 95% CI = 0.749-0.888 for 1-month mortality, 0.799, 95% CI = 0.738-0.861 for 6-month mortality and 0.770, 95% CI = 0.716-0.824 for 12-month mortality. The MPI, calculated from information collected in a standardized CGA, appeared to be effective in estimating short- and long-term all-cause mortality in older patients hospitalized for TIA.
C1 [Pilotto, Alberto] S Antonio Hosp, Geriatr Unit, I-35127 Padua, Italy.
   [Sancarlo, Daniele; Panza, Francesco; Longo, Maria Grazia; D'Ambrosio, Piero; D'Onofrio, Grazia] IRCCS Casa Sollievo Sofferenza, Geriatr Unit, I-71013 Foggia, Italy.
   [Sancarlo, Daniele; Panza, Francesco; Longo, Maria Grazia; D'Ambrosio, Piero; D'Onofrio, Grazia] IRCCS Casa Sollievo Sofferenza, Gerontol Geriatr Res Lab, Dept Med Sci, I-71013 Foggia, Italy.
   [Pilotto, Andrea] Univ Brescia, Neurol Unit, Brescia, Italy.
   [Copetti, Massimiliano] IRCCS Casa Sollievo Sofferenza, Unit Biostat, San Giovanni Rotondo, Italy.
   [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Pilotto, A (reprint author), S Antonio Hosp, Geriatr Unit, Azienda ULSS Padova 16,Via Facciolati 71, I-35127 Padua, Italy.
EM alberto.pilotto@sanita.padova.it; alberto.pilotto@sanita.padova.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;
   Panza, Francesco/0000-0002-7220-0656; Pilotto,
   Andrea/0000-0003-2029-6606
FU Ministero della Salute
FX This work was fully supported by grants from Ministero della Salute,
   IRCCS Research Program 2009-2011, Line 2: "Malattie complesse".
NR 39
TC 15
Z9 17
U1 0
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD APR
PY 2012
VL 259
IS 4
BP 670
EP 678
DI 10.1007/s00415-011-6241-4
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 921PL
UT WOS:000302489400011
PM 21947223
ER

PT J
AU Ramachandran, R
   Gravenstein, KS
   Metter, EJ
   Egan, JM
   Ferrucci, L
   Chia, CW
AF Ramachandran, Ramona
   Gravenstein, Kristofer S.
   Metter, E. Jeffrey
   Egan, Josephine M.
   Ferrucci, Luigi
   Chia, Chee W.
TI Selective Contribution of Regional Adiposity, Skeletal Muscle, and
   Adipokines to Glucose Disposal in Older Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE low muscle mass; regional adiposity; glucose disposal
ID BODY-COMPOSITION; INSULIN-RESISTANCE; LIPID-METABOLISM; FAT
   DISTRIBUTION; GROWTH-HORMONE; LEPTIN; SARCOPENIA; HEALTHY; RISK;
   EPIDEMIOLOGY
AB OBJECTIVES: To study the relationships between muscle mass, regional adiposity, and adipokines and glucose disposal in an older population.
   DESIGN: Cross-sectional analysis.
   SETTING: Community-dwelling volunteers from the Baltimore Longitudinal Study of Aging.
   PARTICIPANTS: Two hundred eighty men and 259 women with a mean age of 71.1 +/- 0.4 (range 55-96) and complete data on fasting plasma adiponectin and leptin, oral glucose tolerance test (OGTT) (plasma glucose available at 0, 20, 40, 60, 80, 100, and 120 minutes), thigh computed tomography (CT), physical activity levels, and anthropometric measures.
   MEASUREMENTS: Participants were classified into eight groups according to the presence of global adiposity (body mass index > 27 kg/m(2)), central adiposity (waist circumference > 88 cm for women and > 102 cm for men), and low muscle mass (CT thigh, lowest sex-specific tertile (93.8 cm(2) in women and 110.7 cm(2) in men) of adjusted thigh muscle area). Linear regression models were used to estimate the contribution of these eight groups to early glucose area under the curve (AUC) (t = 0-40 minutes), late glucose AUC (t = 60-120 minutes), and total glucose AUC (t = 0-120 minutes) from the OGTT.
   RESULTS: Regardless of muscle mass, individuals with a combination of central and global adiposity were more likely to have delayed glucose disposal rates (P < .05). A strong negative association was also found between circulating adiponectin levels and glucose disposal rates (early AUC, beta = -0.14; late AUC, beta = -0.20; and total AUC, beta = -0.20; P < .05 for all three AUCs) after adjusting for regional adiposity, muscle mass, circulating leptin levels, physical activity, age, and sex.
   CONCLUSION: Older individuals with global and central adiposity may be at risk of glucose intolerance unrelated to low muscle mass. J Am Geriatr Soc 60:707-712, 2012.
C1 [Ramachandran, Ramona; Gravenstein, Kristofer S.; Metter, E. Jeffrey; Egan, Josephine M.; Ferrucci, Luigi; Chia, Chee W.] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA.
   [Egan, Josephine M.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21225 USA.
RP Chia, CW (reprint author), NIA, Clin Res Branch, NIH, 3001 S Hanover St,NM 533, Baltimore, MD 21225 USA.
EM chiac@mail.nih.gov
FU National Institutes of Health, National Institute on Aging
FX This work was supported entirely by the Intramural Research Program of
   the National Institutes of Health, National Institute on Aging.
NR 26
TC 5
Z9 5
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
IS 4
BP 707
EP 712
DI 10.1111/j.1532-5415.2011.03865.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 923MR
UT WOS:000302623900015
PM 22417789
ER

PT J
AU Crasto, C
   Semba, RD
   Sun, K
   Ferrucci, L
AF Crasto, Candace
   Semba, Richard D.
   Sun, Kai
   Ferrucci, Luigi
TI Serum Fibroblast Growth Factor 21 Is Associated with Renal Function and
   Chronic Kidney Disease in Community-Dwelling Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Letter
C1 [Crasto, Candace; Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
   [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Crasto, C (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
FU NHLBI NIH HHS [R01 HL094507, R01 HL094507-03]; NIA NIH HHS [R01
   AG027012, R01 AG027012-06]
NR 9
TC 12
Z9 13
U1 0
U2 1
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 APR
PY 2012
VL 60
IS 4
BP 792
EP 793
DI 10.1111/j.1532-5415.2011.03879.x
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 923MR
UT WOS:000302623900031
PM 22494291
ER

PT J
AU Leandri, M
   Ghignotti, M
   Emionite, L
AF Leandri, M.
   Ghignotti, M.
   Emionite, L.
TI NOCICEPTIVE MECHANISMS INVOLVED IN THE TAIL FLICK REFLEX
SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
LA English
DT Meeting Abstract
CT Meeting of the Italian-Association-for-the-Peripheral-Nervous-System and
   Pain and Neuroscience Group of the Italian-Society-of-Neurology
CY APR 12-14, 2012
CL Pisa, ITALY
SP Italian Assoc Peripheral Nervous Syst, Italian Soc Neurol
C1 [Leandri, M.; Ghignotti, M.] Univ Genoa, Interuniv Ctr Pain Neurophysiol, Genoa, Italy.
   [Leandri, M.; Ghignotti, M.] Univ Genoa, Dept Neurol Ophthalmol & Genet, Genoa, Italy.
   [Emionite, L.] Natl Canc Inst, Anim Facil, Genoa, Italy.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1085-9489
J9 J PERIPHER NERV SYST
JI J. Peripher. Nerv. Syst.
PD APR
PY 2012
VL 17
SU 1
BP S31
EP S31
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 921GK
UT WOS:000302465900064
ER

PT J
AU Leandri, M
   Ghignotti, M
   Emionite, L
AF Leandri, M.
   Ghignotti, M.
   Emionite, L.
TI COMPOUND ACTION POTENTIAL OF THE CAUDAL NERVE IN A CIPN ANIMAL MODEL
SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
LA English
DT Meeting Abstract
CT Meeting of the Italian-Association-for-the-Peripheral-Nervous-System and
   Pain and Neuroscience Group of the Italian-Society-of-Neurology
CY APR 12-14, 2012
CL Pisa, ITALY
SP Italian Assoc Peripheral Nervous Syst, Italian Soc Neurol
C1 [Leandri, M.; Ghignotti, M.] Univ Genoa, Interuniv Ctr Pain Neurophysiol, Genoa, Italy.
   [Leandri, M.; Ghignotti, M.] Univ Genoa, Dept Neurol Ophthalmol & Genet, Genoa, Italy.
   [Emionite, L.] Natl Canc Inst, Anim Facil, Genoa, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1085-9489
J9 J PERIPHER NERV SYST
JI J. Peripher. Nerv. Syst.
PD APR
PY 2012
VL 17
SU 1
BP S30
EP S31
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 921GK
UT WOS:000302465900063
ER

PT J
AU Cardone, G
   Newcomb, WW
   Cheng, NQ
   Wingfield, PT
   Trus, BL
   Brown, JC
   Steven, AC
AF Cardone, Giovanni
   Newcomb, William W.
   Cheng, Naiqian
   Wingfield, Paul T.
   Trus, Benes L.
   Brown, Jay C.
   Steven, Alasdair C.
TI The UL36 Tegument Protein of Herpes Simplex Virus 1 Has a Composite
   Binding Site at the Capsid Vertices
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CRYOELECTRON MICROSCOPY; ELECTRON-MICROSCOPY; CELL ENTRY; TYPE-1; DNA;
   UL25; VP26; VISUALIZATION; MICROTUBULES; MATURATION
AB Herpesviruses have an icosahedral nucleocapsid surrounded by an amorphous tegument and a lipoprotein envelope. The tegument comprises at least 20 proteins destined for delivery into the host cell. As the tegument does not have a regular structure, the question arises of how its proteins are recruited. The herpes simplex virus 1 (HSV-1) tegument is known to contact the capsid at its vertices, and two proteins, UL36 and UL37, have been identified as candidates for this interaction. We show that the interaction is mediated exclusively by UL36. HSV-1 nucleocapsids extracted from virions shed their UL37 upon incubation at 37 degrees C. Cryo-electron microscopy (cryo-EM) analysis of capsids with and without UL37 reveals the same penton-capping density in both cases. As no other tegument proteins are retained in significant amounts, it follows that this density feature (similar to 100 kDa) represents the ordered portion of UL36 (336 kDa). It binds between neighboring UL19 protrusions and to an adjacent UL17 molecule. These observations support the hypothesis that UL36 plays a major role in the tegumentation of the virion, providing a flexible scaffold to which other tegument proteins, including UL37, bind. They also indicate how sequential conformational changes in the maturing nucleocapsid control the ordered binding, first of UL25/UL17 and then of UL36.
C1 [Cardone, Giovanni; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, Bethesda, MD 20892 USA.
   [Wingfield, Paul T.] NIAMSD, Prot Express Lab, Bethesda, MD 20892 USA.
   [Trus, Benes L.] NIH, Ctr Informat Technol, Imaging Sci Lab, Bethesda, MD 20892 USA.
   [Newcomb, William W.; Brown, Jay C.] Univ Virginia Hlth Syst, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
FU NIAMS; NIH [R01AI041644]
FX This study was supported by the Intramural Research Program of NIAMS and
   by NIH grant R01AI041644 to J.C.B.
NR 45
TC 28
Z9 30
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 APR
PY 2012
VL 86
IS 8
BP 4058
EP 4064
DI 10.1128/JVI.00012-12
PG 7
WC Virology
SC Virology
GA 917NU
UT WOS:000302185400002
PM 22345483
ER

PT J
AU Bello, NF
   Dussupt, V
   Sette, P
   Rudd, V
   Nagashima, K
   Bibollet-Ruche, F
   Chen, CP
   Montelaro, RC
   Hahn, BH
   Bouamr, F
AF Bello, Nana F.
   Dussupt, Vincent
   Sette, Paola
   Rudd, Victoria
   Nagashima, Kunio
   Bibollet-Ruche, Frederic
   Chen, Chaoping
   Montelaro, Ronald C.
   Hahn, Beatrice H.
   Bouamr, Fadila
TI Budding of Retroviruses Utilizing Divergent L Domains Requires
   Nucleocapsid
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS-ANEMIA VIRUS;
   ROUS-SARCOMA-VIRUS; PROTEIN-SORTING PATHWAY; LATE ASSEMBLY DOMAIN; GAG
   PROTEIN; IN-VITRO; CAPSID PROTEIN; ZINC FINGERS; BRO1 DOMAIN
AB We recently reported that human immunodeficiency virus type 1 (HIV-1) carrying PTAP and LYPXnL L domains ceased budding when the nucleocapsid (NC) domain was mutated, suggesting a role for NC in HIV-1 release. Here we investigated whether NC involvement in virus release is a property specific to HIV-1 or a general requirement of retroviruses. Specifically, we examined a possible role for NC in the budding of retroviruses relying on divergent L domains and structurally homologous NC domains that harbor diverse protein sequences. We found that NC is critical for the release of viruses utilizing the PTAP motif whether it functions within its native Gag in simian immunodeficiency virus cpzGAB2 (SIVcpzGAB2) or SIVsmmE543 or when it is transplanted into the heterologous Gag protein of equine infectious anemia virus (EIAV). In both cases, virus release was severely diminished even though NC mutant Gag proteins retained the ability to assemble spherical particles. Moreover, budding- defective NC mutants, which displayed particles tethered to the plasma membrane, were triggered to release virus when access to the cell endocytic sorting complex required for transport pathway was restored (i. e., in trans expression of Nedd4.2s). We also examined the role of NC in the budding of EIAV, a retrovirus relying exclusively on the (L) YPXnL-type L domain. We found that EIAV late budding defects were rescued by overexpression of the isolated Alix Bro1 domain (Bro1). Bro1-mediated rescue of EIAV release required the wild-type NC. EIAV NC mutants lost interactions with Bro1 and failed to produce viruses despite retaining the ability to self-assemble. Together, our studies establish a role for NC in the budding of retroviruses harboring divergent L domains and evolutionarily diverse NC sequences, suggesting the utilization of a common conserved mechanism and/ or cellular factor rather than a specific motif.
C1 [Bello, Nana F.; Dussupt, Vincent; Sette, Paola; Rudd, Victoria] NIAID, Mol Microbiol Lab, Virus Budding Unit, NIH, Bethesda, MD 20892 USA.
   [Nagashima, Kunio] NCI, Image Anal Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA.
   [Bibollet-Ruche, Frederic; Hahn, Beatrice H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
   [Bibollet-Ruche, Frederic; Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Chen, Chaoping] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA.
   [Montelaro, Ronald C.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
RP Bouamr, F (reprint author), NIAID, Mol Microbiol Lab, Virus Budding Unit, NIH, Bethesda, MD 20892 USA.
EM bouamrf@mail.nih.gov
FU NIAID,NIH [R37 AI050529]
FX This work was supported in part by R37 AI050529 and the Intramural
   Research Program of the NIAID,NIH.
NR 80
TC 10
Z9 10
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2012
VL 86
IS 8
BP 4182
EP 4193
DI 10.1128/JVI.07105-11
PG 12
WC Virology
SC Virology
GA 917NU
UT WOS:000302185400014
PM 22345468
ER

PT J
AU Falkowska, E
   Ramos, A
   Feng, Y
   Zhou, TQ
   Moquin, S
   Walker, LM
   Wu, XL
   Seaman, MS
   Wrin, T
   Kwong, PD
   Wyatt, RT
   Mascola, JR
   Poignard, P
   Burton, DR
AF Falkowska, Emilia
   Ramos, Alejandra
   Feng, Yu
   Zhou, Tongqing
   Moquin, Stephanie
   Walker, Laura M.
   Wu, Xueling
   Seaman, Michael S.
   Wrin, Terri
   Kwong, Peter D.
   Wyatt, Richard T.
   Mascola, John R.
   Poignard, Pascal
   Burton, Dennis R.
TI PGV04, an HIV-1 gp120 CD4 Binding Site Antibody, Is Broad and Potent in
   Neutralization but Does Not Induce Conformational Changes Characteristic
   of CD4
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN;
   MONOCLONAL-ANTIBODIES; RATIONAL DESIGN; IN-VITRO; BREADTH; INDIVIDUALS;
   MECHANISM; EVOLUTION; INFECTION
AB Recently, several broadly neutralizing monoclonal antibodies (bnMAbs) directed to the CD4-binding site (CD4bs) of gp120 have been isolated from HIV-1-positive donors. These include VRC01, 3BNC117, and NIH45-46, all of which are capable of neutralizing about 90% of circulating HIV-1 isolates and all of which induce conformational changes in the HIV-1 gp120 monomer similar to those induced by the CD4 receptor. In this study, we characterize PGV04 (also known as VRC-PG04), a MAb with potency and breadth that rivals those of the prototypic VRC01 and 3BNC117. When screened on a large panel of viruses, the neutralizing profile of PGV04 was distinct from those of CD4, b12, and VRC01. Furthermore, the ability of PGV04 to neutralize pseudovirus containing single alanine substitutions exhibited a pattern distinct from those of the other CD4bs MAbs. In particular, substitutions D279A, I420A, and I423A were found to abrogate PGV04 neutralization. In contrast to VRC01, PGV04 did not enhance the binding of 17b or X5 to their epitopes (the CD4-induced [CD4i] site) in the coreceptor region on the gp120 monomer. Furthermore, in contrast to CD4, none of the anti-CD4bs MAbs induced the expression of the 17b epitope on cell surface-expressed cleaved Env trimers. We conclude that potent CD4bs bnMAbs can display differences in the way they recognize and access the CD4bs and that mimicry of CD4, as assessed by inducing conformational changes in monomeric gp120 that lead to enhanced exposure of the CD4i site, is not uniquely correlated with effective neutralization at the site of CD4 binding on HIV-1.
C1 [Falkowska, Emilia; Ramos, Alejandra; Feng, Yu; Walker, Laura M.; Wyatt, Richard T.; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Falkowska, Emilia; Ramos, Alejandra; Feng, Yu; Walker, Laura M.; Wyatt, Richard T.; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
   [Falkowska, Emilia; Burton, Dennis R.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA.
   [Zhou, Tongqing; Moquin, Stephanie; Wu, Xueling; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Seaman, Michael S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
   [Wrin, Terri] Monogram Biosci Inc, San Francisco, CA USA.
RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM burton@scripps.edu
RI Zhou, Tongqing/A-6880-2010; Feng, Yu/A-3396-2012; poignard,
   pascal/N-6678-2013
OI Zhou, Tongqing/0000-0002-3935-4637; 
FU International AIDS Vaccine Initiative (IAVI); Ragon Institute; United
   States Agency for International Development (USAID); Bill and Melinda
   Gates foundation [38619]; NIAID [AI33292, AI084817]
FX This work was supported by the International AIDS Vaccine Initiative
   (IAVI), NIAID (grants AI33292 to D.R.B. and AI084817 to I.A.W.), the
   Ragon Institute, and the United States Agency for International
   Development (USAID).; The neutralization experiments on the 97-virus
   panel were done by Michael Seaman's group (Beth Israel Deaconess Medical
   Center, Harvard Medical School, Boston, MA), and this work was funded
   through the Bill and Melinda Gates foundation (grant no. 38619).
NR 34
TC 64
Z9 64
U1 1
U2 18
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 APR
PY 2012
VL 86
IS 8
BP 4394
EP 4403
DI 10.1128/JVI.06973-11
PG 10
WC Virology
SC Virology
GA 917NU
UT WOS:000302185400034
PM 22345481
ER

PT J
AU Prasad, A
   Lu, M
   Lukac, DM
   Zeichner, SL
AF Prasad, Alka
   Lu, Michael
   Lukac, David M.
   Zeichner, Steven L.
TI An Alternative Kaposi's Sarcoma-Associated Herpesvirus Replication
   Program Triggered by Host Cell Apoptosis
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LYTIC SWITCH PROTEIN; ACTIVATES GENE-EXPRESSION; RBP-J-KAPPA; COUPLED
   RECEPTOR; NUCLEAR ANTIGEN; DNA-SEQUENCES; TRANSCRIPTIONAL ACTIVATION;
   SMALL-MOLECULE; RTA; PROMOTER
AB Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to several neoplastic diseases: Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV replicates actively, via a controlled gene expression program, but can also remain latent. It had been thought that the transition from latent to lytic replication was controlled exclusively by the replication and transcription activator protein RTA (open reading frame 50 [ORF50] gene product). A dominant-negative (DN) ORF50 mutant, ORF50 Delta STAD, blocks gene expression and replication. We produced a PEL cell line derivative containing both latent KSHV genomes and an inducible ORF50 Delta STAD. We unexpectedly found that induction of apoptosis triggered high-level viral replication, even when DN ORF50 Delta STAD was present, suggesting that apoptosis triggers KSHV replication through a distinct RTA-independent pathway. We verified that apoptosis triggers KSHV replication independent of RTA using ORF50 small interfering RNA (siRNA) and also showed that caspase activity is required to trigger KSHV replication. We showed that when apoptosis triggers KSHV replication, the kinetics of late gene expression is accelerated by 12 to 24 h and that virus produced following apoptosis has reduced infectivity. KSHV therefore appears to replicate via two distinct pathways, a conventional pathway requiring RTA, with slower replication kinetics, producing virus with higher infectivity, and an alternative apoptosis-triggered pathway that does not require RTA, has faster replication kinetics, and produces virus with lower infectivity. The existence of a distinct apoptosis-triggered, accelerated replication pathway may have evolutionary advantages for the virus and clinical significance for the treatment of KSHV-associated neoplasms. It also provides further evidence that KSHV can sense and react to its environment.
C1 [Prasad, Alka; Zeichner, Steven L.] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
   [Lu, Michael] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
   [Lukac, David M.] Univ Med & Dent New Jersey, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA.
   [Zeichner, Steven L.] George Washington Univ, Dept Pediat & Microbiol, Washington, DC USA.
   [Zeichner, Steven L.] George Washington Univ, Dept Immunol, Washington, DC USA.
   [Zeichner, Steven L.] George Washington Univ, Dept Trop Med, Washington, DC USA.
RP Zeichner, SL (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
EM zeichner@gwu.edu
OI Lukac, David /0000-0003-0380-5990
FU George Washington University AIDS Institute; Children's Research
   Institute Research Advisory Committee; Conner Family Foundation;
   District of Columbia Developmental Center for AIDS Research(NIAD,NIH)
   [P30AI0877714]
FX This work was supported in part by a Collaborative Faculty Award for
   AIDS Research from the George Washington University AIDS Institute, a
   Children's Research Institute Research Advisory Committee Award, a gift
   from the Conner Family Foundation, and the District of Columbia
   Developmental Center for AIDS Research (P30AI087714 from NIAID, NIH).
NR 53
TC 9
Z9 9
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2012
VL 86
IS 8
BP 4404
EP 4419
DI 10.1128/JVI.06617-11
PG 16
WC Virology
SC Virology
GA 917NU
UT WOS:000302185400035
PM 22345480
ER

PT J
AU Xiao, P
   Patterson, LJ
   Kuate, S
   Brocca-Cofano, E
   Thomas, MA
   Venzon, D
   Zhao, J
   DiPasquale, J
   Fenizia, C
   Lee, EM
   Kalisz, I
   Kalyanaraman, VS
   Pal, R
   Montefiori, D
   Keele, BF
   Robert-Guroff, M
AF Xiao, Peng
   Patterson, L. Jean
   Kuate, Seraphin
   Brocca-Cofano, Egidio
   Thomas, Michael A.
   Venzon, David
   Zhao, Jun
   DiPasquale, Janet
   Fenizia, Claudio
   Lee, Eun Mi
   Kalisz, Irene
   Kalyanaraman, Vaniambadi S.
   Pal, Ranajit
   Montefiori, David
   Keele, Brandon F.
   Robert-Guroff, Marjorie
TI Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant
   Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA
   Immunity in Rhesus Macaques Correlated with Delayed Acquisition
   following a Repeated Low-Dose Rectal SIVmac251 Challenge
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CLASS-I MOLECULE; T-CELLS; PROTECTIVE EFFICACY; HIV-1 INFECTION;
   NEUTRALIZING ANTIBODIES; SUBLINGUAL IMMUNIZATION; SHIV89.6P CHALLENGE;
   NONHUMAN-PRIMATES; VACCINE REGIMEN; RESPONSES
AB We have shown that sequential replicating adenovirus type 5 host range mutant human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) recombinant priming delivered first intranasally (i.n.) plus orally and then intratracheally (i.t.), followed by envelope protein boosting, elicits broad cellular immunity and functional, envelope-specific serum and mucosal antibodies that correlate with protection from high-dose SIV and simian/human immunodeficiency virus (SHIV) challenges in rhesus macaques. Here we extended these studies to compare the standard i.n./i.t. regimen with additional mucosal administration routes, including sublingual, rectal, and vaginal routes. Similar systemic cellular and humoral immunity was elicited by all immunization routes. Central and effector memory T cell responses were also elicited by the four immunization routes in bronchoalveolar lavage fluid and jejunal, rectal, and vaginal tissue samples. Cellular responses in vaginal tissue were more compartmentalized, being induced primarily by intravaginal administration. In contrast, all immunization routes elicited secretory IgA (sIgA) responses at multiple mucosal sites. Following a repeated low-dose intrarectal (i.r.) challenge with SIVmac251 at a dose transmitting one or two variants, protection against acquisition was not achieved except in one macaque in the i.r. immunized group. All immunized macaques exhibited reduced peak viremia compared to that of controls, correlated inversely with prechallenge serum antienvelope avidity, antibody-dependent cellular cytotoxicity (ADCC) titers, and percent antibody-dependent cell-mediated viral inhibition. Both antibody avidity and ADCC titers were correlated with the number of exposures required for infection. Notably, we show for the first time a significant correlation of vaccine-induced sIgA titers in rectal secretions with delayed acquisition. Further investigation of the characteristics and properties of the sIgA should elucidate the mechanism leading to this protective effect.
C1 [Xiao, Peng; Patterson, L. Jean; Kuate, Seraphin; Brocca-Cofano, Egidio; Thomas, Michael A.; Zhao, Jun; DiPasquale, Janet; Fenizia, Claudio; Robert-Guroff, Marjorie] Natl Canc Inst, Vaccine Branch, Bethesda, MD USA.
   [Venzon, David] Natl Canc Inst, Biostat & Data Management Sect, Bethesda, MD USA.
   [Lee, Eun Mi; Kalisz, Irene; Kalyanaraman, Vaniambadi S.; Pal, Ranajit] Adv Biosci Lab Inc, Kensington, MD USA.
   [Montefiori, David] Duke Univ, Med Ctr, Durham, NC USA.
   [Keele, Brandon F.] SAIC Frederick Inc, AIDS & Canc Virus Program, NCI Frederick, Frederick, MD USA.
RP Robert-Guroff, M (reprint author), Natl Canc Inst, Vaccine Branch, Bethesda, MD USA.
EM guroffm@mail.nih.gov
FU NIH, National Cancer Institute
FX This study was supported by the Intramural Research Program of the NIH,
   National Cancer Institute.
NR 55
TC 63
Z9 65
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 APR
PY 2012
VL 86
IS 8
BP 4644
EP 4657
DI 10.1128/JVI.06812-11
PG 14
WC Virology
SC Virology
GA 917NU
UT WOS:000302185400058
PM 22345466
ER

PT J
AU Bonsignori, M
   Montefiori, DC
   Wu, XL
   Chen, X
   Hwang, KK
   Tsao, CY
   Kozink, DM
   Parks, RJ
   Tomaras, GD
   Crump, JA
   Kapiga, SH
   Sam, NE
   Kwong, PD
   Kepler, TB
   Liao, HX
   Mascola, JR
   Haynesa, BF
AF Bonsignori, Mattia
   Montefiori, David C.
   Wu, Xueling
   Chen, Xi
   Hwang, Kwan-Ki
   Tsao, Chun-Yen
   Kozink, Daniel M.
   Parks, Robert J.
   Tomaras, Georgia D.
   Crump, John A.
   Kapiga, Saidi H.
   Sam, Noel E.
   Kwong, Peter D.
   Kepler, Thomas B.
   Liao, Hua-Xin
   Mascola, John R.
   Haynesa, Barton F.
TI Two Distinct Broadly Neutralizing Antibody Specificities of Different
   Clonal Lineages in a Single HIV-1-Infected Donor: Implications for
   Vaccine Design
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY;
   HIV-ANTIBODIES; EPITOPE; GLYCOPROTEIN; INDIVIDUALS; BREADTH; REVEAL;
   GP41; PG16
AB Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4-binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities.
C1 [Bonsignori, Mattia; Montefiori, David C.; Chen, Xi; Hwang, Kwan-Ki; Tsao, Chun-Yen; Kozink, Daniel M.; Parks, Robert J.; Tomaras, Georgia D.; Kepler, Thomas B.; Liao, Hua-Xin; Haynesa, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
   [Crump, John A.] Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.
   [Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
   [Crump, John A.] Duke Univ, Med Ctr, Duke Global Hlth Inst, Durham, NC 27710 USA.
   [Kepler, Thomas B.] Duke Univ, Med Ctr, Ctr Computat Immunol, Durham, NC 27710 USA.
   [Crump, John A.; Sam, Noel E.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
   [Crump, John A.] Kilimanjaro Christian Med Coll, Moshi, Tanzania.
   [Kapiga, Saidi H.] London Sch Hyg & Trop Med, London WC1, England.
   [Wu, Xueling; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Bonsignori, M (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
EM mattia.bonsignori@duke.edu; barton.haynes@duke.edu
RI Tomaras, Georgia/J-5041-2016; 
OI Kepler, Thomas/0000-0002-1383-6865
FU NIH, NIAID; Division of AIDS; Center for HIV/AIDS Vaccine Immunology
   (CHAVI) [U19 AI067854]; Vaccine Research Center, NIAID, NIH
FX This work was supported by NIH, NIAID, the Division of AIDS with the
   Center for HIV/AIDS Vaccine Immunology (CHAVI; grant U19 AI067854), and
   by the Intramural Research Program of the Vaccine Research Center,
   NIAID, NIH.
NR 26
TC 82
Z9 85
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2012
VL 86
IS 8
BP 4688
EP 4692
DI 10.1128/JVI.07163-11
PG 5
WC Virology
SC Virology
GA 917NU
UT WOS:000302185400062
PM 22301150
ER

PT J
AU Ambrose, Z
   Lee, K
   Ndjomou, J
   Xu, HZ
   Oztop, I
   Matous, J
   Takemura, T
   Unutmaz, D
   Engelman, A
   Hughes, SH
   KewalRamani, VN
AF Ambrose, Zandrea
   Lee, KyeongEun
   Ndjomou, Jean
   Xu, Hongzhan
   Oztop, Ilker
   Matous, James
   Takemura, Taichiro
   Unutmaz, Derya
   Engelman, Alan
   Hughes, Stephen H.
   KewalRamani, Vineet N.
TI Human Immunodeficiency Virus Type 1 Capsid Mutation N74D Alters
   Cyclophilin A Dependence and Impairs Macrophage Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1 INFECTION; DENDRITIC CELLS; NUCLEAR IMPORT; RESTRICTION; COMPLEX;
   PROTEIN; REPLICATION; RESISTANCE; PARTICLES; SAMHD1
AB The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages.
C1 [Ambrose, Zandrea; Ndjomou, Jean; Xu, Hongzhan; Matous, James] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15260 USA.
   [Lee, KyeongEun; Takemura, Taichiro; Hughes, Stephen H.; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
   [Oztop, Ilker; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
   [Unutmaz, Derya] NYU, Sch Med, Dept Pathol & Microbiol, New York, NY USA.
RP Ambrose, Z (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15260 USA.
EM zaa4@pitt.edu; vineet@mail.nih.gov
FU Pittsburgh Center for HIV Protein Interactions; National Cancer
   Institute's intramural Center for Cancer Research; National Center for
   Research Resources (NCRR), a component of the National Institutes of
   Health (NIH) [1 UL1 RR024153]; NIH Roadmap for Medical Research; NIH
   [GM082251, AI078839, AI052014]
FX This work was supported by a contribution from the Pittsburgh Center for
   HIV Protein Interactions and was supported by the National Cancer
   Institute's intramural Center for Cancer Research, which supports the
   HIV Drug Resistance Program (S. H. H. and V.N.K.), grant number 1 UL1
   RR024153 from the National Center for Research Resources (NCRR), a
   component of the National Institutes of Health (NIH) and NIH Roadmap for
   Medical Research (Z.A.), and NIH grants GM082251 (Z.A.), AI078839
   (D.U.), and AI052014 (A.E.).
NR 30
TC 39
Z9 39
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 APR
PY 2012
VL 86
IS 8
BP 4708
EP 4714
DI 10.1128/JVI.05887-11
PG 7
WC Virology
SC Virology
GA 917NU
UT WOS:000302185400066
PM 22301145
ER

PT J
AU Tembhare, P
   Yuan, C
   Korde, N
   Maric, I
   Landgren, O
AF Tembhare, Prashant
   Yuan, Constance
   Korde, Neha
   Maric, Irina
   Landgren, Ola
TI Antigenic drift in relapsed extramedullary multiple myeloma: plasma
   cells without CD38 expression
SO LEUKEMIA & LYMPHOMA
LA English
DT Letter
ID FLOW-CYTOMETRY; IMMUNOPHENOTYPE; DISORDERS; DISEASE
C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA.
   [Tembhare, Prashant; Yuan, Constance] NCI, Flow Cytometry Unit, Bethesda, MD 20892 USA.
   [Korde, Neha] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
   [Maric, Irina] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Metab Branch, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
NR 16
TC 1
Z9 1
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD APR
PY 2012
VL 53
IS 4
BP 721
EP 724
DI 10.3109/10428194.2011.623257
PG 4
WC Oncology; Hematology
SC Oncology; Hematology
GA 915ZV
UT WOS:000302067100031
PM 21942285
ER

PT J
AU George, AK
   Faranesh, AZ
   Ratnayaka, K
   Derbyshire, JA
   Lederman, RJ
   Hansen, MS
AF George, Ashvin K.
   Faranesh, Anthony Z.
   Ratnayaka, Kanishka
   Derbyshire, J. Andrew
   Lederman, Robert J.
   Hansen, Michael S.
TI Virtual Dye Angiography: Flow Visualization for MRI-Guided Interventions
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE real-time MRI; interventional MRI; noncontrast; endogenous contrast;
   visualization
ID STATE FREE PRECESSION; PULSE-WAVE VELOCITY; MAGNETIC-RESONANCE;
   STEADY-STATE; PHASE; EXCITATION; INVERSION; SSFP
AB In magnetic resonance imaging-guided cardiovascular interventional procedures, it is valuable to be able to visualize blood flow immediately and interactively in selected regions. In particular, it is useful to assess normal or pathological communications between specific heart chambers and vessels. Phase-contrast velocity mapping is not suitable for this purpose as it requires too much data and is not capable of determining directly if blood originating in one location travels to a nearby location. This article presents a novel flow visualization method called virtual dye angiography that enables visualization of blood flow analogous to selective catheter angiography. The method uses two-dimensional radio frequency pulses to achieve interactive, intermittent, targeted saturation of a localized region of the blood pool. The flow of the saturated spins is observed directly on real-time images or, in an enhanced manner, using ECG synchronized background subtraction. The modular nature of the technique allows for easy and seamless integration into a real-time, interactive imaging system with minimal overhead. We present initial results in animals and in a healthy human volunteer. Magn Reson Med 67:1013-1021, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [George, Ashvin K.; Faranesh, Anthony Z.; Ratnayaka, Kanishka; Derbyshire, J. Andrew; Lederman, Robert J.; Hansen, Michael S.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [Ratnayaka, Kanishka] Childrens Natl Med Ctr, Childrens Natl Heart Inst, Washington, DC 20010 USA.
RP Hansen, MS (reprint author), 10 Ctr Dr,Bldg 10,B1D405, Bethesda, MD 20892 USA.
EM michael.hansen@nih.gov
RI Hansen, Michael/J-5391-2015; 
OI Hansen, Michael/0000-0002-8087-8731; lederman,
   robert/0000-0003-1202-6673
FU Division of Intramural Research, National Heart Lung and Blood
   Institute, National Institutes of Health USA [Z01-HL006039-01,
   Z01-HL005062-08]
FX Grant sponsor: Division of Intramural Research, National Heart Lung and
   Blood Institute, National Institutes of Health USA; Grant numbers:
   Z01-HL006039-01 and Z01-HL005062-08.
NR 28
TC 5
Z9 5
U1 0
U2 4
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 APR
PY 2012
VL 67
IS 4
BP 1013
EP 1021
DI 10.1002/mrm.23078
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 909AF
UT WOS:000301533500015
PM 21858865
ER

PT J
AU Chowdhuri, SR
   Xi, LQ
   Pham, THT
   Hanson, J
   Rodriguez-Canales, J
   Berman, A
   Rajan, A
   Giaccone, G
   Emmert-Buck, M
   Raffeld, M
   Filie, AC
AF Chowdhuri, Sinchita Roy
   Xi, Liqiang
   Trinh Hoc-Tran Pham
   Hanson, Jeffrey
   Rodriguez-Canales, Jaime
   Berman, Arlene
   Rajan, Arun
   Giaccone, Giuseppe
   Emmert-Buck, Michael
   Raffeld, Mark
   Filie, Armando C.
TI EGFR and KRAS mutation analysis in cytologic samples of lung
   adenocarcinoma enabled by laser capture microdissection
SO MODERN PATHOLOGY
LA English
DT Article
DE cytology; EGFR; KRAS; laser capture microdissection; lung
   adenocarcinoma; mutation
ID GROWTH-FACTOR RECEPTOR; TRANSBRONCHIAL NEEDLE ASPIRATION;
   GENE-MUTATIONS; SENSITIVE METHOD; PARADIGM-SHIFT; CANCER; GEFITINIB;
   SPECIMENS; THERAPY; ERLOTINIB
AB The discovery of activating mutations in EGFR and KRAS in a subset of lung adenocarcinomas was a major advance in our understanding of lung adenocarcinoma biology, and has led to groundbreaking studies that have demonstrated the efficacy of tyrosine kinase inhibitor therapy. Fine-needle aspirates and other cytologic procedures have become increasingly popular for obtaining diagnostic material in lung carcinomas. However, frequently the small amount of material or sparseness of tumor cells obtained from cytologic preparations limit the number of specialized studies, such as mutation analysis, that can be performed. In this study we used laser capture microdissection to isolate small numbers of tumor cells to assess for EGFR and KRAS mutations from cell block sections of 19 cytology samples from patients with known lung adenocarcinomas. We compared our results with previous molecular assays that had been performed on either surgical or cytology specimens as part of the patient's initial clinical work-up. Not only were we able to detect the identical EGFR or KRAS mutation that was present in the patient's prior molecular assay in every case, but we were also able to consistently detect the mutation from as few as 50 microdissected tumor cells. Furthermore, isolating a more pure population of tumor cells resulted in increased sensitivity of mutation detection as we were able to detect mutations from laser capture microdissection-enriched cases where the tumor load was low and traditional methods of whole slide scraping failed. Therefore, this method can not only significantly increase the number of lung adenocarcinoma patients that can be screened for EGFR and KRAS mutations, but can also facilitate the use of cytologic samples in the newly emerging field of molecular-based personalized therapies. Modern Pathology (2012) 25, 548-555; doi:10.1038/modpathol.2011.184; published online 9 December 2011
C1 [Filie, Armando C.] NCI, Cytopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Berman, Arlene; Rajan, Arun; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Filie, AC (reprint author), NCI, Cytopathol Sect, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 2A19, Bethesda, MD 20892 USA.
EM afilie@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017; 
OI Giaccone, Giuseppe/0000-0002-5023-7562; Rodriguez-Canales,
   Jaime/0000-0002-0885-2377
FU NIH, National Cancer Institute; NIH
FX This research was supported by the Intramural Research Program of the
   NIH, National Cancer Institute.; Michael Emmert-Buck is an inventor on
   all NIH-held patents covering laser capture microdissection technology
   and receives royalty payments through the NIH technology transfer
   program.
NR 42
TC 35
Z9 35
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD APR
PY 2012
VL 25
IS 4
BP 548
EP 555
DI 10.1038/modpathol.2011.184
PG 8
WC Pathology
SC Pathology
GA 922AZ
UT WOS:000302520500007
PM 22157931
ER

PT J
AU Campbell, MC
   Ranciaro, A
   Froment, A
   Hirbo, J
   Omar, S
   Bodo, JM
   Nyambo, T
   Lema, G
   Zinshteyn, D
   Drayna, D
   Breslin, PAS
   Tishkoff, SA
AF Campbell, Michael C.
   Ranciaro, Alessia
   Froment, Alain
   Hirbo, Jibril
   Omar, Sabah
   Bodo, Jean-Marie
   Nyambo, Thomas
   Lema, Godfrey
   Zinshteyn, Daniel
   Drayna, Dennis
   Breslin, Paul A. S.
   Tishkoff, Sarah A.
TI Evolution of Functionally Diverse Alleles Associated with PTC Bitter
   Taste Sensitivity in Africa
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE adaptive evolution; genotype-phenotype association; African genetic
   diversity; excess of rare mutations
ID RECEPTOR GENE; HUMAN GENOME; INDIVIDUAL-DIFFERENCES; SELECTIVE
   PRESSURES; LACTASE PERSISTENCE; DEMOGRAPHIC HISTORY; NATURAL-SELECTION;
   HUMAN ORIGINS; PERCEPTION; FOOD
AB Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception. Here, we report striking patterns of variation at TAS2R38, including a significant excess of novel rare nonsynonymous polymorphisms that recently arose only in Africa, high frequencies of haplotypes in Africa associated with intermediate bitter taste sensitivity, a remarkably similar frequency of common haplotypes across genetically and culturally distinct Africans, and an ancient coalescence time of common variation in global populations. Additionally, several of the rare nonsynonymous substitutions significantly modified levels of PTC bitter taste sensitivity in diverse Africans. While ancient balancing selection likely maintained common haplotype variation across global populations, we suggest that recent selection pressures may have also resulted in the unusually high level of rare nonsynonymous variants in Africa, implying a complex model of selection at the TAS2R38 locus in African populations. Furthermore, the distribution of common haplotypes in Africa is not correlated with diet, raising the possibility that common variation may be under selection due to their role in nondietary biological processes. In addition, our data indicate that novel rare mutations contribute to the phenotypic variance of PTC sensitivity, illustrating the influence of rare variation on a common trait, as well as the relatively recent evolution of functionally diverse alleles at this locus.
C1 [Campbell, Michael C.; Ranciaro, Alessia; Hirbo, Jibril; Tishkoff, Sarah A.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   [Froment, Alain] IRD MNHN, Musee Homme, UMR 208, Paris, France.
   [Omar, Sabah] Ctr Biotechnol Res & Dev, Kenya Med Res Inst, Nairobi, Kenya.
   [Bodo, Jean-Marie] Minist Sci Res & Innovat, Yaounde, Cameroon.
   [Nyambo, Thomas; Lema, Godfrey] Muhimbili Univ Hlth & Allied Sci, Dept Biochem, Dar Es Salaam, Tanzania.
   [Zinshteyn, Daniel; Tishkoff, Sarah A.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD USA.
   [Breslin, Paul A. S.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
   [Breslin, Paul A. S.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA.
RP Tishkoff, SA (reprint author), Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
EM tishkoff@mail.med.upenn.edu
FU US National Science Foundation (NSF) [BCS-0552486, BCS-0827436]; US
   National Institutes of Health (NIH) [R01GM076637, DP1-OD-006445, RO1
   DC02995]; David and Lucile Packard Career Award
FX We thank Fathya Abdo, Eva Aluvalla, Angel Carracedo, Graham Coop, Clara
   Elbers, Joseph Jarvis, Daniel Kariuki, Wen-Ya Ko, Joseph Lachance,
   Charla Lambert, Mingyao Li, Trini Miguel, Lilian Alando Nyindodo, Laura
   Scheinfeldt, Mark Shriver, Shamil Sunyaev, and Stephen Wooding for
   sample collection, valuable discussions, and/or statistical advice. We
   also thank the many Africans who generously donated their DNA and time
   so that we could learn more about the genetic basis and evolutionary
   history of bitter taste sensitivity in Africa. This study was funded by
   the US National Science Foundation (NSF) grant BCS-0552486, US NSF grant
   BCS-0827436, US National Institutes of Health (NIH) grant R01GM076637,
   US NIH Director's Pioneer Award Program DP1-OD-006445, and a David and
   Lucile Packard Career Award to S.A.T and a US NIH grant RO1 DC02995 to
   P.A.S.B.
NR 52
TC 29
Z9 29
U1 19
U2 153
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD APR
PY 2012
VL 29
IS 4
BP 1141
EP 1153
DI 10.1093/molbev/msr293
PG 13
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
   Heredity
GA 915IQ
UT WOS:000302018100005
PM 22130969
ER

PT J
AU Thomas, JA
   Weintraub, ST
   Wu, WM
   Winkler, DC
   Cheng, NQ
   Steven, AC
   Black, LW
AF Thomas, Julie A.
   Weintraub, Susan T.
   Wu, Weimin
   Winkler, Dennis C.
   Cheng, Naiqian
   Steven, Alasdair C.
   Black, Lindsay W.
TI Extensive proteolysis of head and inner body proteins by a morphogenetic
   protease in the giant Pseudomonas aeruginosa phage phi KZ
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID BACTERIOPHAGE-T4 PREHEAD PROTEINASE; HIDDEN MARKOV-MODELS; PROHEAD
   PROTEASE; MYOVIRUS 201-PHI-2-1; SEQUENCE-ANALYSIS; DNA; CELLS;
   TRANSGLYCOSYLASE; IDENTIFICATION; INFECTIONS
AB Encased within the 280 kb genome in the capsid of the giant myovirus fKZ is an unusual cylindrical proteinaceous inner body of highly ordered structure. We present here mass spectrometry, bioinformatic and biochemical studies that reveal novel information about the fKZ head and the complex inner body. The identification of 39 cleavage sites in 19 fKZ head proteins indicates cleavage of many prohead proteins forms a major morphogenetic step in fKZ head maturation. The fKZ head protease, gp175, is newly identified here by a bioinformatics approach, as confirmed by a protein expression assay. Gp175 is distantly related to T4 gp21 and recognizes and cleaves head precursors at related but distinct S/A/G-X-E recognition sites. Within the fKZ head there are six high-copy-number proteins that are probable major components of the inner body. The molecular weights of five of these proteins are reduced 3565% by cleavages making their mature form similar (2631 kDa), while their precursors are dissimilar (3688 kDa). Together the six abundant proteins sum to the estimated mass of the inner body (1520 MDa). The identification of these proteins is important for future studies on the composition and function of the inner body.
C1 [Thomas, Julie A.; Black, Lindsay W.] Univ Maryland, Baltimore, MD 21201 USA.
   [Weintraub, Susan T.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
   [Wu, Weimin; Winkler, Dennis C.; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
RP Black, LW (reprint author), Univ Maryland, Baltimore, MD 21201 USA.
EM lblack@umaryland.edu
FU NIH [AI11676]; NIAMS
FX phi KZ and the phi KZ tailless mutant were generously provided by Dr A.
   Fokine (Purdue University) and Dr K. Miroshnikov (Russian Academy of
   Sciences) respectively. P. aeruginosa PAO1 was kindly provided by Dr R.
   Ernst (University of Maryland Baltimore). The pHERD20T vector was
   provided by Dr Yu (Marshall University). We thank Kevin Hakala and Sam
   Pardo for the excellent MS analyses that were conducted in the UTHSCSA
   Institutional Mass Spectrometry Laboratory. We thank Ru-ching Hsia
   (University of Maryland Baltimore) for her help with TEM and Qin Dan for
   her technical support. We are extremely grateful to Dr S.C. Hardies for
   allowing access to his collection of bioinformatics software and the
   UTHSCSA Bioinformatics Center for assistance with computational aspects
   of the project. This work was supported by NIH Grant AI11676 to L.W.B.
   and by the Intramural Research Program of NIAMS.
NR 46
TC 13
Z9 13
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD APR
PY 2012
VL 84
IS 2
BP 324
EP 339
DI 10.1111/j.1365-2958.2012.08025.x
PG 16
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 922IA
UT WOS:000302539400009
PM 22429790
ER

PT J
AU Singleton, AB
AF Singleton, Andrew B.
TI Rapid genetic diagnosis in single-gene movement disorders
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
ID PARKINSON-DISEASE; MUTATIONS; DYSTONIA; ATAXIAS; PLA2G6; VPS35
C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009
FU Intramural NIH HHS [Z01 AG000957-05]; NIA NIH HHS [Z01 AG000957, Z01
   AG000957-09]
NR 23
TC 1
Z9 1
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD APR
PY 2012
VL 27
IS 4
BP 467
EP 469
DI 10.1002/mds.24896
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 921HP
UT WOS:000302469000039
PM 22488858
ER

PT J
AU Callahan, DJ
   Liu, WE
   Li, XH
   Dreher, MR
   Hassouneh, W
   Kim, M
   Marszalek, P
   Chilkoti, A
AF Callahan, Daniel J.
   Liu, Wenge
   Li, Xinghai
   Dreher, Matthew R.
   Hassouneh, Wafa
   Kim, Minkyu
   Marszalek, Piotr
   Chilkoti, Ashutosh
TI Triple Stimulus-Responsive Polypeptide Nanoparticles That Enhance
   Intratumoral Spatial Distribution
SO NANO LETTERS
LA English
DT Article
DE Polypeptides; block copolymers; stimulus-responsive; pH responsive;
   tumor drug delivery
ID ELASTIN-LIKE POLYPEPTIDES; PH-SENSITIVE IMMUNOLIPOSOMES; INTRACELLULAR
   DRUG-DELIVERY; PROTEIN-BASED POLYMERS; SOLID TUMORS; PACLITAXEL
   DELIVERY; MICELLES; DOXORUBICIN; SYSTEM; DESTABILIZATION
AB To address the limited tumor penetration of nanoparticle drug delivery vehicles, we report the first pH-responsive polypeptide micelle that dissociates at the low extracellular pH of solid tumors. This histidine-rich elastin-like polypeptide block copolymer self-assembles at 37 degrees C into spherical micelles that are stabilized by Zn2+ and are disrupted as the pH drops from 7.4 to 6.4. These pH-sensitive micelles demonstrate better in vivo penetration and distribution in tumors than a pH-insensitive control.
C1 [Callahan, Daniel J.; Liu, Wenge; Li, Xinghai; Hassouneh, Wafa; Chilkoti, Ashutosh] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
   [Callahan, Daniel J.; Hassouneh, Wafa; Kim, Minkyu; Marszalek, Piotr; Chilkoti, Ashutosh] Duke Univ, Ctr Biol Inspired Mat & Mat Syst, Durham, NC 27708 USA.
   [Dreher, Matthew R.] NCI, Ctr Intervent Oncol, Ctr Clin, NIH, Bethesda, MD 20892 USA.
   [Kim, Minkyu; Marszalek, Piotr] Duke Univ, Dept Mech Engn & Mat Sci, Durham, NC 27708 USA.
RP Chilkoti, A (reprint author), Duke Univ, Dept Biomed Engn, 136 Hudson Hall,Box 90281, Durham, NC 27708 USA.
EM chilkoti@duke.edu
OI Liu, Wenge/0000-0002-0688-1879; /0000-0002-9476-6351
FU NIH [R01EB007205]; Triangle MRSEC through NSF DMR; NSF
   [NSF-DGE-02-21632]; Center for Interventional Oncology of NIH
FX The authors acknowledge molecular biology assistance from John Andrew
   Pura and Andrew Sobel. This work was supported by NIH Grant R01EB007205
   (A.C.), the Triangle MRSEC through NSF DMR, an NSF-sponsored IGERT
   fellowship to D.J.C. through Grant NSF-DGE-02-21632, and the Center for
   Interventional Oncology in the Intramural Research Program of the NIH.
NR 43
TC 40
Z9 40
U1 8
U2 81
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
J9 NANO LETT
JI Nano Lett.
PD APR
PY 2012
VL 12
IS 4
BP 2165
EP 2170
DI 10.1021/nl300630c
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
   Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
   Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
   Physics
GA 922CO
UT WOS:000302524600071
PM 22417133
ER

PT J
AU Charles, N
   Dema, B
   Rivera, J
AF Charles, Nicolas
   Dema, Barbara
   Rivera, Juan
TI Basophils from humans with systemic lupus erythematosus do not express
   MHC-II reply
SO NATURE MEDICINE
LA English
DT Letter
C1 [Charles, Nicolas; Dema, Barbara; Rivera, Juan] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Immunogenet Mol Lab, US Natl Inst Hlth, Bethesda, MD USA.
   [Charles, Nicolas] Paris Diderot Univ, Inst Natl Sante & Rech Med, UMR 699, Bichat Med Sch, Paris, France.
RP Charles, N (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis, Immunogenet Mol Lab, US Natl Inst Hlth, Bethesda, MD USA.
EM riveraj@arb.niams.nih.gov
RI Charles, Nicolas/P-5430-2014
OI Charles, Nicolas/0000-0002-5416-5834
NR 5
TC 1
Z9 1
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD APR
PY 2012
VL 18
IS 4
BP 488
EP 490
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 923KI
UT WOS:000302617800018
ER

PT J
AU Morales, M
   Bonci, A
AF Morales, Marisela
   Bonci, Antonello
TI Hooking CB2 receptor into drug abuse?
SO NATURE MEDICINE
LA English
DT Editorial Material
ID CANNABINOID RECEPTOR; BRAIN; EXPRESSION; MICROGLIA; SYSTEM
C1 [Morales, Marisela; Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD USA.
   [Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
   [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD USA.
RP Morales, M (reprint author), NIDA, Intramural Res Program, Baltimore, MD USA.
EM antonello.bonci@nih.gov
NR 14
TC 13
Z9 13
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD APR
PY 2012
VL 18
IS 4
BP 504
EP 505
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 923KI
UT WOS:000302617800026
PM 22481411
ER

PT J
AU Sorge, RE
   Trang, T
   Dorfman, R
   Smith, SB
   Beggs, S
   Ritchie, J
   Austin, JS
   Zaykin, DV
   Vander Meulen, H
   Costigan, M
   Herbert, TA
   Yarkoni-Abitbul, M
   Tichauer, D
   Livneh, J
   Gershon, E
   Zheng, M
   Tan, K
   John, SL
   Slade, GD
   Jordan, J
   Woolf, CJ
   Peltz, G
   Maixner, W
   Diatchenko, L
   Seltzer, Z
   Salter, MW
   Mogil, JS
AF Sorge, Robert E.
   Trang, Tuan
   Dorfman, Ruslan
   Smith, Shad B.
   Beggs, Simon
   Ritchie, Jennifer
   Austin, Jean-Sebastien
   Zaykin, Dmitri V.
   Vander Meulen, Heather
   Costigan, Michael
   Herbert, Teri A.
   Yarkoni-Abitbul, Merav
   Tichauer, David
   Livneh, Jessica
   Gershon, Edith
   Zheng, Ming
   Tan, Keith
   John, Sally L.
   Slade, Gary D.
   Jordan, Joanne
   Woolf, Clifford J.
   Peltz, Gary
   Maixner, William
   Diatchenko, Luda
   Seltzer, Ze'ev
   Salter, Michael W.
   Mogil, Jeffrey S.
TI Genetically determined P2X7 receptor pore formation regulates
   variability in chronic pain sensitivity
SO NATURE MEDICINE
LA English
DT Article
ID SPARED NERVE INJURY; NEUROPATHIC PAIN; SPINAL-CORD; P2X(7); MOUSE;
   NOCICEPTION; ANTAGONIST; COMPLEX; RAT; INTERLEUKIN-1-BETA
AB Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary(1). Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da(2,3). Using genome-wide linkage analyses, we discovered an association between nerve-injury-induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain.
C1 [Sorge, Robert E.; Ritchie, Jennifer; Austin, Jean-Sebastien; Mogil, Jeffrey S.] McGill Univ, Dept Psychol, Montreal, PQ, Canada.
   [Sorge, Robert E.; Ritchie, Jennifer; Austin, Jean-Sebastien; Mogil, Jeffrey S.] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada.
   [Trang, Tuan; Dorfman, Ruslan; Beggs, Simon; Vander Meulen, Heather; Salter, Michael W.] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada.
   [Smith, Shad B.; Maixner, William; Diatchenko, Luda] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA.
   [Smith, Shad B.; Slade, Gary D.; Maixner, William; Diatchenko, Luda; Mogil, Jeffrey S.] Algynomics Inc, Chapel Hill, NC USA.
   [Zaykin, Dmitri V.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   [Costigan, Michael; Herbert, Teri A.; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Yarkoni-Abitbul, Merav; Tichauer, David; Seltzer, Ze'ev; Salter, Michael W.] Univ Toronto, Fac Dent, Toronto, ON, Canada.
   [Yarkoni-Abitbul, Merav; Tichauer, David; Seltzer, Ze'ev; Salter, Michael W.] Univ Toronto, Fac Med, Toronto, ON, Canada.
   [Livneh, Jessica] Chaim Sheba Med Ctr, Inst Oncol, Ramat Gan, Israel.
   [Gershon, Edith] Ein Hod, Hof Hacarmel, Israel.
   [Zheng, Ming; Peltz, Gary] Stanford Univ Sch Med, Dept Anesthesia, Stanford, CA USA.
   [Tan, Keith; John, Sally L.] Pfizer Global Res & Dev, Sandwich, Kent, England.
   [Slade, Gary D.] Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27599 USA.
   [Jordan, Joanne] Univ N Carolina, Thurston Arthrit Ctr, Chapel Hill, NC USA.
RP Mogil, JS (reprint author), McGill Univ, Dept Psychol, Montreal, PQ, Canada.
EM mike.salter@utoronto.ca; jeffrey.mogil@mcgill.ca
OI Vandermeulen, Heather/0000-0003-1885-2298
FU US National Institutes of Health (NIH); Louise and Alan Edwards
   Foundation; Canada Research Chairs program; Howard Hughes Medical
   Institute; Canadian Institutes of Health Research; Krembil Foundation;
   Ontario Research Foundation; Algynomics/Pfizer; AstraZeneca-Alan Edwards
   Centre for Research on Pain; NIH; NIH (National Institute of
   Environmental Health Sciences)
FX This research was supported by the US National Institutes of Health
   (NIH) (C.J.W., W.M., L.D., Z.S. and J.S.M.), the Louise and Alan Edwards
   Foundation (J.S.M.), the Canada Research Chairs program (M.W.S., J.S.M.
   and Z.S.), the Howard Hughes Medical Institute (M.W.S.), the Canadian
   Institutes of Health Research (M.W.S. and J.S.M.), the Krembil
   Foundation (M.W.S. and J.S.M.), the Ontario Research Foundation (M.W.S.)
   and Algynomics/Pfizer research funds (W.M., L.D.). R.E.S. was supported
   by an AstraZeneca-Alan Edwards Centre for Research on Pain postdoctoral
   fellowship. T.T. was supported by a Canadian Institutes of Health
   Research Fellowship. S.B.S. was supported by a National Research Service
   Award Fellowship from the NIH. D.V.Z. was supported by the Intramural
   Research Program of the NIH (National Institute of Environmental Health
   Sciences).
NR 30
TC 130
Z9 139
U1 6
U2 36
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD APR
PY 2012
VL 18
IS 4
BP 595
EP 599
DI 10.1038/nm.2710
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 923KI
UT WOS:000302617800037
PM 22447075
ER

PT J
AU Taniguchi, H
   Jacinto, FV
   Villanueva, A
   Fernandez, AF
   Yamamoto, H
   Carmona, FJ
   Puertas, S
   Marquez, VE
   Shinomura, Y
   Imai, K
   Esteller, M
AF Taniguchi, H.
   Jacinto, F. V.
   Villanueva, A.
   Fernandez, A. F.
   Yamamoto, H.
   Carmona, F. J.
   Puertas, S.
   Marquez, V. E.
   Shinomura, Y.
   Imai, K.
   Esteller, M.
TI Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2
   in human cancer
SO ONCOGENE
LA English
DT Article
DE epigenetics; histone methyltransferase; EZH2; KLF2
ID GROUP PROTEIN EZH2; PROSTATE-CANCER; TRANSCRIPTION FACTORS; CELL-GROWTH;
   POLYCOMB; REPRESSION; METHYLATION; PROGRESSION; EXPRESSION; APOPTOSIS
AB The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5'-end of KLF2 is also associated with a gain of trimethylated lysine 27 histone H3 and a depletion of phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A, the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. In this last setting, KLF2 transfection was also associated with decreased dissemination and lower mortality rate. In EZH2-depleted cells, which characteristically have lower tumorigenicity, the induction of KLF2 depletion 'rescued' partially the oncogenic phenotype, suggesting that KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival. Oncogene (2012) 31, 1988-1994; doi:10.1038/onc.2011.387; published online 5 September 2011
C1 [Taniguchi, H.; Jacinto, F. V.; Fernandez, A. F.; Carmona, F. J.; Esteller, M.] Hosp Duran & Reynals, Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain.
   [Taniguchi, H.; Yamamoto, H.; Shinomura, Y.] Sapporo Med Univ, Sch Med, Dept Internal Med 1, Sapporo, Hokkaido, Japan.
   [Taniguchi, H.] Sapporo Med Univ, Sch Med, Tumor Med Examinat & Treatment Ctr, Sapporo, Hokkaido, Japan.
   [Jacinto, F. V.] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
   [Villanueva, A.; Puertas, S.] Bellvitge Biomed Res Inst IDIBELL, ICO, Barcelona, Spain.
   [Marquez, V. E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
   [Imai, K.] Univ Tokyo, Inst Med Sci, Tokyo, Japan.
   [Esteller, M.] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Spain.
   [Esteller, M.] ICREA, Barcelona, Spain.
RP Esteller, M (reprint author), Hosp Duran & Reynals, Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, 3rd Floor,Avda Gran Via LHosp 199-203, Barcelona 08908, Catalonia, Spain.
EM mesteller@idibell.cat
RI Esteller, Manel/L-5956-2014; Fernandez, Agustin/N-7302-2014; 
OI Esteller, Manel/0000-0003-4490-6093; Fernandez,
   Agustin/0000-0002-3792-4085; Carmona Sanz, F Javier/0000-0001-7904-8493
FU Lilly Foundation; Dr Josef Steiner Cancer Research Foundation; NIH,
   National Cancer Institute and Center for Cancer Research; 
   [SAF2007-00027-65134];  [Consolider CSD2006-49]
FX We thank O Dominguez for help with the microarray procedures and
   analysis, F Setien for technical assistance and Miki Kojiya for the flow
   cytometry analysis. This work was supported by Grants
   SAF2007-00027-65134, Consolider CSD2006-49, and Lilly Foundation and Dr
   Josef Steiner Cancer Research Foundation to ME, and the Intramural
   Research Program of the NIH, National Cancer Institute and Center for
   Cancer Research to VEM. HT is supported by the Uehara Memorial
   Foundation and Pancreas Research Foundation of Japan. ME is an ICREA
   Research Professor.
NR 26
TC 41
Z9 43
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD APR
PY 2012
VL 31
IS 15
BP 1988
EP 1994
DI 10.1038/onc.2011.387
PG 7
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 926CW
UT WOS:000302809900010
PM 21892211
ER

PT J
AU Fernandez, AB
   Wong, TY
   Klein, R
   Collins, D
   Burke, G
   Cotch, MF
   Klein, B
   Sadeghi, MM
   Chen, J
AF Fernandez, Antonio B.
   Wong, Tien Y.
   Klein, Ronald
   Collins, Dorothea
   Burke, Gregory
   Cotch, Mary Frances
   Klein, Barbara
   Sadeghi, Mehran M.
   Chen, Jersey
TI Age-Related Macular Degeneration and Incident Cardiovascular Disease:
   The Multi-Ethnic Study of Atherosclerosis
SO OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT FACTOR-H; ENDOTHELIAL DYSFUNCTION; MYOCARDIAL-INFARCTION; EYE
   DISEASE; MACULOPATHY; RISK; NEOVASCULARIZATION; ANGIOGENESIS;
   INFLAMMATION; POLYMORPHISM
AB Objective: To determine whether age-related macular degeneration (AMD) is a risk indicator for coronary heart disease (CHD) and cardiovascular disease (CVD) events independent of other known risk factors in a multi-ethnic cohort.
   Design: Population-based prospective cohort study.
   Participants: A diverse population sample of 6233 men and women aged 45 to 84 years without known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA).
   Methods: Participants in the MESA had retinal photographs taken between 2002 and 2003. Photographs were evaluated for AMD. Incident CHD and CVD events were ascertained during clinical follow-up visits for up to 8 years after the retinal images were taken.
   Main Outcome Measures: Incident CHD and CVD events.
   Results: Of the 6814 persons at risk of CHD, there were 893 participants with early AMD (13.1%) and 27 patients (0.5%) at baseline. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0% vs. 3.9%, P = 0.13 for CHD and 6.6% vs. 5.5%, P = 0.19 for CVD). In Cox regression models adjusting for CVD risk factors, there was no significant relationship between presence of any AMD and any CHD/CVD events (hazard ratio 0.99; 95% confidence interval, 0.74-1.33; P = 0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events.
   Conclusions: In persons without a history of CVD, AMD was not associated with an increased risk of CHD or CVD.
   Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:765-770 (C) 2012 by the American Academy of Ophthalmology.
C1 [Fernandez, Antonio B.] Brown Univ, Warren Alpert Sch Med, Div Cardiol, Providence, RI 02903 USA.
   [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore.
   [Klein, Ronald; Klein, Barbara] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
   [Collins, Dorothea; Sadeghi, Mehran M.] VA Connecticut Healthcare Syst, West Haven, CT USA.
   [Burke, Gregory] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
   [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
   [Sadeghi, Mehran M.; Chen, Jersey] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA.
RP Fernandez, AB (reprint author), Brown Univ, Sch Med, Rhode Isl Hosp, Dept Cardiol, 593 Eddy St, Providence, RI 02903 USA.
EM antoinefernandezt@hotmail.com
OI Cotch, Mary Frances/0000-0002-2046-4350; Klein,
   Ronald/0000-0002-4428-6237
FU National Heart, Lung, and Blood Institute [HL69979-03, N01-HC-95159,
   N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
   N01-HC-95165, N01-HC-95166]; Agency for Healthcare Research and Quality
   [1K08HS018781-01]
FX This research was supported by Grant HL69979-03 to Dr. Klein and Dr.
   Wong and by contracts N01-HC-95159 to N01-HC-95166 from the National
   Heart, Lung, and Blood Institute. Dr. Chen is supported by an award from
   the Agency for Healthcare Research and Quality (1K08HS018781-01).
NR 31
TC 15
Z9 15
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2012
VL 119
IS 4
BP 765
EP 770
DI 10.1016/j.ophtha.2011.09.044
PG 6
WC Ophthalmology
SC Ophthalmology
GA 919UQ
UT WOS:000302355400015
PM 22197438
ER

PT J
AU LaGasse, LL
   Derauf, C
   Smith, LM
   Newman, E
   Shah, R
   Neal, C
   Arria, A
   Huestis, MA
   DellaGrotta, S
   Lin, H
   Dansereau, LM
   Lester, BM
AF LaGasse, Linda L.
   Derauf, Chris
   Smith, Lynne M.
   Newman, Elana
   Shah, Rizwan
   Neal, Charles
   Arria, Amelia
   Huestis, Marilyn A.
   DellaGrotta, Sheri
   Lin, Hai
   Dansereau, Lynne M.
   Lester, Barry M.
TI Prenatal Methamphetamine Exposure and Childhood Behavior Problems at 3
   and 5 Years of Age
SO PEDIATRICS
LA English
DT Article
DE amphetamines; behavior disorders/problems; children; methamphetamine;
   prenatal exposure
ID MATERNAL LIFE-STYLE; INFANT DEVELOPMENT; COCAINE EXPOSURE; INTRAUTERINE
   GROWTH; SUBSTANCE USE; CHILDREN; ENVIRONMENT; AMPHETAMINE; PREGNANCY;
   IMPACT
AB OBJECTIVE: We evaluated behavior problems in children who were prenatally exposed to methamphetamine (MA) at ages 3 and 5 years.
   METHODS: The Infant Development, Environment, and Lifestyle study, a prospective, longitudinal study of prenatal MA exposure and child outcome, enrolled subjects postpartum in Los Angeles, California; Honolulu, Hawaii; Des Moines, Iowa; and Tulsa, Oklahoma. Prenatal exposure was determined by maternal self-report and/or meconium results. Exposed and comparison groups were matched on race, birth weight, public health insurance, and education. Mothers in the comparison group denied use and had a negative meconium screen for amphetamines. Prenatal exposures to tobacco, alcohol, or marijuana occurred in both groups. At ages 3 and 5 years, 330 children (166 exposed and 164 comparison) were assessed for behavior problems by using the caregiver report on the Child Behavior Checklist. General linear mixed models were used to determine the effects of prenatal MA exposure, including heavy exposure (>= 3 days per week), age, and the interaction of exposure and age on behavior problems with adjustment for other drugs of abuse and environmental risk factors.
   RESULTS: MA exposure was associated with increased emotional reactivity and anxious/depressed problems at both ages and externalizing and attention-deficit/hyperactivity disorder problems by age 5 years. Heavy exposure was related to attention problems and withdrawn behavior at both ages. There were no effects of MA on the internalizing or total behavior problems scales.
   CONCLUSIONS: This first report of behavior problems in patients as young as 3 years associated with MA exposure identifies an important public health problem. Continued follow-up can inform the development of preventive intervention programs. Pediatrics 2012;129:681-688
C1 [LaGasse, Linda L.; DellaGrotta, Sheri; Lin, Hai; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Brown Ctr Study Children Risk, Providence, RI 02905 USA.
   [LaGasse, Linda L.; DellaGrotta, Sheri; Lin, Hai; Dansereau, Lynne M.; Lester, Barry M.] Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA.
   [Derauf, Chris; Neal, Charles] Univ Hawaii, Dept Pediat, Honolulu, HI 96822 USA.
   [Smith, Lynne M.] Univ Calif Los Angeles, Dept Pediat, Los Angeles Biomed Res Inst, Harbor UCLA Med Ctr, Los Angeles, CA 90024 USA.
   [Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
   [Shah, Rizwan] Blank Childrens Hosp, Reg Child Protect Ctr, Des Moines, IA USA.
   [Arria, Amelia] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, Family Sci Dept, College Pk, MD 20742 USA.
   [Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
RP LaGasse, LL (reprint author), Brown Univ, Warren Alpert Med Sch, Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA.
EM linda_lagasse@brown.edu
OI Arria, Amelia/0000-0002-6360-9265
FU National Institutes on Drug Abuse [2R01DA014948]; National Center for
   Research Resources [5P20RR11091, 3M01RR00425]; National Institutes of
   Health (NIH)
FX Funding was provided by the National Institutes on Drug Abuse
   (2R01DA014948 to Dr Lester) and in part by the National Center for
   Research Resources (5P20RR11091 and 3M01RR00425). Funded by the National
   Institutes of Health (NIH).
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PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD APR
PY 2012
VL 129
IS 4
BP 681
EP 688
DI 10.1542/peds.2011-2209
PG 8
WC Pediatrics
SC Pediatrics
GA 922IX
UT WOS:000302541700046
PM 22430455
ER

PT J
AU Marcus, MD
   Foster, GD
   El Ghormli, L
   Baranowski, T
   Goldberg, L
   Jago, R
   Linder, B
   Steckler, A
   Trevino, R
AF Marcus, Marsha D.
   Foster, Gary D.
   El Ghormli, Laure
   Baranowski, Tom
   Goldberg, Linn
   Jago, Russell
   Linder, Barbara
   Steckler, Allan
   Trevino, Roberto
TI Shifts in BMI Category and Associated Cardiometabolic Risk: Prospective
   Results From HEALTHY Study
SO PEDIATRICS
LA English
DT Article
DE obesity; overweight; obesity trends; BMI; glucose; insulin; blood
   pressure; lipids
ID BODY-MASS INDEX; CORONARY-HEART-DISEASE; PROSPECTIVE COHORT; METABOLIC
   SYNDROME; CHILDHOOD OBESITY; CHILDREN; ADOLESCENCE; INTERVENTION;
   PREVALENCE; ADIPOSITY
AB OBJECTIVES: To evaluate shifts across BMI categories and associated changes in cardiometabolic risk factors over 2.5 years in an ethnically diverse middle school sample.
   METHODS: As part of HEALTHY, a multisite school-based study designed to mitigate risk for type 2 diabetes, 3993 children participated in health screenings at the start of sixth and end of eighth grades. Assessments included anthropometric measures, blood pressure, and glucose, insulin, and lipids. Students were classified as underweight, healthy weight, overweight, obese, or severely obese. Mixed models controlling for school intervention status and covariates were used to evaluate shifts in BMI category over time and the relation between these shifts and changes in risk factors.
   RESULTS: At baseline, students averaged 11.3 (+/- 0.6) years; 47.6% were boys, 59.6% were Hispanic, and 49.8% were overweight or obese. Shifts in BMI category over time were common. For example, 35.7% of youth who were overweight moved to the healthy weight range, but 13% in the healthy weight range became overweight. BMI shifts were not associated with school intervention condition, household education, or youth gender, race/ethnicity, pubertal status, or changes in height. Increases in BMI category were associated with worsening of cardiometabolic risk factors, and decreases were associated with improvements. Boys who increased BMI category were more vulnerable to negative risk factor changes than girls.
   CONCLUSIONS: There are substantial shifts across BMI categories during middle school that are associated with clinically meaningful changes in cardiometabolic risk factors. Programs to promote decreases in BMI and prevent increases are clearly warranted. Pediatrics 2012;129:e983-e991
C1 [Marcus, Marsha D.] Univ Pittsburgh Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
   [Foster, Gary D.] Temple Univ, Ctr Obes Res & Educ, Philadelphia, PA 19122 USA.
   [El Ghormli, Laure] George Washington Univ, Ctr Biostat, Washington, DC USA.
   [Baranowski, Tom] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Goldberg, Linn] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
   [Jago, Russell] Univ Bristol, Sch Policy Studies, Ctr Exercise Nutr & Hlth, Bristol, Avon, England.
   [Linder, Barbara] NIDDKD, Bethesda, MD 20892 USA.
   [Steckler, Allan] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC USA.
   [Trevino, Roberto] Univ Texas Hlth Sci Ctr San Antonio, Social & Hlth Res Ctr, San Antonio, TX 78229 USA.
RP Marcus, MD (reprint author), Univ Pittsburgh Med Ctr, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM marcusmd@upmc.edu
OI Jago, Russell/0000-0002-3394-0176; Baranowski, Tom/0000-0002-0653-2222
FU National Institute of Diabetes and Digestive and Kidney
   Diseases/National Institutes of Health [U01-DK61230, U01-DK61249,
   U01-DK61231, U01-DK61223]; National Institutes of Health (NIH); American
   Diabetes Association
FX This work was completed with funding from National Institute of Diabetes
   and Digestive and Kidney Diseases/National Institutes of Health grants
   U01-DK61230, U01-DK61249, U01-DK61231, and U01-DK61223, with additional
   support from the American Diabetes Association. Funded by the National
   Institutes of Health (NIH).
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PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD APR
PY 2012
VL 129
IS 4
BP E983
EP E991
DI 10.1542/peds.2011-2696
PG 9
WC Pediatrics
SC Pediatrics
GA 922IX
UT WOS:000302541700017
PM 22430457
ER

PT J
AU Nansel, TR
   Iannotti, RJ
   Liu, AY
AF Nansel, Tonja R.
   Iannotti, Ronald J.
   Liu, Aiyi
TI Clinic-Integrated Behavioral Intervention for Families of Youth With
   Type 1 Diabetes: Randomized Clinical Trial
SO PEDIATRICS
LA English
DT Article
DE type 1 diabetes; children; adolescents; adherence; behavioral
   intervention; glycemic control
ID PERSONAL TRAINER INTERVENTION; METABOLIC-CONTROL; SELF-MANAGEMENT;
   GLYCEMIC CONTROL; TREATMENT ADHERENCE; HEALTH OUTCOMES; ADOLESCENTS;
   CHILDREN; MELLITUS; CARE
AB OBJECTIVE: To test the effect on diabetes management outcomes of a low-intensity, clinic-integrated behavioral intervention for families of youth with type 1 diabetes.
   METHODS: Families (n = 390) obtaining care for type 1 diabetes participated in a 2-year randomized clinical trial of a clinic-integrated behavioral intervention designed to improve family diabetes management practices. Measurement of hemoglobin A1c, the primary outcome, was obtained at each clinic visit and analyzed centrally. Blood glucose meter data were downloaded at each visit. Adherence was assessed by using a semistructured interview at baseline, mid-study, and follow-up. Analyses included 2-sample t tests at predefined time intervals and mixed-effect linear-quadratic models to assess for difference in change in outcomes across the study duration.
   RESULTS: A significant overall intervention effect on change in glycemic control from baseline was observed at the 24-month interval (P = .03). The mixed-effect model showed a significant intervention by age interaction (P < .001). Among participants aged 12 to 14, a significant effect on glycemic control was observed (P = .009 for change from baseline to 24-month interval; P = .035 for mixed-effect model across study duration), but there was no effect among those aged 9 to 11. There was no intervention effect on child or parent report of adherence; however, associations of change in adherence with change in glycemic control were weak.
   CONCLUSIONS: This clinic-integrated behavioral intervention was effective in preventing the deterioration in glycemic control evident during adolescence, offering a potential model for integrating medical and behavioral sciences in clinical care. Pediatrics 2012; 129: e866-e873
C1 [Nansel, Tonja R.; Iannotti, Ronald J.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Nansel, TR (reprint author), 6100 Execut Blvd,Room 7B13R MSC 7510, Bethesda, MD 20892 USA.
EM nanselt@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595; Liu, Aiyi/0000-0002-6618-5082
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
   of Child Health and Human Development [N01-HD-4-3364, N01-HD-4-3361,
   N01-HD-4-3362, N01-HD-4-3363, N01-HD-3-3360]; National Institutes of
   Health (NIH)
FX Supported by the intramural research program of the National Institutes
   of Health, Eunice Kennedy Shriver National Institute of Child Health and
   Human Development, under the following contracts: N01-HD-4-3364, Joslin
   Diabetes Center, Boston, Massachusetts; N01-HD-4-3361, Nemours
   Children's Clinic, Jacksonville, Florida; N01-HD-4-3362, Texas
   Children's Hospital, Houston, Texas; N01-HD-4-3363, Children's Memorial
   Hospital, Chicago, Illinois; and N01-HD-3-3360, James Bell Associates,
   Arlington, Virginia. Funded by the National Institutes of Health (NIH).
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PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD APR
PY 2012
VL 129
IS 4
BP E866
EP E873
DI 10.1542/peds.2011-2858
PG 8
WC Pediatrics
SC Pediatrics
GA 922IX
UT WOS:000302541700002
PM 22392172
ER

PT J
AU Shane, AL
   Hansen, NI
   Stoll, BJ
   Bell, EF
   Sanchez, PJ
   Shankaran, S
   Laptook, AR
   Das, A
   Walsh, MC
   Hale, EC
   Newman, NS
   Schrag, SJ
   Higgins, RD
AF Shane, Andi L.
   Hansen, Nellie I.
   Stoll, Barbara J.
   Bell, Edward F.
   Sanchez, Pablo J.
   Shankaran, Seetha
   Laptook, Abbot R.
   Das, Abhik
   Walsh, Michele C.
   Hale, Ellen C.
   Newman, Nancy S.
   Schrag, Stephanie J.
   Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst
TI Methicillin-Resistant and Susceptible Staphylococcus aureus Bacteremia
   and Meningitis in Preterm Infants
SO PEDIATRICS
LA English
DT Article
DE Staphylococcus aureus; methicillin resistant; infant; newborn
ID INTENSIVE-CARE-UNIT; NEONATAL RESEARCH NETWORK; NECROTIZING
   ENTEROCOLITIS; PREGNANT-WOMEN; ONSET SEPSIS; INFECTIONS; TRANSMISSION;
   PROPHYLAXIS; EXPERIENCE; HEALTH
AB BACKGROUND: Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M).
   METHODS: Neonatal data for VLBW infants (birth weight 401-1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (<= 72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of >= 5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M.
   RESULTS: Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%).
   CONCLUSIONS: Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants. Pediatrics 2012;129:e914-e922
C1 [Shane, Andi L.; Stoll, Barbara J.; Hale, Ellen C.] Emory Univ Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
   [Shane, Andi L.; Stoll, Barbara J.; Hale, Ellen C.] Childrens Healthcare Atlanta, Atlanta, GA USA.
   [Hansen, Nellie I.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
   [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
   [Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
   [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
   [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
   [Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
   [Schrag, Stephanie J.] Ctr Dis Control & Prevent, Atlanta, GA USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Shane, AL (reprint author), Emory Univ Sch Med, Dept Pediat, 2015 Uppergate Dr NE, Atlanta, GA 30322 USA.
EM ashane@emory.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (NICHD)
FX The National Institutes of Health and the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development (NICHD)
   provided grant support for the Neonatal Research Network's (NRN) Generic
   Database Study. The funding source had no direct involvement in study
   design; in the collection, analysis, and interpretation of data; in the
   writing of the report; or in the decision to submit the article for
   publication. Funded by the National Institutes of Health (NIH).
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PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD APR
PY 2012
VL 129
IS 4
BP E914
EP E922
DI 10.1542/peds.2011-0966
PG 9
WC Pediatrics
SC Pediatrics
GA 922IX
UT WOS:000302541700008
PM 22412036
ER

PT J
AU Coiro, MJ
   Riley, A
   Broitman, M
   Miranda, J
AF Coiro, Mary Jo
   Riley, Anne
   Broitman, Marina
   Miranda, Jeanne
TI Effects on Children of Treating Their Mothers' Depression: Results of a
   12-Month Follow-Up
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ONE-YEAR OUTCOMES; MATERNAL DEPRESSION;
   MINORITY WOMEN; SINGLE MOTHERS; MENTAL-HEALTH; UNITED-STATES; SYMPTOMS;
   PARENTS; PREVENTION
AB Objective: This study used a controlled research design to examine the effects on children of treating their mothers' depression and of remission of the mothers' depression. Method: The sample consisted of 60 low-income women with major depression, who were predominantly from minority racial-ethnic groups, and their children ages four to 11. Women were randomly assigned to receive one of two active treatments (medication or cognitive-behavioral therapy) or a referral to existing community services. The mothers' depression was assessed by self-report on the Hamilton Depression Rating Scale, and the children's symptoms and adaptive skills were assessed by their mothers at baseline and six-month and 12-month follow-ups with the Behavior Assessment System for Children. Results.: Mixed-effects random intercept and random slope repeated-measures analyses using an intent-to-treat approach indicated that active treatment of mothers did not result in improvement in their children's behavior problems or adaptive skills. However, at both the six- and the 12-month follow-ups, children of mothers whose depression had remitted, regardless of treatment assignment, had significantly fewer behavior problems than children whose mothers remained depressed. Conclusions: The results support the need to expand access to, and support participation in, depression treatment among low-income women from minority racial-ethnic groups. Although treatment alone of this undertreated population was not associated with improvement in children's outcomes, it is a necessary first step to prevent psychopathology among offspring of depressed parents. (Psychiatric Services 63:357-363, 2012; doi: 10.1176/appi.ps.201100126)
C1 [Coiro, Mary Jo] Loyola Univ Maryland, Dept Psychol, Baltimore, MD 21212 USA.
   [Riley, Anne] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA.
   [Broitman, Marina] NIMH, Div Extramural Act, Bethesda, MD 20892 USA.
   [Miranda, Jeanne] Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA.
   [Miranda, Jeanne] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
RP Coiro, MJ (reprint author), Loyola Univ Maryland, Dept Psychol, 5911 York Rd,Suite 100, Baltimore, MD 21212 USA.
EM mcoiro@loyola.edu
FU National Institute of Mental Health [MH58384, MH56864]
FX This research was supported by grants MH58384 and MH56864 from the
   National Institute of Mental Health. The authors gratefully acknowledge
   data analytic support from Lily Zhang, M.S. This work was conducted
   before Dr. Broitman began official duties as a U.S. government employee.
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U1 2
U2 16
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD APR
PY 2012
VL 63
IS 4
BP 357
EP 363
DI 10.1176/appi.ps.201100126
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health;
   Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health; Psychiatry
GA 925KN
UT WOS:000302760200012
PM 22388476
ER

PT J
AU Choyke, PL
AF Choyke, Peter L.
TI Science to Practice: Imaging of Cellular Microparticles-Magic Dust or
   Just Dirt?
SO RADIOLOGY
LA English
DT Article
ID PROTAGONISTS
AB Al Faraj et al (1) are to be congratulated on having the insight to label endothelial microparticles (MPs) with iron oxides to image their fate in vivo. Their experiment is a good example of how imaging can be an important scientific tool. By bringing the concept of MPs to the attention of the radiology community, this article stimulates thinking about how to make MPs into imaging agents and/or therapeutic agents. MPs are already making an impact as serum biomarkers. Their size and biology make them challenging to develop as general imaging biomarkers; however, their potential as highly targeted natural drug-imaging carrier platforms for vascular disease should not be ignored because they fulfill so many of the desirable preconditions for such platforms. We are just beginning to understand how to harness this magic "dust" for medical purposes.
C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, 9000 Rockville Pike,Bldg 10,Room B3B69F, Bethesda, MD 20892 USA.
EM pchoyke@mail.nih.gov
NR 5
TC 1
Z9 1
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 APR
PY 2012
VL 263
IS 1
BP 1
EP 2
DI 10.1148/radiol.12120076
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 923TP
UT WOS:000302642700001
PM 22438438
ER

PT J
AU Strully, KW
   Fowler, JH
   Murabito, JM
   Benjamin, EJ
   Levy, D
   Christakis, NA
AF Strully, Kate W.
   Fowler, James H.
   Murabito, Joanne M.
   Benjamin, Emelia J.
   Levy, Daniel
   Christakis, Nicholas A.
TI Aspirin use and cardiovascular events in social networks
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE USA; Aspirin; Prevention; Cardiovascular disease; Social networks
ID PRIMARY PREVENTION; UNITED-STATES; DISEASE; RISK; BEHAVIOR; SPREAD;
   UPDATE; ADULTS
AB We tested whether friends' and family members' cardiovascular health events and also their own aspirin use are associated with the likelihood that an individual takes aspirin regularly. Analyses were based on longitudinal data on 2724 members of the Framingham Heart Study (based in Massachusetts, U.S.A.) who were linked to friends and family members who were also participants in the same study. Men were more likely to take aspirin if a male friend had recently been taking aspirin, and women were more likely to take aspirin if a brother had recently been taking aspirin. Men were also more likely to take aspirin if a brother recently had a cardiovascular event, and women were more likely to take aspirin if a female friend recently experienced a cardiovascular event. Aspirin use is correlated with the health and behavior of friends and family. These findings add to a growing body of evidence which suggests that behavioral changes that promote cardiovascular health may spread through social networks. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Strully, Kate W.] SUNY Albany, Dept Sociol, Coll Arts & Sci, Albany, NY 12222 USA.
   [Strully, Kate W.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol, Albany, NY 12222 USA.
   [Fowler, James H.] Univ Calif San Diego, Div Med Genet, La Jolla, CA 92093 USA.
   [Fowler, James H.] Univ Calif San Diego, Dept Polit Sci, La Jolla, CA 92093 USA.
   [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
   [Murabito, Joanne M.; Benjamin, Emelia J.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
   [Levy, Daniel] NHLBI, Bethesda, MD 20892 USA.
   [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
   [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
   [Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Fac Arts & Sci, Cambridge, MA 02138 USA.
RP Strully, KW (reprint author), SUNY Albany, Dept Sociol, Coll Arts & Sci, 1400 Washington Ave, Albany, NY 12222 USA.
EM kstrully@albany.edu
RI Fowler, James/C-2750-2008; 
OI Fowler, James/0000-0001-7795-1638; Murabito, Joanne/0000-0002-0192-7516;
   Benjamin, Emelia/0000-0003-4076-2336
FU NIH [P-01 AG031093]; Robert Wood Johnson Foundation;  [N01-HC-25195]
FX This was work was supported by NIH (P-01 AG031093) and by the Pioneer
   Portfolio of the Robert Wood Johnson Foundation; NHLBI 's Framingham
   Heart Study is supported by contract number N01-HC-25195.
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U2 11
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 APR
PY 2012
VL 74
IS 7
BP 1125
EP 1129
DI 10.1016/j.socscimed.2011.12.033
PG 5
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 920ZW
UT WOS:000302448800022
PM 22361089
ER

PT J
AU Cable, RG
   Glynn, SA
   Kiss, JE
   Mast, AE
   Steele, WR
   Murphy, EL
   Wright, DJ
   Sacher, RA
   Gottschall, JL
   Tobler, LH
   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.
   Tobler, Leslie H.
   Simon, Toby L.
CA NHLBI Retrovirus Epidemiology Dono
TI Iron deficiency in blood donors: the REDS-II Donor Iron Status
   Evaluation (RISE) study
SO TRANSFUSION
LA English
DT Article
ID SERUM TRANSFERRIN RECEPTOR; FERRITIN; HEMOGLOBIN; DONATION; STORES;
   HEMOCHROMATOSIS; DISEASE; ANEMIA
AB BACKGROUND: Blood donors are at risk of iron deficiency. We evaluated the effects of blood donation intensity on iron and hemoglobin (Hb) in a prospective study.
   STUDY DESIGN AND METHODS: Four cohorts of frequent and first-time or reactivated (FT/RA) blood donors (no donation in 2 years), female and male, totaling 2425, were characterized and followed as they donated blood frequently. At enrollment and the final visit, ferritin, soluble transferrin receptor (sTfR), and Hb were determined. Models to predict iron deficiency and Hb deferral were developed. Iron depletion was defined at two levels: iron deficiency erythropoiesis (IDE) [log(sTfR/ferritin) >= 2.07] and absent iron stores (AIS; ferritin < 12 ng/mL).
   RESULTS: Among returning female FT and RA donors, 20 and 51% had AIS and IDE at their final visit, respectively; corresponding proportions for males were 8 and 20%. Among female frequent donors who returned, 27 and 62% had AIS and IDE, respectively, while corresponding proportions for males were 18 and 47%. Predictors of IDE and/or AIS included a higher frequency of blood donation in the past 2 years, a shorter interdonation interval, and being female and young; conversely, taking iron supplements reduced the risk of iron depletion. Predictors of Hb deferral included female sex, black race, and a shorter interdonation interval.
   CONCLUSIONS: There is a high prevalence of iron depletion in frequent blood donors. Increasing the interdonation interval would reduce the prevalence of iron depletion and Hb deferral. Alternatively, replacement with iron supplements may allow frequent donation without the adverse outcome of iron depletion.
C1 [Cable, Ritchard G.] Amer Red Cross Blood Serv, Farmington, CT 06032 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Inst Transfus Med, Pittsburgh, PA USA.
   Med Coll Wisconsin, BloodCtr Wisconsin, Milwaukee, WI 53226 USA.
   Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA.
   Westat Corp, Rockville, MD 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 27
TC 65
Z9 69
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD APR
PY 2012
VL 52
IS 4
BP 702
EP 711
DI 10.1111/j.1537-2995.2011.03401.x
PG 10
WC Hematology
SC Hematology
GA 923LT
UT WOS:000302621500003
PM 22023513
ER

PT J
AU Booth, GS
   Lozier, JN
   Nghiem, K
   Clibourn, D
   Klein, HG
   Flegel, WA
AF Booth, Garrett S.
   Lozier, Jay N.
   Nghiem, Khanh
   Clibourn, Douglas
   Klein, Harvey G.
   Flegel, Willy A.
TI Spray: single-donor plasma product for room temperature storage
SO TRANSFUSION
LA English
DT Article
ID TRAUMA-ASSOCIATED COAGULOPATHY; DRIED ANIMAL PLASMA; FRESH-FROZEN
   PLASMA; MASSIVE TRANSFUSION; LYOPHILIZED PLASMA; BLOOD-TRANSFUSION;
   ESCHERICHIA-COLI
AB BACKGROUND: Spray-drying techniques are commonly utilized in the pharmaceutical, dairy, and animal feed industries for processing liquids into powders but have not been applied to human blood products. Spray-dried protein products are known to maintain stability during storage at room temperature.
   STUDY DESIGN AND METHODS: Plasma units collected at the donor facility were shipped overnight at room temperature to a processing facility where single-use spray drying occurred. After 48 hours' storage at room temperature, the spray-dried plasma product was split in two and rehydrated with 1.5% glycine or deionized water and assayed for chemistry analytes and coagulation factors. Matched fresh-frozen plasma was analyzed in parallel as controls.
   RESULTS: Reconstitution was achieved for both rehydration groups within 5 minutes (n = 6). There was no significant intergroup difference in recovery for total protein, albumin, immunoglobulin (Ig) G, IgA, and IgM (96% or higher). With the exception of Factor VIII (58%), the recovery of clotting factors in the glycine reconstituted products ranged from 72% to 93%. Glycine reconstitution was superior to deionized water.
   CONCLUSION: We documented proteins and coagulation activities were recovered in physiologic quantities in reconstituted spray-dried plasma products. Further optimization of the spray-drying method and reconstitution fluid may result in even better recoveries. Spray drying is a promising technique for preparing human plasma that can be easily stored at room temperature, shipped, and reconstituted. Rapid reconstitution of the microparticles results in a novel plasma product from single donors.
C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
   NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
   Velico Med Inc, Beverly, MA USA.
RP Booth, GS (reprint author), Vanderbilt Univ, Sch Med, Pathol Labs, Blood Bank, TVC 4605, Nashville, TN 37232 USA.
EM garrett.s.booth@vanderbilt.edu
FU Intramural NIH HHS [Z99 CL999999]
NR 27
TC 2
Z9 2
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 APR
PY 2012
VL 52
IS 4
BP 828
EP 833
DI 10.1111/j.1537-2995.2011.03419.x
PG 6
WC Hematology
SC Hematology
GA 923LT
UT WOS:000302621500019
PM 22043873
ER

PT J
AU Summers, RM
AF Summers, Ronald M.
TI Evaluation of Computer-aided Detection Devices: Consensus Is Developing
SO ACADEMIC RADIOLOGY
LA English
DT Editorial Material
ID INTRACRANIAL ANEURYSMS; MR-ANGIOGRAPHY; DIAGNOSIS; CT; COLONOGRAPHY
C1 NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224D,MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
NR 26
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD APR
PY 2012
VL 19
IS 4
BP 377
EP 379
DI 10.1016/j.acra.2012.01.010
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 916NH
UT WOS:000302110000001
PM 22444672
ER

PT J
AU Gallas, BD
   Chan, HP
   D'Orsi, CJ
   Dodd, LE
   Giger, ML
   Gur, D
   Krupinski, EA
   Metz, CE
   Myers, KJ
   Obuchowski, NA
   Sahiner, B
   Toledano, AY
   Zuley, ML
AF Gallas, Brandon D.
   Chan, Heang-Ping
   D'Orsi, Carl J.
   Dodd, Lori E.
   Giger, Maryellen L.
   Gur, David
   Krupinski, Elizabeth A.
   Metz, Charles E.
   Myers, Kyle J.
   Obuchowski, Nancy A.
   Sahiner, Berkman
   Toledano, Alicia Y.
   Zuley, Margarita L.
TI Evaluating Imaging and Computer-aided Detection and Diagnosis Devices at
   the FDA
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Reader studies; designs; methods; ROC; premarket; postmarket; consensus
ID DIGITAL BREAST TOMOSYNTHESIS; FINITE-SAMPLE SIZE; OBSERVER PERFORMANCE;
   FREE-RESPONSE; SCREENING MAMMOGRAPHY; ROC CURVES; RADIOLOGISTS
   PERFORMANCE; LABORATORY ENVIRONMENT; SERIAL MAMMOGRAMS; VERIFICATION
   BIAS
AB This report summarizes the Joint FDA-MIPS Workshop on Methods for the Evaluation of Imaging and Computer-Assist Devices. The purpose of the workshop was to gather information on the current state of the science and facilitate consensus development on statistical methods and study designs for the evaluation of imaging devices to support US Food and Drug Administration submissions. Additionally, participants expected to identify gaps in knowledge and unmet needs that should be addressed in future research. This summary is intended to document the topics that were discussed at the meeting and disseminate the lessons that have been learned through past studies of imaging and computer-aided detection and diagnosis device performance.
C1 [Gallas, Brandon D.; Myers, Kyle J.; Sahiner, Berkman] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
   [Chan, Heang-Ping] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
   [D'Orsi, Carl J.] Emory Univ, Atlanta, GA 30322 USA.
   [Dodd, Lori E.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
   [Giger, Maryellen L.; Metz, Charles E.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
   [Gur, David] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15260 USA.
   [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA.
   [Obuchowski, Nancy A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   [Toledano, Alicia Y.] Stat Collaborat Inc, Washington, DC USA.
RP Gallas, BD (reprint author), US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 3124, Silver Spring, MD 20993 USA.
EM brandon.gallas@fda.hhs.gov
OI Gallas, Brandon/0000-0001-7332-1620; Giger,
   Maryellen/0000-0001-5482-9728
NR 110
TC 16
Z9 16
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD APR
PY 2012
VL 19
IS 4
BP 463
EP 477
DI 10.1016/j.acra.2011.12.016
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 916NH
UT WOS:000302110000014
PM 22306064
ER

PT J
AU Soerensen, M
   Thinggaard, M
   Nygaard, M
   Dato, S
   Tan, QH
   Hjelmborg, J
   Andersen-Ranberg, K
   Stevnsner, T
   Bohr, VA
   Kimura, M
   Aviv, A
   Christensen, K
   Christiansen, L
AF Soerensen, Mette
   Thinggaard, Mikael
   Nygaard, Marianne
   Dato, Serena
   Tan, Qihua
   Hjelmborg, Jacob
   Andersen-Ranberg, Karen
   Stevnsner, Tinna
   Bohr, Vilhelm A.
   Kimura, Masayuki
   Aviv, Abraham
   Christensen, Kaare
   Christiansen, Lene
TI Genetic variation in TERT and TERC and human leukocyte telomere length
   and longevity: a cross-sectional and longitudinal analysis
SO AGING CELL
LA English
DT Article
DE association study; cross-sectional data and longitudinal data; human
   longevity; leukocyte telomere length; telomerase reverse transcriptase;
   telomerase RNA component
ID COMMON VARIANTS; LIFE-SPAN; ASSOCIATION; POPULATION; TWIN; AGE;
   CENTENARIANS; HERITABILITY; MORTALITY; BIOLOGY
AB Telomerase is of key importance for telomere maintenance, and variants of the genes encoding its major subunits, telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), are candidates for interindividual variation in telomere length. Recently, the two SNPs rs3772190 and rs12696304 in the TERC locus were reported to be associated with leukocyte telomere length (LTL) in two genome-wide association studies, while one haplotype of TERT (rs2853669, rs2736098, rs33954691, and rs2853691) has been reported to be associated with both LTL and longevity in a candidate gene study. In this study, we investigated the two TERC and four TERT SNPs in middle-aged, old, and oldest-old Danes (58100 years) and their association with LTL (n = 864) and longevity (n = 1069). Furthermore, data on 11 TERT tagging SNPs in 1089 oldest-old and 736 middle-aged Danes were investigated with respect to longevity. For all SNPs, the association with longevity was investigated using both a cross-sectional and a longitudinal approach. Applying an additive model, we found association of LTL with the minor TERC alleles of rs3772190 (A) and rs12696304 (G), such that a shorter LTL was seen in rs3772190 A carriers (regression coefficient = -0.08, P = 0.011) and in male rs12696304 G carriers (regression coefficient = -0.13, P = 0.014). No TERT variations showed association. Moreover, the A allele of rs3772190 (TERC) was found to be associated with longevity [hazard rate (AG + AA) = 1.31, P = 0.006]. No associations with longevity were observed for the TERT SNPs or haplotypes. Our study, thus, indicates that TERC is associated with both LTL and longevity in humans.
C1 [Soerensen, Mette; Thinggaard, Mikael; Nygaard, Marianne; Dato, Serena; Tan, Qihua; Hjelmborg, Jacob; Andersen-Ranberg, Karen; Christensen, Kaare; Christiansen, Lene] Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, DK-5000 Odense C, Denmark.
   [Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Tan, Qihua; Christensen, Kaare; Christiansen, Lene] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark.
   [Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Tan, Qihua; Christensen, Kaare; Christiansen, Lene] Odense Univ Hosp, Dept Biochem & Clin Pharmacol, DK-5000 Odense C, Denmark.
   [Dato, Serena] Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, Cs, Italy.
   [Stevnsner, Tinna; Bohr, Vilhelm A.] Aarhus Univ, Dept Mol Biol, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark.
   [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
   [Kimura, Masayuki; Aviv, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA.
RP Soerensen, M (reprint author), Univ So Denmark, Inst Publ Hlth, Danish Aging Res Ctr, JB Winsloews Vej 9B, DK-5000 Odense C, Denmark.
EM msoerensen@health.sdu.dk
RI Christensen, Kaare/C-2360-2009; Soerensen, Mette/O-1817-2015;
   Andersen-Ranberg, Karen/P-7053-2015; 
OI Christensen, Kaare/0000-0002-5429-5292; Andersen-Ranberg,
   Karen/0000-0003-1970-7076; Soerensen, Mette/0000-0001-5268-3366; dato,
   serena/0000-0003-2589-7929
FU Max-Planck Institute for Demographic Research, (Rostock, Germany);
   INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N.; EU; National
   Institute on Aging [P01 AG08761, R01AG030678]; Novo Nordisk Foundation;
   Aase and Ejnar Danielsen Foundation; Augustinus Foundation; Brodrene
   Hartmann Foundation; King Christian the 10th Foundation; Einar
   Willumsens Mindelegat Foundation; VELUX Foundation
FX This study was supported by the Max-Planck Institute for Demographic
   Research, (Rostock, Germany), the INTERREG 4 A programme
   Syddanmark-Schleswig-K.E.R.N. (by EU funds from the European Regional
   Development Fund), the National Institute on Aging (P01 AG08761 and
   R01AG030678), the Novo Nordisk Foundation, the Aase and Ejnar Danielsen
   Foundation, the Augustinus Foundation, the Brodrene Hartmann Foundation,
   the King Christian the 10th Foundation, and the Einar Willumsens
   Mindelegat Foundation. The Danish Aging Research Center is supported by
   a grant from the VELUX Foundation. Marlene Graff Sorensen, Susanne
   Knudsen, Steen Gregersen, Ulla Munk, and Shuxia Li are thanked for
   excellent technical work.
NR 29
TC 41
Z9 42
U1 3
U2 22
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD APR
PY 2012
VL 11
IS 2
BP 223
EP 227
DI 10.1111/j.1474-9726.2011.00775.x
PG 5
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 908WF
UT WOS:000301523000006
PM 22136229
ER

PT J
AU Harries, LW
   Pilling, LC
   Hernandez, LDG
   Bradley-Smith, R
   Henley, W
   Singleton, AB
   Guralnik, JM
   Bandinelli, S
   Ferrucci, L
   Melzer, D
AF Harries, Lorna W.
   Pilling, Luke C.
   Hernandez, L. Dena G.
   Bradley-Smith, Rachel
   Henley, William
   Singleton, Andrew B.
   Guralnik, Jack M.
   Bandinelli, Stefania
   Ferrucci, Luigi
   Melzer, David
TI CCAAT-enhancer-binding protein-beta expression in vivo is associated
   with muscle strength
SO AGING CELL
LA English
DT Article
DE inflammation; macrophage; mechanism; population; regeneration;
   transcription
ID C/EBP-BETA; SKELETAL-MUSCLE; MACROPHAGE POLARIZATION; GENE-EXPRESSION;
   OLD RATS; INJURY; ACTIVATION; CELLS; REGENERATION; AGE
AB Declining muscle strength is a core feature of aging. Several mechanisms have been postulated, including CCAAT/enhancer-binding protein-beta (C/EBP-beta)-triggered macrophage-mediated muscle fiber regeneration after micro-injury, evidenced in a mouse model. We aimed to identify in vivo circulating leukocyte gene expression changes associated with muscle strength in the human adult population. We undertook a genome-wide expression microarray screen, using peripheral blood RNA samples from InCHIANTI study participants (aged 30 and 104). Logged expression intensities were regressed with muscle strength using models adjusted for multiple confounders. Key results were validated by real-time PCR. The Short Physical Performance Battery (SPPB) score tested walk speed, chair stand, and balance. CEBPB expression levels were associated with muscle strength (beta coefficient = 0.20560, P = 1.03*10-6, false discovery rate q = 0.014). The estimated handgrip strength in 70-year-old men in the lowest CEBPB expression tertile was 35.2 kg compared with 41.2 kg in the top tertile. CEBPB expression was also associated with hip, knee, ankle, and shoulder strength and the SPPB score (P = 0.018). Near-study-wide associations were also noted for TGF-beta 3 (P = 3.4*10-5, q = 0.12) and CEBPD expression (P = 9.7*10-5, q = 0.18) but not for CEBPA expression. We report here a novel finding that raised CEBPB expression in circulating leukocyte-derived RNA samples in vivo is associated with greater muscle strength and better physical performance in humans. This association may be consistent with mouse model evidence of CEBPB-triggered muscle repair: if this mechanism is confirmed, it may provide a target for intervention to protect and enhance aging muscle.
C1 [Harries, Lorna W.; Bradley-Smith, Rachel; Melzer, David] Univ Exeter, Inst Biomed & Clin Sci, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England.
   [Hernandez, L. Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Henley, William] Univ Plymouth, Sch Math & Stat, Plymouth PL4 8AA, Devon, England.
   [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
   [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Melzer, D (reprint author), Peninsula Med Sch, Barrack Rd, Exeter EX2 5DW, Devon, England.
EM david.melzer@pms.ac.uk
RI Singleton, Andrew/C-3010-2009; Pilling, Luke/E-4917-2013; Harries,
   Lorna/D-2241-2014; 
OI Pilling, Luke/0000-0002-3332-8454; Melzer, David/0000-0002-0170-3838
FU Peninsula College of Medicine and Dentistry (John Bull Building, Tamar
   Science Park, Research Way, Plymouth, UK)
FX The authors declare no conflict of interest. This analysis was supported
   by funding from the Peninsula College of Medicine and Dentistry (John
   Bull Building, Tamar Science Park, Research Way, Plymouth PL6 8BU, UK).
NR 44
TC 10
Z9 11
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD APR
PY 2012
VL 11
IS 2
BP 262
EP 268
DI 10.1111/j.1474-9726.2011.00782.x
PG 7
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 908WF
UT WOS:000301523000011
PM 22152057
ER

PT J
AU Sheydina, A
   Volkova, M
   Jiang, LQ
   Juhasz, O
   Zhang, J
   Tae, HJ
   Perino, MG
   Wang, MY
   Zhu, Y
   Lakatta, EG
   Boheler, KR
AF Sheydina, Anna
   Volkova, Maria
   Jiang, Liqun
   Juhasz, Ondrej
   Zhang, Jing
   Tae, Hyun-Jin
   Perino, Maria G.
   Wang, Mingyi
   Zhu, Yi
   Lakatta, Edward G.
   Boheler, Kenneth R.
TI Linkage of cardiac gene expression profiles and ETS2 with lifespan
   variability in rats
SO AGING CELL
LA English
DT Article
DE aging; mortality; rat; microarrays; prediction analysis of microarrays;
   transcription factors
ID APOPTOSIS-INDUCING FACTOR; PROGRAMMED NECROSIS; CALORIC RESTRICTION;
   DIETARY RESTRICTION; HEART-FAILURE; SENESCENCE; PATTERNS; DISSECTION;
   CARCINOMAS; EXTENSION
AB Longevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets coupled with prediction analysis of microarrays (PAM), we identified a set of 252 cardiac transcripts predictive of relative lifespan in Wistar and Fisher 344 rats. Prediction analysis of microarrays tests of rat heart transcriptomes from a third longer lived Fisher x Norway Brown rat strain validated the predictive value of this gene subset. The expression patterns of these genes were highly conserved, and corresponding promoter regions were employed to identify common ciselements and trans-activating factors implicated in their control. Specifically, four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity-dependent, strain-independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. In heart, ETS2 was prevalent in cardiomyocytes (CMs) and showed a high degree of myocyte-to-myocyte variability predominantly in adult rat hearts prior to the exponential increase in the rate of mortality. Exclusively in this group, elevated ETS2 significantly overlapped with TUNEL staining in heart myocytes. In response to sympathetic stimuli, ETS2 is also up-regulated, and functionally, adenovirus-mediated over-expression of ETS2 promotes apoptosis-inducing factor-mediated, caspase-independent programmed necrosis exclusively in CMs that can be fully inhibited by the PARP-1 inhibitor DPQ. We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis.
C1 [Boheler, Kenneth R.] NIA, Mol Cardiol & Stem Cell Unit, LCS, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA.
RP Boheler, KR (reprint author), NIA, Mol Cardiol & Stem Cell Unit, LCS, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM bohelerk@grc.nia.nih.gov
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
   of the NIH, National Institute on Aging.
NR 43
TC 5
Z9 6
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD APR
PY 2012
VL 11
IS 2
BP 350
EP 359
DI 10.1111/j.1474-9726.2012.00794.x
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 908WF
UT WOS:000301523000021
PM 22247964
ER

PT J
AU Agwu, AL
   Bethel, J
   Hightow-Weidman, LB
   Sleasman, JW
   Wilson, CM
   Rudy, B
   Kapogiannis, BG
AF Agwu, Allison L.
   Bethel, James
   Hightow-Weidman, Lisa B.
   Sleasman, John W.
   Wilson, Craig M.
   Rudy, Bret
   Kapogiannis, Bill G.
CA ATN 061 Team
   Adolescent Med Trials Network HIV
TI Substantial Multiclass Transmitted Drug Resistance and Drug-Relevant
   Polymorphisms Among Treatment-Naive Behaviorally HIV-Infected Youth
SO AIDS PATIENT CARE AND STDS
LA English
DT Letter
ID PREVALENCE; MEN; SEX; TRANSMISSION; TRIALS
C1 [Agwu, Allison L.] Johns Hopkins Univ, Sch Med, Dept Pediat & Adult Infect Dis, Baltimore, MD USA.
   [Bethel, James] WESTAT Corp, Rockville, MD 20850 USA.
   [Hightow-Weidman, Lisa B.] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA.
   [Sleasman, John W.] Univ S Florida, Dept Pediat, Div Allergy Immunol & Rheumatol, St Petersburg, FL 33701 USA.
   [Wilson, Craig M.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
   [Rudy, Bret] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA.
   [Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
RP Agwu, AL (reprint author), Johns Hopkins Med Inst, Dept Pediat Infect Dis, 200 N Wolfe St,Room 3145, Baltimore, MD 21287 USA.
EM ageorg10@jhmi.edu
FU NCRR NIH HHS [M01RR020359, UL1RR024131, UL1 RR024134, UL1 RR025780,
   MO1-RR010284]; NIAID NIH HHS [K23 AI084549]; NICHD NIH HHS [U01
   HD040533, U01 HD068070, U01 HD 040474, U01 HD040474, U01 HD 040533]; PHS
   HHS [U01 A1068632]
NR 12
TC 8
Z9 8
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD APR
PY 2012
VL 26
IS 4
BP 193
EP 196
DI 10.1089/apc.2011.0420
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 918BX
UT WOS:000302225000001
PM 22563607
ER

PT J
AU Mills, KC
   Sangueza, OP
   Beaty, MW
   Raffeld, M
   Pang, CS
AF Mills, Kyle C.
   Sangueeza, Omar P.
   Beaty, Michael W.
   Raffeld, Mark
   Pang, Changlee S.
TI Composite B-cell and T-cell Lineage Post-transplant Lymphoproliferative
   Disorder of the Lung with Unusual Cutaneous Manifestations of Mycosis
   Fungoides
SO AMERICAN JOURNAL OF DERMATOPATHOLOGY
LA English
DT Article
DE post-transplant lymphoproliferative disorder; B-cell; T-cell; composite;
   mycosis fungoides
ID EPSTEIN-BARR-VIRUS; TRANSPLANT RECIPIENT; LYMPHOMA; PATHOGENESIS;
   PATHOLOGY; PATIENT
AB We present the case of a 17-year-old male kidney transplant recipient who presented initially with dermatologic symptoms and was found to have histologic changes in the skin that were consistent with mycosis fungoides. Shortly after this diagnosis was made, imaging studies demonstrated multifocal interstitial and airspace consolidation in both lungs. Physical examination revealed no lymphadenopathy or hepatosplenomegaly, but an open lung biopsy revealed an Epstein-Barr virus (EBV)-negative monomorphic T-cell posttransplant lymphoproliferative disorder (PTLD) with a concomitant EBV-positive B-cell PTLD involving the same lesion of the lung. Polymerase chain reaction analysis demonstrated clonal T-cell receptor gene rearrangements in both the skin and the lung biopsies. Interestingly, 1 clone was shared between the skin and lung while a second clone was present only in the lung. To our knowledge, this is the first reported case of a PTLD presenting in the skin in which there was a subsequent discovery of composite, bilineal B-and T-cell PTLD of the lung.
C1 [Mills, Kyle C.] Wake Forest Univ, Baptist Med Ctr, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA.
   [Sangueeza, Omar P.] Wake Forest Univ, Dept Dermatol, Sch Med, Winston Salem, NC 27157 USA.
   [Raffeld, Mark] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Mills, KC (reprint author), Wake Forest Univ, Baptist Med Ctr, Sch Med, Dept Pathol, 2nd Floor,Watlington Hall,Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM kmills@wfubmc.edu
NR 15
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0193-1091
J9 AM J DERMATOPATH
JI Am. J. Dermatopathol.
PD APR
PY 2012
VL 34
IS 2
BP 220
EP 225
DI 10.1097/DAD.0b013e31823067f8
PG 6
WC Dermatology
SC Dermatology
GA 917AD
UT WOS:000302143400021
PM 22214855
ER

PT J
AU Pazmino, PA
AF Pazmino, Patricio A.
TI DABIGATRAN ASSOCIATED ACUTE RENAL FAILURE (DAARF)
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Meeting Abstract
CT Spring Clinical Meeting of the National-Kidney-Foundation
CY MAY 09-13, 2012
CL Washington, DC
SP Natl Kidney Fdn
C1 [Pazmino, Patricio A.] Internal Med & Hypertens NIH Ctr, El Paso, TX USA.
   [Pazmino, Patricio A.] PFSM Texas Tech Univ, Hlth Sci Ctr, El Paso, TX USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD APR
PY 2012
VL 59
IS 4
MA 196
BP A63
EP A63
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 916QE
UT WOS:000302117500198
ER

PT J
AU Pattabiraman, PP
   Lih, FB
   Tomer, KB
   Rao, PV
AF Pattabiraman, Padmanabhan P.
   Lih, Fred B.
   Tomer, Kenneth B.
   Rao, Ponugoti Vasantha
TI The role of calcium-independent phospholipase A(2)gamma in modulation of
   aqueous humor drainage and Ca2+ sensitization of trabecular meshwork
   contraction
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE Rho GTPase; arachidonic acid; glaucoma
ID OPEN-ANGLE GLAUCOMA; MECHANISM-BASED DISCRIMINATION; VASCULAR
   SMOOTH-MUSCLE; NONMUSCLE MYOSIN-II; PROTEIN-KINASE-C; RHO-KINASE;
   ARACHIDONIC-ACID; GENETIC ABLATION; A(2) ENZYMES; P388D(1) MACROPHAGES
AB Pattabiraman PP, Lih FB, Tomer KB, Rao PV. The role of calcium-independent phospholipase A(2)gamma in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction. Am J Physiol Cell Physiol 302: C979-C991, 2012. First published January 11, 2012; doi:10.1152/ajpcell.00396.2011.-The contractile and relaxation characteristics of trabecular meshwork (TM) are presumed to influence aqueous humor (AH) drainage and intraocular pressure. The mechanisms underlying regulation of TM cell contractile properties, however, are not well understood. This study investigates the role of calcium-independent phospholipase A(2) (iPLA(2)), which controls eicosanoid synthesis, in regulation of TM cell contraction and AH outflow using mechanism-based isoform specific inhibitors (R)-bromoenol lactone (R-BEL, iPLA(2)gamma specific) and (S)bromoenol lactone (S-BEL, iPLA(2)beta specific). Immunohistochemical analysis revealed intense staining for both iPLA(2)gamma and gamma isoforms throughout the TM, juxtacanalicular tissue, and Schlemm's canal of human eye. Inhibition of iPLA(2)gamma by R-BEL or small interfering RNA-mediated silencing of iPLA(2)gamma expression induced dramatic changes in TM cell morphology, and decreased actin stress fibers, focal adhesions, and myosin light-chain (MLC) phosphorylation. AH outflow facility increased progressively and significantly in enucleated porcine eyes perfused with R-BEL. This response was associated with a significant decrease in TM tissue MLC phosphorylation and alterations in the morphology of aqueous plexi in R-BEL-perfused eyes. In contrast, S-BEL did not affect either of these parameters. Additionally, R-BEL-induced cellular relaxation of the TM was associated with a significant decrease in the levels of active Rho GTPase, phospho-MLC phosphatase, phospho-CPI-17, and arachidonic acid. Taken together, these observations demonstrate that iPLA(2)gamma plays a significant and isoform-specific role in regulation of AH outflow facility by altering the contractile characteristics of the TM. The effects of iPLA(2)gamma on TM contractile status appear to involve arachidonic acid and Rho GTPase signaling pathways.
C1 [Pattabiraman, Padmanabhan P.; Rao, Ponugoti Vasantha] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC 27710 USA.
   [Lih, Fred B.; Tomer, Kenneth B.] NIEHS, Mass Spectrometry Grp, Res Triangle Pk, NC 27709 USA.
   [Rao, Ponugoti Vasantha] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
RP Rao, PV (reprint author), Duke Univ, Sch Med, Dept Ophthalmol, AERI Bldg,Rm 4010, Durham, NC 27710 USA.
EM rao00011@mc.duke.edu
RI Tomer, Kenneth/E-8018-2013
FU National Institutes of Health [EY018590, EY12201]; National Eye
   Institute [P30-EY5722]; National Institute of Environmental Health
   Sciences/National Institutes of Health [ES050167]
FX This work was supported in part by National Institutes of Health Grants
   to P. V. Rao (EY018590 and EY12201), National Eye Institute Core Grant
   for Vision Research (P30-EY5722), and by the Intramural Research Program
   of the National Institute of Environmental Health Sciences/National
   Institutes of Health, ES050167.
NR 57
TC 10
Z9 10
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD APR
PY 2012
VL 302
IS 7
BP C979
EP C991
DI 10.1152/ajpcell.00396.2011
PG 13
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 919QG
UT WOS:000302342700004
PM 22237407
ER

PT J
AU Miettinen, M
   Rikala, MS
   Rys, J
   Lasota, J
   Wang, ZF
AF Miettinen, Markku
   Rikala, Maarit-Sarlomo
   Rys, Janusz
   Lasota, Jerzy
   Wang, Zeng-Feng
TI Vascular Endothelial Growth Factor Receptor 2 as a Marker for Malignant
   Vascular Tumors and Mesothelioma: An Immunohistochemical Study of 262
   Vascular Endothelial and 1640 Nonvascular Tumors
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE angiosarcoma; Kaposi sarcoma; malignant mesothelioma; VEGFR2;
   endothelial cell; mesothelial cell; fetal tissue; adult tissue
ID COLORECTAL-CANCER; KAPOSIS-SARCOMA; BREAST-CANCER; EXPRESSION; VEGF;
   ANGIOSARCOMA; ANGIOGENESIS; HEMANGIOMA; INHIBITOR; CARCINOMA
AB Vascular endothelial growth factor receptor 2 (VEGFR2) is a primary responder to vascular endothelial growth factor signal and thereby regulates endothelial migration and proliferation. This receptor is expressed in endothelial cells and in some vascular tumors, but many reports also detail its expression in carcinomas and lymphomas. VEGFR2 is a potential cell-type marker, and data on VEGFR2 expression may also have therapeutic significance in view of recent availability of VEGFR2 inhibitors. In this study, we immunohistochemically examined 262 vascular endothelial and 1640 nonvascular tumors and selected non-neoplastic tissues with a VEGFR2-specific rabbit monoclonal antibody 55B11. In early human embryo, VEFGR2 was expressed in endothelia of developing capillaries and in the thoracic duct, great vessels, hepatic sinusoids, epidermis, and mesothelia. In late first trimester fetus peripheral soft tissues, VEGFR2 was restricted to capillary endothelia, chondrocytes, and superficial portion of the epidermis. In normal adult tissues, it was restricted to endothelia and mesothelia. VEGFR2 was consistently expressed in angiosarcomas, Kaposi sarcomas, and retiform hemangioendotheliomas. It was detected in only half of epithelioid hemangioendotheliomas (15/27), usually focally. VEGFR2 was strongly expressed in most capillary hemangiomas and weakly or focally in cavernous, venous, and spindle cell hemangiomas and in lymphangiomas. Malignant epithelial mesothelioma was found to be a unique epithelial neoplasm with a strong and nearly consistent VEGFR2 expression, including membrane staining (35/38). Approximately 10% of squamous cell carcinomas and 23% of pulmonary adenocarcinomas contained focal positivity. The only nonendothelial mesenchymal tumors found to be VEGFR2 positive were biphasic synovial sarcoma (focal epithelial expression) and chordoma. All melanomas and lymphomas were negative. VEGFR2 is a promising marker for malignant vascular tumors and malignant epithelioid mesothelioma. Expression in biphasic synovial sarcoma epithelium, chordoma, and some carcinomas has to be considered in differential diagnosis. Information on VEGFR2 tissue expression may be useful in development of targeted oncologic therapy through VEGFR2-specific tyrosine kinase inhibitors.
C1 [Miettinen, Markku; Lasota, Jerzy; Wang, Zeng-Feng] NCI, Pathol Lab, Bethesda, MD 20892 USA.
   [Rikala, Maarit-Sarlomo] Univ Helsinki, Cent Hosp, Dept Pathol, HUSLAB, Helsinki, Finland.
   [Rys, Janusz] Maria Sklodowska Curie Mem Inst Oncol, Krakow Branch, Ctr Oncol, Dept Tumor Pathol, Krakow, Poland.
RP Miettinen, M (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU NCI
FX The authors have disclosed that they have no significant relationships
   with, or financial interest in, any commercial companies pertaining to
   this article. Supported as a part of NCI's intramural research program.
NR 37
TC 18
Z9 19
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD APR
PY 2012
VL 36
IS 4
BP 629
EP 639
DI 10.1097/PAS.0b013e318243555b
PG 11
WC Pathology; Surgery
SC Pathology; Surgery
GA 916ZQ
UT WOS:000302142100017
PM 22314185
ER

PT J
AU Ali, M
   Keen, L
   Bygrave, D
   Jones, V
   Gholson, G
   Mwendwa, D
   Sims, R
   Ricks, M
   Callender, C
   Sumner, A
AF Ali, Mana
   Keen, Larry
   Bygrave, Desiree
   Jones, Victor
   Gholson, Georica
   Mwendwa, Denee
   Sims, Regina
   Ricks, Madia
   Callender, Clive
   Sumner, Anne
TI CHRONIC KIDNEY DISEASE RISK IN AFRICAN IMMIGRANTS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Ali, Mana; Keen, Larry; Bygrave, Desiree; Jones, Victor; Gholson, Georica; Mwendwa, Denee] Howard Univ, Washington, DC 20059 USA.
   [Sims, Regina] Univ Delaware, Newark, DE USA.
   [Ricks, Madia; Sumner, Anne] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA.
   [Callender, Clive] Howard Univ Hosp, Washington, DC USA.
EM ms.manaali@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S244
EP S244
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092401036
ER

PT J
AU Allen, AJ
   McNeely, JM
   Waldstein, SR
   Evans, MK
   Zonderman, AB
AF Allen, Allyssa J.
   McNeely, Jessica M.
   Waldstein, Shari R.
   Evans, Michele K.
   Zonderman, Alan B.
TI RACIAL DIFFERENCES IN THE RELATION OF SUBJECTIVE SOCIOECONOMIC STATUS TO
   CARDIOVASCULAR DISEASE RISK IN THE HEALTHY AGING IN NEIGHBORHOODS OF
   DIVERSITY ACROSS THE LIFESPAN STUDY
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Allen, Allyssa J.; McNeely, Jessica M.; Waldstein, Shari R.] UMBC, Baltimore, MD 21212 USA.
   [McNeely, Jessica M.; Evans, Michele K.; Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
EM allyssaallen@gmail.com
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S16
EP S16
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400057
ER

PT J
AU Bennett, GG
   Warner, E
   Glasgow, R
   Askew, S
   Emmons, KM
   Rosner, B
   Colditz, GA
AF Bennett, Gary G.
   Warner, Erica
   Glasgow, Russell
   Askew, Sandy
   Emmons, Karen M.
   Rosner, Bernard
   Colditz, Graham A.
TI WEIGHT LOSS AMONG SOCIOECONOMICALLY DISADVANTAGED PRIMARY CARE PATIENTS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Bennett, Gary G.; Askew, Sandy] Duke Univ, Durham, NC 27608 USA.
   [Warner, Erica; Emmons, Karen M.; Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
   [Glasgow, Russell] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci,Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
EM gary.bennett@duke.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S272
EP S272
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092401145
ER

PT J
AU Cerully, JL
   Klein, WMP
AF Cerully, Jennifer L.
   Klein, William M. P.
TI USING A SELF-AFFIRMATION INTERVENTION TO DECREASE ALCOHOL CONSUMPTION
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Cerully, Jennifer L.] RAND Corp, Pittsburgh, PA 15213 USA.
   [Klein, William M. P.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
EM jcerully@rand.org
NR 0
TC 0
Z9 0
U1 2
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S125
EP S125
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400486
ER

PT J
AU Chou, WYS
   Glasgow, R
   Hesse, B
AF Chou, Wen-ying Sylvia
   Glasgow, Russell
   Hesse, Bradford
TI FOSTERING COMMUNITY ENGAGEMENT THROUGH SOCIAL MEDIA: EXAMPLES FROM
   HEALTH PROMOTION PROGRAMS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Chou, Wen-ying Sylvia; Glasgow, Russell; Hesse, Bradford] NCI, Bethesda, MD 20892 USA.
EM chouws@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S73
EP S73
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400284
ER

PT J
AU Czajkowski, SM
   Davidson, KW
   Fitz-Simmons, SC
   Keefe, FJ
   Nilsen, WJ
   Stirratt, MJ
   Wiebe, DJ
AF Czajkowski, Susan M.
   Davidson, Karina W.
   Fitz-Simmons, Stacey C.
   Keefe, Francis J.
   Nilsen, Wendy J.
   Stirratt, Michael J.
   Wiebe, Deborah J.
TI NIH GRANT WRITING SEMINAR FOR EARLY CAREER RESEARCHERS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Czajkowski, Susan M.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Davidson, Karina W.] Columbia Univ, Med Ctr, New York, NY USA.
   [Fitz-Simmons, Stacey C.] NIH, Ctr Sci Review, Bethesda, MD 20892 USA.
   [Keefe, Francis J.] Duke Univ, Durham, NC USA.
   [Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
   [Stirratt, Michael J.] NIMH, NIH, Bethesda, MD 20892 USA.
   [Wiebe, Deborah J.] UT SW Med Ctr, Dallas, TX USA.
EM Czajkows@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S1
EP S1
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400002
ER

PT J
AU Diefenbach, MA
   Marcus, A
   Stanton, AL
   Raich, P
   Miller, SM
   Tran, Z
   Hesse, B
AF Diefenbach, Michael A.
   Marcus, Al
   Stanton, Annette L.
   Raich, Peter
   Miller, Susan M.
   Tran, Zung
   Hesse, Bradford
TI CANCER PATIENT AND SURVIVOR RESEARCH FROM THE CANCER INFORMATION SERVICE
   RESEARCH CONSORTIUM: INITIAL RESULTS FROM THREE RANDOMIZED TRIALS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Diefenbach, Michael A.] Mt Sinai Sch Med, New York, NY 10029 USA.
   [Stanton, Annette L.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
   [Marcus, Al; Raich, Peter; Tran, Zung] U CO Ca Ctr, Aurora, CO USA.
   [Miller, Susan M.] Fox Chase Ca Ctr, Philadelphia, PA USA.
   [Hesse, Bradford] NCI, Bethesda, MD 20892 USA.
EM michael.diefenbach@mountsinai.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S64
EP S64
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400248
ER

PT J
AU Driscoll, M
   Davis, M
   Aiken, L
   Nelson, L
AF Driscoll, Mary
   Davis, Mary
   Aiken, Leona
   Nelson, Lawrence
TI DISTINCT COPING PATTERNS: IMPLICATIONS FOR ADAPTATION IN INFERTILITY
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Driscoll, Mary; Davis, Mary; Aiken, Leona] Arizona State Univ, Tempe, AZ USA.
   [Nelson, Lawrence] NIMH, Bethesda, MD 20892 USA.
   [Driscoll, Mary] VA CT Healthcare Syst, West Haven, CT USA.
EM mary.a.driscoll@asu.edu
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S115
EP S115
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400445
ER

PT J
AU Duffecy, J
   Begale, M
   Mohr, DC
   Riley, W
AF Duffecy, Jennifer
   Begale, Mark
   Mohr, David C.
   Riley, William
TI GOING DIGITAL: BUILDING EVIDENCE BASED EHEALTH AND MHEALTH INTERVENTIONS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Duffecy, Jennifer; Begale, Mark; Mohr, David C.] Northwestern Univ, Ctr Behav Intervent Technol, Chicago, IL 60611 USA.
   [Riley, William] NHLBI, Bethesda, MD 20892 USA.
EM jduffecy@hotmail.com
NR 0
TC 0
Z9 0
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S4
EP S4
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400011
ER

PT J
AU Medina-Mora, ME
   Buenabad, NA
   Pentz, MA
   Sevilla, CA
   Baler, R
   Lloyd, J
AF Elena Medina-Mora, Maria
   Amador Buenabad, Nancy
   Ann Pentz, Mary
   Sevilla, Celina A.
   Baler, Ruben
   Lloyd, Jacqueline
TI THE MEXICO AMBAR MUSEUM INITIATIVE
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Elena Medina-Mora, Maria; Amador Buenabad, Nancy] Inst Natl Psiquiatria Ramon Fuente, Delegac Tlalpan, Mexico.
   [Ann Pentz, Mary] Univ So Calif, Inst Hlth Promot & Dis Prevent Res, Los Angeles, CA 90032 USA.
   [Sevilla, Celina A.] Ctr Nacl Prevenc & Control Adicciones, Subsecretaria Prevenc Promoc Salud, Mexico City, DF, Mexico.
   [Lloyd, Jacqueline] NIDA, NIH, Bethesda, MD 20892 USA.
EM pentz@usc.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S67
EP S67
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400260
ER

PT J
AU Forsythe, L
   Alfano, CM
   George, SM
   McTiernan, A
   Baumgartner, KB
   Bernstein, L
   Ballard-Barbash, R
AF Forsythe, Laura
   Alfano, Catherine M.
   George, Stephanie M.
   McTiernan, Anne
   Baumgartner, Kathy B.
   Bernstein, Leslie
   Ballard-Barbash, Rachel
TI PAIN IN LONG-TERM BREAST CANCER SURVIVORS: THE EFFECT OF BODY MASS INDEX
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Forsythe, Laura; Alfano, Catherine M.; George, Stephanie M.; Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA.
   [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Baumgartner, Kathy B.] Univ Louisville, Louisville, KY 40292 USA.
   [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
EM laura.forsythe@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S75
EP S75
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400288
ER

PT J
AU Goergen, A
   Wilkinson, AV
   Koehly, LM
AF Goergen, Andrea
   Wilkinson, Anna V.
   Koehly, Laura M.
TI BARRIERS TO FHH KNOWLEDGE WITHIN IMMIGRANT FAMILIES OF MEXICAN ORIGIN IN
   PROJECT RAMA
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Goergen, Andrea; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
   [Wilkinson, Anna V.] Univ Texas Austin, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth Austin, Austin, TX 78712 USA.
EM girouxag@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S117
EP S117
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400455
ER

PT J
AU Hamilton, JG
   Han, PKJ
   Hutson, SP
   Rife, SC
   Kobrin, SC
   Moser, RP
   Alter, BP
AF Hamilton, Jada G.
   Han, Paul K. J.
   Hutson, Sadie P.
   Rife, Sean C.
   Kobrin, Sarah C.
   Moser, Richard P.
   Alter, Blanche P.
TI RESPONSES TO MEDICAL AMBIGUITY ARE NOT UNIVERSAL: THE MODERATING ROLE OF
   NEED FOR COGNITIVE CLOSURE
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Hamilton, Jada G.] NCI, Canc Prevent Fellowship Program, Rockville, MD 20892 USA.
   [Hamilton, Jada G.; Kobrin, Sarah C.] NCI, Proc Care Res Branch, DCCPS, Rockville, MD 20892 USA.
   [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Scarborough, ME USA.
   [Hutson, Sadie P.] Univ Tennessee, Coll Nursing, Knoxville, TN USA.
   [Hutson, Sadie P.; Alter, Blanche P.] NCI, Clin Genet Branch, DCEG, Rockville, MD 20892 USA.
   [Rife, Sean C.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA.
   [Moser, Richard P.] NCI, Sci Res & Technol Branch, DCCPS, Rockville, MD 20892 USA.
EM hamiltonjg@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S167
EP S167
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400647
ER

PT J
AU Kaufman, A
   Kennedy, CE
   Moore, PJ
AF Kaufman, Annette
   Kennedy, Caitlin E.
   Moore, Philip J.
TI IMPLICIT THEORIES OF HEALTH: PEOPLE WHO SMOKE (PROBABLY WON'T) QUIT
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Kaufman, Annette] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Kennedy, Caitlin E.; Moore, Philip J.] George Washington Univ, Washington, DC USA.
EM kaufmana@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S144
EP S144
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400558
ER

PT J
AU Kent, EE
   Alfano, CM
   Smith, AW
   McTiernan, A
   Bernstein, L
   Baumgartner, KB
   Ballard-Barbash, R
AF Kent, Erin E.
   Alfano, Catherine M.
   Smith, Ashley Wilder
   McTiernan, Anne
   Bernstein, Leslie
   Baumgartner, Kathy B.
   Ballard-Barbash, Rachel
TI THE RELATIONSHIPS BETWEEN SEEKING SUPPORT FROM HEALTHCARE PROVIDERS AND
   GROUPS, RACE/ETHNICITY, AND POSTTRAUMATIC GROWTH IN A DIVERSE POPULATION
   OF BREAST CANCER SURVIVORS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Kent, Erin E.; Alfano, Catherine M.] NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, Rockville, MD 20892 USA.
   [Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Appl Res Program, Rockville, MD 20892 USA.
   [McTiernan, Anne] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Hlth Sci, Seattle, WA 98195 USA.
   [McTiernan, Anne] Univ Washington, Sch Med, Seattle, WA 98195 USA.
   [McTiernan, Anne] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
   [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA.
   [Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Clin Informat Sci, Louisville, KY USA.
   [Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM Erin.Kent@nih.gov
NR 0
TC 0
Z9 0
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S9
EP S9
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400028
ER

PT J
AU King, DK
   Toobert, DJ
   Dickman, JM
   Strycker, LA
   Doty, A
   Martin, C
   Boggs, J
   Faber, A
   Geno, C
   Glasgow, RE
AF King, Diane K.
   Toobert, Deborah J.
   Dickman, Jennifer M.
   Strycker, Lisa A.
   Doty, Alyssa
   Martin, Carmen
   Boggs, Jennifer
   Faber, Andrew
   Geno, Cristy
   Glasgow, Russell E.
TI WHAT PATIENTS WANT: RELEVANT HEALTH INFORMATION TECHNOLOGY FOR DIABETES
   SELF-MANAGEMENT
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [King, Diane K.] Univ Alaska, Ctr Behav Hlth Res & Serv, Anchorage, AK 99508 USA.
   [Toobert, Deborah J.; Strycker, Lisa A.] Oregon Res Inst, Eugene, OR 97403 USA.
   [Dickman, Jennifer M.; Doty, Alyssa; Martin, Carmen; Boggs, Jennifer; Faber, Andrew; Geno, Cristy] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
   [Glasgow, Russell E.] NCI, Rockville, MD USA.
EM dkking@uaa.alaska.edu
NR 0
TC 0
Z9 0
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S99
EP S99
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400382
ER

PT J
AU Kisser, J
   Sprung, MR
   Waldstein, SR
   Evans, MK
   Zonderman, AB
AF Kisser, Jason
   Sprung, Mollie R.
   Waldstein, Shari R.
   Evans, Michele K.
   Zonderman, Alan B.
TI PERCEIVED SOCIAL SUPPORT IS ASSOCIATED WITH POORER COGNITIVE PERFORMANCE
   IN AFRICAN-AMERICAN MEN
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Kisser, Jason; Sprung, Mollie R.; Waldstein, Shari R.] UMBC, Baltimore, MD 21250 USA.
   [Evans, Michele K.; Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
EM jason.kisser@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S23
EP S23
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400086
ER

PT J
AU Mustian, K
   Alfano, C
   Piper, B
   Smith, T
   Sprod, L
   Scarpato, J
   Leach, C
   Peppone, L
   Palesh, O
   Jing, L
   Mohr, D
   Spring, B
   Berendsen, M
   Heckler, C
   Miller, S
AF Mustian, Karen
   Alfano, C.
   Piper, B.
   Smith, T.
   Sprod, L.
   Scarpato, J.
   Leach, C.
   Peppone, L.
   Palesh, O.
   Jing, L.
   Mohr, D.
   Spring, B.
   Berendsen, M.
   Heckler, C.
   Miller, S.
TI A META-ANALYTIC COMPARISON OF EXERCISE, PSYCHOLOGICAL, EXERCISE COMBINED
   WITH PSYCHOLOGICAL AND PHARMACEUTICAL INTERVENTIONS FOR CANCER-RELATED
   FATIGUE
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Mustian, Karen; Sprod, L.; Peppone, L.; Heckler, C.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
   [Scarpato, J.; Miller, S.] FCCC, Philadelphia, PA USA.
   [Alfano, C.] NCI, Bethesda, MD 20892 USA.
   [Smith, T.; Leach, C.] ACS, Atlanta, GA USA.
   [Jing, L.; Mohr, D.; Spring, B.; Berendsen, M.] Northwestern, Chicago, IL USA.
   [Palesh, O.] Standford, Palo Alto, CA USA.
   [Piper, B.] Univ Arizona, Scottsdale, AZ USA.
EM karen_mustian@urmc.rochester.edu
NR 0
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S54
EP S54
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400207
ER

PT J
AU Nansel, TR
   Iannotti, RJ
   Liu, AY
AF Nansel, Tonja R.
   Iannotti, Ronald J.
   Liu, Aiyi
TI CLINIC-INTEGRATED BEHAVIORAL INTERVENTION FOR FAMILIES OF YOUTH WITH
   TYPE 1 DIABETES: EFFECTS ON GLYCEMIC AND FAMILY MANAGEMENT OUTCOMES
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Nansel, Tonja R.; Iannotti, Ronald J.; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
EM nanselt@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S81
EP S81
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400313
ER

PT J
AU Naveed, S
   Kerr, J
   Norman, GJ
   Adams, MA
   Morgan, CG
   Langer, RD
   Macera, CA
   Alcaraz, JE
   Sallis, JF
   Allison, MA
AF Naveed, Sana
   Kerr, Jacqueline
   Norman, Gregory J.
   Adams, Marc A.
   Morgan, Cindy G.
   Langer, Robert D.
   Macera, Caroline A.
   Alcaraz, John E.
   Sallis, James F.
   Allison, Matthew A.
TI NEIGHBORHOOD FOOD ENVIRONMENTS AND INCIDENT MYOCARDIAL INFARCTION IN
   POST MENOPAUSAL WOMEN
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Naveed, Sana] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20852 USA.
   [Kerr, Jacqueline; Norman, Gregory J.; Adams, Marc A.; Morgan, Cindy G.; Langer, Robert D.] Univ Calif San Diego, San Diego, CA 92103 USA.
   [Macera, Caroline A.; Alcaraz, John E.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA.
   [Sallis, James F.; Allison, Matthew A.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA.
EM naveeds@mail.nih.gov
RI Adams, Marc/C-3513-2013
OI Adams, Marc/0000-0001-6310-1472
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S97
EP S97
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400372
ER

PT J
AU Nilsen, W
AF Nilsen, Wendy
TI NIH ADHERENCE RESEARCH NETWORK: FUNDING OPPORTUNITIES IN ADHERENCE
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
EM nilsenwj@od.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S145
EP S145
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400562
ER

PT J
AU Nilsen, W
AF Nilsen, Wendy
TI HEALTH BRANDING: MARKETING AND BRANDING TECHNIQUES IN HEALTH BEHAVIOR
   CHANGE
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Nilsen, Wendy] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
EM nilsenwj@od.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S142
EP S142
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400551
ER

PT J
AU Patrick, H
   Canevello, A
   Williams, GC
AF Patrick, Heather
   Canevello, Amy
   Williams, Geoffrey C.
TI TESTING THE TENETS OF SELF-DETERMINATION THEORY IN THE DIGITAL WORLD TO
   PROMOTE PHYSICAL ACTIVITY
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Patrick, Heather] NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA.
   [Canevello, Amy] Univ N Carolina, Charlotte, NC 28223 USA.
   [Williams, Geoffrey C.] Univ Rochester, Rochester, NY USA.
EM patrickha@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S143
EP S143
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400557
ER

PT J
AU Patrick, H
AF Patrick, Heather
TI PERSONALITY AND SOCIAL CONTEXT: MOTIVATIONAL PERSPECTIVES ON HEALTH
   BEHAVIOR
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Patrick, Heather] NCI, Hlth Behav Res Branch, Bethesda, MD 20892 USA.
EM patrickha@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S143
EP S143
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400556
ER

PT J
AU Pinard, C
   Finney-Rutten, L
   Nebeling, L
   Yaroch, A
AF Pinard, Courtney
   Finney-Rutten, Lila
   Nebeling, Linda
   Yaroch, Amy
TI EXPLORATION OF GROCERY SHOPPING BEHAVIORS AND SOCIODEMOGRAPHIC FACTORS
   ASSOCIATED WITH VENUE OF MEAL CONSUMPTION: RESULTS FROM THE NATIONAL
   CANCER INSTITUTE'S FOOD ATTITUDES AND BEHAVIORS (FAB) SURVEY
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Pinard, Courtney; Finney-Rutten, Lila; Yaroch, Amy] Gretchen Swanson Ctr Nutr, Omaha, NE 68105 USA.
   [Finney-Rutten, Lila] SAIC Inc Frederick, NCI, Frederick, MD 21701 USA.
   [Nebeling, Linda] NCI, Bethesda, MD 20892 USA.
EM cpinard@centerfornutrition.org
NR 0
TC 0
Z9 0
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S110
EP S110
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400427
ER

PT J
AU Portnoy, DB
AF Portnoy, David B.
TI HOW INFORMATIONAL GOALS AND UNCERTAINTY AFFECT HEALTH DECISION MAKING:
   OVERVIEW AND RECENT FINDINGS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Portnoy, David B.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
   [Portnoy, David B.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
EM portnoydb@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S166
EP S166
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400645
ER

PT J
AU Prados, S
   Skeath, P
   Berger, A
   Katheria, V
AF Prados, Sheila
   Skeath, Perry
   Berger, Ann
   Katheria, Vani
TI EXPLORING THE PSYCHO-SOCIO-SPIRITUAL RESPONSES OF CANCER PATIENTS AND
   SURVIVORS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Skeath, Perry; Berger, Ann] NIH, Pain & Palliat Care Serv, Bethesda, MD 20892 USA.
   [Prados, Sheila] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
   [Katheria, Vani] Georgetown Univ, Washington, DC USA.
EM pradossm@cc.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S6
EP S6
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400019
ER

PT J
AU Prestin, A
   Chou, WYS
AF Prestin, Abby
   Chou, Wen-Ying Sylvia
TI THE DESIGN AND EVALUATION OF A MEDIA-BASED COPING INTERVENTION
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Prestin, Abby; Chou, Wen-Ying Sylvia] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20852 USA.
   [Prestin, Abby] Univ Calif Santa Barbara, Goleta, CA USA.
EM abigail.prestin@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S49
EP S49
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400191
ER

PT J
AU Robertson, LB
   Schoen, RE
   Zimmerman, RK
   Terry, M
   Silverman, M
   Cooper, KL
   Dzubinski, L
   Land, SR
   Bovbjerg, DH
AF Robertson, Linda B.
   Schoen, Robert E.
   Zimmerman, Richard K.
   Terry, Martha
   Silverman, Myrna
   Cooper, Kristine L.
   Dzubinski, Lynda
   Land, Stephanie R.
   Bovbjerg, Dana H.
TI EXPLORATION OF DECISION MAKING PROCESSES OF INDIVIDUALS REGARDING A
   PREVENTATIVE VACCINE FOR COLORECTAL CANCER
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Zimmerman, Richard K.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15232 USA.
   [Land, Stephanie R.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
EM robertsonlk@upmc.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S8
EP S8
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400027
ER

PT J
AU Shah, M
   Waldstein, SR
   Zonderman, AB
AF Shah, Mauli
   Waldstein, Shari R.
   Zonderman, Alan B.
TI NONLINEAR LONGITUDINAL ASSOCIATIONS OF SLEEP DURATION WITH BLOOD
   PRESSURE
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Shah, Mauli; Waldstein, Shari R.] Univ Maryland, Baltimore, MD 21250 USA.
   [Shah, Mauli; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM maulishah@umbc.edu
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S209
EP S209
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400812
ER

PT J
AU Smith, TM
   Pinard, CA
   Oh, A
   Yaroch, AL
AF Smith, Teresa M.
   Pinard, Courtney A.
   Oh, April
   Yaroch, Amy L.
TI PSYCHOSOCIAL CORRELATES OF PHYSICAL ACTIVITY IN ADOLESCENTS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Smith, Teresa M.; Pinard, Courtney A.; Yaroch, Amy L.] Gretchen Swanson Ctr Nutr, Omaha, NE USA.
   [Smith, Teresa M.; Pinard, Courtney A.; Yaroch, Amy L.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
   [Oh, April] NCI, SAIC Inc Frederick, Frederick, MD 21701 USA.
EM tgrosser@unmc.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S274
EP S274
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092401152
ER

PT J
AU Sprung, MR
   Kisser, J
   Waldstein, SR
   Evans, MK
   Zonderman, AB
AF Sprung, Mollie R.
   Kisser, Jason
   Waldstein, Shari R.
   Evans, Michele K.
   Zonderman, Alan B.
TI PERCEIVED SOCIAL SUPPORT IS ASSOCIATED DIFFERENTIALLY WITH
   CARDIOVASCULAR RISK FACTORS IN AFRICAN AMERICAN AND WHITE MEN AND WOMEN
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Sprung, Mollie R.; Kisser, Jason; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA.
   [Evans, Michele K.; Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
EM mollie.sprung@gmail.com
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S17
EP S17
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400060
ER

PT J
AU Stover, AM
   Reeve, B
   Piper, B
   Alfano, C
   Bernstein, L
   Baumgartner, KB
   McTiernan, A
   Ballard-Barbash, R
AF Stover, Angela M.
   Reeve, Bryce
   Piper, Barbara
   Alfano, Catherine
   Bernstein, Leslie
   Baumgartner, Katherine B.
   McTiernan, Anne
   Ballard-Barbash, Rachel
TI THE PIPER FATIGUE SCALE-SHORT FORM (PFS-SF): PSYCHOMETRIC FINDINGS AND
   ITEM REDUCTION IN A COHORT OF BREAST CANCER SURVIVORS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Stover, Angela M.; Reeve, Bryce] Univ N Carolina, Chapel Hill, NC 27514 USA.
   [Piper, Barbara] Univ Arizona, Tucson, AZ USA.
   [Alfano, Catherine; Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA.
   [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
   [Baumgartner, Katherine B.] Univ Louisville, Louisville, KY 40292 USA.
   [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
EM stoveram@email.unc.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S92
EP S92
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400354
ER

PT J
AU von Wagner, C
   Klein, W
AF von Wagner, Christian
   Klein, William
TI INFORMATION PROCESSING AND DECISION MAKING ABOUT CANCER SCREENING:
   CHALLENGES AND OPPORTUNITIES
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [von Wagner, Christian] UCL, London WC1E 6BT, England.
   [Klein, William] NCI, Bethesda, MD USA.
   [Klein, William] Univ Pittsburgh, Pittsburgh, PA USA.
EM c.wagner@ucl.ac.uk
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S135
EP S135
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400523
ER

PT J
AU Wallen, GR
   Middleton, KR
   Velummylum, S
   Miller-Davis, C
   Koratich, C
   Krumlauf, K
   Handel, D
AF Wallen, Gwenyth R.
   Middleton, K. R.
   Velummylum, S.
   Miller-Davis, C.
   Koratich, C.
   Krumlauf, K.
   Handel, D.
TI CLINICAL HYPNOSIS: A STRATEGY TO MODIFY PAIN IMPACT AND DEPRESSION IN
   SICKLE CELL PATIENTS
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Wallen, Gwenyth R.; Middleton, K. R.; Velummylum, S.; Miller-Davis, C.; Koratich, C.; Krumlauf, K.; Handel, D.] NIH, Ctr Clin, Olney, MD 20832 USA.
EM gwallen@cc.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S266
EP S266
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092401120
ER

PT J
AU Waters, EA
   Kincaid, CS
   Stock, ML
   Peterson, L
   Kaufman, AR
   Muscanell, NL
   Guadagno, RE
AF Waters, Erika A.
   Kincaid, Caroline S.
   Stock, Michelle L.
   Peterson, Laurel
   Kaufman, Annette R.
   Muscanell, Nicole L.
   Guadagno, Rosanna E.
TI LIMITATIONS OF USING MULTIFACTORIAL GENETIC RISK INFORMATION TO EDUCATE
   SMOKERS ABOUT THE RISK OF TOBACCO USE
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Waters, Erika A.; Kincaid, Caroline S.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO 63110 USA.
   [Stock, Michelle L.; Peterson, Laurel] George Washington Univ, Washington, DC USA.
   [Kaufman, Annette R.] Univ Alabama, Tuscaloosa, AL USA.
   [Muscanell, Nicole L.; Guadagno, Rosanna E.] NCI, Behav Res Program, Rockville, MD USA.
EM waterse@wudosis.wustl.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S126
EP S126
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400488
ER

PT J
AU Weaver, K
   Alfano, C
   Foraker, R
   Arora, N
   Bellizzi, K
   Rowland, J
AF Weaver, Kathryn
   Alfano, Catherine
   Foraker, Randi
   Arora, Neeraj
   Bellizzi, Keith
   Rowland, Julia
TI ARE BEHAVIORAL RISK FACTORS FOR CVD ADDRESSED AMONG LONG-TERM CANCER
   SURVIVORS?
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Meeting Abstract
C1 [Weaver, Kathryn] Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA.
   [Alfano, Catherine; Arora, Neeraj; Rowland, Julia] NCI, Bethesda, MD 20892 USA.
   [Foraker, Randi] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA.
   [Bellizzi, Keith] Univ Connecticut, Storrs, CT USA.
EM keweaver@wfubmc.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD APR
PY 2012
VL 43
SU 1
BP S7
EP S7
PG 1
WC Psychology, Multidisciplinary
SC Psychology
GA 916HQ
UT WOS:000302092400024
ER

PT J
AU Miller, FW
AF Miller, Frederick W.
TI New approaches to the assessment and treatment of the idiopathic
   inflammatory myopathies
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID INCLUSION-BODY MYOSITIS; JUVENILE DERMATOMYOSITIS; INTERNATIONAL
   CONSENSUS; REFRACTORY POLYMYOSITIS; MYCOPHENOLATE-MOFETIL; ADULT;
   THERAPY; DISEASE; PATHOGENESIS; RITUXIMAB
AB The rarity and heterogeneity of the idiopathic inflammatory myopathies (IIM), and the few validated assessment tools available, have limited information to guide the management of patients with polymyositis, dermatomyositis or inclusion body myositis. In light of the need for such tools, the International Myositis Assessment and Clinical Studies Group (IMACS) was formed as a multidisciplinary consortium of rheumatologists, neurologists, dermatologists, physiatrists and other myositis experts to develop consensus and standards for the conduct and reporting of myositis studies, and to facilitate myositis research. IMACS has developed consensus core set measures of disease activity, disease damage and patient-reported outcomes, and compiled a preliminary definition of improvement. The IMACS tools assist in the evaluation of the extent of disease activity and damage, although other approaches-including key clinical features, laboratory tests, muscle T1 and short tau inversion recovery MRI and immunological markers-are also helpful. Clinical remission is a realistic objective for most patients and should be pursued aggressively to optimise outcomes. Physical therapy and rehabilitation should be applied early and consistently to achieve optimal strength and function. Treatments that have been developed for other immune-mediated diseases are also being used and tested in the IIM, and some have shown anecdotal evidence of benefit. Recent advances in understanding the pathogenesis of myositis, development of assessments and treatments for other diseases that can be applied to myositis, and international collaborations and consensus standards for evaluating the IIM, all promise improvements in the assessment and treatment of myositis in the future.
C1 NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH,Clin Res Ctr, Bethesda, MD 20892 USA.
RP Miller, FW (reprint author), NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH,Clin Res Ctr, NIH 10,Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA.
EM millerf@mail.nih.gov
OI Miller, Frederick/0000-0003-2831-9593
FU Office of Rare Diseases, NIH; Myositis Association; UK Myositis Support
   Group; American College of Rheumatology; NIH, National Institute of
   Environmental Health Sciences
FX The IMACS project has been supported in part by the Office of Rare
   Diseases, NIH; the Myositis Association; the UK Myositis Support Group
   and the American College of Rheumatology. This research was also
   supported in part by the Intramural Research Program of the NIH,
   National Institute of Environmental Health Sciences.
NR 39
TC 24
Z9 24
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD APR
PY 2012
VL 71
SU 2
BP 82
EP 85
DI 10.1136/annrheumdis-2011-200587
PG 4
WC Rheumatology
SC Rheumatology
GA 917ME
UT WOS:000302180400010
ER

PT J
AU Sanchez, C
   Pesesse, L
   Gabay, O
   Delcour, JP
   Msika, P
   Baudouin, C
   Henrotin, YE
AF Sanchez, Christelle
   Pesesse, Laurence
   Gabay, Odile
   Delcour, Jean-Pierre
   Msika, Philippe
   Baudouin, Caroline
   Henrotin, Yves E.
TI Regulation of Subchondral Bone Osteoblast Metabolism by Cyclic
   Compression
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID DEGENERATIVE JOINT DISEASE; ENDOTHELIAL GROWTH-FACTOR; PROSTAGLANDIN
   E-2; CYNOMOLGUS MACAQUES; OSTEOARTHRITIC BONE; PARATHYROID-HORMONE;
   MECHANICAL-STRESS; IN-VITRO; CELLS; EXPRESSION
AB Objective. Recent data have shown that abnormal subchondral bone remodeling plays an important role in osteoarthritis (OA) onset and progression, and it was suggested that abnormal mechanical pressure applied to the articulation was responsible for these metabolic changes. This study was undertaken to evaluate the effects of cyclic compression on osteoblasts from OA subchondral bone.
   Methods. Osteoblasts were isolated from sclerotic and nonsclerotic areas of human OA subchondral bone. After 28 days, the osteoblasts were surrounded by an abundant extracellular matrix and formed a resistant membrane, which was submitted to cyclic compression (1 MPa at 1 Hz) for 4 hours. Gene expression was evaluated by reverse transcription-polymerase chain reaction. Protein production in culture supernatants was quantified by enzyme-linked immunosorbent assay or visualized by immunohistochemistry.
   Results. Compression increased the expression of genes coding for interleukin-6 (IL-6), cyclooxygenase 2, RANKL, fibroblast growth factor 2, IL-8, matrix metalloproteinase 3 (MMP-3), MMP-9, and MMP-13 but reduced the expression of osteoprotegerin in osteoblasts in both sclerotic and nonsclerotic areas. Col alpha 1(I) and MMP-2 were not significantly affected by mechanical stimuli. Nonsclerotic osteoblasts were significantly more sensitive to compression than sclerotic ones, but after compression, differences in messenger RNA levels between nonsclerotic and sclerotic osteoblasts were largely reduced or even abolished. Under basal conditions, sclerotic osteoblasts expressed similar levels of alpha 5, alpha v, beta 1, and beta 3 integrins and CD44 as nonsclerotic osteoblasts but 30% less connexin 43, an important mechanoreceptor.
   Conclusion. Genes involved in subchondral bone sclerosis are mechanosensitive. After compression, nonsclerotic and sclerotic osteoblasts expressed a similar phenotype, suggesting that compression could be responsible for the phenotype changes in OA subchondral osteoblasts.
C1 [Sanchez, Christelle; Pesesse, Laurence; Henrotin, Yves E.] Univ Liege, Liege, Belgium.
   [Gabay, Odile] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Delcour, Jean-Pierre] Ctr Hosp Bois de Abbaye, Seraing, Belgium.
   [Msika, Philippe; Baudouin, Caroline] Labs Expansci, Epernon, France.
RP Henrotin, YE (reprint author), Inst Pathol, Bone & Cartilage Res Unit, CHU Bat B23, B-4000 Liege, Belgium.
EM yhenrotin@ulg.ac.be
FU National Institute of Arthritis and Musculoskeletal Diseases, NIH; FNRS
FX Supported in part by the Intramural Research Program of the National
   Institute of Arthritis and Musculoskeletal Diseases, NIH. Dr. Sanchez is
   a postdoctoral researcher at the FNRS; her work was supported by a
   postdoctoral research grant from the FNRS.
NR 49
TC 29
Z9 29
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD APR
PY 2012
VL 64
IS 4
BP 1193
EP 1203
DI 10.1002/art.33445
PG 11
WC Rheumatology
SC Rheumatology
GA 921KC
UT WOS:000302475500030
PM 22034083
ER

PT J
AU Pang, T
   Wang, J
   Benicky, J
   Saavedra, JM
AF Pang, Tao
   Wang, Juan
   Benicky, Julius
   Saavedra, Juan M.
TI Minocycline ameliorates LPS-induced inflammation in human monocytes by
   novel mechanisms including LOX-1, Nur77 and LITAF inhibition
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Article
DE Minocycline; Lipopolysaccharide; Nuclear receptor; LITAF; Inflammation;
   Human monocytes
ID NUCLEAR RECEPTOR NUR77; INNATE IMMUNE-RESPONSE; TNF-ALPHA FACTOR;
   NF-KAPPA-B; SIGNALING PATHWAYS; PI3K-AKT PATHWAY; INDUCED CYTOKINE;
   GENE-EXPRESSION; CELL-CULTURES; OXIDIZED LDL
AB Background: Minocycline exhibits anti-inflammatory properties independent of its antibiotic activity, ameliorating inflammatory responses in monocytes and macrophages. However, the mechanisms of minocycline anti-inflammatory effects are only partially understood.
   Methods: Human circulating monocytes were cultured in the presence of lipopolysaccharide (LPS), 50 ng/ml, and minocycline (10-40 mu M). Gene expression was determined by RT-PCR, cytokine and prostaglandin E-2 (PGE(2)) release by ELISA, protein expression, phosphorylation and nuclear translocation by Western blotting.
   Results: Minocycline significantly reduced the inflammatory response in LPS-challenged monocytes, decreasing U'S-induced transcription of pro-inflammatory tumor-necrosis factor alpha (TNF-alpha), interleukin-1 beta, interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), and the LPS-stimulated TNF-alpha, IL-6 and PGE(2) release. Minocycline inhibited LPS-induced activation of the lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), NF-kappa B, LPS-induced TNF-alpha factor (LITAF) and the Nur77 nuclear receptor. Mechanisms involved in the anti-inflammatory effects of minocycline include a reduction of LPS-stimulated p38 mitogen-activated protein kinase (p38 MAPK) activation and stimulation of the phosphoinositide 3-kinase (PI3K)/Ala pathway.
   Conclusions: We provide novel evidence demonstrating that the anti-inflammatory effects of minocycline in human monocytes include, in addition to decreased NF-kappa B activation, abrogation of the U'S-stimulated LOX-1, LITAF, Nur77 pathways, p38 MAPK inhibition and PI3K/Akt activation. Our results reveal that minocycline inhibits points of convergence of distinct and interacting signaling pathways mediating multiple inflammatory signals which may influence monocyte activation, traffic and recruitment into the brain.
   General significance: Our results in primary human monocytes contribute to explain the profound anti-inflammatory and protective effects of minocycline in cardiovascular and neurological diseases and may have direct translational relevance. Published by Elsevier B.V.
C1 [Pang, Tao; Wang, Juan; Benicky, Julius; Saavedra, Juan M.] NIMH, Pharmacol Sect, DIRP, NIH,DHHS, Bethesda, MD 20892 USA.
RP Pang, T (reprint author), NIMH, Pharmacol Sect, DIRP, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 20-57, Bethesda, MD 20892 USA.
EM pangt@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health,
   Department of Health and Human Services, USA
FX This study was supported by the Division of Intramural Research
   Programs, National Institute of Mental Health, National Institutes of
   Health, Department of Health and Human Services, USA.
NR 43
TC 24
Z9 26
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD APR
PY 2012
VL 1820
IS 4
BP 503
EP 510
DI 10.1016/j.bbagen.2012.01.011
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 921OK
UT WOS:000302486700007
PM 22306153
ER

PT J
AU Huang, JD
   Amaral, J
   Lee, JW
   Larrayoz, IM
   Rodriguez, IR
AF Huang, Jiahn-Dar
   Amaral, Juan
   Lee, Jung Wha
   Larrayoz, Ignacio M.
   Rodriguez, Ignacio R.
TI Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and
   inhibits choroidal neovascularization
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE ER stress; 7-ketocholesterol; Inflammation; Sterculic acid; CHOP; RPE
ID LOW-DENSITY-LIPOPROTEIN; MACULAR DEGENERATION; CYTOTOXICITY;
   CHOLESTEROL; OXIDATION; PRODUCTS; CELLS
AB Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer's disease and age-related macular degeneration. Sterculic acid demonstrated to be 5-10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration. Published by Elsevier B.V.
C1 [Huang, Jiahn-Dar; Amaral, Juan; Lee, Jung Wha; Larrayoz, Ignacio M.; Rodriguez, Ignacio R.] NEI, NIH, Sect Mech Retinal Dis, LRCMB, Bethesda, MD 20892 USA.
   [Larrayoz, Ignacio M.] Ctr Biomed Res La Rioja CIBIR, Angiogenesis Unit, La Rioja, Spain.
RP Rodriguez, IR (reprint author), NEI, NIH, Sect Mech Retinal Dis, LRCMB, 6 Ctr Dr,MSC0608,Bldg 6 Rm 136, Bethesda, MD 20892 USA.
EM rodriguezi@nei.nih.gov
RI Larrayoz, Ignacio/I-5613-2012
OI Larrayoz, Ignacio/0000-0003-1629-152X
FU National Eye Institute
FX The authors would like to thank Dr. Maria Campos at the NEI's Biological
   Imaging Core facility for her assistance in imaging of the laser
   lesions. This work is supported by National Eye Institute Intramural
   Research Program.
NR 44
TC 12
Z9 12
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD APR
PY 2012
VL 1821
IS 4
BP 637
EP 646
DI 10.1016/j.bbalip.2012.01.013
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 921OI
UT WOS:000302486500009
PM 22342272
ER

PT J
AU Aghaeepour, N
   Chattopadhyay, PK
   Ganesan, A
   O'Neill, K
   Zare, H
   Jalali, A
   Hoos, HH
   Roederer, M
   Brinkman, RR
AF Aghaeepour, Nima
   Chattopadhyay, Pratip K.
   Ganesan, Anuradha
   O'Neill, Kieran
   Zare, Habil
   Jalali, Adrin
   Hoos, Holger H.
   Roederer, Mario
   Brinkman, Ryan R.
TI Early immunologic correlates of HIV protection can be identified from
   computational analysis of complex multivariate T-cell flow cytometry
   assays(*)
SO BIOINFORMATICS
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; VACCINE ENTERPRISE; MASS CYTOMETRY; SIV
   INFECTION; STEM-CELLS; FUTURE; TETRAMERS; RESPONSES; SURVIVAL; HAART
AB Motivation: Polychromatic flow cytometry (PFC), has enormous power as a tool to dissect complex immune responses (such as those observed in HIV disease) at a single cell level. However, analysis tools are severely lacking. Although high-throughput systems allow rapid data collection from large cohorts, manual data analysis can take months. Moreover, identification of cell populations can be subjective and analysts rarely examine the entirety of the multidimensional dataset (focusing instead on a limited number of subsets, the biology of which has usually already been well-described). Thus, the value of PFC as a discovery tool is largely wasted.
   Results: To address this problem, we developed a computational approach that automatically reveals all possible cell subsets. From tens of thousands of subsets, those that correlate strongly with clinical outcome are selected and grouped. Within each group, markers that have minimal relevance to the biological outcome are removed, thereby distilling the complex dataset into the simplest, most clinically relevant subsets. This allows complex information from PFC studies to be translated into clinical or resource-poor settings, where multiparametric analysis is less feasible. We demonstrate the utility of this approach in a large (n=466), retrospective, 14-parameter PFC study of early HIV infection, where we identify three T-cell subsets that strongly predict progression to AIDS (only one of which was identified by an initial manual analysis).
C1 [Aghaeepour, Nima; O'Neill, Kieran; Zare, Habil; Jalali, Adrin; Brinkman, Ryan R.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
   [Chattopadhyay, Pratip K.; Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
   [Ganesan, Anuradha] Walter Reed Natl Mil Med Ctr, Rockville, MD 20889 USA.
   [Zare, Habil; Hoos, Holger H.] Univ British Columbia, Dept Comp Sci, Vancouver, BC V5Z 4S6, Canada.
   [Brinkman, Ryan R.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4S6, Canada.
   [Aghaeepour, Nima] Univ British Columbia, CIHR MSFHR Strateg Training Bioinformat Hlth Res, Vancouver, BC V5Z 4S6, Canada.
RP Brinkman, RR (reprint author), British Columbia Canc Agcy, Terry Fox Lab, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM rbrinkman@bccrc.ca
RI Brinkman, Ryan/B-1108-2008; 
OI Brinkman, Ryan/0000-0002-9765-2990; O'Neill, Kieran/0000-0001-7609-5905;
   Zare, Habil/0000-0001-5902-6238; Chattopadhyay,
   Pratip/0000-0002-5457-9666
FU NIAID; NIH/NIBIB [EB008400]; NSERC; NIH [HSN261200800001E]; NCI;
   Infectious Disease Clinical Research Program; Uniformed Services
   University of the Health Sciences; Terry Foundation; Terry Fox Research
   Institute; UBC4YF; CIHR/MSFHR; Michael Smith Foundation for Health
   Research
FX This work was supported by NIAID Intramural Research Program; NIH/NIBIB
   grant EB008400; an NSERC discovery grant held by HHH; NIH (contract
   HSN261200800001E); NCI; Infectious Disease Clinical Research Program;
   Uniformed Services University of the Health Sciences, The Terry
   Foundation and The Terry Fox Research Institute. NA was supported by a
   UBC4YF scholarship and a CIHR/MSFHR scholarship. RRB was supported in
   part by a Michael Smith Foundation for Health Research Scholar Award.
   This research was enabled by the use of computing resources provided by
   the Western Canada Research Grid (WestGrid) and Compute/Calcul Canada.
NR 41
TC 36
Z9 36
U1 2
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD APR 1
PY 2012
VL 28
IS 7
BP 1009
EP 1016
DI 10.1093/bioinformatics/bts082
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Computer Science, Interdisciplinary Applications; Mathematical &
   Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Computer Science; Mathematical & Computational Biology; Mathematics
GA 919CR
UT WOS:000302298900014
PM 22383736
ER

PT J
AU Samson, F
   Shrager, R
   Tai, CH
   Sam, V
   Lee, B
   Munson, PJ
   Gibrat, JF
   Garnier, J
AF Samson, Franck
   Shrager, Richard
   Tai, Chin-Hsien
   Sam, Vichetra
   Lee, Byungkook
   Munson, Peter J.
   Gibrat, Jean-Francois
   Garnier, Jean
TI DOMIRE: a web server for identifying structural domains and their
   neighbors in proteins
SO BIOINFORMATICS
LA English
DT Article
AB The DOMIRE web server implements a novel, automatic, protein structural domain assignment procedure based on 3D substructures of the query protein which are also found within structures of a non-redundant protein database. These common 3D substructures are transformed into a co-occurrence matrix that offers a global view of the protein domain organization. Three different algorithms are employed to define structural domain boundaries from this co-occurrence matrix. For each query, a list of structural neighbors and their alignments are provided. DOMIRE, by displaying the protein structural domain organization, can be a useful tool for defining protein common cores and for unravelling the evolutionary relationship between different proteins.
C1 [Samson, Franck; Gibrat, Jean-Francois; Garnier, Jean] INRA, UR1077, Unite Math Informat & Genome, F-78350 Jouy En Josas, France.
   [Shrager, Richard; Sam, Vichetra; Munson, Peter J.; Garnier, Jean] NCI, Math & Stat Comp Lab, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA.
   [Tai, Chin-Hsien; Lee, Byungkook] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Garnier, J (reprint author), INRA, UR1077, Unite Math Informat & Genome, F-78350 Jouy En Josas, France.
EM jean.garnier@jouy.inra.fr
FU Center for Cancer Research, National Cancer Institute; Division of
   Computational Bioscience, Center for Information Technology, NIH in USA;
   Institut National de la Recherche Agronomique in France
FX Intramural Research Program of the Center for Cancer Research, National
   Cancer Institute and of the Division of Computational Bioscience, Center
   for Information Technology, NIH in USA and financially supported by the
   Institut National de la Recherche Agronomique in France (in part).
NR 5
TC 2
Z9 2
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 APR 1
PY 2012
VL 28
IS 7
BP 1040
EP 1041
DI 10.1093/bioinformatics/bts076
PG 2
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 919CR
UT WOS:000302298900024
PM 22345617
ER

PT J
AU Xie, G
   Nie, T
   Mackenzie, GG
   Sun, Y
   Huang, L
   Ouyang, N
   Alston, N
   Zhu, C
   Murray, OT
   Constantinides, PP
   Kopelovich, L
   Rigas, B
AF Xie, G.
   Nie, T.
   Mackenzie, G. G.
   Sun, Y.
   Huang, L.
   Ouyang, N.
   Alston, N.
   Zhu, C.
   Murray, O. T.
   Constantinides, P. P.
   Kopelovich, L.
   Rigas, B.
TI The metabolism and pharmacokinetics of phospho-sulindac (OXT-328) and
   the effect of difluoromethylornithine
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE metabolism; pharmacokinetics; phospho-sulindac; difluoromethylornithine;
   liver microsomes; gastrointestinal toxicity
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER; SULFOXIDE REDUCTION;
   LIVER-MICROSOMES; RAT-LIVER; IN-VITRO; NSAIDS; ASPIRIN; PREVENTION;
   APOPTOSIS
AB BACKGROUND AND PURPOSE
   Phospho-sulindac (PS; OXT-328) prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO). Here, we explored its metabolism and pharmacokinetics.
   EXPERIMENTAL APPROACH
   PS metabolism was studied in cultured cells, liver microsomes and cytosol, intestinal microsomes and in mice. Pharmacokinetics and biodistribution of PS were studied in mice.
   KEY RESULTS
   PS undergoes reduction and oxidation yielding PS sulphide and PS sulphone; is hydrolysed releasing sulindac, which generates sulindac sulphide (SSide) and sulindac sulphone (SSone), all of which are glucuronidated. Liver and intestinal microsomes metabolized PS extensively but cultured cells converted only 10% of it to PS sulphide and PS sulphone. In mice, oral PS is rapidly absorbed, metabolized and distributed to the blood and other tissues. PS survives only partially intact in blood; of its three major metabolites (sulindac, SSide and SSone), sulindac has the highest Cmax and SSone the highest t1/ 2; their AUC0-24h are similar. Compared with conventional sulindac, PS generated more SSone but less SSide, which may contribute to the safety of PS. In the gastroduodenal wall of mice, 71% of PS was intact; sulindac, SSide and SSone together accounted for < 30% of the total. This finding may explain the lack of gastrointestinal toxicity by PS. DFMO had no effect on PS metabolism but significantly reduced drug level in mouse plasma and other tissues.
   CONCLUSIONS AND IMPLICATIONS
   Our findings establish the metabolism of PS define its pharmacokinetics and biodistribution, describe its interactions with DFMO and largely explain its gastrointestinal safety.
C1 [Rigas, B.] SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, Stony Brook, NY 11794 USA.
   [Constantinides, P. P.] Medicon Pharmaceut Inc, Stony Brook, NY USA.
   [Kopelovich, L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Rigas, B (reprint author), SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, T17-080, Stony Brook, NY 11794 USA.
EM basil.rigas@stonybrook.edu
FU National Institute of Health [R01-CA139453, N01-CN-43302, RCA153662A,
   HHSN261201000109C]; National Cancer Institute; NIH/NCRR [1 S10
   RR023680-1]
FX This work was supported by the National Institute of Health Grants
   R01-CA139453, N01-CN-43302 WA#7, RCA153662A and HHSN261201000109C. This
   research was also supported in part by the Intramural Research Program
   of the National Cancer Institute. We thank R. Rieger and T. Koller,
   Stony Brook University, for the expert LC-MS/MS analysis of our samples
   and the shared instrumentation grant, NIH/NCRR 1 S10 RR023680-1.
NR 48
TC 12
Z9 12
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD APR
PY 2012
VL 165
IS 7
BP 2152
EP 2166
DI 10.1111/j.1476-5381.2011.01705.x
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 905OJ
UT WOS:000301281700015
PM 21955327
ER

PT J
AU DuBois, SG
   Shusterman, S
   Reid, JM
   Ingle, AM
   Ahern, CH
   Baruchel, S
   Glade-Bender, J
   Ivy, P
   Adamson, PC
   Blaney, SM
AF DuBois, Steven G.
   Shusterman, Suzanne
   Reid, Joel M.
   Ingle, Ashish M.
   Ahern, Charlotte H.
   Baruchel, Sylvain
   Glade-Bender, Julia
   Ivy, Percy
   Adamson, Peter C.
   Blaney, Susan M.
TI Tolerability and pharmacokinetic profile of a sunitinib powder
   formulation in pediatric patients with refractory solid tumors: a
   Children's Oncology Group study
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Sunitinib; Pediatric; Pharmacokinetics; Formulation
ID TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; ANTITUMOR-ACTIVITY;
   PHASE-I; MALATE SU11248; GROWTH-FACTOR; IMATINIB; CANCER; VIVO
AB Purpose Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m(2)/day. This study was conducted to evaluate sunitinib given as a powder formulation.
   Methods Sunitinib 15 mg/m(2) was administered orally daily for 4 weeks on/2 weeks off to patients <21 years old with refractory solid tumors. Sunitinib capsules were opened, and the powder sprinkled onto applesauce or yogurt. Plasma levels of sunitinib and an active metabolite, SU12662, were measured, and pharmacokinetic parameters were estimated.
   Results 12 patients, median age 13 (range 4-21) years, were treated. The most common first-cycle toxicities were leucopenia (n = 6), fatigue (n = 5), neutropenia (n = 4), and hypertension (n = 4). Three patients had dose-limiting toxicities (DLTs) in cycle 1 (dizziness/back pain, hand-foot syndrome, and intratumoral hemorrhage/hypoxia). A median peak plasma sunitinib concentration of 21 (range 636) ng/ml was reached at a median of 4 (range 4-8) h after the first dose. The median exposure (AUC(0-48)) was 585 (range 196-1,059) h ng/l. The median half-life was 23 (range 13-36) h. The median trough concentration measured before day 14 dosing was 32 (range 12-58) ng/ml.
   Conclusions The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules. The powder formulation allows patients unable to swallow capsules to receive sunitinib.
C1 [DuBois, Steven G.] UCSF Sch Med, Dept Pediat, San Francisco, CA 94143 USA.
   [Shusterman, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Dept Pediat, Boston, MA 02115 USA.
   [Reid, Joel M.] Mayo Coll Med, Dept Pharmacol, Rochester, MN USA.
   [Ingle, Ashish M.] Childrens Oncol Grp Operat Ctr, Arcadia, CA USA.
   [Ahern, Charlotte H.] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Baruchel, Sylvain] Hosp Sick Children, Dept Hematol Oncol, Toronto, ON M5G 1X8, Canada.
   [Glade-Bender, Julia] Columbia Univ, Dept Pediat, Morgan Stanley Childrens Hosp, Sch Med, New York, NY 10027 USA.
   [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   [Adamson, Peter C.] Univ Penn, Childrens Hosp Philadelphia, Dept Oncol, Philadelphia, PA 19104 USA.
   [Blaney, Susan M.] Baylor Coll Med, Dept Pediat, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
RP DuBois, SG (reprint author), UCSF Sch Med, Dept Pediat, 505 Parnassus Ave,M646, San Francisco, CA 94143 USA.
EM duboiss@peds.ucsf.edu
FU Campini Foundation; Pfizer; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130]; NCI
   [U01 CA97452]
FX This study was supported by the Campini Foundation, Pfizer, NIH/NCRR/OD
   UCSF-CTSI Grant Number KL2 RR024130, and NCI U01 CA97452. Pfizer
   provided partial support for the analyses of sunitinib pharmacokinetics.
NR 18
TC 13
Z9 14
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD APR
PY 2012
VL 69
IS 4
BP 1021
EP 1027
DI 10.1007/s00280-011-1798-2
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 919LF
UT WOS:000302327300020
PM 22179104
ER

PT J
AU Iyer, G
   Morris, MJ
   Rathkopf, D
   Slovin, SF
   Steers, M
   Larson, SM
   Schwartz, LH
   Curley, T
   DeLaCruz, A
   Ye, Q
   Heller, G
   Egorin, MJ
   Ivy, SP
   Rosen, N
   Scher, HI
   Solit, DB
AF Iyer, Gopa
   Morris, Michael J.
   Rathkopf, Dana
   Slovin, Susan F.
   Steers, Macaulay
   Larson, Steven M.
   Schwartz, Lawrence H.
   Curley, Tracy
   DeLaCruz, Anthony
   Ye, Qing
   Heller, Glenn
   Egorin, Merrill J.
   Ivy, S. Percy
   Rosen, Neal
   Scher, Howard I.
   Solit, David B.
TI A phase I trial of docetaxel and pulse-dose
   17-allylamino-17-demethoxygeldanamycin in adult patients with solid
   tumors
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE 17-AAG; Geldanamycin; Hsp90; Docetaxel; Phase I
ID ADVANCED CANCER; HSP90 FUNCTION; BREAST-CANCER; LUNG-CANCER;
   17-ALLYLAMINO; GELDANAMYCIN; PACLITAXEL; INHIBITOR; COMPLEX;
   17-DEMETHOXYGELDANAMYCIN
AB Purpose To define maximum tolerated dose (MTD), clinical toxicities, and pharmacokinetics of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when administered in combination with docetaxel once every 21 days in patients with advanced solid tumor malignancies.
   Experimental design Docetaxel was administered over 1 h at doses of 55, 70, and 75 mg/m(2). 17-AAG was administered over 1-2 h, following the completion of the docetaxel infusion, at escalating doses ranging from 80 to 650 mg/m(2) in 12 patient cohorts. Serum was collected for pharmacokinetic and pharmacodynamic studies during cycle 1. Docetaxel, 17-AAG, and 17-AG levels were determined by high-performance liquid chromatography. Biologic effects of 17-AAG were monitored in peripheral blood mononuclear cells by immunoblot.
   Results Forty-nine patients received docetaxel and 17-AAG. The most common all-cause grade 3 and 4 toxicities were leukopenia, lymphopenia, and neutropenia. An MTD was not deWned; however, three dose-limiting toxicities were observed, including 2 incidences of neutropenic fever and 1 of junctional bradycardia. Dose escalation was halted at docetaxel 75 mg/m(2)-17-AAG 650 mg/m(2) due to delayed toxicities attributed to patient intolerance of the DMSO-based 17-AAG formulation. Of 46 evaluable patients, 1 patient with lung cancer experienced a partial response. Minor responses were observed in patients with lung, prostate, melanoma, and bladder cancers. A correlation between reduced docetaxel clearance and 17-AAG dose level was observed.
   Conclusions The combination of docetaxel and 17-AAG was well tolerated in adult patients with solid tumors, although patient intolerance to the DMSO formulation precluded further dose escalation. The recommended phase II dose is docetaxel 70 mg/m(2) and 17-AAG 500 mg/m(2).
C1 [Iyer, Gopa; Morris, Michael J.; Rathkopf, Dana; Slovin, Susan F.; Steers, Macaulay; Curley, Tracy; DeLaCruz, Anthony; Rosen, Neal; Scher, Howard I.; Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
   [Larson, Steven M.] Mem Sloan Kettering Canc Ctr, Dept Nucl Med, New York, NY 10021 USA.
   [Schwartz, Lawrence H.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
   [Ye, Qing; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol & Chem, New York, NY 10021 USA.
   [Heller, Glenn] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10021 USA.
   [Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Mol Therapeut Drug Discovery Program, Pittsburgh, PA USA.
   [Ivy, S. Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Ctr, Bethesda, MD 20892 USA.
RP Solit, DB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
EM solitd@mskcc.org
OI Rathkopf, Dana/0000-0002-4503-7582; Morris, Michael
   J./0000-0002-9454-0096
FU National Cancer Institute [P50-CA92629, U01-CA69856]
FX We would like to thank Kin Tse for his assistance with data collection
   and analysis. National Cancer Institute grants P50-CA92629 and
   U01-CA69856 and the generous support of the Prostate Cancer Foundation.
NR 33
TC 18
Z9 18
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD APR
PY 2012
VL 69
IS 4
BP 1089
EP 1097
DI 10.1007/s00280-011-1789-3
PG 9
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 919LF
UT WOS:000302327300027
PM 22124669
ER

PT J
AU Huo, DZ
   Zheng, YL
   Ogundiran, TO
   Adebamowo, C
   Nathanson, KL
   Domchek, SM
   Rebbeck, TR
   Simon, MS
   John, EM
   Hennis, A
   Nemesure, B
   Wu, SY
   Leske, MC
   Ambs, S
   Niu, Q
   Zhang, J
   Cox, NJ
   Olopade, OI
AF Huo, Dezheng
   Zheng, Yonglan
   Ogundiran, Temidayo O.
   Adebamowo, Clement
   Nathanson, Katherine L.
   Domchek, Susan M.
   Rebbeck, Timothy R.
   Simon, Michael S.
   John, Esther M.
   Hennis, Anselm
   Nemesure, Barbara
   Wu, Suh-Yuh
   Leske, M. Cristina
   Ambs, Stefan
   Niu, Qun
   Zhang, Jing
   Cox, Nancy J.
   Olopade, Olufunmilayo I.
TI Evaluation of 19 susceptibility loci of breast cancer in women of
   African ancestry
SO CARCINOGENESIS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; AMERICAN WOMEN; CONFER SUSCEPTIBILITY;
   POPULATION-STRUCTURE; COMMON VARIANTS; GENOTYPE DATA; RISK; FGFR2;
   ESTROGEN; POLYMORPHISMS
AB Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case-control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04-1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10-1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00-1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer.
C1 [Huo, Dezheng] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
   [Zheng, Yonglan; Niu, Qun; Zhang, Jing; Cox, Nancy J.; Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Ogundiran, Temidayo O.] Univ Ibadan, Dept Surg, Coll Med, Ibadan, Nigeria.
   [Adebamowo, Clement] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
   [Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
   [Rebbeck, Timothy R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA.
   [John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
   [John, Esther M.] Stanford Canc Inst, Stanford, CA USA.
   [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
   [Hennis, Anselm] Univ W Indies, Res Inst, Chron Dis Res Ctr & Trop Med, Bridgetown, Barbados.
   [Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
   [Ambs, Stefan] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
RP Huo, DZ (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM dhuo@health.bsd.uchicago.edu
OI Nathanson, Katherine/0000-0002-6740-0901; Adebamowo,
   Clement/0000-0002-6571-2880
FU National Cancer Institute [R01CA141712, P01CA82707]; Breast Cancer
   Research Foundation; United States National Cancer Institute, National
   Institutes of Health [RFA-CA-06-503]; Georgetown University Medical
   Center Informatics Support Center [HHSN261200900010C]
FX National Cancer Institute (R01CA141712 and P01CA82707). Support was also
   given by the Breast Cancer Research Foundation. The Northern California
   site of the Breast Cancer Family Registry (BCFR) was supported by the
   United States National Cancer Institute, National Institutes of Health
   under (RFA-CA-06-503) and through cooperative agreements with members of
   the BCFR and Principal Investigators, including the Northern California
   Cancer Center (U01 CA69417) and Georgetown University Medical Center
   Informatics Support Center (HHSN261200900010C).
NR 44
TC 39
Z9 40
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD APR
PY 2012
VL 33
IS 4
BP 835
EP 840
DI 10.1093/carcin/bgs093
PG 6
WC Oncology
SC Oncology
GA 921RC
UT WOS:000302493800014
PM 22357627
ER

PT J
AU Ahmet, I
   Turner, T
   Lakatta, EG
   Talan, MI
AF Ahmet, Ismayil
   Turner, Tia
   Lakatta, Edward G.
   Talan, Mark I.
TI Fenoterol Enantiomers Do Not Possess Beneficial Therapeutic Properties
   of Their Racemic Mixture in the Rat Model of Post Myocardial Infarction
   Dilated Cardiomyopathy
SO CARDIOVASCULAR DRUGS AND THERAPY
LA English
DT Article
DE Chronic heart failure; Cardiac remodeling; beta(2) adrenergic receptor
   agonists; Fenoterol; Stereoisomers of fenoterol
ID CARDIAC MYOCYTES; ISCHEMIC CARDIOMYOPATHY; CELL-DEATH;
   BETA(2)-ADRENOCEPTOR; STIMULATION; DERIVATIVES; PROTEINS; SURVIVAL;
   AGONIST
AB A salutary effect of beta(2) adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM.
   Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography.
   Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first 2 months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective.
   The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM.
C1 [Ahmet, Ismayil; Turner, Tia; Lakatta, Edward G.; Talan, Mark I.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA.
RP Talan, MI (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM talanm@grc.nia.nih.gov
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
   of the NIH, National Institute on Aging.
NR 17
TC 2
Z9 2
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-3206
J9 CARDIOVASC DRUG THER
JI Cardiovasc. Drugs Ther.
PD APR
PY 2012
VL 26
IS 2
BP 101
EP 108
DI 10.1007/s10557-011-6366-9
PG 8
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 918XS
UT WOS:000302285500003
PM 22328006
ER

PT J
AU Liu, XD
   Xu, LQ
   Chen, QQ
   Sun, LG
   Wang, YH
   Yan, H
   Liu, Y
   Luo, YH
   Huang, J
AF Liu, Xiaodong
   Xu, Liqiang
   Chen, Qianqian
   Sun, Liguang
   Wang, Yuhong
   Yan, Hong
   Liu, Yi
   Luo, Yuhan
   Huang, Jing
TI Historical change of mercury pollution in remote Yongle archipelago,
   South China Sea
SO CHEMOSPHERE
LA English
DT Article
DE South China Sea; Yongle archipelago; Hg pollution; Anthropogenic Hg
   flux; Ornithogenic sediments
ID POLYCYCLIC AROMATIC-HYDROCARBONS; LAKE SEDIMENT CORES; PEARL RIVER
   ESTUARY; ATMOSPHERIC MERCURY; GEOCHEMICAL EVIDENCE; EMISSIONS;
   DEPOSITION; TRENDS; FLUXES; SILVER
AB We collected three ornithogenic coral sand sedimentary profiles from Jinyin Island, Jinqing Island and Guangjin Island of Yongle archipelago, South China Sea and reconstructed the deposition flux of anthropogenic Hg over the past 700 years in the study area. On the whole, the anthropogenic Hg flux is relatively low; it remained at a low level before the Industrial Revolution with a small peak at about 1450-1550 AD, which may record the enhanced metallurgy activity in Ming Dynasty of China. During the 20th century, the deposition flux of anthropogenic Hg increased rapidly, but two troughs occurred during the periods around 1940s and 1970s, corresponding to the economic depression caused by World War II, Civil War in China (1945-1949), and the Culture Revolution (1966-1976) in China. Since the 1970s the deposition flux of anthropogenic Hg has been persistently increasing, apparently the result of fast economic development in East and Southeast Asia countries around South China Sea. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Liu, Xiaodong; Xu, Liqiang; Chen, Qianqian; Sun, Liguang; Yan, Hong; Liu, Yi; Luo, Yuhan; Huang, Jing] Univ Sci & Technol China, Inst Polar Environm, Sch Earth & Space Sci, Hefei 230026, Anhui, Peoples R China.
   [Wang, Yuhong] NIH, NIH Chem Genom Ctr, Rockville, MD 20850 USA.
RP Liu, XD (reprint author), Univ Sci & Technol China, Inst Polar Environm, Sch Earth & Space Sci, Hefei 230026, Anhui, Peoples R China.
EM ycx@ustc.edu.cn; slg@ustc.edu.cn
RI Yan, Hong/I-8970-2014
FU National Natural Science Foundation of China [40730107, 40876096];
   Ministry of Education of China's Ph.D. Programs Foundation for the new
   teachers [20093402120004]; CAS [KZCX2-EW-QN50]
FX This work was funded by the National Natural Science Foundation of China
   (Nos. 40730107, 40876096), the Ministry of Education of China's Ph.D.
   Programs Foundation for the new teachers (20093402120004), Knowledge
   Innovation Program of CAS (KZCX2-EW-QN50). All members of field study
   team, including the Chinese People's Liberation Army, are acknowledged
   for their help in sample collection. We thank two anonymous reviewers
   and editor for their constructive comments on this manuscript.
NR 60
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U1 7
U2 52
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0045-6535
J9 CHEMOSPHERE
JI Chemosphere
PD APR
PY 2012
VL 87
IS 5
BP 549
EP 556
DI 10.1016/j.chemosphere.2011.12.065
PG 8
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 922CJ
UT WOS:000302524100016
PM 22284978
ER

PT J
AU Lee, D
   Schwope, DM
   Milman, G
   Barnes, AJ
   Gorelick, DA
   Huestis, MA
AF Lee, Dayong
   Schwope, David M.
   Milman, Garry
   Barnes, Allan J.
   Gorelick, David A.
   Huestis, Marilyn A.
TI Cannabinoid Disposition in Oral Fluid after Controlled Smoked Cannabis
SO CLINICAL CHEMISTRY
LA English
DT Article
ID 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; CYTOCHROME-P450
   EXPRESSION; PHARMACOKINETIC PROPERTIES; DELTA(9)-TETRAHYDROCANNABINOL;
   METABOLISM; MARIJUANA; DRUGS; THC; TETRAHYDROCANNABINOL; IDENTIFICATION
AB BACKGROUND: We measured Delta(9)-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) disposition in oral fluid (OF) following controlled cannabis smoking to evaluate whether monitoring multiple cannabinoids in OF improved OF test interpretation.
   METHODS: Cannabis smokers provided written informed consent for this institutional review board-approved study. OF was collected with the Quantisal (TM) device following ad libitum smoking of one 6.8% THC cigarette. Cannabinoids were quantified by 2-dimensional GC-MS. We evaluated 8 alternative cutoffs based on different drug testing program needs.
   RESULTS: 10 participants provided 86 OF samples -0.5 h before and 0.25, 0.5, 1, 2, 3, 4, 6, and 22 h after initiation of smoking. Before smoking, OF samples of 4 and 9 participants were positive for THC and THCCOOH, respectively, but none were positive for CBD and CBN. Maximum THC, CBD, and CBN concentrations occurred within 0.5 h, with medians of 644, 30.4, and 49.0 mu g/L, respectively. All samples were THC positive at 6 h (2.1-44.4 mu g/L), and 4 of 6 were positive at 22 h. CBD and CBN were positive only up to 6 h in 3 (0.6-2.1 mu g/L) and 4 (1.0-4.4 mu g/L) participants, respectively. The median maximum THCCOOH OF concentration was 115 ng/L, with all samples positive to 6 h (14.8-263 ng/L) and 5 of 6 positive at 22 h.
   CONCLUSIONS: By quantifying multiple cannabinoids and evaluating different analytical cutoffs after controlled cannabis smoking, we determined windows of drug detection, found suggested markers of recent smoking, and minimized the potential for passive contamination. (C) 2011 American Association for Clinical Chemistry
C1 [Huestis, Marilyn A.] NIDA, IRP, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd Ste 200,Rm 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse, NIH
FX The Intramural Research Program, National Institute on Drug Abuse, NIH.
NR 40
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U1 2
U2 20
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 APR
PY 2012
VL 58
IS 4
BP 748
EP 756
DI 10.1373/clinchem.2011.177881
PG 9
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 917NW
UT WOS:000302185700018
PM 22273566
ER

PT J
AU Frye, R
   Myers, M
   Axelrod, KC
   Ness, EA
   Piekarz, RL
   Bates, SE
   Booher, S
AF Frye, Robin
   Myers, Mary
   Axelrod, Karen C.
   Ness, Elizabeth A.
   Piekarz, Richard L.
   Bates, Susan E.
   Booher, Susan
TI Romidepsin: A New Drug for the Treatment of Cutaneous T-Cell Lymphoma
SO CLINICAL JOURNAL OF ONCOLOGY NURSING
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITORS; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME;
   CANCER-THERAPY; DEPSIPEPTIDE FR901228; CLINICAL DEVELOPMENT; TRIAL
AB Patients with cutaneous T-cell lymphoma (CTCL) have a rare, disfiguring, and life-threatening subtype of non-Hodgkin lymphoma primarily localized to the skin. Their immune systems are altered and their skin is compromised. In addition, they are highly prone to infections-the most common cause of death in patients with this disease. Patients presenting with early-stage disease involvement typically are treated with topical therapies; patients with advanced-stage and recurrent disease require systemic treatment. Specialized knowledge is required by oncology healthcare providers to manage the wide array of symptoms experienced by these patients as a part of the natural course of this disease. A new drug, romidepsin, approved by the U.S. Food and Drug Administration, is indicated in the treatment of relapsed CTCL. The authors discuss use of romidepsin in the context of CTCL and the information needed to safely administer romidepsin and manage its side effects.
C1 [Frye, Robin] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Myers, Mary; Axelrod, Karen C.] NIH, Nursing Serv, Ctr Clin, Bethesda, MD 20892 USA.
   [Myers, Mary; Axelrod, Karen C.] NIH, Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
   [Piekarz, Richard L.] NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD USA.
   [Booher, Susan] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Frye, R (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM nurserobinf@yahoo.com
FU NIH, NCI, Center for Cancer Research; CRADA; Gloucester Pharmaceuticals
FX Robin Frye, RN, BSN, is a research nurse specialist in the Medical
   Oncology Branch at the Center for Cancer Research, National Cancer
   Institute (NCI), National Institutes of Health (NIH); Mary Myers, BSN,
   PCCN, is a clinical research nurse and Karen C. Axelrod, RN, CWOCN, is a
   wound, ostomy, and continence nurse consultant, both in Nursing and
   Patient Care Services at the Clinical Center at NIH; Elizabeth A. Ness,
   RN, MS, is the director of staff development at the Center for Cancer
   Research, NCI, NIH, all in Bethesda, MD; Richard L. Piekarz, MD, PhD, is
   a medical officer of the Cancer Therapy Evaluation Program at NCI, NIH,
   in Rockville, MD; and Susan E. Bates, MD, is a senior investigator in
   the Medical Oncology Branch and Susan Booher, RN, MS, is a research
   nurse specialist in the Dermatology Branch, both at NCI, NIH, in
   Bethesda. The authors take full responsibility for the content of the
   article. Romidepsin, NSC 630176, was provided by the Cancer Therapy
   Evaluation Program. This research was supported, in part, by the
   Intramural Research Program of the NIH, NCI, Center for Cancer Research,
   and by a CRADA with Gloucester Pharmaceuticals. 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. The content of this article has been reviewed by
   independent peer reviewers to ensure that it is balanced, objective, and
   free from commercial bias. No financial relationships relevant to the
   content of this article have been disclosed by the independent peer
   reviewers or editorial staff. Mention of specific products and opinions
   related to those products do not indicate or imply endorsement by the
   Clinical Journal of Oncology Nursing or the Oncology Nursing Society.
   Frye can be reached at nurserobinf@yahoo.com, with copy to editor at
   CJONEditor@ons.org. (First submission December 2010. Revision submitted
   July 2011. Accepted for publication July 25, 2011.)
NR 38
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U1 0
U2 3
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD APR
PY 2012
VL 16
IS 2
BP 195
EP 204
DI 10.1188/12.CJON.195-204
PG 10
WC Oncology; Nursing
SC Oncology; Nursing
GA 918VS
UT WOS:000302280000014
PM 22459529
ER

PT J
AU Redford, KH
   Segre, JA
   Salafsky, N
   del Rio, CM
   McAloose, D
AF Redford, Kent H.
   Segre, Julia A.
   Salafsky, Nick
   del Rio, Carlos Martinez
   McAloose, Denise
TI Conservation and the Microbiome
SO CONSERVATION BIOLOGY
LA English
DT Editorial Material
ID INFECTIOUS-DISEASES; PROJECT
C1 [Redford, Kent H.] Wildlife Conservat Soc, WCS Inst, Bronx, NY 10460 USA.
   [Segre, Julia A.] Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Salafsky, Nick] Fdn Success, Bethesda, MD 20816 USA.
   [del Rio, Carlos Martinez] Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82070 USA.
   [McAloose, Denise] Wildlife Conservat Soc, Bronx, NY 10460 USA.
RP Redford, KH (reprint author), Archipelago Consulting, Irvington, NY 10533 USA.
EM kredford@wcs.org
FU Intramural NIH HHS [ZIA HG000180-11]
NR 17
TC 9
Z9 9
U1 4
U2 27
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0888-8892
J9 CONSERV BIOL
JI Conserv. Biol.
PD APR
PY 2012
VL 26
IS 2
BP 195
EP 197
DI 10.1111/j.1523-1739.2012.01829.x
PG 3
WC Biodiversity Conservation; Ecology; Environmental Sciences
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA 914VO
UT WOS:000301981100001
PM 22443125
ER

PT J
AU Rosenberg, HF
   Domachowske, JB
AF Rosenberg, H. F.
   Domachowske, J. B.
TI Inflammatory Responses to Respiratory Syncytial Virus (RSV) Infection
   and the Development of Immunomodulatory Pharmacotherapeutics
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Cytokines; Inflammation; Granulocytes; Pneumovirus; Leukocytes; Innate
   Immunity
ID EOSINOPHIL CATIONIC PROTEIN; PNEUMOVIRUS INFECTION; IMMUNE-RESPONSES;
   COTTON RATS; BALB/C MICE; TNF-ALPHA; IN-VIVO; AIRWAY
   HYPERRESPONSIVENESS; CHEMOKINE EXPRESSION; LUNG INFLAMMATION
AB Respiratory syncytial virus (RSV; Family Paramyxoviridae, Genus Pneumovirus) is a major respiratory pathogen of infants and children and an emerging pathogen of the elderly. Current management of RSV disease includes monoclonal antibody prophylaxis for infants identified as high risk and supportive care for those with active infection; there is no vaccine, although several are under study. In this manuscript, we review published findings from human autopsy studies, as well as experiments that focus on human clinical samples and mouse models of acute pneumovirus infection that elucidate basic principles of disease pathogenesis. Consideration of these data suggests that the inflammatory responses to RSV and related pneumoviral pathogens can be strong, persistent, and beyond the control of conventional antiviral and anti-inflammatory therapies, and can have profound negative consequences to the host. From this perspective, we consider the case for specific immunomodulatory strategies that may have the potential to alleviate some of the more serious sequelae of this disease.
C1 [Rosenberg, H. F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
   [Domachowske, J. B.] SUNY Upstate Med Univ, Dept Pediat, Div Infect Dis, Syracuse, NY USA.
RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU NIAID Division of Intramural Research [AI000943]; Children's Miracle
   Network of New York
FX Dr. Rosenberg's laboratory is supported by NIAID Division of Intramural
   Research (AI000943). Dr. Domachowske's laboratory is supported by the
   Children's Miracle Network of New York.
NR 97
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U1 0
U2 7
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD APR
PY 2012
VL 19
IS 10
BP 1424
EP 1431
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
   Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 916QP
UT WOS:000302118600002
PM 22360479
ER

PT J
AU Bray, GA
   Edelstein, SL
   Crandall, JP
   Aroda, VR
   Franks, PW
   Fujimoto, W
   Horton, E
   Jeffries, S
   Montez, M
   Mudaliar, S
   Pi-Sunyer, FX
   White, NH
   Knowler, WC
AF Bray, George A.
   Edelstein, Sharon L.
   Crandall, Jill P.
   Aroda, Vanita R.
   Franks, Paul W.
   Fujimoto, Wilfred
   Horton, Edward
   Jeffries, Susan
   Montez, Maria
   Mudaliar, Sunder
   Pi-Sunyer, F. Xavier
   White, Neil H.
   Knowler, William C.
CA Diabet Prevention Program Res Grp
TI Long-Term Safety, Tolerability, and Weight Loss Associated With
   Metformin in the Diabetes Prevention Program Outcomes Study
SO DIABETES CARE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; LIFE-STYLE INTERVENTION; TYPE-2; EXERCISE;
   MELLITUS; THERAPY; OBESITY; MUSCLE; DIET
AB OBJECTIVE-Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up.
   RESEARCH DESIGN AND METHODS-The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference.
   RESULTS-No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 +/- 5.65% vs. 0.02 +/- 5.52%, P < 0.001, and waist circumference by 2.13 +/- 7.06 cm vs. 0.79 +/- 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001).
   CONCLUSIONS-Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.
C1 [Bray, George A.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
   [Edelstein, Sharon L.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
   [Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Aroda, Vanita R.] Medstar Hlth Res Inst, Hyattsville, MD USA.
   [Franks, Paul W.] Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden.
   [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Fujimoto, Wilfred] Univ Washington, Seattle, WA 98195 USA.
   [Horton, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA.
   [Jeffries, Susan] Univ Pittsburgh, Pittsburgh, PA USA.
   [Montez, Maria] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
   [Mudaliar, Sunder] Univ Calif San Diego, San Diego, CA 92103 USA.
   [Pi-Sunyer, F. Xavier] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA.
   [White, Neil H.] Washington Univ, Sch Med, St Louis, MO USA.
   [Knowler, William C.] NIDDK, Phoenix, AZ USA.
RP Bray, GA (reprint author), Pennington Biomed Res Ctr, Baton Rouge, LA USA.
OI Franks, Paul/0000-0002-0520-7604
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
   of the National Institutes of Health; NIDDK; Indian Health Service;
   National Institute of Child Health and Human Development; National
   Institute on Aging; National Eye Institute; National Heart, Lung, and
   Blood Institute; Office of Research on Women's Health; National
   Institute on Minority Health and Health Disparities; Centers for Disease
   Control and Prevention; American Diabetes Association; Bristol-Myers
   Squibb; Parke-Davis; Novo Nordisk; Swedish Heart-Lung Foundation;
   Swedish Diabetes Association; Swedish Research Council
FX The National Institute of Diabetes and Digestive and Kidney Diseases
   (NIDDK) of the National Institutes of Health provided funding to the
   clinical centers and the DPP Coordinating Center for the design and
   conduct of the study, and collection, management, analysis, and
   interpretation of the data. The Southwestern American Indian Centers
   were supported directly by the NIDDK, including its Intramural Research
   Program, and the Indian Health Service. The General Clinical Research
   Center Program, National Center for Research Resources, supported data
   collection at many of the clinical centers. Funding was also provided by
   the National Institute of Child Health and Human Development; the
   National Institute on Aging; the National Eye Institute; the National
   Heart, Lung, and Blood Institute; the Office of Research on Women's
   Health; the National Institute on Minority Health and Health
   Disparities; the Centers for Disease Control and Prevention; and the
   American Diabetes Association.; Bristol-Myers Squibb and Parke-Davis
   provided additional funding and material support during the DPP. Lipha
   (Merck-Sante) provided medication, and Life Scan Inc. donated materials
   during the DPP and the DPPOS. P.W.F. was supported in part by grants
   from Novo Nordisk, the Swedish Heart-Lung Foundation, the Swedish
   Diabetes Association, and the Swedish Research Council. No other
   potential conflicts of interest relevant to this article were reported.
NR 22
TC 53
Z9 54
U1 2
U2 11
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 APR
PY 2012
VL 35
IS 4
BP 731
EP 737
DI 10.2337/dc11-1299
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 914OB
UT WOS:000301959600013
ER

PT J
AU Punthakee, Z
   Miller, ME
   Launer, LJ
   Williamson, JD
   Lazar, RM
   Cukierman-Yaffee, T
   Seaquist, ER
   Ismail-Beigi, F
   Sullivan, MD
   Lovato, LC
   Bergenstal, RM
   Gerstein, HC
AF Punthakee, Zubin
   Miller, Michael E.
   Launer, Lenore J.
   Williamson, Jeff D.
   Lazar, Ronald M.
   Cukierman-Yaffee, Tali
   Seaquist, Elizabeth R.
   Ismail-Beigi, Faramarz
   Sullivan, Mark D.
   Lovato, Laura C.
   Bergenstal, Richard M.
   Gerstein, Hertzel C.
CA ACCORD Grp Investigators
   ACCORD-MIND Investigators
TI Poor Cognitive Function and Risk of Severe Hypoglycemia in Type 2
   Diabetes Post hoc epidemiologic analysis of the ACCORD trial
SO DIABETES CARE
LA English
DT Article
ID PSYCHOMOTOR PERFORMANCE; ATHEROSCLEROSIS RISK; MELLITUS; ADULTS; AGE;
   COMPLICATIONS; ASSOCIATION; COMMUNITIES; DYSFUNCTION; MORTALITY
AB OBJECTIVE-Self-management of type 2 diabetes including avoidance of hypoglycemia is complex, but the impact of cognition on safe self-management is not well understood. This study aimed to assess the effect of baseline cognitive function and cognitive decline on subsequent risk of severe hypoglycemia and to assess the effect of different glycemic strategies on these relationships.
   RESEARCH DESIGN AND METHODS-Prospective cohort analysis of data from the ACCORD trial included 2,956 adults aged >= 55 years with type 2 diabetes and additional cardiovascular risk factors. Cognitive tests (Digit Symbol Substitution Test [DSST], Rey Auditory Verbal Learning Test, Stroop Test, and Mini Mental Status Examination) were conducted at baseline and 20 months. Study outcomes were incident confirmed severe hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any assistance (HAA).
   RESULTS-After a median 3.25-year follow-up, a 5-point-poorer baseline score on the DSST was predictive of a first episode of HMA (hazard ratio 1.13 [95% CI 1.08-1.18]). Analyses of the other cognitive tests and of HAA were consistent with the DSST results. Cognitive decline over 20 months increased the risk of subsequent hypoglycemia to a greater extent in those with lower baseline cognitive function (P-interaction = 0.037). Randomization to an intensive versus standard glycemic strategy had no impact on the relationship between cognitive function and the risk of severe hypoglycemia.
   CONCLUSIONS-Poor cognitive function increases the risk of severe hypoglycemia in patients with type 2 diabetes. Clinicians should consider cognitive function in assessing and guiding their patients regarding safe diabetes self-management regardless of their glycemic targets.
C1 [Punthakee, Zubin; Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
   [Miller, Michael E.] Wake Forest Univ, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
   [Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
   [Williamson, Jeff D.] Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA.
   [Williamson, Jeff D.] Wake Forest Univ, Kulynych Ctr Memory & Cognit Res, Winston Salem, NC 27109 USA.
   [Lazar, Ronald M.] Columbia Univ, Dept Neurol, New York, NY USA.
   [Cukierman-Yaffee, Tali] Tel Aviv Univ, Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Inst Endocrinol,Epidemiol Dept, IL-69978 Tel Aviv, Israel.
   [Seaquist, Elizabeth R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
   [Ismail-Beigi, Faramarz] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
   [Sullivan, Mark D.] Univ Washington, Seattle, WA 98195 USA.
   [Lovato, Laura C.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
   [Bergenstal, Richard M.] Int Diabet Ctr Pk Nicollet, Minneapolis, MN USA.
RP Punthakee, Z (reprint author), McMaster Univ, Dept Med, Hamilton, ON, Canada.
EM zubin.punthakee@mcmaster.ca
RI Gerstein, Hertzel/B-1235-2013
OI Gerstein, Hertzel/0000-0001-8072-2836
FU National Heart, Lung, and Blood Institute (NHLBI); National Institute of
   Diabetes and Digestive and Kidney Diseases; National Eye Institute;
   National Institute on Aging (NIA); Centers for Disease Control and
   Prevention
FX ACCORD was sponsored by the National Heart, Lung, and Blood Institute
   (NHLBI), and ACCORD-MIND was sponsored by NHLBI, the National Institute
   of Diabetes and Digestive and Kidney Diseases, the National Eye
   Institute, the National Institute on Aging (NIA) and the Intramural
   Research Program at NIA, and the Centers for Disease Control and
   Prevention.
NR 33
TC 82
Z9 84
U1 1
U2 10
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 APR
PY 2012
VL 35
IS 4
BP 787
EP 793
DI 10.2337/dc11-1855
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 914OB
UT WOS:000301959600022
PM 22374637
ER

PT J
AU McDannald, MA
   Takahashi, YK
   Lopatina, N
   Pietras, BW
   Jones, JL
   Schoenbaum, G
AF McDannald, Michael A.
   Takahashi, Yuji K.
   Lopatina, Nina
   Pietras, Brad W.
   Jones, Josh L.
   Schoenbaum, Geoffrey
TI Model-based learning and the contribution of the orbitofrontal cortex to
   the model-free world
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE model-based; model-free; orbitofrontal cortex; Pavlovian; striatum
ID NUCLEUS-ACCUMBENS CORE; DOPAMINE NEURONS ENCODE; BASOLATERAL AMYGDALA;
   VENTRAL STRIATUM; UNCONDITIONED STIMULUS; INSTRUMENTAL TRANSFER;
   DEVALUATION TASK; DORSAL STRIATUM; REWARD; LESIONS
AB Learning is proposed to occur when there is a discrepancy between reward prediction and reward receipt. At least two separate systems are thought to exist: one in which predictions are proposed to be based on model-free or cached values; and another in which predictions are model-based. A basic neural circuit for model-free reinforcement learning has already been described. In the model-free circuit the ventral striatum (VS) is thought to supply a common-currency reward prediction to midbrain dopamine neurons that compute prediction errors and drive learning. In a model-based system, predictions can include more information about an expected reward, such as its sensory attributes or current, unique value. This detailed prediction allows for both behavioral flexibility and learning driven by changes in sensory features of rewards alone. Recent evidence from animal learning and human imaging suggests that, in addition to model-free information, the VS also signals model-based information. Further, there is evidence that the orbitofrontal cortex (OFC) signals model-based information. Here we review these data and suggest that the OFC provides model-based information to this traditional model-free circuitry and offer possibilities as to how this interaction might occur.
C1 [McDannald, Michael A.; Jones, Josh L.; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
   [Takahashi, Yuji K.; Schoenbaum, Geoffrey] NIDA IRP, Baltimore, MD USA.
   [Lopatina, Nina; Pietras, Brad W.] Univ Maryland, Program Neurosci, College Pk, MD 20742 USA.
RP Schoenbaum, G (reprint author), Univ Maryland, Sch Med, 20 Penn St HSF 2, Baltimore, MD 21201 USA.
EM schoenbg@schoenbaumlab.org
FU  [R01DA015718]
FX This study was supported by R01DA015718 to G.S.
NR 57
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U1 3
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD APR
PY 2012
VL 35
IS 7
SI SI
BP 991
EP 996
DI 10.1111/j.1460-9568.2011.07982.x
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 919VX
UT WOS:000302360500002
PM 22487030
ER

PT J
AU Hilario, M
   Holloway, T
   Jin, X
   Costa, RM
AF Hilario, Monica
   Holloway, Terrell
   Jin, Xin
   Costa, Rui M.
TI Different dorsal striatum circuits mediate action discrimination and
   action generalization
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE basal ganglia; goal-directed; habit; learning; motor; mouse
ID MULTIPLE MEMORY-SYSTEMS; BASAL GANGLIA; DORSOMEDIAL STRIATUM;
   CAUDATE-NUCLEUS; CONTINGENCY; LESIONS; CORTEX; ROLES; INACTIVATION;
   DEVALUATION
AB Generalization is an important process that allows animals to extract rules from regularities of past experience and apply them to analogous situations. In particular, the generalization of previously learned actions to novel instruments allows animals to use past experience to act faster and more efficiently in an ever-changing environment. However, generalization of actions to a dissimilar instrument or situation may also be detrimental. In this study, we investigated the neural bases of action generalization and discrimination in mice trained on a lever-pressing task. Using specific schedules of reinforcement known to bias animals towards habitual or goal-directed behaviors, we confirmed that action generalization is more prominent in animals using habitual rather than goal-directed strategies. We discovered that selective excitotoxic lesions of the dorsolateral and dorsomedial striatum have opposite effects on the generalization of a previously learned action to a novel lever. Whereas lesions of the dorsolateral striatum impair action generalization, dorsomedial striatum lesions affect action discrimination and bias subjects towards action generalization. Importantly, these lesions do not affect the ability of animals to explore or match their lever-pressing rate to the reinforcement rate, or the ability to distinguish between different levers. The data presented here reveal that dorsolateral and dorsomedial striatal circuits have opposing roles in the generalization of previously learned actions to novel instruments, and suggest that these circuits compete for the expression of generalization in novel situations.
C1 [Costa, Rui M.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
   [Hilario, Monica; Holloway, Terrell; Jin, Xin; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD USA.
RP Costa, RM (reprint author), Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, Av Brasilia, P-1400038 Lisbon, Portugal.
EM ruicosta@fchampalimaud.org
OI Costa, Rui/0000-0003-0495-8374
FU National Institute on Alcohol Abuse and Alcoholism [239527]; European
   Research Council [STG 243393]
FX We thank M. Child for comments on the manuscript. This work was
   supported by the Intramural Research Program at the National Institute
   on Alcohol Abuse and Alcoholism, Marie Curie International Reintegration
   Grant 239527, and European Research Council STG 243393.
NR 38
TC 15
Z9 15
U1 2
U2 11
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 APR
PY 2012
VL 35
IS 7
SI SI
BP 1105
EP 1114
DI 10.1111/j.1460-9568.2012.08073.x
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 919VX
UT WOS:000302360500012
PM 22487040
ER

PT J
AU Roesch, MR
   Esber, GR
   Li, J
   Daw, ND
   Schoenbaum, G
AF Roesch, Matthew R.
   Esber, Guillem R.
   Li, Jian
   Daw, Nathaniel D.
   Schoenbaum, Geoffrey
TI Surprise! Neural correlates of Pearce-Hall and Rescorla-Wagner coexist
   within the brain
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Review
DE amygdala; attention; dopamine; learning; prediction error
ID ANTERIOR CINGULATE CORTEX; VENTRAL TEGMENTAL AREA; MIDBRAIN DOPAMINE
   NEURONS; AMYGDALA CENTRAL NUCLEUS; REWARD-SEEKING BEHAVIOR;
   ORBITOFRONTAL CORTEX; LATERAL HABENULA; PREDICTION ERRORS; BASOLATERAL
   AMYGDALA; DECISION-MAKING
AB Learning theory and computational accounts suggest that learning depends on errors in outcome prediction as well as changes in processing of or attention to events. These divergent ideas are captured by models, such as RescorlaWagner (RW) and temporal difference (TD) learning on the one hand, which emphasize errors as directly driving changes in associative strength, vs. models such as PearceHall (PH) and more recent variants on the other hand, which propose that errors promote changes in associative strength by modulating attention and processing of events. Numerous studies have shown that phasic firing of midbrain dopamine (DA) neurons carries a signed error signal consistent with RW or TD learning theories, and recently we have shown that this signal can be dissociated from attentional correlates in the basolateral amygdala and anterior cingulate. Here we will review these data along with new evidence: (i) implicating habenula and striatal regions in supporting error signaling in midbrain DA neurons; and (ii) suggesting that the central nucleus of the amygdala and prefrontal regions process the amygdalar attentional signal. However, while the neural instantiations of the RW and PH signals are dissociable and complementary, they may be linked. Any linkage would have implications for understanding why one signal dominates learning in some situations and not others, and also for appreciating the potential impact on learning of neuropathological conditions involving altered DA or amygdalar function, such as schizophrenia, addiction or anxiety disorders.
C1 [Esber, Guillem R.; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
   [Roesch, Matthew R.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
   [Roesch, Matthew R.] Univ Maryland, Program Neurosci & Cognit Sci, College Pk, MD 20742 USA.
   [Li, Jian; Daw, Nathaniel D.] NYU, Dept Psychol, New York, NY 10003 USA.
   [Li, Jian; Daw, Nathaniel D.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
   [Schoenbaum, Geoffrey] NIDA Intramural Res Program, Baltimore, MD 21224 USA.
RP Schoenbaum, G (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
EM schoenbg@schoenbaumlab.org
FU NIDA; NIMH; NIA
FX This work was supported by grants to G.S. from NIDA, NIMH and NIA, and
   to M. R. from NIDA. This article was prepared, in part, while G. S. was
   employed at UMB. The opinions expressed in this article are the author's
   own and do not reflect the view of the National Institutes of Health,
   the Department of Health and Human Services, or the United States
   government.
NR 121
TC 39
Z9 39
U1 3
U2 30
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 APR
PY 2012
VL 35
IS 7
SI SI
BP 1190
EP 1200
DI 10.1111/j.1460-9568.2011.07986.x
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 919VX
UT WOS:000302360500019
PM 22487047
ER

PT J
AU Zanotti-Fregonara, P
   Maroy, R
   Peyronneau, MA
   Trebossen, R
   Bottlaender, M
AF Zanotti-Fregonara, Paolo
   Maroy, Renaud
   Peyronneau, Marie-Anne
   Trebossen, Regine
   Bottlaender, Michel
TI Minimally invasive input function for 2-F-18-fluoro-A-85380 brain PET
   studies
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Input function; 2-F-18-Fluoro-A-85380; Brain studies with PET
ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL METABOLIC-RATE; NICOTINIC
   ACETYLCHOLINE-RECEPTORS; BLOOD-SAMPLING SITE; FDG-PET; SIMPLIFIED
   QUANTIFICATION; GLUCOSE-METABOLISM; DRUG CONCENTRATION; MARKED
   DEPENDENCE; QUANTITATIVE PET
AB Quantitative neuroreceptor positron emission tomography (PET) studies often require arterial cannulation to measure input function. While population-based input function (PBIF) would be a less invasive alternative, it has only rarely been used in conjunction with neuroreceptor PET tracers. The aims of this study were (1) to validate the use of PBIF for 2-F-18-fluoro-A-85380, a tracer for nicotinic receptors; (2) to compare the accuracy of measures obtained via PBIF to those obtained via blood-scaled image-derived input function (IDIF) from carotid arteries; and (3) to explore the possibility of using venous instead of arterial samples for both PBIF and IDIF.
   Ten healthy volunteers underwent a dynamic 2-F-18-fluoro-A-85380 brain PET scan with arterial and, in seven subjects, concurrent venous serial blood sampling. PBIF was obtained by averaging the normalized metabolite-corrected arterial input function and subsequently scaling each curve with individual blood samples. IDIF was obtained from the carotid arteries using a blood-scaling method. Estimated Logan distribution volume (V (T)) values were compared to the reference values obtained from arterial cannulation.
   For all subjects, PBIF curves scaled with arterial samples were similar in shape and magnitude to the reference arterial input function. The Logan V (T) ratio was 1.00 +/- 0.05; all subjects had an estimation error < 10%. IDIF gave slightly less accurate results (V (T) ratio 1.03 +/- 0.07; eight of ten subjects had an error < 10%). PBIF scaled with venous samples yielded inaccurate results (V (T) ratio 1.13 +/- 0.13; only three of seven subjects had an error < 10%). Due to arteriovenous differences at early time points, IDIF could not be calculated using venous samples.
   PBIF scaled with arterial samples accurately estimates Logan V (T) for 2-F-18-fluoro-A-85380. Results obtained with PBIF were slightly better than those obtained with IDIF. Due to arteriovenous concentration differences, venous samples cannot be substituted for arterial samples.
C1 [Zanotti-Fregonara, Paolo] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
   [Maroy, Renaud; Peyronneau, Marie-Anne; Trebossen, Regine] Serv Hosp Frederic Joliot, CEA, DSV, I2BM, F-91401 Orsay, France.
   [Bottlaender, Michel] CEA, DSV, I2BM, F-91191 Gif Sur Yvette, France.
RP Zanotti-Fregonara, P (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr,MSC 1026, Bethesda, MD 20892 USA.
EM zanottifregonp@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
   (NIMH-NIH)
FX This study was supported in part by the Intramural Research Program of
   the National Institute of Mental Health, National Institutes of Health
   (IRP-NIMH-NIH).
NR 42
TC 10
Z9 10
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD APR
PY 2012
VL 39
IS 4
BP 651
EP 659
DI 10.1007/s00259-011-2004-9
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 918YL
UT WOS:000302287500012
PM 22231015
ER

PT J
AU Gao, HK
   Lang, LX
   Guo, N
   Cao, F
   Quan, QM
   Hu, S
   Kiesewetter, DO
   Niu, G
   Chen, XY
AF Gao, Haokao
   Lang, Lixin
   Guo, Ning
   Cao, Feng
   Quan, Qimeng
   Hu, Shuo
   Kiesewetter, Dale O.
   Niu, Gang
   Chen, Xiaoyuan
TI PET imaging of angiogenesis after myocardial infarction/reperfusion
   using a one-step labeled integrin-targeted tracer F-18-AlF-NOTA-PRGD2
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE PET imaging; Angiogenesis; Myocardial infarction; Integrin; RGD peptide
ID ALPHA(V)BETA(3) EXPRESSION; INFARCTION; PEPTIDES; THERAPY; F-18-FPPRGD2;
   ANTAGONISTS; AGENT; ACID; MICE
AB The alpha(v)beta(3) integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin alpha(v)beta(3)-targeting positron emission tomography (PET) probe, F-18-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infarction/reperfusion (MI/R) animal model.
   Male Sprague-Dawley rats underwent 45-min transient left coronary artery occlusion followed by reperfusion. The myocardial infarction was confirmed by ECG, F-18-fluorodeoxyglucose (FDG) imaging, and cardiac ultrasound. In vivo PET imaging was used to determine myocardial uptake of F-18-AlF-NOTA-PRGD2 at different time points following reperfusion. The control peptide RAD was labeled with a similar procedure and used to confirm the specificity. Ex vivo autoradiographic analysis and CD31/CD61 double immunofluorescence staining were performed to validate the PET results.
   Myocardial origin of the F-18-AlF-NOTA-PRGD2 accumulation was confirmed by F-18-FDG and autoradiography. PET imaging demonstrated increased focal accumulation of F-18-AlF-NOTA-PRGD2 in the infarcted area which started at day 3 (0.28 +/- 0.03%ID/g, p < 0.05) and peaked between 1 and 3 weeks (0.59 +/- 0.16 and 0.55 +/- 0.13%ID/g, respectively). The focal accumulation decreased but still kept at a higher level than the sham group after 4 months of reperfusion (0.31 +/- 0.01%ID/g, p < 0.05). Pretreatment with unlabeled arginine-glycine-aspartic acid (RGD) peptide significantly decreased tracer uptake, indicating integrin specificity of this tracer. At 1 week after MI/R, uptake of the control tracer F-18-AlF-NOTA-RAD that does not bind to integrin, in the infarcted area, was only 0.21 +/- 0.01%ID/g. Autoradiographic imaging showed the same trend of uptake in the myocardial infarction area. The time course of focal tracer uptake was consistent with the pattern of vascular density and integrin beta(3) expression as measured by CD31 and CD61 immunostaining analysis.
   PET imaging using one-step labeled F-18-AlF-NOTA-PRGD2 allows noninvasive visualization of ischemia/reperfusion-induced myocardial angiogenesis longitudinally. The favorable in vivo kinetics and easy production method of this integrin-targeted PET tracer facilitates its future clinical translation for lesion evaluation and therapy response monitoring in patients with occlusive cardiovascular diseases.
C1 [Gao, Haokao; Lang, Lixin; Guo, Ning; Quan, Qimeng; Hu, Shuo; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
   [Gao, Haokao; Cao, Feng] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM niug@mail.nih.gov; shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB),
   National Institutes of Health (NIH); National Science Foundation of
   China (NSFC) [81028009, 81100234]
FX This project was supported by the Intramural Research Program of the
   National Institute of Biomedical Imaging and Bioengineering (NIBIB),
   National Institutes of Health (NIH) and the International Cooperative
   Program of the National Science Foundation of China (NSFC) (81028009).
   H. G. is partly supported by the National Science Foundation of China
   (NSFC) (81100234).
NR 35
TC 36
Z9 36
U1 1
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD APR
PY 2012
VL 39
IS 4
BP 683
EP 692
DI 10.1007/s00259-011-2052-1
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 918YL
UT WOS:000302287500016
PM 22274731
ER

PT J
AU Bentley, AR
   Kritchevsky, SB
   Harris, TB
   Holvoet, P
   Jensen, RL
   Newman, AB
   Lee, JS
   Yende, S
   Bauer, D
   Cassano, PA
AF Bentley, A. R.
   Kritchevsky, S. B.
   Harris, T. B.
   Holvoet, P.
   Jensen, R. L.
   Newman, A. B.
   Lee, J. S.
   Yende, S.
   Bauer, D.
   Cassano, P. A.
CA Hlth ABC Study
TI Dietary antioxidants and forced expiratory volume in 1 s decline: the
   Health, Aging and Body Composition study
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
DE Ageing; dietary intake; lung function measurements;
   oxidants/antioxidants; smoking and health
ID OBSTRUCTIVE PULMONARY-DISEASE; LUNG-FUNCTION DECLINE; MIDDLE-AGED MEN;
   GENERAL-POPULATION; AIRWAY-OBSTRUCTION; OXIDATIVE STRESS; WEIGHT CHANGE;
   OLDER-ADULTS; COPD; LIMITATION
AB Increased antioxidant defences are hypothesised to decrease age-and smoking-related decline in lung function.
   The relationship between dietary antioxidants, smoking and forced expiratory volume in 1 s (FEV1) was investigated in community-dwelling older adults in the Health, Aging and Body Composition study. 1,443 participants completed a food frequency questionnaire, self-reported smoking history and had measurements taken of FEV1 at both baseline and after 4 yrs of follow-up. The association of dietary intake of nutrients and foods with antioxidant properties and rate of FEV1 decline was investigated using hierarchical linear regression models.
   In continuing smokers (current smokers at both time-points), higher vitamin C intake and higher intake of fruit and vegetables were associated with an 18 and 24 mL.yr(-1) slower rate of FEV1 decline compared with a lower intake (p<0.0001 and p=0.003, respectively). In quitters (a current smoker at study baseline who had quit during follow-up), higher intake was associated with an attenuated rate of decline for each nutrient studied (p <= 0.003 for all models). In nonsmoking participants, there was little or no association of diet and rate of decline in FEV1.
   The intake of nutrients with antioxidant properties may modulate lung function decline in older adults exposed to cigarette smoke.
C1 [Bentley, A. R.; Cassano, P. A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Kritchevsky, S. B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
   [Harris, T. B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Jensen, R. L.] Univ Utah, Sch Med, Div Pulm, LDS Hosp, Salt Lake City, UT USA.
   [Newman, A. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
   [Yende, S.] Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA USA.
   [Lee, J. S.] Univ Georgia, Athens, GA 30602 USA.
   [Bauer, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Holvoet, P.] Katholieke Univ Leuven, Dept Cardiovasc Dis, Louvain, Belgium.
RP Cassano, PA (reprint author), Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
EM pac6@cornell.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU National Institutes of Health (NIH) [T32 DK007158-31, R01HL74104,
   R01HL071022]; National Institute on Aging [N01-AG-6-2101, N01-AG-2103,
   N01-AG-6-2106]; NIH, National Institute on Aging
FX This work was supported by the National Institutes of Health (NIH)
   (grant number T32 DK007158-31 to A. R. Bentley; grant number R01HL74104
   to S. B. Kritchevsky; grant number R01HL071022 to P. A. Cassano) and the
   National Institute on Aging (grant numbers N01-AG-6-2101, N01-AG-2103
   and N01-AG-6-2106 to the Health ABC Study). This research was supported
   in part by the Intramural Research Program of the NIH, National
   Institute on Aging.
NR 29
TC 16
Z9 17
U1 1
U2 8
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
J9 EUR RESPIR J
JI Eur. Resp. J.
PD APR
PY 2012
VL 39
IS 4
BP 979
EP 984
DI 10.1183/09031936.00190010
PG 6
WC Respiratory System
SC Respiratory System
GA 919UL
UT WOS:000302354900027
PM 22005919
ER

PT J
AU Becker, RE
   Greig, NH
AF Becker, Robert E.
   Greig, Nigel H.
TI Increasing the success rate for Alzheimer's disease drug discovery and
   development
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Editorial Material
DE Alzheimer's disease; clinical trials; drug development; methodological
   errors
ID CLINICAL-TRIALS; FUTURE
AB This paper responds to the fact that over 200 Alzheimer's disease (AD) drug candidates have failed to date and draws on searches of the literature for studies of error effects in drug developments and the authors' published works. In the same period, basic knowledge of AD pathology has greatly expanded providing both potential therapeutic targets and rationales for modifications in strategies for testing AD drug candidates. Current opinion generally holds that AD drug candidates have failed because they address pathology that is already too advanced. Less attention is paid to numerous reported methodological weaknesses capable of biasing AD clinical trials and drug developments and thus invalidating conclusions to be reached about the drugs being tested. The costs of quality controls possibly needed to better insure validity in AD drug developments raises concerns that progress toward success in AD drug development may be hindered by the costs of intervening against current methodological barriers to the successful completions of AD drug developments.
C1 [Becker, Robert E.] Aristea Translat Med Corp, S Freeport, ME 04078 USA.
   [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Becker, RE (reprint author), Aristea Translat Med Corp, POB 442, S Freeport, ME 04078 USA.
EM rebecker2008@comcast.net
FU Intramural NIH HHS
NR 18
TC 6
Z9 6
U1 1
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1746-0441
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD APR
PY 2012
VL 7
IS 4
BP 367
EP 370
DI 10.1517/17460441.2012.672409
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 917HO
UT WOS:000302163700007
PM 22439785
ER

PT J
AU Meliopoulos, VA
   Andersen, LE
   Birrer, KF
   Simpson, KJ
   Lowenthal, JW
   Bean, AGD
   Stambas, J
   Stewart, CR
   Tompkins, SM
   van Beusechem, VW
   Fraser, I
   Mhlanga, M
   Barichievy, S
   Smith, Q
   Leake, D
   Karpilow, J
   Buck, A
   Jona, G
   Tripp, RA
AF Meliopoulos, Victoria A.
   Andersen, Lauren E.
   Birrer, Katherine F.
   Simpson, Kaylene J.
   Lowenthal, John W.
   Bean, Andrew G. D.
   Stambas, John
   Stewart, Cameron R.
   Tompkins, S. Mark
   van Beusechem, Victor W.
   Fraser, Iain
   Mhlanga, Musa
   Barichievy, Samantha
   Smith, Queta
   Leake, Devin
   Karpilow, Jon
   Buck, Amy
   Jona, Ghil
   Tripp, Ralph A.
TI Host gene targets for novel influenza therapies elucidated by
   high-throughput RNA interference screens
SO FASEB JOURNAL
LA English
DT Review
DE antivirals; HTS; genome; pathway; meta-analysis
ID PROTEIN-PROTEIN INTERACTIONS; MICROARRAY EXPERIMENT MIAME;
   VIRUS-REPLICATION; A VIRUS; IMMUNE-RESPONSE; NS1 PROTEIN;
   CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; MINIMUM INFORMATION;
   SIGNAL-TRANSDUCTION
AB Influenza virus encodes only 11 viral proteins but replicates in a broad range of avian and mammalian species by exploiting host cell functions. Genome-wide RNA interference (RNAi) has proven to be a powerful tool for identifying the host molecules that participate in each step of virus replication. Meta-analysis of findings from genome-wide RNAi screens has shown influenza virus to be dependent on functional nodes in host cell pathways, requiring a wide variety of molecules and cellular proteins for replication. Because rapid evolution of the influenza A viruses persistently complicates the effectiveness of vaccines and therapeutics, a further understanding of the complex host cell pathways coopted by influenza virus for replication may provide new targets and strategies for antiviral therapy. RNAi genome screening technologies together with bioinformatics can provide the ability to rapidly identify specific host factors involved in resistance and susceptibility to influenza virus, allowing for novel disease intervention strategies.-Meliopoulos, V. A., Andersen, L. E., Birrer, K. F., Simpson, K. J., Lowenthal, J. W., Bean, A. G. D., Stambas, J., Stewart, C. R., Tompkins, S. M., van Beusechem, V. W., Fraser, I., Mhlanga, M., Barichievy, S., Smith, Q., Leake, D., Karpilow, J., Buck, A., Jona, G., Tripp, R. A. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. FASEB J. 26, 1372-1386 (2012). www.fasebj.org
C1 [Tripp, Ralph A.] Univ Georgia, Dept Infect Dis, Anim Hlth Res Ctr, Athens, GA 30602 USA.
   [Birrer, Katherine F.; Lowenthal, John W.; Bean, Andrew G. D.; Stewart, Cameron R.] Commonwealth Sci & Ind Res Org, Australian Anim Hlth Lab, Geelong, Vic, Australia.
   [Simpson, Kaylene J.] Peter MacCallum Canc Ctr, Victorian Ctr Funct Genom, Melbourne, Vic, Australia.
   [Birrer, Katherine F.; Stambas, John] Deakin Univ, Sch Med, Geelong, Vic 3217, Australia.
   [van Beusechem, Victor W.] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands.
   [Fraser, Iain] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
   [Mhlanga, Musa; Barichievy, Samantha] CSIR, Synthet Biol Emerging Res Area, Gene Express & Biophys Grp, Pretoria, South Africa.
   [Smith, Queta; Leake, Devin; Karpilow, Jon] Thermo Fisher Sci, Lafayette, CO USA.
   [Simpson, Kaylene J.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
   [Buck, Amy] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
   [Jona, Ghil] Weizmann Inst Sci, Dept Biol Serv, IL-76100 Rehovot, Israel.
RP Tripp, RA (reprint author), Univ Georgia, Dept Infect Dis, Anim Hlth Res Ctr, 111 Carlton St, Athens, GA 30602 USA.
EM ratripp@uga.edu
RI Tompkins, Stephen/A-3317-2008; lowenthal, john/G-4459-2010; Mhlanga,
   Musa/D-1283-2011; Stewart, Cameron/E-6823-2011; 
OI Tompkins, Stephen/0000-0002-1523-5588; lowenthal,
   john/0000-0002-0548-2497; Mhlanga, Musa/0000-0003-1381-3409; Simpson,
   Kaylene/0000-0001-9136-1781; Tripp, Ralph/0000-0002-2924-9956; Stambas,
   John/0000-0002-5690-2551
FU Biotechnology and Biological Sciences Research Council [BB/G01552X/1];
   Intramural NIH HHS [ZIA AI001107-04, ZIA AI001106-04]
NR 137
TC 24
Z9 26
U1 0
U2 19
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
IS 4
BP 1372
EP 1386
DI 10.1096/fj.11-193466
PG 15
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 919VS
UT WOS:000302359700001
PM 22247330
ER

PT J
AU Hwang, SY
   Putney, JW
AF Hwang, Sung-Yong
   Putney, James W.
TI Orai1-mediated calcium entry plays a critical role in osteoclast
   differentiation and function by regulating activation of the
   transcription factor NFATc1
SO FASEB JOURNAL
LA English
DT Article
DE store-operated channels; bone remodeling; osteoporosis; receptor
   activator of nuclear factor kappa B ligand; tartrate-resistant acid
   phosphatase
ID KAPPA-B LIGAND; T-CELLS C1; BONE-RESORPTION; GENE-EXPRESSION; TERMINAL
   DIFFERENTIATION; OSTEOPROTEGERIN LIGAND; RECEPTOR ACTIVATOR; SIGNALING
   PATHWAY; PROTEIN-KINASE; NUCLEAR FACTOR
AB Bone diseases such as postmenopausal osteoporosis are primarily caused by excessive formation and activity of osteoclasts (OCLs). Receptor activator of nuclear factor-kappa B ligand (RANKL) is a key initiating cytokine for OCL differentiation and function. RANKL induces calcium (Ca2+) oscillations, resulting in selective and robust induction of nuclear factor of activated T cells c1 (NFATc1), a Ca2+-responsive transcription factor that drives osteoclastogenesis. Store-operated Ca2+ entry (SOCE) is a major Ca2+ influx pathway in most nonexcitable cell types and is activated by any stimulus that depletes Ca2+ stores in the endoplasmic reticulum. Although the role of Orai1, a SOCE channel in the plasma membrane, in maintaining Ca2+ oscillations and transactivation of NFAT in other cell types is well known, its contribution to osteoclastogenesis remains unclear. We show here that silencing of the Orai1 gene with viral delivery of shRNA reduces SOCE and inhibits RANKL-induced osteoclastogenesis of RAW264.7 cells, a murine monocyte/macrophage cell line, by suppressing the induction of NFATc1. This was accompanied by defective induction of OCL-specific genes, such as tartrate-resistant acid phosphatase and immunoreceptor OCL-associated receptor, which are known to be direct transcriptional targets of NFATc1 during osteoclastogenesis. In addition, maturation of OCLs was abrogated by defective cell fusion of pre-OCLs depleted of Orai1, consistent with defective RANKL-mediated induction of d2 isoform of vacuolar ATPase V-o domain that is involved in cell fusion of pre-OCLs. We found that the functional bone resorbing capacity was severely impaired in OCLs depleted of Orai1, potentially related to the observed decrease in the induction of cathepsin K, a major bone matrix degrading protease. Our results indicate that Orai1 plays a critical role in the differentiation and function of OCLs, suggesting that Orai1 might be a potential therapeutic target for the treatment or prevention of bone loss caused by OCLs.-Hwang, S.-Y., Putney, J. W. Orai1-mediated calcium entry plays a critical role in osteoclast differentiation and function by regulating activation of the transcription factor NFATc1. FASEB J. 26, 1484 -1492 (2012). www.fasebj.org
C1 [Hwang, Sung-Yong; Putney, James W.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Hwang, SY (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM hwangs3@niehs.nih.gov
FU U.S. National Institutes of Health, National Institute of Environmental
   Health Sciences (NIEHS)
FX This research was supported by the Intramural Research Program of the
   U.S. National Institutes of Health, National Institute of Environmental
   Health Sciences (NIEHS). The authors thank Dr. Xiaoling Li and Dr.
   Robert Oakley for helpful comments. The authors thank Dr. Gary Bird for
   technical advice and helpful discussion. The authors also thank Dr.
   Charles Romeo and Dr. Negin Martin (Viral Vector Core, NIEHS) for
   lentivirus preparations.
NR 48
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U2 6
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
IS 4
BP 1484
EP 1492
DI 10.1096/fj.11-194399
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 919VS
UT WOS:000302359700011
PM 22198385
ER

PT J
AU Beall, SA
   DeCherney, A
AF Beall, Stephanie A.
   DeCherney, Alan
TI History and challenges surrounding ovarian stimulation in the treatment
   of infertility
SO FERTILITY AND STERILITY
LA English
DT Review
DE Gonadotropin; ovarian stimulation; ovulation induction; history;
   multiple births
ID IN-VITRO FERTILIZATION; RECOMBINANT HUMAN FSH; OVULATION INDUCTION;
   HUMAN EMBRYO; PREGNANCY; FOLLICLE; HORMONE; SEQUENCE; SUPEROVULATION;
   REIMPLANTATION
AB Objective: To examine the history of superovulation for ovulation induction, its contributions to reproductive medicine, and its impact on multiple births.
   Design: A search of the relevant literature using PubMed and other online tools.
   Result(s): Infertility has been a condition known and studied for thousands of years. However, it was not until this past century that effective treatments were developed. With the advancement of our knowledge of the hypothalamic-pituitary axis, therapies utilizing gonadotropins were developed to stimulate ovulation. Not only could we now treat anovulatory infertility but also induce superovulation for IVF. With these successes came consequences, including increased multiple pregnancies. Several countries recognized the high costs associated with multiple births and implemented regulations on the infertility industry. The rate of triplet and higher-order multiples has declined over the past decade. This is largely attributed to a decreased number of embryos transferred. Nonetheless, the twin rate has remained consistently high.
   Conclusion(s): Superovulation has become a routine medical therapy used for ovulation induction and IVF. With the development of this technology have come effective therapies for infertility and new ethical and medical challenges. Since the advent of gonadotropin therapy we have already developed technologies to improve monitoring and decrease hyperstimulation and high-order multiple pregnancies. In the future we anticipate new tools devised to optimize one embryo for one singleton live birth. (Fertil Steril (R) 2012;97:795-801. (C)2012 by American Society for Reproductive Medicine.)
C1 [DeCherney, Alan] NICHHD, Reprod Biol & Med Branch, NIH, CRC, Bethesda, MD 20892 USA.
RP DeCherney, A (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, CRC, Bldg 10,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM decherna@mail.nih.gov
FU Intramural NIH HHS [Z01 HD008737-08]
NR 40
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U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD APR
PY 2012
VL 97
IS 4
BP 795
EP 801
DI 10.1016/j.fertnstert.2012.02.030
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 917AE
UT WOS:000302143500006
PM 22463773
ER

PT J
AU Harlow, SD
   Gass, M
   Hall, JE
   Lobo, R
   Maki, P
   Rebar, RW
   Sherman, S
   Sluss, PM
   de Villiers, TJ
AF Harlow, Sioban D.
   Gass, Margery
   Hall, Janet E.
   Lobo, Roger
   Maki, Pauline
   Rebar, Robert W.
   Sherman, Sherry
   Sluss, Patrick M.
   de Villiers, Tobie J.
CA STRAW Collaborative Group
TI Executive summary of the Stages of Reproductive Aging Workshop+10:
   addressing the unfinished agenda of staging reproductive aging
SO FERTILITY AND STERILITY
LA English
DT Article
DE Reproductive aging; ovarian aging; menopause; follicle-stimulating
   hormone; antimullerian hormone; antral follicle count; inhibin-B
ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; EARLY MENOPAUSAL
   TRANSITION; POLYCYSTIC-OVARY-SYNDROME; MIDDLE-AGED WOMEN; REGULAR
   MENSTRUAL CYCLES; INHIBIN-B; ANTIMULLERIAN HORMONE; LONGITUDINAL
   CHANGES; DEPRESSIVE SYMPTOMS
AB Objective: The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.
   Method(s): Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimullerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.
   Result(s): STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.
   Conclusion(s): STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. (Fertil Steril (R) 2012;97:843-51. (C)2012 by American Society for Reproductive Medicine.)
C1 [Harlow, Sioban D.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Gass, Margery] N Amer Menopause Soc, Mayfield Hts, OH USA.
   [Hall, Janet E.] Harvard Univ, Sch Med, Dept Med, Endocrine Soc, Boston, MA USA.
   [Lobo, Roger] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
   [Maki, Pauline] Univ Illinois, Dept Psychiat & Psychol, Chicago, IL USA.
   [Rebar, Robert W.] Amer Soc Reprod Med, Birmingham, AL USA.
   [Sherman, Sherry] NIA, Bethesda, MD 20892 USA.
   [Sluss, Patrick M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [de Villiers, Tobie J.] Int Menopause Soc, Cape Town, South Africa.
RP Harlow, SD (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM harlow@umich.edu
FU National Institute on Aging (NIA); Eunice Kennedy Shriver National
   Institute of Child Health and Human Development (NICHD); North American
   Menopause Society (NAMS); Endocrine Society; National Institute on
   Mental Health (NIMH); National Institute of Allergy and Infectious
   Diseases (NIAID); National Institute on Drug Abuse (NIDA); Royal Ottawa
   Foundation for Mental Health; Mayo Clinic; Baycrest; Northwestern
   University; Society for Women's Health Research; International Menopause
   Society; Pfizer; Australasian Pacific Menopause Society; Virginia
   Commonwealth University Institute for Women's Health; Adcock Ingram;
   Servier; Amgen; Bayer; National Institutes of Health (NIH); Department
   of Health and Human Services (DHHS), through the National Institute on
   Aging (NIA) [AG039961]; NIH Office of Research on Women's Health (ORWH);
   International Menopause Society (IMS)
FX S. D. H. has grant support from the National Institute on Aging (NIA)
   and Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD) and receives travel support from NAMS. M. G.
   receives salary support from The North American Menopause Society
   (NAMS). J.E.H. has grant support from NIA and receives travel support
   from the Endocrine Society. R. L. is past president of the American
   Society for Reproductive Medicine (ASRM). P. M. receives grant support
   from the National Institute on Mental Health (NIMH), the NIA, the
   National Institute of Allergy and Infectious Diseases (NIAID), and the
   National Institute on Drug Abuse (NIDA); is on the Board of Trustees for
   NAMS; and has previously consulted for Noven Pharmaceuticals, received
   lecture fees from the Royal Ottawa Foundation for Mental Health, the
   Mayo Clinic, Baycrest, and Northwestern University and received travel
   support from the Society for Women's Health Research, the International
   Menopause Society, Pfizer, the Australasian Pacific Menopause Society,
   Virginia Commonwealth University Institute for Women's Health. R. W. R.
   receives salary support from ASRM. S. S. has nothing to disclose. P. M.
   S. has nothing to disclose. T.J.d.V. declares no direct conflict of
   interest as regards the submitted article but has in the past received
   consultancy fees from Adcock Ingram and Pfizer; speaker's fees from
   Servier; and travel support from Amgen, Pfizer, and Bayer.; The Stages
   of Reproductive Aging Workshop (STRAW) + 10 had grant support from the
   National Institutes of Health (NIH), Department of Health and Human
   Services (DHHS), through the National Institute on Aging (NIA)
   (AG039961), and the NIH Office of Research on Women's Health (ORWH) as
   well as from The North American Menopause Society (NAMS), the American
   Society for Reproductive Medicine (ASRM), the International Menopause
   Society (IMS), and the Endocrine Society.
NR 90
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD APR
PY 2012
VL 97
IS 4
BP 843
EP 851
DI 10.1016/j.fertnstert.2012.01.128
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 917AE
UT WOS:000302143500013
PM 22341880
ER

PT J
AU Huang, H
   Hansen, KR
   Factor-Litvak, P
   Carson, SA
   Guzick, DS
   Santoro, N
   Diamond, MP
   Eisenberg, E
   Zhang, HP
AF Huang, Hao
   Hansen, Karl R.
   Factor-Litvak, Pamela
   Carson, Sandra A.
   Guzick, David S.
   Santoro, Nanette
   Diamond, Michael P.
   Eisenberg, Esther
   Zhang, Heping
CA Natl Inst Child Hlth Human Dev
TI Predictors of pregnancy and live birth after insemination in couples
   with unexplained or male-factor infertility
SO FERTILITY AND STERILITY
LA English
DT Article
DE Infertility; lifestyle; pregnancy; live birth; insemination;
   superovulation
ID ALCOHOL-CONSUMPTION; CAFFEINE INTAKE; CIGARETTE-SMOKING; LIFE-STYLE;
   INTRAUTERINE INSEMINATION; EUROPEAN MULTICENTER; OCCUPATIONAL FACTORS;
   SEMEN QUALITY; FECUNDABILITY; FERTILITY
AB Objective: To identify risk factors for pregnancy outcomes in couples treated with intracervical or intrauterine insemination, with or without superovulation for unexplained or male-factor infertility.
   Design: Secondary analysis of data from a randomized superovulation and intrauterine insemination trial.
   Setting: Academic medical centers.
   Intervention(s): Treatment continued for four cycles unless pregnancy was achieved.
   Patient(s): Out of 932 couples randomized to four treatment groups, 664 couples who had completed the lifestyle questionnaires were assessed for occurrence of pregnancy and live birth.
   Main Outcome Measure(s): Pregnancy and live birth.
   Result(s): The pregnancy and live birth rates were significantly higher in couples in which the female partners reported that they had consumed coffee or tea in the past or drank alcoholic beverages in the past (past users) compared with those who had never consumed coffee, tea, or alcoholic beverages. Past users also had significantly higher pregnancy and live birth rates than those currently consuming coffee or tea or alcoholic beverages. Demographic, occupational exposure, and other lifestyle factors were not significant.
   Conclusion(s): Couples in which the female partners drank coffee, tea, or alcoholic beverages in the past had higher pregnancy and live birth rates compared with never or current users. When discontinuing these habits, they might have made other lifestyle changes to improve the pregnancy outcome. (Fertil Steril (R) 2012; 97: 959-67. (C) 2012 by American Society for Reproductive Medicine.)
C1 [Huang, Hao; Zhang, Heping] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
   [Hansen, Karl R.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Sect Reprod Endocrinol & Infertil, Oklahoma City, OK 73190 USA.
   [Factor-Litvak, Pamela] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
   [Carson, Sandra A.] Women & Infants Hosp Rhode Isl, Div Reprod Endocrinol & Infertil, Providence, RI 02908 USA.
   [Guzick, David S.] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA.
   [Santoro, Nanette] Univ Colorado, Sch Med, Dept Obstet & Gynecol, Aurora, CO USA.
   [Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Detroit, MI USA.
   [Eisenberg, Esther] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Nashville, TN 37232 USA.
   [Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Med Network, Reprod Sci Branch, Ctr Populat Res,NIH, Bethesda, MD USA.
RP Zhang, HP (reprint author), 60 Coll St, New Haven, CT 06520 USA.
EM heping.zhang@yale.edu
OI Diamond, Michael/0000-0001-6353-4489
FU National Institutes of Health (NIH)/National Institute of Child Health
   and Human Development (NICHD) [HD55925, U10 HD39005]
FX Supported by National Institutes of Health (NIH)/National Institute of
   Child Health and Human Development (NICHD) grants HD55925 and U10
   HD39005. The content is solely the responsibility of the authors and
   does not necessarily represent the official views of the NICHD or NIH.
NR 39
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD APR
PY 2012
VL 97
IS 4
BP 959
EP U374
DI 10.1016/j.fertnstert.2012.01.090
PG 14
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 917AE
UT WOS:000302143500031
PM 22270557
ER

PT J
AU Rasmussen, DL
   Kobayashi, SD
   DeLeo, FR
AF Rasmussen, Devon L.
   Kobayashi, Scott D.
   DeLeo, Frank R.
TI Flexicate molecules as a potential new class of antibiotics
SO FUTURE MICROBIOLOGY
LA English
DT Article
DE antibiotic; antimicrobial; flexicate; helicate
ID OPTICALLY PURE; DNA-BINDING; SUPRAMOLECULAR CYLINDERS; BIS(PYRIDYLIMINE)
   LIGAND; DINUCLEAR COMPLEXES
AB Evaluation of: Howson SE, Bolhuis A, Brabec V et al. Optically pure, water-stable metallo-helical 'flexicate' assemblies with antibiotic activity. Nat. Chem. 4(1), 31-36 (2011). Helicates are a-helical, nonpeptide complexes that bind to DNA and exhibit antimicrobial activity. In the past, enthusiasm for the use of helicates in biological applications was limited, at least in part, by the presence of a racemic mixture of enantiomers or the formation of complexes that are insoluble in aqueous solutions. Recently, Howson et al, overcame the barriers associated with helicate synthesis by generating helicate-like complexes that are soluble and stable in water, optically pure and synthetically flexible. The mechanism synthesizes nonpeptide mimetic a-helical 'flexicates' that bind to DNA and show broad-spectrum antimicrobial activity against representative Gram-positive and Gram-negative bacterial pathogens. Although the application of flexicates as an antimicrobial therapy remains to be determined, this study provides important insight into flexicate activity and the prospective use of flexicates as microbicidal agents.
C1 [Rasmussen, Devon L.; Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Bacteriol Pathogenesis, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA.
RP DeLeo, FR (reprint author), NIAID, Lab Bacteriol Pathogenesis, Rocky Mt Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516
FU National Institute of Allergy and Infectious Diseases, NIH
FX The authors are supported by the Intramural Research Program of the
   National Institute of Allergy and Infectious Diseases, NIH. The authors
   have no other relevant affiliations or financial involvement with any
   organization or entity with a financial interest in or financial
   conflict with the subject matter or materials discussed in the
   manuscript apart from those disclosed.
NR 18
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PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
   1QB, ENGLAND
SN 1746-0913
J9 FUTURE MICROBIOL
JI Future Microbiol.
PD APR
PY 2012
VL 7
IS 4
BP 445
EP 448
DI 10.2217/FMB.12.26
PG 4
WC Microbiology
SC Microbiology
GA 917SN
UT WOS:000302199000008
PM 22439721
ER

PT J
AU Cook, MB
   Shaheen, NJ
   Anderson, LA
   Giffen, C
   Chow, WH
   Vaughan, TL
   Whiteman, DC
   Corley, DA
AF Cook, Michael B.
   Shaheen, Nicholas J.
   Anderson, Lesley A.
   Giffen, Carol
   Chow, Wong-Ho
   Vaughan, Thomas L.
   Whiteman, David C.
   Corley, Douglas A.
TI Cigarette Smoking Increases Risk of Barrett's Esophagus: An Analysis of
   the Barrett's and Esophageal Adenocarcinoma Consortium
SO GASTROENTEROLOGY
LA English
DT Article
DE BEACON; Esophageal Cancer; Population Study; Tobacco
ID GASTROESOPHAGEAL-REFLUX DISEASE; GASTRIC CARDIA; GENERAL-POPULATION;
   LUNG-CANCER; ACID REFLUX; ESOPHAGOGASTRIC JUNCTION; PROSPECTIVE COHORT;
   TOTAL EXPOSURE; ALCOHOL; TOBACCO
AB BACKGROUND & AIMS: Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett's esophagus. We investigated whether tobacco smoking and other factors increase risk for Barrett's esophagus.
   METHODS: We analyzed data from 5 case-control studies included in the international Barrett's and Esophageal Adenocarcinoma Consortium. We compared data from subjects with Barrett's esophagus (n = 1059) with those from subjects with gastroesophageal reflux disease (gastroesophageal reflux disease controls, n = 1332), and population-based controls (n = 1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for Barrett's esophagus.
   RESULTS: Subjects with Barrett's esophagus were significantly more likely to have ever smoked cigarettes than the population-based controls (odds ratio [OR] = 1.67; 95% confidence interval [CI]: 1.04-2.67) or gastroesophageal reflux disease controls (OR = 1.61; 95% CI: 1.33-1.96). Increasing pack-years of smoking increased the risk for Barrett's esophagus. There was evidence of a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (95% CI: 0.25-0.52).
   CONCLUSIONS: Cigarette smoking is a risk factor for Barrett's esophagus. The association was strengthened with increased exposure to smoking until similar to 20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to development of Barrett's esophagus.
C1 [Cook, Michael B.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
   [Shaheen, Nicholas J.] Univ N Carolina, Chapel Hill, NC USA.
   [Anderson, Lesley A.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
   [Giffen, Carol] Informat Management Serv Inc, Bethesda, MD USA.
   [Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
   [Whiteman, David C.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
   [Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA.
   [Corley, Douglas A.] Kaiser Permanente, Oakland Med Ctr, Oakland, CA USA.
RP Cook, MB (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS,Suite 550,Room 5014, Bethesda, MD 20852 USA.
EM michael.cook@nih.gov
RI Shaheen, Nicholas/A-1898-2013; Cook, Michael/A-5641-2009; Whiteman,
   David/P-2728-2014; 
OI Cook, Michael/0000-0002-0533-7302; Whiteman, David/0000-0003-2563-9559;
   Anderson, Lesley/0000-0002-1000-3649
FU National Institutes of Health; National Institute of Diabetes and
   Digestive and Kidney Diseases [K23DK59311, R03DK75842]; Ireland-Northern
   Ireland Co-operation Research Project; Northern Ireland Research and
   Development Office; Health Research Board, Ireland; Ulster Cancer
   Foundation (Belfast, Northern Ireland); National Institutes of Health
   Epidemiology and Incidence of Barrett's Esophagus [RO1 DK63616-01];
   Barrett's Esophagus and Women [1R21DK077742-01A1]; National Cancer
   Institute [5 RO1 CA 001833-02, R01 CA72866]; Established Investigator
   Award in Cancer Prevention and Control [K05 CA124911]
FX M.B.C. and W.-H.C. were supported by the Intramural Program of the
   National Institutes of Health. The Epidemiologic Case-Control Study of
   Barrett's Esophagus was funded by the National Institute of Diabetes and
   Digestive and Kidney Diseases (K23DK59311 and R03DK75842) awarded to
   N.J.S. The Factors Influencing the Barrett's Adenocarcinoma Relationship
   Study was funded by an Ireland-Northern Ireland Co-operation Research
   Project Grant sponsored by the Northern Ireland Research and Development
   Office, and the Health Research Board, Ireland (All-Ireland Case-Control
   Study of Oesophageal Adenocarcinoma and Barrett's Oesophagus, awarded to
   L.J.M. and Harry Comber). Additional funding was provided by the Ulster
   Cancer Foundation (Belfast, Northern Ireland) and the Northern Ireland
   Research and Development Office Clinical Fellowship. The Kaiser
   Permanente Barrett's Esophagus studies and the data integration for the
   current project were funded by National Institutes of Health
   Epidemiology and Incidence of Barrett's Esophagus RO1 DK63616-01
   (D.A.C.) and Barrett's Esophagus and Women 1R21DK077742-01A1 (D.A.C.,
   N.J.S.). The Study of Digestive Health was supported by grant number 5
   RO1 CA 001833-02 from the National Cancer Institute awarded to D.C.W.,
   Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, Sandra J. Pavey,
   David M. Purdie, Penelope M. Webb, David Gotley, B. Mark Smithers, Glyn
   G. Jamieson, Paul Drew, David I. Watson, Andrew Clouston. Its contents
   are solely the responsibility of the authors and do not necessarily
   represent the official views of the National Cancer Institute. The Study
   of Reflux Disease was funded by the National Cancer Institute (R01
   CA72866) awarded to T.L.V. and Diana Farrow; Established Investigator
   Award in Cancer Prevention and Control (K05 CA124911) awarded to T.L.V.
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PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2012
VL 142
IS 4
BP 744
EP 753
DI 10.1053/j.gastro.2011.12.049
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 919BU
UT WOS:000302296400023
PM 22245667
ER

PT J
AU Roessler, S
   Long, EL
   Budhu, A
   Chen, YD
   Zhao, XL
   Ji, JF
   Walker, R
   Jia, HL
   Ye, QH
   Qin, LX
   Tang, ZY
   He, P
   Hunter, KW
   Thorgeirsson, SS
   Meltzer, PS
   Wang, XW
AF Roessler, Stephanie
   Long, Ezhou Lori
   Budhu, Anuradha
   Chen, Yidong
   Zhao, Xuelian
   Ji, Junfang
   Walker, Robert
   Jia, Hu-Liang
   Ye, Qing-Hai
   Qin, Lun-Xiu
   Tang, Zhao-You
   He, Ping
   Hunter, Kent W.
   Thorgeirsson, Snorri S.
   Meltzer, Paul S.
   Wang, Xin Wei
TI Integrative Genomic Identification of Genes on 8p Associated With
   Hepatocellular Carcinoma Progression and Patient Survival
SO GASTROENTEROLOGY
LA English
DT Article
DE Liver Cancer; Tumor Profiling; Cancer Driver Genes
ID GTPASE-ACTIVATING PROTEIN; NEGATIVE BREAST-CANCER; ARRAY CGH DATA;
   TUMOR-SUPPRESSOR; LIVER-CANCER; EXPRESSION; DLC-1; METASTASIS; CELLS;
   PREDICTION
AB BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is an aggressive malignancy; its mechanisms of development and progression are poorly understood. We used an integrative approach to identify HCC driver genes, defined as genes whose copy numbers associate with gene expression and cancer progression. METHODS: We combined data from high-resolution, array-based comparative genomic hybridization and transcriptome analysis of HCC samples from 76 patients with hepatitis B virus infection with data on patient survival times. Candidate genes were functionally validated using in vitro and in vivo models. RESULTS: Unsupervised analyses of array comparative genomic hybridization data associated loss of chromosome 8p with poor outcome (reduced survival time); somatic copy number alterations correlated with expression of 27.3% of genes analyzed. We associated expression levels of 10 of these genes with patient survival times in 2 independent cohorts (comprising 319 cases of HCC with mixed etiology) and 3 breast cancer cohorts (637 cases). Among the 10-gene signature, a cluster of 6 genes on 8p, (DLC1, CCDC25, ELP3, PROSC, SH2D4A, and SORBS3) were deleted in HCCs from patients with poor outcomes. In vitro and in vivo analyses indicated that the products of PROSC, SH2D4A, and SORBS3 have tumor-suppressive activities, along with the known tumor suppressor gene DLC1. CONCLUSIONS: We used an unbiased approach to identify 10 genes associated with HCC progression. These might be used in assisting diagnosis and to stage tumors based on gene expression patterns.
C1 [Roessler, Stephanie; Budhu, Anuradha; Zhao, Xuelian; Ji, Junfang; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
   [Long, Ezhou Lori; Chen, Yidong; Walker, Robert] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Jia, Hu-Liang; Ye, Qing-Hai; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China.
   [He, Ping] FDA CBER OBRR, Div Hematol, Bethesda, MD USA.
   [Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
   [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009
FU Center for Cancer Research, the US National Cancer Institute [Z01 BC
   010313, Z01 BC 010876]
FX Supported in part by the Intramural Research Program of the Center for
   Cancer Research, the US National Cancer Institute (Z01 BC 010313 and Z01
   BC 010876).
NR 48
TC 71
Z9 73
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2012
VL 142
IS 4
BP 957
EP U451
DI 10.1053/j.gastro.2011.12.039
PG 22
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 919BU
UT WOS:000302296400045
PM 22202459
ER

PT J
AU Thomas, E
   Gonzalez, VD
   Li, QS
   Modi, AA
   Chen, WP
   Noureddin, M
   Rotman, Y
   Liang, TJ
AF Thomas, Emmanuel
   Gonzalez, Veronica D.
   Li, Qisheng
   Modi, Ankit A.
   Chen, Weiping
   Noureddin, Mazen
   Rotman, Yaron
   Liang, T. Jake
TI HCV Infection Induces a Unique Hepatic Innate Immune Response Associated
   With Robust Production of Type III Interferons
SO GASTROENTEROLOGY
LA English
DT Article
DE IRF; Cytokine; IL29; Nonresponder
ID C VIRUS-INFECTION; ADAPTIVE IMMUNITY; CHIMPANZEES; REPLICATION;
   RECOGNITION; MECHANISM; KINETICS; CULTURE; SYSTEM; GENOME
AB BACKGROUND & AIMS: Polymorphisms in the IL28B gene have been associated with clearance of hepatitis C virus (HCV), indicating a role for type III interferons (IFNs) in HCV infection. Little is known about the function of type III IFNs in intrinsic antiviral innate immunity. METHODS: We used in vivo and in vitro models to characterize the role of the type III IFNs in HCV infection and analyzed gene expression in liver biopsy samples from HCV-infected chimpanzees and patients. Messenger RNA and protein expression were studied in HCV-infected hepatoma cell lines and primary human hepatocytes. RESULTS: HCV infection of primary human hepatocytes induced production of chemokines and type III IFNs, including interleukin (IL)-28, and led to expression of IFN-stimulated genes (ISGs). Chimpanzees infected with HCV showed rapid induction of hepatic type III IFN, associated with up-regulation of ISGs and minimal induction of type I IFNs. In liver biopsy specimens from HCV-infected patients, hepatic expression of IL-28 correlated with levels of ISGs but not of type I IFNs. HCV infection produced extensive changes with gene expression in addition to ISGs in primary human hepatocytes. The induction of type III IFNs is regulated by IFN regulatory factor 3 and nuclear factor kappa B. Type III IFNs up-regulate ISGs with a different kinetic profile than type 1 IFNs and induce a distinct set of genes, which might account for their functional differences. CONCLUSIONS: HCV infection results predominantly in induction of type III IFNs in livers of humans and chimpanzees; the level of induction correlates with hepatic levels of ISGs. These findings might account for the association among IL-28, level of ISGs, and recovery from HCV infection and provide a therapeutic strategy for patients who do not respond to IFN therapy.
C1 [Thomas, Emmanuel; Gonzalez, Veronica D.; Li, Qisheng; Modi, Ankit A.; Noureddin, Mazen; Rotman, Yaron; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
   [Chen, Weiping] NIDDK, Microarray Core Facil, NIH, Bethesda, MD 20892 USA.
RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM jakel@bdg10.niddk.nih.gov
RI Li, Qisheng/K-1909-2013; 
OI Rotman, Yaron/0000-0002-7549-8216
FU National Institute of Diabetes and Digestive and Kidney Diseases;
   National Institutes of Health [N01-DK-7-0004/HHSN26700700004C]; Swedish
   Research Council; Wenner-Gren Foundation
FX Supported by the Intramural Research Program of the National Institute
   of Diabetes and Digestive and Kidney Diseases. E. T. was supported by
   funding from the National Institutes of Health Loan Repayment Program.
   V. D. G. was supported by the Swedish Research Council and the
   Wenner-Gren Foundation. PHH cultures were provided by the National
   Institutes of Health-funded Liver Tissue Procurement and Cell
   Distribution System (N01-DK-7-0004/HHSN26700700004C) (principal
   investigator: Stephen Strom, University of Pittsburgh).
NR 27
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U1 0
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2012
VL 142
IS 4
BP 978
EP 988
DI 10.1053/j.gastro.2011.12.055
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 919BU
UT WOS:000302296400047
PM 22248663
ER

PT J
AU Andersen, JB
   Spee, B
   Blechacz, BR
   Avital, I
   Komuta, M
   Barbour, A
   Conner, EA
   Gillen, MC
   Roskams, T
   Roberts, LR
   Factor, VM
   Thorgeirsson, SS
AF Andersen, Jesper B.
   Spee, Bart
   Blechacz, Boris R.
   Avital, Itzhak
   Komuta, Mina
   Barbour, Andrew
   Conner, Elizabeth A.
   Gillen, Matthew C.
   Roskams, Tania
   Roberts, Lewis R.
   Factor, Valentina M.
   Thorgeirsson, Snorri S.
TI Genomic and Genetic Characterization of Cholangiocarcinoma Identifies
   Therapeutic Targets for Tyrosine Kinase Inhibitors
SO GASTROENTEROLOGY
LA English
DT Article
DE Genetic Analysis; Gene Expression; CCA; Hepatic
ID HEPATOCELLULAR-CARCINOMA; INTRAHEPATIC CHOLANGIOCARCINOMA; BILIARY
   CANCER; EXPRESSION PROFILES; BREAST-CANCER; LUNG-CANCER; PHASE-II;
   RECEPTOR; MUTATIONS; SURVIVAL
AB BACKGROUND & AIMS: Cholangiocarcinoma is a heterogeneous disease with a poor outcome that accounts for 5% - 10% of primary liver cancers. We characterized its genomic and genetic features and associated these with patient responses to therapy. METHODS: We profiled the transcriptomes from 104 surgically resected cholangiocarcinoma samples collected from patients in Australia, Europe, and the United States; epithelial and stromal compartments from 23 tumors were laser capture micro-dissected. We analyzed mutations in KRAS, epidermal growth factor receptor (EGFR), and BRAF in samples from 69 tumors. Changes in gene expression were validated by immunoblotting and immunohistochemistry; integrative genomics combined data from the patients with data from 7 human cholangiocarcinoma cell lines, which were then exposed to trastuzumab and lapatinib. RESULTS: Patients were classified into 2 subclasses, based on 5-year survival rate (72% vs 30%; chi(2) = 11.61; P < .0007), time to recurrence (13.7 vs 22.7 months; P < .001), and the absence or presence of KRAS mutations (24.6%), respectively. Class comparison identified 4 survival subgroups (SGI-IV; chi(2) = 8.34; P < .03); SGIII was characterized by genes associated with proteasomal activity and the worst prognosis. The tumor epithelium was defined by deregulation of the HER2 network and frequent overexpression of EGFR, the hepatocyte growth factor receptor (MET), pRPS6, and Ki67, whereas stroma was enriched in inflammatory cytokines. Lapatinib, an inhibitor of HER2 and EGFR, was more effective in inhibiting growth of cholangiocarcinoma cell lines than trastuzumab. CONCLUSIONS: We provide insight into the pathogenesis of cholangiocarcinoma and identify previously unrecognized subclasses of patients, based on KRAS mutations and increased levels of EGFR and HER2 signaling, who might benefit from dual-target tyrosine kinase inhibitors. The group of patients with the worst prognosis was characterized by transcriptional enrichment of genes that regulate proteasome activity, indicating new therapeutic targets.
C1 [Andersen, Jesper B.; Conner, Elizabeth A.; Gillen, Matthew C.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
   [Avital, Itzhak] NIH, Surg Branch, Bethesda, MD 20892 USA.
   [Spee, Bart; Komuta, Mina; Roskams, Tania] Univ Leuven, Louvain, Belgium.
   [Blechacz, Boris R.; Roberts, Lewis R.] Mayo Clin, Rochester, MN USA.
   [Barbour, Andrew] Univ Queensland, Brisbane, Qld, Australia.
RP Thorgeirsson, SS (reprint author), NCI, Bldg 37,Room 4146A,37 Convent Dr, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
RI Barbour, Andrew/F-4717-2010; 
OI Roberts, Lewis/0000-0001-7885-8574; Andersen , Jesper
   B/0000-0003-1760-5244
FU Center for Cancer Research, National Cancer Institute, National
   Institutes of Health; National Institutes of Health [CA100882, CA128633,
   P30DK084567]; Danish Medical Research Council [271-070712]
FX Supported by the Intramural Research Program of the Center for Cancer
   Research, National Cancer Institute, National Institutes of Health;
   National Institutes of Health grants CA100882 and CA128633 (to L.R.R.)
   and P30DK084567 (Mayo Clinic Center for Cell Signaling in
   Gastroenterology); and grant 271-070712 from the Danish Medical Research
   Council (to J.B.A.).
NR 31
TC 115
Z9 120
U1 0
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2012
VL 142
IS 4
BP 1021
EP U552
DI 10.1053/j.gastro.2011.12.005
PG 26
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 919BU
UT WOS:000302296400051
PM 22178589
ER

PT J
AU Logue, JS
   Morrison, DK
AF Logue, Jeremy S.
   Morrison, Deborah K.
TI Complexity in the signaling network: insights from the use of targeted
   inhibitors in cancer therapy
SO GENES & DEVELOPMENT
LA English
DT Review
DE cancer therapy; signal transduction; targeted inhibitors
ID SRC FAMILY KINASES; CELL LUNG-CANCER; TYROSINE KINASE;
   ACQUIRED-RESISTANCE; BREAST-CANCER; TUMOR-SUPPRESSOR;
   PHOSPHATIDYLINOSITOL 3-KINASE/AKT; TRASTUZUMAB RESISTANCE; PATHWAY
   ACTIVATION; MET AMPLIFICATION
AB Cancer often arises when normal cellular growth goes awry due to defects in critical signal transduction pathways. A growing number of inhibitors that target specific components of these pathways are in clinical use, but the success of these agents has been limited by the resistance to inhibitor therapy that ultimately develops. Studies have now shown that cancer cells respond to chronic drug treatment by adapting their signaling circuitry, taking advantage of pathway redundancy and routes of feedback and cross-talk to maintain their function. This review focuses on the compensatory signaling mechanisms highlighted by the use of targeted inhibitors in cancer therapy.
C1 [Logue, Jeremy S.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM morrisod@mail.nih.gov
FU National Cancer Institute
FX Our work is supported by federal funds from the National Cancer
   Institute.
NR 80
TC 87
Z9 88
U1 0
U2 12
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD APR 1
PY 2012
VL 26
IS 7
BP 641
EP 650
DI 10.1101/gad.186965.112
PG 10
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 921UJ
UT WOS:000302502900003
PM 22474259
ER

PT J
AU Biesecker, LG
AF Biesecker, Leslie G.
TI Opportunities and challenges for the integration of massively parallel
   genomic sequencing into clinical practice: lessons from the ClinSeq
   project
SO GENETICS IN MEDICINE
LA English
DT Article
DE genetic mutation; incidental findings; inherited disease; massively
   parallel sequencing
ID MEDICINE; MUTATION; DNA
AB Purpose: The debate surrounding the return of results from high-throughput genomic interrogation encompasses many important issues including ethics, law, economics, and social policy. As well, the debate is also informed by the molecular, genetic, and clinical foundations of the emerging field of clinical genomics, which is based on this new technology. This article outlines the main biomedical considerations of sequencing technologies and demonstrates some of the early clinical experiences with the technology to enable the debate to stay focused on real-world practicalities.
   Methods: These experiences are based on early data from the ClinSeq project, which is a project to pilot the use of massively parallel sequencing in a clinical research context with a major aim to develop modes of returning results individual subjects.
   Results: The study has enrolled >900 subjects and generated exome sequence data on 572 subjects. These data are beginning to be interpreted and returned to the subjects, which provides examples of the potential usefulness and pitfalls of clinical genomics.
   Conclusion: There are numerous genetic results that can be readily derived from a genome including rare, high-penetrance traits, and carrier states. However, much work needs to be done to develop the tools and resources for genomic interpretation. The main lesson learned is that a genome sequence may be better considered as a health-care resource, rather than a test, one that can be interpreted and used over the lifetime of the patient.
C1 [Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
   [Biesecker, Leslie G.] NHGRI, Natl Inst Hlth Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
EM leslieb@helix.nih.gov
FU National Institutes of Health, National Human Genome Research Institute
   [2-R01-HG003178]
FX The author acknowledges and thanks all members of both the ClinSeq and
   the rare disease research teams for their outstanding efforts in these
   programs, which have generated and pursued many of the ideas described
   here. The author is supported entirely by the Intramural Research
   Program of the National Human Genome Research Institute of the National
   Institutes of Health. The symposium at which the oral version of this
   article was presented was supported by National Institutes of Health,
   National Human Genome Research Institute grant no. 2-R01-HG003178 on
   "Managing Incidental Findings and Research Results in Genomic Biobanks &
   Archives" (S. Wolf, principal investigator).
NR 14
TC 83
Z9 85
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD APR
PY 2012
VL 14
IS 4
SI SI
BP 393
EP 398
DI 10.1038/gim.2011.78
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 922RL
UT WOS:000302565600005
PM 22344227
ER

PT J
AU Green, RC
   Berg, JS
   Berry, GT
   Biesecker, LG
   Dimmock, DP
   Evans, JP
   Grody, WW
   Hegde, MR
   Kalia, S
   Korf, BR
   Krantz, I
   McGuire, AL
   Miller, DT
   Murray, MF
   Nussbaum, RL
   Plon, SE
   Rehm, HL
   Jacob, HJ
AF Green, Robert C.
   Berg, Jonathan S.
   Berry, Gerard T.
   Biesecker, Leslie G.
   Dimmock, David P.
   Evans, James P.
   Grody, Wayne W.
   Hegde, Madhuri R.
   Kalia, Sarah
   Korf, Bruce R.
   Krantz, Ian
   McGuire, Amy L.
   Miller, David T.
   Murray, Michael F.
   Nussbaum, Robert L.
   Plon, Sharon E.
   Rehm, Heidi L.
   Jacob, Howard J.
TI Exploring concordance and discordance for return of incidental findings
   from clinical sequencing
SO GENETICS IN MEDICINE
LA English
DT Article
DE incidental findings; whole-exome sequencing; whole-genome sequencing
ID GENOMIC MEDICINE; PATIENT
AB Purpose: The aim of this study was to explore specific conditions and types of genetic variants that specialists in genetics recommend should be returned as incidental findings in clinical sequencing.
   Methods: Sixteen specialists in clinical genetics and/or molecular medicine selected variants in 99 common conditions to return to the ordering physician if discovered incidentally through whole-genome sequencing. For most conditions, the specialists independently considered three molecular scenarios for both adults and minor children: a known pathogenic mutation, a truncating variant presumed pathogenic (where other truncating variants are known to be pathogenic), and a missense variant predicted in silico to be pathogenic.
   Results: On average, for adults and children, respectively, each specialist selected 83.5 and 79.0 conditions or genes of 99 in the known pathogenic mutation categories, 57.0 and 53.5 of 72 in the truncating variant categories, and 33.4 and 29.7 of 72 in the missense variant categories. Concordance in favor of disclosure within the adult/known pathogenic mutation category was 100% for 21 conditions or genes and 80% or higher for 64 conditions or genes.
   Conclusion: Specialists were highly concordant for the return of findings for 64 conditions or genes if discovered incidentally during whole-exome sequencing or whole-genome sequencing.
C1 [Green, Robert C.; Kalia, Sarah; Murray, Michael F.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Green, Robert C.; Berry, Gerard T.; Kalia, Sarah; Miller, David T.; Murray, Michael F.; Rehm, Heidi L.] Harvard Univ, Sch Med, Boston, MA USA.
   [Green, Robert C.; Murray, Michael F.; Rehm, Heidi L.] Partners Ctr Personalized Genet Med, Boston, MA USA.
   [Berg, Jonathan S.; Evans, James P.] Univ N Carolina Chapel Hill Sch Med, Dept Genet, Chapel Hill, NC USA.
   [Berry, Gerard T.; Miller, David T.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
   [Berry, Gerard T.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
   [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Dimmock, David P.] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA.
   [Grody, Wayne W.] Univ Calif Los Angeles, Sch Med, Dept Human Genet, Div Med Genet, Los Angeles, CA USA.
   [Grody, Wayne W.] Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Div Mol Pathol, Los Angeles, CA 90024 USA.
   [Grody, Wayne W.] Univ Calif Los Angeles, Sch Med, Dept Pediat, Div Pediat Genet, Los Angeles, CA 90024 USA.
   [Hegde, Madhuri R.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
   [Korf, Bruce R.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA.
   [Krantz, Ian] Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA.
   [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
   [Miller, David T.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
   [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, Div Med Genet, San Francisco, CA USA.
   [Plon, Sharon E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Plon, Sharon E.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Rehm, Heidi L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Jacob, Howard J.] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA.
RP Green, RC (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM rcgreen@genetics.med.harvard.edu
RI Dimmock, David/I-7913-2015; 
OI Dimmock, David/0000-0001-6690-2523; Berry, Gerard/0000-0001-5299-3313
FU National Institutes of Health [HG02213, AG027841, HG005491, HG005092,
   HG006615, HG003178, HG006500, CA138836, HG006485]; Manton Center for
   Orphan Disease Research; National Human Genome Research Institute;
   Baylor College of Medicine; Baylor Annual Fund
FX Funding for this work was provided by National Institutes of Health
   grants HG02213, AG027841, HG005491, HG005092, HG006615, HG003178,
   HG006500, CA138836, and HG006485. G.T.B. is supported by the Manton
   Center for Orphan Disease Research. L.G.B. is supported by intramural
   funding from the National Human Genome Research Institute. A.L.M. is
   supported by the Baylor College of Medicine Clinical and Translational
   Research Program and the Baylor Annual Fund.
NR 18
TC 93
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U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD APR
PY 2012
VL 14
IS 4
SI SI
BP 405
EP 410
DI 10.1038/gim.2012.21
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 922RL
UT WOS:000302565600007
PM 22422049
ER

PT J
AU Lockhart, NC
   Yassin, R
   Weil, CJ
   Compton, CC
AF Lockhart, Nicole C.
   Yassin, Rihab
   Weil, Carol J.
   Compton, Carolyn C.
TI Intersection of biobanking and clinical care: should discrepant
   diagnoses and pathological findings be returned to research
   participants?
SO GENETICS IN MEDICINE
LA English
DT Article
DE biobank; biospecimen; diagnostic discrepancy; incidental finding; return
   of research results
ID MANAGING INCIDENTAL FINDINGS
AB Diagnostic discrepancies occur when the diagnosis made on a biospecimen during the course of review at a biobank differs from the original clinical diagnosis. These diagnostic discrepancies detected during biobanking present: unique challenges that are distinct from other types of research results or incidental findings. The proposed process for reporting diagnostic discrepancies or pathological incidental findings identified through a quality assurance evaluation at the biobank includes verification of the biospecimen identity, verification of the diagnosis within the biobank, and re-review of the case by the pathologist at the biospecimen collection site. If the pathologist at the biobank and the original pathologist do not reach agreement, an impartial and knowledgeable third party is consulted. The decision as to whether and how to notify research participants of any confirmed changes in diagnosis would be determined by institutional procedures. Implementation of this proposed process will require clear delineation of the roles and responsibilities of all involved parties in order to promote excellence in patient care and ensure that researchers have access to biospecimens of requisite quality.
C1 [Lockhart, Nicole C.; Weil, Carol J.; Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA.
   [Yassin, Rihab] NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA.
RP Lockhart, NC (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA.
EM lockhani@mail.nih.gov
FU National Cancer Institute (NCI); National Institutes of Health
   (NIH)/National Human Genome Research Institute [2-R01-HG003178]
FX We thank all who participated in discussions at the National Cancer
   Institute (NCI)-sponsored workshop on Release of Research Results to
   Participants in Biospecimen Studies, particularly participants in the
   diagnostic discrepancy session. The diagnostic discrepancy session was
   chaired by Jared Schwartz and cochaired by N.C.L. Participants in the
   diagnostic discrepancy session included Joy Boyer, Lynn Dressler, Symma
   Finn, Marianne Henderson, Jennifer Hunt, Jennifer Loud, Mary Majumder,
   Mary Lou Smith, and Sheila Cohen Zimmet. Andrea Kelly of Rose Li and
   associates prepared the meeting summary. The meeting was held 8-9 July
   2010, and the complete meeting summary and attendee list may be found at
   http://biospecimens.cancer.gov/resources/publications/workshop/rrra.asp.
   This article was prepared for this symposium as part of work on National
   Institutes of Health (NIH)/National Human Genome Research Institute
   grant no. 2-R01-HG003178 on "Managing Incidental Findings and Research
   Results in Genomic Biobanks & Archives" (S. Wolf, principal
   investigator), although the authors did not receive direct NIH funding
   for the preparation of this article. The opinions expressed in this
   article are the authors' own. The contents of this publication should
   not be construed to reflect the views or policies of the Department of
   Health and Human Services, the NIH, or the NCI. The work was supported
   by general appropriations to the NCI.
NR 22
TC 3
Z9 3
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD APR
PY 2012
VL 14
IS 4
SI SI
BP 417
EP 423
DI 10.1038/gim.2012.11
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 922RL
UT WOS:000302565600009
PM 22344228
ER

PT J
AU Fullerton, SM
   Wolf, WA
   Brothers, KB
   Clayton, EW
   Crawford, DC
   Denny, JC
   Greenland, P
   Koenig, BA
   Leppig, KA
   Lindor, NM
   McCarty, CA
   McGuire, AL
   Hinz, ERM
   Mirel, DB
   Ramos, EM
   Ritchie, MD
   Smith, ME
   Waudby, CJ
   Burke, W
   Jarvik, GP
AF Fullerton, Stephanie M.
   Wolf, Wendy A.
   Brothers, Kyle B.
   Clayton, Ellen Wright
   Crawford, Dana C.
   Denny, Joshua C.
   Greenland, Philip
   Koenig, Barbara A.
   Leppig, Kathleen A.
   Lindor, Noralane M.
   McCarty, Catherine A.
   McGuire, Amy L.
   Hinz, Eugenia R. McPeek
   Mirel, Daniel B.
   Ramos, Erin M.
   Ritchie, Marylyn D.
   Smith, Maureen E.
   Waudby, Carol J.
   Burke, Wylie
   Jarvik, Gail P.
TI Return of individual research results from genome-wide association
   studies: experience of the Electronic Medical Records and Genomics
   (eMERGE) Network
SO GENETICS IN MEDICINE
LA English
DT Article
DE biorepository; context; deliberation; electronic medical records; result
   return
ID V-LEIDEN R506Q; TURNER-SYNDROME; HEREDITARY HEMOCHROMATOSIS;
   KLINEFELTER-SYNDROME; WORKING GROUP; PERSONALIZED MEDICINE; VENOUS
   THROMBOSIS; PARTICIPANTS; RECOMMENDATIONS; CONSORTIUM
AB Purpose: Return of individual genetic results to research participants, including participants in archives and biorepositories, is receiving increased attention. However, few groups have deliberated on specific results or weighed deliberations against relevant local contextual factors.
   Methods: The Electronic Medical Records and Genomics (eMERGE) Network, which includes five biorepositories conducting genome-wide association studies, convened a return of results oversight committee to identify potentially returnable results. Network-wide deliberations were then brought to local constituencies for final decision making.
   Results: Defining results that should be considered for return required input from clinicians with relevant expertise and much deliberation. The return of results oversight committee identified two sex chromosomal anomalies, Klinefelter syndrome and Turner syndrome, as well as homozygosity for factor V Leiden, as findings that could warrant reporting. Views about returning findings of HFE gene mutations associated with hemochromatosis were mixed due to low penetrance. Review of electronic medical records suggested that most participants with detected abnormalities were unaware of these findings. Local considerations relevant to return varied and, to date, four sites have elected not to return findings (return was not possible at one site).
   Conclusion: The eMERGE experience reveals the complexity of return of results decision making and provides a potential deliberative model for adoption in other collaborative contexts.
C1 [Fullerton, Stephanie M.; Burke, Wylie; Jarvik, Gail P.] Univ Washington, Seattle, WA 98195 USA.
   [Wolf, Wendy A.] Childrens Hosp, Boston, MA 02115 USA.
   [Brothers, Kyle B.; Clayton, Ellen Wright; Crawford, Dana C.; Denny, Joshua C.; Hinz, Eugenia R. McPeek] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
   [Greenland, Philip; Smith, Maureen E.] Northwestern Univ, Chicago, IL 60611 USA.
   [Koenig, Barbara A.; Lindor, Noralane M.] Mayo Clin, Rochester, MN USA.
   [Koenig, Barbara A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Leppig, Kathleen A.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA.
   [McCarty, Catherine A.; Waudby, Carol J.] Marshfield Clin Res Fdn, Marshfield, WI USA.
   [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN USA.
   [McGuire, Amy L.] Baylor Coll Med, Houston, TX 77030 USA.
   [Mirel, Daniel B.] Broad Inst Harvard & MIT, Cambridge, MA USA.
   [Ramos, Erin M.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Ritchie, Marylyn D.] Penn State Univ, University Pk, PA 16802 USA.
RP Fullerton, SM (reprint author), Univ Washington, Seattle, WA 98195 USA.
EM smfllrtn@uw.edu
RI Ritchie, Marylyn/C-1114-2012; Crawford, Dana/C-1054-2012; Jarvik,
   Gail/N-6476-2014; 
OI Jarvik, Gail/0000-0002-6710-8708; Clayton, Ellen/0000-0002-0308-4110;
   Fullerton, Stephanie/0000-0002-0938-6048
FU NHGRI; National Institutes of Health, Bethesda, Maryland [HG004610,
   AG06781, HG004608, HG04599, HG004609, HG004438, HG004424, HG004603, R01
   HG003178]; State of Washington Life Sciences Discovery Fund award
FX This work was supported by the following U01 grants from the NHGRI, a
   component of the National Institutes of Health, Bethesda, Maryland:
   HG004610, AG06781 (Group Health Cooperative); HG004608 (Marshfield
   Clinic); HG04599 (Mayo Clinic); HG004609 (Northwestern University);
   HG004438 (Center for Inherited Disease Research, Johns Hopkins
   University); HG004424 (Broad Institute); HG004603 (Vanderbilt
   University, also serving as the eMERGE Administrative Coordinating
   Center), and R01 HG003178 (University of Minnesota). Additional support
   was provided by a State of Washington Life Sciences Discovery Fund award
   to the Northwest Institute of Genetic Medicine.
NR 41
TC 47
Z9 47
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD APR
PY 2012
VL 14
IS 4
SI SI
BP 424
EP 431
DI 10.1038/gim.2012.15
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 922RL
UT WOS:000302565600010
PM 22361898
ER

PT J
AU Tavora, F
   Zhang, MC
   Franco, M
   Oliveira, JB
   Li, L
   Fowler, D
   Zhao, ZQ
   Cresswell, N
   Burke, A
AF Tavora, Fabio
   Zhang, Mingchang
   Franco, Marcello
   Oliveira, Joao Bosco
   Li, Ling
   Fowler, David
   Zhao, Ziqin
   Cresswell, Nathaniel
   Burke, Allen
TI Distribution of biventricular disease in arrhythmogenic cardiomyopathy:
   an autopsy study
SO HUMAN PATHOLOGY
LA English
DT Article
DE Arrhythmia; Right ventricular cardiomyopathy; Sudden death; Myocarditis
ID RIGHT-VENTRICULAR CARDIOMYOPATHY; SUDDEN-DEATH; DYSPLASIA; INVOLVEMENT;
   DYSPLASIA/CARDIOMYOPATHY; ABNORMALITIES; DIAGNOSIS
AB Arrhythmogenic cardiomyopathy is a rare cardiomyopathy characterized by fibrofatty replacement primarily of the right ventricular myocardium. It is a major cause of sudden death in the young and in athletes. There are few autopsy studies of the ventricular distribution of the disease. Fifty cases of sudden cardiac death with fibrofatty replacement in either ventricle from a single medical examiner's office were studied. Distribution of disease as determined grossly and microscopically was correlated with activity at time of death, race, and presence of inflammation. Extent of disease was right ventricular in 6 cases (12%; age, 25 +/- 5 years), biventricular in 25 (50%; age, 36 +/- 3 years), and left ventricular in 19 (38%; age, 37 +/- 3 years) (P = .13). Inflammation was present in 44% of biventricular arrhythmogenic cardiomyopathy versus 74% of left ventricular arrhythmogenic cardiomyopathy and 83% of right ventricular arrhythmogenic cardiomyopathy (P = .06). Arrhythmogenic cardiomyopathy, when presenting with sudden death, is usually biventricular. There is a trend that univentricular involvement occurs at an earlier age and that right ventricular involvement shows more inflammation, suggesting different stages of disease. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Burke, Allen] Univ Maryland, Dept Pathol, Med Ctr, Baltimore, MD 21201 USA.
   [Zhang, Mingchang; Oliveira, Joao Bosco] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
   [Zhang, Mingchang; Zhao, Ziqin] Fudan Univ, Shanghai Med Coll, Dept Forens Med, Shanghai 200032, Peoples R China.
   [Tavora, Fabio; Franco, Marcello] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pathol, BR-04023900 Sao Paulo, Brazil.
RP Burke, A (reprint author), Univ Maryland, Dept Pathol, Med Ctr, Baltimore, MD 21201 USA.
EM allen.burke@gmail.com
RI Tavora, Fabio/A-7561-2009; 
OI Oliveira, Joao/0000-0001-9388-8173
NR 24
TC 9
Z9 10
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 0046-8177
J9 HUM PATHOL
JI Hum. Pathol.
PD APR
PY 2012
VL 43
IS 4
BP 592
EP 596
DI 10.1016/j.humpath.2011.06.014
PG 5
WC Pathology
SC Pathology
GA 913RE
UT WOS:000301894300014
PM 21937076
ER

PT J
AU Anto, JM
   Pinart, M
   Akdis, M
   Auffray, C
   Bachert, C
   Basagana, X
   Carlsen, KH
   Guerra, S
   von Hertzen, L
   Illi, S
   Kauffmann, F
   Keil, T
   Kiley, JP
   Koppelman, GH
   Lupinek, C
   Martinez, FD
   Nawijn, MC
   Postma, DS
   Siroux, V
   Smit, HA
   Sterk, PJ
   Sunyer, J
   Valenta, R
   Valverde, S
   Akdis, CA
   Annesi-Maesano, I
   Ballester, F
   Benet, M
   Cambon-Thomsen, A
   Chatzi, L
   Coquet, J
   Demoly, P
   Gan, WN
   Garcia-Aymerich, J
   Gimeno-Santos, E
   Guihenneuc-Jouyaux, C
   Haahtela, T
   Heinrich, J
   Herr, M
   Hohmann, C
   Jacquemin, B
   Just, J
   Kerkhof, M
   Kogevinas, M
   Kowalski, ML
   Lambrecht, BN
   Lau, S
   Carlsen, KCL
   Maier, D
   Momas, I
   Noel, P
   Oddie, S
   Palkonen, S
   Pin, I
   Porta, D
   Punturieri, A
   Ranciere, F
   Smith, RA
   Stanic, B
   Stein, RT
   van de Veen, W
   van Oosterhout, AJM
   Varraso, R
   Wickman, M
   Wijmenga, C
   Wright, J
   Yaman, G
   Zuberbier, T
   Bousquet, J
AF Anto, Josep M.
   Pinart, Mariona
   Akdis, Muebeccel
   Auffray, Charles
   Bachert, Claus
   Basagana, Xavier
   Carlsen, Kai-Hakon
   Guerra, Stefano
   von Hertzen, Leena
   Illi, Sabina
   Kauffmann, Francine
   Keil, Thomas
   Kiley, James P.
   Koppelman, Gerard H.
   Lupinek, Christian
   Martinez, Fernando D.
   Nawijn, Martijn C.
   Postma, Dirkje S.
   Siroux, Valerie
   Smit, Henriette A.
   Sterk, Peter J.
   Sunyer, Jordi
   Valenta, Rudolf
   Valverde, Sergio
   Akdis, Cezmi A.
   Annesi-Maesano, Isabella
   Ballester, Ferran
   Benet, Marta
   Cambon-Thomsen, Anne
   Chatzi, Leda
   Coquet, Jonathan
   Demoly, Pascal
   Gan, Weiniu
   Garcia-Aymerich, Judith
   Gimeno-Santos, Elena
   Guihenneuc-Jouyaux, Chantal
   Haahtela, Tari
   Heinrich, Joachim
   Herr, Marie
   Hohmann, Cynthia
   Jacquemin, Benedicte
   Just, Jocelyne
   Kerkhof, Marjan
   Kogevinas, Manolis
   Kowalski, Marek L.
   Lambrecht, Bart N.
   Lau, Susanne
   Carlsen, Karin C. Lodrup
   Maier, Dieter
   Momas, Isabelle
   Noel, Patricia
   Oddie, Sam
   Palkonen, Susanna
   Pin, Isabelle
   Porta, Daniela
   Punturieri, Antonello
   Ranciere, Fanny
   Smith, Robert A.
   Stanic, Barbara
   Stein, Renato T.
   van de Veen, Willem
   van Oosterhout, Antoon J. M.
   Varraso, Raphaelle
   Wickman, Magnus
   Wijmenga, Cisca
   Wright, John
   Yaman, Gorkem
   Zuberbier, Torsten
   Bousquet, Jean
CA WHO Collaborating Ctr Asthma
TI Understanding the complexity of IgE-related phenotypes from childhood to
   young adulthood: A Mechanisms of the Development of Allergy (MeDALL)
   Seminar
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Allergy; Mechanisms of the Development of Allergy; Seventh Framework
   Program; phenotypes; IgE; asthma
ID ASTHMA RESEARCH-PROGRAM; OBSTRUCTIVE PULMONARY-DISEASE;
   WORLD-HEALTH-ORGANIZATION; T-REGULATORY-CELLS; BIRTH-COHORT;
   CLUSTER-ANALYSIS; RUSSIAN KARELIA; LUNG-FUNCTION; BRONCHIAL
   HYPERRESPONSIVENESS; DIAGNOSTIC GATEKEEPERS
AB Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster analysis, scale-free models, candidate biomarkers, and IgE microarrays; the particular case of severe asthma was reviewed. Then novel approaches to the IgE-associated phenotypes are reviewed from the individual mechanisms to the systems, including epigenetics, human in vitro immunology, systems biology, and animal models. The last chapter deals with the understanding of the population-based IgE-associated phenotypes in children and adolescents, including age effect in terms of maturation, observed effects of early-life exposures and shift of focus from early life to pregnancy, gene-environment interactions, cohort effects, and time trends in patients with allergic diseases. This review helps to define phenotypes of allergic diseases in MeDALL. (J Allergy Clin Immunol 2012;129:943-54.)
C1 [Anto, Josep M.; Pinart, Mariona; Basagana, Xavier; Guerra, Stefano; Sunyer, Jordi; Benet, Marta; Garcia-Aymerich, Judith; Gimeno-Santos, Elena; Kogevinas, Manolis; Stein, Renato T.] CREAL Ctr Res Environm Epidemiol, Barcelona 08003, Spain.
   [Anto, Josep M.; Pinart, Mariona; Basagana, Xavier; Guerra, Stefano; Sunyer, Jordi; Benet, Marta; Garcia-Aymerich, Judith; Gimeno-Santos, Elena; Kogevinas, Manolis] Hosp Mar Res Inst IMIM, Barcelona, Spain.
   [Anto, Josep M.; Pinart, Mariona; Basagana, Xavier; Guerra, Stefano; Sunyer, Jordi; Ballester, Ferran; Benet, Marta; Garcia-Aymerich, Judith; Gimeno-Santos, Elena; Kogevinas, Manolis] CIBERESP, Barcelona, Spain.
   [Anto, Josep M.; Sunyer, Jordi; Garcia-Aymerich, Judith] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain.
   [Akdis, Muebeccel; Akdis, Cezmi A.; Stanic, Barbara; van de Veen, Willem; Yaman, Gorkem] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland.
   [Auffray, Charles] CNRS Inst Biol Sci, Villejuif, France.
   [Bachert, Claus] Univ Hosp Ghent, URL Upper Airways Res Lab, Ghent, Belgium.
   [Carlsen, Kai-Hakon; Carlsen, Karin C. Lodrup] Oslo Univ Hosp, Dept Paediat, Oslo, Norway.
   [Carlsen, Kai-Hakon; Carlsen, Karin C. Lodrup] Univ Oslo, N-0316 Oslo, Norway.
   [Guerra, Stefano; Martinez, Fernando D.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA.
   [von Hertzen, Leena; Haahtela, Tari] Helsinki Univ Hosp, Dept Allergy, Skin & Allergy Hosp, Helsinki, Finland.
   [Illi, Sabina] Univ Munich, Dept Pulm & Allergy, Univ Childrens Hosp Munich, Munich, Germany.
   [Kauffmann, Francine; Jacquemin, Benedicte; Varraso, Raphaelle; Bousquet, Jean] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Resp & Environm Epidemiol Team, Villejuif, France.
   [Kauffmann, Francine; Jacquemin, Benedicte; Varraso, Raphaelle] Univ Paris 11, UMRS 1018, F-94807 Villejuif, France.
   [Keil, Thomas; Hohmann, Cynthia] Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany.
   [Kiley, James P.; Gan, Weiniu; Noel, Patricia; Punturieri, Antonello; Smith, Robert A.] NHLBI, Div Lung Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Koppelman, Gerard H.] Univ Groningen, Dept Pediat Pulmonol & Pediat Allergol, Beatrix Childrens Hosp, GRIAC Res Inst,Univ Med Ctr Groningen, Groningen, Netherlands.
   [Lupinek, Christian; Valenta, Rudolf] Med Univ Vienna, Div Immunopathol, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Vienna, Austria.
   [Nawijn, Martijn C.; van Oosterhout, Antoon J. M.] Univ Groningen, Univ Med Ctr Groningen, Lab Allergol & Pulm Dis, Dept Pathol & Med Biol,GRIAC Res Inst, Groningen, Netherlands.
   [Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Resp Med, Beatrix Childrens Hosp,GRIAC Res Inst, Groningen, Netherlands.
   [Siroux, Valerie] Univ Grenoble 1, INSERM, Team Environm Epidemiol Appl Reprod & Resp Hlth, U823, Grenoble, France.
   [Smit, Henriette A.] Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, Univ Med Ctr Utrecht, NL-3508 TC Utrecht, Netherlands.
   [Sterk, Peter J.] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
   [Sterk, Peter J.] Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, NL-1105 AZ Amsterdam, Netherlands.
   [Valverde, Sergio] Univ Pompeu Fabra, ICREA Complex Syst Lab, Barcelona, Spain.
   [Annesi-Maesano, Isabella] EPAR U707 INSERM, Paris, France.
   [Annesi-Maesano, Isabella] EPAR UMR S UPMC, Paris, France.
   [Ballester, Ferran] Ctr Publ Hlth Res CSISP, Div Environm & Hlth, Valencia, Spain.
   [Ballester, Ferran] Univ Valencia, Sch Nursing, E-46003 Valencia, Spain.
   [Cambon-Thomsen, Anne] UMR Inserm U1027, Toulouse, France.
   [Cambon-Thomsen, Anne] Univ Toulouse 3, F-31062 Toulouse, France.
   [Chatzi, Leda] Univ Crete, Dept Social Med, Iraklion, Greece.
   [Coquet, Jonathan] Univ Ghent, Dept Resp Dis, Lab Immunoregulat & Mucosal Immunol, Ghent, Belgium.
   [Demoly, Pascal; Lambrecht, Bart N.] World Hlth Org Collaborating Ctr Asthma & Rhiniti, Montpellier, France.
   [Demoly, Pascal; Bousquet, Jean] Hop Arnaud de Villeneuve, Univ Hosp Montpellier, Montpellier, France.
   [Guihenneuc-Jouyaux, Chantal; Herr, Marie; Just, Jocelyne; Momas, Isabelle; Ranciere, Fanny] Paris Descartes Univ, Dept Publ Hlth & Biostat, Paris, France.
   [Heinrich, Joachim] Helmholtz Zentrum, Inst Epidemiol 1, Munich, Germany.
   [Just, Jocelyne] Univ Paris 06, Grp Hosp Trousseau La Roche Guyon, APHP, Ctr Asthme & Allergies, Paris, France.
   [Kerkhof, Marjan] Univ Groningen, Dept Epidemiol, GRIAC Res Inst, Univ Med Ctr Groningen, Groningen, Netherlands.
   [Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
   [Kowalski, Marek L.] Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland.
   [Lau, Susanne] Charite Campus Virchow, Dept Pneumol & Immunol, Berlin, Germany.
   [Maier, Dieter] Biomax Informat AG, Munich, Germany.
   [Momas, Isabelle; Ranciere, Fanny] Paris Municipal Dept Social Act Childhood & Hlth, Paris, France.
   [Oddie, Sam; Wright, John] Bradford Teaching Hosp Fdn Trust, Bradford Inst Hlth Res, Bradford, W Yorkshire, England.
   [Oddie, Sam; Wright, John] Bradford Royal Infirm, Bradford, W Yorkshire, England.
   [Palkonen, Susanna] EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium.
   [Pin, Isabelle] CHU Grenoble, F-38043 Grenoble, France.
   [Pin, Isabelle] Univ Grenoble 1, INSERM, U823, Inst Albert Bonniot, Grenoble, France.
   [Porta, Daniela] Reg Hlth Serv Lazio Reg, Dept Epidemiol, Rome, Italy.
   [Stein, Renato T.] Pontificia Univ Catolica RGS, Sch Med, Porto Alegre, RS, Brazil.
   [Wickman, Magnus] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden.
   [Wickman, Magnus] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
   [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
   [Zuberbier, Torsten] Charite, Allergy Ctr Charite, Dept Dermatol, D-13353 Berlin, Germany.
RP Anto, JM (reprint author), CREAL Ctr Res Environm Epidemiol, Barcelona Biomedical Res Pk,Dr Aiguader 88, Barcelona 08003, Spain.
EM jmanto@creal.cat
RI Varraso, Raphaelle/R-8740-2016; Coquet, Jonathan/A-5551-2015; Basagana,
   Xavier/C-3901-2017; Kogevinas, Manolis/C-3918-2017; Sunyer,
   J/G-6909-2014; Anto, J/H-2676-2014; Wright, John/H-1624-2012; Stein,
   Renato/G-2975-2012; siroux, valerie/N-1865-2013; PIN,
   Isabelle/N-3020-2013; Wijmenga, Cisca/D-2173-2009; Garcia-Aymerich,
   J/G-6867-2014; Valverde, Sergi/J-3275-2012; Stein, Renato/K-2568-2014;
   Annesi-Maesano, Isabella/D-9173-2016; Pinart, Mariona/L-1931-2015;
   Porta, Daniela/J-9042-2016; Lambrecht, Bart/K-2484-2014
OI Varraso, Raphaelle/0000-0002-3338-7825; Coquet,
   Jonathan/0000-0002-5967-4857; Basagana, Xavier/0000-0002-8457-1489;
   Sunyer, J/0000-0002-2602-4110; Anto, J/0000-0002-4736-8529; Ranciere,
   Fanny/0000-0003-3485-2247; Wijmenga, Cisca/0000-0002-5635-1614; Wright,
   John/0000-0001-9572-7293; Garcia-Aymerich, J/0000-0002-7097-4586;
   Valverde, Sergi/0000-0002-2150-9610; Pinart,
   Mariona/0000-0002-8223-1325; Porta, Daniela/0000-0002-3431-2729;
   Lambrecht, Bart/0000-0003-4376-6834
FU Swiss National Foundation; European Union; Helse Sor-Ost; Juselius
   Foundation; Helsinki University; French Agency of Research; Netherlands
   Asthma Foundation; GlaxoSmithKline; Abbott; National Institutes of
   Health; Nycomed, Topinstitute Pharma; AstraZeneca; Innovative Medicines
   Initiative by IMI-EU (U-BIOPRED); Novartis; Stallergenes; Swiss National
   Science Foundation; Global Allergy and Asthma European Network;
   Christine Kuhne Center for Allergy Research; European Commission;
   Norwegian Research Council; University of Oslo; Eastern Norway Regional
   Health Authority; Norwegian Institute of Public Health; Norwegian
   Foundation for Health and Rehabilitation; Norwegian Association for
   Asthma and Allergy; Kloster Foundation; Voksentoppen BKL; Ulleval
   University Hospital; Phadia; Novartis, GlaxoSmithKline; Boehringer
   Ingelheim; Pfizer; Chiesi; ALK-Abello; Nycomed; Air Liquid Healthcare;
   Christne Kuhne Center for Allergy Research
FX M. Akdis has received research support from the Swiss National
   Foundation and the European Union. C. Auffray has received research
   support from the European Union. K.-H. Carlsen has received research
   support from Helse Sor-Ost. L. von Hertzen has received research support
   from the Juselius Foundation and Helsinki University. F. Kauffmann has
   received research support from the French Agency of Research and the
   European Union. T. Keil has received research support from the European
   Union. G. H. Koppelman has received research support from the European
   Union, the Netherlands Asthma Foundation, and GlaxoSmithKline. F. D.
   Martinez is a consultant for MedImmune, has received lecture fees from
   Abbott, and has received research support from the National Institutes
   of Health. D. S. Postma has received research support from Nycomed,
   Topinstitute Pharma, and AstraZeneca. P. J. Sterk has received research
   support from Innovative Medicines Initiative by IMI-EU (U-BIOPRED). C.
   A. Akdis has received research support from Novartis, Stallergenes, the
   Swiss National Science Foundation, the Global Allergy and Asthma
   European Network, and the Christine Kuhne Center for Allergy Research;
   has provided legal consultation/expert witness testimony on the topics
   of Actellion T<INF>H</INF>2-specific receptors, Aventis T-cell, B-cell
   regulation, and Allergopharma allergen-specific immunotherapy; is an
   American Academy of Allergy, Asthma & Immunology (AAAAI) fellow and
   interest group member; is Vice President of the European Academy of
   Allergy and Clinical Immunology (EAACI); and is a GA<SUP>2</SUP>LEN
   ex-committee member WP leader. A. Cambon-Thomsen has received research
   support from the European Commission FP7. K. C. Lodrup Carlsen has
   received research support from the Norwegian Research Council, the
   University of Oslo, the Eastern Norway Regional Health Authority, the
   Norwegian Institute of Public Health, the Norwegian Foundation for
   Health and Rehabilitation, the Norwegian Association for Asthma and
   Allergy, the Kloster Foundation, Voksentoppen BKL, AstraZeneca, Ulleval
   University Hospital, and Phadia; was an EACCI member at large; is chair
   of the Asthma and Allergy group in the pediatric section of the European
   Respiratory Society; and is on the GA<SUP>2</SUP>LEN executive board. D.
   Maier has received research support from the European Commission. S.
   Palkonen is employed by the European Federation of Allergy and Airways
   Diseases Patients' Associations, which has received grants from
   Novartis, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Chiesi,
   ALK-Abello, Stallergenes, Nycomed, AstraZeneca, and Air Liquid
   Healthcare. B. Stanic has received research support from the Christne
   Kuhne Center for Allergy Research and Education and the European
   Commission's Seventh Framework Programme. W. van de Veen has received
   research support from the Swiss National Science Foundation and the
   European Commission's Seventh Framework Programme. T.; Zuberbier has
   provided consultation for Ansell, Bayer Schering, DST, Fujisawa, HAL,
   Henkel, Kryolan, Leti, MSD, Novartis, Procter & Gamble, Sanofi-Aventis,
   Schering-Plough, Stallergenes, and UCB; is on the Scientific Advisory
   Board, German Society for Allergy and Clinical Immunology; is on the
   Expert Commission "Novel Food'' of the German Federal Ministry of
   Consumer Protection; is Head of the European Centre for Allergy Research
   Foundation (ECARF); is a committee member of the World Health
   Organization Initiative Allergic Rhinitis and its Impact on Asthma
   (ARIA); is a member of the World Allergy Organization Communications
   Council; and is Secretary General of the Global Allergy and Asthma
   European Network (GA<SUP>2</SUP>LEN). J. Bousquet has received honoraria
   from Stallergenes, Actelion, Almirall, AstraZeneca, Chiesi,
   GlaxoSmithKline, Merck, MSD, Novartis, OM Pharma, Sanofi-Aventis,
   Schering-Plough, Teva, and Uriach. The rest of the authors declare that
   they have no relevant conflicts of interest.
NR 137
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U1 1
U2 25
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD APR
PY 2012
VL 129
IS 4
BP 943
EP U421
DI 10.1016/j.jaci.2012.01.047
PG 16
WC Allergy; Immunology
SC Allergy; Immunology
GA 917AP
UT WOS:000302144600008
PM 22386796
ER

PT J
AU Haleem-Smith, H
   Calderon, R
   Song, YJ
   Tuan, RS
   Chen, FH
AF Haleem-Smith, Hana
   Calderon, Raul
   Song, Yingjie
   Tuan, Rocky S.
   Chen, Faye H.
TI Cartilage oligomeric matrix protein enhances matrix assembly during
   chondrogenesis of human mesenchymal stem cells
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE CARTILAGE OLIGOMERIC MATRIX PROTEIN; MESENCHYMAL STEM CELLS;
   EXTRACELLULAR MATRIX; CARTILAGE DEVELOPMENT
ID MULTIPLE EPIPHYSEAL DYSPLASIA; BONE-MARROW; ARTICULAR-CARTILAGE;
   INTERSTITIAL FLUID; IN-VITRO; COMP; PSEUDOACHONDROPLASIA; MUTATIONS;
   COLLAGEN; GENE
AB Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention. J. Cell. Biochem. 113: 12451252, 2012. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Tuan, Rocky S.] Univ Pittsburgh, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Pittsburgh, PA 15219 USA.
   [Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S.; Chen, Faye H.] NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
   [Calderon, Raul] NIAMSD, Dept Hlth & Human Serv, Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program,NIH, Bethesda, MD 20892 USA.
RP Tuan, RS (reprint author), Univ Pittsburgh, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Room 221,Bridgeside Point 2,450 Technol Dr, Pittsburgh, PA 15219 USA.
EM rst13@pitt.edu
FU National Institutes of Health [Z01AR41131]; Howard Hughes Medical
   Institute-National Institutes of Health; Commonwealth of Pennsylvania
   Department of Health
FX Grant sponsor: Intramural Research Program of the National Institutes of
   Health; Grant number: Z01AR41131; Grant sponsor: Howard Hughes Medical
   Institute-National Institutes of Health Research Scholars Program; Grant
   sponsor: Commonwealth of Pennsylvania Department of Health.
NR 46
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Z9 24
U1 1
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD APR
PY 2012
VL 113
IS 4
BP 1245
EP 1252
DI 10.1002/jcb.23455
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 898EN
UT WOS:000300719000018
PM 22095699
ER

PT J
AU Thambisetty, M
   Gallardo, KA
   Liow, JS
   Beason-Held, LL
   Umhau, JC
   Bhattacharjee, AK
   Der, M
   Herscovitch, P
   Rapoport, JL
   Rapoport, SI
AF Thambisetty, Madhav
   Gallardo, Kathy A.
   Liow, Jeih-San
   Beason-Held, Lori L.
   Umhau, John C.
   Bhattacharjee, Abesh K.
   Der, Margaret
   Herscovitch, Peter
   Rapoport, Judith L.
   Rapoport, Stanley I.
TI The utility of C-11-arachidonate PET to study in vivo dopaminergic
   neurotransmission in humans
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE apomorphine; cPLA(2); D-1/D-2 receptors; [1-C-11]arachidonate PET;
   regional cerebral blood flow
ID POSITRON-EMISSION-TOMOGRAPHY; ARACHIDONIC-ACID RELEASE; UNANESTHETIZED
   RATS; PARKINSONS-DISEASE; BRAIN INCORPORATION; SIGNAL-TRANSDUCTION;
   BLOOD-FLOW; HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; PHOSPHOLIPASE A(2)
AB We developed a novel method to study dopaminergic neurotransmission using positron emission tomography (PET) with [1-C-11] arachidonic acid ([1-C-11]AA). Previous preclinical studies have shown the utility of [1-C-11] AA as a marker of signal transduction coupled to cytosolic phospholipase A(2) (cPLA(2)). Using [1-C-11] AA and [O-15] water PET, we measured regional incorporation coefficients K* for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D-1/D-2 agonist (10 or 20 mu g/kg subcutaneous) apomorphine. We confirmed a robust central dopaminergic response to apomorphine by observing significant increases in the serum concentration of growth hormone. We observed significant increases, as well as decreases in K* and increases in rCBF in response to apomorphine. These changes remained significant after covarying for handedness and apomorphine dosage. The magnitude of increases in K* was lower than those in our previous animal experiments, likely reflecting the smaller dose of apomorphine used in the current human study. Changes in K* may reflect neuronal signaling downstream of activated D-2-like receptors coupled to cPLA(2). Changes in rCBF are consistent with previous studies showing net functional effects of D-1/D-2 activation. [1-C-11]AA PET may be useful for studying disturbances of dopaminergic neurotransmission in conditions such as Parkinson's disease and schizophrenia. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 676-684; doi:10.1038/jcbfm.2011.171; published online 14 December 2011
C1 [Thambisetty, Madhav; Bhattacharjee, Abesh K.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
   [Gallardo, Kathy A.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
   [Liow, Jeih-San] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
   [Beason-Held, Lori L.] NIA, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA.
   [Umhau, John C.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
   [Der, Margaret; Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
RP Thambisetty, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Room 1S-126,Bluiding 9,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM thambisettym@mail.nih.gov
FU National Institute of Mental Health; National Institute on Aging;
   National Institute of Neurological Disorders and Stroke; National
   Institute of Alcohol Abuse and Alcoholism
FX This study was supported by the Intramural Program of the National
   Institute of Mental Health, National Institute on Aging, National
   Institute of Neurological Disorders and Stroke, and National Institute
   of Alcohol Abuse and Alcoholism.
NR 58
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Z9 9
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD APR
PY 2012
VL 32
IS 4
BP 676
EP 684
DI 10.1038/jcbfm.2011.171
PG 9
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 921IU
UT WOS:000302472100009
PM 22167235
ER

PT J
AU Sant'Anna, G
   Laptook, AR
   Shankaran, S
   Bara, R
   McDonald, SA
   Higgins, RD
   Tyson, JE
   Ehrenkranz, RA
   Das, A
   Goldberg, RN
   Walsh, MC
AF Sant'Anna, Guilherme
   Laptook, Abbot R.
   Shankaran, Seetha
   Bara, Rebecca
   McDonald, Scott A.
   Higgins, Rosemary D.
   Tyson, Jon E.
   Ehrenkranz, Richard A.
   Das, Abhik
   Goldberg, Ronald N.
   Walsh, Michele C.
CA Eunice Kennedy Shriver Natl Inst C
   Human Dev Neonatal Res Network
TI Phenobarbital and Temperature Profile During Hypothermia for
   Hypoxic-Ischemic Encephalopathy
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE phenobarbital; hypoxic-ischemic encephalopathy; hypothermia; temperature
   control; anticonvulsant; seizures; barbiturates
ID WHOLE-BODY HYPOTHERMIA; NEONATAL ENCEPHALOPATHY; REGULATED HYPOTHERMIA;
   BRAIN-INJURY; SYSTEMIC HYPOTHERMIA; OXYGEN-CONSUMPTION; NEWBORN RATS;
   THERMOGENESIS; MANAGEMENT; ASPHYXIA
AB Data from the whole-body hypothermia trial was analyzed to examine the effects of phenobarbital administration prior to cooling (+PB) on the esophageal temperature (T-e) profile, during the induction phase of hypothermia. A total of 98 infants were analyzed. At enrollment, +PB infants had a higher rate of severe hypoxic-ischemic encephalopathy and clinical seizures and lower T-e and cord pH than infants that have not received phenobarbital (-PB). There was a significant effect of phenobarbital itself and an interaction between phenobarbital and time in the T-e profile. Mean T-e in the +PB group was lower than in the -PB group, and the differences decreased over time. In +PB infants, the time to surpass target T-e of 33.5 degrees C and to reach the minimum T-e during overshoot were shorter. In conclusion, the administration of phenobarbital before cooling was associated with changes that may reflect a reduced thermogenic response associated with barbiturates.
C1 [Sant'Anna, Guilherme] McGill Univ, Div Neonatol, Dept Pediat, Ctr Hlth, Montreal, PQ H3H 1P3, Canada.
   [Laptook, Abbot R.] Brown Univ, Providence, RI 02912 USA.
   [Shankaran, Seetha; Bara, Rebecca] Wayne State Univ, Sch Med, Detroit, MI USA.
   [McDonald, Scott A.; Das, Abhik] RTI Int, Dept Stat & Epidemiol, Res Triangle Pk, NC USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Tyson, Jon E.] Univ Texas Houston, Houston, TX USA.
   [Ehrenkranz, Richard A.] Yale Univ, New Haven, CT USA.
   [Goldberg, Ronald N.] Duke Univ, Durham, NC USA.
   [Walsh, Michele C.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Sant'Anna, G (reprint author), McGill Univ, Div Neonatol, Dept Pediat, Ctr Hlth, 2300 Tupper St,Room C912, Montreal, PQ H3H 1P3, Canada.
EM guilherme.santanna@mcgill.ca
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (NICHD)
FX The National Institutes of Health and the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development (NICHD)
   provided grant support for the NICHD Neonatal Research Network's
   Whole-Body Cooling for Hypoxic Ischemic Encephalopathy Study.
   Participating NRN sites collected data and transmitted it to RTI
   International, the data coordinating center (DCC) for the network, which
   stored, managed, and analyzed the data for this study. On behalf of the
   NRN, Dr Abhik Das (DCC Principal Investigator) and Mr Scott A. McDonald
   (DCC Statisticians) had full access to all the data in the study and
   take responsibility for the integrity of the data and accuracy of data
   analysis.
NR 36
TC 10
Z9 10
U1 0
U2 5
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 APR
PY 2012
VL 27
IS 4
BP 451
EP 457
DI 10.1177/0883073811419317
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 918EK
UT WOS:000302231900004
PM 21960671
ER

PT J
AU Shibusawa, Y
   Yanagida, A
   Ogihara, A
   Ma, Y
   Chen, XY
   Ito, Y
AF Shibusawa, Yoichi
   Yanagida, Akio
   Ogihara, Atsushi
   Ma, Ying
   Chen, Xiaoyuan
   Ito, Yoichiro
TI Separation of nucleobases and their derivatives with organic-high ionic
   strength aqueous phase systems by spiral high-speed counter-current
   chromatography
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
   AND LIFE SCIENCES
LA English
DT Article
ID SOLVENT SYSTEM
AB A set of nucleic acid constituents were separated with ultra polar two-phase solvent systems by a spiral multilayer coil mounted on the rotary frame of a type-J coil planet centrifuge. These two-phase systems were composed of 1-butanol/ethanol/50% saturated aqueous ammonium sulfate at various volume ratios. Nucleobases including adenine, cytosine, uracil, and thymine; nucleosides including adenosine, guanosine, cytidine, and uridine; and nucleotides including, AMP, GMP, CMP, UMP, and TMP are partitioned in each group with suitable solvent ratios. Adenine derivatives such as adenosine, AMP, ADP, and ATP were well resolved in the most polar solvent system composed of ethanol/50% saturated aqueous ammonium sulfate at a volume ratio of 1:2. It was found that cytosine and cytidine peaks showed some irregular two peaks probably due to their keto and enol isomers, while the separation of AMP forms two peaks especially when TMP was added in the sample solution, the mechanism of which is now under investigation in our laboratory. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
   [Ma, Ying; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
   [Shibusawa, Yoichi; Yanagida, Akio; Ogihara, Atsushi] Tokyo Univ Pharm & Life Sci, Sch Pharm, Div Pharmaceut & Biomed Anal, Hachioji, Tokyo 1920392, Japan.
RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230,10 Ctr Dr, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
FU Intramural NIH HHS [ZIA HL005107-04]
NR 15
TC 9
Z9 9
U1 4
U2 19
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 APR 1
PY 2012
VL 891
BP 94
EP 97
DI 10.1016/j.jchromb.2012.02.012
PG 4
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 922YO
UT WOS:000302585100015
PM 22391329
ER

PT J
AU Mattson, MP
AF Mattson, Mark P.
TI Parkinson's disease: don't mess with calcium
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID NEUROTROPHIC FACTOR; STRESS; MITOCHONDRIA; SYNUCLEIN; NEURONS
AB The hallmark of the movement disorder Parkinson's disease (PD) is progressive degeneration of dopaminergic neurons. Mitochondrial dysfunction, impaired ubiquitin-mediated proteolysis of a-synuclein, and ER stress are each implicated in the complex and poorly understood sequence of events leading to dopaminergic neuron demise. In this issue of the JCI, Selvaraj et al. report that in a mouse neurotoxin-based model of PD, reduced Ca2+ influx through transient receptor potential Cl (TRPC1) channels in the plasma membrane of dopaminergic neurons triggers a cell death-inducing ER stress response. These new findings suggest that TRPC1 channels normally function in Ca2+-mediated signaling pathways that couple adaptive/neurotrophic responses to metabolic and oxidative stress and suggest that disruption of these pathways may contribute to PD.
C1 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 Mattson, Mark/F-6038-2012
FU Intramural NIH HHS
NR 17
TC 13
Z9 14
U1 2
U2 9
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 APR
PY 2012
VL 122
IS 4
BP 1195
EP 1198
DI 10.1172/JCI62835
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 918WJ
UT WOS:000302281800014
PM 22446181
ER

PT J
AU Rachel, RA
   May-Simera, HL
   Veleri, S
   Gotoh, N
   Choi, BY
   Murga-Zamalloa, C
   McIntyre, JC
   Marek, J
   Lopez, I
   Hackett, AN
   Brooks, M
   den Hollander, AI
   Beales, PL
   Li, TS
   Jacobson, SG
   Sood, R
   Martens, JR
   Liu, P
   Friedman, TB
   Khanna, H
   Koenekoop, RK
   Kelley, MW
   Swaroop, A
AF Rachel, Rivka A.
   May-Simera, Helen L.
   Veleri, Shobi
   Gotoh, Norimoto
   Choi, Byung Yoon
   Murga-Zamalloa, Carlos
   McIntyre, Jeremy C.
   Marek, Jonah
   Lopez, Irma
   Hackett, Alice N.
   Brooks, Matthew
   den Hollander, Anneke I.
   Beales, Philip L.
   Li, Tiansen
   Jacobson, Samuel G.
   Sood, Raman
   Martens, Jeffrey R.
   Liu, Paul
   Friedman, Thomas B.
   Khanna, Hemant
   Koenekoop, Robert K.
   Kelley, Matthew W.
   Swaroop, Anand
TI Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory
   defects and restores ciliogenesis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID BARDET-BIEDL-SYNDROME; LEBER CONGENITAL AMAUROSIS; INTRAFLAGELLAR
   TRANSPORT MOTORS; PLANAR CELL POLARITY; JOUBERT-SYNDROME; PRIMARY
   CILIUM; RETINAL DEGENERATION; KUPFFERS VESICLE; ZEBRAFISH MODEL; NPHP6
   GENE
AB Cilia are highly specialized microtubule-based organelles that have pivotal roles in numerous biological processes, including transducing sensory signals. Defects in cilia biogenesis and transport cause pleiotropic human ciliopathies. Mutations in over 30 different genes can lead to cilia defects, and complex interactions exist among ciliopathy-associated proteins. Mutations of the centrosomal protein 290 kDa (CEP290) lead to distinct clinical manifestations, including Leber congenital amaurosis (LCA), a hereditary cause of blindness due to photoreceptor degeneration. Mice homozygous for a mutant Cep290 allele (Cep290(rd16) mice) exhibit LCA-like early-onset retinal degeneration that is caused by an in-frame deletion in the CEP290 protein. Here, we show that the domain deleted in the protein encoded by the Cep290(rd16) allele directly interacts with another ciliopathy protein, MKKS. MKKS mutations identified in patients with the ciliopathy Bardet-Biedl syndrome disrupted this interaction. In zebrafish embryos, combined subminimal knockdown of mkks and cep290 produced sensory defects in the eye and inner ear. Intriguingly, combinations of Cep290(rd16) and Mkks(ko) alleles in mice led to improved ciliogenesis and sensory functions compared with those of either mutant alone. We propose that altered association of CEP290 and MKKS affects the integrity of multiprotein complexes at the cilia transition zone and basal body. Amelioration of the sensory phenotypes caused by specific mutations in one protein by removal of an interacting domain/protein suggests a possible novel approach for treating human ciliopathies.
C1 [Rachel, Rivka A.; Veleri, Shobi; Gotoh, Norimoto; Hackett, Alice N.; Brooks, Matthew; Li, Tiansen; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
   [May-Simera, Helen L.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD USA.
   [Choi, Byung Yoon; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Bethesda, MD USA.
   [Murga-Zamalloa, Carlos; Khanna, Hemant] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
   [McIntyre, Jeremy C.; Martens, Jeffrey R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Marek, Jonah; Lopez, Irma; Koenekoop, Robert K.] McGill Univ, Ctr Hlth, McGill Ocular Genet Lab, Montreal, PQ, Canada.
   [den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6525 ED Nijmegen, Netherlands.
   [den Hollander, Anneke I.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
   [Beales, Philip L.] UCL Inst Child Hlth, Mol Med Unit, London, England.
   [Jacobson, Samuel G.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Sood, Raman; Liu, Paul] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI Liu, Paul/A-7976-2012; Hollander, Anneke/N-4911-2014; 
OI Liu, Paul/0000-0002-6779-025X; Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute; National Institute on Deafness and Other
   Communication Disorders; National Human Genome Research Institute
FX We are grateful to Chi-Chao Chan, Robert Fariss, Jun Zhang, Jacob
   Nellissery, Awais Zia, Milton English, Kevin Bishop, Anastasia
   Krasnoperova, Rima Kikani, Tiziana Cogliati, Christopher Brinson, and
   Corey Williams for discussions or assistance. This work was supported by
   intramural and extramural funds from the National Eye Institute,
   National Institute on Deafness and Other Communication Disorders, and
   National Human Genome Research Institute. Additional support was
   provided by CIHR, FFB-C, FRSQ, Midwest Eye Banks and Transplantation
   Center, Reseau Vision, and TFFR. P.L. Beales is a Wellcome Trust Senior
   Research Fellow.
NR 68
TC 32
Z9 32
U1 2
U2 6
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 APR
PY 2012
VL 122
IS 4
BP 1233
EP 1245
DI 10.1172/JCI60981
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 918WJ
UT WOS:000302281800020
PM 22446187
ER

PT J
AU Selvaraj, S
   Sun, YY
   Watt, JA
   Wang, SP
   Lei, SB
   Birnbaumer, L
   Singh, BB
AF Selvaraj, Senthil
   Sun, Yuyang
   Watt, John A.
   Wang, Shouping
   Lei, Saobo
   Birnbaumer, Lutz
   Singh, Brij B.
TI Neurotoxin-Induced ER stress in mouse dopaminergic neurons involves
   downregulation of TRPC1 and inhibition of AKT/mTOR signaling
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; OPERATED CA2+
   ENTRY; PARKINSONS-DISEASE; STORE DEPLETION; CALCIUM-CHANNEL;
   MONOAMINE-OXIDASE; DEATH; ORAI; ACTIVATION
AB Individuals with Parkinson's disease (PD) experience a progressive decline in motor function as a result of selective loss of dopaminergic (DA) neurons in the substantia nigra. The mechanism(s) underlying the loss of DA neurons is not known. Here, we show that a neurotoxin that causes a disease that mimics PD upon administration to mice, because it induces the selective loss of DA neurons in the substantia nigra, alters Ca2+ homeostasis and induces ER stress. In a human neuroblastoma cell line, we found that endogenous store-operated Ca2+ entry (SOCE), which is critical for maintaining ER Ca2+ levels, is dependent on transient receptor potential channel 1 (TRPC1) activity. Neurotoxin treatment decreased TRPC1 expression, TRPC1 interaction with the SOCE modulator stromal interaction molecule 1 (STIM1), and Ca2+ entry into the cells. Overexpression of functional TRPC1 protected against neurotoxin-induced loss of SOCE, the associated decrease in ER Ca2+ levels, and the resultant unfolded protein response (UPR). In contrast, silencing of TRPC1 or STIM1 increased the UPR. Furthermore, Ca2+ entry via TRPC1 activated the AKT pathway, which has a known role in neuroprotection. Consistent with these in vitro data, Trpc1(-/-) mice had an increased UPR and a reduced number of DA neurons. Brain lysates of patients with PD also showed an increased UPR and decreased TRPC1 levels. Importantly, overexpression of TRPC1 in mice restored AKT/mTOR signaling and increased DA neuron survival following neurotoxin administration. Overall, these results suggest that TRPC1 is involved in regulating Ca2+ homeostasis and inhibiting the UPR and thus contributes to neuronal survival.
C1 [Selvaraj, Senthil; Sun, Yuyang; Singh, Brij B.] Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Grand Forks, ND 58201 USA.
   [Watt, John A.] Univ N Dakota, Sch Med & Hlth Sci, Dept Anat & Cell Biol, Grand Forks, ND 58201 USA.
   [Watt, John A.; Wang, Shouping; Lei, Saobo] Univ N Dakota, Sch Med & Hlth Sci, Dept Physiol Pharmacol & Therapeut, Grand Forks, ND 58201 USA.
   [Birnbaumer, Lutz] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Singh, BB (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, 501 N Columbia Rd, Grand Forks, ND 58201 USA.
EM senthilbio@gmail.com; brij.singh@med.und.edu
OI selvaraj, senthil/0000-0002-0185-6033; Singh, Brij/0000-0003-0535-5997
FU National Science Foundation [0548733]; NIH [DE017102, 5P20RR017699,
   Z01-ES-101684]; National Institute of Neurological Disorders and Stroke
   (NINDS) [P50 NS-053488]
FX We greatly acknowledge the use of the Edward C. Carlson Imaging and
   Image Analysis Core Facility. We especially thank Laura Leiphon and
   Virginia Achen for their help. We greatly acknowledge the UK Parkinson's
   Disease Society Tissue Bank at Imperial College and John Trojanowski
   (University of Pennsylvania) for providing the PD and control samples.
   Also, grant support from the National Science Foundation (no. 0548733)
   and the NIH (DE017102 and 5P20RR017699) awarded to B.B Singh; from the
   NIH Intramural Program (project Z01-ES-101684) to L. Birnbaumer; and
   from the National Institute of Neurological Disorders and Stroke (NINDS;
   P50 NS-053488) awarded to John Trojanowski is acknowledged.
NR 59
TC 63
Z9 66
U1 0
U2 12
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 APR
PY 2012
VL 122
IS 4
BP 1354
EP 1367
DI 10.1172/JCI61332
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 918WJ
UT WOS:000302281800029
PM 22446186
ER

PT J
AU Higashimoto, Y
   Ohta, A
   Nishiyama, Y
   Ihira, M
   Sugata, K
   Asano, Y
   Peterson, DL
   Ablashi, DV
   Lusso, P
   Yoshikawa, T
AF Higashimoto, Yuki
   Ohta, Akane
   Nishiyama, Yukihiro
   Ihira, Masaru
   Sugata, Ken
   Asano, Yoshizo
   Peterson, Daniel L.
   Ablashi, Dharam V.
   Lusso, Paolo
   Yoshikawa, Tetsushi
TI Development of a Human Herpesvirus 6 Species-Specific Immunoblotting
   Assay
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID INDUCED HYPERSENSITIVITY SYNDROME; MARROW TRANSPLANT RECIPIENTS;
   POLYMERASE CHAIN-REACTION; VARIANT-B; HUMAN-HERPESVIRUS-6 INFECTION;
   HEALTHY-INDIVIDUALS; EXANTHEM-SUBITUM; IDENTIFICATION; BLOOD; DNA
AB In order to assess the full spectrum of human herpesvirus 6A (HHV-6A)- and HHV-6B-associated diseases, we sought to develop an HHV-6 species-specific serological assay based on immunoblot analysis. The immunodominant proteins encoded by open reading frame U11, p100 for HHV-6A (strain U1102) and 101K for HHV-6B (strain Z29), were selected to generate virus species-specific antigens. Recombinant p100 and 101K were produced in a prokaryotic expression system. The expression of these proteins was confirmed by using anti-His tag and 101K-specific monoclonal antibodies. HHV-6 species-specific antibodies were detected by immunoblotting in patient sera. Eighty-seven serum samples obtained from various subjects were utilized to determine the reliability of the method for clinical use. Ten of twelve exanthem subitum convalescent-phase sera reacted exclusively with 101K, whereas none of twelve acute-phase sera reacted with either protein. Two of three sera collected from HHV-6A-infected patients reacted with p100 and 101K. Although all five acute and convalescent-phase sera obtained from transplant recipients reacted exclusively with 101K, two of six convalescent-phase sera obtained from patients with drug-induced hypersensitivity syndrome reacted with both p100 and 101K. Of 38 sera obtained from healthy adults, 31 were positive for 101K antibody, while 4 reacted with both proteins. However, PCR analysis of peripheral blood mononuclear cells and saliva from these subjects did not detect HHV-6A DNA. In conclusion, this novel serological assay based on immunoblot analysis using recombinant HHV-6A p100 and HHV-6B 101K allowed us to discriminate between HHV-6A- and HHV-6B-specific antibodies.
C1 [Higashimoto, Yuki; Sugata, Ken; Asano, Yoshizo; Yoshikawa, Tetsushi] Fujita Hlth Univ, Sch Med, Dept Pediat, Toyoake, Aichi 47011, Japan.
   [Ihira, Masaru] Fujita Hlth Univ, Sch Hlth Sci, Fac Clin Engn, Toyoake, Aichi, Japan.
   [Ohta, Akane; Nishiyama, Yukihiro] Nagoya Univ, Grad Sch Med, Dept Virol, Nagoya, Aichi 4648601, Japan.
   [Peterson, Daniel L.] Sierra Internal Med, Incline Village, NV USA.
   [Ablashi, Dharam V.] HHV 6 Fdn, Santa Barbara, CA USA.
   [Lusso, Paolo] NIAID, Sect Viral Pathogenesis, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Yoshikawa, T (reprint author), Fujita Hlth Univ, Sch Med, Dept Pediat, Toyoake, Aichi 47011, Japan.
EM tetsushi@fujita-hu.ac.jp
RI Asano, Yoshizo/F-6870-2012
FU Ministry of Education, Culture, Sports, Science, and Technology;
   Ministry of Health, Labor, and Welfare of Japan [H21-Shinko-009,
   H21-Shinko-011]
FX This study was supported by research grants from the Ministry of
   Education, Culture, Sports, Science, and Technology and the Ministry of
   Health, Labor, and Welfare of Japan (H21-Shinko-009 and H21-Shinko-011).
NR 35
TC 7
Z9 7
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD APR
PY 2012
VL 50
IS 4
BP 1245
EP 1251
DI 10.1128/JCM.05834-11
PG 7
WC Microbiology
SC Microbiology
GA 917CC
UT WOS:000302148700019
PM 22278837
ER

PT J
AU Conville, PS
   Brown-Elliott, BA
   Wallace, RJ
   Witebsky, FG
   Koziol, D
   Hall, GS
   Killian, SB
   Knapp, CC
   Warshauer, D
   Van, T
   Wengenack, NL
   Deml, S
   Woods, GL
AF Conville, Patricia S.
   Brown-Elliott, Barbara A.
   Wallace, Richard J., Jr.
   Witebsky, Frank G.
   Koziol, Deloris
   Hall, Geraldine S.
   Killian, Scott B.
   Knapp, Cindy C.
   Warshauer, David
   Van, Tam
   Wengenack, Nancy L.
   Deml, Sharon
   Woods, Gail L.
TI Multisite Reproducibility of the Broth Microdilution Method for
   Susceptibility Testing of Nocardia Species
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID LABORATORY FEATURES; BETA-LACTAMASE; FARCINICA; BRASILIENSIS; RESISTANCE
AB Antimicrobial susceptibility testing (AST) of clinical isolates of Nocardia is recommended to detect resistance to commonly used antimicrobial agents; such testing is complicated by difficulties in inoculum preparation and test interpretation. In this study, six laboratories performed repetitive broth microdilution testing on single strains of Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica, Nocardia nova, and Nocardia wallacei. For each isolate, a total of 30 microdilution panels from three different lots were tested at most sites. The goal of the study was to determine the inter-and intralaboratory reproducibility of susceptibility testing of this group of isolates. Acceptable agreement (>90% agreement at +/- 1 dilution of the MIC mode) was found for amikacin, ciprofloxacin, clarithromycin, and moxifloxacin. After eliminating MIC values from single laboratories whose results showed the greatest deviation from those of the remaining laboratories, acceptable agreement was also found for amoxicillin-clavulanic acid, linezolid, minocycline, and tobramycin. Results showed unsatisfactory reproducibility of broth microdilution testing of ceftriaxone with N. cyriacigeorgica and N. wallacei, tigecycline with N. brasiliensis and N. cyriacigeorgica, and sulfonamides with N. farcinica and N. wallacei. N. nova ATCC BAA-2227 is proposed as a quality control organism for AST of Nocardia sp., and the use of a disk diffusion test for sulfisoxazole is proposed as a check of the adequacy of the inoculum and to confirm sulfonamide MIC results.
C1 [Conville, Patricia S.; Witebsky, Frank G.] NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Koziol, Deloris] NIH, Biostat & Clin Epidemiol Serv, Warren G Magnuson Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Brown-Elliott, Barbara A.; Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr, Dept Microbiol, Tyler, TX USA.
   [Hall, Geraldine S.] Cleveland Clin, Cleveland, OH 44106 USA.
   [Warshauer, David; Van, Tam] Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA.
   [Killian, Scott B.; Knapp, Cindy C.] ThermoFisher Sci, Cleveland, OH USA.
   [Wengenack, Nancy L.; Deml, Sharon] Mayo Clin, Div Clin Microbiol, Rochester, MN USA.
   [Woods, Gail L.] Cent Arkansas Vet Healthcare Syst, Pathol & Lab Med Serv, Little Rock, AR USA.
RP Conville, PS (reprint author), NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA.
EM patricia.conville@fda.hhs.gov
FU Pfizer (New York, NY); Wyeth (Madison, NJ); ThermoFisher Scientific
   (Cleveland, OH); BD (Franklin Lakes, NJ)
FX This work was supported in part by grants from Pfizer (New York, NY),
   Wyeth (Madison, NJ), ThermoFisher Scientific (Cleveland, OH), and BD
   (Franklin Lakes, NJ).
NR 19
TC 19
Z9 21
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD APR
PY 2012
VL 50
IS 4
BP 1270
EP 1280
DI 10.1128/JCM.00994-11
PG 11
WC Microbiology
SC Microbiology
GA 917CC
UT WOS:000302148700023
PM 22219309
ER

PT J
AU Orru, CD
   Hughson, AG
   Race, B
   Raymond, GJ
   Caughey, B
AF Orru, Christina D.
   Hughson, Andrew G.
   Race, Brent
   Raymond, Gregory J.
   Caughey, Byron
TI Time Course of Prion Seeding Activity in Cerebrospinal Fluid of
   Scrapie-Infected Hamsters after Intratongue and Intracerebral
   Inoculations
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID CONVERSION; PROTEIN; DISEASE
AB To assess prospects for early diagnosis of prion disease based on prion seeding activity in cerebrospinal fluid (CSF), we measured the activity over time in scrapie-infected hamsters by real-time quaking-induced conversion (RT-QuIC). After intracerebral inoculation, activity appeared in CSF within 1 day and plateaued weeks before the onset of clinical signs. However, after intratongue inoculation, activity first appeared in CSF with the onset of clinical signs, well after higher-level accumulation of seeding activity in brain.
C1 [Orru, Christina D.; Hughson, Andrew G.; Race, Brent; Raymond, Gregory J.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM bcaughey@nih.gov
FU NIAID; NIH
FX This work was supported by the Intramural Research Program of the NIAID,
   NIH.
NR 12
TC 13
Z9 13
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD APR
PY 2012
VL 50
IS 4
BP 1464
EP 1466
DI 10.1128/JCM.06099-11
PG 3
WC Microbiology
SC Microbiology
GA 917CC
UT WOS:000302148700060
ER

PT J
AU Grady, KL
   Naftel, DC
   Stevenson, L
   Dew, MA
   Weidner, G
   Pagani, FD
   Kirklin, JK
   Myers, S
   Baldwin, JT
   Shah, MR
   Young, JB
AF Grady, K. L.
   Naftel, D. C.
   Stevenson, L.
   Dew, M. A.
   Weidner, G.
   Pagani, F. D.
   Kirklin, J. K.
   Myers, S.
   Baldwin, J. T.
   Shah, M. R.
   Young, J. B.
TI Improvement in Quality of Life after Left Ventricular Assist Device
   Implant Is Similar, Regardless of Baseline Severity of Heart Failure
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 32nd Annual Meeting and Scientific Sessions of the
   International-Society-for-Heart-and-Lung-Transplantation/Meeting of the
   ISHLT Academy - Core Competencies in Mechanical Circulatory Support
CY APR 17-21, 2012
CL Prague, CZECH REPUBLIC
SP Int Soc Heart & Lung Transplantat (ISHLT), Int Soc Heart & Lung Transplantat Acad (ISHLT)
C1 [Grady, K. L.] Northwestern Univ, Chicago, IL 60611 USA.
   [Naftel, D. C.; Kirklin, J. K.; Myers, S.] Univ Alabama, Birmingham, AL USA.
   [Stevenson, L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Dew, M. A.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   [Weidner, G.] San Francisco State Univ, Tiburon, CA USA.
   [Pagani, F. D.] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Baldwin, J. T.; Shah, M. R.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Young, J. B.] Cleveland Clin, Cleveland, OH 44106 USA.
NR 0
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 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2012
VL 31
IS 4
SU S
MA 28
BP S18
EP S19
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
   Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
   Transplantation
GA 917VY
UT WOS:000302207900028
ER

PT J
AU Naftel, DC
   Kirklin, JK
   Myers, SL
   Clark, ML
   Hollifield, KA
   Collum, SC
   Miller, MA
AF Naftel, D. C.
   Kirklin, J. K.
   Myers, S. L.
   Clark, M. L.
   Hollifield, K. A.
   Collum, S. C.
   Miller, M. A.
TI Can a Registry Match the Data Quality of a Clinical Trial? Lessons
   Learned from INTERMACS
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 32nd Annual Meeting and Scientific Sessions of the
   International-Society-for-Heart-and-Lung-Transplantation/Meeting of the
   ISHLT Academy - Core Competencies in Mechanical Circulatory Support
CY APR 17-21, 2012
CL Prague, CZECH REPUBLIC
SP Int Soc Heart & Lung Transplantat (ISHLT), Int Soc Heart & Lung Transplantat Acad (ISHLT)
C1 [Naftel, D. C.; Kirklin, J. K.; Myers, S. L.; Clark, M. L.; Hollifield, K. A.; Collum, S. C.] Univ Alabama, Birmingham, AL USA.
   [Miller, M. A.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2012
VL 31
IS 4
SU S
MA 765
BP S261
EP S261
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
   Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
   Transplantation
GA 917VY
UT WOS:000302207900765
ER

PT J
AU Dutta, M
   Schwartzberg, PL
AF Dutta, Mala
   Schwartzberg, Pamela L.
TI Characterization of Ly108 in the Thymus: Evidence for Distinct
   Properties of a Novel Form of Ly108
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LINKED LYMPHOPROLIFERATIVE-DISEASE; ACTIVATION MOLECULE SLAM;
   SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE-PRODUCT SAP/SH2D1A;
   NATURAL-KILLER-CELLS; SH2 DOMAIN; TYROSINE PHOSPHORYLATION;
   INFECTIOUS-MONONUCLEOSIS; DIFFERENTIAL EXPRESSION; HOMOPHILIC
   INTERACTION
AB Ly108 (CD352) is a member of the signaling lymphocyte activation molecule (SLAM) family of receptors that signals through SLAM-associated protein (SAP), an SH2 domain protein that can function by the recruitment of Src family kinases or by competition with phosphatases. Ly108 is expressed on a variety of hematopoietic cells, with especially high levels on developing thymocytes. We find that Ly108 is constitutively tyrosine phosphorylated in murine thymi in a SAP- and Fyn kinase-dependent manner. Phosphorylation of Ly108 is rapidly lost after thymocyte disaggregation, suggesting dynamic contact-mediated regulation of Ly108. Similar to recent reports, we find at least three isoforms of Ly108 mRNA and protein in the thymus, which are differentially expressed in the thymi of C57BL/6 and 129S6 mice that express the lupus-resistant and lupus-prone haplotypes of Ly108, respectively. Notably, the recently described novel isoform Ly108-H1 is not expressed in mice having the lupus-prone haplotype of Ly108, but is expressed in C57BL/6 mice. We further provide evidence for differential phosphorylation of these isoforms; the novel Ly108-H1does not undergo tyrosine phosphorylation, suggesting that it functions as a decoy isoform that contributes to the reduced overall phosphorylation of Ly108 seen in C57BL/6 mice. Our study suggests that Ly108 is dynamically regulated in the thymus, shedding light on Ly108 isoform expression and phosphorylation. The Journal of Immunology, 2012, 188: 3031-3041.
C1 [Dutta, Mala; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Dutta, Mala] George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA.
RP Schwartzberg, PL (reprint author), NHGRI, NIH, 49 Convent Dr,Room 4A38, Bethesda, MD 20892 USA.
EM pams@mail.nih.gov
FU National Human Genome Research Institute
FX This work was supported by intramural funding of the National Human
   Genome Research Institute.
NR 53
TC 6
Z9 6
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD APR 1
PY 2012
VL 188
IS 7
BP 3031
EP 3041
DI 10.4049/jimmunol.1103226
PG 11
WC Immunology
SC Immunology
GA 917CP
UT WOS:000302150300017
PM 22393150
ER

PT J
AU Davey, AM
   Pierce, SK
AF Davey, Angel M.
   Pierce, Susan K.
TI Intrinsic Differences in the Initiation of B Cell Receptor Signaling
   Favor Responses of Human IgG(+) Memory B Cells over IgM(+) Naive B Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FC-GAMMA-RIIB; ANTIGEN-RECEPTOR; LYMPH-NODE; T-CELLS; SUBCAPSULAR SINUS;
   SYNAPSE FORMATION; IMMUNE-RESPONSES; ACTIVATION; BCR; EXPRESSION
AB The acquisition of long-lived memory B cells (MBCs) is critical for the defense against many infectious diseases. Despite their importance, little is known about how Ags trigger human MBCs, even though our understanding of the molecular basis of Ag activation of B cells in model systems has advanced considerably. In this study, we use quantitative, high-resolution, live-cell imaging at the single-cell and single-molecule levels to describe the earliest Ag-driven events in human isotype-switched, IgG-expressing MBCs and compare them with those in IgM-expressing naive B cells. We show that human MBCs are more robust than naive B cells at each step in the initiation of BCR signaling, including interrogation of Ag-containing membranes, formation of submicroscopic BCR oligomers, and recruitment and activation of signaling-associated kinases. Despite their robust response to Ag, MBCs remain highly sensitive to Fc gamma RIIB-mediated inhibition. We also demonstrate that in the absence of Ag, a portion of MBC receptors spontaneously oligomerized, and phosphorylated kinases accumulated at the membrane and speculate that heightened constitutive signaling may play a role in maintaining MBC longevity. Using high-resolution imaging, we have provided a description of the earliest events in the Ag activation of MBCs and evidence for acquired cell-intrinsic differences in the initiation of BCR signaling in human naive and MBCs. The Journal of Immunology, 2012, 188: 3332-3341.
C1 [Davey, Angel M.; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 200B,MSC 8180, Rockville, MD 20852 USA.
EM spierce@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
   Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Allergy and Infectious Diseases, National
   Institutes of Health.
NR 50
TC 14
Z9 14
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 APR 1
PY 2012
VL 188
IS 7
BP 3332
EP 3341
DI 10.4049/jimmunol.1102322
PG 10
WC Immunology
SC Immunology
GA 917CP
UT WOS:000302150300047
PM 22379037
ER

PT J
AU Beurskens, FJ
   Lindorfer, MA
   Farooqui, M
   Beum, PV
   Engelberts, P
   Mackus, WJM
   Parren, PWHI
   Wiestner, A
   Taylor, RP
AF Beurskens, Frank J.
   Lindorfer, Margaret A.
   Farooqui, Mohammed
   Beum, Paul V.
   Engelberts, Patrick
   Mackus, Wendy J. M.
   Parren, Paul W. H. I.
   Wiestner, Adrian
   Taylor, Ronald P.
TI Exhaustion of Cytotoxic Effector Systems May Limit Monoclonal
   Antibody-Based Immunotherapy in Cancer Patients
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DEPENDENT CELLULAR CYTOTOXICITY;
   FRESH-FROZEN PLASMA; B-CELLS; COMPLEMENT ACTIVATION; ALTERNATIVE
   PATHWAY; NK ACTIVATION; KILLER-CELLS; TUMOR-CELLS; HUMAN CD20
AB The CD20 mAb of atumumab (OFA) induces complement-mediated lysis of B cells. In an investigator-initiated phase II trial of OFA plus chemotherapy for chronic lymphocytic leukemia (CLL), OFA treatment promoted partial CLL B cell depletion that coincided with reduced complement titers. Remaining CLL B cells circulated with bound OFA and covalently bound complement breakdown product C3d, indicative of ongoing complement activation. Presumably, neither complement-nor effector cell-based mechanisms were sufficiently robust to clear these remaining B cells. Instead, almost all of the bound OFA and CD20 was removed from the cells, in accordance with previous clinical studies that demonstrated comparable loss of CD20 from B cells after treatment of CLL patients with rituximab. In vitro experiments with OFA and rituximab addressing these observations suggest that host effector mechanisms that support mAb-mediated lysis and tumor cell clearance are finite, and they can be saturated or exhausted at high B cell burdens, particularly at high mAb concentrations. Interestingly, only a fraction of available complement was required to kill cells with CD20 mAbs, and killing could be tuned by titrating the mAb concentration. Consequently, maximal B cell killing of an initial and secondary B cell challenge was achieved with intermediate mAb concentrations, whereas high concentrations promoted lower overall killing. Therefore, mAb therapies that rely substantially on effector mechanisms subject to exhaustion, including complement, may benefit from lower, more frequent dosing schemes optimized to sustain and maximize killing by cytotoxic immune effector systems. The Journal of Immunology, 2012, 188: 3532-3541.
C1 [Lindorfer, Margaret A.; Beum, Paul V.; Taylor, Ronald P.] Univ Virginia, Dept Biochem & Mol Genet, Sch Med, Charlottesville, VA 22908 USA.
   [Beurskens, Frank J.; Engelberts, Patrick; Mackus, Wendy J. M.; Parren, Paul W. H. I.] Genmab, NL-3584 CM Utrecht, Netherlands.
   [Farooqui, Mohammed; Wiestner, Adrian] NHLBI, Hematol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Taylor, RP (reprint author), Univ Virginia, Dept Biochem & Mol Genet, Sch Med, POB 800733, Charlottesville, VA 22908 USA.
EM rpt@virginia.edu
OI Parren, Paul/0000-0002-4365-3859
FU GlaxoSmithKline; Genmab; National Heart, Lung and Blood Institute,
   National Institutes of Health
FX This work was supported by GlaxoSmithKline, which supported the
   correlative studies and provided ofatumumab for the trial, and by
   Genmab, which supported the in vitro studies. The clinical trial was
   funded by the National Heart, Lung and Blood Institute, National
   Institutes of Health.
NR 51
TC 54
Z9 54
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 APR 1
PY 2012
VL 188
IS 7
BP 3532
EP 3541
DI 10.4049/jimmunol.1103693
PG 10
WC Immunology
SC Immunology
GA 917CP
UT WOS:000302150300067
PM 22368276
ER

PT J
AU Millum, J
AF Millum, Joseph
TI Sharing the benefits of research fairly: two approaches
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID DEVELOPING-COUNTRIES; INTERNATIONAL RESEARCH; CLINICAL-TRIALS
AB Research projects sponsored by rich countries or companies and carried out in developing countries are often described as exploitative. One important debate about the prevention of exploitation in research centres on whether and how clinical research in developing countries should be responsive to local health problems. This paper analyses the responsiveness debate and draws out more general lessons for how policy makers can prevent exploitation in various research contexts. There are two independent ways to do this in the face of entrenched power differences: to impose restrictions on the content of benefit-sharing arrangements, and to institute independent effective oversight. Which method should be chosen is highly dependent on context.
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 10,1C118,10 Ctr Dr, Bethesda, MD 20892 USA.
EM millumj@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 25
TC 10
Z9 10
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD APR
PY 2012
VL 38
IS 4
BP 219
EP 223
DI 10.1136/medethics-2011-100118
PG 5
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
   Biomedical Social Sciences
GA 916SQ
UT WOS:000302123900008
PM 21947808
ER

PT J
AU Gainer, H
AF Gainer, H.
TI Cell-Type Specific Expression of Oxytocin and Vasopressin Genes: An
   Experimental Odyssey
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Review
DE cell-type specific gene expression; transcription factors; transcription
   factor binding sites; magnocellular neurones; phenotype
ID GREEN FLUORESCENT PROTEIN; HYPOTHALAMIC SUPRAOPTIC NEURONS;
   ADENOASSOCIATED VIRAL VECTOR; MESSENGER RIBONUCLEIC-ACIDS; TRANSGENIC
   MICE; MAGNOCELLULAR NEURONS; DIABETES-INSIPIDUS; ARGININE-VASOPRESSIN;
   RAT VASOPRESSIN; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM
AB The supraoptic nucleus (SON) is a particularly good model for the study of cell-type specific gene expression because it contains two distinct neuronal phenotypes, the oxytocin (OT) and vasopressin (AVP) synthesising magnocellular neurones (MCNs). The MCNs are found in approximately equal numbers and selectively express either the OT or the AVP gene in approximately 97% of the MCN population in the SON. An unresolved issue has been to determine what mechanisms are responsible for the highly selective regulation of the cell-type specific expression of OT and AVP genes in the MCNs. Previous attempts to address this question have used various bioinformatic and molecular approaches, which included using heterologous cell lines to study the putative cis-elements in the OT and AVP genes, and the use of OT and/or AVP transgenes in transgenic rodents. The data from all of the above studies identified a region < 0.6 kbp upstream of OT exon I and approximately 3 kb upstream of AVP exon I as being sufficient to produce cell-specific expression of the OT and AVP genes, respectively, although they failed to identify the specific cis-domains responsible for the MCN-specific gene expression. An alternative experimental approach to perform promoter deletion analysis in vivo (i.e. to use stereotaxic viral vector gene transfer into the SON to further dissect the cis-elements in the OT and AVP genes) will be described here. This in vivo method uses adeno-associated viral (AAV) vectors expressing OT-promoter deletion constructs and utilises the enhanced green fluorescent protein (EGFP) as the reporter. The AAV constructs are stereotaxically injected into the rat brain above the SON and, 2 weeks post injection, the rats are sacrificed and assayed for EGFP expression. Using this method, it has been possible to identify specific regions upstream of the transcription start site in the OT and AVP gene promoters that are responsible for conferring the cell-type specificity of the OT and AVP gene expression in the SON.
C1 NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Gainer, H (reprint author), NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bldg 49,Room 5A78, Bethesda, MD 20892 USA.
EM gainerh@ninds.nih.gov
FU NINDS, NIH
FX This research was supported by the Intramural Research Program of the
   NINDS, NIH. I thank my many colleagues who contributed to this work,
   including Ray Fields, Todd Ponzio, Shirley House, Daniel Lubelski,
   Makoto Kawasaki, Madison Stevens, Omar Rashid, Yasmmyn Salinas, Yijun
   Shi, Babru Samal and Korey Johnson.
NR 84
TC 16
Z9 17
U1 3
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD APR
PY 2012
VL 24
IS 4
BP 528
EP 538
DI 10.1111/j.1365-2826.2011.02236.x
PG 11
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 914CA
UT WOS:000301925100002
PM 21985498
ER

PT J
AU Williams, SK
   Barber, JS
   Jamieson-Drake, AW
   Enns, JA
   Townsend, LB
   Walker, CH
   Johns, JM
AF Williams, S. K.
   Barber, J. S.
   Jamieson-Drake, A. W.
   Enns, J. A.
   Townsend, L. B.
   Walker, C. H.
   Johns, J. M.
TI Chronic Cocaine Exposure During Pregnancy Increases Postpartum
   Neuroendocrine Stress Responses
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Article
DE cocaine; postpartum; stress; oxytocin; corticosterone
ID SPRAGUE-DAWLEY RATS; MESSENGER-RNA EXPRESSION; MATERNAL-BEHAVIOR;
   OXYTOCIN RELEASE; PLASMA-LEVELS; BRAIN OXYTOCIN; BLOOD-PRESSURE; FEMALE
   RATS; ANXIETY; DEPRESSION
AB The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, SpragueDawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 120). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P = 0.05). CC-treated dams also exhibited altered FST behaviour (P = 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P = 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P = 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.
C1 [Williams, S. K.; Jamieson-Drake, A. W.; Enns, J. A.; Walker, C. H.; Johns, J. M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
   [Barber, J. S.; Enns, J. A.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA.
   [Townsend, L. B.; Johns, J. M.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
RP Williams, SK (reprint author), NIMH, Sect Neural Gene Express, 49 Convent Rd,RM 5A51, Bethesda, MD 20892 USA.
EM williamssk@mail.nih.gov
RI Williams, Sarah/K-4118-2012
FU National Institute on Drug Abuse [P01DA022446]
FX We thank the invaluable assistance of Dr Hsiao Tien, Dr Matthew
   McMurray, Dr Sheryl Moy, Elizabeth Cox, Dave Gardner, Thomas Jarrett,
   Cara Heaton, Nisel Desai, Marlana Radcliffe and Ben Thompson for their
   help in the preparation of this manuscript and data collection, as well
   as their thoughtful discussions with the authors. The authors were
   supported by Award Number P01DA022446 (J.M.J.) from the National
   Institute on Drug Abuse. The content is solely the responsibility of the
   authors and does not necessarily represent the official views of the
   National Institute on Drug Abuse or the National Institutes of Health.
NR 69
TC 3
Z9 3
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD APR
PY 2012
VL 24
IS 4
BP 701
EP 711
DI 10.1111/j.1365-2826.2012.02291.x
PG 11
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 914CA
UT WOS:000301925100017
PM 22309318
ER

PT J
AU Jain, P
   Manuel, S
   Makedonas, G
   Betts, M
   Gardner, J
   Goedert, J
   Khan, ZK
AF Jain, P.
   Manuel, S.
   Makedonas, G.
   Betts, M.
   Gardner, J.
   Goedert, J.
   Khan, Z. K.
TI Dynamics of Dendritic Cells and T Cells in HTLV-1 Associated Oncogenesis
   and Neuroinflammation: Implications in Immunomodulatory Therapies and
   Diagnostic Tools
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Jain, P.; Manuel, S.; Khan, Z. K.] Drexel Univ, Dept Microbiol & Immunol, Coll Med, Doylestown, PA 18902 USA.
   [Makedonas, G.; Betts, M.; Gardner, J.] Univ Penn, Dept Microbiol & Immunol, Sch Med, Philadelphia, PA 19104 USA.
   [Goedert, J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD APR
PY 2012
VL 7
SU 1
BP S70
EP S70
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 918YY
UT WOS:000302288800169
ER

PT J
AU Karn, J
   Alvarez, D
   Dobrowolski, C
   Das, B
   Harvey, BK
AF Karn, J.
   Alvarez, D.
   Dobrowolski, C.
   Das, B.
   Harvey, B. K.
TI Distinct Epigenetic Control Mechanisms Regulating HIV Silencing in
   T-cells and Microglial Cells.
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Karn, J.; Alvarez, D.; Dobrowolski, C.; Das, B.] Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
   [Harvey, B. K.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD APR
PY 2012
VL 7
SU 1
BP S18
EP S18
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 918YY
UT WOS:000302288800017
ER

PT J
AU Hafed, ZM
   Krauzlis, RJ
AF Hafed, Ziad M.
   Krauzlis, Richard J.
TI Similarity of superior colliculus involvement in microsaccade and
   saccade generation
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE voluntary eye movement; fixational eye movement; fixation
ID DORSOLATERAL PREFRONTAL CORTEX; FIXATIONAL EYE-MOVEMENTS;
   NEURONAL-ACTIVITY; VOLUNTARY CONTROL; COVERT ATTENTION; MOTOR
   PREPARATION; NEURAL ACTIVITY; VISUAL-CORTEX; GAZE SHIFTS; MONKEY
AB Hafed ZM, Krauzlis RJ. Similarity of superior colliculus involvement in microsaccade and saccade generation. J Neurophysiol 107: 1904-1916, 2012. First published January 11, 2012; doi: 10.1152/jn.01125.2011.-The characteristics of microsaccades, or small fixational saccades, and their influence on visual function have been studied extensively. However, the detailed mechanisms for generating these movements are less understood. We recently found that the superior colliculus (SC), a midbrain structure involved in saccade generation, also plays a role in microsaccade generation. Here we compared the dynamics of neuronal activity in the SC associated with microsaccades to those observed in this structure in association with larger voluntary saccades. We found that microsaccade-related activity in the SC is characterized by a gradual increase in firing rate starting similar to 100 ms prior to microsaccade onset, a peak of neuronal discharge just after movement onset, and a subsequent gradual decrease in firing rate until similar to 100 ms after movement onset. These properties were shared with saccade-related SC neurons, recorded from the same monkeys but preferring larger eye movements, suggesting that at the level of the SC the neuronal control of microsaccades is similar to that for larger voluntary saccades. We also found that neurons exhibiting microsaccade-related activity often also exhibited saccade-related activity for slightly larger movements of similar direction, suggesting a continuity of the spatial representation in the SC, in both amplitude and direction, down to the smallest movements. Our results indicate that the mechanisms controlling microsaccades may be fundamentally the same as those for larger saccades, and thus shed new light on the functional role of these eye movements and their possible influence on sensory and sensory-motor processes.
C1 [Hafed, Ziad M.] Werner Reichardt Ctr Integrat Neurosci, D-72076 Tubingen, Germany.
   [Krauzlis, Richard J.] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA.
   [Krauzlis, Richard J.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
RP Hafed, ZM (reprint author), Werner Reichardt Ctr Integrat Neurosci, Paul Ehrlich Str 17, D-72076 Tubingen, Germany.
EM ziad.m.hafed@cin.uni-tuebingen.de
FU Werner Reichardt Centre for Integrative Neuroscience; National Eye
   Institute (NEI) [EY-12212]; National Institutes of Health
FX Z. M. Hafed was funded by the Werner Reichardt Centre for Integrative
   Neuroscience and the National Eye Institute (NEI) (Grant EY-12212). R.
   J. Krauzlis was funded by NEI (Grant EY-12212) and the NEI Intramural
   Research Program at the National Institutes of Health.
NR 74
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Z9 42
U1 0
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD APR
PY 2012
VL 107
IS 7
BP 1904
EP 1916
DI 10.1152/jn.01125.2011
PG 13
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 922GG
UT WOS:000302534600011
PM 22236714
ER

PT J
AU Mena, E
   Turkbey, B
   Mani, H
   Adler, S
   Valera, VA
   Bernardol, M
   Shah, V
   Pohida, T
   McKinney, Y
   Kwarteng, G
   Daar, D
   Lindenberg, ML
   Eclarinal, P
   Wade, R
   Linehan, WM
   Merino, MJ
   Pinto, PA
   Choyke, PL
   Kurdziel, KA
AF Mena, Esther
   Turkbey, Baris
   Mani, Haresh
   Adler, Stephen
   Valera, Vladimir A.
   Bernardol, Marcelino
   Shah, Vijay
   Pohida, Thomas
   McKinney, Yolanda
   Kwarteng, Gideon
   Daar, Dagane
   Lindenberg, Maria L.
   Eclarinal, Philip
   Wade, Revia
   Linehan, W. Marston
   Merino, Maria J.
   Pinto, Peter A.
   Choyke, Peter L.
   Kurdziel, Karen A.
TI C-11-Acetate PET/CT in Localized Prostate Cancer: A Study with MRI and
   Histopathologic Correlation
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE prostate cancer; C-11-acetate PET; multiparametric prostate MRI
ID POSITRON-EMISSION-TOMOGRAPHY; RADICAL PROSTATECTOMY; 1-C-11-ACETATE;
   DIAGNOSIS; RELAPSE; DISEASE
AB This work characterizes the uptake of C-11-acetate in prostate cancer (PCa), benign prostate hyperplasia, and normal prostate tissue in comparison with multiparametric MRI, whole-mount histopathology, and clinical markers to evaluate the potential utility of C-11-acetate for delineating intraprostatic tumors in a population of patients with localized PCa. Methods: Thirtynine men with presumed localized PCa underwent dynamicstatic abdominal-pelvic C-11-acetate PET/CT for 30 min and 3-T multiparametric MRI before prostatectomy. PET/CT images were registered to MR images using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient-specific mold resulting in improved registration between the MRI, PET, and pathology. C-11-acetate PET standardized uptake values were compared with multiparametric MRI and pathology. Results: C-11-acetate uptake was rapid but reversible, peaking at 3-5 min after injection and reaching a relative plateau at approximately 10 min. The average maximum standardized uptake value (10-12 min) of tumors was significantly higher than that of normal prostate tissue (4.4 +/- 2.05 [range, 1.8-9.2] vs. 2.1 +/- 0.94 [range, 0.7-3.4], respectively; P < 0.001); however, it was not significantly different from that of benign prostatic hyperplasia (4.8 +/- 2.01 [range, 1.8-8.8]). A sector-based comparison with histopathology, including all tumors greater than 0.5 cm, revealed a sensitivity and specificity of 61.6% and 80.0%, respectively, for C-11-acetate PET/CT and 82.3% and 95.1%, respectively, for MRI. The C-11-acetate accuracy was comparable to that of MRI when only tumors greater than 0:9 cm were considered. In a small cohort (n = 9), C-11-acetate uptake was independent of fatty acid synthase expression using immunohistochemistry. Conclusion: C-11-acetate PET/CT demonstrates higher uptake in tumor foci than in normal prostate tissue; however, C-11-acetate uptake in tumors is similar to that in benign prostate hyperplasia nodules. Although C-11-acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy when tissue damage after therapy may limit anatomic imaging methods.
C1 [Mena, Esther; Turkbey, Baris; Adler, Stephen; Bernardol, Marcelino; Shah, Vijay; McKinney, Yolanda; Kwarteng, Gideon; Daar, Dagane; Lindenberg, Maria L.; Eclarinal, Philip; Wade, Revia; Choyke, Peter L.; Kurdziel, Karen A.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
   [Mani, Haresh; Valera, Vladimir A.; Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   [Bernardol, Marcelino; Shah, Vijay] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
   [Pohida, Thomas] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
   [Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Kurdziel, KA (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM karen.kurdziel@nih.gov
RI Shah, Vijay/D-4083-2014
OI Shah, Vijay/0000-0003-3856-156X
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Michael Channing and the NIH Clinical Center PET Department for
   providing the <SUP>11</SUP>C-acetate. This research was supported by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research. No other potential conflict of interest
   relevant to this article was reported.
NR 25
TC 53
Z9 53
U1 0
U2 5
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD APR
PY 2012
VL 53
IS 4
BP 538
EP 545
DI 10.2967/jnumed.111.096032
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 920BV
UT WOS:000302377300034
PM 22343504
ER

PT J
AU Zhou, Y
   Sojkoval, J
   Resnick, SM
   Wong, DF
AF Zhou, Yun
   Sojkoval, Jitka
   Resnick, Susan M.
   Wong, Dean F.
TI Relative Equilibrium Plot Improves Graphical Analysis and Allows Bias
   Correction of Standardized Uptake Value Ratio in Quantitative C-11-PiB
   PET Studies
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE RE plot; C-11-PiB; PET; SUVR; bias
ID POSITRON-EMISSION-TOMOGRAPHY; REFERENCE TISSUE MODEL; MILD COGNITIVE
   IMPAIRMENT; PITTSBURGH COMPOUND-B; RECEPTOR DYNAMIC PET;
   ALZHEIMERS-DISEASE; SEROTONIN TRANSPORTER; AMYLOID DEPOSITION; SPATIAL
   CONSTRAINT; HUMAN BRAIN
AB Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVRs) in ligand-receptor dynamic PET studies. The objective of this study was to use a recently developed relative equilibrium-based graphical (RE) plot method to improve and simplify the 2 commonly used methods for quantification of C-11-Pittsburgh compound B (C-11-PiB) PET. Methods: The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight C-11-PiB dynamic PET scans (66 from controls and 12 from participants with mild cognitive impaired [MCI] from the Baltimore Longitudinal Study of Aging) were acquired over 90 min. Regions of interest (ROIs) were defined on coregistered MR images. Both the ROI and the pixelwise time-activity curves were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI time-activity curves were used as a reference for comparison of DVR estimates. Results: Results from the theoretic analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI time-activity curves. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, and cingulate regions and the striatum were underestimated by the Logan plot (controls, 4%-12%; MCI, 9%-16%) and overestimated by the SUVR (controls, 8%-16%; MCI, 16%-24%). This bias was higher in the MCI group than in controls (P < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. Conclusion: The RE plot improves pixelwise quantification of C-11-PiB dynamic PET, compared with the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates than of SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of C-11-PiB studies.
C1 [Zhou, Yun; Sojkoval, Jitka; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
   [Sojkoval, Jitka; Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD USA.
RP Zhou, Y (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 601 N Caroline St,JHOC Room 3245, Baltimore, MD 21287 USA.
EM yunzhou@jhmi.edu
FU NIH; National Institute on Aging (NIA) [N01-AG-0012, N01-AG-3-2124]
FX We thank the cyclotron staff, PET staff, and MRI staff of the Johns
   Hopkins Medical Institutions and Andrew H. Crabb for data transfer and
   computer administration. This study was supported in part by the
   Intramural Research Program of the NIH and by the National Institute on
   Aging (NIA) (R&D contracts N01-AG-0012 and N01-AG-3-2124). No other
   potential conflict of interest relevant to this article was reported.
   This work was presented in part at the 56th Society of Nuclear Medicine
   conference, June 13-17, 2009, Toronto, Canada, and at the 57th Society
   of Nuclear Medicine conference, June 5-9, 2010, Salt Lake City, Utah.
NR 39
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U1 0
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD APR
PY 2012
VL 53
IS 4
BP 622
EP 628
DI 10.2967/jnumed.111.095927
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 920BV
UT WOS:000302377300045
PM 22414634
ER

PT J
AU Kramer-Marek, G
   Gijsen, M
   Kiesewetter, DO
   Bennett, R
   Roxanis, I
   Zielinski, R
   Kong, A
   Capala, J
AF Kramer-Marek, Gabriela
   Gijsen, Mere
   Kiesewetter, Dale O.
   Bennett, Ruth
   Roxanis, Ioannis
   Zielinski, Rafal
   Kong, Anthony
   Capala, Jacek
TI Potential of PET to Predict the Response to Trastuzumab Treatment in an
   ErbB2-Positive Human Xenograft Tumor Model
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE breast cancer HER2/ErbB2; trastuzumab; PET imaging; Affibody molecules
ID METASTATIC BREAST-CANCER; ADJUVANT CHEMOTHERAPY; THERAPY; TARGETS; HER2;
   EFFICACY; ANTIBODY; SAFETY
AB Currently, an alteration in the gross volume of a tumor is used to assess its response to trastuzumab; however, this approach provides only a late indication of response. Tissue-sample ex vivo assays are potentially valuable, but their procurement through biopsies is invasive and might be biased by tumor heterogeneity. We studied the feasibility of using PET to quantify changes in ErbB2 (HER2/neu) expression and to predict the response to trastuzumab in BT474 breast cancer xenografts with N-[2-(4-F-18-fluorobenzamido)ethyl]maleimide (F-18-FBEM)-HER2:342 Affibody. Methods: Mice bearing BT474 tumors were given trastuzumab (50 mg/kg loading dose, 25 mg/kg maintenance dose, administered intraperitoneally twice a week) or saline (control) for a total of 5 doses. Tumor size was monitored twice a week. Animals were scanned before the treatment, at 48 h, and 2 wk after the beginning of therapy. After the final scan, PET results were correlated with tumor response and immunohistochemical assessment of ErbB2 level, as well as with vasculature in the treated tumors. Results: Analysis of PET images indicated that tracer uptake was significantly reduced after 1 dose of trastuzumab, compared with baseline, suggesting applicability as an early indicator of changes in ErbB2 expression. After 5 doses of trastuzumab, the overall decrease in F-18-FBEM-HER2:342 Affibody uptake also correlated with tumor response and downregulation of ErbB2 expression by immunohistochemical assessment. However, individual animals had different responses. There was a correlation between bigger PET changes and a higher vessel count in the tumors, suggesting that an increased number of vessels could lead to better trastuzumab delivery. We confirmed that the difference in average vessel count in the tumors was not related to the size of the tumors and therefore was not due to the selection of more vascular tumors. This finding is consistent with previous findings demonstrating that the number of vessels in a tumor could be a useful prognostic marker for treatment response. Conclusion: Our data suggest that Affibody-based PET can noninvasively provide specific information on changes in receptor expression and could be a valuable strategy for predicting tumor response to trastuzumab.
C1 [Kramer-Marek, Gabriela; Zielinski, Rafal; Capala, Jacek] Natl Canc Inst, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20852 USA.
   [Gijsen, Mere; Bennett, Ruth; Kong, Anthony] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
   [Kiesewetter, Dale O.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
   [Roxanis, Ioannis] Oxford Univ Hosp, Dept Cellular Pathol, Oxford, England.
   [Roxanis, Ioannis] Oxford Biomed Res Ctr, Oxford, England.
RP Capala, J (reprint author), Natl Canc Inst, NIH, 6130 Executive Blvd,Room 6010, Rockville, MD 20852 USA.
EM anthony.kong@imm.ox.ac.uk; capalaj@mail.nih.gov
FU Center for Cancer Research; National Cancer Institute [N01-CO-12400,
   N01-CO-12401]; Imaging Probe Development Center; National Heart, Lung,
   and Blood Institute; Breast Cancer Research Stamp Fund; NIHR Biomedical
   Research Centre, Oxford; Breakthrough Breast Cancer through the Holbeck
   Charitable Trust
FX We appreciate the support of Affibody AB and the technical assistance of
   Monika Kuban and Alesia Holly. The content of this publication does not
   necessarily reflect the views or policies of the Department of Health
   and Human Services, nor does mention of trade names, commercial
   products, or organizations imply endorsement by the U.S. government.
   This research was supported in part by the Center for Cancer Research,
   an Intramural Research Program of the National Cancer Institute; the
   Imaging Probe Development Center, National Heart, Lung, and Blood
   Institute; the Breast Cancer Research Stamp Fund, awarded through
   competitive peer review; the National Cancer Institute under contracts
   N01-CO-12400 and N01-CO-12401; the NIHR Biomedical Research Centre,
   Oxford; and Breakthrough Breast Cancer through the Holbeck Charitable
   Trust. No other potential conflict of interest relevant to this article
   was reported.
NR 23
TC 21
Z9 21
U1 0
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD APR
PY 2012
VL 53
IS 4
BP 629
EP 637
DI 10.2967/jnumed.111.096685
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 920BV
UT WOS:000302377300046
PM 22410461
ER

PT J
AU Abd-Elmoniem, KZ
   Zahiri, H
   Pettigrew, RI
   Gharib, AM
AF Abd-Elmoniem, K. Z.
   Zahiri, H.
   Pettigrew, R. I.
   Gharib, A. M.
TI Assessment of coronary artery wall remodeling using phase-sensitive dual
   inversion recovery MRI
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT 3rd Symposium on Multimodality Cardiovascular Molecular Imaging
CY APR 19-21, 2012
CL Natl Inst Hlth (NIH), Bethesda, MD
HO Natl Inst Hlth (NIH)
C1 [Abd-Elmoniem, K. Z.; Pettigrew, R. I.; Gharib, A. M.] NIDDK, NIH, Bethesda, MD USA.
   [Zahiri, H.] NIH, CC, Bethesda, MD 20892 USA.
RI Gharib, Ahmed/O-2629-2016; Abd-Elmoniem, Khaled/B-9289-2008
OI Gharib, Ahmed/0000-0002-2476-481X; Abd-Elmoniem,
   Khaled/0000-0002-1001-1702
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD APR
PY 2012
VL 53
IS 4
MA 1
BP 665
EP 665
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 920BV
UT WOS:000302377300055
ER

PT J
AU Xu, B
   Wu, H
   Bhattacharyya, F
   Lane, K
   Li, C
   Sulima, A
   Griffiths, GL
   Jagoda, E
   Green, M
   Seidel, J
   Choyke, P
AF Xu, B.
   Wu, H.
   Bhattacharyya, F.
   Lane, K.
   Li, C.
   Sulima, A.
   Griffiths, G. L.
   Jagoda, E.
   Green, M.
   Seidel, J.
   Choyke, P.
TI F-18 radiolabeling of preformed liposomes for PET imaging of the
   vascular system
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT 3rd Symposium on Multimodality Cardiovascular Molecular Imaging
CY APR 19-21, 2012
CL Natl Inst Hlth (NIH), Bethesda, MD
HO Natl Inst Hlth (NIH)
C1 [Xu, B.; Wu, H.; Bhattacharyya, F.; Lane, K.; Li, C.; Sulima, A.; Griffiths, G. L.] NHLBI, Rockville, MD USA.
   [Jagoda, E.; Green, M.; Seidel, J.; Choyke, P.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD APR
PY 2012
VL 53
IS 4
MA 21
BP 670
EP 671
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 920BV
UT WOS:000302377300075
ER

PT J
AU Shankaran, S
   Laptook, AR
   Tyson, JE
   Ehrenkranz, RA
   Bann, CM
   Das, A
   Higgins, RD
   Bara, R
   Pappas, A
   McDonald, SA
   Goldberg, RN
   Walsh, MC
AF Shankaran, Seetha
   Laptook, Abbot R.
   Tyson, Jon E.
   Ehrenkranz, Richard A.
   Bann, Carla M.
   Das, Abhik
   Higgins, Rosemary D.
   Bara, Rebecca
   Pappas, Athina
   McDonald, Scott A.
   Goldberg, Ronald N.
   Walsh, Michele C.
CA Eunice Kennedy Shriver Natl Inst
TI Evolution of Encephalopathy during Whole Body Hypothermia for Neonatal
   Hypoxic-Ischemic Encephalopathy
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID CEREBRAL-PALSY; SYSTEMIC HYPOTHERMIA; ANTECEDENTS; OUTCOMES; INFANTS
AB Objective To examine the predictive ability of stage of hypoxic-ischemic encephalopathy (HIE) for death or moderate/severe disability at 18 months among neonates undergoing hypothermia.
   Study design Stage of encephalopathy was evaluated at <6 hours of age, during study intervention, and at discharge among 204 participants in the National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for HIE. HIE was examined as a predictor of outcome by regression models.
   Results Moderate and severe HIE occurred at <6 hours of age among 68% and 32% of 101 hypothermia group infants and 60% and 40% of 103 control group infants, respectively. At 24 and 48 hours of study intervention, infants in the hypothermia group had less severe HIE than infants in the control group. Persistence of severe HIE at 72 hours increased the risk of death or disability after controlling for treatment group. The discharge exam improved the predictive value of stage of HIE at <6 hours for death/disability.
   Conclusions On serial neurologic examinations, improvement in stage of HIE was associated with cooling. Persistence of severe HIE at 72 hours and an abnormal neurologic exam at discharge were associated with a greater risk of death or disability. (J Pediatr 2012;160:567-72).
C1 [Shankaran, Seetha; Bara, Rebecca; Pappas, Athina] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
   [Laptook, Abbot R.] Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02908 USA.
   [Tyson, Jon E.] Univ Texas Houston, Dept Pediat, Houston, TX USA.
   [Ehrenkranz, Richard A.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA.
   [Bann, Carla M.; Das, Abhik; McDonald, Scott A.] RTI Int, Stat Design & Epidemiol, Res Triangle Pk, NC USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
   [Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
   [Walsh, Michele C.] Case Western Univ, Dept Pediat, Cleveland, OH USA.
RP Shankaran, S (reprint author), Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
FU 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]
FX Supported in part by the following grants from the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development: U10
   HD21364 (Case), U10 HD21373 (Houston), U10 HD21385 (Wayne), U10 HD21397
   (Miami), U10 HD27851 (Emory), U10 HD27853 (Cincinnati), 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).
NR 20
TC 31
Z9 31
U1 0
U2 9
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 APR
PY 2012
VL 160
IS 4
BP 567
EP +
DI 10.1016/j.jpeds.2011.09.018
PG 9
WC Pediatrics
SC Pediatrics
GA 921PP
UT WOS:000302489800010
PM 22050871
ER

PT J
AU Johnson, LH
   Mapp, DC
   Rouse, DJ
   Spong, CY
   Mercer, BM
   Leveno, KJ
   Varner, MW
   Iams, JD
   Sorokin, Y
   Ramin, SM
   Miodovnik, M
   O'Sullivan, MJ
   Peaceman, AM
   Caritis, SN
AF Johnson, Lynn H.
   Mapp, Delicia C.
   Rouse, Dwight J.
   Spong, Catherine Y.
   Mercer, Brian M.
   Leveno, Kenneth J.
   Varner, Michael W.
   Iams, Jay D.
   Sorokin, Yoram
   Ramin, Susan M.
   Miodovnik, Menachem
   O'Sullivan, Mary J.
   Peaceman, Alan M.
   Caritis, Steve N.
CA Eunice Kennedy Shriver Natl Inst
TI Association of Cord Blood Magnesium Concentration and Neonatal
   Resuscitation
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID PRETERM BIRTH; CONTROLLED-TRIAL; SULFATE; HYPERMAGNESEMIA; NEWBORN;
   INFANT
AB Objective To assess the relationship between umbilical cord blood magnesium concentration and level of delivery room resuscitation received by neonates.
   Study design This was a secondary analysis of a controlled fetal neuroprotection trial that enrolled women at imminent risk for delivery between 24 and 31 weeks' gestation and randomly allocated them to receive either intravenous magnesium sulfate or placebo. The cohort included 1507 infants with data available on total cord blood Mg concentration and delivery room resuscitation. Multivariate logistic regression was used to estimate the association between cord blood Mg concentration and highest level of delivery room resuscitation, using the following hierarchy: none, oxygen only, bag-mask ventilation with oxygen, intubation, and chest compressions.
   Results There was no relationship between cord blood Mg and delivery room resuscitation (OR, 0.92 for each 1.0-mEq/L increase in Mg; 95% CI, 0.83-1.03). Maternal general anesthesia was associated with increased neonatal resuscitation (OR, 2.51; 95% CI, 1.72-3.68). Each 1-week increase in gestational age at birth was associated with decreased neonatal resuscitation (OR, 0.63; 95% CI, 0.60-0.66).
   Conclusion Cord blood Mg concentration does not correlate with the level of delivery room resuscitation of infants exposed to magnesium sulfate for fetal neuroprotection. (J Pediatr 2012;160:573-7).
C1 [Johnson, Lynn H.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
   [Mapp, Delicia C.] George Washington Univ, Ctr Biostat, Washington, DC USA.
   [Rouse, Dwight J.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
   [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Mercer, Brian M.] Case Western Reserve Univ, Metro Hlth Med Ctr, Cleveland, OH 44106 USA.
   [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
   [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
   [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
   [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
   [Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA.
   [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA.
   [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
   [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
RP Johnson, LH (reprint author), UNC Hosp, Div Neonatal Perinatal Med, CB7596, Chapel Hill, NC 27599 USA.
EM lynn.johnson@me.com
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
   Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [HD27869, HD34208, HD34116, HD40544, HD27915, HD34136,
   HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905,
   HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801, HD19897,
   MO1-RR-000080]; National Institute of Neurological Disorders and Stroke;
   US government [National Institutes of Health] [1K23HL092225-01]
FX Supported by the Eunice Kennedy Shriver National Institute of Child
   Health and Human Development (Grants HD27869, HD34208, HD34116, HD40544,
   HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485,
   HD40500, HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410,
   HD36801, HD19897, MO1-RR-000080) and the National Institute of
   Neurological Disorders and Stroke. This report does not necessarily
   represent the official views of the National Institute of Child Health
   and Human Development, National Institute of Neurological Disorders and
   Stroke, or the National Institutes of Health. The authors declare no
   conflicts of interest.; We thank the subcommittee members who
   participated in protocol development and coordination between clinical
   research centers (Allison T. Northen, MSN, RN), protocol/data management
   and statistical analysis (Elizabeth Thom, PhD and Steven J. Weiner, MS),
   and protocol development and oversight (Deborah G. Hirtz, MD and John M.
   Thorp, Jr, MD). We also thank Matthew M. Laughon, MD, MPH (supported by
   the US government for his work in pediatric and neonatal clinical
   pharmacology [National Institutes of Health Grant 1K23HL092225-01]),
   University of North Carolina at Chapel Hill, for providing additional
   support with analysis and manuscript review.
NR 20
TC 15
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U1 0
U2 1
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 APR
PY 2012
VL 160
IS 4
BP 573
EP +
DI 10.1016/j.jpeds.2011.09.016
PG 6
WC Pediatrics
SC Pediatrics
GA 921PP
UT WOS:000302489800011
PM 22056282
ER

PT J
AU Boztug, K
   Rosenberg, PS
   Dorda, M
   Banka, S
   Moulton, T
   Curtin, J
   Rezaei, N
   Corns, J
   Innis, JW
   Avci, Z
   Tran, HC
   Pellier, I
   Pierani, P
   Fruge, R
   Parvaneh, N
   Mamishi, S
   Mody, R
   Darbyshire, P
   Motwani, J
   Murray, J
   Buchanan, GR
   Newman, WG
   Alter, BP
   Boxer, LA
   Donadieu, J
   Welte, K
   Klein, C
AF Boztug, Kaan
   Rosenberg, Philip S.
   Dorda, Marie
   Banka, Siddharth
   Moulton, Thomas
   Curtin, Julie
   Rezaei, Nima
   Corns, John
   Innis, Jeffrey W.
   Avci, Zekai
   Hung Chi Tran
   Pellier, Isabelle
   Pierani, Paolo
   Fruge, Rachel
   Parvaneh, Nima
   Mamishi, Setareh
   Mody, Rajen
   Darbyshire, Phil
   Motwani, Jayashree
   Murray, Jennie
   Buchanan, George R.
   Newman, William G.
   Alter, Blanche P.
   Boxer, Laurence A.
   Donadieu, Jean
   Welte, Karl
   Klein, Christoph
TI Extended Spectrum of Human Glucose-6-Phosphatase Catalytic Subunit 3
   Deficiency: Novel Genotypes and Phenotypic Variability in Severe
   Congenital Neutropenia
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; LEUKEMIC TRANSFORMATION; MUTATIONS; G6PC3;
   EXPERIENCE; MORTALITY; ELASTASE; DISEASE; RISK; HAX1
AB Objective To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3).
   Study design Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis.
   Results In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations. We show that nonhematologic features of G6PC3 deficiency are good predictive indicators for mutations in G6PC3. Additionally, we demonstrate genetic variability in this disease and define novel features such as growth hormone deficiency, genital malformations, disrupted bone remodeling, and abnormalities of the integument. G6PC3 mutations may be associated with hydronephrosis or facial dysmorphism. The risk of transition to myelodysplastic syndrome/acute myeloid leukemia may be lower than in other genetically defined SCN subgroups.
   Conclusions The phenotypic and molecular spectrum in G6PC3 deficiency is wider than previously appreciated. The risk of transition to myelodysplastic syndrome or acute myeloid leukemia may be lower in G6PC3 deficiency compared with other subgroups of SCN. (J Pediatr 2012;160:679-83).
C1 [Boztug, Kaan] Austrian Acad Sci CeMM, Res Ctr Mol Med, A-1090 Vienna, Austria.
   [Boztug, Kaan] Med Univ Vienna, Dept Pediat & Adolescent Med, Vienna, Austria.
   [Boztug, Kaan; Dorda, Marie; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany.
   [Welte, Karl] Hannover Med Sch, Dept Mol Hematopoiesis, D-3000 Hannover, Germany.
   [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
   [Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
   [Banka, Siddharth; Newman, William G.] St Marys Hosp, Manchester Acad Hlth Sci Ctr, Manchester M13 0JH, Lancs, England.
   [Moulton, Thomas] Bronx Lebanon Hosp Ctr, Dept Pediat Hematol Oncol, Bronx, NY USA.
   [Curtin, Julie] Childrens Hosp Westmead, Dept Hematol, Sydney, NSW, Australia.
   [Rezaei, Nima] Univ Tehran Med Sci, Mol Immunol Res Ctr, Tehran, Iran.
   [Rezaei, Nima] Univ Tehran Med Sci, Dept Immunol, Sch Med, Tehran, Iran.
   [Rezaei, Nima; Parvaneh, Nima] Univ Tehran Med Sci, Childrens Med Ctr, Res Ctr Immunodeficiencies, Tehran, Iran.
   [Mamishi, Setareh] Univ Tehran Med Sci, Infect Dis Res Ctr, Tehran, Iran.
   [Corns, John] Nationwide Childrens Hosp, Dept Pediat Hematol Oncol, Columbus, OH USA.
   [Innis, Jeffrey W.] Univ Michigan, Div Pediat Genet, Ann Arbor, MI 48109 USA.
   [Mody, Rajen; Boxer, Laurence A.] Univ Michigan Hosp, Dept Pediat, Ann Arbor, MI 48109 USA.
   [Avci, Zekai] Kecioren Res & Training Hosp, Dept Pediat Hematol, Ankara, Turkey.
   [Hung Chi Tran] Childrens Hosp Los Angeles, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA.
   [Pellier, Isabelle] CHU Angers, Angers, France.
   [Pierani, Paolo] Polytech Univ Marche, G Salesi Womens & Childrens Hosp, Inst Mother & Child Hlth, Div Pediat Hematol Oncol, Ancona, Italy.
   [Fruge, Rachel] Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75235 USA.
   [Buchanan, George R.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Div Hematol Oncol, Dallas, TX 75390 USA.
   [Darbyshire, Phil; Motwani, Jayashree] Birmingham Childrens Hosp, Dept Haematol, Birmingham, W Midlands, England.
   [Murray, Jennie] Western Gen Hosp, SE Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Donadieu, Jean] Hop Trousseau, Serv Hemato Oncol Pediat, F-75571 Paris, France.
   [Klein, Christoph] Univ Munich, Univ Childrens Hosp, Munich, Germany.
RP Boztug, K (reprint author), Austrian Acad Sci CeMM, Res Ctr Mol Med, Lazarettgasse 14,AKH BT 25-3, A-1090 Vienna, Austria.
EM kboztug@cemm.oeaw.ac.at
RI Rezaei, Nima/B-4245-2008; isabelle, pellier/L-5683-2015; 
OI Rezaei, Nima/0000-0002-3836-1827; Banka, Siddharth/0000-0002-8527-2210;
   Newman, William/0000-0002-6382-4678
FU Fritz-Thyssen-Foundation; BMBF E-RARE; NIHR Manchester Biomedical
   Research Centre; National Institutes of Health; National Cancer
   Institute of the United States
FX Supported by grants from the Fritz-Thyssen-Foundation (to C. K. and K.
   B.), the BMBF E-RARE program (to C. K.), the NIHR Manchester Biomedical
   Research Centre (S. B.), and the Intramural Research Program of the
   National Institutes of Health and the National Cancer Institute of the
   United States (to P. R. and B. A.). The authors declare no conflicts of
   interest.
NR 34
TC 26
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U1 0
U2 6
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 APR
PY 2012
VL 160
IS 4
BP 679
EP +
DI 10.1016/j.jpeds.2011.09.019
PG 7
WC Pediatrics
SC Pediatrics
GA 921PP
UT WOS:000302489800031
PM 22050868
ER

PT J
AU Higgins, RD
   Raju, TNK
   Edwards, AD
AF Higgins, Rosemary D.
   Raju, Tonse N. K.
   Edwards, A. David
TI Hypothermia for neonatal encephalopathy in resource-poor environments
   Reply
SO JOURNAL OF PEDIATRICS
LA English
DT Letter
C1 [Higgins, Rosemary D.; Raju, Tonse N. K.; Edwards, A. David] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD USA.
RP Higgins, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
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 APR
PY 2012
VL 160
IS 4
BP 709
EP 710
DI 10.1016/j.jpeds.2012.01.013
PG 3
WC Pediatrics
SC Pediatrics
GA 921PP
UT WOS:000302489800043
ER

PT J
AU Fowler, CB
   Waybright, TJ
   Veenstra, TD
   O'Leary, TJ
   Mason, JT
AF Fowler, Carol B.
   Waybright, Timothy J.
   Veenstra, Timothy D.
   O'Leary, Timothy J.
   Mason, Jeffrey T.
TI Pressure-Assisted Protein Extraction: A Novel Method for Recovering
   Proteins from Archival Tissue for Proteomic Analysis
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE FFPE; formalin-fixed paraffin-embedded; high-pressure protein
   extraction; mouse liver; mass spectrometry; heat and pressure;
   proteomics
ID PARAFFIN-EMBEDDED TISSUES; MODELING FORMALIN FIXATION; ANTIGEN
   RETRIEVAL; MASS-SPECTROMETRY; PROSTATE-CANCER; SPECIMENS;
   IMMUNOHISTOCHEMISTRY; SURROGATES; BIOMARKER; SECTIONS
AB Formaldehyde-fixed, paraffin-embedded (FFPE) tissue repositories represent a valuable resource for the retrospective study of disease progression and response to therapy. However, the proteomic analysis of FFPE tissues has been hampered by formaldehyde-induced protein modifications, which reduce protein extraction efficiency and may lead to protein misidentification. Here, we demonstrate the use of heat augmented with high hydrostatic pressure (40,000 psi) as a novel method for the recovery of intact proteins from FFPE mouse liver. When FFPE mouse liver was extracted using heat and elevated pressure, there was a 4-fold increase in protein extraction efficiency, a 3-fold increase in the extraction of intact proteins, and up to a 30-fold increase in the number of nonredundant proteins identified by mass spectrometry, compared to matched tissue extracted with heat alone. More importantly, the number of nonredundant proteins identified in the FFPE tissue was nearly identical to that of matched fresh-frozen tissue.
C1 [Fowler, Carol B.; Mason, Jeffrey T.] Armed Forces Inst Pathol, Dept Biophys, Rockville, MD USA.
   [Fowler, Carol B.; O'Leary, Timothy J.] Vet Hlth Adm, Biomed Lab, Res & Dev Serv, Washington, DC USA.
   [Waybright, Timothy J.; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA.
RP Mason, JT (reprint author), Armed Forces Inst Pathol, Dept Biophys, Rockville, MD USA.
EM jeffrey.mason.afip@gmail.com
FU National Cancer Institute, National Institutes of Health [1R21 CA134359,
   NO1-CO-12400]; Veterans Health Administration
FX The authors declare the following competing financial interest(s): This
   project has been funded in whole or in part with federal funds from the
   National Cancer Institute, National Institutes of Health, under grant
   1R21 CA134359 (C.B.F.), and contract NO1-CO-12400 (T.D.V.), and the
   Veterans Health Administration under a Merit Review award (J.T.M. and
   T,J.O.). Carol B Fowler, Jeffrey T Mason, and Timothy J O'Leary are
   named as lead contributors in a patent application filed with the USPTO
   by the Veterans Health Administration and the Armed Forces Institute of
   Pathology.
NR 33
TC 17
Z9 17
U1 0
U2 8
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 APR
PY 2012
VL 11
IS 4
BP 2602
EP 2608
DI 10.1021/pr201005t
PG 7
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 920FL
UT WOS:000302388100048
PM 22352854
ER

PT J
AU Pope, K
   Luna, B
   Thomas, CR
AF Pope, Kayla
   Luna, Beatriz
   Thomas, Christopher R.
TI Developmental Neuroscience and the Courts: How Science Is Influencing
   the Disposition of Juvenile Offenders
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
C1 [Pope, Kayla] NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA.
   [Luna, Beatriz] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA.
   [Thomas, Christopher R.] Univ Texas Med Branch Galveston, Galveston, TX USA.
RP Pope, K (reprint author), NIMH, Unit Affect Cognit Neurosci, Bldg 15K,Room 115, Bethesda, MD 20892 USA.
EM pkayla@mail.nih.gov
NR 6
TC 6
Z9 6
U1 0
U2 3
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 APR
PY 2012
VL 51
IS 4
BP 341
EP 342
DI 10.1016/j.jaac.2012.01.003
PG 2
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 918SQ
UT WOS:000302271800001
PM 22449636
ER

PT J
AU Swedo, SE
   Baird, G
   Cook, EH
   Happe, FG
   Harris, JC
   Kaufmann, WE
   King, BH
   Lord, CE
   Piven, J
   Rogers, SJ
   Spence, SJ
   Wetherby, A
   Wright, HH
AF Swedo, Susan E.
   Baird, Gillian
   Cook, Edwin H., Jr.
   Happe, Francesca G.
   Harris, James C.
   Kaufmann, Walter E.
   King, Bryan H.
   Lord, Catherine E.
   Piven, Joseph
   Rogers, Sally J.
   Spence, Sarah J.
   Wetherby, Amy
   Wright, Harry H.
TI Commentary from the DSM-5 Workgroup on Neurodevelopmental Disorders
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
ID AUTISM SPECTRUM DISORDER; CRITERIA
RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA.
EM swedos@mail.nih.gov
OI Happe, Francesca/0000-0001-9226-4000
NR 5
TC 29
Z9 29
U1 2
U2 27
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 APR
PY 2012
VL 51
IS 4
BP 347
EP 349
DI 10.1016/j.jaac.2012.02.013
PG 3
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 918SQ
UT WOS:000302271800004
PM 22449639
ER

PT J
AU DeKlotz, CC
   DeWitt, CA
   Cardin, E
   Ried, T
AF DeKlotz, Cynthia Carver
   DeWitt, Christine A.
   Cardin, Eric
   Ried, Thomas
TI All-trans-retinoic acid and cetuximab: Effects on colon adenocarcinoma
   cell viability
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 16-20, 2012
CL San Diego, CA
SP Amer Acad Dermatol (AAD)
C1 [DeKlotz, Cynthia Carver] Georgetown Univ Hosp, Washington Hosp Ctr, Washington, DC 20007 USA.
   [Cardin, Eric; Ried, Thomas] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2012
VL 66
IS 4
SU S
BP AB34
EP AB34
PG 1
WC Dermatology
SC Dermatology
GA 919JF
UT WOS:000302319800136
ER

PT J
AU Smith, G
   Franks, A
   Cronstein, B
   Chan, E
   Liu, HL
   Fernandez, P
AF Smith, Gideon
   Franks, Andrew
   Cronstein, Bruce
   Chan, Edwin
   Liu, Hailing
   Fernandez, Patricia
TI Adenosine-mediated dermal fibrosis and Fli-1 expression in CD39 and CD73
   knockout mice
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 16-20, 2012
CL San Diego, CA
SP Amer Acad Dermatol (AAD)
C1 [Smith, Gideon; Cronstein, Bruce; Chan, Edwin; Liu, Hailing] NYU, Dept Translat Med, New York, NY USA.
   [Smith, Gideon; Franks, Andrew] NYU, Dept Dermatol, New York, NY 10016 USA.
   [Fernandez, Patricia] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2012
VL 66
IS 4
SU S
BP AB2
EP AB2
PG 1
WC Dermatology
SC Dermatology
GA 919JF
UT WOS:000302319800006
ER

PT J
AU Brown, M
   Simonsick, E
   Thorpe, R
   Ferrucci, L
AF Brown, M.
   Simonsick, E.
   Thorpe, R.
   Ferrucci, L.
TI Do Race-Related Functional Disparities Exist in Well-Educated
   Financially Secure Older Adults? Findings from the BLSA.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Brown, M.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
   [Simonsick, E.; Ferrucci, L.] NIA IRP Intramural Res Program, Baltimore, MD USA.
   [Thorpe, R.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S107
EP S107
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800310
ER

PT J
AU Cleinman, A
   Griswold, ME
   Simonsick, E
   Meeks, WM
   Gregg, K
   Ferrucci, L
   Windham, BG
AF Cleinman, A.
   Griswold, M. E.
   Simonsick, E.
   Meeks, W. M.
   Gregg, K.
   Ferrucci, L.
   Windham, B. G.
TI Falls and Orthostatic Hypotension: Re-examining Limits
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Cleinman, A.; Meeks, W. M.; Gregg, K.; Windham, B. G.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA.
   [Griswold, M. E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
   [Simonsick, E.; Ferrucci, L.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S11
EP S11
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800029
ER

PT J
AU Hanlon, JT
   Zheng, Y
   Boudreau, RM
   Strotmeyer, ES
   Newman, AB
   Simonsick, EM
   Shorr, RI
   Bauer, DC
   Donohue, JM
AF Hanlon, J. T.
   Zheng, Y.
   Boudreau, R. M.
   Strotmeyer, E. S.
   Newman, A. B.
   Simonsick, E. M.
   Shorr, R. I.
   Bauer, D. C.
   Donohue, J. M.
TI Antilipemic Use and Lipid Control in Older Black and White Adults with
   Coronary Heart Disease and/or Diabetes Mellitus Pre- and Post- Medicare
   Part D.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Hanlon, J. T.; Zheng, Y.; Boudreau, R. M.; Strotmeyer, E. S.; Newman, A. B.; Donohue, J. M.] UPITT, Pittsburgh, PA USA.
   [Simonsick, E. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Shorr, R. I.] VA GRECC, Gainesville, FL USA.
   [Bauer, D. C.] UCSF, San Francisco, CA USA.
RI Strotmeyer, Elsa/F-3015-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S110
EP S110
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800320
ER

PT J
AU Higuchi, M
   Chen, R
   Bell, C
   Wongvarcharoen, L
   Ross, W
   Petrovitch, H
   Launer, L
   Abbott, R
   Masaki, K
AF Higuchi, M.
   Chen, R.
   Bell, C.
   Wongvarcharoen, L.
   Ross, W.
   Petrovitch, H.
   Launer, L.
   Abbott, R.
   Masaki, K.
TI Proteinuria in Mid-Life and Cognitive Function in Late-Life: The
   Honolulu-Asia Aging Study.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Higuchi, M.; Bell, C.; Wongvarcharoen, L.; Ross, W.; Petrovitch, H.; Abbott, R.; Masaki, K.] Univ Hawaii, Honolulu, HI 96822 USA.
   [Chen, R.; Petrovitch, H.; Masaki, K.] Kuakini Med Ctr, Honolulu, HI USA.
   [Ross, W.] VA Pacific Isl Healthcare Syst, Honolulu, HI USA.
   [Launer, L.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S115
EP S115
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800333
ER

PT J
AU Hile, ES
   Brach, JS
   Yang, M
   Studenski, SA
   Boudreau, RM
   Caserotti, P
   Satterfield, S
   Schwartz, AV
   Simonsick, E
   Ferrucci, L
   Harris, TB
   Newman, AB
   Strotmeyer, ES
AF Hile, E. S.
   Brach, J. S.
   Yang, M.
   Studenski, S. A.
   Boudreau, R. M.
   Caserotti, P.
   Satterfield, S.
   Schwartz, A. V.
   Simonsick, E.
   Ferrucci, L.
   Harris, T. B.
   Newman, A. B.
   Strotmeyer, E. S.
TI Sensory and motor nerve function differentially relate to gait
   parameters: the Health ABC Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Hile, E. S.; Brach, J. S.; Yang, M.; Studenski, S. A.; Boudreau, R. M.; Newman, A. B.; Strotmeyer, E. S.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Caserotti, P.; Simonsick, E.; Ferrucci, L.; Harris, T. B.] NIA, Bethesda, MD 20892 USA.
   [Caserotti, P.] Univ So Denmark, Odense, Denmark.
   [Schwartz, A. V.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Satterfield, S.] Univ Tennessee, Memphis, TN USA.
RI Strotmeyer, Elsa/F-3015-2014
NR 0
TC 0
Z9 0
U1 0
U2 4
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 APR
PY 2012
VL 60
SU 4
SI SI
BP S11
EP S11
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800030
ER

PT J
AU Kojima, G
   Lui, F
   Chen, R
   Bell, C
   Abbott, RD
   Launer, L
   Ross, GW
   Curb, JD
   Masaki, KH
AF Kojima, G.
   Lui, F.
   Chen, R.
   Bell, C.
   Abbott, R. D.
   Launer, L.
   Ross, G. W.
   Curb, J. D.
   Masaki, K. H.
TI D as in Death - Dietary Vitamin D in Mid-Life and Total Mortality: The
   Honolulu Heart Program.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Kojima, G.; Lui, F.; Bell, C.; Abbott, R. D.; Ross, G. W.; Curb, J. D.; Masaki, K. H.] Univ Hawaii, John A Hartford Fdn Ctr Excellence Geriatr, Dept Geriatr Med, Honolulu, HI 96822 USA.
   [Chen, R.; Curb, J. D.; Masaki, K. H.] Kuakini Med Ctr, Honolulu, HI USA.
   [Ross, G. W.] Vet Affairs Pacific Isl Healthcare Syst, Honolulu, HI USA.
   [Launer, L.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S150
EP S150
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800435
ER

PT J
AU Liu, C
   Lyass, A
   Massaro, J
   D'Agostino, R
   Fox, CS
   Murabito, JM
AF Liu, C.
   Lyass, A.
   Massaro, J.
   D'Agostino, R.
   Fox, C. S.
   Murabito, J. M.
TI Chronic kidney disease as defined by cystatin C predicts mobility
   disability: The Framingham Offspring Study.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Liu, C.; Murabito, J. M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Liu, C.] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Lyass, A.; Massaro, J.; D'Agostino, R.; Fox, C. S.; Murabito, J. M.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
   [Massaro, J.; D'Agostino, R.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
   [Fox, C. S.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S117
EP S117
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800339
ER

PT J
AU Marcum, ZA
   Zheng, Y
   Perera, S
   Strotmeyer, E
   Newman, A
   Simonsick, E
   Shorr, R
   Bauer, DC
   Donohue, JM
   Hanlon, JT
AF Marcum, Z. A.
   Zheng, Y.
   Perera, S.
   Strotmeyer, E.
   Newman, A.
   Simonsick, E.
   Shorr, R.
   Bauer, D. C.
   Donohue, J. M.
   Hanlon, J. T.
TI Prevalence and Correlates of Self-Reported Medication Non-Adherence
   among Older Adults with Diabetes Mellitus, Coronary Heart Disease,
   and/or Hypertension.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Marcum, Z. A.; Zheng, Y.; Perera, S.; Strotmeyer, E.; Newman, A.; Donohue, J. M.; Hanlon, J. T.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Simonsick, E.] NIA Intramural Res Program, Baltimore, MD USA.
   [Shorr, R.] VA GRECC, Gainesville, FL USA.
   [Bauer, D. C.] UCSF, San Francisco, CA USA.
RI Perera, Subashan/D-7603-2014; Strotmeyer, Elsa/F-3015-2014
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S90
EP S90
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800260
ER

PT J
AU Peron, EP
   Zheng, Y
   Perera, S
   Newman, AB
   Resnick, NM
   Shorr, RI
   Bauer, DC
   Simonsick, EM
   Gray, SL
   Hanlon, JT
   Ruby, CM
AF Peron, E. P.
   Zheng, Y.
   Perera, S.
   Newman, A. B.
   Resnick, N. M.
   Shorr, R. I.
   Bauer, D. C.
   Simonsick, E. M.
   Gray, S. L.
   Hanlon, J. T.
   Ruby, C. M.
TI Antihypertensive Drug Class Use Associated with Urinary Incontinence in
   Community-Dwelling Elderly Women?
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Peron, E. P.; Zheng, Y.; Perera, S.; Newman, A. B.; Resnick, N. M.; Hanlon, J. T.; Ruby, C. M.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Shorr, R. I.] Gainesville VA Geriatr Res Educ & Clin Ctr, Gainesville, FL USA.
   [Simonsick, E. M.] Johns Hopkins Univ, Baltimore, MD USA.
   [Bauer, D. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Simonsick, E. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Gray, S. L.] Univ Washington, Seattle, WA 98195 USA.
RI Perera, Subashan/D-7603-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S101
EP S101
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800292
ER

PT J
AU Wilson, V
   Neiberg, R
   Tooze, JA
   Sink, KM
   Shea, K
   Williamson, J
   Kitzman, DW
   Hausman, DB
   Cauley, J
   Bauer, D
   Harris, T
   Kritchevsky, SB
   Houston, DK
AF Wilson, V.
   Neiberg, R.
   Tooze, J. A.
   Sink, K. M.
   Shea, K.
   Williamson, J.
   Kitzman, D. W.
   Hausman, D. B.
   Cauley, J.
   Bauer, D.
   Harris, T.
   Kritchevsky, S. B.
   Houston, D. K.
TI 25-hydroxyvitamin D and Cardiovascular Disease in the Health ABC Study.
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Meeting Abstract
CT Annual Scientific Meeting of the American-Geriatrics-Society
CY MAY 03-05, 2012
CL Seattle, WA
SP Amer Geriatr Soc
C1 [Wilson, V.; Neiberg, R.; Tooze, J. A.; Sink, K. M.; Shea, K.; Williamson, J.; Kitzman, D. W.; Kritchevsky, S. B.; Houston, D. K.] Wake Forest Univ, Winston Salem, NC 27109 USA.
   [Hausman, D. B.] Univ Georgia, Athens, GA 30602 USA.
   [Cauley, J.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Bauer, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Harris, T.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD APR
PY 2012
VL 60
SU 4
SI SI
BP S89
EP S89
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 921FZ
UT WOS:000302464800259
ER

PT J
AU Daugirdas, JT
   Chertow, GM
   Larive, B
   Pierratos, A
   Greene, T
   Ayus, JC
   Kendrick, CA
   James, SH
   Miller, BW
   Schulman, G
   Salusky, IB
   Kliger, AS
AF Daugirdas, John T.
   Chertow, Glenn M.
   Larive, Brett
   Pierratos, Andreas
   Greene, Tom
   Ayus, Juan Carlos
   Kendrick, Cynthia A.
   James, Sam H.
   Miller, Brent W.
   Schulman, Gerald
   Salusky, Isidro B.
   Kliger, Alan S.
CA FHN Trial Grp
TI Effects of Frequent Hemodialysis on Measures of CKD Mineral and Bone
   Disorder
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; PHOSPHATE BINDERS; CONVENTIONAL HEMODIALYSIS;
   METABOLISM; MORTALITY; TRIALS
AB More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P<0.001). At month 12, 42% of patients on nocturnal hemodialysis required the addition of phosphorus into the dialysate to prevent hypophosphatemia. Frequent hemodialysis did not have major effects on calcium or parathyroid hormone concentrations in either trial. In conclusion, frequent hemodialysis facilitates control of hyperphosphatemia and extended session lengths could allow more liberal diets and freedom from phosphorus binders.
C1 [Daugirdas, John T.] Univ Illinois, Chicago, IL 60612 USA.
   [Chertow, Glenn M.] Stanford Univ, Stanford, CA 94305 USA.
   [Kendrick, Cynthia A.] Cleveland Clin, Cleveland, OH 44106 USA.
   [Pierratos, Andreas] Univ Toronto, Toronto, ON, Canada.
   [Greene, Tom] Univ Utah, Salt Lake City, UT USA.
   [Ayus, Juan Carlos] Renal Consultants Houston, Houston, TX USA.
   [James, Sam H.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Miller, Brent W.] Washington Univ, St Louis, MO USA.
   [Schulman, Gerald] Vanderbilt Univ, Nashville, TN USA.
   [Salusky, Isidro B.] Univ Calif Los Angeles, Los Angeles, CA USA.
   [Kliger, Alan S.] Yale Univ, New Haven, CT USA.
   NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Daugirdas, JT (reprint author), Univ Illinois, 820 S Wood St, Chicago, IL 60612 USA.
EM jtdaugir@uic.edu
FU National Institutes of Health (NIH), National Institutes of Diabetes and
   Digestive and Kidney Diseases; Center for Medicare and Medical Services;
   NIH Research Foundation; FHN trials included Amgen; Baxter; Dialysis
   Clinics Inc.; DaVita; Dialysis Clinics Inc; Fresenius Medical Care;
   Renal Advantage; Renal Research Institute; Satellite Healthcare
FX This study was supported by the National Institutes of Health (NIH),
   National Institutes of Diabetes and Digestive and Kidney Diseases, the
   Center for Medicare and Medical Services, and the NIH Research
   Foundation. Contributors to the NIH Foundation in support of the FHN
   trials included Amgen, Baxter, and Dialysis Clinics Inc. Additional
   support was provided by DaVita, Dialysis Clinics Inc, Fresenius Medical
   Care, Renal Advantage, Renal Research Institute, and Satellite
   Healthcare.
NR 22
TC 55
Z9 57
U1 0
U2 16
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 APR
PY 2012
VL 23
IS 4
BP 727
EP 738
DI 10.1681/ASN.2011070688
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 919MZ
UT WOS:000302333300020
PM 22362907
ER

PT J
AU Brown, P
AF Brown, Patricia
TI A word from OLAW
SO LAB ANIMAL
LA English
DT Editorial Material
C1 NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD APR
PY 2012
VL 41
IS 4
BP 98
EP 98
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 918TU
UT WOS:000302274800015
PM 22430472
ER

PT J
AU Chen, ZD
   Mantha, RR
   Chen, JS
   Slivano, OJ
   Takahashi, H
AF Chen, Zhidong
   Mantha, Rebecca R.
   Chen, Janice S.
   Slivano, Orazio J.
   Takahashi, Hideko
TI Non-invasive genotyping of transgenic animals using fecal DNA
SO LAB ANIMAL
LA English
DT Article
ID PCR AMPLIFICATION; EXTRACTION; MICE; FECES; SAMPLES; IDENTIFICATION;
   BACTERIAL
AB For genotyping of transgenic animals, many IACUC guidelines recommend the use of fecal DNA when possible because this approach is non-invasive. Existing methods for extracting fecal DNA may be costly or involve the use of toxic organic solvents. Furthermore, feces contain an abundance of PCR inhibitors that may hinder DNA amplification when they are co-purified with fecal DNA. Here the authors describe a cost-effective, non-toxic method for genotyping transgenic animals by using the reagent Aqua Stool to extract fecal DNA and remove PCR inhibitors. Genotyping results obtained from fecal DNA samples extracted using Aqua Stool were reliably accurate when compared with results obtained from tail DNA samples. Because it is non-invasive, the authors believe that use of this method for genotyping transgenic animals using fecal DNA samples may improve animal welfare.
C1 [Chen, Zhidong] MultiTarget Pharmaceut LLC, Salt Lake City, UT 84103 USA.
   [Mantha, Rebecca R.] Atom Energy Canada Ltd, Chalk River Labs, Chalk River, ON K0J 1J0, Canada.
   [Chen, Janice S.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
   [Slivano, Orazio J.] Univ Rochester, Sch Med & Dent, Aab Cardiovasc Res Inst, Rochester, NY USA.
   [Takahashi, Hideko] NEI, NIH, Bethesda, MD 20892 USA.
RP Chen, ZD (reprint author), MultiTarget Pharmaceut LLC, Salt Lake City, UT 84103 USA.
EM zchen@multitargetpharm.com
FU Johns Hopkins Center for Alternatives to Animal Testing (CAAT)
FX This work was funded in part by a grant from the Johns Hopkins Center
   for Alternatives to Animal Testing (CAAT).
NR 20
TC 0
Z9 1
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD APR
PY 2012
VL 41
IS 4
BP 102
EP 107
PG 6
WC Veterinary Sciences
SC Veterinary Sciences
GA 918TU
UT WOS:000302274800017
PM 22430476
ER

PT J
AU Roberts, DD
   Miller, TW
   Rogers, NM
   Yao, MY
   Isenberg, JS
AF Roberts, David D.
   Miller, Thomas W.
   Rogers, Natasha M.
   Yao, Mingyi
   Isenberg, Jeffrey S.
TI The matricellular protein thrombospondin-1 globally regulates
   cardiovascular function and responses to stress via CD47
SO MATRIX BIOLOGY
LA English
DT Review
DE Thrombospondin-1; Nitric oxide; Blood pressure; Ischemia; CD47; cGMP
ID ENDOTHELIAL GROWTH-FACTOR; SOLUBLE GUANYLATE-CYCLASE;
   ISCHEMIA-REPERFUSION INJURY; INTEGRIN-ASSOCIATED PROTEIN; MUSCLE-CELL
   RESPONSES; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE; HUMAN PLATELETS;
   BLOOD-PRESSURE; ENDOGENOUS THROMBOSPONDIN-1
AB Matricellular proteins play diverse roles in modulating cell behavior by engaging specific cell surface receptors and interacting with extracellular matrix proteins, secreted enzymes, and growth factors. Studies of such interactions involving thrombospondin-1 have revealed several physiological functions and roles in the pathogenesis of injury responses and cancer, but the relatively mild phenotypes of mice lacking thrombospondin-1 suggested that thrombospondin-1 would not be a central player that could be exploited therapeutically. Recent research focusing on signaling through its receptor CD47, however, has uncovered more critical roles for thrombospondin-1 in acute regulation of cardiovascular dynamics, hemostasis, immunity, and mitochondrial homeostasis. Several of these functions are mediated by potent and redundant inhibition of the canonical nitric oxide pathway. Conversely, elevated tissue thrombospondin-1 levels in major chronic diseases of aging may account for the deficient nitric oxide signaling that characterizes these diseases, and experimental therapeutics targeting CD47 show promise for treating such chronic diseases as well as acute stress conditions that are associated with elevated thrombospondin-1 expression. Published by Elsevier B.V.
C1 [Roberts, David D.; Miller, Thomas W.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Isenberg, Jeffrey S.] Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
   [Rogers, Natasha M.; Yao, Mingyi; Isenberg, Jeffrey S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10 Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov; jsi5@pitt.edu
RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011
OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785
FU National Cancer Institute, NIH; NIH [K22CA128616, R01 HL-108954];
   American Heart Association [11BGIA7210001, 1P01HL103455-01]; Vascular
   Medicine Institute; Institute for Transfusion Medicine; Hemophilia
   Center of Western PA
FX This work was supported by the Intramural Research Program of the
   National Cancer Institute, NIH to DDR and K22CA128616, R01 HL-108954
   (NIH), American Heart Association grant 11BGIA7210001, 1P01HL103455-01
   (NIH), the Vascular Medicine Institute, the Institute for Transfusion
   Medicine, and the Hemophilia Center of Western PA to JSI.
NR 94
TC 46
Z9 47
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0945-053X
J9 MATRIX BIOL
JI Matrix Biol.
PD APR
PY 2012
VL 31
IS 3
BP 162
EP 169
DI 10.1016/j.matbio.2012.01.005
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 921AE
UT WOS:000302449600003
PM 22266027
ER

PT J
AU Glaser, R
   Dimitrakakis, C
   Trimble, N
   Martin, V
AF Glaser, Rebecca
   Dimitrakakis, Constantine
   Trimble, Nancy
   Martin, Vincent
TI Testosterone pellet implants and migraine headaches: A pilot study
SO MATURITAS
LA English
DT Article
DE Androgens; Testosterone; Implant; Migraine headache; Pre-menopausal;
   Post-menopausal
ID POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; ANDROGENS; AGE
AB The purpose of this prospective pilot study was to determine the therapeutic effect of continuous testosterone, delivered as a subcutaneous implant, on the severity of migraine headaches in pre- and post-menopausal patients. Twenty-seven women with a history of documented migraine headache were asked to rate their headache severity using a five-point scale at baseline (prior to therapy); and again, 3 months following treatment with testosterone implants. Improvement in headache severity was noted by 92% of patients and the mean level of improvement was statistically significant (3.3 on a 5 point scale). In addition, there was no difference in the level of improvement between pre- and post-menopausal cohorts. Seventy-four percent of patients reported a headache severity score of '0' (none) on testosterone implant therapy for the 3-month treatment period. Continuous testosterone was effective therapy in reducing the severity of migraine headaches in both pre- and post-menopausal women. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Glaser, Rebecca] Millennium Wellness Ctr, Dayton, OH 45458 USA.
   [Glaser, Rebecca] Wright State Univ, Boonshoft Sch Med, Dept Surg, Dayton, OH 45435 USA.
   [Dimitrakakis, Constantine] Univ Athens, Sch Med, Dept Ob Gyn 1, Athens 11528, Greece.
   [Dimitrakakis, Constantine] NICHD, NIH, Bethesda, MD 20892 USA.
   [Trimble, Nancy] Hosp Dayton, Dayton, OH 45420 USA.
   [Martin, Vincent] Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH 45267 USA.
RP Glaser, R (reprint author), Millennium Wellness Ctr, 228 E Spring Valley Rd, Dayton, OH 45458 USA.
EM rglaser@woh.rr.com; dimitrac@mail.nih.gov; ntrimble@woh.rr.com;
   martinvt@ucmail.uc.edu
NR 21
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0378-5122
EI 1873-4111
J9 MATURITAS
JI Maturitas
PD APR
PY 2012
VL 71
IS 4
BP 385
EP 388
DI 10.1016/j.maturitas.2012.01.006
PG 4
WC Geriatrics & Gerontology; Obstetrics & Gynecology
SC Geriatrics & Gerontology; Obstetrics & Gynecology
GA 920US
UT WOS:000302434200012
PM 22310106
ER

PT J
AU Harlow, SD
   Gass, M
   Hall, JE
   Lobo, R
   Maki, P
   Rebar, RW
   Sherman, S
   Sluss, PM
   de Villiers, TJ
AF Harlow, Sioban D.
   Gass, Margery
   Hall, Janet E.
   Lobo, Roger
   Maki, Pauline
   Rebar, Robert W.
   Sherman, Sherry
   Sluss, Patrick M.
   de Villiers, Tobie J.
CA STRAW 10 Collaborative Grp
TI Executive summary of the Stages of Reproductive Aging Workshop+10:
   addressing the unfinished agenda of staging reproductive aging
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Reproductive aging; Ovarian aging; Menopause; Follicle-stimulating
   hormone; Antimullerian hormone; Antral follicle count; Inhibin-B
ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; EARLY MENOPAUSAL
   TRANSITION; POLYCYSTIC-OVARY-SYNDROME; MIDDLE-AGED WOMEN; REGULAR
   MENSTRUAL CYCLES; INHIBIN-B; ANTIMULLERIAN HORMONE; LONGITUDINAL
   CHANGES; DEPRESSIVE SYMPTOMS
AB Objective: The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.
   Methods: Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimullerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.
   Results: STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage + 1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage + 1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.
   Conclusions: STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.
C1 [Harlow, Sioban D.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Gass, Margery] N Amer Menopause Soc, Mayfield Hts, OH USA.
   [Hall, Janet E.] Harvard Univ, Sch Med, Dept Med, Endocrine Soc, Boston, MA USA.
   [Lobo, Roger] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
   [Maki, Pauline] Univ Illinois, Dept Psychiat & Psychol, Chicago, IL USA.
   [Rebar, Robert W.] Amer Soc Reprod Med, Birmingham, AL USA.
   [Sherman, Sherry] NIA, Bethesda, MD 20892 USA.
   [Sluss, Patrick M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [de Villiers, Tobie J.] Internat Menopause Soc, Cape Town, South Africa.
RP Harlow, SD (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM harlow@umich.edu
FU National Institutes of Health (NIH), Department of Health and Human
   Services (DHHS), through the National Institute on Aging (NIA)
   [AG039961]; NIH Office of Research on Women's Health (ORWH); North
   American Menopause Society (NAMS); American Society for Reproductive
   Medicine (ASRM); International Menopause Society (IMS); Endocrine
   Society; National Institute on Aging (NIA); Eunice Kennedy Shriver
   National Institute of Child Health and Human Development (NICHD);
   National Institute on Mental Health (NIMH); National Institute of
   Allergy and Infectious Diseases (NIAID); National Institute on Drug
   Abuse (NIDA); Royal Ottawa Foundation for Mental Health; Mayo Clinic;
   Northwestern University; ASRM; Adcock Ingram; Pfizer; Servier; Amgen;
   Bayer; Board of Trustees for NAMS; Baycrest
FX Funding/support: The Stages of Reproductive Aging Workshop (STRAW) + 10
   had grant support from the National Institutes of Health (NIH),
   Department of Health and Human Services (DHHS), through the National
   Institute on Aging (NIA) (AG039961), and the NIH Office of Research on
   Women's Health (ORWH) as well as from The North American Menopause
   Society (NAMS), the American Society for Reproductive Medicine (ASRM),
   the International Menopause Society (IMS), and the Endocrine Society.;
   Financial disclosure/conflicts of interest: P. M. S. and S. S. declare
   no conflict of interest. M. G. receives salary support from The North
   American Menopause Society (NAMS). S. D. H. has grant support from the
   National Institute on Aging (NIA) and Eunice Kennedy Shriver National
   Institute of Child Health and Human Development (NICHD) and receives
   travel support from NAMS. J.E.H. has grant support from NIA and receives
   travel support from the Endocrine Society. R. L. is past president of
   the American Society for Reproductive Medicine (ASRM). P. M. receives
   grant support from the National Institute on Mental Health (NIMH), the
   NIA, the National Institute of Allergy and Infectious Diseases (NIAID),
   and the National Institute on Drug Abuse (NIDA); is on the Board of
   Trustees for NAMS; and has previously consulted for Noven
   Pharmaceuticals, received lecture fees from the Royal Ottawa Foundation
   for Mental Health, the Mayo Clinic, Baycrest, and Northwestern
   University and received travel support from the Society for Women's
   Health Research, the International Menopause Society, Pfizer, the
   Australasian Pacific Menopause Society, Virginia Commonwealth University
   Institute for Women's Health. R. W. R. receives salary support from
   ASRM. T.J.d.V. declares no direct conflict of interest as regards the
   submitted article but has in the past received consultancy fees from
   Adcock Ingram and Pfizer; speaker's fees from Servier; and travel
   support from Amgen, Pfizer, and Bayer.
NR 90
TC 72
Z9 78
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD APR
PY 2012
VL 19
IS 4
BP 387
EP 395
DI 10.1097/gme.0b013e31824d8f40
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 916ZM
UT WOS:000302141700005
PM 22343510
ER

PT J
AU Cheung, GYC
   Duong, AC
   Otto, M
AF Cheung, Gordon Y. C.
   Duong, Anthony C.
   Otto, Michael
TI Direct and synergistic hemolysis caused by Staphylococcus phenol-soluble
   modulins: implications for diagnosis and pathogenesis
SO MICROBES AND INFECTION
LA English
DT Article
DE Staphylococcus aureus; Staphylococcus epidermidis; Hemolysis;
   Beta-toxin; Delta-toxin; Phenol-soluble modulin
ID VIRULENCE DETERMINANTS; AUREUS; AGR; EXPRESSION; EPIDERMIDIS; MUTATION;
   IDENTIFICATION; PEPTIDES; STREPTOCOCCI; EVOLUTION
AB Phenol-soluble modulins are secreted staphylococcal peptides with an amphipathic alpha-helical structure. Some PSMs are strongly cytolytic toward human neutrophils and represent major virulence determinants during Staphylococcus aureus skin and blood infection. However, capacities of PSMs to lyse human erythrocytes have not been investigated. Here, we demonstrate that many S. aureus and Staphylococcus epidermidis PSMs lyse human erythrocytes. Furthermore, synergism with S. aureus beta-toxin considerably increased the hemolytic capacities of several PSMs. This synergism may be of key importance in PSM and beta-toxin-producing S. aureus or in mixed-strain or -species infections with PSM and beta-toxin producers. Of specific interest, several PSMs, in particular PSM alpha peptides, contributed to a considerable extent to synergistic hemolysis with beta-toxin or when using the beta-toxin-producing strain RN4220 in CAMP assays. Thus, CAMP-type assays should not be used to detect or quantify S. aureus delta-toxin production, but may be used for an overall assessment of Agr functionality. Our study suggests an additional role of PSMs in staphylococcal pathogenesis and demonstrates that the repertoire of staphylococcal hemolysins is not limited to S. aureus and is much larger and diverse than previously thought. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Cheung, Gordon Y. C.; Duong, Anthony C.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bldg 33,Room 1W10A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
RI Cheung, Yiu Chong /K-3565-2012; 
OI Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases (NIAID), The
   National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program of the
   National Institute of Allergy and Infectious Diseases (NIAID), The
   National Institutes of Health (NIH).
NR 33
TC 38
Z9 38
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD APR
PY 2012
VL 14
IS 4
BP 380
EP 386
DI 10.1016/j.micinf.2011.11.013
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 920SR
UT WOS:000302428300011
PM 22178792
ER

PT J
AU Kagan, BL
   Jang, H
   Capone, R
   Arce, FT
   Ramachandran, S
   Lal, R
   Nussinov, R
AF Kagan, Bruce L.
   Jang, Hyunbum
   Capone, Ricardo
   Arce, Fernando Teran
   Ramachandran, Srinivasan
   Lal, Ratnesh
   Nussinov, Ruth
TI Antimicrobial Properties of Amyloid Peptides
SO MOLECULAR PHARMACEUTICS
LA English
DT Review
DE amyloid ion channels; beta-strand-turn-beta-strand motif; cytotoxicity;
   antimicrobial activity
ID LIPID-BILAYER-MEMBRANES; CATION-SELECTIVE CHANNELS; PRION
   PROTEIN-FRAGMENT; LONG-TERM POTENTIATION; FORMS ION CHANNELS;
   ALZHEIMERS-DISEASE; BETA-PROTEIN; PRECURSOR PROTEIN; CALCIUM-CHANNELS;
   CORTICAL-NEURONS
AB More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-beta structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular. membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape beta-strand-turn-beta-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids not only are toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function.
C1 [Kagan, Bruce L.] Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
   [Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA.
   [Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Mat Sci Program, La Jolla, CA 92093 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
RP Kagan, BL (reprint author), Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
EM bkagan@mednet.ucla.edu; rlal@ucsd.edu
RI Capone, Ricardo/D-1943-2010; Ramachandran, Srinivasan/G-5300-2010
OI Capone, Ricardo/0000-0002-7327-9837; Ramachandran,
   Srinivasan/0000-0002-4912-0279
FU National Institutes of Health (National Institute on Aging) [AG028709];
   National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
   Research
FX This research was supported by the National Institutes of Health
   (National Institute on Aging AG028709 to RL.). 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. This research was supported (in part) by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research. All simulations had been performed using the
   high-performance computational facilities of the Biowulf PC/Linux
   cluster at the National Institutes of Health, Bethesda, MD
   (http://biowulf.nih.gov).
NR 91
TC 41
Z9 41
U1 3
U2 37
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD APR
PY 2012
VL 9
IS 4
BP 708
EP 717
DI 10.1021/mp200419b
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 917OE
UT WOS:000302186700003
PM 22081976
ER

PT J
AU Bahta, M
   Liu, F
   Kim, SE
   Stephen, AG
   Fisher, RJ
   Burke, TR
AF Bahta, Medhanit
   Liu, Fa
   Kim, Sung-Eun
   Stephen, Andrew G.
   Fisher, Robert J.
   Burke, Terrence R., Jr.
TI Oxime-based linker libraries as a general approach for the rapid
   generation and screening of multidentate inhibitors
SO NATURE PROTOCOLS
LA English
DT Article
ID PROTEIN-TYROSINE-PHOSPHATASE; SITU CLICK CHEMISTRY; TSG101 UEV DOMAIN;
   YERSINIA-PESTIS; SUBSTRATE-SPECIFICITY; ENZYME-INHIBITORS; TERMINAL
   ALKYNES; STRUCTURAL BASIS; SALICYLIC-ACID; SOLID-PHASE
AB The described oxime-based library protocol provides detailed procedures for the linkage of aminooxy functionality with aldehyde building blocks that result in the generation of libraries of multidentate inhibitors. Synthesis of inhibitors for protein tyrosine phosphatases (PTPs) and antagonists directed against the human tumor susceptibility gene 101 (TSG101) are shown as examples. Three steps are involved: (i) the design and synthesis of aminooxy platforms; (ii) tethering with aldehydes to form oxime-based linkages with sufficient purity; and (iii) direct in vitro biological evaluation of oxime products without purification. Each coupling reaction is (i) performed in capped microtubes at room temperature (20-23 degrees C); (ii) diluted for inhibitory evaluation; and (iii) screened with targets in microplates to provide IC50 or K-d values. The synthesis of the aminooxy platforms takes 3-5 d; tethering with the aldehydes takes 24 h; and inhibition assay of enzymes and protein-protein interactions takes 30 min and 2 h, respectively.
C1 [Bahta, Medhanit; Liu, Fa; Kim, Sung-Eun; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,US Natl Inst Hlth, Frederick, MD 21701 USA.
   [Stephen, Andrew G.; Fisher, Robert J.] SAIC Frederick Inc, Adv Technol Program, Prot Chem Lab, Frederick, MD USA.
RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,US Natl Inst Hlth, Frederick, MD 21701 USA.
EM tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU US National Institutes of Health, Center for Cancer Research, National
   Cancer Institute-Frederick [HHSN261200800001E]; National Cancer
   Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program and
   under the Contract No. HHSN261200800001E of the US National Institutes
   of Health, Center for Cancer Research, National Cancer
   Institute-Frederick and the National Cancer Institute, National
   Institutes of Health. 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 53
TC 12
Z9 12
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD APR
PY 2012
VL 7
IS 4
BP 686
EP 702
DI 10.1038/nprot.2012.007
PG 17
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 917AU
UT WOS:000302145100006
PM 22422315
ER

PT J
AU Joffe, S
   Miller, FG
AF Joffe, Steven
   Miller, Franklin G.
TI Equipoise: asking the right questions for clinical trial design
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Article
ID BREAST-CANCER; THERAPY; ETHICS; TAMOXIFEN; CHEMOTHERAPY; ONDANSETRON;
   LETROZOLE; WOMEN; RISK
AB Randomized controlled trials (RCTs) are central to evidence-based clinical and health-policy decisions. However, RCTs highlight the tension between the therapeutic obligations of the physician and the scientific obligations of the investigator. Clinical equipoise, defined as honest professional disagreement among expert clinicians about the preferred treatment, is often cited as the solution to this RCT dilemma. Nevertheless, there are numerous practical and conceptual problems with the notion of equipoise. These problems include its mistaken imposition of therapeutic norms on the scientific enterprise of research, the difficulty of knowing when a state of equipoise exists, the susceptibility of expert judgment to bias and weak evidence, and its inability to support evidence necessary for health-policy decisions. An alternate approach to risk-benefit assessment that is congruent with the scientific purpose of RCTs can better guide ethical evaluation of these trials, as discussed in this Perspective.
C1 [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
   [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM steven_joffe@dfci.harvard.edu
OI Joffe, Steven/0000-0002-0667-7384
NR 36
TC 8
Z9 8
U1 0
U2 9
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 APR
PY 2012
VL 9
IS 4
BP 230
EP 235
DI 10.1038/nrclinonc.2011.211
PG 6
WC Oncology
SC Oncology
GA 916VD
UT WOS:000302130400010
PM 22231753
ER

PT J
AU Bromberg, JE
   Augustson, EM
   Backinger, CL
AF Bromberg, Julie E.
   Augustson, Erik M.
   Backinger, Cathy L.
TI Portrayal of Smokeless Tobacco in YouTube Videos
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID SMOKING INITIATION; MOVIE SMOKING; YOUNG-ADULTS; INFORMATION; WEB;
   EXPOSURE; INTERNET
AB Videos of smokeless tobacco (ST) on YouTube are abundant and easily accessible, yet no studies have examined the content of ST videos. This study assesses the overall portrayal, genre, and messages of ST YouTube videos.
   In August 2010, researchers identified the top 20 search results on YouTube by "relevance" and "view count" for the following search terms: "ST," "chewing tobacco," "snus," and "Skoal." After eliminating videos that were not about ST (n = 26), non-English (n = 14), or duplicate (n = 42), a final sample of 78 unique videos was coded for overall portrayal, genre, and various content measures.
   Among the 78 unique videos, 15.4% were anti-ST, while 74.4% were pro-ST. Researchers were unable to determine the portrayal of ST in the remaining 10.3% of videos because they involved excessive or "sensationalized" use of the ST, which could be interpreted either positively or negatively, depending on the viewer. The most common ST genre was positive video diaries (or "vlogs"), which made up almost one third of the videos (29.5%), followed by promotional advertisements (20.5%) and anti-ST public service announcements (12.8%). While YouTube is intended for user-generated content, 23.1% of the videos were created by professional organizations.
   These results demonstrate that ST videos on YouTube are overwhelmingly pro-ST. More research is needed to determine who is viewing these ST YouTube videos and how they may affect people's knowledge, attitudes, and behaviors regarding ST use.
C1 [Bromberg, Julie E.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Backinger, Cathy L.] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA.
RP Bromberg, JE (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4047, Bethesda, MD 20892 USA.
EM brombergje@mail.nih.gov
FU National Cancer Institute
FX This research was funded by the National Cancer Institute [Cancer
   Research Training Award (CRTA) Program].
NR 35
TC 21
Z9 21
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD APR
PY 2012
VL 14
IS 4
BP 455
EP 462
DI 10.1093/ntr/ntr235
PG 8
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 919CM
UT WOS:000302298400010
PM 22080585
ER

PT J
AU Michos, ED
   Reis, JP
   Post, WS
   Lutsey, PL
   Gottesman, RF
   Mosley, TH
   Sharrett, AR
   Melamed, ML
AF Michos, Erin D.
   Reis, Jared P.
   Post, Wendy S.
   Lutsey, Pamela L.
   Gottesman, Rebecca F.
   Mosley, Thomas H.
   Sharrett, A. Richey
   Melamed, Michal L.
TI 2.5-Hydroxyvitamin D deficiency is associated with fatal stroke among
   whites but not blacks: The NHANES-III linked mortality files
SO NUTRITION
LA English
DT Article
DE Vitamin D; Stroke; Racial differences
ID NUTRITION EXAMINATION SURVEY; VITAMIN-D DEFICIENCY; 3RD NATIONAL-HEALTH;
   UNITED-STATES; 25-HYDROXYVITAMIN-D LEVELS; CARDIOVASCULAR-DISEASE; RISK;
   POPULATION; ADULTS
AB Objective: Deficient 25-hydroxyvitamin D (25[OH ID) levels are associated with cardiovascular disease (CVD) events and mortality. 25(OH)D deficiency and stroke are more prevalent in blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared with whites.
   Methods: The Third National Health and Nutrition Examination Survey, a probability sample of U.S. civilians, measured 25(OH)D levels and CVD risk factors from 1988 through 1994. Vital status through December 2006 was obtained by a linkage with the National Death Index. In white and black adults without CVD reported at baseline (n = 7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race.
   Results: During a median of 14.1 y, there were 116 and 60 fatal strokes in whites and blacks, respectively. The risk of fatal stroke was greater in blacks compared with whites in models adjusted for socioeconomic status and CVD risk factors (HR 1.60, 95% confidence interval 1.01-2.53). Mean baseline 25(OH)D levels were significantly lower in blacks compared with whites (19.4 versus 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels lower than 15 ng/mL were associated with fatal stroke in whites (HR 2.13.1.01-4.50) but not blacks (HR 0.93, 0.49-1.80).
   Conclusions: Vitamin D deficiency was associated with an increased risk of stroke death in whites but not in blacks. Although blacks had a higher rate of fatal stroke compared with whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence. Therefore 25(OH)D levels did not explain this excess risk. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Michos, Erin D.; Post, Wendy S.] Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD 21205 USA.
   [Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
   [Lutsey, Pamela L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
   [Gottesman, Rebecca F.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
   [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA.
   [Michos, Erin D.; Post, Wendy S.; Sharrett, A. Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Melamed, Michal L.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
   [Melamed, Michal L.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Michos, ED (reprint author), Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD 21205 USA.
EM edonnell@jhmi.edu
FU NIH/NINDS [R01N5072243-01]; NIH/NIDDK [K23-078774]
FX Dr. Michos is supported by grant R01N5072243-01 from the NIH/NINDS and
   the P. J. Schafer Cardiovascular Research Fund. Dr. Melamed is supported
   by grant K23-078774 from the NIH/NIDDK.
NR 31
TC 46
Z9 46
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0899-9007
J9 NUTRITION
JI Nutrition
PD APR
PY 2012
VL 28
IS 4
BP 367
EP 371
DI 10.1016/j.nut.2011.10.015
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 920HV
UT WOS:000302395800005
PM 22261577
ER

PT J
AU Reddy, UM
   Page, GP
   Saade, GR
AF Reddy, Uma M.
   Page, Grier P.
   Saade, George R.
TI The role of DNA microarrays in the evaluation of fetal death
SO PRENATAL DIAGNOSIS
LA English
DT Article
DE Array CGH; General cytogenetics; Spontaneous abortion; Stillbirth; Fetal
   death; Fetal demise
ID COMPARATIVE GENOMIC HYBRIDIZATION; SPONTANEOUS-ABORTIONS;
   PRENATAL-DIAGNOSIS; GENETIC EVALUATION; STILLBIRTH; PREGNANCY
AB Fetal death occurs in 15% of clinically recognized pregnancies. Cytogenetic abnormalities are present in 50% of spontaneous abortions (fetal deaths?<?20?weeks) whereas the rate is 6% to 13% for stillbirths (fetal deaths?=?20?weeks). Microarray has been demonstrated to increase the diagnosis of genetic abnormalities by providing coverage of the entire genome at a higher density, detecting as small as 50 to 100?kb deletions or duplications, known as copy number changes. Microarray is particularly suited for evaluation of fetal death because DNA can still be analyzed in macerated fetuses and nonviable tissue, two situations where culturing and karyotyping is known to have low yield. Microarray has already proven successful in providing additional genetic information beyond karyotype in spontaneous abortion. The few studies on the use of microarray in stillbirth evaluation have been promising, demonstrating an increase in the diagnosis of clinically relevant genetic abnormalities when compared with karyotype. As the cost and technology improve, microarray may ultimately become the first line screen for genetic abnormalities in stillbirth. The accurate diagnosis of a genetic abnormality as the cause for fetal death may provide closure for families, prevent unnecessary treatments, and enable clinicians to more accurately counsel and manage subsequent pregnancies. (c) 2012 John Wiley & Sons, Ltd.
C1 [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
   [Page, Grier P.] RTI Int, Atlanta, GA USA.
   [Saade, George R.] Univ Texas Med Branch, Galveston, TX USA.
RP Reddy, UM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
EM reddyu@mail.nih.gov
NR 21
TC 10
Z9 12
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0197-3851
J9 PRENATAL DIAG
JI Prenat. Diagn.
PD APR
PY 2012
VL 32
IS 4
SI SI
BP 371
EP 375
DI 10.1002/pd.3825
PG 5
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 917CH
UT WOS:000302149400010
PM 22467168
ER

PT J
AU Thomsen, M
   Lindsley, CW
   Conn, PJ
   Wessell, JE
   Fulton, BS
   Wess, J
   Caine, SB
AF Thomsen, Morgane
   Lindsley, Craig W.
   Conn, P. Jeffrey
   Wessell, Jeffrey E.
   Fulton, Brian S.
   Wess, Jurgen
   Caine, S. Barak
TI Contribution of both M-1 and M-4 receptors to muscarinic
   agonist-mediated attenuation of the cocaine discriminative stimulus in
   mice
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Acetylcholine receptor; Muscarinic; Cocaine; Addiction; Knockout; Drug
   discrimination
ID VENTRAL TEGMENTAL AREA; CHOLINERGIC CELL ABLATION; NUCLEUS-LESIONED
   RATS; ACETYLCHOLINE-RECEPTOR; SUBSTANTIA-NIGRA; BRAIN-STIMULATION; HUMAN
   VOLUNTEERS; DOPAMINE EFFLUX; DEFICIENT MICE; KNOCKOUT MICE
AB We previously showed that muscarinic agonists with M-1 and/or M-4 receptor affinities attenuated cocaine discrimination and self-administration in wild-type mice but not in M-1/M-4 double-knockout mice.
   This study aims to elucidate the respective contributions of M-1 and M-4 receptors to this effect.
   Knockout mice lacking either the M-1 subtype (M (1) (-/-) ) or the M-4 subtype (M (4) (-/-) ) and wild-type mice were trained to discriminate 10 mg/kg cocaine from saline. Muscarinic ligands were tested for modulation of cocaine discrimination: xanomeline (M-1/M-4-preferring agonist), VU0357017 (M-1-selective partial agonist), 77-LH-28-1 (M-1 agonist), and BQCA (M-1-selective positive allosteric modulator).
   Xanomeline produced rightward shifts in the cocaine dose-effect curve in all three genotypes, but most robustly in wild-type mice. VU0357017 produced rightward shifts in the cocaine dose-effect curve in wild-type and M (4) (-/-) mice, but not in M (1) (-/-) mice. Response rates were suppressed by xanomeline in wild-type and M (1) (-/-) but not in M (4) (-/-) mice and were unaltered by VU0357017. 77-LH-28-1 and BQCA also showed evidence of attenuating cocaine's discriminative stimulus, but at doses that suppressed responding or had other undesirable effects. Intriguingly, both VU0357017 and 77-LH-28-1 exhibited U-shaped dose-effect functions in attenuating cocaine discrimination. None of the drugs substituted for the cocaine stimulus.
   Attenuation of the cocaine stimulus by VU0357017 depended upon M-1 receptors, and full effects of xanomeline depended upon both M-1 and M-4 receptors. Therefore M-1-selective agonists and mixed M-1/M-4 agonists may be promising leads for developing medications that block cocaine's effects.
C1 [Thomsen, Morgane; Wessell, Jeffrey E.; Fulton, Brian S.; Caine, S. Barak] Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA USA.
   [Lindsley, Craig W.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol,Mol Lib Probe Prod Ctr Network,MLP, Vanderbilt Program Drug Discovery,Vanderbilt Spec, Nashville, TN 37232 USA.
   [Wess, Jurgen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Thomsen, M (reprint author), Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA USA.
EM mthomsen@mclean.harvard.edu
RI Conn, Peter/D-7848-2012
FU National Institute of Diabetes and Digestive and Kidney Disorders;
   Molecular Libraries Probe Production Centers Network [U54MH084659];
   National Institutes on Drug Abuse [DA027825]
FX This research was supported by the Intramural Research Program of the
   National Institute of Diabetes and Digestive and Kidney Disorders
   (J.W.), by the Molecular Libraries Probe Production Centers Network
   (U54MH084659, P.J.C and C. W. L.), and by a grant from the National
   Institutes on Drug Abuse (DA027825, M. T.). All procedures were carried
   out in accordance with the Guidelines for the Care and Use of Mammals in
   Neuroscience and Behavioral Research (National Research Council 2003)
   and US laws. We thank Joon Y. Boon for technical assistance.
NR 62
TC 10
Z9 10
U1 6
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD APR
PY 2012
VL 220
IS 4
BP 673
EP 685
DI 10.1007/s00213-011-2516-9
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 918NL
UT WOS:000302256700003
PM 21964721
ER

PT J
AU Hildesheim, A
   Wang, CP
AF Hildesheim, Allan
   Wang, Cheng-Ping
TI Genetic predisposition factors and nasopharyngeal carcinoma risk: A
   review of epidemiological association studies, 2000-2011 Rosetta Stone
   for NPC: Genetics, viral infection, and other environmental factors
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Nasopharyngeal carcinoma; Genetics; Epidemiology; Review
ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISM; SOUTHERN
   CHINESE POPULATION; LYMPH-NODE METASTASIS; CLASS-II ALLELES; HLA
   CLASS-I; SUSCEPTIBILITY LOCUS; PROMOTER POLYMORPHISMS; RECEPTOR
   POLYMORPHISMS; CANTONESE POPULATION
AB While infection with Epstein-Barr virus (EBV) is known to be an essential risk factor for the development of nasopharyngeal carcinoma (NPC), other co-factors including genetic factors are thought to play an important role. In this review, we summarize association studies conducted over the past decade to evaluate the role of genetic polymorphisms in NPC development. A review of the literature identified close to 100 studies, including 3 genome-wide association studies (GWAS), since 2000 that evaluated genetic polymorphisms and NPC risk in at least 100 NPC cases and 100 controls. Consistent evidence for associations were reported for a handful of genes, including immune-related HLA Class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2. However, for most of the genes evaluated, there was no effort to replicate findings and studies were largely modest in size, typically consisting of no more than a few hundred cases and controls. The small size of most studies, and the lack of attempts at replication have limited progress in understanding the genetics of NPC. Moving forward, if we are to advance our understanding of genetic factors involved in the development of NPC, and of the impact of gene-gene and gene-environment interations in the development of this disease, consortial efforts that pool across multiple, well-designed and coordinated efforts will most likely be required. Published by Elsevier Ltd.
C1 [Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, DCEG, Rockville, MD 20852 USA.
   [Wang, Cheng-Ping] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan.
   [Wang, Cheng-Ping] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan.
RP Hildesheim, A (reprint author), NCI, Infect & Immunoepidemiol Branch, DCEG, 6120 Execut Blvd,Room 7066, Rockville, MD 20852 USA.
EM hildesha@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015; 
OI Hildesheim, Allan/0000-0003-0257-2363; WANG,
   CHENG-PING/0000-0001-7872-1463
FU Intramural NIH HHS [ZIA CP010211-02]
NR 96
TC 55
Z9 61
U1 2
U2 19
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD APR
PY 2012
VL 22
IS 2
BP 107
EP 116
DI 10.1016/j.semcancer.2012.01.007
PG 10
WC Oncology
SC Oncology
GA 921AJ
UT WOS:000302450100005
PM 22300735
ER

PT J
AU Klion, AD
AF Klion, Amy D.
TI Eosinophilia: Introduction
SO SEMINARS IN HEMATOLOGY
LA English
DT Editorial Material
ID HYPEREOSINOPHILIC SYNDROME; INTERLEUKIN-5
C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM aklion@niaid.nih.gov
OI Klion, Amy/0000-0002-4986-5326
FU Intramural NIH HHS [Z99 AI999999]
NR 8
TC 0
Z9 0
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 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD APR
PY 2012
VL 49
IS 2
BP 111
EP 112
DI 10.1053/j.seminhematol.2012.01.004
PG 2
WC Hematology
SC Hematology
GA 920SI
UT WOS:000302427300001
PM 22449620
ER

PT J
AU Mejia, R
   Nutman, TB
AF Mejia, Rojelio
   Nutman, Thomas B.
TI Evaluation and Differential Diagnosis of Marked, Persistent Eosinophilia
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID OF-THE-LITERATURE; HYPEREOSINOPHILIC-SYNDROMES; SYSTEMIC MASTOCYTOSIS;
   PUSTULAR FOLLICULITIS; EPISODIC ANGIOEDEMA; DISEASE; PNEUMONIA; IGE;
   MANIFESTATIONS; DERMATITIS
AB High-grade eosinophilia can be a diagnostic dilemma, as the etiologies are extensive and varied. Hypereosinophilic syndromes (HES) are a group of heterogeneous disorders, many of which remain poorly defined. By definition, HES must be distinguished from other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, non-infectious causes must be considered, and include drug reactions, malignancies, and immunologic, inflammatory and allergic diseases. Semin Hematol 49:149-159. Published by Elsevier Inc.
C1 [Mejia, Rojelio; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
FU Division of Intramural Research (DIR) of the National Institute of
   Allergy and Infectious Diseases
FX This study was supported in part by the Division of Intramural Research
   (DIR) of the National Institute of Allergy and Infectious Diseases.
NR 79
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U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
EI 1532-8686
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD APR
PY 2012
VL 49
IS 2
BP 149
EP 159
DI 10.1053/j.seminhematol.2012.01.006
PG 11
WC Hematology
SC Hematology
GA 920SI
UT WOS:000302427300006
PM 22449625
ER

PT J
AU Simon, HU
   Klion, A
AF Simon, Hans-Uwe
   Klion, Amy
TI Therapeutic Approaches to Patients With Hypereosinophilic Syndromes
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID CHURG-STRAUSS-SYNDROME; CHRONIC EOSINOPHILIC LEUKEMIA; DOSE IMATINIB
   MESYLATE; MYELOPROLIFERATIVE VARIANT; FIP1L1-PDGFRA FUSION; POTENTIAL
   MECHANISM; MOLECULAR REMISSION; EPISODIC ANGIOEDEMA; INTERFERON-ALPHA;
   POOR-PROGNOSIS
AB Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders that range from asymptomatic eosinophilia >1,500/mL to aggressive disease complicated by life-threatening end organ involvement, including endomyocardial fibrosis and thromboembolism. To complicate matters further, similar clinical manifestations can occur in the setting of marked eosinophilia due to helminth infection, drug hypersensitivity, and other causes. In the past, therapy was guided only by the exclusion of these secondary causes of eosinophilia and the severity of the clinical manifestations. More recently, the availability of novel targeted therapies and a better understanding of the etiologies of some subtypes of HES have necessitated a more structured approach. Semin Hematol 49:160-170. Published by Elsevier Inc.
C1 [Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland.
   [Klion, Amy] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Klion, A (reprint author), Bldg 4,Room B1-28,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM AKLION@niaid.nih.gov
OI Simon, Hans-Uwe/0000-0002-9404-7736; Klion, Amy/0000-0002-4986-5326
FU NIAID/NIH; Swiss National Science Foundation
FX This work was supported by the Intramural Program of the NIAID/NIH
   (A.K.) and the Swiss National Science Foundation (H-.U.S.).
NR 58
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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 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD APR
PY 2012
VL 49
IS 2
BP 160
EP 170
DI 10.1053/j.seminhematol.2012.01.002
PG 11
WC Hematology
SC Hematology
GA 920SI
UT WOS:000302427300007
PM 22449626
ER

PT J
AU Boulanger, CA
   Bruno, RD
   Rosu-Myles, M
   Smith, GH
AF Boulanger, Corinne A.
   Bruno, Robert D.
   Rosu-Myles, Michael
   Smith, Gilbert H.
TI The Mouse Mammary Microenvironment Redirects Mesoderm-Derived Bone
   Marrow Cells to a Mammary Epithelial Progenitor Cell Fate
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; IN-VIVO; GLAND; MORPHOGENESIS; EXPRESSION;
   MICE; DIFFERENTIATION; PROLIFERATION; MULTIPOTENT; PHENOTYPE
AB Mammary stem cells reside in protected tissue locales (niches), where their reproductive potency remains essentially unchanged through life. Disruption of the tissue leads to a reduced capacity of dispersed epithelial cells to recapitulate complete functional mammary structures. Previous studies demonstrate that during the reformation of mammary stem cell niches by dispersed epithelial cells in the mammary stroma, nonmammary cells of ectodermal germ origin may be sequestered and reprogrammed to perform mammary epithelial cell (MEC) functions, including those ascribed to mammary stem/progenitor cells. To test whether tissue cells from organs derived from different germ layers could respond to mammary epithelial-specific signals, we utilized fluorescence-activated cell sorting-purified Lin(-) and Lin(-)/cKit+ adult male bone marrow cells to mix with MECs. Our evidence shows that the signals provided by the mammary microenvironment are capable of redirecting mesoderm-derived adult progenitor cells to produce functional MEC progeny.
C1 [Boulanger, Corinne A.; Bruno, Robert D.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
   [Rosu-Myles, Michael] Biol & Genet Therapies Directorate, Ottawa, ON, Canada.
RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
EM gs4d@nih.gov
OI Bruno, Robert/0000-0003-3329-9478
NR 25
TC 10
Z9 10
U1 0
U2 1
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 APR
PY 2012
VL 21
IS 6
BP 948
EP 954
DI 10.1089/scd.2011.0148
PG 7
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
   Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
   Transplantation
GA 918BB
UT WOS:000302222700012
PM 21649558
ER

PT J
AU Korthuis, PT
   Feaster, DJ
   Gomez, ZL
   Das, M
   Tross, S
   Wiest, K
   Douaihy, A
   Mandler, RN
   Sorensen, JL
   Colfax, G
   McCarty, D
   Cohen, SE
   Penn, PE
   Lape, D
   Metsch, LR
AF Korthuis, P. Todd
   Feaster, Daniel J.
   Gomez, Zoilyn L.
   Das, Moupali
   Tross, Susan
   Wiest, Katharina
   Douaihy, Antoine
   Mandler, Raul N.
   Sorensen, James L.
   Colfax, Grant
   McCarty, Dennis
   Cohen, Stephanie E.
   Penn, Patricia E.
   Lape, Diane
   Metsch, Lisa R.
TI Injection behaviors among injection drug users in treatment: The role of
   hepatitis C awareness
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Injection drug use; Hepatitis C; Syringe/needle sharing; Alcoholism;
   Opioid-related disorders
ID 5 US CITIES; RISK BEHAVIORS; UNITED-STATES; VIRUS-INFECTION; PEER
   INFLUENCES; HIV RISK; INTERVENTIONS; KNOWLEDGE; BLEACH; LEVEL
AB Background: Injection drug use (IDU) is a primary vector for blood-borne infections. Awareness of Hepatitis C virus (HCV) infection status may affect risky injection behaviors. This study determines the prevalence of risky injection practices and examines associations between awareness of positive HCV status and risky injection behaviors.
   Methods: We surveyed individuals seeking treatment for substance use at 12 community treatment programs as part of a national HIV screening trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants reported socio-demographic characteristics, substance use, risk behaviors, and HCV status. We used multivariable logistic regression to test associations between participant characteristics and syringe/needle sharing.
   Results: The 1281 participants included 244 (19.0%) individuals who reported injecting drugs in the past 6 months and 37.7% of IDUs reported being HCV positive. During the six months preceding baseline assessment, the majority of IDUs reported obtaining sterile syringes from pharmacies (51.6%) or syringe exchange programs (25.0%), but fewer than half of IDUs always used a sterile syringe (46.9%). More than one-third (38.5%) shared syringe/needles with another injector in the past 6 months. Awareness of positive HCV vs. negative/unknown status was associated with increased recent syringe/needle sharing (aOR 2.37, 95% Cl 1.15, 4.88) in multivariable analysis.
   Conclusions: Risky injection behaviors remain prevalent and awareness of HCV infection was associated with increased risky injection behaviors. New approaches are needed to broadly implement HCV prevention interventions for IDUs seeking addiction treatment. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Korthuis, P. Todd; McCarty, Dennis; Lape, Diane] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA.
   [Korthuis, P. Todd; McCarty, Dennis; Lape, Diane] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
   [Feaster, Daniel J.; Gomez, Zoilyn L.; Metsch, Lisa R.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
   [Das, Moupali; Sorensen, James L.] Univ Calif San Francisco, San Francisco, CA 94110 USA.
   [Das, Moupali; Colfax, Grant; Cohen, Stephanie E.] San Francisco Dept Publ Hlth, San Francisco, CA 94103 USA.
   [Tross, Susan] NYS Psychiat Inst, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA.
   [Wiest, Katharina] CODA, Portland, OR 97214 USA.
   [Douaihy, Antoine] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA.
   [Mandler, Raul N.] NIDA, NIH, Bethesda, MD 20892 USA.
   [Penn, Patricia E.] La Frontera Arizona, Tucson, AZ 85713 USA.
RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA.
EM korthuis@ohsu.edu
RI Ghartouchent, malek/B-9088-2012; Feaster, Daniel/I-6079-2013; 
OI Feaster, Daniel/0000-0002-6172-7460
FU National Institute on Drug Abuse : California-Arizona Node [U10
   DA15815]; National Institute on Drug Abuse : Florida Node Alliance [U10
   DA13720]; National Institute on Drug Abuse : Mid-Atlantic Node [U10
   DA13034]; National Institute on Drug Abuse : New England Node [U10
   DA13038]; National Institute on Drug Abuse : New York Node [U10
   DA13046]; National Institute on Drug Abuse : Ohio Valley Node [U10
   DA13732]; National Institute on Drug Abuse : Oregon/Hawaii Node [U10
   DA13036]; National Institute on Drug Abuse : Appalachian Tri-State Node
   [U10 DA020036]; National Institute on Drug Abuse : Southern Consortium
   Node [U10 DA13727]; National Institute on Drug Abuse : Southwest Node
   [U10 DA15833]; National Institute on Drug Abuse [K23 DA019809]
FX Cooperative agreements from the National Institute on Drug Abuse
   supported the design, distribution, collection and analysis of the
   clinical trial: California-Arizona Node (U10 DA15815), Florida Node
   Alliance (U10 DA13720), Mid-Atlantic Node (U10 DA13034), New England
   Node (U10 DA13038), New York Node (U10 DA13046), Ohio Valley Node (U10
   DA13732), Oregon/Hawaii Node (U10 DA13036), Appalachian Tri-State Node
   (U10 DA020036). Southern Consortium Node (U10 DA13727), and Southwest
   Node (U10 DA15833). Dr. Korthuis' time was supported through a grant
   from the National Institute on Drug Abuse (K23 DA019809). The contents
   of the publication are solely the responsibility of the authors and do
   not necessarily represent the views of the funding agencies or the U.S.
   government.
NR 25
TC 10
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U1 3
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD APR
PY 2012
VL 37
IS 4
BP 552
EP 555
DI 10.1016/j.addbeh.2011.12.001
PG 4
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 911BD
UT WOS:000301691400033
PM 22209655
ER

PT J
AU Chen, CH
   Walker, J
   Momenan, R
   Rawlings, R
   Heilig, M
   Hommer, DW
AF Chen, Chun-Hsin
   Walker, Jonathan
   Momenan, Reza
   Rawlings, Robert
   Heilig, Markus
   Hommer, Daniel W.
TI Relationship Between Liver Function and Brain Shrinkage in Patients with
   Alcohol Dependence
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Dependence; MRI; Liver Function; Brain Shrinkage
ID GAMMA-GLUTAMYL-TRANSPEPTIDASE; OXIDATIVE STRESS STATUS;
   LIPID-PEROXIDATION; CELL-DEATH; DISEASE; CONSUMPTION; WOMEN; GRAY;
   VOLUMES; ENZYME
AB Background: Oxidative stress has been proposed as one of the mechanisms of alcohol-induced brain shrinkage and alcohol-induced hepatotoxicity. The aim of this study was to assess the correlations between liver function and brain volume (BV) measurements in patients with alcohol dependence.
   Methods: We recruited 124 patients with alcohol dependence and 111 healthy control subjects from National Institute of Health, National Institute on Alcohol Abuse and Alcoholism inpatient alcohol treatment program. Gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as hematocrit (Hct) and albumin were assayed shortly after admission. Magnetic resonance imaging examination was conducted in both groups (after 3-week abstinence in the patient group). We used stepwise linear regression analyses to determine the variables most strongly correlated with brain shrinkage.
   Results: Patients with alcohol dependence had lower BV, and greater brain shrinkage as measured by gray matter ratio (GMR), white matter ratio (WMR), brain ratio (BR), and higher cerebrospinal fluid ratio ratio (CSFR) compared with their healthy counterparts. Age and sex were significantly correlated with some BV measurements in both patient and control groups. Body mass index (BMI) was significantly correlated with CSFR, BR, GMR, and WMR; Hct with CSFR and BR; serum GGT level with BV, CSFR, BR, GMR, and WMF in the patient group. No biological variables were correlated with BV indices in the control group. In gender-stratified analysis, age was significantly correlated with brain shrinkage in male patients but not in female patients. Serum GGT level in male and female patients, Hct in male patients, and AST levels in female patients were significantly correlated with brain shrinkage.
   Conclusions: Our results showed that the higher levels of liver function indices, especially GGT, correlated with BV shrinkage as measured using CSFR, BR, GMR, and WMR in patients with alcohol dependence but not in controls. Serum GGT level outweighed aging effect on brain shrinkage in female patients.
C1 [Chen, Chun-Hsin; Walker, Jonathan; Momenan, Reza; Rawlings, Robert; Heilig, Markus; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
   [Chen, Chun-Hsin] Taipei Med Univ, Wan Fang Hosp, Dept Psychiat, Taipei, Taiwan.
   [Chen, Chun-Hsin] Taipei Med Univ, Sch Med, Dept Psychiat, Taipei, Taiwan.
RP Hommer, DW (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,Bldg 10 CRC Hatfield Clin Res Ctr,Room, Bethesda, MD 20892 USA.
EM danh@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482
FU Laboratory of Clinical and Translational Studies; National Institute on
   Alcohol Abuse and Alcoholism
FX The study was funded by the Laboratory of Clinical and Translational
   Studies, National Institute on Alcohol Abuse and Alcoholism. The authors
   thank Michael Kerich for computer system management and programming, and
   the nursing and social work staff of the Alcohol Treatment Unit of NIH
   Clinical Center. Finally, we thank all participants in this study.
NR 51
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Z9 6
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD APR
PY 2012
VL 36
IS 4
BP 625
EP 632
DI 10.1111/j.1530-0277.2011.01662.x
PG 8
WC Substance Abuse
SC Substance Abuse
GA 916AN
UT WOS:000302068900010
PM 21995416
ER

PT J
AU Chou, SP
   Lee, HK
   Cho, MJ
   Park, JI
   Dawson, DA
   Grant, BF
AF Chou, S. Patricia
   Lee, Hae K.
   Cho, Maeng J.
   Park, Jong-Ik
   Dawson, Deborah A.
   Grant, Bridget F.
TI Alcohol Use Disorders, Nicotine Dependence, and Co-Occurring Mood and
   Anxiety Disorders in the United States and South KoreauA Cross-National
   Comparison
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Use Disorders; Nicotine Dependence; Comorbidity; Mood and
   Anxiety Disorders; Multivariate Logistic Regression
ID SUBSTANCE USE DISORDERS; MENTAL-DISORDERS; AUDADIS-ADR; DRUG MODULES;
   DEPRESSION; COMORBIDITY; RELIABILITY; HEALTH; CONCORDANCE; DIAGNOSES
AB Background: The strong comorbidity between substance use disorders (SUDs) and mood and anxiety disorders has been well documented. In view of lack of research findings addressing the co-occurrence of SUDs and mood and anxiety disorders, this study examined the pattern of comorbidity of alcohol use disorders (AUDs) and nicotine dependence (ND) between 2 culturally diverse countries, the United States and South Korea.
   Methods: Using the nationally representative samples of the U. S. and Korean general populations, we directly compared rates and comorbidity patterns of AUDs, ND, and mood and anxiety disorders between the 2 countries. We further examined the rates and the comorbidity pattern among individuals with AUDs who sought treatment in the last 12 months. Twelve-month prevalence rates were derived to estimate country differentials, and odds ratios (ORs) and 95% confidence intervals were estimated to measure the strength of comorbid associations while adjusting for all sociodemographic characteristics in multivariate logistic models specific to each country.
   Results: The 12-month prevalence rates of AUDs, ND, and any mood disorder and any anxiety disorder were 9.7, 14.4, 9.5, and 11.9% among Americans, whereas the corresponding rates were 7.1, 6.6, 2.0, and 5.2% among Koreans. These rates were significantly greater (except for any AUD) among Americans than among their Korean counterparts. With respect to comorbidity, both countries showed comparable patterns that the prevalence rates of mood and anxiety disorders were consistently the highest among persons with alcohol dependence (AD). Also, a disparate pattern was observed in Korea that the prevalence rates of mood and anxiety disorders were generally lower among individuals with ND than among those with alcohol abuse and AD. Furthermore, despite significantly greater prevalence of AD in Korea (5.1%) than in the United States (4.4%), alcohol-dependent Americans were 4 times (OR = 3.93) more likely to seek treatment compared to their Korean counterparts.
   Conclusions: Our results indicated that the prevalence of AD in Korea was substantially greater than that in both Western and other Asian countries, suggesting a maladaptive pattern of alcohol use in Korea, which is different from the general use pattern of other East Asian countries. The low rate of treatment utilization among Koreans might be attributable to perceived social stigma toward SUDs or mental health problems despite the fact that the Korean government offers national health insurance.
C1 [Lee, Hae K.] Catholic Univ Korea, Dept Psychiat, Uijongbu St Marys Hosp, Seoul, South Korea.
   [Chou, S. Patricia; Dawson, Deborah A.; Grant, Bridget F.] NIAAA, US Natl Inst Hlth, Bethesda, MD USA.
   [Cho, Maeng J.] Seoul Natl Univ, Coll Med, Dept Psychiat & Behav Sci, Inst Behav Med, Seoul, South Korea.
   [Park, Jong-Ik] Kangwon Natl Univ, Coll Med, Dept Psychiat, Chunchon, South Korea.
RP Lee, HK (reprint author), Catholic Univ Korea, Dept Psychiat, Uijongbu St Marys Hosp, Seoul, South Korea.
EM nplhk@catholic.ac.kr
RI Cho, Maeng Je/F-8837-2012
NR 41
TC 14
Z9 15
U1 3
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD APR
PY 2012
VL 36
IS 4
BP 654
EP 662
DI 10.1111/j.1530-0277.2011.01639.x
PG 9
WC Substance Abuse
SC Substance Abuse
GA 916AN
UT WOS:000302068900013
PM 21919925
ER

PT J
AU McKinnon, RA
   Reedy, J
   Berrigan, D
   Krebs-Smith, SM
AF McKinnon, Robin A.
   Reedy, Jill
   Berrigan, David
   Krebs-Smith, Susan M.
CA NCCOR Catalogue & Registry Working
TI The National Collaborative on Childhood Obesity Research Catalogue of
   Surveillance Systems and Measures Registry New Tools to Spur Innovation
   and Increase Productivity in Childhood Obesity Research
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
C1 [McKinnon, Robin A.; Reedy, Jill; Berrigan, David; Krebs-Smith, Susan M.; NCCOR Catalogue & Registry Working] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP McKinnon, RA (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4028,MSC 7344, Bethesda, MD 20892 USA.
EM mckinnonr@mail.nih.gov
NR 0
TC 4
Z9 4
U1 0
U2 4
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 APR
PY 2012
VL 42
IS 4
BP 433
EP 435
DI 10.1016/j.amepre.2012.01.004
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 912LQ
UT WOS:000301799900016
PM 22424259
ER

PT J
AU Doubeni, CA
   Schootman, M
   Major, JM
   Stone, RAT
   Laiyemo, AO
   Park, Y
   Lian, M
   Messer, L
   Graubard, BI
   Sinha, R
   Hollenbeck, AR
   Schatzkin, A
AF Doubeni, Chyke A.
   Schootman, Mario
   Major, Jacqueline M.
   Stone, Rosalie A. Torres
   Laiyemo, Adeyinka O.
   Park, Yikyung
   Lian, Min
   Messer, Lynne
   Graubard, Barry I.
   Sinha, Rashmi
   Hollenbeck, Albert R.
   Schatzkin, Arthur
TI Health Status, Neighborhood Socioeconomic Context, and Premature
   Mortality in the United States: The National Institutes of Health-AARP
   Diet and Health Study
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID SELF-RATED HEALTH; ACUTE MYOCARDIAL-INFARCTION; RETIRED-PERSONS DIET;
   SOCIAL INEQUALITIES; LIFE EXPECTANCY; AMERICAN-ASSOCIATION; FOLLOW-UP;
   US; POPULATION; COHORT
AB Objectives. We examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to the health status of individuals.
   Methods. Community-dwelling adults (n=566402; age=50-71 years) in 6 US states and 2 metropolitan areas participated in the ongoing prospective National Institutes of Health-AARP Diet and Health Study, which began in 1995. We used baseline data for 565679 participants on health behaviors, self-rated health status, and medical history, collected by mailed questionnaires. Participants were linked to 2000 census data for an index of census tract socioeconomic deprivation. The main outcome was all-cause mortality ascertained through 2006.
   Results. In adjusted survival analyses of persons in good-to-excellent health at baseline, risk of mortality increased with increasing levels of census tract socioeconomic deprivation. Neighborhood socioeconomic mortality disparities among persons in fair-to-poor health were not statistically significant after adjustment for demographic characteristics, educational achievement, lifestyle, and medical conditions.
   Conclusions. Neighborhood socioeconomic inequalities lead to large disparities in risk of premature mortality among healthy US adults but not among those in poor health. (Am J Public Health. 2012;102:680-688. doi:10.2105/AJPH.2011.300158)
C1 [Doubeni, Chyke A.] Univ Massachusetts, Dept Family Med & Community Hlth, Sch Med, Worcester, MA 01655 USA.
   [Stone, Rosalie A. Torres] Univ Massachusetts, Dept Psychiat, Sch Med, Worcester, MA 01655 USA.
   [Schootman, Mario; Lian, Min] Washington Univ, Sch Med, Dept Med, Div Hlth Behav Res, St Louis, MO 63110 USA.
   [Major, Jacqueline M.; Park, Yikyung; Graubard, Barry I.; Sinha, Rashmi; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Laiyemo, Adeyinka O.] Howard Univ, Dept Med, Washington, DC 20059 USA.
   [Messer, Lynne] Duke Univ, Ctr Hlth Policy, Durham, NC USA.
   [Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Doubeni, CA (reprint author), Univ Massachusetts, Dept Family Med & Community Hlth, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA.
EM chyke.doubeni@umassmed.edu
RI Sinha, Rashmi/G-7446-2015; 
OI Sinha, Rashmi/0000-0002-2466-7462; Schootman, Mario/0000-0003-1162-8824;
   Doubeni, Chyke/0000-0001-7495-0285; Park, Yikyung/0000-0002-6281-489X
FU NIH; National Cancer Institute [5K01CA127118-04, 1R01CA151736-01,
   5R01CA137750-02]
FX This research was supported in part by the Intramural Research Program
   of the NIH and the National Cancer Institute. C. A. Doubeni was
   supported by grants from the National Cancer Institute (5K01CA127118-04
   and 1R01CA151736-01). M. Schootman and H. Lian were supported in part by
   a grant from the National Cancer Institute (5R01CA137750-02).
NR 45
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U1 2
U2 11
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD APR
PY 2012
VL 102
IS 4
BP 680
EP 688
DI 10.2105/AJPH.2011.300158
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 913IF
UT WOS:000301870000020
PM 21852636
ER

PT J
AU Zafrani, L
   Gerotziafas, G
   Byrnes, C
   Hu, XZ
   Perez, J
   Levi, C
   Placier, S
   Letavernier, E
   Leelahavanichkul, A
   Haymann, JP
   Elalamy, I
   Miller, JL
   Star, RA
   Yuen, PST
   Baud, L
AF Zafrani, Lara
   Gerotziafas, Grigoris
   Byrnes, Colleen
   Hu, Xuzhen
   Perez, Joelle
   Levi, Charlene
   Placier, Sandrine
   Letavernier, Emmanuel
   Leelahavanichkul, Asada
   Haymann, Jean-Philippe
   Elalamy, Ismail
   Miller, Jeffrey L.
   Star, Robert A.
   Yuen, Peter S. T.
   Baud, Laurent
TI Calpastatin Controls Polymicrobial Sepsis by Limiting Procoagulant
   Microparticle Release
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE sepsis/multiple organ failure; calpain; calpastatin; microparticles;
   disseminated intravascular coagulation
ID ACUTE KIDNEY INJURY; SEPTIC SHOCK; CIRCULATING MICROPARTICLES; KAPPA-B;
   MYOCARDIAL DYSFUNCTION; CALPAIN ACTIVATION; INFLAMMATION; MICE;
   INHIBITION; EXPRESSION
AB Rationale: Sepsis, a leading cause of death worldwide, involves widespread activation of inflammation, massive activation of coagulation, and lymphocyte apoptosis. Calpains, calcium-activated cysteine proteases, have been shown to increase inflammatory reactions and lymphocyte apoptosis. Moreover, calpain plays an essential role in microparticle release.
   Objectives: We investigated the contribution of calpain in eliciting tissue damage during sepsis.
   Methods: To test our hypothesis, we induced polymicrobial sepsis by cecal ligation and puncture in wild-type (WT) mice and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor.
   Measurements and Main Results: In WT mice, calpain activity increased transiently peaking at 6 hours after cecal ligation and puncture surgery. Calpastatin overexpression improved survival, organ dysfunction (including lung, kidney, and liver damage), and lymphocyte apoptosis. It decreased the sepsis-induced systemic proinflammatory response and disseminated intravascular coagulation, by reducing the number of procoagulant circulating microparticles and therefore delaying thrombin generation. The deleterious effect of microparticles in this model was confirmed by transferring microparticles from septic WT to septic transgenic mice, worsening their survival and coagulopathy.
   Conclusions: These results demonstrate an important role of the calpain/calpastatin system in coagulation/inflammation pathways during sepsis, because calpain inhibition is associated with less severe disseminated intravascular coagulation and better overall outcomes in sepsis.
C1 [Zafrani, Lara; Perez, Joelle; Levi, Charlene; Placier, Sandrine; Letavernier, Emmanuel; Haymann, Jean-Philippe; Baud, Laurent] Univ Paris 06, UMR S 702, Paris, France.
   [Zafrani, Lara; Hu, Xuzhen; Leelahavanichkul, Asada; Star, Robert A.; Yuen, Peter S. T.] NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA.
   [Byrnes, Colleen; Miller, Jeffrey L.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
   [Gerotziafas, Grigoris; Elalamy, Ismail] Tenon Hosp, AP HP, Serv Hematol Biol, Paris, France.
RP Zafrani, L (reprint author), Unite INSERM U702, 4 Rue Chine, F-75020 Paris, France.
EM larazafrani@hotmail.com
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
FU Institut National de la Sante et de la Recherche Medicale; National
   Institutes of Health, National Institute of Diabetes and Digestive and
   Kidney Diseases
FX Supported by the Institut National de la Sante et de la Recherche
   Medicale and by the Intramural Research Program at National Institutes
   of Health, National Institute of Diabetes and Digestive and Kidney
   Diseases.
NR 48
TC 18
Z9 19
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD APR 1
PY 2012
VL 185
IS 7
BP 744
EP 755
DI 10.1164/rccm.201109-1686OC
PG 12
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 915QY
UT WOS:000302043700013
PM 22268136
ER

PT J
AU Liu, J
   Cai, WD
   Liu, WS
   Han, BQ
   Chang, J
   Yang, Y
AF Liu, Ji
   Cai, Wendi
   Liu, Wanshun
   Han, Baoqin
   Chang, Jing
   Yang, Yan
TI Modulation of Liver L-gamma-Glutamyl-L-cysteinylglycine Homeostasis By
   N-Acetyl-Glucosamine-thiazolidine-4(R)-carboxylic Acid in Mice
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE GlcNAcCys; GCLc; GSH; BSO
ID OXIDATIVE STRESS; GLUTATHIONE SYNTHESIS; N-ACETYLCYSTEINE; CELL INJURY;
   L-CYSTEINE; SYNTHETASE; PROTECTION; INDUCTION; PROTEIN; TRANSCRIPTION
AB The properties of modulating liver L-gamma-glutamyl-L-cysteinylglycine (GSH) homeostasis by thiazolidine derivative N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid (GlcNAcCys) and the underlying mechanisms were investigated in L-buthionine-[S,R]-sulfoximine (BSO)-induced mice liver GSH depletion model. The data show that BSO (6 mmol/kg body weight; intraperitoneally) significantly decreased liver total sulfhydryl and GSH concentrations when compared with control. When mice were treated with different doses of GlcNAcCys (200, 400, 900 mg/kg body weight; intraperitoneally, respectively), total sulfhydryl and GSH concentrations were significantly increased when measured 6 hours after treatment. The activities of GSH-associated enzymes were also measured. Liver glutathione S-transferase (GST) activities were significantly decreased by BSO compared with the control, and GlcNAcCys significantly increased GST activity. Moreover, reverse-transcriptase polymerase chain reaction data indicated that GlcNAcCys could significantly induce glutamylcysteine ligase catalytic subunit c mRNA transcription. The mRNA levels of transcription factors c-jun and c-fos were increased by BSO administration but were decreased back to normal after the administration of GlcNAcCys. In a conclusion, GlcNAcCys can modulate liver GSH homeostasis, which may be related to its ability to induce glutamylcysteine ligase catalytic subunit transcription. GlcNAcCys has potential hepatoprotective properties by increasing GSH content, increasing GST activity.
C1 [Liu, Ji; Liu, Wanshun; Han, Baoqin; Chang, Jing; Yang, Yan] Ocean Univ China, Coll Marine Life Sci, Qingdao 266003, Peoples R China.
   [Yang, Yan] NCI, Lab Mol Inflammat, Ctr Canc Res, Frederick, MD 21701 USA.
   [Cai, Wendi] Weifang Med Coll, Dept Biochem, Weifang, Peoples R China.
RP Yang, Y (reprint author), Ocean Univ China, Coll Marine Life Sci, Yushan Rd 5, Qingdao 266003, Peoples R China.
EM yany@ouc.edu.cn
FU Natural Science Foundation of Shandong Province [2007BS07001, Y2008D17]
FX This study was supported by Natural Science Foundation of Shandong
   Province graft 2007BS07001 and Y2008D17.
NR 34
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD APR
PY 2012
VL 343
IS 4
BP 310
EP 315
DI 10.1097/MAJ.0b013e31822b02f4
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 917FR
UT WOS:000302158400009
PM 21825963
ER

PT J
AU Lohse, B
   Bailey, RL
   Krall, JS
   Wall, DE
   Mitchell, DC
AF Lohse, Barbara
   Bailey, Regan L.
   Krall, Jodi Stotts
   Wall, Denise E.
   Mitchell, Diane C.
TI Diet quality is related to eating competence in cross-sectional sample
   of low-income females surveyed in Pennsylvania
SO APPETITE
LA English
DT Article
DE Eating competence; Dietary quality; Low-income; Eating behavior; Dietary
   guidance
ID CARDIOVASCULAR-DISEASE RISK; PATTERNS; CANCER; WOMEN; ASSOCIATION;
   ADULTS; BIOMARKERS; OBESITY; PROFILE; ENERGY
AB Women participants of two federally administered nutrition education programs (n = 149, 56% white, 64% food secure, 86% 18-50 years of age,) completed telephone interviews that included three 24-hour dietary recalls and the Satter Eating Competence Inventory. Eating competence is delineated by an Inventory score >= 32. Competent eaters had significantly greater intakes of fiber, vitamin A, vitamin E, vitamin C, most B-vitamins, magnesium, iron, zinc, potassium and a higher Healthy Eating Index. Two dietary patterns defined as Prudent and Western were observed. The Prudent pattern was correlated with eating competence and characterized by more healthful foods such as fruits, vegetables and low-fat dairy products. The Western pattern, characterized by foods higher in fat, salt, and sugar, was not related to eating competence. Findings suggest that dietary guidance using an eating competence approach for low-income women is compatible with goals to improve dietary quality and eating patterns. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Lohse, Barbara; Mitchell, Diane C.] Penn State Univ, Dept Nutr Sci, Diet Assessment Ctr, University Pk, PA 16802 USA.
   [Bailey, Regan L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
   [Krall, Jodi Stotts] Univ Pittsburgh, Med Ctr, Weight Management Div, Pittsburgh, PA 15213 USA.
   [Wall, Denise E.] Penn State Univ, Penn Nutr Educ TRACKS, State Coll, PA 16801 USA.
RP Lohse, B (reprint author), Penn State Univ, Dept Nutr Sci, Diet Assessment Ctr, University Pk, PA 16802 USA.
EM lohseb@psu.edu
FU Pennsylvania Department of Public Welfare through the Pennsylvania
   Nutrition Education TRACKS, USDA
FX Research was supported by the Pennsylvania Department of Public Welfare
   through the Pennsylvania Nutrition Education TRACKS as part of USDA's
   Supplemental Nutrition Assistance Program. We sincerely thank
   Cooperative Extension Nutrition Links and The Diet Assessment Center,
   both of The Pennsylvania State University. Competing interest: The
   authors declare that they have no competing interest.
NR 51
TC 17
Z9 17
U1 1
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
J9 APPETITE
JI Appetite
PD APR
PY 2012
VL 58
IS 2
BP 645
EP 650
DI 10.1016/j.appet.2011.11.022
PG 6
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA 913SX
UT WOS:000301898800034
PM 22142509
ER

PT J
AU Kessler, RC
   Avenevoli, S
   Costello, EJ
   Georgiades, K
   Green, JG
   Gruber, MJ
   He, JP
   Koretz, D
   McLaughlin, KA
   Petukhova, M
   Sampson, NA
   Zaslavsky, AM
   Merikangas, KR
AF Kessler, Ronald C.
   Avenevoli, Shelli
   Costello, E. Jane
   Georgiades, Katholiki
   Green, Jennifer Greif
   Gruber, Michael J.
   He, Jian-ping
   Koretz, Doreen
   McLaughlin, Katie A.
   Petukhova, Maria
   Sampson, Nancy A.
   Zaslavsky, Alan M.
   Merikangas, Kathleen Ries
TI Prevalence, Persistence, and Sociodemographic Correlates of DSM-IV
   Disorders in the National Comorbidity Survey Replication Adolescent
   Supplement
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID GREAT SMOKY MOUNTAINS; NCS-A; LIFETIME PREVALENCE; MENTAL-DISORDERS;
   PSYCHIATRIC-DISORDERS; DEPRESSION; CHILDREN; PSYCHOPATHOLOGY;
   EPIDEMIOLOGY; 10-YEAR
AB Context: Community epidemiological data on the prevalence and correlates of adolescent mental disorders are needed for policy planning purposes. Only limited data of this sort are available.
   Objective: To present estimates of 12-month and 30-day prevalence, persistence (12-month prevalence among lifetime cases and 30-day prevalence among 12-month cases), and sociodemographic correlates of commonly occurring DSM-IV disorders among adolescents in the National Comorbidity Survey Replication Adolescent Supplement.
   Design: The National Comorbidity Survey Replication Adolescent Supplement is a US national survey of DSM-IV anxiety, mood, behavior, and substance disorders among US adolescents based on face-to-face interviews in the homes of respondents with supplemental parent questionnaires.
   Setting: Dual-frame household and school samples of US adolescents.
   Participants: A total of 10 148 adolescents aged 13 to 17 years (interviews) and 1 parent of each adolescent (questionnaires).
   Main Outcome Measures: The DSM-IV disorders assessed with the World Health Organization Composite International Diagnostic Interview and validated with blinded clinical interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Good concordance (area under the receiver operating characteristic curve >= 0.80) was found between Composite International Diagnostic Interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children diagnoses.
   Results: The prevalence estimates of any DSM-IV disorder are 40.3% at 12 months (79.5% of lifetime cases) and 23.4% at 30 days (57.9% of 12-month cases). Anxiety disorders are the most common class of disorders, followed by behavior, mood, and substance disorders. Although relative disorder prevalence is quite stable over time, 30-day to 12-month prevalence ratios are higher for anxiety and behavior disorders than mood or substance disorders, suggesting that the former are more chronic than the latter. The 30-day to 12-month prevalence ratios are generally lower than the 12-month to lifetime ratios, suggesting that disorder persistence is due more to episode recurrence than to chronicity. Sociodemographic correlates are largely consistent with previous studies.
   Conclusions: Among US adolescents, DSM-IV disorders are highly prevalent and persistent. Persistence is higher for adolescents than among adults and appears to be due more to recurrence than chronicity of child-adolescent onset disorders.
C1 [Kessler, Ronald C.; Gruber, Michael J.; Petukhova, Maria; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
   [McLaughlin, Katie A.] Harvard Univ, Sch Med, Div Gen Pediat, Childrens Hosp Boston, Boston, MA 02115 USA.
   [Green, Jennifer Greif] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Koretz, Doreen] Harvard Univ, Off Provost, Boston, MA 02115 USA.
   [Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
   [He, Jian-ping; Merikangas, Kathleen Ries] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA.
   [Costello, E. Jane] Duke Univ, Sch Med, Ctr Dev Epidemiol, Dept Psychiat & Behav Sci, Durham, NC USA.
   [Georgiades, Katholiki] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM ncs@hcp.med.harvard.edu
OI McLaughlin, Katie/0000-0002-1362-2410
FU Analysis Group; Bristol-Myers Squibb; Eli Lilly and Co; EPI-Q;
   GlaxoSmithKline; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Janssen
   Scientific Affairs; Pfizer Inc; sanofi-aventis; Shire US Inc.; National
   Institute of Mental Health [U01-MH60220, R01-MH66627, U01MH060220-09S1,
   R01-MH070884, R13-MH066849, R01-MH069864, R01-MH077883]; Robert Wood
   Johnson Foundation [044780]; John W. Alden Trust; National Institute on
   Drug Abuse; Fogarty International Center of the National Institutes of
   Health [FIRCA R03-TW006481]; John D. and Catherine T. MacArthur
   Foundation; Pfizer Foundation; Pan American Health Organization;
   AstraZeneca; Ortho-McNeil; Pfizer; Wyeth
FX Financial Disclosure: Dr Kessler has been a consultant for AstraZeneca,
   Analysis Group, Bristol-Myers Squibb, Cerner-Galt Associates, Eli Lilly
   and Co, GlaxoSmithKline, HealthCore Inc, Health Dialog, Integrated
   Benefits Institute, John Snow Inc, Kaiser Permanente, Matria Inc,
   Mensante, Merck and Co Inc, Ortho-McNeil Janssen Scientific Affairs,
   Pfizer Inc, Primary Care Network, Research Triangle Institute,
   sanofi-aventis, Shire US Inc, SRA International Inc, Takeda Global
   Research and Development, Transcept Pharmaceuticals Inc, and
   Wyeth-Ayerst; has served on advisory boards for Appliance Computing II,
   Eli Lilly and Co, Mindsite, Ortho-McNeil Janssen Scientific Affairs, and
   Wyeth-Ayerst; and has had research support for his epidemiological
   studies from Analysis Group, Bristol-Myers Squibb, Eli Lilly and Co,
   EPI-Q, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil
   Janssen Scientific Affairs, Pfizer Inc, sanofi-aventis, and Shire US
   Inc.; The NCS-A is supported by grants U01-MH60220, R01-MH66627, and
   U01MH060220-09S1 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 044780
   from the Robert Wood Johnson Foundation, and the John W. Alden Trust.
   The work of Ms He and Dr Merikangas is supported by the Intramural
   Research Program of the National Institute of Mental Health. The World
   Mental Health Data Coordination Centres have been supported by grants
   R01-MH070884, R13-MH066849, R01-MH069864, and R01-MH077883 from the
   National Institute of Mental Health, grant R01-DA016558 from the
   National Institute on Drug Abuse, grant FIRCA R03-TW006481 from the
   Fogarty International Center of the National Institutes of Health, the
   John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation,
   the Pan American Health Organization, and unrestricted educational
   grants from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Co,
   GlaxoSmithKline, Ortho-McNeil, Pfizer, sanofi-aventis, and Wyeth.
NR 37
TC 210
Z9 214
U1 5
U2 72
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 APR
PY 2012
VL 69
IS 4
BP 372
EP 380
DI 10.1001/archgenpsychiatry.2011.160
PG 9
WC Psychiatry
SC Psychiatry
GA 919JL
UT WOS:000302320600005
PM 22147808
ER

PT J
AU Kessler, RC
   Avenevoli, S
   Costello, J
   Green, JG
   Gruber, MJ
   McLaughlin, KA
   Petukhova, M
   Sampson, NA
   Zaslavsky, AM
   Merikangas, KR
AF Kessler, Ronald C.
   Avenevoli, Shelli
   Costello, Jane
   Green, Jennifer Greif
   Gruber, Michael J.
   McLaughlin, Katie A.
   Petukhova, Maria
   Sampson, Nancy A.
   Zaslavsky, Alan M.
   Merikangas, Kathleen Ries
TI Severity of 12-Month DSM-IV Disorders in the National Comorbidity Survey
   Replication Adolescent Supplement
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID SERIOUS EMOTIONAL DISTURBANCE; NCS-A; PSYCHIATRIC-DISORDERS;
   MENTAL-DISORDERS; BIRTH COHORT; PREVALENCE; DEPRESSION; YOUTH;
   CONSEQUENCES; EPIDEMIOLOGY
AB Context: Estimates of DSM-IV disorder prevalence are high; stringent criteria to define need for services are desired.
   Objective: To present US national data on the prevalence and sociodemographic correlates of 12-month serious emotional disturbance (SED), defined by the US Substance Abuse and Mental Health Services Administration, from the National Comorbidity Survey Replication Adolescent Supplement.
   Design: The National Comorbidity Survey Replication Adolescent Supplement is a national survey of DSM-IV anxiety, mood, behavior, and substance disorders among US adolescents.
   Setting: Dual-frame household and school samples of US adolescents.
   Participants: Total of 6483 pairs of adolescents aged 13 to 17 (interviews) and parents (questionnaires).
   Main Outcome Measures: The DSM-IV disorders were assessed with the World Health Organization Composite International Diagnostic Interview and validated with blinded clinical interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Serious emotional disturbance was operationalized as a DSM-IV/Composite International Diagnostic Interview disorder with a score of 50 or less on the Children's Global Assessment Scale (ie, moderate impairment in most areas of functioning or severe impairment in at least 1 area). Concordance of Composite International Diagnostic Interview SED diagnoses with blinded Schedule for Affective Disorders and Schizophrenia for School-Age Children diagnoses was good.
   Results: The estimated prevalence of SED was 8.0%. Most SEDs were due to behavior (54.5%) or mood (31.4%) disorders. Although respondents with 3 or more disorders made up only 29.0% of those with 12-month DSM-IV/Composite International Diagnostic Interview disorders, they constituted 63.5% of SEDs. Predictive effects of high comorbidity were significantly greater than the product of their disorder-specific odds ratios and consistent across disorder types. Associations of sociodemographic variables with SED were generally nonsignificant after controlling for disorder type and number.
   Conclusions: The high estimated 12-month prevalence of DSM-IV disorders among US adolescents is largely due to mild cases. The significant between-disorder differences in risk of SED and the significant effect of high comorbidity have important public health implications for targeting interventions.
C1 [Kessler, Ronald C.; Gruber, Michael J.; Petukhova, Maria; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
   [McLaughlin, Katie A.] Harvard Univ, Sch Med, Div Gen Pediat, Childrens Hosp Boston, Boston, MA 02115 USA.
   [Green, Jennifer Greif] Boston Univ, Sch Educ, Boston, MA 02215 USA.
   [Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
   [Merikangas, Kathleen Ries] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA.
   [Costello, Jane] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Ctr Dev Epidemiol, Durham, NC USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM ncs@hcp.med.harvard.edu
OI McLaughlin, Katie/0000-0002-1362-2410
FU Analysis Group, Inc; Bristol-Myers Squibb; Eli Lilly and Company; EPI-Q;
   GlaxoSmithKline, Inc; Johnson & Johnson Pharmaceuticals; Ortho-McNeil
   Janssen Scientific Affairs; Pfizer, Inc; sanofi-aventis; Shire US, Inc.;
   National Institute of Mental Health [U01-MH60220, R01-MH66627,
   U01MH060220-09S1, R01-MH070884, R13-MH066849, R01-MH069864,
   R01-MH077883, R01-DA016558]; Substance Abuse and Mental Health Services
   Administration; Robert Wood Johnson Foundation [044780]; John W. Alden
   Trust; National Institute on Drug Abuse; Fogarty International Center of
   the National Institutes of Health [FIRCA R03-TW006481]; John D. and
   Catherine T. MacArthur Foundation; Pfizer Foundation; Pan American
   Health Organization; AstraZeneca; BristolMyers Squibb; Ortho-McNeil;
   Wyeth
FX Dr Kessler has been a consultant for AstraZeneca; Analysis Group;
   Bristol-Myers Squibb; Cerner-Galt Associates; Eli Lilly and Company;
   GlaxoSmithKline, Inc; HealthCore, Inc; Health Dialog; Integrated
   Benefits Institute; John Snow, Inc; Kaiser Permanente; Matria, Inc;
   Mensante; Merck & Co, Inc; Ortho-McNeil Janssen Scientific Affairs;
   Pfizer, Inc; Primary Care Network; Research Triangle Institute;
   sanofi-aventis; Shire US, Inc; SRA International, Inc; Takeda Global
   Research & Development; Transcept Pharmaceuticals, Inc; and
   Wyeth-Ayerst; has served on advisory boards for Appliance Computing II;
   Eli Lilly & Company; Mindsite; Ortho-McNeil Janssen Scientific Affairs;
   and Wyeth-Ayerst; and has had research support for his epidemiologic
   studies from Analysis Group, Inc; Bristol-Myers Squibb; Eli Lilly and
   Company; EPI-Q; GlaxoSmithKline, Inc; Johnson & Johnson Pharmaceuticals;
   Ortho-McNeil Janssen Scientific Affairs; Pfizer, Inc; sanofi-aventis;
   and Shire US, Inc.; The NCS-A is supported by grants U01-MH60220,
   R01-MH66627, and U01MH060220-09S1 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,
   the Robert Wood Johnson Foundation (grant 044780), and the John W. Alden
   Trust. The work of Dr Merikangas is supported by the National Institute
   of Mental Health Intramural Research Program. The work of Dr Zaslavsky
   is supported by grant R01-MH66627 from the National Institute of Mental
   Health. The World Mental Health Data Coordination Centers have received
   grants R01-MH070884, R13-MH066849, R01-MH069864, and R01-MH077883 from
   the National Institute of Mental Health; R01-DA016558 from the National
   Institute on Drug Abuse; and FIRCA R03-TW006481 from the Fogarty
   International Center of the National Institutes of Health; and support
   from the John D. and Catherine T. MacArthur Foundation, the Pfizer
   Foundation, and the Pan American Health Organization. The World Mental
   Health Data Coordination Centers have also received unrestricted
   educational grants from AstraZeneca; BristolMyers Squibb; Eli Lilly and
   Company; GlaxoSmithKline, Inc; Ortho-McNeil; Pfizer, Inc;
   sanofi-aventis; and Wyeth.
NR 40
TC 54
Z9 54
U1 5
U2 29
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
EI 1538-3636
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD APR
PY 2012
VL 69
IS 4
BP 381
EP 389
PG 9
WC Psychiatry
SC Psychiatry
GA 919JL
UT WOS:000302320600006
PM 22474106
ER

PT J
AU Swendsen, J
   Burstein, M
   Case, B
   Conway, KP
   Dierker, L
   He, JP
   Merikangas, KR
AF Swendsen, Joel
   Burstein, Marcy
   Case, Brady
   Conway, Kevin P.
   Dierker, Lisa
   He, Jianping
   Merikangas, Kathleen R.
TI Use and Abuse of Alcohol and Illicit Drugs in US Adolescents Results of
   the National Comorbidity Survey-Adolescent Supplement
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID SUBSTANCE USE DISORDERS; 10-YEAR FOLLOW-UP; SURVEY REPLICATION;
   UNITED-STATES; EPIDEMIOLOGIC SURVEY; NCS-A; MENTAL-DISORDERS; LIFETIME
   PREVALENCE; EARLY ADULTHOOD; RISK-FACTORS
AB Context: Comprehensive descriptions of substance use and abuse trajectories have been lacking in nationally representative samples of adolescents.
   Objective: To examine the prevalence, age at onset, and sociodemographic correlates of alcohol and illicit drug use and abuse among US adolescents.
   Design: Cross-sectional survey of adolescents using a modified version of the Composite International Diagnostic Interview.
   Setting: Combined household and school adolescent samples.
   Participants: Nationally representative sample of 10 123 adolescents aged 13 to 18 years.
   Main Outcome Measures: Lifetime estimates of alcohol and illicit substance use and DSM-IV diagnoses of abuse, with or without dependence.
   Results: By late adolescence, 78.2% of US adolescents had consumed alcohol, 47.1% had reached regular drinking levels defined by at least 12 drinks within a given year, and 15.1% met criteria for lifetime abuse. The opportunity to use illicit drugs was reported by 81.4% of the oldest adolescents, drug use by 42.5%, and drug abuse by 16.4%. The median age at onset was 14 years for alcohol abuse with or without dependence, 14 years for drug abuse with dependence, and 15 years for drug abuse without dependence. The associations observed by age, sex, and race/ethnicity often varied significantly by previous stage of use.
   Conclusions: Alcohol and drug use is common in US adolescents, and the findings of this study indicate that most cases of abuse have their initial onset in this important period of development. Prevention and treatment efforts would benefit from careful attention to the correlates and risk factors that are specific to the stage of substance use in adolescents.
C1 [Burstein, Marcy; He, Jianping; Merikangas, Kathleen R.] NIMH, Intramural Res Program, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
   [Case, Brady] Emma Pendleton Bradley Hosp, Hlth Serv Res Program, E Providence, RI USA.
   [Conway, Kevin P.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Rockville, MD USA.
   [Dierker, Lisa] Wesleyan Univ, Dept Psychol, Middletown, CT USA.
   [Swendsen, Joel] Univ Bordeaux, Natl Ctr Sci Res, CNRS 5287, Bordeaux, France.
RP Merikangas, KR (reprint author), NIMH, Intramural Res Program, Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM merikank@mail.nih.gov
RI Case, Brady/M-1879-2015; 
OI Case, Brady/0000-0001-9512-0416; Conway, Kevin/0000-0002-7638-339X
FU National Institute of Mental Health [Z01 MH002808-08, U01-MH60220]
FX This work was supported by grant Z01 MH002808-08 from the Intramural
   Research Program of the National Institute of Mental Health. The NCS-A
   and the larger program of related National Comorbidity Surveys are
   supported by grant U01-MH60220 from the National Institute of Mental
   Health.
NR 44
TC 97
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U1 8
U2 42
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 APR
PY 2012
VL 69
IS 4
BP 390
EP 398
PG 9
WC Psychiatry
SC Psychiatry
GA 919JL
UT WOS:000302320600007
PM 22474107
ER

PT J
AU Tektonidou, MG
   Ward, MM
AF Tektonidou, Maria G.
   Ward, Michael M.
TI Screening for depression and risk of suicide in patients with arthritis:
   Comment on the article by Tektonidou et al Reply
SO ARTHRITIS CARE & RESEARCH
LA English
DT Letter
C1 [Tektonidou, Maria G.] Natl Tech Univ Athens, Athens, Greece.
   [Ward, Michael M.] NIAMSD, Bethesda, MD 20892 USA.
RP Tektonidou, MG (reprint author), Natl Tech Univ Athens, Athens, Greece.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD APR
PY 2012
VL 64
IS 4
BP 623
EP 624
DI 10.1002/acr.21561
PG 2
WC Rheumatology
SC Rheumatology
GA 915YR
UT WOS:000302064000022
ER

PT J
AU Haring, R
   Volzke, H
   Vasan, RS
   Felix, SB
   Nauck, M
   Dorr, M
   Wallaschofski, H
AF Haring, Robin
   Voelzke, Henry
   Vasan, Ramachandran S.
   Felix, Stephan B.
   Nauck, Matthias
   Doerr, Marcus
   Wallaschofski, Henri
TI Sex-specific associations of serum prolactin concentrations with cardiac
   remodeling: Longitudinal results from the Study of Health Pomerania
   (SHIP)
SO ATHEROSCLEROSIS
LA English
DT Article
DE Prolactin; Cardiac remodeling; Left ventricular mass; Hypertrophy;
   Population-based cohort
ID LEFT-VENTRICULAR MASS; CONGESTIVE-HEART-FAILURE; CARDIOVASCULAR HEALTH;
   CHAMBER QUANTIFICATION; POSTMENOPAUSAL WOMEN; EJECTION FRACTION; RISK;
   HYPERPROLACTINEMIA; MORTALITY; DISEASE
AB Background: Previous experimental and patient-based studies suggest that prolactin (PRL) and its 16 kDa fragment influence cardiovascular phenotypes by modulating angiogenesis. The association between serum PRL and cardiac remodeling in the general population is unknown.
   Methods: We evaluated 804 individuals (441 women) from the population-based Study of Health in Pomerania, aged >= 45 years, with available baseline serum PRL who underwent serial echocardiography at baseline and five-year follow-up. Left ventricular mass (LVM) was calculated and left ventricular hypertrophy (LVH) defined by sex-specific distributions of LVM. LV geometry was defined on the basis of relative wall thickness (RWT) and LVH. Sex-specific multivariable regression analyses were performed relating PRL (independent variable modelled as a continuous variable and as sex-specific quartiles) to change in LVM, RWT, and to incident LVH and abnormal geometry.
   Results: Baseline PRL concentrations were inversely associated with LVM change in men, but not in women (beta per 10% decrease in PRL: 0.37; 95% CI, 0.13-0.60 in men and -0.02; 95% CI, -0.21 to 0.17 in women, respectively). In men, baseline PRL concentrations were also inversely associated with incident LVH [first vs. fourth PRL quartile: relative risk (RR) 2.26 (95% CI, 1.20-4.24)] and altered LV geometry on follow-up [RR for incident concentric hypertrophy per 10% decrease in PRL: 1.20 (95% CI, 1.06-1.37)]. None of the longitudinal associations were observed in women.
   Conclusion: We observed inverse associations of PRL with LVM change, incident LVH, and altered LV geometry in men, but not in women. Additional studies are warranted to confirm our findings and to elucidate the mechanisms underlying these sex-specific associations. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Haring, Robin; Nauck, Matthias; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany.
   [Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
   [Vasan, Ramachandran S.] Boston Univ, Prevent Med & Epidemiol Sect, Sch Med, Boston, MA 02215 USA.
   [Vasan, Ramachandran S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
   [Felix, Stephan B.; Doerr, Marcus] Univ Med Greifswald, Dept Cardiol, D-17475 Greifswald, Germany.
RP Haring, R (reprint author), Univ Med Greifswald, Inst Clin Chem & Lab Med, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany.
EM robin.haring@uni-greifswald.de
OI Ramachandran, Vasan/0000-0001-7357-5970
FU Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103,
   01ZZ0403]; Ministry of Cultural Affairs; Social Ministry of the Federal
   State of Mecklenburg-West Pomerania; Federal Ministry of Education and
   Research; Ministry of Cultural Affairs of the Federal State of
   Mecklenburg, West Pomerania, Germany; Pfizer; DPC Biermann GmbH, Bad
   Nauheim, Germany
FX SHIP is part of the Community Medicine Research net of the University of
   Greifswald, Germany, which is funded by the Federal Ministry of
   Education and Research (grants nos. 01ZZ9603, 01ZZ0103, and 01ZZ0403),
   the Ministry of Cultural Affairs as well as the Social Ministry of the
   Federal State of Mecklenburg-West Pomerania. This study was carried out
   in collaboration with the German Centre for Cardiovascular Research
   (GCCR), which is funded by the Federal Ministry of Education and
   Research and the Ministry of Cultural Affairs of the Federal State of
   Mecklenburg, West Pomerania, Germany. Robin Haring had full access to
   all of the data in the study and takes responsibility for the integrity
   of the data and the accuracy of the data analysis. Pfizer provided
   partial grant support for the determination of plasma samples and data
   analysis. The PRL reagent used was sponsored DPC Biermann GmbH, Bad
   Nauheim, Germany.
NR 46
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U1 0
U2 4
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 APR
PY 2012
VL 221
IS 2
BP 570
EP 576
DI 10.1016/j.atherosclerosis.2012.01.017
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 914TI
UT WOS:000301974900043
PM 22293228
ER

PT J
AU Gao, S
   Liu, ZP
   Li, H
   Little, PJ
   Liu, PQ
   Xu, SW
AF Gao, Si
   Liu, Zhiping
   Li, Hong
   Little, Peter J.
   Liu, Peiqing
   Xu, Suowen
TI Cardiovascular actions and therapeutic potential of tanshinone IIA (vol
   220, pg 3, 2012)
SO ATHEROSCLEROSIS
LA English
DT Correction
C1 [Gao, Si; Liu, Zhiping; Li, Hong; Liu, Peiqing; Xu, Suowen] Sun Yat Sen Univ, Dept Pharmacol & Toxicol, Sch Pharmaceut Sci, Higher Educ Mega Ctr, Guangzhou 510006, Guangdong, Peoples R China.
   [Little, Peter J.] RMIT Univ, Discipline Pharm, Sch Med Sci, Melbourne, Vic 3086, Australia.
   [Little, Peter J.] RMIT Univ, Diabet Complicat Grp, Hlth Innovat Res Inst, Melbourne, Vic 3086, Australia.
   [Xu, Suowen] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Liu, PQ (reprint author), Sun Yat Sen Univ, Dept Pharmacol & Toxicol, Sch Pharmaceut Sci, Higher Educ Mega Ctr, 132 E Wai Huan Rd, Guangzhou 510006, Guangdong, Peoples R China.
EM liupq@mail.sysu.edu.cn; suo-wen.xu@nih.gov
NR 1
TC 0
Z9 0
U1 4
U2 9
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 APR
PY 2012
VL 221
IS 2
BP 604
EP 604
DI 10.1016/j.atherosclerosis.2012.01.014
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 914TI
UT WOS:000301974900049
ER

PT J
AU Rhodes, SEV
   Charles, DP
   Howland, EJ
   Murray, EA
AF Rhodes, Sarah E. V.
   Charles, David P.
   Howland, Emily J.
   Murray, Elisabeth A.
TI Amygdala Lesions in Rhesus Monkeys Fail to Disrupt Object Choices Based
   on Internal Context
SO BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE satiety; reward; internal state; motivation; hunger; thirst
ID BASOLATERAL AMYGDALA; DEVALUATION; HIPPOCAMPUS; CORTEX; STIMULI
AB We assessed the involvement of the amygdala in a task in which object choices were guided by internal context. Rhesus monkeys were trained on a biconditional discrimination whereby objects associated with food (but not water) were baited when the monkey was hungry, and objects associated with water (but not food) were baited when the monkey was thirsty. To solve this task, monkeys were required to choose objects yielding the reward congruent with their internal motivational state. Lesions of the amygdala did not disrupt learning or performance of this task. We conclude that the involvement of the amygdala in selective-satiation tasks, which depends in part on a change in internal context, is not due to the amygdala playing a general role in representing, or using, internal context.
C1 [Rhodes, Sarah E. V.; Charles, David P.; Howland, Emily J.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Rhodes, SEV (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA.
EM sarah.rhodes@mail.nih.gov
OI Murray, Elisabeth/0000-0003-1450-1642
FU National Institute of Mental Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Mental Health. We thank Alicia Izquierdo for
   assisting with surgical procedures and Luke J. Humphrey for help testing
   monkeys.
NR 19
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U1 0
U2 1
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7044
J9 BEHAV NEUROSCI
JI Behav. Neurosci.
PD APR
PY 2012
VL 126
IS 2
BP 270
EP 278
DI 10.1037/a0027229
PG 9
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 913WY
UT WOS:000301909300006
PM 22352788
ER

PT J
AU Cao, YFA
   Featherstone, RE
   Gandal, MJ
   Liang, YL
   Jutzeler, C
   Saunders, J
   Tatard-Leitman, V
   Chen, JS
   Weinberger, DR
   Lerman, C
   Siegel, SJ
AF Cao, Yufei A.
   Featherstone, Robert E.
   Gandal, Michael J.
   Liang, Yuling
   Jutzeler, Catherine
   Saunders, John
   Tatard-Leitman, Valerie
   Chen, Jingshan
   Weinberger, Daniel R.
   Lerman, Caryn
   Siegel, Steven J.
TI Nicotine Normalizes Event Related Potentials in COMT-Val-tg Mice and
   Increases Gamma and Theta Spectral Density
SO BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE catechol-O-methyltransferase; COMT; mouse; nicotine; event-related
   potential; EEG; gamma; theta
ID CATECHOL-O-METHYLTRANSFERASE; AUDITORY-EVOKED POTENTIALS; DORSOLATERAL
   PREFRONTAL CORTEX; PARKINSONS-DISEASE; WORKING-MEMORY; ANTIPSYCHOTIC
   MEDICATIONS; VAL(158)MET POLYMORPHISM; FREQUENCY OSCILLATIONS; COGNITIVE
   PERFORMANCE; PREPULSE INHIBITION
AB Regulation of dopamine neurotransmission is essential for cognitive processes. In humans and rodents, the relationship between dopamine signaling and cognitive performance is described as a dose-dependent, inverted-U curve whereby excess or insufficiency of dopamine in prefrontal cortex has detrimental effects. Previous studies have indicated that prefrontal dopamine levels are associated with genetic variation in catechol-O-methyltransferase (COMT), a regulatory enzyme that controls dopamine availability. Furthermore, smokers who carry the high-activity COMT-Val allele are more prone to cognitive deficits and have an increased risk of smoking relapse. The present study employed transgenic mice expressing the human COMT-Val variant to determine the effects of the high-activity COMT allele on electrophysiological markers, including the P20, N40, and P80 components of the auditory event-related potential, as well as baseline and auditory event-related power and phase-synchrony in theta and gamma ranges. We also examined the effects of nicotine on these measures to investigate the potential effects of smoking on COMT-mediated electrophysiological activity. COMT-Val-tg mice displayed increased N40 latency and decreased P80 amplitude as well as reduced baseline theta and gamma power. Nicotine increased P20 and P80 amplitudes, decreased N40 amplitude, increased P20 and N40 latencies, and reduced P80 latency. Nicotine also increased the event-related power and phase synchrony, yielding an increase in signal-to-noise ratio across theta and gamma ranges. COMT activity specifically alters long-latency components of the event-related response. Nicotine restored normal event-related activity among COMT-Val-tg mice, suggesting one mechanism through which nicotine may normalize cognitive function among people with the high-activity allele.
C1 [Siegel, Steven J.] Univ Penn, Dept Psychiat, Translat Res Labs, Translat Neurosci Program, Philadelphia, PA 19104 USA.
   [Chen, Jingshan; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA.
   [Lerman, Caryn] Univ Penn, Dept Psychiat, Ctr Res Nicotine Addict, Philadelphia, PA 19104 USA.
RP Siegel, SJ (reprint author), Univ Penn, Dept Psychiat, Translat Res Labs, Translat Neurosci Program, Room 2202,125 S 31st St, Philadelphia, PA 19104 USA.
EM siegels@upenn.edu
OI Gandal, Michael/0000-0001-5800-5128; Siegel, Steven/0000-0001-8058-9713
FU Academic Development Funds; National Institute of Mental Health; Astra
   Zeneca; Glaxo SmithKline; Novartis; Pfizer; NuPathe; Merck; 
   [1-P50-DA143187]
FX Supported by Grant 1-P50-DA143187; Academic Development Funds, to
   University of Pennsylvania; and the Genes, Cognition and Psychosis
   Program, National Institute of Mental Health. Yufei Cao, Robert
   Featherstone, Michael Gandal, Yuling Liang, Catherine Jutzeler, John
   Saunders, Jingshan Chen, and Daniel Weinberger have no financial
   conflicts of interest; Caryn Lerman has been a consultant and/or has
   received grant support from the following companies that develop and/or
   market smoking cessation medications: Astra Zeneca, Glaxo SmithKline,
   Novartis, and Pfizer; Steven Siegel has been a consultant and/or has
   received grant support from the following companies that develop and/or
   market medications: NuPathe, AstraZeneca, and Merck.
NR 103
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U1 1
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7044
J9 BEHAV NEUROSCI
JI Behav. Neurosci.
PD APR
PY 2012
VL 126
IS 2
BP 332
EP 343
DI 10.1037/a0027047
PG 12
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 913WY
UT WOS:000301909300012
PM 22309446
ER

PT J
AU Adamczyk, A
   Mejias, R
   Takamiya, K
   Yocum, J
   Krasnova, IN
   Calderon, J
   Cadet, JL
   Huganir, RL
   Pletnikov, MV
   Wang, T
AF Adamczyk, Abby
   Mejias, Rebeca
   Takamiya, Kogo
   Yocum, Jennifer
   Krasnova, Irina N.
   Calderon, Juan
   Cadet, Jean Lud
   Huganir, Richard L.
   Pletnikov, Mikhail V.
   Wang, Tao
TI GluA3-deficiency in mice is associated with increased social and
   aggressive behavior and elevated dopamine in striatum
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Glutamate receptor; GluA3; Striatum; Dopamine; Serotonin; Olfactory
   bulb; Aggression; Sociability; Social interaction; Mice
ID GLUTAMATE-RECEPTOR SUBUNITS; AMPA RECEPTORS; CHANNELS; EXPRESSION;
   PLASTICITY; SEROTONIN; NEURONS; IDENTIFICATION; VULNERABILITY;
   TESTOSTERONE
AB Glutamate signaling has been implicated in the regulation of social behavior. AMPA-glutamate receptors are assembled from four subunits (GluA1-4) of mainly GluA1/2 and GluA2/3 tetramers that form ion channels of distinct functional properties. Mice lacking GluA1 showed a reduced anxiety and male aggression. To understand the role of GluA3 in modulating social behavior, we investigated GluA3-deficient mice (Gria3 -/Y) on C57BL/6J background. Compared to wild type (WT) littermates (n = 14), Gria3 -/Y mice (n = 13) showed an increase in isolation-induced male aggression (p = 0.011) in home cage resident-intruder test; an increase in sociability (p = 0.01), and increase in male-male social interactions in neutral arena (p = 0.005); an increase in peripheral activities in open field test (p = 0.037) with normal anxiety levels in elevated plus maze and light-dark box; and minor deficits in motor and balance function in accelerating rotarod test (p = 0.016) with normal grip strength. Gria3 -/Y mice showed no significant deficit in spatial memory function in Morris-water maze and Y-maze tests, and normal levels of testosterone. Increased dopamine concentrations in stratum (p = 0.034) and reduced serotonin turnover in olfactory bulb (p = 0.002) were documented in Gria3 -/Y mice. These results support a role of GluA3 in the modulation of social behavior through brain dopamine and/or serotonin signaling and different AMPA receptor subunits affect social behavior through distinct mechanisms. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Adamczyk, Abby; Mejias, Rebeca; Calderon, Juan; Wang, Tao] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Dept Pediat, Baltimore, MD 21205 USA.
   [Takamiya, Kogo; Huganir, Richard L.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
   [Takamiya, Kogo; Huganir, Richard L.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
   [Yocum, Jennifer; Pletnikov, Mikhail V.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
   [Krasnova, Irina N.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, DHHS, Baltimore, MD 21224 USA.
RP Wang, T (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Dept Pediat, 733 N Broadway BRB 513, Baltimore, MD 21205 USA.
EM twang9@jhmi.edu
RI Adamczyk, Abby/E-4457-2014; Mejias-Estevez, Rebeca/B-4696-2008; 
OI Adamczyk, Abby/0000-0001-7653-295X; Mejias-Estevez,
   Rebeca/0000-0003-1936-7219; Calderon, Juan/0000-0003-2072-704X
FU March of Dimes Foundation; NICHD [HD044789, HD052680]; Ministry of
   Education and Science of Spain
FX This study was supported in part by research grants from a Basil
   O'Connor Award of the March of Dimes Foundation (to T.W.) and NICHD
   (HD044789 and HD052680, to T.W.): a postdoctoral fellowship from
   Ministry of Education and Science of Spain (to R.M.); RH is an
   Investigator with the Howard Hughes Medical Institute.
NR 42
TC 19
Z9 20
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD APR 1
PY 2012
VL 229
IS 1
BP 265
EP 272
DI 10.1016/j.bbr.2012.01.007
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 915SL
UT WOS:000302047600033
PM 22285418
ER

PT J
AU Batkai, S
   Mukhopadhyay, P
   Horvath, B
   Rajesh, M
   Gao, RY
   Mahadevan, A
   Amere, M
   Battista, N
   Lichtman, AH
   Gauson, LA
   Maccarrone, M
   Pertwee, RG
   Pacher, P
AF Batkai, Sandor
   Mukhopadhyay, Partha
   Horvath, Bela
   Rajesh, Mohanraj
   Gao, Rachel Y.
   Mahadevan, Anu
   Amere, Mukkanti
   Battista, Natalia
   Lichtman, Aron H.
   Gauson, Lisa A.
   Maccarrone, Mauro
   Pertwee, Roger G.
   Pacher, Pal
TI Delta(8)-Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion
   injury by decreasing oxidative stress and inflammatory responses through
   cannabinoid CB2 receptors
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE cannabinoids; oxidative stress; inflammation; ischaemia-reperfusion
ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE; CELL-DEATH; IN-VIVO;
   ISCHEMIA/REPERFUSION INJURY; DIABETIC CARDIOMYOPATHY;
   DELTA(9)-TETRAHYDROCANNABIVARIN; PEROXYNITRITE; DYSFUNCTION; PROTECTS
AB BACKGROUND AND PURPOSE
   Activation of cannabinoid CB2 receptors protects against various forms of ischaemia-reperfusion (I/R) injury. Delta(8)-Tetrahydrocannabivarin (Delta(8)-THCV) is a synthetic analogue of the plant cannabinoid Delta(9)-tetrahydrocannabivarin, which exhibits anti-inflammatory effects in rodents involving activation of CB2 receptors. Here, we assessed effects of Delta(8)-THCV and its metabolite 11-OH-Delta(8)-THCV on CB2 receptors and against hepatic I/R injury.
   EXPERIMENTAL APPROACH
   Effects in vitro were measured with human CB2 receptors expressed in CHO cells. Hepatic I/R injury was assessed in mice with 1h ischaemia and 2, 6 or 24h reperfusion in vivo.
   KEY RESULTS
   Displacement of [H-3]CP55940 by Delta(8)-THCV or 11-OH-Delta(8)-THCV from specific binding sites in CHO cell membranes transfected with human CB2 receptors (hCB(2)) yielded K-i values of 68.4 and 59.95 nM respectively. Delta(8)-THCV or 11-OH-Delta(8)-THCV inhibited forskolin-stimulated cAMP production by hCB(2) CHO cells (EC50 = 12.95 and 14.3 nM respectively). Delta(8)-THCV, given before induction of I/R, attenuated hepatic injury (measured by serum alanine aminotransferase and aspartate aminotransferase levels), decreased tissue protein carbonyl adducts, 4-hydroxy-2-nonenal, the chemokines CCL3 and CXCL2, TNF-alpha, intercellular adhesion molecule 1 (CD54) mRNA levels, tissue neutrophil infiltration, caspase 3/7 activity and DNA fragmentation. Protective effects of Delta(8)-THCV against liver damage were still present when the compound was given at the beginning of reperfusion. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of Delta(8)-THCV, while a CB1 antagonist tended to enhance it.
   CONCLUSIONS AND IMPLICATIONS
   Delta(8)-THCV activated CB2 receptors in vitro, and decreased tissue injury and inflammation in vivo, associated with I/R partly via CB2 receptor activation.
C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
   [Mahadevan, Anu; Amere, Mukkanti] Organix Inc, Woburn, MA USA.
   [Battista, Natalia; Maccarrone, Mauro] Univ Teramo, Dept Biomed Sci, Teramo, Italy.
   [Battista, Natalia; Maccarrone, Mauro] Santa Lucia Fdn, European Ctr Brain Res CERC, Rome, Italy.
   [Lichtman, Aron H.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA.
   [Gauson, Lisa A.; Pertwee, Roger G.] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen, Scotland.
   [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary.
RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI perumal, murugiah/D-1565-2012; Pacher, Pal/B-6378-2008; Ji,
   Haofeng/G-6206-2012; MUKHOPADHYAY, PARTHA/G-3890-2010; Horvath,
   Bela/A-7368-2009; Batkai, Sandor/H-7983-2014
OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY,
   PARTHA/0000-0002-1178-1274; 
FU National Institutes of Health [DA-03672, DA-005488, DA-009789];
   NIH/NIAAA; Hungarian Research Council [MB08-80238]; GW Pharmaceuticals
FX This study was supported by the National Institutes of Health (DA-03672,
   DA-005488 and DA-009789) and Intramural Research Program of NIH/NIAAA.
   Dr Horvath is a recipient of a Hungarian Research Council Scientific
   Research Fund Fellowship (NKTH-OTKA-EU, MB08-80238). The authors are
   indebted to Dr George Kunos for providing key resources and support.;
   R.G.P. receives funding from GW Pharmaceuticals; other authors have no
   conflicts.
NR 39
TC 14
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U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD APR
PY 2012
VL 165
IS 8
SI SI
BP 2450
EP 2461
DI 10.1111/j.1476-5381.2011.01410.x
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 914CB
UT WOS:000301925200006
PM 21470208
ER

PT J
AU Horvath, B
   Magid, L
   Mukhopadhyay, P
   Batkai, S
   Rajesh, M
   Park, O
   Tanchian, G
   Gao, RY
   Goodfellow, CE
   Glass, M
   Mechoulam, R
   Pacher, P
AF Horvath, Bela
   Magid, Lital
   Mukhopadhyay, Partha
   Batkai, Sandor
   Rajesh, Mohanraj
   Park, Ogyi
   Tanchian, Galin
   Gao, Rachel Y.
   Goodfellow, Catherine E.
   Glass, Michelle
   Mechoulam, Raphael
   Pacher, Pal
TI A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative
   stress, inflammation and cell death associated with hepatic
   ischaemia/reperfusion injury
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE cannabinoids; oxidative stress; inflammation; ischaemia-reperfusion
ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE; LIVER-INJURY;
   ISCHEMIA/REPERFUSION INJURY; DIABETIC CARDIOMYOPATHY; ENDOCANNABINOID
   SYSTEM; REACTIVE OXYGEN; IN-VIVO; PEROXYNITRITE; DYSFUNCTION
AB BACKGROUND AND PURPOSE
   Cannabinoid CB2 receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischaemia-reperfusion (I/R) injury.
   EXPERIMENTAL APPROACH
   We have investigated the effects of a novel CB2 receptor agonist ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en-1-yl) methanol (HU-910) on liver injury induced by 1 h of ischaemia followed by 2, 6 or 24 h of reperfusion, using a well-established mouse model of segmental hepatic I/R.
   KEY RESULTS
   Displacement of [H-3]CP55940 by HU-910 from specific binding sites in CHO cell membranes transfected with human CB2 or CB1 receptors (hCB(1/2)) yielded K-i values of 6 nM and 1.4 mM respectively. HU-910 inhibited forskolin-stimulated cyclic AMP production by hCB(2) CHO cells (EC50 = 162 nM) and yielded EC50 of 26.4 nM in [S-35]GTP gamma S binding assays using hCB(2) expressing CHO membranes. HU-910 given before ischaemia significantly attenuated levels of I/R-induced hepatic proinflammatory chemokines (CCL3 and CXCL2), TNF-alpha, inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1 h after the ischaemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-alpha production in isolated Kupffer cells and expression of adhesion molecules in primary human liver sinusoidal endothelial cells stimulated with TNF-alpha. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of HU-910, while pretreatment with a CB1 antagonist tended to enhance them.
   CONCLUSION AND IMPLICATIONS
   HU-910 is a potent CB2 receptor agonist which may exert protective effects in various diseases associated with inflammation and tissue injury.
C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
   [Magid, Lital] Hebrew Univ Jerusalem, Inst Drug Res, Fac Med, Jerusalem, Israel.
   [Goodfellow, Catherine E.; Glass, Michelle] Univ Auckland, Fac Med & Hlth Sci, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand.
   [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary.
RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI Pacher, Pal/B-6378-2008; Ji, Haofeng/G-6206-2012; MUKHOPADHYAY,
   PARTHA/G-3890-2010; Horvath, Bela/A-7368-2009; Batkai,
   Sandor/H-7983-2014; 
OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY,
   PARTHA/0000-0002-1178-1274; Gao, Yue/0000-0002-7890-1605; Glass,
   Michelle/0000-0002-5997-6898
FU NIH/NIAAA; NIDA [9789]; Hungarian Research Council [OTKA-NKTH-EU
   MB08-80238]
FX This study was supported by the Intramural Research Program of NIH/NIAAA
   (to P. P.) and by NIDA grant #9789 (to R. M.). Dr Bela Horvath is a
   recipient of a Hungarian Research Council Scientific Research Fund
   Fellowship (OTKA-NKTH-EU MB08-80238). The authors are indebted to Drs
   George Kunos and Bin Gao for providing key resources and support.
NR 39
TC 37
Z9 40
U1 1
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD APR
PY 2012
VL 165
IS 8
SI SI
BP 2462
EP 2478
DI 10.1111/j.1476-5381.2011.01381.x
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 914CB
UT WOS:000301925200007
PM 21449982
ER

PT J
AU Panlilio, LV
   Ferre, S
   Yasar, S
   Thorndike, EB
   Schindler, CW
   Goldberg, SR
AF Panlilio, Leigh V.
   Ferre, Sergi
   Yasar, Sevil
   Thorndike, Eric B.
   Schindler, Charles W.
   Goldberg, Steven R.
TI Combined effects of THC and caffeine on working memory in rats
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE delayed spatial matching; mediating response; rehearsal; marijuana;
   adenosine receptor antagonist; caffeine; THC
ID ADENOSINE A(1) RECEPTORS; SHORT-TERM-MEMORY; A(2A) RECEPTORS;
   BEHAVIORAL-ANALYSIS; RHESUS-MONKEYS; INVOLVEMENT; IMPAIRMENT; DRUGS;
   DELTA(9)-TETRAHYDROCANNABINOL; DELTA-9-TETRAHYDROCANNABINOL
AB BACKGROUND AND PURPOSE
   Cannabis and caffeine are two of the most widely used psychoactive substances. Delta(9)-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory.
   EXPERIMENTAL APPROACH
   Rats were given THC (0, 1 and 3 mg.kg(-1), i.p.) along with caffeine (0, 1, 3 and 10 mg.kg(-1), i.p.), the selective adenosine A(1)-receptor antagonist CPT (0, 3 and 10 mg.kg(-1)) or the selective adenosine A(2A)-receptor antagonist SCH58261 (0 and 5 mg.kg(-1)) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal.
   KEY RESULTS
   THC alone produced memory deficits at 3 mg.kg(-1). The initial exposure to caffeine (10 mg.kg(-1)) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg.kg(-1)) was combined with caffeine (10 mg.kg(-1)) or CPT (10 mg.kg(-1)), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered.
   CONCLUSION AND IMPLICATIONS
   Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus.
C1 [Panlilio, Leigh V.; Ferre, Sergi; Thorndike, Eric B.; Schindler, Charles W.; Goldberg, Steven R.] 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 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
RI Ferre, Sergi/K-6115-2014
OI Ferre, Sergi/0000-0002-1747-1779
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.
NR 41
TC 10
Z9 10
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD APR
PY 2012
VL 165
IS 8
SI SI
BP 2529
EP 2538
DI 10.1111/j.1476-5381.2011.01554.x
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 914CB
UT WOS:000301925200012
PM 21699509
ER

PT J
AU Scherma, M
   Justinova, Z
   Zanettini, C
   Panlilio, LV
   Mascia, P
   Fadda, P
   Fratta, W
   Makriyannis, A
   Vadivel, SK
   Gamaleddin, I
   Le Foll, B
   Goldberg, SR
AF Scherma, Maria
   Justinova, Zuzana
   Zanettini, Claudio
   Panlilio, Leigh V.
   Mascia, Paola
   Fadda, Paola
   Fratta, Walter
   Makriyannis, Alexandros
   Vadivel, Subramanian K.
   Gamaleddin, Islam
   Le Foll, Bernard
   Goldberg, Steven R.
TI The anandamide transport inhibitor AM404 reduces the rewarding effects
   of nicotine and nicotine-induced dopamine elevations in the nucleus
   accumbens shell in rats
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE reward; tobacco dependence; nicotine; anandamide; AM404; conditioned
   place preference; reinstatement; microdialysis; dopamine
ID ACID AMIDE HYDROLASE; CONDITIONED PLACE PREFERENCES; CANNABINOID
   RECEPTORS; ENDOCANNABINOID SYSTEM; HIPPOCAMPAL-NEURONS;
   MEMBRANE-TRANSPORT; CB1 RECEPTORS; ESTER URB597; ADDICTION; ACTIVATION
AB BACKGROUND AND PURPOSE
   The fatty acid amide hydrolase inhibitor URB597 can reverse the abuse-related behavioural and neurochemical effects of nicotine in rats. Fatty acid amide hydrolase inhibitors block the degradation (and thereby magnify and prolong the actions) of the endocannabinoid anandamide (AEA), and also the non-cannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). OEA and PEA are endogenous ligands for peroxisome proliferator-activated receptors alpha (PPAR-alpha). Since recent evidence indicates that PPAR-alpha can modulate nicotine reward, it is unclear whether AEA plays a role in the effects of URB597 on nicotine reward.
   EXPERIMENTAL APPROACH
   A way to selectively increase endogenous levels of AEA without altering OEA or PEA levels is to inhibit AEA uptake into cells by administering the AEA transport inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404). To clarify AEA's role in nicotine reward, we investigated the effect of AM404 on conditioned place preference (CPP), reinstatement of abolished CPP, locomotor suppression and anxiolysis in an open field, and dopamine elevations in the nucleus accumbens shell induced by nicotine in Sprague-Dawley rats.
   KEY RESULTS
   AM404 prevented the development of nicotine-induced CPP and impeded nicotine-induced reinstatement of the abolished CPP. Furthermore, AM404 reduced nicotine-induced increases in dopamine levels in the nucleus accumbens shell, the terminal area of the brain's mesolimbic reward system. AM404 did not alter the locomotor suppressive or anxiolytic effect of nicotine.
   CONCLUSIONS AND IMPLICATIONS
   These findings suggest that AEA transport inhibition can counteract the addictive effects of nicotine and that AEA transport may serve as a new target for development of medications for treatment of tobacco dependence.
C1 [Scherma, Maria; Justinova, Zuzana; Zanettini, Claudio; Panlilio, Leigh V.; Mascia, Paola; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neuroscience Res Branch, IRP,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
   [Scherma, Maria; Fadda, Paola; Fratta, Walter] Univ Cagliari, Bb Brodie Dept Neurosci, I-09124 Cagliari, Italy.
   [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, MPRC, Baltimore, MD 21201 USA.
   [Makriyannis, Alexandros; Vadivel, Subramanian K.] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA.
   [Gamaleddin, Islam; Le Foll, Bernard] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON, Canada.
   [Gamaleddin, Islam; Le Foll, Bernard] Ctr Addict & Mental Hlth, Addict Program, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
   [Le Foll, Bernard] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada.
   [Le Foll, Bernard] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada.
RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neuroscience Res Branch, IRP,NIH,Dept Hlth & Human Serv, Bayview Blvd, Baltimore, MD 21224 USA.
EM sgoldber@mail.nih.gov
RI Justinova, Zuzana/A-9109-2011; Le Foll, Bernard/K-2952-2014; 
OI Justinova, Zuzana/0000-0001-5793-7484; Le Foll,
   Bernard/0000-0002-6406-4973; FADDA, PAOLA/0000-0002-0642-6710
FU National Institute on Drug Abuse, National Institutes of Health,
   Department of Health and Human Services, Baltimore, MD, USA; Italian
   Ministry of University and Scientific Research; Centre of Excellence on
   'Neurobiology of Dependence', Cagliari, Italy; Division of Geriatric
   Medicine and Gerontology of Johns Hopkins University School of Medicine,
   Baltimore, MD, USA; Center for Drug Discovery, Northeastern University,
   Boston, MA, USA; Centre for Addiction and Mental Health of the
   University of Toronto, Toronto, Canada
FX This study was supported in part by the Intramural Research Program of
   the National Institute on Drug Abuse, National Institutes of Health,
   Department of Health and Human Services, Baltimore, MD, USA, by the
   Italian Ministry of University and Scientific Research and the Centre of
   Excellence on 'Neurobiology of Dependence', Cagliari, Italy, by the
   Division of Geriatric Medicine and Gerontology of Johns Hopkins
   University School of Medicine, Baltimore, MD, USA, by the Center for
   Drug Discovery, Northeastern University, Boston, MA, USA, and by the
   Centre for Addiction and Mental Health of the University of Toronto,
   Toronto, Canada.
NR 55
TC 17
Z9 18
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD APR
PY 2012
VL 165
IS 8
SI SI
BP 2539
EP 2548
DI 10.1111/j.1476-5381.2011.01467.x
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 914CB
UT WOS:000301925200013
PM 21557729
ER

PT J
AU Thun, MJ
   Hoover, RN
   Hunter, DJ
AF Thun, Michael J.
   Hoover, Robert N.
   Hunter, David J.
TI Bigger, Better, Sooner-Scaling Up for Success
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ESTROGEN-PROGESTIN REPLACEMENT; GENOME-WIDE ASSOCIATION; BREAST-CANCER;
   POSTMENOPAUSAL WOMEN; PLUS PROGESTIN; RISK; THERAPY; MORTALITY; OBESITY;
   SCIENCE
AB Over the last twenty years, the field of epidemiology has seen a rapidly increasing interest in, and need for, addressing low-level risks, interactions as well as main effects, and simultaneous assessment of vast numbers of biomarkers. Multiple examples over this time have shown the necessity for very large, high-quality individual studies (e. g., biobanks) or consortia of studies for these efforts to be successful. The need for this will continue to increase in the foreseeable future. It will also be important to analyze and publish aggregated data much earlier in the discovery process than typical for past efforts. Cancer Epidemiol Biomarkers Prev; 21(4); 571-5. (C) 2012 AACR.
C1 [Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
   [Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA.
   [Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
   [Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
RP Hoover, RN (reprint author), 6120 Execut Blvd,EPS 8094, Bethesda, MD 20892 USA.
EM hooverr@mail.nih.gov
FU NIEHS NIH HHS [P30 ES002109]
NR 36
TC 7
Z9 7
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD APR
PY 2012
VL 21
IS 4
BP 571
EP 575
DI 10.1158/1055-9965.EPI-12-0191
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 918AG
UT WOS:000302220600001
PM 22374992
ER

PT J
AU Couch, FJ
   Gaudet, MM
   Antoniou, AC
   Ramus, SJ
   Kuchenbaecker, KB
   Soucy, P
   Beesley, J
   Chen, XQ
   Wang, XS
   Kirchhoff, T
   McGuffog, L
   Barrowdale, D
   Lee, A
   Healey, S
   Sinilnikova, OM
   Andrulis, IL
   Ozcelik, H
   Mulligan, AM
   Thomassen, M
   Gerdes, AM
   Jensen, UB
   Skytte, AB
   Kruse, TA
   Caligo, MA
   von Wachenfeldt, A
   Barbany-Bustinza, G
   Loman, N
   Soller, M
   Ehrencrona, H
   Karlsson, P
   Nathanson, KL
   Rebbeck, TR
   Domchek, SM
   Jakubowska, A
   Lubinski, J
   Jaworska, K
   Durda, K
   Zlowocka, E
   Huzarski, T
   Byrski, T
   Gronwald, J
   Cybulski, C
   Gorski, B
   Osorio, A
   Duran, M
   Tejada, MI
   Benitez, J
   Hamann, U
   Hogervorst, FBL
   van Os, TA
   van Leeuwen, FE
   Meijers-Heijboer, HEJ
   Wijnen, J
   Blok, MJ
   Kets, M
   Hooning, MJ
   Oldenburg, RA
   Ausems, MGEM
   Peock, S
   Frost, D
   Ellis, SD
   Platte, R
   Fineberg, E
   Evans, DG
   Jacobs, C
   Eeles, RA
   Adlard, J
   Davidson, R
   Eccles, DM
   Cole, T
   Cook, J
   Paterson, J
   Brewer, C
   Douglas, F
   Hodgson, SV
   Morrison, PJ
   Walker, L
   Porteous, ME
   Kennedy, MJ
   Side, LE
   Bove, B
   Godwin, AK
   Stoppa-Lyonnet, D
   Fassy-Colcombet, M
   Castera, L
   Cornelis, F
   Mazoyer, S
   Leone, M
   Boutry-Kryza, N
   Bressac-de Paillerets, B
   Caron, O
   Pujol, P
   Coupier, I
   Delnatte, C
   Akloul, L
   Lynch, HT
   Snyder, CL
   Buys, SS
   Daly, MB
   Terry, M
   Chung, WK
   John, EM
   Miron, A
   Southey, MC
   Hopper, JL
   Goldgar, DE
   Singer, CF
   Rappaport, C
   Tea, MKM
   Fink-Retter, A
   Hansen, TVO
   Nielsen, FC
   Arason, A
   Vijai, J
   Shah, S
   Sarrel, K
   Robson, ME
   Piedmonte, M
   Phillips, K
   Basil, J
   Rubinstein, WS
   Boggess, J
   Wakeley, K
   Ewart-Toland, A
   Montagna, M
   Agata, S
   Imyanitov, EN
   Isaacs, C
   Janavicius, R
   Lazaro, C
   Blanco, I
   Feliubadalo, L
   Brunet, J
   Gayther, SA
   Pharoah, PPD
   Odunsi, KO
   Karlan, BY
   Walsh, CS
   Olah, E
   Teo, SH
   Ganz, PA
   Beattie, MS
   van Rensburg, EJ
   Dorfling, CM
   Diez, O
   Kwong, A
   Schmutzler, RK
   Wappenschmidt, B
   Engel, C
   Meindl, A
   Ditsch, N
   Arnold, N
   Heidemann, S
   Niederacher, D
   Preisler-Adams, S
   Gadzicki, D
   Varon-Mateeva, R
   Deissler, H
   Gehrig, A
   Sutter, C
   Kast, K
   Fiebig, B
   Heinritz, W
   Caldes, T
   de la Hoya, M
   Muranen, TA
   Nevanlinna, H
   Tischkowitz, M
   Spurdle, AB
   Neuhausen, SL
   Ding, YC
   Lindor, NM
   Fredericksen, Z
   Pankratz, VS
   Peterlongo, P
   Manoukian, S
   Peissel, B
   Zaffaroni, D
   Barile, M
   Bernard, L
   Viel, A
   Giannini, G
   Varesco, L
   Radice, P
   Greene, MH
   Mai, PL
   Easton, DF
   Chenevix-Trench, G
   Offit, K
   Simard, J
AF Couch, Fergus J.
   Gaudet, Mia M.
   Antoniou, Antonis C.
   Ramus, Susan J.
   Kuchenbaecker, Karoline B.
   Soucy, Penny
   Beesley, Jonathan
   Chen, Xiaoqing
   Wang, Xianshu
   Kirchhoff, Tomas
   McGuffog, Lesley
   Barrowdale, Daniel
   Lee, Andrew
   Healey, Sue
   Sinilnikova, Olga M.
   Andrulis, Irene L.
   Ozcelik, Hilmi
   Mulligan, Anna Marie
   Thomassen, Mads
   Gerdes, Anne-Marie
   Jensen, Uffe Birk
   Skytte, Anne-Bine
   Kruse, Torben A.
   Caligo, Maria A.
   von Wachenfeldt, Anna
   Barbany-Bustinza, Gisela
   Loman, Niklas
   Soller, Maria
   Ehrencrona, Hans
   Karlsson, Per
   Nathanson, Katherine L.
   Rebbeck, Timothy R.
   Domchek, Susan M.
   Jakubowska, Ania
   Lubinski, Jan
   Jaworska, Katarzyna
   Durda, Katarzyna
   Zlowocka, Elzbieta
   Huzarski, Tomasz
   Byrski, Tomasz
   Gronwald, Jacek
   Cybulski, Cezary
   Gorski, Bohdan
   Osorio, Ana
   Duran, Mercedes
   Isabel Tejada, Maria
   Benitez, Javier
   Hamann, Ute
   Hogervorst, Frans B. L.
   van Os, Theo A.
   van Leeuwen, Flora E.
   Meijers-Heijboer, Hanne E. J.
   Wijnen, Juul
   Blok, Marinus J.
   Kets, Marleen
   Hooning, Maartje J.
   Oldenburg, Rogier A.
   Ausems, Margreet G. E. M.
   Peock, Susan
   Frost, Debra
   Ellis, Steve D.
   Platte, Radka
   Fineberg, Elena
   Evans, D. Gareth
   Jacobs, Chris
   Eeles, Rosalind A.
   Adlard, Julian
   Davidson, Rosemarie
   Eccles, Diana M.
   Cole, Trevor
   Cook, Jackie
   Paterson, Joan
   Brewer, Carole
   Douglas, Fiona
   Hodgson, Shirley V.
   Morrison, Patrick J.
   Walker, Lisa
   Porteous, Mary E.
   Kennedy, M. John
   Side, Lucy E.
   Bove, Betsy
   Godwin, Andrew K.
   Stoppa-Lyonnet, Dominique
   Fassy-Colcombet, Marion
   Castera, Laurent
   Cornelis, Francois
   Mazoyer, Sylvie
   Leone, Melanie
   Boutry-Kryza, Nadia
   Bressac-de Paillerets, Brigitte
   Caron, Olivier
   Pujol, Pascal
   Coupier, Isabelle
   Delnatte, Capucine
   Akloul, Linda
   Lynch, Henry T.
   Snyder, Carrie L.
   Buys, Saundra S.
   Daly, Mary B.
   Terry, MaryBeth
   Chung, Wendy K.
   John, Esther M.
   Miron, Alexander
   Southey, Melissa C.
   Hopper, John L.
   Goldgar, David E.
   Singer, Christian F.
   Rappaport, Christine
   Tea, Muy-Kheng M.
   Fink-Retter, Anneliese
   Hansen, Thomas V. O.
   Nielsen, Finn C.
   Arason, Adalgeir
   Vijai, Joseph
   Shah, Sohela
   Sarrel, Kara
   Robson, Mark E.
   Piedmonte, Marion
   Phillips, Kelly
   Basil, Jack
   Rubinstein, Wendy S.
   Boggess, John
   Wakeley, Katie
   Ewart-Toland, Amanda
   Montagna, Marco
   Agata, Simona
   Imyanitov, Evgeny N.
   Isaacs, Claudine
   Janavicius, Ramunas
   Lazaro, Conxi
   Blanco, Ignacio
   Feliubadalo, Lidia
   Brunet, Joan
   Gayther, Simon A.
   Pharoah, Paul P. D.
   Odunsi, Kunle O.
   Karlan, Beth Y.
   Walsh, Christine S.
   Olah, Edith
   Teo, Soo Hwang
   Ganz, Patricia A.
   Beattie, Mary S.
   van Rensburg, Elizabeth J.
   Dorfling, Cecelia M.
   Diez, Orland
   Kwong, Ava
   Schmutzler, Rita K.
   Wappenschmidt, Barbara
   Engel, Christoph
   Meindl, Alfons
   Ditsch, Nina
   Arnold, Norbert
   Heidemann, Simone
   Niederacher, Dieter
   Preisler-Adams, Sabine
   Gadzicki, Dorothea
   Varon-Mateeva, Raymonda
   Deissler, Helmut
   Gehrig, Andrea
   Sutter, Christian
   Kast, Karin
   Fiebig, Britta
   Heinritz, Wolfram
   Caldes, Trinidad
   de la Hoya, Miguel
   Muranen, Taru A.
   Nevanlinna, Heli
   Tischkowitz, Marcd.
   Spurdle, Amanda B.
   Neuhausen, Susan L.
   Ding, Yuan Chun
   Lindor, Noralane M.
   Fredericksen, Zachary
   Pankratz, V. Shane
   Peterlongo, Paolo
   Manoukian, Siranoush
   Peissel, Bernard
   Zaffaroni, Daniela
   Barile, Monica
   Bernard, Loris
   Viel, Alessandra
   Giannini, Giuseppe
   Varesco, Liliana
   Radice, Paolo
   Greene, Mark H.
   Mai, Phuong L.
   Easton, Douglas F.
   Chenevix-Trench, Georgia
   Offit, Kenneth
   Simard, Jacques
CA OCGN
   SWE-BRCA
   HEBON
   EMBRACE
   GEMO Study Collaborators
   kConFab Investigators
   Consortium Investigators Modifiers
TI Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER
   Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2
   Mutation Carriers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; URIC-ACID NEPHROLITHIASIS; SUSCEPTIBILITY LOCI;
   TUMOR SUBTYPES; ALLELES; CONSORTIUM; RECEPTOR; DISEASE; GENE; 8Q24
AB Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
   Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined.
   Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 x 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 x 10(-3)).
   Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers.
   Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.
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   [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
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RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Stabile 2-42,200 1st St SW, Rochester, MN 55905 USA.
EM couch.fergus@mayo.edu
RI Spurdle, Amanda/A-4978-2011; Feliubadalo, Lidia/G-4577-2016; ,
   Ivan/D-6804-2012; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014;
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   (Lizette)/B-9104-2011; Blanco, Ignacio/D-2565-2013; Ditsch,
   Nina/F-6267-2014; Teo,  Soo-hwang/H-2353-2014; Arnold,
   Norbert/E-3012-2010; montagna, marco/E-2225-2012; M Isabel,
   Tejada/E-2394-2012
OI Evans, Gareth/0000-0002-8482-5784; Spurdle, Amanda/0000-0003-1337-7897;
   Phillips, Kelly-Anne/0000-0002-0475-1771; Feliubadalo,
   Lidia/0000-0002-1736-0112; Kirchhoff, Tomas/0000-0002-9055-2364; Brunet,
   Joan/0000-0003-1945-3512; Nevanlinna, Heli/0000-0002-0916-2976; Jacobs,
   Chris/0000-0002-9557-9080; Muranen, Taru/0000-0002-5895-1808;
   Barrowdale, Daniel/0000-0003-1661-3939; TEJADA,
   Maria-Isabel/0000-0002-7334-1864; , Ivan/0000-0002-3108-058X; Eeles,
   Rosalind/0000-0002-3698-6241; Janavicius, Ramunas/0000-0002-3773-8485;
   Nathanson, Katherine/0000-0002-6740-0901; Ramus,
   Susan/0000-0003-0005-7798; Osorio, Ana/0000-0001-8124-3984; Ehrencrona,
   Hans/0000-0002-5589-3622; Gronwald, Jacek/0000-0002-3643-2871;
   manoukian, siranoush/0000-0002-6034-7562; Peissel,
   Bernard/0000-0001-9233-3571; Rappaport-Fuerhauser,
   Christine/0000-0002-6820-0020; Giannini, Giuseppe/0000-0003-0299-4056;
   Kwong, Ava/0000-0002-6968-9489; Joseph, Vijai/0000-0002-7933-151X;
   Blanco, Ignacio/0000-0002-7414-7481; Arnold,
   Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; 
FU NIH [CA128978]; NCI [CA116201]; U.S. Department of Defence
   [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen Foundation
   for the Cure; Cancer Research UK (CR-UK) [C12292/A11174, C1287/A10118];
   European Community [223175 (HEALTH-F2-2009-223175)]; Canadian Institutes
   of Health Research; Canadian Breast Cancer Research Alliance [019511];
   Research Council of Lithuania [LIG-19/2010]; Cancer Association of South
   Africa (CANSA); National Cancer Institute, NIH [RFA-CA-06-503]; Breast
   Cancer Family Registry (BCFR); Neye Foundation; Fundacion Mutua
   Madrilena; Asociacion Espanola Contra el Cancer; Spanish Ministry of
   Science and Innovation [FIS PI08 1120]; Basque Foundation for Health
   Innovation and Research (BIOEF) [BIO07/CA/006]; Ministero della Salute;
   Ministero dell'Universita' e Ricerca [RBLAO3-BETH]; Fondazione Italiana
   per la Ricerca sul Cancro; Associazione Italiana per la Ricerca
   sulCancro [4017]; Fondazione IRCCS Istituto Nazionale Tumori; DKFZ;
   CR-UK [C1287/A10118, C1287/A11990]; NIHR; Royal Marsden NHS Foundation
   Trust; German Cancer Aid [109076]; Centre of Molecular Medicine Cologne
   (CMMC); Ligue National Contre le Cancer; Association for International
   Cancer Research Grant [AICR-07-0454]; Association "Le cancer du sein,
   parlons-en!"; Familial Cancer Registry at Georgetown University
   (NIH/NCI) [P30-CA051008]; Cancer Genetics Network [HHSN261200744000C];
   Swing Fore the Cure; Clinical Genetics Branch, DCEG; Community Oncology
   and Prevention Trials Program-COPTRG; Helsinki University Central
   Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid
   Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088,
   NKI2007-3756]; ZonMW [91109024]; Hungarian Research Grant
   [KTIA-OTKACK-80745]; Spanish Health Research Fund; Carlos III Health
   Institute; Catalan Health Institute; Autonomous Government of Catalonia;
   Polish Foundation of Science; Postgraduate School of Molecular Medicine,
   Warsaw Medical University; Icelandic Association "Walking for Breast
   Cancer Research"; Landspitali University Hospital; Ministero
   dell'Istruzione, dell'Universita e della Ricerca (MIUR); "Ministero
   della Salute" [RFPS 2006-5-341353, ACC2/R6.9]; National Breast Cancer
   Foundation; National Health and Medical Research Council (NHMRC);
   Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria,
   Tasmania; Cancer Foundation of Western Australia; NHMRC [145684, 288704,
   454508]; FCCC; University of Kansas Cancer Center; Kansas Bioscience
   Authority Eminent Scholar Program; Jewish General Hospital; Starr Cancer
   Consortium; Norman and Carol Stone Cancer Research Initiative; Kate and
   Robert Niehaus Clinical Cancer Research Initiative; Lymphoma Foundation;
   Sabin Family Research Initiative; U.S. National Cancer Institute;
   Westat, Inc.; Russian Federation for Basic Research [10-04-92601,
   10-04-92110, 11-04-00227]; Federal Agency for Science and Innovations
   [16.512.11.2237]; Cancer Care Ontario; U.S. National Cancer Institute,
   NIH under RFA [CA-06-503]; Ohio State University Comprehensive Cancer
   Center; Instituto Toscano Tumori grant; CARIF; University Malaya; Helen
   Diller Family Comprehensive Cancer Center at UCSF; Avon Foundation;
   Center for Translational and Policy Research in Personalized Medicine
   (TRANSPERS); NIH/NCI [P01 CA130818-02A1]; CRUK; American Cancer Society
   [SIOP-06-258-06-COUN];  [ISCIIIRETIC RD06/0020/1051];  [PI10/01422]; 
   [PI10/31488];  [2009SGR290];  [U01CA69631];  [5U01CA113916]; 
   [NO2-CP-11019-50];  [N02-CP-65504]
FX This research was supported by NIH grant CA128978, an NCI Specialized
   Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a
   U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341),
   and grants from the Breast Cancer Research Foundation and the Komen
   Foundation for the Cure. This work was also supported by Cancer Research
   UK (CR-UK) grants C12292/A11174 and C1287/A10118. The research leading
   to these results has received funding from the European Community's
   Seventh Framework Programme under grant agreement no. 223175
   (HEALTH-F2-2009-223175). Support was also provided by the Canadian
   Institutes of Health Research for the "CIHR Team in Familial Risks of
   Breast Cancer" program and by the Canadian Breast Cancer Research
   Alliance-grant #019511. A. C. Antoniou is a CR-UK Senior Cancer Research
   Fellow. D. F. Easton is CR-UK Principal Research Fellow. G.
   Chenevix-Trench6 is a NHMRC Senior Principal Research Fellow. BFBOCC was
   supported by the Research Council of Lithuania grant LIG-19/2010 to R.
   Janavicius. BMBSA was supported by grants from the Cancer Association of
   South Africa (CANSA) to E.J. van Rensburg. BCFR was supported by the
   National Cancer Institute, NIH under RFA-CA-06-503 and through
   cooperative agreements with members of the Breast Cancer Family Registry
   (BCFR) and Principal Investigators, including Cancer Care Ontario (U01
   CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center
   (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer
   Prevention Institute of California (formerly the Northern California
   Cancer Center; U01 CA69417), University of Melbourne (U01 CA69638), and
   Research Triangle Institute Informatics Support Center (RFP No.
   N02PC45022-46). CBCS was supported by The Neye Foundation. CNIO was
   partially supported by Fundacion Mutua Madrilena, Asociacion Espanola
   Contra el Cancer, the Spanish Ministry of Science and Innovation (FIS
   PI08 1120), and the Basque Foundation for Health Innovation and Research
   (BIOEF): BIO07/CA/006. CONSIT TEAM was supported by grants from
   Ministero della Salute (Extraordinary National Cancer Program 2006
   "Alleanza contro il Cancro" to L. Varesco and P. Radice, and "Progetto
   Tumori Femminili" to P. Radice), Ministero dell'Universita' e Ricerca
   (RBLAO3-BETH to P. Radice), Fondazione Italiana per la Ricerca sul
   Cancro (Special Project "Hereditary tumors" to P. Radice), Associazione
   Italiana per la Ricerca sulCancro (4017 to P. Pujol), and by funds from
   Italian citizens who allocated the 5 x 1,000 share of their tax payment
   in support of the Fondazione IRCCS Istituto Nazionale Tumori, according
   to Italian laws (INT-Institutional strategic projects "5 x 1000"). The
   DKFZ study was supported by funds from the DKFZ. EMBRACE was supported
   by CR-UK Grants C1287/A10118 and C1287/A11990. D. G. Evans and Fiona
   Lalloo were supported by an NIHR grant to the Biomedical Research
   Centre, Manchester, UK. The Investigators at The Institute of Cancer
   Research and The Royal Marsden NHS Foundation Trust were supported by an
   NIHR grant to the Biomedical Research Centre at The Institute of Cancer
   Research and The Royal Marsden NHS Foundation Trust. R. A. Eeles,
   Elizabeth Bancroft, and Lucia D'Mello were supported by CR-UK Grant
   C5047/A8385. GC-HBOC was supported by a grant of the German Cancer Aid
   (grant 109076) and by the Centre of Molecular Medicine Cologne (CMMC).
   The GEMO study was supported by the Ligue National Contre le Cancer;
   Association for International Cancer Research Grant (AICR-07-0454); and
   the Association "Le cancer du sein, parlons-en!" Award.; The Georgetown
   study was supported by the Familial Cancer Registry at Georgetown
   University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network
   (HHSN261200744000C), and Swing Fore the Cure. GOG was supported through
   funding provided by both intramural (Clinical Genetics Branch, DCEG) and
   extramural (Community Oncology and Prevention Trials Program-COPTRG) NCI
   programs. K. Phillips is the Cancer Council Victoria, Colebatch Clinical
   Research Fellow. HEBCS was supported by the Helsinki University Central
   Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer
   Society, and the Sigrid Juselius Foundation. The HEBON study was
   supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088,
   NKI2007-3756, and the ZonMW grant 91109024. HUNBOCS was supported by the
   Hungarian Research Grant KTIA-OTKACK-80745. ICO was supported by
   Asociacion Espanola Contra el Cancer, Spanish Health Research Fund;
   Carlos III Health Institute; Catalan Health Institute and Autonomous
   Government of Catalonia; contract grant numbers ISCIIIRETIC
   RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. IHCC was
   supported by a Polish Foundation of Science award to K. Jaworska, a
   fellow of International PhD program, Postgraduate School of Molecular
   Medicine, Warsaw Medical University. ILUH was supported by the Icelandic
   Association "Walking for Breast Cancer Research" and by the Landspitali
   University Hospital Research Fund. INHERIT was supported with J. Simard,
   Chairholder of the Canada Research Chair in Oncogenetics. IOVHBOCS was
   supported by Ministero dell'Istruzione, dell'Universita e della Ricerca
   (MIUR), and "Ministero della Salute" ("Progetto Tumori Femminili and
   grant numbers RFPS 2006-5-341353, ACC2/R6.9"). kConFab was supported by
   grants from the National Breast Cancer Foundation, the National Health
   and Medical Research Council (NHMRC), and by the Queensland Cancer Fund,
   the Cancer Councils of New South Wales, Victoria, Tasmania, and South
   Australia, and the Cancer Foundation of Western Australia. The kConFab
   Clinical Follow-Up Study was funded by the NHMRC [145684, 288704,
   454508]. A.-B. Skytte is supported by a NHMRC Senior Research
   Fellowship. A. K. Godwin was funded by U01CA69631, 5U01CA113916, and the
   Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support
   from The University of Kansas Cancer Center and the Kansas Bioscience
   Authority Eminent Scholar Program. A. K. Godwin is the Chancellors
   Distinguished Chair in Biomedical Sciences endowed Professor. The McGill
   study was supported by the Jewish General Hospital Weekend to End Breast
   Cancer. M. Thomassen holds a Fonds de la Recherche en Sante du Quebec
   clinician-scientist award. The MSKCC study was supported by the Starr
   Cancer Consortium, the Breast Cancer Research Foundation, the Norman and
   Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus
   Clinical Cancer Research Initiative, the Lymphoma Foundation, and the
   Sabin Family Research Initiative. The NCI study was supported by the
   Intramural Research Program of the U.S. National Cancer Institute and by
   support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat,
   Inc. NNPIO was supported by the Russian Federation for Basic Research
   (grants 10-04-92601, 10-04-92110, 11-04-00227) and the Federal Agency
   for Science and Innovations (contract 16.512.11.2237). OCGN was
   supported by Cancer Care Ontario and the U.S. National Cancer Institute,
   NIH under RFA # CA-06-503 and through cooperative agreements with
   members of the Breast Cancer Family Registry (BCFR) and Principal
   Investigators.; OSU-CCG was supported by the Ohio State University
   Comprehensive Cancer Center. PBCS was supported by an Instituto Toscano
   Tumori grant to M. A. Caligo. SEABASS was supported by CARIF and
   University Malaya. The UCSF study was supported by the Helen Diller
   Family Comprehensive Cancer Center at UCSF, the Avon Foundation, and the
   Center for Translational and Policy Research in Personalized Medicine
   (TRANSPERS), NIH/NCI P01 CA130818-02A1. UKFOCR was supported by a
   project grant from CRUK to P. P. D. Pharoah. The UPENN study was
   supported Komen Foundation for the Cure to S. M. Domchek, the Breast
   Cancer Research Foundation to K. L. Nathanson, and NIH grants
   R01-CA083855 and R01-CA102776 to T. R. Rebbeck. WCRI was supported by
   the American Cancer Society Clinical Research Professorship #
   SIOP-06-258-06-COUN.
NR 24
TC 24
Z9 24
U1 2
U2 24
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 APR
PY 2012
VL 21
IS 4
BP 645
EP 657
DI 10.1158/1055-9965.EPI-11-0888
PG 13
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 918AG
UT WOS:000302220600010
PM 22351618
ER

PT J
AU Orom, UA
   Lim, MK
   Savage, JE
   Jin, LJ
   Saleh, AD
   Lisanti, MP
   Simone, NL
AF Orom, Ulf Andersson
   Lim, Meng K.
   Savage, Jason E.
   Jin, Lianjin
   Saleh, Anthony D.
   Lisanti, Michael P.
   Simone, Nicole L.
TI MicroRNA-203 regulates caveolin-1 in breast tissue during caloric
   restriction
SO CELL CYCLE
LA English
DT Article
DE microRNA; caloric restriction; breast cancer; caveolin-1; p63; longevity
ID PROSTATE-CANCER; MESSENGER-RNAS; EXPRESSION; MIR-203; CELLS;
   TRANSLATION; MECHANISMS; CARCINOMA; STEMNESS; TARGETS
AB Caloric restriction has been shown to increase lifespan in several organisms and to delay onset of age-related diseases. The transcriptional response to caloric restriction has been studied for mRNAs, while the microRNA signature following caloric restriction remains unexplored. Here, we characterize the microRNA expression in mouse breast tissue before and after caloric restriction, reporting several changes in the microRNA expression profile. In particular, miR-203 is found to be highly induced by caloric restriction, and we demonstrate that caveolin-1 as well as p63 are direct targets of miR-203 in vivo during caloric restriction. Using tissue culture models, we suggest that this regulation is important in both mouse and human. In conclusion, we show that the microRNA response induced by caloric restriction can regulate important factors in processes such as longevity and aging and is an integral and important component of the cellular response to caloric restriction.
C1 [Orom, Ulf Andersson; Lim, Meng K.; Jin, Lianjin; Simone, Nicole L.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
   [Savage, Jason E.; Saleh, Anthony D.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [Lisanti, Michael P.] Thomas Jefferson Univ, Jefferson Med Coll, Stem Cell Biol & Regenerat Med Ctr, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
RP Simone, NL (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
EM nicole.simone@jeffersonhospital.org
RI Lisanti, Michael/C-6866-2013; 
OI Orom, Ulf/0000-0002-0643-0592
FU NIH; Kimmel Cancer Center Radiation Oncology Facility; NCI Cancer Center
   [P30 CA56036]
FX This research was supported in part by the Intramural Research Program
   of the NIH and also the Kimmel Cancer Center Radiation Oncology
   Facility, which is supported partly by NCI Cancer Center Grant P30
   CA56036.
NR 35
TC 19
Z9 20
U1 2
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 APR 1
PY 2012
VL 11
IS 7
BP 1291
EP 1295
DI 10.4161/cc.11.7.19704
PG 5
WC Cell Biology
SC Cell Biology
GA 918XQ
UT WOS:000302285300011
PM 22421148
ER

PT J
AU Quijano, C
   Cao, L
   Fergusson, MM
   Romero, H
   Liu, J
   Gutkind, S
   Rovira, II
   Mohney, RP
   Karoly, ED
   Finkel, T
AF Quijano, Celia
   Cao, Liu
   Fergusson, Maria M.
   Romero, Hector
   Liu, Jie
   Gutkind, Sarah
   Rovira, Ilsa I.
   Mohney, Robert P.
   Karoly, Edward D.
   Finkel, Toren
TI Oncogene-induced senescence results in marked metabolic and bioenergetic
   alterations
SO CELL CYCLE
LA English
DT Article
DE oncogene-induced senescence; metabolomics; Ras; fatty acid oxidation
ID CELLULAR SENESCENCE; LIFE-SPAN; CELLS; STRESS; PURIFICATION;
   CONTRIBUTES; CARBOXYLASE; MORTALITY; OXIDATION; ELEGANS
AB Oncogene-induced senescence (OIS) is characterized by permanent growth arrest and the acquisition of a secretory, pro-inflammatory state. Increasingly, OIS is viewed as an important barrier to tumorgenesis. Surprisingly, relatively little is known about the metabolic changes that accompany and therefore may contribute to OIS. Here, we have performed a metabolomic and bioenergetic analysis of Ras-induced senescence. Profiling approximately 300 different intracellular metabolites reveals that cells that have undergone OIS develop a unique metabolic signature that differs markedly from cells undergoing replicative senescence. A number of lipid metabolites appear uniquely increased in OIS cells, including a marked increase in the level of certain intracellular long chain fatty acids. Functional studies reveal that this alteration in the metabolome reflects substantial changes in overall lipid metabolism. In particular, Ras-induced senescent cells manifest a decline in lipid synthesis and a significant increase in fatty acid oxidation. Increased fatty acid oxidation results in an unexpectedly high rate of basal oxygen consumption in cells that have undergone OIS. Pharmacological or genetic inhibition of carnitine palmitoyltransferase 1, the rate-limiting step in mitochondrial fatty acid oxidation, restores a pre-senescent metabolic rate and, surprisingly, selectively inhibits the secretory, pro-inflammatory state that accompanies OIS. Thus, Ras-induced senescent cells demonstrate profound alterations in their metabolic and bioenergetic profiles, particularly with regards to the levels, synthesis and oxidation of free fatty acids. Furthermore, the inflammatory phenotype that accompanies OIS appears to be related to these underlying changes in cellular metabolism.
C1 [Quijano, Celia; Cao, Liu; Fergusson, Maria M.; Liu, Jie; Gutkind, Sarah; Rovira, Ilsa I.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
   [Quijano, Celia] Univ Republica, Dept Bioquim, Fac Med, Montevideo, Uruguay.
   [Romero, Hector] Univ Republica, Lab Org & Evoluc Genoma, Fac Ciencias CURE, Montevideo, Uruguay.
   [Mohney, Robert P.; Karoly, Edward D.] Metabolon Incorporated, Res Triangle Pk, NC USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
FU NIH
FX This work was supported by NIH Intramural funds.
NR 50
TC 23
Z9 24
U1 0
U2 15
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD APR 1
PY 2012
VL 11
IS 7
BP 1383
EP 1392
DI 10.4161/cc.11.7.19800
PG 10
WC Cell Biology
SC Cell Biology
GA 918XQ
UT WOS:000302285300021
PM 22421146
ER

PT J
AU Samoshkin, A
   Dulev, S
   Loukinov, D
   Rosenfeld, JA
   Strunnikov, AV
AF Samoshkin, Alexander
   Dulev, Stanimir
   Loukinov, Dmitry
   Rosenfeld, Jeffrey A.
   Strunnikov, Alexander V.
TI Condensin dysfunction in human cells induces nonrandom chromosomal
   breaks in anaphase, with distinct patterns for both unique and repeated
   genomic regions
SO CHROMOSOMA
LA English
DT Article
ID DNA-DAMAGE RESPONSE; CENTROMERIC CHROMATIN; SOMATIC MUTATIONS; CANCER
   GENOME; TRANSCRIPTION; SEGREGATION; RDNA; CATALOG; COHESIN
AB Condensin complexes are essential for chromosome condensation and segregation in mitosis, while condensin dysfunction, among other pathways leading to chromosomal bridging in mitosis, may play a role in tumor genomic instability, including recently discovered chromotripsis. To characterize potential double-strand breaks specifically occurring in late anaphase, human chromosomes depleted of condensin were analyzed by gamma-H2AX ChIP followed by high-throughput sequencing (ChIP-seq). In condensin-depleted cells, the nonrepeated parts of the genome were shown to contain distinct gamma-H2AX enrichment zones 75% of which overlapped with known hemizygous deletions in cancers. Furthermore, some tandemly repeated DNA sequences, analyzed separately from the rest of the genome, showed significant gamma-H2AX enrichment in condensin-depleted anaphases. The most commonly occurring targets of such enrichment included simple repeats, centromeric satellites, and rDNA. The two latter categories indicate that acrocentric human chromosomes are especially susceptible to breaks upon condensin deficiency. The genomic regions that are specifically destabilized upon condensin dysfunction may constitute a condensin-specific chromosome destabilization pattern.
C1 [Loukinov, Dmitry; Strunnikov, Alexander V.] NIAID, NIH, Immunopathol Lab, Rockville, MD 20852 USA.
   [Samoshkin, Alexander] NCI, NIH, Genome Struct & Funct Sect, Bethesda, MD 20892 USA.
   [Dulev, Stanimir] Univ Munich, Adolf Butenandt Inst, D-80539 Munich, Germany.
   [Rosenfeld, Jeffrey A.] Univ Med & Dent New Jersey, Div High Performance & Res Comp, Newark, NJ 07103 USA.
RP Strunnikov, AV (reprint author), NIAID, NIH, Immunopathol Lab, Rockville, MD 20852 USA.
EM strunnik@mail.nih.gov
RI perumal, murugiah/D-1565-2012; 
OI Strunnikov, Alexander/0000-0002-9058-2256
NR 31
TC 11
Z9 11
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-5915
EI 1432-0886
J9 CHROMOSOMA
JI Chromosoma
PD APR
PY 2012
VL 121
IS 2
BP 191
EP 199
DI 10.1007/s00412-011-0353-6
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 915UZ
UT WOS:000302054300007
PM 22179743
ER

PT J
AU Tarique, AA
   Kalsy, A
   Arifuzzaman, M
   Rollins, SM
   Charles, RC
   Leung, DT
   Harris, JB
   LaRocque, RC
   Sheikh, A
   Bhuiyan, MS
   Saksena, R
   Clements, JD
   Calderwood, SB
   Qadri, F
   Kovac, P
   Ryan, ET
AF Tarique, A. A.
   Kalsy, A.
   Arifuzzaman, M.
   Rollins, S. M.
   Charles, R. C.
   Leung, D. T.
   Harris, J. B.
   LaRocque, R. C.
   Sheikh, A.
   Bhuiyan, M. S.
   Saksena, R.
   Clements, J. D.
   Calderwood, S. B.
   Qadri, F.
   Kovac, P.
   Ryan, E. T.
TI Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic
   Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination
   Boosts Vibriocidal Responses and Induces Protective Immunity in Mice
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID HEAT-LABILE ENTEROTOXIN; INFECTION-DERIVED IMMUNITY; ADP-RIBOSYLATING
   EXOTOXINS; ESCHERICHIA-COLI; MUCOSAL ADJUVANTS; VECTOR STRAINS; SEROTYPE
   OGAWA; CVD 103-HGR; EL-TOR; TOXIN
AB A shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of Vibrio cholerae O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P < 0.01) responses as well as in anti-Ogawa (P < 0.01) and anti-Inaba (P < 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P < 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses against V. cholerae.
C1 [Tarique, A. A.; Kalsy, A.; Arifuzzaman, M.; Rollins, S. M.; Charles, R. C.; Leung, D. T.; Harris, J. B.; LaRocque, R. C.; Calderwood, S. B.; Ryan, E. T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
   [Tarique, A. A.; Arifuzzaman, M.; Sheikh, A.; Bhuiyan, M. S.; Qadri, F.] Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh.
   [Charles, R. C.; Leung, D. T.; LaRocque, R. C.; Calderwood, S. B.; Ryan, E. T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
   [Harris, J. B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   [Saksena, R.; Kovac, P.] NIDDK, LBC, NIH, Bethesda, MD USA.
   [Clements, J. D.] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA.
   [Calderwood, S. B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
   [Ryan, E. T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM etryan@partners.org
RI Tarique, Abdullah/M-2860-2013; Kovac, Pavol/B-8813-2008; 
OI Tarique, Abdullah/0000-0003-3782-345X; Kovac, Pavol/0000-0001-5044-3449;
   Rollins, Sean/0000-0002-3724-1989; leung, daniel/0000-0001-8401-0801
FU National Institutes of Health-NIDDK; International Centre for Diarrheal
   Diseases Research, Bangladesh (icddr,b); National Institutes of Health;
   National Institute of Allergy & Infectious Diseases [U01 AI077883, U01
   AI058935, R03 AI063079]; Fogarty International Center [D43 TW005572];
   American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in
   Global Infectious Diseases [TW005572, K01 TW07409, TW07144, K08
   AI089721]; Howard Hughes Medical Institute; Harvard Initiative for
   Global Health Postdoctoral Fellowship in Global Infectious Diseases
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health-NIDDK, the International Centre for
   Diarrheal Diseases Research, Bangladesh (icddr,b) (F. Q., A. A. T.),
   grants from the National Institutes of Health, including the National
   Institute of Allergy & Infectious Diseases (U01 AI077883 [E. T. R.], U01
   AI058935 [S. B. C., E. T. R.], and R03 AI063079 [F. Q.]), the Fogarty
   International Center Training Grant in Vaccine Development and Public
   Health (D43 TW005572 [A. A. T., M. A., A. S., M. S. B., F. Q., E. T.
   R.]), an American Recovery and Reinvestment Act (ARRA) Postdoctoral
   Fellowship in Global Infectious Diseases (TW005572 [D. T. L., R. C.
   L.]), and Career Development Awards (K01 TW07409 [J.B.H.], TW07144 [R.
   C. L.], and K08 AI089721 [R. C. C.]), a Physician-Scientist Early Career
   Award from the Howard Hughes Medical Institute (R. C. L.), and a Harvard
   Initiative for Global Health Postdoctoral Fellowship in Global
   Infectious Diseases (D.T.L.).
NR 49
TC 11
Z9 12
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD APR
PY 2012
VL 19
IS 4
BP 594
EP 602
DI 10.1128/CVI.05689-11
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 917FA
UT WOS:000302156700018
PM 22357651
ER

PT J
AU Bowen, RAR
   Dowdell, KC
   Dale, JK
   Drake, SK
   Fleisher, TA
   Hortin, GL
   Remaley, AT
   Nexo, E
   Rao, VK
AF Bowen, Raffick A. R.
   Dowdell, Kennichi C.
   Dale, Janet K.
   Drake, Steven K.
   Fleisher, Thomas A.
   Hortin, Glen L.
   Remaley, Alan T.
   Nexo, Ebba
   Rao, V. Koneti
TI Elevated vitamin B-12 levels in autoimmune lymphoproliferative syndrome
   attributable to elevated haptocorrin in lymphocytes
SO CLINICAL BIOCHEMISTRY
LA English
DT Article
DE ALPS; Vitamin B12; Cobalamin; Germline; Haptocorrin; Transcobolamin
ID TRANSCOBALAMIN; COBALAMIN; APOPTOSIS
AB Objective: Identify the etiology of elevated B-12 in autoimmune lymphoproliferative syndrome (ALPS).
   Design: Peripheral blood of ALPS patients with elevated B-12 and controls were evaluated.
   Results: Total and holo-haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively. No abnormal B-12-binding proteins were found. Western blot revealed HC in lymphocyte lysates only from ALPS patients.
   Conclusion: Elevated concentrations of B-12 found in ALPS patients were due to increased lymphocyte expression of HC. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
C1 [Bowen, Raffick A. R.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Dowdell, Kennichi C.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Dale, Janet K.] NIAID, DAIT, Clin Res Program, NIH, Bethesda, MD 20892 USA.
   [Drake, Steven K.] NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA.
   [Fleisher, Thomas A.; Remaley, Alan T.] NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA.
   [Hortin, Glen L.; Nexo, Ebba] Aarhus Univ Hosp, Dept Clin Biochem, DK-8000 Aarhus, Denmark.
   [Rao, V. Koneti] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Bowen, RAR (reprint author), Stanford Univ, Sch Med, Dept Pathol, 300 Pasteur Dr,Room H1507B, Stanford, CA 94305 USA.
EM rbowen@stanfordmed.org
FU National Institute of Allergy and Infectious Diseases; Warren Grant
   Magnuson Clinical Center
FX This research was supported by the intramural programs of the National
   Institute of Allergy and Infectious Diseases and the Warren Grant
   Magnuson Clinical Center.
NR 10
TC 7
Z9 8
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0009-9120
J9 CLIN BIOCHEM
JI Clin. Biochem.
PD APR
PY 2012
VL 45
IS 6
BP 490
EP 492
DI 10.1016/j.clinbiochem.2012.01.016
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 916OA
UT WOS:000302111900023
PM 22306884
ER

PT J
AU Marchbanks, PA
   Curtis, KM
   Mandel, MG
   Wilson, HG
   Jeng, G
   Folger, SG
   McDonald, JA
   Daling, JR
   Bernstein, L
   Malone, KE
   Wingo, PA
   Simon, MS
   Norman, SA
   Strom, BL
   Ursin, G
   Weiss, LK
   Burkman, RT
   Spirtas, R
AF Marchbanks, Polly A.
   Curtis, Kathryn M.
   Mandel, Michele G.
   Wilson, Hoyt G.
   Jeng, Gary
   Folger, Suzanne G.
   McDonald, Jill A.
   Daling, Janet R.
   Bernstein, Leslie
   Malone, Kathleen E.
   Wingo, Phyllis A.
   Simon, Michael S.
   Norman, Sandra A.
   Strom, Brian L.
   Ursin, Giske
   Weiss, Linda K.
   Burkman, Ronald T.
   Spirtas, Robert
TI Oral contraceptive formulation and risk of breast cancer
SO CONTRACEPTION
LA English
DT Article
DE Oral contraceptives; Breast cancer; Hormones; Epidemiology; Case-control
   studies
ID YOUNG-WOMEN; POTENCY
AB Background: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required.
   Study Design: We used data from a multicenter, population-based, case control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC.
   Results: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk.
   Conclusions: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk. Published by Elsevier Inc.
C1 [Marchbanks, Polly A.; Curtis, Kathryn M.; Mandel, Michele G.; Wilson, Hoyt G.; Jeng, Gary; Folger, Suzanne G.; McDonald, Jill A.; Wingo, Phyllis A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30333 USA.
   [Daling, Janet R.; Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
   [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA.
   [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA.
   [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Populat Studies & Prevent Program, Detroit, MI USA.
   [Norman, Sandra A.; Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Norman, Sandra A.; Strom, Brian L.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Ursin, Giske] Canc Registry Norway, Oslo, Norway.
   [Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway.
   [Ursin, Giske] Univ So Calif, Los Angeles, CA USA.
   [Weiss, Linda K.] NCI, Off Canc Ctr, Bethesda, MD 20892 USA.
   [Burkman, Ronald T.] Tufts Univ, Sch Med, Dept Obstet & Gynecol, Springfield, MA 01199 USA.
   [Burkman, Ronald T.] Baystate Med Ctr, Springfield, MA USA.
   [Spirtas, Robert] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
RP Marchbanks, PA (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA 30333 USA.
EM pam2@cdc.gov
FU National Institute of Child Health and Human Development; National
   Cancer institute; Emory University [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]
FX This study was supported by the National Institute of Child Health and
   Human Development, with additional support from the National Cancer
   institute, through contracts with Emory University (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) and 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). The Centers for
   Disease Control and Prevention contributed additional staff and computer
   support. Surveillance, Epidemiology and End Results (SEER) Programs of
   the National Cancer Institute provided assistance for study sites in
   Atlanta (N01-PC-67006), Detroit (N01-CN-65064), Los Angeles
   (N01-PC-67010) and Seattle (N01-CN-0532).
NR 30
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Z9 13
U1 3
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0010-7824
J9 CONTRACEPTION
JI Contraception
PD APR
PY 2012
VL 85
IS 4
BP 342
EP 350
DI 10.1016/j.contraception.2011.08.007
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 915BY
UT WOS:000301999100004
PM 22067757
ER

PT J
AU Cassidy, OL
   Matheson, B
   Osborn, R
   Vannucci, A
   Kozlosky, M
   Shomaker, LB
   Yanovski, SZ
   Tanofsky-Kraff, M
AF Cassidy, Omni L.
   Matheson, Brittany
   Osborn, Robyn
   Vannucci, Anna
   Kozlosky, Merel
   Shomaker, Lauren B.
   Yanovski, Susan Z.
   Tanofsky-Kraff, Marian
TI Loss of control eating in African-American and Caucasian youth
SO EATING BEHAVIORS
LA English
DT Article
DE African-American; Loss of control eating; Child; Adolescent; Energy
   intake; Obesity
ID BODY-MASS INDEX; WEIGHT-GAIN; INTERPERSONAL PSYCHOTHERAPY; OVERWEIGHT
   CHILDREN; ADOLESCENT GIRLS; PUBERTAL CHANGES; FOOD INSECURITY;
   COLLEGE-WOMEN; US CHILDREN; WHITE
AB Loss of control (LOC) eating, a disinhibited eating behavior shown to predict excessive weight gain in youth, has been reported by African-American children and adolescents. Yet, little is known about how LOC-eating manifests in this population. To investigate potential racial differences in LOC-eating, the Eating Disorder Examination was administered to 185 non-Hispanic African-American and Caucasian youth ages 8-17 y. Objective eating was assessed at two test meals during which youth ate ad libitum from a multi-item lunchtime food array. African-American and Caucasian youth reported a similar prevalence of LOC episodes (24.2% vs. 28.9%, p=.75). Yet, accounting for sex, age, fat-free mass, percent fat mass, height, and socioeconomic status, African-Americans consumed more total energy at both laboratory meals (1608 +/- 57 kcal vs. 1362 +/- 44 kcal; p<.001). Furthermore, African-American youth reporting LOC consumed the most total energy across both meals (1855 +/- 104 kcal) compared to African-Americans without LOC (1524 +/- 60 kcal), Caucasians with LOC (1278 +/- 68 kcal), and Caucasians without LOC (1399 +/- 46 kcal; p<.001). Future research is required to examine whether LOC-eating contributes to the high rates of obesity in African-American youth. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Cassidy, Omni L.; Matheson, Brittany; Osborn, Robyn; Vannucci, Anna; Shomaker, Lauren B.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
   [Cassidy, Omni L.; Matheson, Brittany; Shomaker, Lauren B.; Yanovski, Susan Z.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20814 USA.
   [Kozlosky, Merel] Ctr Clin, Dept Nutr, Bethesda, MD 20814 USA.
   [Yanovski, Susan Z.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD 20814 USA.
RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mtanofsky@usuhs.edu
FU Intramural NIH HHS [Z01 HD000641-12]; NICHD NIH HHS [ZIA HD000641]; PHS
   HHS [1ZIAHD000641]
NR 49
TC 7
Z9 7
U1 2
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1471-0153
J9 EAT BEHAV
JI Eat. Behav.
PD APR
PY 2012
VL 13
IS 2
BP 174
EP 178
DI 10.1016/j.eatbeh.2012.01.003
PG 5
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 915BI
UT WOS:000301997500021
PM 22365807
ER

PT J
AU Appel, S
   Duke, ES
   Martinez, AR
   Khan, OI
   Dustin, IM
   Reeves-Tyer, P
   Berl, MB
   Sato, S
   Gaillard, WD
   Theodore, WH
AF Appel, Shmuel
   Duke, Elizabeth S.
   Martinez, Ashley R.
   Khan, Omar I.
   Dustin, Irene M.
   Reeves-Tyer, Patricia
   Berl, Madison B.
   Sato, Susumu
   Gaillard, William D.
   Theodore, William H.
TI Cerebral blood flow and fMRI BOLD auditory language activation in
   temporal lobe epilepsy
SO EPILEPSIA
LA English
DT Article
DE Positron emission tomography; Cerebral blood flow; Functional magnetic
   resonance imaging; Temporal lobe epilepsy; Language; Blood oxygen
   level-dependent
ID LOCALIZATION-RELATED EPILEPSY; VASCULAR MALFORMATIONS; CORTICAL
   STIMULATION; FUNCTIONAL-ANATOMY; ATYPICAL LANGUAGE; FOCAL EPILEPSY;
   HUMAN-BRAIN; LATERALIZATION; CHILDREN; REORGANIZATION
AB Purpose: Blood oxygen leveldependent (BOLD) functional magnetic resonance imaging (fMRI), an important research and clinical tool, depends on relatively greater transient increases in (regional cerebral blood flow) rCBF than cerebral metabolic rate for oxygen during neural activity. We investigated whether reduced resting rCBF in patients with temporal lobe epilepsy affects BOLD signal during fMRI language mapping.
   Methods: We used [O-15] water positron emission tomography (PET) to measure rCBF, and 3 Tesla echo planar imaging (EPI) BOLD fMRI with an auditory description decision task in 33 patients with temporal lobe epilepsy (16 men; mean age 33.6 +/- standard deviation [SD] 10.6 years; epilepsy onset 14.8 +/- 10.6 years; mean duration 18.8 +/- 13.2 years; 23 left focus, 10 right focus). Anatomic regions drawn on structural MRI, based on the Wake Forest Pick Atlas, included Wernicke's area (WA), inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and hippocampus (HC). Laterality indices (LIs), and asymmetry indices (AIs), were calculated on coregistered fMRI and PET.
   Key Findings: Twelve patients had mesial temporal sclerosis (seven on the left), two patients had a tumor or malformation of cortical development (both left), one patient a right temporal cyst, and 18 patients had normal MRI (14 left). Decreasing relative left WA CBF correlated with decreased left IFG voxel activation and decreasing left IFG LI. However, CBF WA AI was not related to left WA voxel activation itself or WA LI. There was a weak positive correlation between absolute CBF and fMRI activation in left IFG, right IFG, and left WA. Patients with normal and abnormal MRI did not differ in fMRI activation or rCBF AIs.
   Significance: Reduced WA rCBF is associated with reduced fMRI activation in IFG but notWAitself, suggesting distributed network effects, but not impairment of underlying BOLD response. Hypoperfusion in TLE does not affect fMRI clinical value.
C1 [Appel, Shmuel; Duke, Elizabeth S.; Martinez, Ashley R.; Khan, Omar I.; Dustin, Irene M.; Reeves-Tyer, Patricia; Gaillard, William D.; Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
   [Appel, Shmuel; Khan, Omar I.; Sato, Susumu] NINDS, EEG Lab, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   [Duke, Elizabeth S.; Berl, Madison B.; Gaillard, William D.] Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC 20010 USA.
RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 7C-103, Bethesda, MD 20892 USA.
EM theodorw@ninds.nih.gov
FU NINDS NIH Division of Intramural Research
FX Supported by NINDS NIH Division of Intramural Research.
NR 42
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Z9 5
U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD APR
PY 2012
VL 53
IS 4
BP 631
EP 638
DI 10.1111/j.1528-1167.2012.03403.x
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 915ZG
UT WOS:000302065600011
PM 22332720
ER

PT J
AU Cabib, E
   Blanco, N
   Arroyo, J
AF Cabib, Enrico
   Blanco, Noelia
   Arroyo, Javier
TI Presence of a Large beta(1-3)Glucan Linked to Chitin at the
   Saccharomyces cerevisiae Mother-Bud Neck Suggests Involvement in
   Localized Growth Control
SO EUKARYOTIC CELL
LA English
DT Article
ID YEAST-CELL WALL; ONE-STEP PURIFICATION; BUDDING YEAST; CROSS-LINKING;
   ARCHITECTURE; PROTEIN; CYCLE; RING; CYTOKINESIS; SEPTINS
AB Previous results suggested that the chitin ring present at the yeast mother-bud neck, which is linked specifically to the nonreducing ends of beta(1-3) glucan, may help to suppress cell wall growth at the neck by competing with beta(1-6) glucan and thereby with mannoproteins for their attachment to the same sites. Here we explored whether the linkage of chitin to beta(1-3) glucan may also prevent the remodeling of this polysaccharide that would be necessary for cell wall growth. By a novel mild procedure, beta(1-3) glucan was isolated from cell walls, solubilized by carboxymethylation, and fractionated by size exclusion chromatography, giving rise to a very high-molecular-weight peak and to highly polydisperse material. The latter material, soluble in alkali, may correspond to glucan being remodeled, whereas the large-size fraction would be the final cross-linked structural product. In fact, the beta(1-3) glucan of buds, where growth occurs, is solubilized by alkali. A gas1 mutant with an expected defect in glucan elongation showed a large increase in the polydisperse fraction. By a procedure involving sodium hydroxide treatment, carboxymethylation, fractionation by affinity chromatography on wheat germ agglutinin-agarose, and fractionation by size chromatography on Sephacryl columns, it was shown that the beta(1-3) glucan attached to chitin consists mostly of high-molecular-weight material. Therefore, it appears that linkage to chitin results in a polysaccharide that cannot be further remodeled and does not contribute to growth at the neck. In the course of these experiments, the new finding was made that part of the chitin forms a noncovalent complex with beta(1-3) glucan.
C1 [Cabib, Enrico] NIDDK, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Biochem & Genet, Bethesda, MD USA.
   [Blanco, Noelia; Arroyo, Javier] Univ Complutense Madrid, Fac Farm, Dept Microbiol 2, Madrid, Spain.
RP Cabib, E (reprint author), NIDDK, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Biochem & Genet, Bethesda, MD USA.
EM enricoc@bdg10.niddk.nih.gov
RI Arroyo, Javier/E-9308-2016
OI Arroyo, Javier/0000-0002-1971-1721
FU National Institutes of Health (NIDDK); Ministerio de Ciencia e
   Innovacion [MICINN], Spain [BIO2010-22146, GR58/08, 920640]; Universidad
   Complutense de Madrid; European Science Foundation [06-RNP-132]; MICINN
   [BES-2008-003171]
FX This study was supported by a National Institutes of Health grant
   (Intramural Research Program, NIDDK). J.A. and N.B. were supported by
   projects BIO2010-22146 (Ministerio de Ciencia e Innovacion [MICINN],
   Spain) and GR58/08 (reference no. 920640; Universidad Complutense de
   Madrid) and the European Science Foundation Research Networking
   Programme (06-RNP-132). N.B. is the recipient of an FPI Ph.D. fellowship
   (BES-2008-003171) from MICINN.
NR 30
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Z9 9
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1535-9778
J9 EUKARYOT CELL
JI Eukaryot. Cell
PD APR
PY 2012
VL 11
IS 4
BP 388
EP 400
DI 10.1128/EC.05328-11
PG 13
WC Microbiology; Mycology
SC Microbiology; Mycology
GA 917ZT
UT WOS:000302219300002
PM 22366124
ER

PT J
AU Kemmerich, K
   Drechsler, M
   Weber, C
   Murphy, PM
   Soehnlein, O
AF Kemmerich, K.
   Drechsler, M.
   Weber, C.
   Murphy, P. M.
   Soehnlein, O.
TI Lack of Formyl-peptide receptor 1 reduces atherosclerotic lesion
   formation
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Meeting Abstract
C1 [Kemmerich, K.; Drechsler, M.; Weber, C.; Soehnlein, O.] Univ Munich, Inst Cardiovasc Prevent, Munich, Germany.
   [Murphy, P. M.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD APR
PY 2012
VL 42
SU 1
BP 22
EP 22
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 914WY
UT WOS:000301985000058
ER

PT J
AU Peng, F
   Tao, QF
   Wu, XM
   Dou, H
   Spencer, S
   Mang, CY
   Xu, L
   Sun, LL
   Zhao, Y
   Li, HB
   Zeng, S
   Liu, GM
   Hao, XJ
AF Peng, Fang
   Tao, Qiaofeng
   Wu, Xiumei
   Dou, Hui
   Spencer, Shawn
   Mang, Chaoyong
   Xu, Lu
   Sun, Lianli
   Zhao, Yu
   Li, Haibo
   Zeng, Su
   Liu, Guangming
   Hao, Xiaojiang
TI Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic
   compounds from fresh ginger
SO FITOTERAPIA
LA English
DT Article
DE Ginger phenolics; Antioxidant; Cytotoxicity; Neuroprotection;
   Hepatoprotectant; alpha-Glucosidase; QSAR
ID ZINGIBER-OFFICINALE ROSCOE; NEONATAL-RAT HEPATOCYTES; XANTHINE-OXIDASE;
   ALPINIA-OFFICINARUM; LIPID-PEROXIDATION; DIABETIC-RATS; IN-VITRO;
   HYDROGEN-PEROXIDE; CURCUMIN ANALOGS; OXIDATIVE STRESS
AB Twenty-nine phenolic compounds were isolated from the root bark of fresh (Yunnan) ginger and their structures fully characterized. Selected compounds were divided into structural categories and twelve compounds subjected to in-vitro assays including DPPH radical scavenging, xanthine-oxidase inhibition, monoamine oxidase inhibition, rat-brain homogenate lipid peroxidation, and rat pheochromocytoma PC12 cell and primary liver cell viability to determine their antioxidant and cytoprotective properties. Isolated compounds were also tested against nine human tumor cell lines to characterize anticancer potency. Several diarylheptanoids and epoxidic diarylheptanoids were effective DPPH radical scavengers and moderately effective at inhibiting xanthine oxidase. An enone-dione analog of 6-shogaol (compound 2) was isolated and identified to be most effective at protecting PC12 cells from H2O2-induced damage. Almost all tested compounds inhibited lipid peroxidation. Three compounds, 6-shogaol, 10-gingerol and an enone-diatylheptanoid analog of curcumin (compound 6) were identified to be cytotoxic in cell lines tested, with KB and HL60 cells most susceptible to 6-shogaol and the curcumin analog with IC50<10 mu M. QSAR analysis revealed cytotoxicity was related to compound lipophilicity and chemical reactivity. In conclusion, we observed distinct compounds in fresh ginger to have biological activities relevant in diseases associated with reactive oxygen species. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Peng, Fang; Wu, Xiumei; Mang, Chaoyong; Xu, Lu; Zhao, Yu; Li, Haibo; Liu, Guangming] Dali Univ, Coll Pharmaceut Sci, Key Lab Yunnan Insect Drug R&D, Dali 671000, Peoples R China.
   [Tao, Qiaofeng; Dou, Hui; Sun, Lianli; Li, Haibo; Zeng, Su] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China.
   [Spencer, Shawn] NCI, Clin Pharmacol Program, Ctr Canc Res, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Hao, Xiaojiang] Key Lab Chem & Nat Prod Guizhou Prov, Guiyang 550002, Peoples R China.
   [Hao, Xiaojiang] Chinese Acad Sci, Guiyang 550002, Peoples R China.
RP Zhao, Y (reprint author), Dali Univ, Coll Pharmaceut Sci, Key Lab Yunnan Insect Drug R&D, Wanhua Rd, Dali 671000, Peoples R China.
EM dryuzhao@126.com; zengsu@zju.edu.cn
FU High Rank Talents Invited Project [2009CI121]; Yunnan Science and
   Technology Department (Modernization of Chinese Technology Industry Base
   Construction in Yunnan Province) [2008IF012]; Foundation for the Science
   and Technology Innovation Team of Yunnan Universities [11]; Zhejiang
   University
FX The authors thank the High Rank Talents Invited Project (No. 2009CI121),
   Key Industrialization Innovation Project of Yunnan Science and
   Technology Department (Modernization of Chinese Technology Industry Base
   Construction in Yunnan Province, No. 2008IF012), Foundation for the
   Science and Technology Innovation Team of Yunnan Universities
   (2010-No.11) and 985 fund of Zhejiang University for the financial
   supports.
NR 92
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Z9 29
U1 5
U2 45
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0367-326X
J9 FITOTERAPIA
JI Fitoterapia
PD APR
PY 2012
VL 83
IS 3
BP 568
EP 585
DI 10.1016/j.fitote.2011.12.028
PG 18
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 916NB
UT WOS:000302109400020
PM 22248534
ER

PT J
AU Lee, TL
   Raygada, MJ
   Rennert, OM
AF Lee, Tin-Lap
   Raygada, Margarita J.
   Rennert, Owen M.
TI Integrative gene network analysis provides novel regulatory
   relationships, genetic contributions and susceptible targets in autism
   spectrum disorders
SO GENE
LA English
DT Article
DE Autism; Genetics; Genomics; CNV; Systems biology
ID COPY NUMBER VARIATION; CHILDREN; ASSOCIATION; VARIANTS; EXPRESSION;
   REVEALS; 5P14.1; COMMON; BRAIN
AB Autism spectrum disorders (ASDs) are a group of diseases exhibiting impairment in social drive, communication/language skills and stereotyped behaviors. Though an increased number of candidate genes and molecular interactions have been identified by various approaches, the pathogenesis remains elusive. Based on clinical observations, data from accessible GWAS and expression datasets we identified ASDs gene candidates. Integrative gene network and a novel CNV-centric Node Network (CNN) analysis method highlighted ASDs-associated key elements and biological processes. Functional analysis identified neurological functions including synaptic cholinergic receptor (CHRNA) families, dopamine receptor (DRD2), and correlations between social behavior and oxytocin related pathways. CNN analysis of genome-wide genetic and expression data identified inheritance-related clusters related to PTEN/TSC1/FMR1 and mTor/PI3K regulation. Integrative analysis identified potential regulators of networks, specifically TNF and beta-estradiol, suggesting a potential central role in ASDs. Our data provide information on potential disease mechanisms. and key regulators that may generate novel postulations, and diagnostic molecular biomarkers. Published by Elsevier B.V.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Gen, Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Lee, Tin-Lap] Chinese Univ Hong Kong, Sch Biomed Sci, Sha Tin, Hong Kong, Peoples R China.
   [Lee, Tin-Lap] Chinese Univ Hong Kong, Sch Biomed Sci, Dev & Endocrinol Program, Hong Kong, Hong Kong, Peoples R China.
RP Rennert, OM (reprint author), 49 Convent Dr Room 2A06,MSC 4429, Bethesda, MD 20892 USA.
EM leetl@mail.nih.gov; RaygadaM@mail.nih.gov; rennerto@mail.nih.gov
RI Lee, Tin-Lap/A-7853-2009
OI Lee, Tin-Lap/0000-0002-6654-0988
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health
FX This work was supported by the Intramural Research Program of Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health.
NR 36
TC 18
Z9 19
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD APR 1
PY 2012
VL 496
IS 2
BP 88
EP 96
DI 10.1016/j.gene.2012.01.020
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 915CE
UT WOS:000301999700003
PM 22306264
ER

PT J
AU Nogales, FF
   Goyenaga, P
   Preda, O
   Nicolae, A
   Vieites, B
   Ruiz-Marcellan, MC
   Pedrosa, A
   Merino, MJ
AF Nogales, Francisco F.
   Goyenaga, Pablo
   Preda, Ovidiu
   Nicolae, Alina
   Vieites, Begona
   Carmen Ruiz-Marcellan, Maria
   Pedrosa, Alberto
   Merino, Maria J.
TI An analysis of five clear cell papillary cystadenomas of mesosalpinx and
   broad ligament: four associated with von Hippel-Lindau disease and one
   aggressive sporadic type
SO HISTOPATHOLOGY
LA English
DT Article
DE clear cell papillary cystadenoma; clear cell papillary renal cell
   carcinoma; mesonephric rests; mesosalpinx; sporadic; von Hippel-Lindau
   disease
ID TUMOR; CARCINOMA; EPIDIDYMIS; ADENOCARCINOMA; EXPRESSION; DIAGNOSIS;
   MUTATION; TISSUES; CERVIX; TRACT
AB Aims: Clear cell papillary cystadenoma (CCPC) is associated with von Hippel- Lindau disease (VHLD), but rarely involves mesosalpinx and broad ligament (M/BL). This study provides new data about its behaviour and immunophenotype.
   Methods and results: We performed an analysis of four benign cases of CCPC of M/BL with either characteristic clinical features or genetic markers [loss of heterozygosity (LOH)] of VHLD in patients ranging from 24 to 36 years and a sporadic case in a 52- yearold presenting with peritoneal metastases. All CCPCs were papillary but had solid and tubular areas. Haemorrhage, thrombosis and scarring were constant features and related to an unusual pattern of subepithelial vascularity. All clear or oxyphilic cells coexpressed cytokeratin 7 (CK7), CAM5.2 and vimentin, with strong apical CD10 and nuclear paired box gene 2 (PAX2) immunoreactivity. Three cases also showed positivity for VHL40, epithelial membrane antigen (EMA), Wilms' tumour suppressor gene (WT-1) and cancer antigen 125 (CA125) but only one expressed renal cell carcinoma (RCC) antigen. Vascular plexus overexpressed nuclear and cytoplasmic WT-1.
   Conclusion: The VHLD-associated cases appeared to be benign, but the sporadic case exhibited a low malignant potential. CCPCs show histological and immunophenotypical similarities with the recently reported clear cell papillary RCC, although the previously unreported apical CD10 and nuclear PAX2 expression may be related to their mesonephric origin. CCPC has a distinctive sub-epithelial vascular pattern that is consistent with its pathogenesis.
C1 [Nogales, Francisco F.; Goyenaga, Pablo; Preda, Ovidiu; Nicolae, Alina] Hosp Univ San Cecilio, Dept Pathol, Granada 18012, Spain.
   [Vieites, Begona] Hosp Univ Virgen Rocio, Seville, Spain.
   [Carmen Ruiz-Marcellan, Maria] Hosp Gen Valle Hebron, Barcelona, Spain.
   [Pedrosa, Alberto] Complejo Hosp Univ, Vigo, Spain.
   NCI, Translat Surg Pathol Sect, Bethesda, MD 20892 USA.
RP Nogales, FF (reprint author), Hosp Univ San Cecilio, Dept Pathol, Av Madrid 11, Granada 18012, Spain.
EM fnogales@ugr.es
NR 26
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0309-0167
J9 HISTOPATHOLOGY
JI Histopathology
PD APR
PY 2012
VL 60
IS 5
BP 748
EP 757
DI 10.1111/j.1365-2559.2011.04151.x
PG 10
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 915GO
UT WOS:000302012300007
PM 22296276
ER

PT J
AU Zhang, MF
   Liang, LM
   Morar, N
   Dixon, AL
   Lathrop, GM
   Ding, J
   Moffatt, MF
   Cookson, WOC
   Kraft, P
   Qureshi, AA
   Han, JL
AF Zhang, Mingfeng
   Liang, Liming
   Morar, Nilesh
   Dixon, Anna L.
   Lathrop, G. Mark
   Ding, Jun
   Moffatt, Miriam F.
   Cookson, William O. C.
   Kraft, Peter
   Qureshi, Abrar A.
   Han, Jiali
TI Integrating pathway analysis and genetics of gene expression for
   genome-wide association study of basal cell carcinoma
SO HUMAN GENETICS
LA English
DT Article
ID RENAL-TRANSPLANT RECIPIENTS; SKIN-CANCER; MOLECULAR TARGETS; COMPLEX
   DISEASES; COMMON VARIANTS; HLA ANTIGENS; RISK; SUSCEPTIBILITY; LOCI;
   INTERLEUKIN-6
AB Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value < 0.05 and false discovery rate (FDR) < 0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.
C1 [Zhang, Mingfeng; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Sch Med, Brigham & Womens Hosp, Clin Res Program,Dept Dermatol, Boston, MA 02115 USA.
   [Zhang, Mingfeng] Nanjing Med Univ, Dept Epidemiol & Biostat, Ctr Canc, Nanjing, Jiangsu, Peoples R China.
   [Liang, Liming; Kraft, Peter; Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Liang, Liming; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Morar, Nilesh; Dixon, Anna L.; Moffatt, Miriam F.; Cookson, William O. C.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
   [Lathrop, G. Mark] Ctr Natl Genotypage, Evry, France.
   [Ding, Jun] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
   [Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA.
RP Han, JL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Clin Res Program,Dept Dermatol, 181 Longwood Ave,5th Floor, Boston, MA 02115 USA.
EM jiali.han@channing.harvard.edu
RI Ding, Jun/G-3918-2011
FU NIH [CA87969, CA055075, CA49449]
FX The authors thank Dr. David Hunter, Dr. Frank B. Hu, and Dr. Eric B.
   Rimm for their work on the five GWAS sets (BC_NHS, T2D_NHS, T2D_HPFS
   CHD_NHS and CHD_HPFS). They thank Dr. Hongmei Nan for her work in BCC
   GWAS dataset construction and Dr. Mousheng Xu for his technical support
   in programing. They thank the participants in the Nurses' Health Study
   and the Health Professionals Follow-Up Study for their dedication and
   commitment. They also thank the following state cancer registries for
   their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA,
   ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX,
   VA, WA, WY. The NHS and HPFS cohorts are supported by NIH grants
   CA87969, CA055075, and CA49449.
NR 55
TC 14
Z9 15
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD APR
PY 2012
VL 131
IS 4
BP 615
EP 623
DI 10.1007/s00439-011-1107-5
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 911NX
UT WOS:000301725900007
PM 22006220
ER

PT J
AU Crosslin, DR
   McDavid, A
   Weston, N
   Nelson, SC
   Zheng, XW
   Hart, E
   de Andrade, M
   Kullo, IJ
   McCarty, CA
   Doheny, KF
   Pugh, E
   Kho, A
   Hayes, MG
   Pretel, S
   Saip, A
   Ritchie, MD
   Crawford, DC
   Crane, PK
   Newton, K
   Li, RL
   Mirel, DB
   Crenshaw, A
   Larson, EB
   Carlson, CS
   Jarvik, GP
AF Crosslin, David R.
   McDavid, Andrew
   Weston, Noah
   Nelson, Sarah C.
   Zheng, Xiuwen
   Hart, Eugene
   de Andrade, Mariza
   Kullo, Iftikhar J.
   McCarty, Catherine A.
   Doheny, Kimberly F.
   Pugh, Elizabeth
   Kho, Abel
   Hayes, M. Geoffrey
   Pretel, Stephanie
   Saip, Alexander
   Ritchie, Marylyn D.
   Crawford, Dana C.
   Crane, Paul K.
   Newton, Katherine
   Li, Rongling
   Mirel, Daniel B.
   Crenshaw, Andrew
   Larson, Eric B.
   Carlson, Chris S.
   Jarvik, Gail P.
CA Med Records Genomics eMERGE
TI Genetic variants associated with the white blood cell count in 13,923
   subjects in the eMERGE Network
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; LARGE-SCALE; ASTHMA;
   RISK; LOCI; SUSCEPTIBILITY; POPULATION; CONSORTIUM; COMMON
AB White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association (p value = 6.71e-55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy-/-). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA, (2) MED24, and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn's disease.
C1 [Crosslin, David R.; Nelson, Sarah C.; Zheng, Xiuwen] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
   [McDavid, Andrew; Carlson, Chris S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [Weston, Noah; Hart, Eugene; Newton, Katherine; Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA 98124 USA.
   [de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
   [Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA.
   [McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN 55805 USA.
   [Doheny, Kimberly F.; Pugh, Elizabeth] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21224 USA.
   [Kho, Abel] Northwestern Univ, Div Gen Internal Med, Chicago, IL 60611 USA.
   [Kho, Abel] Northwestern Univ, Div Hlth & Biomed Informat, Chicago, IL 60611 USA.
   [Hayes, M. Geoffrey] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
   [Pretel, Stephanie] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Saip, Alexander] Vanderbilt Univ, Vanderbilt Inst Clin & Translat Res, Nashville, TN 37232 USA.
   [Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
   [Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
   [Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Crane, Paul K.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA.
   [Li, Rongling] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
   [Mirel, Daniel B.; Crenshaw, Andrew] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
RP Crosslin, DR (reprint author), Univ Washington, Dept Biostat, Floor 15,UW Tower,Campus Mail Box 359461, Seattle, WA 98195 USA.
EM davidcr@u.washington.edu
RI Ritchie, Marylyn/C-1114-2012; Crawford, Dana/C-1054-2012; Crane,
   Paul/C-8623-2014; Jarvik, Gail/N-6476-2014; 
OI McDavid, Andrew/0000-0002-6581-1213; Zheng, Xiuwen/0000-0002-1390-0708;
   Jarvik, Gail/0000-0002-6710-8708; Crane, Paul/0000-0003-4278-7465;
   Nelson, Sarah/0000-0002-2109-6465
FU National Human Genome Research Institute (NHGRI), National Institutes of
   Health (NIH), Bethesda, MD, USA [HG004610, AG06781, HG04599, HG004608,
   HG004609, HG004438, HG004424, HG004603]; University of Washington's
   Northwest Institute of Genetic Medicine [265508]
FX The authors are grateful to all the participants in the eMERGE study.
   They also acknowledge Xiuwen Zheng and the fast PCA program to make
   principal component analysis on this many subjects achievable. This
   study was supported by the following U01 grants from the National Human
   Genome Research Institute (NHGRI), a component of the National
   Institutes of Health (NIH), Bethesda, MD, USA: (1) HG004610, AG06781
   (Group Health Cooperative), (2) HG04599 (Mayo Clinic), (3) HG004608
   (Marsh-field Clinic), (4) HG004609 (Northwestern University), (5)
   HG004438 (CIDR), (6) HG004424 (BROAD), and (7) HG004603 (Vanderbilt
   University). Additional support was provided by the University of
   Washington's Northwest Institute of Genetic Medicine from Washington
   State Life Sciences Discovery funds (Grant 265508).
NR 35
TC 52
Z9 52
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD APR
PY 2012
VL 131
IS 4
BP 639
EP 652
DI 10.1007/s00439-011-1103-9
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 911NX
UT WOS:000301725900009
PM 22037903
ER

PT J
AU Mendonca, VRR
   Luz, NF
   Santos, NJG
   Borges, VM
   Goncalves, MS
   Andrade, BB
   Barral-Netto, M
AF Mendonca, Vitor R. R.
   Luz, Nivea F.
   Santos, Nadja J. G.
   Borges, Valeria M.
   Goncalves, Marilda S.
   Andrade, Bruno B.
   Barral-Netto, Manoel
TI Association between the Haptoglobin and Heme Oxygenase 1 Genetic
   Profiles and Soluble CD163 in Susceptibility to and Severity of Human
   Malaria
SO INFECTION AND IMMUNITY
LA English
DT Article
ID HEMOGLOBIN SCAVENGER RECEPTOR; PLASMODIUM-FALCIPARUM MALARIA;
   MICROSATELLITE POLYMORPHISM; HUMAN MONOCYTES; RISK-FACTOR;
   HEMOPHAGOCYTIC SYNDROME; RHEUMATOID-ARTHRITIS; BRAZILIAN AMAZON;
   CEREBRAL MALARIA; ELEVATED LEVELS
AB Intravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria.
C1 [Mendonca, Vitor R. R.; Luz, Nivea F.; Santos, Nadja J. G.; Borges, Valeria M.; Goncalves, Marilda S.; Barral-Netto, Manoel] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil.
   [Mendonca, Vitor R. R.; Luz, Nivea F.; Borges, Valeria M.; Barral-Netto, Manoel] Univ Fed Bahia, Fac Med, Salvador, BA, Brazil.
   [Borges, Valeria M.; Barral-Netto, Manoel] Inst Nacl Ciencia & Tecnol Invest Imunol Iii INCT, Sao Paulo, Brazil.
   [Goncalves, Marilda S.] Univ Fed Bahia, Fac Farm, Salvador, BA, Brazil.
   [Andrade, Bruno B.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Barral-Netto, M (reprint author), Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil.
EM mbarral@bahia.fiocruz.br
RI Andrade, Bruno/J-9111-2012; Barral Netto, Manoel/B-3904-2009;
   Imunologia, Inct/I-2124-2013; Goncalves, Marilda/B-5904-2014; Borges,
   Valeria/G-2009-2014; 
OI Andrade, Bruno/0000-0001-6833-3811; Barral Netto,
   Manoel/0000-0002-5823-7903; Borges, Valeria/0000-0002-2775-5409
NR 70
TC 26
Z9 26
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2012
VL 80
IS 4
BP 1445
EP 1454
DI 10.1128/IAI.05933-11
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 914EL
UT WOS:000301931900016
PM 22290142
ER

PT J
AU Tutterrow, YL
   Avril, M
   Singh, K
   Long, CA
   Leke, RJ
   Sama, G
   Salanti, A
   Smith, JD
   Leke, RGF
   Taylor, DW
AF Tutterrow, Yeung L.
   Avril, Marion
   Singh, Kavita
   Long, Carole A.
   Leke, Robert J.
   Sama, Grace
   Salanti, Ali
   Smith, Joseph D.
   Leke, Rose G. F.
   Taylor, Diane W.
TI High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA
   Correlate with the Absence of Placental Malaria in Cameroonian Women
   Living in an Area of High Plasmodium falciparum Transmission
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PREGNANCY-ASSOCIATED MALARIA; CHONDROITIN-SULFATE-A; LOW-BIRTH-WEIGHT;
   ADHESION-INHIBITORY ANTIBODIES; VACCINE CANDIDATE VAR2CSA; VARIANT
   SURFACE-ANTIGENS; INFECTED ERYTHROCYTES; INFANT-MORTALITY; PROTEIN
   VAR2CSA; VAR GENES
AB Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity.
C1 [Tutterrow, Yeung L.; Taylor, Diane W.] Univ Hawaii, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol, Honolulu, HI 96822 USA.
   [Avril, Marion; Smith, Joseph D.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
   [Singh, Kavita] NIAID, Struct Biol Sect, Res Technol Branch, NIH, Rockville, MD USA.
   [Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
   [Leke, Robert J.; Sama, Grace; Leke, Rose G. F.] Univ Yaounde I, Fac Med & Biomed Res, Ctr Biotechnol, Yaounde, Cameroon.
   [Salanti, Ali] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Ctr Med Parasitol, Copenhagen, Denmark.
   [Salanti, Ali] Copenhagen Univ Hosp, Rigshosp, Dept Infect Dis, Copenhagen, Denmark.
RP Taylor, DW (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol, Honolulu, HI 96822 USA.
EM dwtaylor@hawaii.edu
FU Malaria Research Team at the Biotechnology Center, University of Yaounde
   I, Cameroon; NIAID, NIH [UO1AI43888, RO1AI071160, U19AI089688]; Division
   of Intramural Research, NIAID, NIH; STOPPAM [200889]
FX We acknowledge the support of the Malaria Research Team at the
   Biotechnology Center, University of Yaounde I, Cameroon, for their
   outstanding work. A special thank you goes to the women and their
   families who participated in the studies. We also thank Ian Pagano,
   Cancer Research Center, University of Hawaii, for statistical support
   and Kazutoyo Miura for helpful suggestions in manuscript preparation.;
   The work was supported by grants UO1AI43888 and RO1AI071160 (D.W.T. and
   R.G.F.L.) and U19AI089688 (J.D.S.) from NIAID, NIH, by the intramural
   research program of the Division of Intramural Research, NIAID, NIH
   (K.S. and C.A.L.), and by FP7/2007-2013 under grant agreement no. 200889
   (STOPPAM) (A.S.).
NR 56
TC 32
Z9 32
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2012
VL 80
IS 4
BP 1479
EP 1490
DI 10.1128/IAI.00071-12
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 914EL
UT WOS:000301931900019
PM 22331427
ER

PT J
AU Clark, EH
   Silva, CJ
   Weiss, GE
   Li, SP
   Padilla, C
   Crompton, PD
   Hernandez, JN
   Branch, OH
AF Clark, Eva H.
   Silva, Claudia J.
   Weiss, Greta E.
   Li, Shanping
   Padilla, Carlos
   Crompton, Peter D.
   Hernandez, Jean N.
   Branch, OraLee H.
TI Plasmodium falciparum Malaria in the Peruvian Amazon, a Region of Low
   Transmission, Is Associated with Immunologic Memory
SO INFECTION AND IMMUNITY
LA English
DT Article
ID MEROZOITE SURFACE PROTEIN-1; C-TERMINAL FRAGMENT; BAY COHORT PROJECT;
   ANTIBODY-RESPONSES; CLINICAL IMMUNITY; CHILDREN; ANTIGEN; INFECTIONS;
   PARASITE; INVASION
AB The development of clinical immunity to Plasmodium falciparum malaria is thought to require years of parasite exposure, a delay often attributed to difficulties in developing protective antibody levels. In this study, we evaluated several P. falciparum vaccine candidate antigens, including apical membrane antigen 1 (AMA-1), circumsporozoite protein (CSP), erythrocyte binding antigen 175 (EBA-175), and the 19-kDa region of merozoite surface protein 1 (MSP1(19)). After observing a more robust antibody response to MSP1(19), we evaluated the magnitude and longevity of IgG responses specific to this antigen in Peruvian adults and children before, during, and after P. falciparum infection. In this low-transmission region, even one reported prior infection was sufficient to produce a positive anti-MSP1(19) IgG response for > 5 months in the absence of reinfection. We also observed an expansion of the total plasmablast (CD19(+) CD27(+) CD38(high)) population in the majority of individuals shortly after infection and detected MSP1-specific memory B cells in a subset of individuals at various postinfection time points. This evidence supports our hypothesis that effective antimalaria humoral immunity can develop in low-transmission regions.
C1 [Clark, Eva H.; Branch, OraLee H.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
   [Silva, Claudia J.; Hernandez, Jean N.] Univ Nacl Amazonia Peruana, Lab Invest Prod Nat Antiparasitarios Amazonia, Iquitos, Peru.
   [Weiss, Greta E.; Li, Shanping; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
   [Padilla, Carlos] Inst Nacl Salud, Lab Biotecnol & Biol Mol, Lima, Peru.
   [Branch, OraLee H.] NYU, Sch Med, Dept Med Parasitol, New York, NY USA.
RP Branch, OH (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
EM Oralee.Branch@nyumc.org
RI Crompton, Peter/N-1130-2016
FU National Institutes of Health/National Institute of Allergy and
   Infectious Disease [AI064831]
FX This study was supported by R01 grant AI064831 from the National
   Institutes of Health/National Institute of Allergy and Infectious
   Disease (from 2005 to the present).
NR 43
TC 24
Z9 24
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2012
VL 80
IS 4
BP 1583
EP 1592
DI 10.1128/IAI.05961-11
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 914EL
UT WOS:000301931900030
PM 22252876
ER

PT J
AU Zanella, A
   Cressoni, M
   Epp, M
   Hoffmann, V
   Stylianou, M
   Kolobow, T
AF Zanella, Alberto
   Cressoni, Massimo
   Epp, Myra
   Hoffmann, Viktoria
   Stylianou, Mario
   Kolobow, Theodor
TI Effects of tracheal orientation on development of ventilator-associated
   pneumonia: an experimental study
SO INTENSIVE CARE MEDICINE
LA English
DT Article
DE Mechanical ventilation; Pneumonia; Ventilator-associated pneumonia;
   Semirecumbent position; Intubation; Postural drainage; Pulmonary; Pigs;
   Nosocomial infections; Respiration; Artificial/adverse effects;
   Intratracheal/adverse effects; Respiratory tract infections/prevention
   and control; Aspiration/prevention and control
ID CARE-UNIT PATIENTS; NOSOCOMIAL PNEUMONIA; RESPIRATORY-TRACT; MECHANICAL
   VENTILATION; SEMIRECUMBENT POSITION; BACTERIAL-COLONIZATION; PULMONARY
   ASPIRATION; ENDOTRACHEAL-TUBE; BODY POSITION; PATHOGENESIS
AB Orientation of the trachea and tracheal tube below horizontal may prevent aspiration of oropharyngeal secretions into the lungs, which is a pivotal pathway in the pathogenesis of ventilator-associated pneumonia (VAP). The incidence of VAP was evaluated in swine with orientation of trachea and tracheal tube above horizontal (model of semirecumbent position, currently recommended in patients) and below horizontal.
   Twenty-six mini-pigs were randomized into four groups: (A) eight mechanically ventilated with orientation of trachea 45A degrees above horizontal for 72 h. In the remaining groups (B, C, D) the trachea was oriented 10A degrees below horizontal, with (B) six mechanically ventilated for 72 h, (C) six mechanically ventilated for 72 h with enteral feeding, and (D) six mechanically ventilated for 168 h with enteral feeding. At the end of the study period, all pigs were sacrificed and the clinical diagnosis of VAP was microbiologically evaluated. No antibiotics were administered.
   All eight pigs kept orientated with the trachea 45A degrees above horizontal developed VAP and respiratory failure (PaO2/FiO2 = 132 +/- A 139 mmHg) with a median of 5.5 pulmonary lobes out of 6 colonized with average colonization of 9.3 x 10(7) CFU/g. None of the 18 pigs kept oriented with the trachea below horizontal developed VAP; 16 had sterile lungs, while 2, ventilated for 7 days, developed a low level of colonization.
   Orientation of the trachea above horizontal was uniformly associated with VAP and respiratory failure; positioning the trachea below horizontal consistently prevented development of VAP.
C1 [Cressoni, Massimo] Univ Milan, Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dipartimento Anestesiol Terapia Intens & Sci Derm, Milan, Italy.
   [Zanella, Alberto; Cressoni, Massimo; Epp, Myra; Kolobow, Theodor] NHLBI, NIH, Sect Pulm & Cardiac Assist Devices, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA.
   [Zanella, Alberto] Milano Bicocca Univ, San Gerardo Hosp, Dept Expt Med, Monza, Italy.
   [Hoffmann, Viktoria] NIH, Div Vet Res, Bethesda, MD 20892 USA.
   [Stylianou, Mario] NHLBI, NIH, Off Biostat Res, Bethesda, MD 20892 USA.
   [Cressoni, Massimo] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dipartimento Anestesia Rianimaz Intens & Subinten, Milan, Italy.
RP Cressoni, M (reprint author), Univ Milan, Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Dipartimento Anestesiol Terapia Intens & Sci Derm, Milan, Italy.
EM mcressoni@hotmail.com
RI Cressoni, Massimo/B-7315-2017; 
OI Cressoni, Massimo/0000-0002-0089-2905; zanella,
   Alberto/0000-0002-2967-2527
FU Intramural NIH HHS
NR 25
TC 15
Z9 16
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
J9 INTENS CARE MED
JI Intensive Care Med.
PD APR
PY 2012
VL 38
IS 4
BP 677
EP 685
DI 10.1007/s00134-012-2495-2
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA 912EQ
UT WOS:000301777900018
PM 22349422
ER

PT J
AU Guiard, BP
   El Mansari, M
   Murphy, DL
   Blier, P
AF Guiard, Bruno P.
   El Mansari, Mostafa
   Murphy, Dennis L.
   Blier, Pierre
TI Altered response to the selective serotonin reuptake inhibitor
   escitalopram in mice heterozygous for the serotonin transporter: an
   electrophysiological and neurochemical study
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Depression; electrophysiology; escitalopram; microdialysis; SERT
ID MAJOR DEPRESSIVE DISORDER; GENE REGULATORY REGION; ANTIDEPRESSANT
   RESPONSE; KNOCKOUT MICE; FUNCTIONAL POLYMORPHISM; CLINICAL-RESPONSE;
   5-HT1A RECEPTORS; PROMOTER REGION; DORSAL RAPHE; HUMAN BRAIN
AB A serotonin (5-HT) transporter (5-HTT; SERT) polymorphism has been associated with depressive states and poor responses to selective serotonin reuptake inhibitors (SSRIs). Given the similar attenuation of SERT activity in SERT+/- mice and in humans with short allele(s) of SERT in its promoter region, it is conceivable that SERT+/- mice offer an adequate model to mimic the human subpopulation with respect to their altered response to SSRIs. This study investigated the effects of the most selective SSRI escitalopram, in heterozygous SERT+/- mice using a combined electrophysiological and neurochemical approach. Results indicated that administration of escitalopram for 2 d resulted in a 72% and 63% decrease in dorsal raphe 5-HT neuronal firing rate in SERT+/+ and SERT+/- mice, respectively. In contrast, administration of escitalopram for 21 d produced a gradual recovery of 5-HT neuronal firing rate to basal level in SERT+/+, but not in SERT+/- mice. In the hippocampus, microdialysis revealed that sustained administration of escitalopram produced a greater increase in extracellular 5-HT ([ 5-HT](ext)) outflow in SERT+/- than in the wild-types with or without a washout of the SSRI. Nevertheless, the ability of microiontophoretically applied 5-HT to inhibit the firing rate of CA3 pyramidal neurons was not different between SERT+/+ and SERT+/- mice given escitalopram for 21 d. The data indicate that the poor response to SSRIs of depressive patients with short allele(s) of SERT is not attributable to a lesser increase in 5-HT transmission in the hippocampus.
C1 [Guiard, Bruno P.; El Mansari, Mostafa; Blier, Pierre] Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON K1Z 7K4, Canada.
   [Guiard, Bruno P.] Univ Paris 11, Fac Pharm, EA3544, Neuropharmacol Lab, F-92290 Chatenay Malabry, France.
   [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
RP Blier, P (reprint author), Univ Ottawa, Mental Hlth Res Inst, 1145 Carling Ave, Ottawa, ON K1Z 7K4, Canada.
EM pierre.blier@rohcg.on.ca
RI Guiard, Bruno/A-3955-2016
FU Lundbeck
FX This work was funded in part by Lundbeck. We acknowledge Dr A. M.
   Gardier for assistance with microdialysis experiments.
NR 60
TC 6
Z9 6
U1 1
U2 8
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD APR
PY 2012
VL 15
IS 3
BP 349
EP 361
DI 10.1017/S1461145711000484
PG 13
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 915JQ
UT WOS:000302020900006
PM 21439106
ER

PT J
AU Mirabello, L
   Sun, C
   Ghosh, A
   Rodriguez, AC
   Schiffman, M
   Wentzensen, N
   Hildesheim, A
   Herrero, R
   Wacholder, S
   Lorincz, A
   Burk, RD
AF Mirabello, Lisa
   Sun, Chang
   Ghosh, Arpita
   Rodriguez, Ana C.
   Schiffman, Mark
   Wentzensen, Nicolas
   Hildesheim, Allan
   Herrero, Rolando
   Wacholder, Sholom
   Lorincz, Attila
   Burk, Robert D.
TI Methylation of Human Papillomavirus Type 16 Genome and Risk of Cervical
   Precancer in a Costa Rican Population
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID L1 GENE METHYLATION; EPSTEIN-BARR-VIRUS; 16 E6 GENE; DNA METHYLATION;
   INTRAEPITHELIAL NEOPLASIA; CARCINOGENIC PROGRESSION; EPIGENETIC
   MECHANISMS; NATURAL-HISTORY; CPG METHYLATION; LIFE-CYCLE
AB Background Previous studies have suggested an association between human papillomavirus type 16 (HPV16) genome methylation and cervical intraepithelial neoplasia grade 3 (CIN3) (ie, cervical precancer) and cancer, but the results have been inconsistent.
   Methods We designed a case-control study within a large prospective cohort of women who underwent multiple screenings for cervical cancer in Guanacaste, Costa Rica. Diagnostic specimens were collected at the time of CIN3 diagnosis (n = 30 case subjects) and persistent HPV16 infection (persistence; n = 35 case subjects), prediagnostic specimens at the first HPV16-positive screening visit (n = 20 CIN3 case subjects; n = 35 persistence case subjects), and control specimens from women with infection clearance within 2 years (n = 34 control subjects). DNA extracted from specimens (cervical cells) was analyzed for methylation levels at 67 CpG sites throughout the HPV16 genome using pyrosequencing. Benjamini-Hochberg method was used to account for multiple testing. Associations between methylation levels and risk of CIN3 or persistence were assessed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
   Results Increased methylation in diagnostic vs control specimens at nine CpG sites, three in each L1, L2, and E2/E4 genomic regions, was associated with an increased risk of CIN3 (third tertile [high] vs first and second tertiles combined [low], OR = 3.29 [95% CI = 1.16 to 9.34] to 11.12 [95% CI = 2.29 to 76.80]) and persistence. High methylation at three of these CpG sites was associated with a much higher risk when combined compared with low methylation at these sites (OR = 52, 95% CI = 4.0 to 670). In prediagnostic vs control specimens, increased methylation at a CpG site (nucleotide position 4261) in L2 was associated with an increased risk of CIN3.
   Conclusion In this HPV16-infected cohort, increased methylation of CpG sites within the HPV16 genome before diagnosis and at the time of diagnosis was associated with cervical precancer. J Natl Cancer Inst 2012; 104: 556-565
C1 [Mirabello, Lisa] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20892 USA.
   [Sun, Chang; Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
   [Rodriguez, Ana C.; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
   [Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
   [Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
   [Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10461 USA.
   [Lorincz, Attila] Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, London, England.
RP Mirabello, L (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,EPS 7101, Rockville, MD 20892 USA.
EM mirabellol@mail.nih.gov; robert.burk@einstein.yu.edu
RI perumal, murugiah/D-1565-2012; Sun, Chang/I-6326-2012; Hildesheim,
   Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Institutes of Health (NIH), National Cancer Institute
   [5U01CA078527]; Division of Cancer Epidemiology and Genetics; NIH
   [AI-51519]; Einstein Cancer Research Center [P30CA013330]
FX This work was supported in part by the Intramural Research Program of
   the National Institutes of Health (NIH), National Cancer Institute
   (5U01CA078527 to RDB); Division of Cancer Epidemiology and Genetics
   Intramural Research Award (to LM) and through use of core facilities
   (CS, RDB) of the Einstein-Montefiore Center for AIDS funded by the NIH
   (AI-51519) and the Einstein Cancer Research Center (P30CA013330).
NR 50
TC 40
Z9 43
U1 2
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD APR
PY 2012
VL 104
IS 7
BP 556
EP 565
DI 10.1093/jnci/djs135
PG 10
WC Oncology
SC Oncology
GA 919AO
UT WOS:000302293200011
PM 22448030
ER

PT J
AU Sun, YC
   Guo, XP
   Hinnebusch, BJ
   Darby, C
AF Sun, Yi-Cheng
   Guo, Xiao-Peng
   Hinnebusch, B. Joseph
   Darby, Creg
TI The Yersinia pestis Rcs Phosphorelay Inhibits Biofilm Formation by
   Repressing Transcription of the Diguanylate Cyclase Gene hmsT
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID STORAGE HMS(+) PHENOTYPE; ESCHERICHIA-COLI; CAENORHABDITIS-ELEGANS;
   ACETOBACTER-XYLINUM; CELLULOSE SYNTHESIS; FLEA VECTOR; PLAGUE;
   PSEUDOTUBERCULOSIS; SYSTEM; PATHOGENESIS
AB Yersinia pestis, which causes bubonic plague, forms biofilms in fleas, its insect vectors, as a means to enhance transmission. Biofilm development is positively regulated by hmsT, encoding a diguanylate cyclase that synthesizes the bacterial second messenger cyclic-di-GMP. Biofilm development is negatively regulated by the Rcs phosphorelay signal transduction system. In this study, we show that Rcs-negative regulation is accomplished by repressing transcription of hmsT.
C1 [Sun, Yi-Cheng; Guo, Xiao-Peng] Chinese Acad Med Sci, MOH Key Lab Syst Biol Pathogens, Inst Pathogen Biol, Beijing 100730, Peoples R China.
   [Sun, Yi-Cheng; Guo, Xiao-Peng] Peking Union Med Coll, Beijing 100021, Peoples R China.
   [Sun, Yi-Cheng; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
   [Sun, Yi-Cheng; Darby, Creg] Univ Calif San Francisco, Dept Cell & Tissue Biol, Program Microbial Pathogenesis & Host Response, San Francisco, CA 94143 USA.
RP Sun, YC (reprint author), Chinese Acad Med Sci, MOH Key Lab Syst Biol Pathogens, Inst Pathogen Biol, Beijing 100730, Peoples R China.
EM sunyc@ipbcams.ac.cn
OI Yang, Ruifu/0000-0003-3219-7269
FU NIH [AI057512]; Division of Intramural Research, National Institute of
   Allergy and Infectious Diseases (NIAID), National Institutes of Health
   (NIH); Institute of Pathogen Biology, Chinese Academy of Medical
   Sciences
FX This work was supported by NIH grant AI057512 (to C.D.); the Division of
   Intramural Research, National Institute of Allergy and Infectious
   Diseases (NIAID), National Institutes of Health (NIH), and by the
   Institute of Pathogen Biology, Chinese Academy of Medical Sciences.
NR 35
TC 19
Z9 20
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD APR
PY 2012
VL 194
IS 8
BP 2020
EP 2026
DI 10.1128/JB.06243-11
PG 7
WC Microbiology
SC Microbiology
GA 917MC
UT WOS:000302180200019
PM 22328676
ER

PT J
AU Bolton, KL
   Ganda, C
   Berchuck, A
   Pharaoh, PDP
   Gayther, SA
AF Bolton, K. L.
   Ganda, C.
   Berchuck, A.
   Pharaoh, P. D. P.
   Gayther, S. A.
TI Role of common genetic variants in ovarian cancer susceptibility and
   outcome: progress to date from the ovarian cancer association consortium
   (OCAC)
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Review
DE clinical outcome; ovarian cancer; susceptibility SNPs
ID GENOME-WIDE ASSOCIATION; PROGESTERONE-RECEPTOR GENE; SINGLE-NUCLEOTIDE
   POLYMORPHISMS; PLATINUM-BASED CHEMOTHERAPY; S-TRANSFERASE POLYMORPHISMS;
   NEGATIVE BREAST-CANCER; DNA-REPAIR GENES; MUTATION CARRIERS;
   PROGNOSTIC-FACTORS; COLORECTAL-CANCER
AB In this article, we review the current knowledge of the inherited genetics of epithelial ovarian cancer (EOC) susceptibility and clinical outcome. We focus on recent developments in identifying low-penetrance susceptibility genes and the role of the ovarian cancer association consortium (OCAC) in these discoveries. The OCAC was established to facilitate large-scale replication analyses for reported genetic associations for EOC. Since its inception, the OCAC has conducted both candidate gene and genome-wide association studies (GWAS); the latter has identified six established loci for EOC susceptibility, most of which showed stronger association with the serous histological subtype. Future GWAS and sequencing studies are likely to result in the discovery of additional susceptibility loci and may result in established associations with clinical outcome. Additional rare and uncommon ovarian cancer loci will likely be uncovered from high-throughput next-generation sequencing studies. Applying these novel findings to establish improved preventative and clinical intervention strategies will be one of the major challenges of future work.
C1 [Gayther, S. A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Bolton, K. L.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
   [Ganda, C.] UCL, EGA Inst Womens Hlth, Gynaecol Canc Res Labs, London, England.
   [Berchuck, A.] Duke Univ, Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynaecol, Durham, NC USA.
   [Pharaoh, P. D. P.] Univ Cambridge, Dept Oncol, Cambridge, England.
RP Gayther, SA (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1450 Biggy St,Rm 2517G,LG591,MC9601, Los Angeles, CA 90033 USA.
EM gayther@usc.edu
NR 102
TC 30
Z9 30
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-6820
J9 J INTERN MED
JI J. Intern. Med.
PD APR
PY 2012
VL 271
IS 4
BP 366
EP 378
DI 10.1111/j.1365-2796.2011.02509.x
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 914CT
UT WOS:000301927100007
PM 22443200
ER

PT J
AU Bell, JA
   Saikus, CE
   Ratnayaka, K
   Wu, V
   Sonmez, M
   Faranesh, AZ
   Colyer, JH
   Lederman, RJ
   Kocaturk, O
AF Bell, Jamie A.
   Saikus, Christina E.
   Ratnayaka, Kanishka
   Wu, Vincent
   Sonmez, Merdim
   Faranesh, Anthony Z.
   Colyer, Jessica H.
   Lederman, Robert J.
   Kocaturk, Ozgur
TI A deflectable guiding catheter for real-time MRI-guided interventions
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE interventional MRI; structural heart disease; catheter engineering;
   active MRI catheters
ID REMOTE-CONTROL; TIP; OPPORTUNITY; DESIGN; MODEL
AB Purpose: To design a deflectable guiding catheter that omits long metallic components yet preserves mechanical properties to facilitate therapeutic interventional MRI procedures.
   Materials and Methods: The catheter shaft incorporated Kevlar braiding. A 180 degrees deflection was attained with a 5-cm nitinol slotted tube, a nitinol spring, and a Kevlar pull string. We tested three designs: passive, passive incorporating an inductively coupled coil, and active receiver. We characterized mechanical properties, MRI properties, RF induced heating, and in vivo performance in swine.
   Results: Torque and tip deflection force were satisfactory. Representative procedures included hepatic and azygos vein access, laser cardiac septostomy, and atrial septal defect crossing. Visualization was best in the active configuration, delineating profile and tip orientation. The passive configuration could be used in tandem with an active guidewire to overcome its limited conspicuity. There was no RF-induced heating in all configurations under expected use conditions in vitro and in vivo.
   Conclusion: Kevlar and short nitinol component substitutions preserved mechanical properties. The active design offered the best visibility and usability but reintroduced metal conductors. We describe versatile deflectable guiding catheters with a 0.057'' lumen for interventional MRI catheterization. Implementations are feasible using active, inductive, and passive visualization strategies to suit application requirements.
C1 [Bell, Jamie A.; Saikus, Christina E.; Ratnayaka, Kanishka; Wu, Vincent; Sonmez, Merdim; Faranesh, Anthony Z.; Colyer, Jessica H.; Lederman, Robert J.; Kocaturk, Ozgur] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [Ratnayaka, Kanishka; Colyer, Jessica H.] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA.
RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2C713, Bethesda, MD 20892 USA.
EM lederman@nih.gov
RI Kocaturk, Ozgur/A-1419-2016; 
OI lederman, robert/0000-0003-1202-6673
FU Division of Intramural Research, National Heart Lung and Blood
   Institute, National Institutes of Health [Z01-HL005062-08,
   Z01-HL006041-01]
FX Contract grant sponsor: Division of Intramural Research, National Heart
   Lung and Blood Institute, National Institutes of Health; Contract grant
   numbers: Z01-HL005062-08, Z01-HL006041-01.
NR 15
TC 8
Z9 8
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD APR
PY 2012
VL 35
IS 4
BP 908
EP 915
DI 10.1002/jmri.23520
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 911JF
UT WOS:000301712400019
PM 22128071
ER

PT J
AU Pacher, P
   Mackie, K
AF Pacher, Pal
   Mackie, Ken
TI Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases,
   oxidative and nitrative stress, and cell death during remote
   neurodegeneration
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
ID SYSTEM
AB Remote neuronal degeneration and death/injury, which often occur in regions remote but functionally connected to the primary lesion site, may play a pivotal role in extending neuronal damage/dysfunction following traumatic brain injury, stroke, or peripheral nerve injury, as well as in chronic neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. Even though the precise mechanisms of remote neuronal injury are poorly understood and no efficacious treatment options are available, it involves glial activation, inflammation, oxidative/nitrative stress, and apoptotic cell death. The newly discovered endocannabinoid signaling system consisting of endocannabinoids (endogenous bioactive lipid mediators), their synthetic and metabolizing enzymes, and their primary G protein-coupled cannabinoid 1 and 2 (CB1 and CB2) receptors has been implicated in the regulation of numerous physiological and pathological processes/functions, including those associated with neurodegeneration. Using a well-characterized rodent model of remote neuronal degeneration, Oddi et al. (J Mol Med 2012, in press, DOI 10.1007/s00109-012-0884-1) have demonstrated that targeting CB2 cannabinoid receptors may represent a promising novel approach to attenuate this pathological process. This editorial discusses the clinical significance of these interesting observations and the mechanisms of the possible interplay of CB2 receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration.
C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
   [Mackie, Ken] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI Pacher, Pal/B-6378-2008; Mackie, Ken/E-3715-2013
OI Pacher, Pal/0000-0001-7036-8108; Mackie, Ken/0000-0001-8501-6199
FU Intramural NIH HHS [Z01 AA000375-03, Z99 AA999999, Z01 AA000375-02, ZIA
   AA000375-04, ZIA AA000375-05, ZIA AA000375-06]
NR 16
TC 12
Z9 13
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
EI 1432-1440
J9 J MOL MED
JI J. Mol. Med.
PD APR
PY 2012
VL 90
IS 4
BP 347
EP 351
DI 10.1007/s00109-012-0884-1
PG 5
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 916XM
UT WOS:000302136500001
PM 22371074
ER

PT J
AU Lee, YH
   Kim, JH
   Zhou, H
   Kim, BW
   Wong, DT
AF Lee, Yu-Hsiang
   Kim, Jae Hoon
   Zhou, Hui
   Kim, Bo Wook
   Wong, David T.
TI Salivary transcriptomic biomarkers for detection of ovarian cancer: for
   serous papillary adenocarcinoma
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Saliva; RNA; Salivary diagnostics; Ovarian cancer
ID IDENTIFICATION; SERUM; UTILITY; CA-125
AB Ovarian cancer is the most lethal gynecological cancer due to lack of clear symptom and reliable screening biomarker in the early stage. The capability to detect the initiation of malignancy with a sensitive and effective approach is one of the most desirable goals for ovarian cancer therapy. In this study, we spearheaded noninvasive detection of ovarian cancer by salivary transcriptomic biomarkers, and evaluated the clinical utilities of discovered biomarkers using a clinical case-control study. To find salivary mRNA biomarkers, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled by Affymetrix HG-U133-Plus-2.0 array. The biomarker candidates selected from the microarray results were then subjected to clinical validation by RT-qPCR using an independent sample cohort including 21 ovarian cancer patients and 35 healthy controls. Seven downregulated mRNA biomarkers were validated. The logistic regression model revealed the combination of five validated biomarkers (AGPAT1, B2M, BASP2, IER3, and IL1B) can significantly discriminate ovarian cancer patients (n=21) from the healthy controls (n=35), yielding a receiver operating characteristic plot, area under the curve value of 0.909 with 85.7% sensitivity and 91.4% specificity. In summary, we have demonstrated that the RNA signatures in saliva could serve as biomarkers for detection of ovarian cancer with high sensitivity and specificity. This emerging approach with high-throughput, noninvasive, and effective advantages provides a feasible means for detection of systemic cancer, and opens a new avenue for early disease detection.
C1 [Lee, Yu-Hsiang; Zhou, Hui; Wong, David T.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA.
   [Lee, Yu-Hsiang; Zhou, Hui; Wong, David T.] Dent Res Inst, Los Angeles, CA 90095 USA.
   [Lee, Yu-Hsiang] Natl Cent Univ, Grad Inst Biomed Engn, Jhongli 32001, Taiwan.
   [Wong, David T.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA.
   [Wong, David T.] Inst Mol Biol, Los Angeles, CA USA.
   [Wong, David T.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg Otolaryngol, Los Angeles, CA 90095 USA.
   [Wong, David T.] Univ Calif Los Angeles, Henry Samuel Sch Engn & Appl Sci, Los Angeles, CA 90095 USA.
   [Kim, Jae Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol,Gangnam Biomed Res Ctr, Seoul, South Korea.
   [Kim, Bo Wook] NCI, Tissue Array Res Program, Pathol Lab, Bethesda, MD 20892 USA.
RP Wong, DT (reprint author), Univ Calif Los Angeles, Sch Dent, 73-017 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM dtww@ucla.edu
FU National Research Foundation of Korean government [KRF-2008-314-E00121,
   2011-0010286]
FX This work was supported by National Research Foundation of Korean
   government (KRF-2008-314-E00121 and 2011-0010286).
NR 35
TC 32
Z9 32
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD APR
PY 2012
VL 90
IS 4
BP 427
EP 434
DI 10.1007/s00109-011-0829-0
PG 8
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 916XM
UT WOS:000302136500008
PM 22095100
ER

PT J
AU Moolgavkar, SH
   Holford, TR
   Levy, DT
   Kong, CY
   Foy, M
   Clarke, L
   Jeon, J
   Hazelton, WD
   Meza, R
   Schultz, F
   McCarthy, W
   Boer, R
   Gorlova, O
   Gazelle, GS
   Kimmel, M
   McMahon, PM
   de Koning, HJ
   Feuer, EJ
AF Moolgavkar, Suresh H.
   Holford, Theodore R.
   Levy, David T.
   Kong, Chung Yin
   Foy, Millenia
   Clarke, Lauren
   Jeon, Jihyoun
   Hazelton, William D.
   Meza, Rafael
   Schultz, Frank
   McCarthy, William
   Boer, Robert
   Gorlova, Olga
   Gazelle, G. Scott
   Kimmel, Marek
   McMahon, Pamela M.
   de Koning, Harry J.
   Feuer, Eric J.
TI Impact of Reduced Tobacco Smoking on Lung Cancer Mortality in the United
   States During 1975-2000
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID MULTISTAGE CARCINOGENESIS; COLORECTAL-CANCER; CIGARETTE-SMOKING; MODEL;
   AGE; DURATION; SMOKERS; COHORTS; HEALTH; TRENDS
AB Background Considerable effort has been expended on tobacco control strategies in the United States since the mid-1950s. However, we have little quantitative information on how changes in smoking behaviors have impacted lung cancer mortality. We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000.
   Methods A consortium of six groups of investigators used common inputs consisting of simulated cohort-wise smoking histories for the birth cohorts of 1890 through 1970 and independent models to estimate the number of US lung cancer deaths averted during 1975-2000 as a result of changes in smoking behavior that began in the mid-1950s. We also estimated the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking after the Surgeon General's first report on Smoking and Health in 1964.
   Results Approximately 795 851 US lung cancer deaths were averted during the period 1975-2000: 552 574 among men and 243 277 among women. In the year 2000 alone, approximately 70 218 lung cancer deaths were averted: 44 135 among men and 26 083 among women. However, these numbers are estimated to represent approximately 32% of lung cancer deaths that could have potentially been averted during the period 1975-2000, 38% of the lung cancer deaths that could have been averted in 1991-2000, and 44% of lung cancer deaths that could have been averted in 2000.
   Conclusions Our results reflect the cumulative impact of changes in smoking behavior since the 1950s. Despite a large impact of changing smoking behaviors on lung cancer deaths, lung cancer remains a major public health problem. Continued efforts at tobacco control are critical to further reduce the burden of this disease. J Natl Cancer Inst 2012; 104: 541-548
C1 [Moolgavkar, Suresh H.; Jeon, Jihyoun; Hazelton, William D.; Meza, Rafael] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98109 USA.
   [Holford, Theodore R.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
   [Levy, David T.] Univ Baltimore, Dept Econ, Baltimore, MD 21201 USA.
   [Levy, David T.] Pacific Inst Res & Evaluat, Calverton, MD USA.
   [Kong, Chung Yin; Gazelle, G. Scott; McMahon, Pamela M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Kong, Chung Yin; Gazelle, G. Scott; McMahon, Pamela M.] Harvard Univ, Sch Med, Boston, MA USA.
   [Foy, Millenia] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX USA.
   [Gorlova, Olga] UT MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA.
   [Foy, Millenia; Kimmel, Marek] Rice Univ, Dept Stat, Houston, TX 77251 USA.
   [Clarke, Lauren] Cornerstone Syst NW Inc, Lynden, WA USA.
   [Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Schultz, Frank; Boer, Robert; de Koning, Harry J.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
   [McCarthy, William] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA.
   [McCarthy, William] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
   [Kimmel, Marek] Silesian Tech Univ, Syst Engn Grp, Gliwice, Poland.
   [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Levy, David T.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Moolgavkar, SH (reprint author), Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, 1100 Fairview Ave N, Seattle, WA 98109 USA.
EM smoolgav@fhcrc.org
RI Boer, Rob/E-6473-2015
OI Boer, Rob/0000-0003-0680-001X
FU National Cancer Institute's Cancer Intervention and Surveillance
   Modeling Network (CISNET); National Cancer Institute at the National
   Institutes of Health [5U01CA097415-04, 2U01CA097432-04, 5U01CA097450-04,
   5U01CA097416-04, 2U01CA097431-04, 1U01CA152956-01, 5R01CA097337-02,
   K25CA133141, R00CA126147]; American Cancer Society (ACS) [RSG
   2008A060554]
FX The research reported in this article was funded by the National Cancer
   Institute's Cancer Intervention and Surveillance Modeling Network
   (CISNET; http://cisnet.cancer.gov/). Specifically, this work was
   supported by grants from the National Cancer Institute at the National
   Institutes of Health (5U01CA097415-04 to SHM, 2U01CA097432-04 to TRH,
   5U01CA097450-04 to DTL, 5U01CA097416-04 to RB and HJK, 2U01CA097431-04
   to MK, 1U01CA152956-01 to PMM HJK, DTL, SHM, TRH). GSG acknowledges
   support from the National Cancer Institute at the National Institutes of
   Health (5R01CA097337-02) and the American Cancer Society (ACS RSG
   2008A060554), PMM from the National Cancer Institute at the National
   Institutes of Health (R00CA126147), and CYK from the National Cancer
   Institute at the National Institutes of Health (K25CA133141).
NR 29
TC 57
Z9 58
U1 0
U2 11
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 APR
PY 2012
VL 104
IS 7
BP 541
EP 548
DI 10.1093/jnci/djs136
PG 8
WC Oncology
SC Oncology
GA 919AO
UT WOS:000302293200009
PM 22423009
ER

PT J
AU Raval, Z
   Liu, K
   Tian, L
   Ferrucci, L
   Guralnik, JM
   Liao, YH
   Criqui, MH
   McDermott, MM
AF Raval, Zankhana
   Liu, Kiang
   Tian, Lu
   Ferrucci, Luigi
   Guralnik, Jack M.
   Liao, Yihua
   Criqui, Michael H.
   McDermott, Mary M.
TI Higher body mass index is associated with more adverse changes in calf
   muscle characteristics in peripheral arterial disease
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 59th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 14-16, 2010
CL Atlanta, GA
SP Amer Coll Cardiol
ID LOWER-EXTREMITY ISCHEMIA; FUNCTIONAL IMPAIRMENT; CLASSIFICATION;
   OSTEOARTHRITIS; VALIDITY; CRITERIA; DECLINE
AB Objective: This study investigated whether higher body mass index (BMI) is associated with more adverse lower extremity muscle characteristics at baseline and more adverse changes in muscle over time among participants with lower extremity peripheral arterial disease (PAD).
   Methods: This was a longitudinal, observational study of 425 men and women with PAD and 261 without PAD. Computed tomography was used to measure calf muscle characteristics at baseline and every 2 years. Knee extension isometric strength, power, and 6-minute walk distance were measured at baseline and annually. Baseline BMI (kg/m(2)) categories were ideal (20-25), overweight (>25-30), and obese (>30). Analyses adjust for age, race, sex, ankle brachial index, comorbidities, and other covariates.
   Results: At baseline, higher BMI among participants with PAD was associated with greater calf muscle area (ideal BMI: 5181 mm(2); overweight: 5513 mm(2); obese: 5695 mm(2); P = .0009 for trend), higher calf muscle percentage of fat (6.38%, 10.28%, 17.44%, respectively, P < .0001 for trend), lower calf muscle density (P < .0001 for trend), and higher isometric knee extension strength (P = .015 for trend). Among participants with PAD, higher BMI was associated with greater declines in calf muscle area (P = .030 for trend) and greater increases in calf muscle percentage of fat (P = .023 for trend). Among participants without PAD, there were no significant associations of baseline BMI with changes in lower extremity muscle outcomes over time.
   Conclusions: Among PAD participants, higher BMI is associated with greater calf muscle area at baseline. However, higher BMI is associated with more adverse calf muscle density and calf muscle percentage of fat at baseline and greater declines in calf muscle area over time. (J Vasc Surg 2012;55:1015-24.)
C1 [Raval, Zankhana; McDermott, Mary M.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Liu, Kiang; Liao, Yihua; McDermott, Mary M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Tian, Lu] Stanford Univ, Dept Hlth & Res Policy, Palo Alto, CA 94304 USA.
   [Ferrucci, Luigi] Univ Maryland, Sch Med, Longitudinal Studies Sect, NIA, Baltimore, MD 21201 USA.
   [Tian, Lu] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
   [Criqui, Michael H.] Univ Calif San Diego, Div Prevent Med, Dept Family Med, San Diego, CA 92103 USA.
RP McDermott, MM (reprint author), 750 Lake Shore Dr,10th Flr, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU NHLBI NIH HHS [R01 HL064739-03, R01 HL058099, R01 HL058099-03, R01
   HL064739, R01 HL064739-01A1, R01 HL071223, R01 HL071223-01, R01
   HL071223-03, R01 HL076298-02, R01 HL076298-04, R01 HL083064, R01
   HL083064-03, R01 HL058099-02, R01 HL058099-04, R01 HL064739-02, R01
   HL064739-04, R01 HL071223-02, R01 HL071223-04, R01 HL076298, R01
   HL076298-01A1, R01 HL076298-03, R01 HL083064-04]
NR 16
TC 4
Z9 4
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD APR
PY 2012
VL 55
IS 4
BP 1015
EP 1024
DI 10.1016/j.jvs.2011.10.105
PG 10
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 917BA
UT WOS:000302145700016
PM 22365177
ER

PT J
AU Shin, YK
   Cong, WN
   Cai, H
   Kim, W
   Maudsley, S
   Egan, JM
   Martin, B
AF Shin, Yu-Kyong
   Cong, Wei-na
   Cai, Huan
   Kim, Wook
   Maudsley, Stuart
   Egan, Josephine M.
   Martin, Bronwen
TI Age-Related Changes in Mouse Taste Bud Morphology, Hormone Expression,
   and Taste Responsivity
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Taste buds; Aging; Sweet taste; Glucagon-like peptide-1; T1R3
ID RECEPTOR-CELLS; MAMMALIAN TASTE; UMAMI TASTE; PGP 9.5; SWEET; MICE;
   LEPTIN; COMMUNICATION; PAPILLAE; BITTER
AB Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact.
C1 [Shin, Yu-Kyong; Kim, Wook; Egan, Josephine M.] Natl Inst Aging, Diabet Sect, Clin Invest Lab, Baltimore, MD 21224 USA.
   [Cong, Wei-na; Cai, Huan; Martin, Bronwen] Natl Inst Aging, Metab Unit, Clin Invest Lab, Baltimore, MD 21224 USA.
   [Maudsley, Stuart] Natl Inst Aging, Receptor Pharmacol Unit, Neurosci Lab, Baltimore, MD 21224 USA.
RP Egan, JM (reprint author), Natl Inst Aging, Diabet Sect, Clin Invest Lab, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM eganj@mail.nih.gov
RI Cai, Huan/B-6578-2016
OI Cai, Huan/0000-0001-7731-8891
FU National Institutes of Health, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Institute on Aging.
NR 58
TC 13
Z9 14
U1 2
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2012
VL 67
IS 4
BP 336
EP 344
DI 10.1093/gerona/glr192
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 914TE
UT WOS:000301974500003
PM 22056740
ER

PT J
AU Sanders, JL
   Fitzpatrick, AL
   Boudreau, RM
   Arnold, AM
   Aviv, A
   Kimura, M
   Fried, LF
   Harris, TB
   Newman, AB
AF Sanders, Jason L.
   Fitzpatrick, Annette L.
   Boudreau, Robert M.
   Arnold, Alice M.
   Aviv, Abraham
   Kimura, Masayuki
   Fried, Linda F.
   Harris, Tamara B.
   Newman, Anne B.
TI Leukocyte Telomere Length Is Associated With Noninvasively Measured
   Age-Related Disease: The Cardiovascular Health Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
DE Leukocyte telomere length; Disease burden; Noninvasive measurements;
   Aging
ID CAROTID ATHEROSCLEROSIS; OXIDATIVE STRESS; RISK-FACTORS; MORTALITY;
   ADULTS; DEMENTIA; DYNAMICS; PERFORMANCE; SENESCENCE; DEPRESSION
AB Background. Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression).
   Methods. LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima-media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4% male, 86.8% white, and 13.2% black).
   Results. Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (beta[SE] = -132 [47] bp, p < .01), age (beta[SE] = -107 [46], p = .02) or carotid thickness (beta[SE] = -95 [40] bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35%.
   Conclusion. LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age.
C1 [Sanders, Jason L.; Boudreau, Robert M.; Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
   [Sanders, Jason L.] Univ Pittsburgh, Sch Med, Med Scientist Training Program, Pittsburgh, PA 15213 USA.
   [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Aviv, Abraham; Kimura, Masayuki] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA.
   [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
   [Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
   [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Sanders, JL (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Bellefield Profess Bldg,4th Floor,130 N Bellefiel, Pittsburgh, PA 15213 USA.
EM sanders.jason@medstudent.pitt.edu
RI Newman, Anne/C-6408-2013; 
OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187
FU Royalty Research Fund; University of Washington; Healthcare Foundation
   of New Jersey; National Institute on Aging [R01-AG-023629,
   5-P30-AG-024827, AG-021593, AG-020132]; National Heart, Lung, and Blood
   Institute [R01-HL-80698-01, N01-HC-85079, N01-HC-85086, N01-HC-35129,
   N01-HC-15103, N01-HC-45133, N01-HC-75150, N01-HC-55222, U01 HL080295];
   National Institute of Neurological Disorders and Stroke
FX This research was supported by the Royalty Research Fund, the University
   of Washington, the Healthcare Foundation of New Jersey, the National
   Institute on Aging (grants R01-AG-023629 and 5-P30-AG-024827), and the
   National Heart, Lung, and Blood Institute (R01-HL-80698-01). The CHS is
   supported by the National Heart, Lung, and Blood Institute (contracts
   N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103,
   N01-HC-45133, N01-HC-75150, N01-HC-55222, and U01 HL080295), the
   National Institute on Aging (grants AG-021593 and AG-020132), and the
   National Institute of Neurological Disorders and Stroke. A full list of
   participating Cardiovascular Health Study investigators and institutions
   can be found at the study's website (http://www.chs-nhlbi.org). Role of
   sponsor(s): The investigators retained full independence in the conduct
   of this research.
NR 45
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U1 4
U2 15
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 APR
PY 2012
VL 67
IS 4
BP 409
EP 416
DI 10.1093/gerona/glr173
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 914TE
UT WOS:000301974500011
PM 21934123
ER

PT J
AU Majounie, E
   Renton, AE
   Mok, K
   Dopper, EGP
   Waite, A
   Rollinson, S
   Chio, A
   Restagno, G
   Nicolaou, N
   Simon-Sanchez, J
   van Swieten, JC
   Abramzon, Y
   Johnson, JO
   Sendtner, M
   Pamphlett, R
   Orrell, RW
   Mead, S
   Sidle, KC
   Houlden, H
   Rohrer, JD
   Morrison, KE
   Pall, H
   Talbot, K
   Ansorge, O
   Hernandez, DG
   Arepalli, S
   Sabatelli, M
   Mora, G
   Corbo, M
   Giannini, F
   Calvo, A
   Englund, E
   Borghero, G
   Foris, GL
   Remes, AM
   Laaksovirta, H
   McCluskey, L
   Trojanowski, JQ
   Van Deerlin, VM
   Schellenberg, GD
   Nalls, MA
   Drory, VE
   Lu, CS
   Yeh, TH
   Ishiura, H
   Takahashi, Y
   Tsuji, S
   Le Ber, I
   Brice, A
   Drepper, C
   Williams, N
   Kirby, J
   Shaw, P
   Hardy, J
   Tienari, PJ
   Heutink, P
   Morris, HR
   Pickering-Brown, S
   Traynor, BJ
AF Majounie, Elisa
   Renton, Alan E.
   Mok, Kin
   Dopper, Elise G. P.
   Waite, Adrian
   Rollinson, Sara
   Chio, Adrian
   Restagno, Gabriella
   Nicolaou, Nayia
   Simon-Sanchez, Javier
   van Swieten, John C.
   Abramzon, Yevgeniya
   Johnson, Janel O.
   Sendtner, Michael
   Pamphlett, Roger
   Orrell, Richard W.
   Mead, Simon
   Sidle, Katie C.
   Houlden, Henry
   Rohrer, Jonathan D.
   Morrison, Karen E.
   Pall, Hardev
   Talbot, Kevin
   Ansorge, Olaf
   Hernandez, Dena G.
   Arepalli, Sampath
   Sabatelli, Mario
   Mora, Gabriele
   Corbo, Massimo
   Giannini, Fabio
   Calvo, Andrea
   Englund, Elisabet
   Borghero, Giuseppe
   Foris, Gian Luca
   Remes, Anne M.
   Laaksovirta, Hannu
   McCluskey, Leo
   Trojanowski, John Q.
   Van Deerlin, Vivianna M.
   Schellenberg, Gerard D.
   Nalls, Michael A.
   Drory, Vivian E.
   Lu, Chin-Song
   Yeh, Tu-Hsueh
   Ishiura, Hiroyuki
   Takahashi, Yuji
   Tsuji, Shoji
   Le Ber, Isabelle
   Brice, Alexis
   Drepper, Carsten
   Williams, Nigel
   Kirby, Janine
   Shaw, Pamela
   Hardy, John
   Tienari, Pentti J.
   Heutink, Peter
   Morris, Huw R.
   Pickering-Brown, Stuart
   Traynor, Bryan J.
CA Chromosome 9-ALS FTD Consortium
   French Res Network FTLD FTLD ALS
   ITALSGEN Consortium
TI Frequency of the C9orf72 hexanucleotide repeat expansion in patients
   with amyotrophic lateral sclerosis and frontotemporal dementia: a
   cross-sectional study
SO LANCET NEUROLOGY
LA English
DT Article
ID POPULATION-BASED COHORT; LOBAR DEGENERATION; ALS; PREVALENCE; MUTATIONS;
   GENETICS; CRITERIA; TDP-43; FTD
AB Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
   Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion.
   Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7.0%) of 3377 white individuals from the USA, Europe, and Australia, two (4.1%) of 49 black individuals from the USA, and six (8.3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39.3%) of 552 white individuals with familial MS from Europe and the USA. 59 (6.0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24.8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic MS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years.
   Interpretation A common Mendelian genetic lesion in C9472 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.
C1 [Renton, Alan E.; Abramzon, Yevgeniya; Johnson, Janel O.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Majounie, Elisa; Hernandez, Dena G.; Arepalli, Sampath; Nalls, Michael A.] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Mok, Kin; Sidle, Katie C.; Houlden, Henry; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
   [Mok, Kin; Sidle, Katie C.; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London, England.
   [Orrell, Richard W.] UCL, Dept Clin Neurosci, Inst Neurol, London, England.
   [Mead, Simon] UCL, Inst Neurol, MRC Prion Unit, Dept Neurodegenerat Dis, London, England.
   [Houlden, Henry] UCL, Inst Neurol, MRC Ctr Neuromuscular Dis, London, England.
   [Rohrer, Jonathan D.] UCL, Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England.
   [Dopper, Elise G. P.; Nicolaou, Nayia; Simon-Sanchez, Javier; van Swieten, John C.; Heutink, Peter] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands.
   [Dopper, Elise G. P.; Nicolaou, Nayia; Simon-Sanchez, Javier; van Swieten, John C.; Heutink, Peter] Vrije Univ Amsterdam, Med Ctr, Sect Med Genom, Dept Clin Genet, Amsterdam, Netherlands.
   [Dopper, Elise G. P.; Nicolaou, Nayia; Simon-Sanchez, Javier; van Swieten, John C.] Erasmus MC Univ Med Ctr Rotterdam, Dept Neurol, Rotterdam, Netherlands.
   [Waite, Adrian; Williams, Nigel; Morris, Huw R.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales.
   [Rollinson, Sara; Pickering-Brown, Stuart] Univ Manchester, Fac Human & Med Sci, Manchester, Lancs, England.
   [Chio, Adrian; Calvo, Andrea] Univ Turin, Dept Neurosci, Turin, Italy.
   [Restagno, Gabriella] Azienda Osped Osped Infantile Regina Margherita S, Dept Clin Pathol, Mol Genet Unit, Turin, Italy.
   [Sendtner, Michael; Drepper, Carsten] Univ Wurzburg, Inst Clin Neurobiol, Wurzburg, Germany.
   [Pamphlett, Roger] Univ Sydney, Sydney Med Sch, Dept Pathol, Sydney, NSW 2006, Australia.
   [Morrison, Karen E.] Univ Birmingham, Coll Med & Dent Sci, Inst Biomed Res, Dept Neurol, Birmingham, W Midlands, England.
   [Pall, Hardev] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Queen Elizabeth Med Ctr, Birmingham, W Midlands, England.
   [Talbot, Kevin; Ansorge, Olaf] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
   [Sabatelli, Mario] Catholic Univ, Neurol Inst, Rome, Italy.
   [Sabatelli, Mario] ICOMM Assoc ALS Res, Rome, Italy.
   [Mora, Gabriele] Salvatore Maugeri Fdn, ALS Ctr, Milan, Italy.
   [Corbo, Massimo] Osped Niguarda Ca Granda, NeuroMuscular Omnictr, Milan, Italy.
   [Giannini, Fabio] Univ Siena, Dept Neurol Neurosurg & Behav Sci, Neurol Sect, I-53100 Siena, Italy.
   [Englund, Elisabet] Lund Univ, Dept Pathol, Reg Labs Reg Skane, Lund, Sweden.
   [Borghero, Giuseppe; Foris, Gian Luca] Azienda Univ Osped Cagliari, Dept Neurol, Cagliari, Italy.
   [Borghero, Giuseppe; Foris, Gian Luca] Univ Cagliari, Cagliari, Italy.
   [Remes, Anne M.] Oulu Univ Hosp, Clin Res Ctr, Oulu, Finland.
   [Remes, Anne M.] Univ Oulu, Inst Clin Med, Oulu, Finland.
   [Laaksovirta, Hannu; Tienari, Pentti J.] Univ Helsinki, Mol Neurol Programme, Biomedicum, Helsinki, Finland.
   [Laaksovirta, Hannu; Tienari, Pentti J.] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
   [McCluskey, Leo] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
   [Trojanowski, John Q.; Van Deerlin, Vivianna M.; Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Drory, Vivian E.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel.
   [Lu, Chin-Song; Yeh, Tu-Hsueh] Chang Gang Univ, Tao Yuan, Taiwan.
   [Lu, Chin-Song; Yeh, Tu-Hsueh] Chang Gung Mem Hosp, Linkou Med Ctr, Dept Neurol, Tao Yuan, Taiwan.
   [Lu, Chin-Song; Yeh, Tu-Hsueh] Chang Gung Mem Hosp, Linkou Med Ctr, Neurosci Res Ctr, Tao Yuan, Taiwan.
   [Ishiura, Hiroyuki; Takahashi, Yuji] Tokyo Univ Hosp, Dept Neurol, Bunkyo Ku, Tokyo 113, Japan.
   [Le Ber, Isabelle; Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Paris, France.
   [Le Ber, Isabelle; Brice, Alexis] INSERM, U975, Paris, France.
   [Le Ber, Isabelle; Brice, Alexis] CNRS, UMR 7225, Paris, France.
   [Kirby, Janine; Shaw, Pamela] Univ Sheffield, Dept Neurosci, Sheffield, S Yorkshire, England.
   [Morris, Huw R.] Univ Wales Hosp, Cardiff CF4 4XW, S Glam, Wales.
   [Traynor, Bryan J.] Johns Hopkins Univ Hosp, Brain Sci Inst, Dept Neurol, Baltimore, MD 21287 USA.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A-1000, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
RI Pickering-Brown, Stuart/D-4008-2009; Hardy, John/C-2451-2009; Morris,
   Huw/B-8527-2008; Tienari, Pentti/A-4893-2012; Mok, Kin/F-5860-2012;
   Guerreiro, Rita/A-1327-2011; Traynor, Bryan/G-5690-2010; Mead,
   Simon/E-9414-2011; Houlden, Henry/C-1532-2008; Orrell,
   Richard/L-2123-2013; LICEND, CEMND/F-1296-2015; Battistini,
   Stefania/N-2596-2015; QUATTRONE, Aldo/A-6734-2016; Calvo,
   Andrea/K-4141-2016; LOGROSCINO, GIANCARLO/K-5148-2016; Spataro,
   Rossella/B-3656-2016; Lunetta, Christian/K-9214-2016; Sendtner,
   Michael/J-1542-2012; MANDRIOLI, JESSICA/K-7235-2016; Conforti, Francesca
   Luisa/K-8877-2016; 
OI Pickering-Brown, Stuart/0000-0003-1561-6054; Morris,
   Huw/0000-0002-5473-3774; Mead, Simon/0000-0002-4326-1468; Houlden,
   Henry/0000-0002-2866-7777; Battistini, Stefania/0000-0003-2887-7624;
   QUATTRONE, Aldo/0000-0003-2001-957X; Calvo, Andrea/0000-0002-5122-7243;
   Rohrer, Jonathan/0000-0002-6155-8417; Blanc,
   Frederic/0000-0002-6714-3247; Bayer, Antony/0000-0002-7514-248X;
   Gambardella , Antonio/0000-0001-7384-3074; Turner,
   Martin/0000-0003-0267-3180; Gwinn, Katrina/0000-0002-8277-651X; Scholz,
   Sonja/0000-0002-6623-0429; LOGROSCINO, GIANCARLO/0000-0003-0423-3242;
   Spataro, Rossella/0000-0002-8910-3131; Lunetta,
   Christian/0000-0002-4788-1875; Sendtner, Michael/0000-0002-4737-2974;
   Mandich, Paola/0000-0003-3123-3512; Simone, Isabella
   Laura/0000-0002-7429-3091; Kirby, Janine/0000-0002-7468-5917; MANDRIOLI,
   JESSICA/0000-0002-9244-9782; Sabatelli, Mario/0000-0001-6635-4985;
   Conforti, Francesca Luisa/0000-0001-8364-1783; Chio,
   Adriano/0000-0001-9579-5341
FU US National Institutes of Health (NIH); National Institute on Aging
   [Z01-AG000949-02]; National Institute of Neurological Disorders and
   Stroke (NINDS); Packard Center for ALS Research at Hopkins; ALS
   Association; Microsoft Research; AriSLA; Hersenstichting Nederland
   Fellowship [B08.03]; Neuroscience Campus Amsterdam; Nuts Ohra Fonds;
   Stichting Dioraphte [09020300]; UK Motor Neurone Disease Association
   [6057, 6700/3]; Medical Research Council UK; Wellcome Trust
   [069388/z/02/z]; Oxford National Institute for Health Research
   Biomedical Research Centre; Helsinki University Central Hospital;
   Finnish Academy; Finnish Medical Society Duodecim; Kuopio University;
   Italian Health Ministry; Fondazione Vialli e Mauro ONLUS; Federazione
   Italiana Giuoco Calcio; Compagnia di San Paolo; French Agency for
   Research [ANR-08-MNPS-009-01]; France Alzheimer Union Nationale des
   Associations Alzheimer; Institut de France Subvention de la Fondation
   Thierry et Annick DESMAREST; European Community [259867]; Deutsche
   Forschungsgemeinschaft [SFT.581, TP4]; National Health and Medical
   Research Council [402703]
FX This work was supported in part by the Intramural Research Programs of
   the US National Institutes of Health (NIH), National Institute on Aging
   (Z01-AG000949-02), and National Institute of Neurological Disorders and
   Stroke (NINDS). The work was also supported by the Packard Center for
   ALS Research at Hopkins (BJT), the ALS Association (BJT, ACh), Microsoft
   Research (BIT, PIT), AriSLA (BJT, ACh, MSa), Hersenstichting Nederland
   Fellowship project B08.03 and the Neuroscience Campus Amsterdam (JS-S),
   Nuts Ohra Fonds (JvS), Stichting Dioraphte (JvS; grant 09020300), the UK
   Motor Neurone Disease Association (HM [Motor Neurone Disease Association
   grant 6057], JH, RWO, KEM, PJS MNDA Grant 6700/3), The Medical Research
   Council UK (JH, HH, SP-B), the Wellcome Trust (JH, HH, 069388/z/02/z),
   The Oxford National Institute for Health Research Biomedical Research
   Centre (OA), the Helsinki University Central Hospital, the Finnish
   Academy (PJT), the Finnish Medical Society Duodecim, Kuopio University,
   the Italian Health Ministry (Ricerca Sanitaria Finalizzata 2007 to ACh),
   Fondazione Vialli e Mauro ONLUS (ACh), Federazione Italiana Giuoco
   Calcio (ACh, MSa, BJT) and Compagnia di San Paolo (ACh, GR), the French
   Agency for Research (ANR-08-MNPS-009-01; AB and ILB), France Alzheimer
   Union Nationale des Associations Alzheimer (ILB) and Institut de France
   Subvention de la Fondation Thierry et Annick DESMAREST (ILB), and the
   European Community's Health Seventh Framework Programme under grant
   agreements 259867 (ACh, JK, PJS, MS, CD), Deutsche
   Forschungsgemeinschaft (MSe; grant SFT.581, TP4). DNA samples for this
   study were obtained in part from the NINDS repository at the Coriell
   Cell Repositories (NJ, USA), and from the Australian Motor Neuron
   Disease DNA Bank, which is funded by National Health and Medical
   Research Council grant 402703. We thank the DNA extraction and storage
   facility of the NIH and Welfare/FIMM, Helsinki, Finland and the
   Institute for Ageing and Health, Campus for Ageing and Vitality,
   Newcastle University, Newcastle upon Tyne, UK, for their help in
   extraction of DNA from patients with amyotrophic lateral sclerosis; and
   also the patients and research participants who contributed samples for
   this study.
NR 28
TC 356
Z9 365
U1 12
U2 74
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD APR
PY 2012
VL 11
IS 4
BP 323
EP 330
DI 10.1016/S1474-4422(12)70043-1
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 915CD
UT WOS:000301999600008
PM 22406228
ER

PT J
AU Demirer, E
   Miller, AC
   Kunter, E
   Kartaloglu, Z
   Barnett, SD
   Elamin, M
AF Demirer, Ersin
   Miller, Andrew C.
   Kunter, Erdogan
   Kartaloglu, Zafer
   Barnett, Scott D.
   Elamin, M.
TI Predictive Models for Tuberculous Pleural Effusions in a High
   Tuberculosis Prevalence Region
SO LUNG
LA English
DT Article
DE Adenosine deaminase enzyme; Lactate dehydrogenase enzyme; Pulmonary
   tuberculosis; Tuberculous pleural effusion
ID DIAGNOSIS; BIOPSY; SPECIFICITY
AB Patients with pleural effusions who reside in geographic areas with a high prevalence of tuberculosis frequently have similar clinical manifestations of other diseases. The aim of our study was to develop a simple but accurate clinical score for differential diagnosis of tuberculosis pleural effusion (TPE) from non-TB pleural effusion (NTPE).
   This was an unblinded, prospective study of Turkish patients 18 years of age or older with pleural effusion of indeterminate etiology conducted from June 2003 to June 2005. Unconditional logistic regression models were used to discriminate TPE cases from NTPE cases. Standard errors for the area under the curve (AUC) were calculated using the Mann-Whitney method. Data were statistically significance if two-tailed P < 0.05.
   A total of 63.3% (157/248) of the patients had TPE while 36.7% (91/248) of the patients had other etiologies for pleural effusions. We were able to provide a predictive model of TPE that included age < 47 years and either pleural fluid adenosine deaminase enzyme (PADA) > 35 U/l or pleural serum protein ratio > 0.710. However, only the combination of age < 47 and PADA > 35 U/l was significant (odds ratio [OR]: 7.46; 95% confidence interval [CI]: 3.99-13.96). The generated summary score (range = 0-6) was significantly predictive of TPE (OR: 2.91; 95% CI: 2.18-3.89) and with high AUC (0.79).
   We propose an affordable model that includes age < 47 years and PADA > 35 U/l for timely diagnosis of TPE in geographical regions with a high prevalence of TB.
C1 [Demirer, Ersin; Kartaloglu, Zafer] GATA Haydarpasa Training Hosp, Dept Thorac Med, Istanbul, Turkey.
   [Miller, Andrew C.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
   [Miller, Andrew C.] Univ Pittsburgh, Med Ctr, Dept Med Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
   [Kunter, Erdogan] Istanbul Medipol Univ, Dept Thorac Med, Istanbul, Turkey.
   [Barnett, Scott D.] James A Haley Vet Hosp, Res Ctr Excellence, Tampa, FL 33612 USA.
   [Elamin, M.] Univ S Florida, Div Pulm Crit Care & Sleep Med, Sect 111C, James A Haley Vet Hosp, Tampa, FL 33612 USA.
   [Elamin, M.] Univ S Florida, Div Pulm Crit Care Med & Sleep, Tampa, FL 33612 USA.
RP Elamin, M (reprint author), Univ S Florida, Div Pulm Crit Care & Sleep Med, Sect 111C, James A Haley Vet Hosp, 13000 Bruce B Downs Blvd, Tampa, FL 33612 USA.
EM eelamin@health.usf.edu
OI Miller, Andrew/0000-0001-8474-5090
NR 27
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0341-2040
J9 LUNG
JI Lung
PD APR
PY 2012
VL 190
IS 2
BP 239
EP 248
DI 10.1007/s00408-011-9342-z
PG 10
WC Respiratory System
SC Respiratory System
GA 917BL
UT WOS:000302146900015
PM 22057296
ER

PT J
AU Yu, SSK
   Castillo, DC
   Courville, AB
   Sumner, AE
AF Yu, Sophia S. K.
   Castillo, Darleen C.
   Courville, Amber B.
   Sumner, Anne E.
TI The Triglyceride Paradox in People of African Descent
SO METABOLIC SYNDROME AND RELATED DISORDERS
LA English
DT Article
ID CORONARY-HEART-DISEASE; HYPERTRIGLYCERIDEMIC-WAIST PHENOTYPE;
   LIPOPROTEIN CHOLESTEROL RATIO; INCIDENT DIABETES-MELLITUS; LOW-DENSITY
   LIPOPROTEINS; INSULIN-RESISTANCE; METABOLIC SYNDROME;
   ETHNIC-DIFFERENCES; GLUCOSE-INTOLERANCE; HEPATIC STEATOSIS
AB Even though insulin resistance, cardiovascular disease (CVD), and type 2 diabetes (T2D) are associated with hypertriglyceridemia, blacks with these conditions usually have normal triglyceride (TG) levels. This is often called a lipid paradox. More precisely, it is a "TG paradox." The pathways that lead to hypertriglyceridemia have been intensively explored. Yet, the pathways that allow TG levels to be normal in the presence of insulin resistance have received little attention and this is problematic. Tests designed for the early detection of insulin-resistant conditions often use elevated TG levels as a diagnostic criterion. However, insulin resistance, CVD, and T2D are not usually associated with hypertriglyceridemia in people of African descent; therefore, the widespread use of TG levels to predict these conditions needs re-evaluation. This review focuses on black-white differences in: (1) the lipid profile across North America, Europe, and Africa; (2) the efficacy of TG-based screening tests, specifically the metabolic syndrome and its two abbreviated versions, the hypertriglycerdemic waist and TG/high-density lipoprotein cholesterol (HDL-C) ratio; and (3) the mechanisms that allow TG to be normal even in the presence of insulin resistance. Overall, a broader understanding of how TG physiology varies by race could lead to better diagnostic tests and improved health outcomes.
C1 [Yu, Sophia S. K.; Castillo, Darleen C.; Sumner, Anne E.] NIDDK, DEOB, NIH, Bethesda, MD 20892 USA.
   [Courville, Amber B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
RP Sumner, AE (reprint author), NIDDK, DEOB, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM annes@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
   of the National Institutes of Health (NIH); NIH; Pfizer Inc; Clinical
   Center, NIH
FX S.S.K.Y., D.C.C., and A.E.S. are supported by the intramural research
   program of the National Institute of Diabetes and Digestive and Kidney
   Diseases (NIDDK) of the National Institutes of Health (NIH). S.S.K.Y. is
   also supported through the Clinical Research Training Program, a
   public-private partnership supported jointly by the NIH and Pfizer Inc
   (via a grant to the Foundation for NIH from Pfizer Inc). A.B.C. is
   supported by the Clinical Center, NIH.
NR 52
TC 17
Z9 17
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-4196
J9 METAB SYNDR RELAT D
JI Metab. Syndr. Relat. Disord.
PD APR
PY 2012
VL 10
IS 2
BP 77
EP 82
DI 10.1089/met.2011.0108
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 914NM
UT WOS:000301957500001
PM 22224930
ER

PT J
AU Ebong, IA
   Bertoni, AG
   Soliman, EZ
   Guo, MY
   Sibley, CT
   Chen, YDI
   Rotter, JI
   Chen, YC
   Goff, DC
AF Ebong, Imo A.
   Bertoni, Alain G.
   Soliman, Elsayed Z.
   Guo, Mengye
   Sibley, Christopher T.
   Chen, Yii-Der I.
   Rotter, Jerome I.
   Chen, Yi-Chun
   Goff, David C., Jr.
TI Electrocardiographic Abnormalities Associated with the Metabolic
   Syndrome and Its Components: The Multi-Ethnic Study of Atherosclerosis
SO METABOLIC SYNDROME AND RELATED DISORDERS
LA English
DT Article
ID INTERNATIONAL-DIABETES-FEDERATION; CARDIOVASCULAR-DISEASE MORTALITY;
   CORONARY-ARTERY-DISEASE; HEART-DISEASE; ABDOMINAL OBESITY;
   BLOOD-PRESSURE; RISK; MEN; WOMEN; DEFINITION
AB Background: The association between metabolic syndrome and electrocardiographic (ECG) abnormalities is not well established.
   Methods: ECG tracings of 6,765 men and women aged 45-84 years, free of clinical cardiovascular disease, from the Multi-Ethnic Study of Atherosclerosis were obtained (2000-2002) and classified as normal or having major or minor abnormalities. We evaluated the associations of metabolic syndrome and its components with ECG abnormalities, adjusting for age, ethnicity, and gender and testing for effect modification by ethnicity and gender.
   Results: The associations of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied significantly by gender. In males, metabolic syndrome and hypertension were significantly associated with major ECG abnormality [1.69 (1.33-2.13), and 2.22 (1.72-2.86), respectively] after adjusting for ethnicity and gender. Hypertension was also associated significantly with minor ECG abnormality in males after adjusting for age and ethnicity. In females, metabolic syndrome and hypertension were significantly associated with major [1.84 (1.44-2.37), and 1.68 (1.27-2.22), respectively] and minor [1.38 (1.19-1.59), and 1.53 (1.32-1.79), respectively] ECG abnormalities after adjusting for age and ethnicity. High triglycerides were only significantly associated with major ECG abnormality in females after adjusting for age and ethnicity. After adjusting for age, ethnicity, and gender, central obesity and high fasting blood glucose were significantly associated with major and minor ECG abnormalities, whereas low high-density lipoprotein cholesterol was significantly associated with major ECG abnormality only.
   Conclusions: Metabolic syndrome and its components are associated with major and/or minor ECG abnormalities. The relationship of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied according to gender.
C1 [Ebong, Imo A.; Bertoni, Alain G.; Soliman, Elsayed Z.; Goff, David C., Jr.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
   [Ebong, Imo A.; Bertoni, Alain G.; Soliman, Elsayed Z.; Goff, David C., Jr.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA.
   [Guo, Mengye] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   [Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA.
   [Chen, Yii-Der I.; Rotter, Jerome I.; Chen, Yi-Chun] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Chen, Yi-Chun] Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan.
   [Chen, Yi-Chun] Chang Gung Univ, Coll Med, Taipei, Taiwan.
RP Ebong, IA (reprint author), Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM iebong@wfubmc.edu
RI Sibley, Christopher/C-9900-2013
FU National Heart, Lung and Blood Institute [N01-HC-95159, N01-HC-95169]
FX The authors thank the other investigators, the staff, and the
   participants of the MESA study for their valuable contributions. A full
   list of participating MESA investigators and institutions can be found
   at www.mesa-nhlbi.org. We thank Charles N. Campbell, Jr., at Wake Forest
   University School of Medicine for assistance with ECG coding. The MESA
   study was supported by contracts N01-HC-95159 through N01-HC-95169 from
   the National Heart, Lung and Blood Institute.
NR 29
TC 9
Z9 9
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-4196
J9 METAB SYNDR RELAT D
JI Metab. Syndr. Relat. Disord.
PD APR
PY 2012
VL 10
IS 2
BP 92
EP 97
DI 10.1089/met.2011.0090
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 914NM
UT WOS:000301957500003
PM 22053762
ER

PT J
AU Fera, A
   Farrington, JE
   Zimmerberg, J
   Reese, TS
AF Fera, Andrea
   Farrington, Jane E.
   Zimmerberg, Joshua
   Reese, Thomas S.
TI A Negative Stain for Electron Microscopic Tomography
SO MICROSCOPY AND MICROANALYSIS
LA English
DT Article
DE tomography; influenza virus; negative staining; back projection method;
   individual molecule imaging; native state imaging
ID INFLUENZA-VIRUS; HEMAGGLUTININ; NEURAMINIDASE; RESOLUTION;
   RECONSTRUCTIONS; MACROMOLECULES; GLYCOPROTEIN; ORGANIZATION;
   IRRADIATION; MEMBRANE
AB While negative staining can provide detailed, two-dimensional images of biological structures, the potential of combining tomography with negative staining to provide three-dimensional views has yet to be fully realized. Basic requirements of a negative stain for tomography are that the density and atomic number of the stain are optimal, and that the stain does not degrade or rearrange with the intensive electron dose (similar to 10(6) e/nm(2)) needed to collect a full set of tomographic images. A commercially available, tungsten-based stain appears to satisfy these prerequisites. Comparison of the surface structure of negatively stained influenza A virus with previous structural results served to evaluate this negative stain. The combination of many projections of the same structure yielded detailed images of single proteins on the viral surface. Corresponding surface renderings are a good fit to images of the viral surface derived from cryomicroscopy as well as to the shapes of crystallized surface proteins. Negative stain tomography with the appropriate stain yields detailed images of individual molecules in their normal setting on the surface of the influenza A virus.
C1 [Fera, Andrea; Reese, Thomas S.] Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, Bethesda, MD 20892 USA.
   [Farrington, Jane E.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Cellular Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Fera, A (reprint author), Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, Bethesda, MD 20892 USA.
EM feraandr@ninds.nih.gov
FU Intramural NIH HHS [ZIA HD001409-26]
NR 28
TC 2
Z9 2
U1 1
U2 6
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1431-9276
J9 MICROSC MICROANAL
JI Microsc. microanal.
PD APR
PY 2012
VL 18
IS 2
BP 331
EP 335
DI 10.1017/S1431927611012797
PG 5
WC Materials Science, Multidisciplinary; Microscopy
SC Materials Science; Microscopy
GA 916FM
UT WOS:000302084700010
PM 22364718
ER

PT J
AU Virden, RA
   Thiele, CJ
   Liu, ZH
AF Virden, Ryan A.
   Thiele, Carol J.
   Liu, Zhihui
TI Characterization of Critical Domains within the Tumor Suppressor CASZ1
   Required for Transcriptional Regulation and Growth Suppression
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NERVOUS-SYSTEM; NEUROBLASTOMA-CELLS; GENE-EXPRESSION; IN-VIVO;
   DROSOPHILA; CASTOR; DIFFERENTIATION; TRKA; IDENTITY; RECEPTOR
AB CASZ1 is a zinc finger (ZF) transcription factor that is critical for controlling the normal differentiation of subtypes of neural and cardiac muscle cells. In neuroblastoma tumors, loss of CASZ1 is associated with poor prognosis and restoration of CASZ1 function suppresses neuroblastoma tumorigenicity. However, the key domains by which CASZ1 transcription controls developmental processes and neuroblastoma tumorigenicity have yet to be elucidated. In this study, we show that loss of any one of ZF1 to ZF4 resulted in a 58 to 79% loss in transcriptional activity, as measured by induction of tyrosine hydroxylase promoter-luciferase activity, compared to that of wild-type (WT) CASZ1b. Mutation of ZF5 or deletion of the C-terminal sequence of amino acids (aa) 728 to 1166 (a truncation of 38% of the protein) does not significantly alter transcriptional function. A series of N-terminal truncations reveals a critical transcriptional activation domain at aa 31 to 185 and a nuclear localization signal at aa 23 to 29. Soft agar colony formation assays and xenograft studies show that WT CASZ1b is more active in suppressing neuroblastoma growth than CASZ1b with a ZF4 mutation or a deletion of aa 31 to 185. This study identifies key domains needed for CASZ1b to regulate gene transcription. Furthermore, we establish a link between loss of CASZ1b transcriptional activity and attenuation of CASZ1b-mediated inhibition of neuroblastoma growth and tumorigenicity.
C1 [Virden, Ryan A.; Thiele, Carol J.; Liu, Zhihui] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
RP Liu, ZH (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
EM thielec@mail.nih.gov; liuzhihu@mail.nih.gov
FU NIH, National Cancer Institute, and Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
   NIH, National Cancer Institute, and Center for Cancer Research.
NR 32
TC 7
Z9 7
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD APR
PY 2012
VL 32
IS 8
BP 1518
EP 1528
DI 10.1128/MCB.06039-11
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 917DK
UT WOS:000302152500017
PM 22331471
ER

PT J
AU Villar, J
   Tsai-Morris, CH
   Dai, LS
   Dufau, ML
AF Villar, Joaquin
   Tsai-Morris, Chon-Hwa
   Dai, Lisheng
   Dufau, Maria L.
TI Androgen-Induced Activation of Gonadotropin-Regulated Testicular RNA
   Helicase (GRTH/Ddx25) Transcription: Essential Role of a Nonclassical
   Androgen Response Element Half-Site
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID HORMONE RECEPTOR GENE; HUMAN PROSTATE; IN-VITRO; SPERMATOGENESIS;
   PROTEIN; COACTIVATOR; EXPRESSION; BINDING; FAMILY; GROWTH
AB GRTH, a testis-specific member of the DEAD-box family of RNA helicases essential for spermatogenesis, is present in Leydig cells (LC) and germ cells. In LC, it exerts an autocrine negative regulation on androgen production induced by gonadotropin. GRTH is transcriptionally upregulated by gonadotropin via cyclic AMP/androgen through androgen receptors (AR). For studies of GRTH regulation by androgen in LC, we utilized in vitro/in vivo models. Androgen-induced GRTH expression was prevented by an AR antagonist. Two putative atypical ARE half-sites are present at bp -200 and -827 (ARE1 and ARE2). Point mutation of ARE2 prevented androgen-induced AR binding/function and upregulation of GRTH transcription. Chromatin immunoprecipitation (ChIP) assays showed recruitment of AR, SRC-1, Med-1, transcription factor IIB (TFIIB), and polymerase II (PolII) to GRTH ARE2 (bp -980/-702) and to the promoter region (bp -80/+63). ChIP3C assays revealed short-range chromosomal looping between AR/ARE2 and the core transcriptional machinery at the promoter. Knockdown of Med-1 and/or SRC-1 demonstrated the presence of a nonproductive complex which included AR, TFIIB, and PolII and the essential role of these coactivators in the transcriptional activation of GRTH. Our findings provide new insights into the molecular mechanism of androgen-regulated transcription in LC.
C1 [Villar, Joaquin; Tsai-Morris, Chon-Hwa; Dai, Lisheng; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
EM dufaum@mail.nih.gov
NR 37
TC 4
Z9 5
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD APR
PY 2012
VL 32
IS 8
BP 1566
EP 1580
DI 10.1128/MCB.06002-11
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 917DK
UT WOS:000302152500021
PM 22331472
ER

PT J
AU Roessler, E
   Velez, JI
   Zhou, N
   Muenke, M
AF Roessler, Erich
   Velez, Jorge I.
   Zhou, Nan
   Muenke, Maximilian
TI Utilizing prospective sequence analysis of SHH, ZIC2, SIX3 and TGIF in
   holoprosencephaly probands to describe the parameters limiting the
   observed frequency of mutant gene x gene interactions
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Holoprosencephaly; Digenic inheritance; Mutation spectrum; SHH; ZIC2;
   SIX3 and TGIF
ID MAXILLARY CENTRAL INCISOR; GENOTYPE-PHENOTYPE CORRELATIONS; SONIC
   HEDGEHOG MUTATION; CLINICAL SPECTRUM; TERMINAL DOMAIN; VARIABILITY;
   REARRANGEMENTS; FAMILIES; MODELS; RATES
AB Clinical molecular diagnostic centers routinely screen SHH, ZIC2, SIX3 and TGIF for mutations that can help to explain holoprosencephaly and related brain malformations. Here we report a prospective Sanger sequence analysis of 189 unrelated probands referred to our diagnostic lab for genetic testing. We identified 28 novel unique mutations in this group (15%) and no instances of deleterious mutations in two genes in the same subject. Our result extends that of other diagnostic centers and suggests that among the aggregate 475 prospectively sequenced holoprosencephaly probands there is negligible evidence for direct gene-gene interactions among these tested genes. We model the predictions of the observed mutation frequency in the context of the hypothesis that gene x gene interactions are a prerequisite for forebrain malformations, i.e. the "multiple-hit" hypothesis. We conclude that such a direct interaction would be expected to be rare and that more subtle genetic and environmental interactions are a better explanation for the clinically observed inter- and intra-familial variability. Published by Elsevier Inc.
C1 [Roessler, Erich; Velez, Jorge I.; Zhou, Nan; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mmuenke@nhgri.nih.gov
FU Division of Intramural Research of the National Human Genome Research
   Institute, National Institutes of Health
FX The authors wish to thank the patients who participated in this research
   and the many clinicians who referred them. We thank BD Solomon and D
   Pineda-Alvarez for constructive comments. JIV would like to thank Prof.
   Juan Carlos Correa for helpful comments and suggestions on the
   statistical model. This research was supported by the Division of
   Intramural Research of the National Human Genome Research Institute,
   National Institutes of Health.
NR 59
TC 15
Z9 15
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD APR
PY 2012
VL 105
IS 4
BP 658
EP 664
DI 10.1016/j.ymgme.2012.01.005
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 917OW
UT WOS:000302188700021
PM 22310223
ER

PT J
AU Markello, TC
   Carlson-Donohoe, H
   Sincan, M
   Adams, D
   Bodine, DM
   Farrar, JE
   Vlachos, A
   Lipton, JM
   Auerbach, AD
   Ostrander, EA
   Chandrasekharappa, SC
   Boerkoel, CF
   Gahl, WA
AF Markello, Thomas C.
   Carlson-Donohoe, Hannah
   Sincan, Murat
   Adams, David
   Bodine, David M.
   Farrar, Jason E.
   Vlachos, Adrianna
   Lipton, Jeffrey M.
   Auerbach, Arleen D.
   Ostrander, Elaine A.
   Chandrasekharappa, Settara C.
   Boerkoel, Cornelius F.
   Gahl, William A.
TI Sensitive quantification of mosaicism using high density SNP arrays and
   the cumulative distribution function
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Mosaicism; Continuous Distribution Function; Distribution Analysis by
   Fitting Integrated; Probabilities; DANFIP; CGH; Array comparative
   genomic hybridization
ID TURNER-SYNDROME; MICROARRAY; CGH
AB Medicine is rapidly applying exome and genome sequencing to the diagnosis and management of human disease. Somatic mosaicism, however, is not readily detectable by these means, and yet it accounts for a significant portion of undiagnosed disease. We present a rapid and sensitive method, the Continuous Distribution Function as applied to single nucleotide polymorphism (SNP) array data, to quantify somatic mosaic-ism throughout the genome. We also demonstrate application of the method to novel diseases and mechanisms. Published by Elsevier Inc.
C1 [Markello, Thomas C.; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   [Carlson-Donohoe, Hannah; Sincan, Murat; Adams, David; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Adams, David; Boerkoel, Cornelius F.] NIH, NIH Undiagnosed Dis Program, Bethesda, MD 20892 USA.
   [Bodine, David M.] NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Farrar, Jason E.] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Pediat Oncol,Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
   [Vlachos, Adrianna; Lipton, Jeffrey M.] Steven & Alexandra Cohen Childrens Med Ctr New Yo, Bone Marrow Failure Program, New Hyde Pk, NY USA.
   [Vlachos, Adrianna; Lipton, Jeffrey M.] Long Isl Sch Med, Dept Pediat & Mol Med, Hempstead, NY USA.
   [Auerbach, Arleen D.] Rockefeller Univ, New York, NY USA.
   [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Chandrasekharappa, Settara C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Markello, TC (reprint author), NHGRI, Off Clin Director, NIH, Bldg 10-10C107,10 Ctr Dr, Bethesda, MD 20892 USA.
EM markellot@mail.nih.gov
OI Farrar, Jason/0000-0003-2148-5839; Auerbach, Arleen/0000-0002-6911-8379;
   Ostrander, Elaine/0000-0001-6075-9738
FU National Human Genome Research Institute; NIH [K08 HL092224];  [RO1 HL
   079571]
FX This study was supported in part by the Intramural Program of the
   National Human Genome Research Institute.; We thank Roxanne Fischer,
   Richard Hess, MaryPat Jones and Ursula Harper in the NHGRI Genomics Core
   for their excellent technical contributions. This work was supported in
   part by the Intramural Research Program of the National Human Genome
   Research Institute. Dr. Farrar was supported by NIH grant K08 HL092224.
   Dr. Lipton and Dr. Vlachos are supported by RO1 HL 079571.
NR 15
TC 4
Z9 4
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
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD APR
PY 2012
VL 105
IS 4
BP 665
EP 671
DI 10.1016/j.ymgme.2011.12.015
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 917OW
UT WOS:000302188700022
PM 22277120
ER

PT J
AU Thomason, MK
   Fontaine, F
   De Lay, N
   Storz, G
AF Thomason, Maureen K.
   Fontaine, Fanette
   De Lay, Nicholas
   Storz, Gisela
TI A small RNA that regulates motility and biofilm formation in response to
   changes in nutrient availability in Escherichia coli
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID MESSENGER-RNA; POLYSACCHARIDE ADHESIN; OUTER-MEMBRANE;
   EXTRACELLULAR-MATRIX; POSITIVE REGULATION; ANTISENSE RNAS; NONCODING
   RNAS; CURLI; EXPRESSION; GENES
AB In bacteria, many small regulatory RNAs (sRNAs) are induced in response to specific environmental signals or stresses and act by base-pairing with mRNA targets to affect protein translation or mRNA stability. In Escherichia coli, the gene for the sRNA IS061/IsrA, here renamed McaS, was predicted to reside in an intergenic region between abgR, encoding a transcription regulator and ydaL, encoding a small MutS-related protein. We show that McaS is a similar to 95 nt transcript whose expression increases over growth, peaking in early-to-mid stationary phase, or when glucose is limiting. McaS uses three discrete single-stranded regions to regulate mRNA targets involved in various aspects of biofilm formation. McaS represses csgD, the transcription regulator of curli biogenesis and activates flhD, the master transcription regulator of flagella synthesis leading to increased motility, a process not previously reported to be regulated by sRNAs. McaS also regulates pgaA, a porin required for the export of the polysaccharide poly beta-1,6-N-acetyl-d-glucosamine. Consequently, high levels of McaS result in increased biofilm formation while a strain lacking mcaS shows reduced biofilm formation. Based on our observations, we propose that, in response to limited nutrient availability, increasing levels of McaS modulate steps in the progression to a sessile lifestyle.
C1 [Thomason, Maureen K.; Fontaine, Fanette; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
   [Thomason, Maureen K.] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA.
   [De Lay, Nicholas] NCI, Mol Biol Lab, 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
FX We thank M. Jarnik for help with the electron microscopy, S. Adhya for
   providing the purified CRP and N. Majdalani for providing the anti-RpoS
   antibody. We would like to thank S. Gottesman and current and former
   members of the Storz lab for comments on the manuscript. This work was
   supported by the Intramural Research Program of the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development.
NR 75
TC 84
Z9 87
U1 2
U2 32
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 APR
PY 2012
VL 84
IS 1
BP 17
EP 35
DI 10.1111/j.1365-2958.2012.07965.x
PG 19
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 915HA
UT WOS:000302013500003
PM 22289118
ER

PT J
AU Lee, H
   Lamichhane, AK
   Garraffo, HM
   Kwon-Chung, KJ
   Chang, YC
AF Lee, Hyeseung
   Lamichhane, Ami Khanal
   Garraffo, H. Martin
   Kwon-Chung, Kyung J.
   Chang, Yun C.
TI Involvement of PDK1, PKC and TOR signalling pathways in basal
   fluconazole tolerance in Cryptococcus neoformans
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID CELL-WALL INTEGRITY; FUNGAL DRUG-RESISTANCE; CANDIDA-ALBICANS;
   SACCHAROMYCES-CEREVISIAE; AZOLE RESISTANCE; SCHIZOSACCHAROMYCES-POMBE;
   PROTEIN-KINASES; FISSION YEAST; MULTIDRUG-RESISTANCE; ANTIFUNGAL AGENTS
AB This study shows the importance of PDK1, TOR and PKC signalling pathways to the basal tolerance of Cryptococcus neoformans towards fluconazole, the widely used drug for treatment of cryptococcosis. Mutations in genes integral to these pathway resulted in hypersensitivity to the drug. Upon fluconazole treatment, Mpk1, the downstream target of PKC was phosphorylated and its phosphorylation required Pdk1. We show genetically that the PDK1 and TOR phosphorylation sites in Ypk1 as well as the kinase activity of Ypk1 are required for the fluconazole basal tolerance. The involvement of these pathways in fluconazole basal tolerance was associated with sphingolipid homeostasis. Deletion of PDK1, SIN1 or YPK1 but not MPK1 affected cell viability in the presence of sphingolipid biosynthesis inhibitors. Concurrently, pdk1?, sin1?, ypk1? and mpk1? exhibited altered sphingolipid content and elevated fluconazole accumulation compared with the wild type. The fluconazole hypersensitivity phenotype of these mutants, therefore, appears to be the result of malfunction of the influx/efflux systems due to modifications of membrane sphingolipid content. Interestingly, the reduced virulence of these strains in mice suggests that the cryptococcal PDK1, PKC, and likely the TOR pathways play an important role in managing stress exerted either by fluconazole or by the host environment.
C1 [Lee, Hyeseung; Lamichhane, Ami Khanal; Kwon-Chung, Kyung J.; Chang, Yun C.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
   [Garraffo, H. Martin] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Chang, YC (reprint author), NIAID, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ychang@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH
FX We thank Y.J. Kim, T. Balla, M.A. Singh and M. Del Poeta for suggestion
   and technical help in analysis of complex sphingolipids, Andy Han for
   technical help in initial screening of the mutants and A. Varma for
   critical discussions and reading of the manuscript. This study was
   supported by funds from the intramural programme of the National
   Institute of Allergy and Infectious Diseases, NIH. The funders had no
   role in study design, data collection and analysis, decision to publish
   or preparation of the manuscript.
NR 91
TC 16
Z9 17
U1 0
U2 7
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 APR
PY 2012
VL 84
IS 1
BP 130
EP 146
DI 10.1111/j.1365-2958.2012.08016.x
PG 17
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 915HA
UT WOS:000302013500011
PM 22339665
ER

PT J
AU Willour, VL
   Seifuddin, F
   Mahon, PB
   Jancic, D
   Pirooznia, M
   Steele, J
   Schweizer, B
   Goes, FS
   Mondimore, FM
   MacKinnon, DF
   Perlis, RH
   Lee, PH
   Huang, J
   Kelsoe, JR
   Shilling, PD
   Rietschel, M
   Nothen, M
   Cichon, S
   Gurling, H
   Purcell, S
   Smoller, JW
   Craddock, N
   DePaulo, JR
   Schulze, TG
   McMahon, FJ
   Zandi, PP
   Potash, JB
AF Willour, V. L.
   Seifuddin, F.
   Mahon, P. B.
   Jancic, D.
   Pirooznia, M.
   Steele, J.
   Schweizer, B.
   Goes, F. S.
   Mondimore, F. M.
   MacKinnon, D. F.
   Perlis, R. H.
   Lee, P. H.
   Huang, J.
   Kelsoe, J. R.
   Shilling, P. D.
   Rietschel, M.
   Noethen, M.
   Cichon, S.
   Gurling, H.
   Purcell, S.
   Smoller, J. W.
   Craddock, N.
   DePaulo, J. R., Jr.
   Schulze, T. G.
   McMahon, F. J.
   Zandi, P. P.
   Potash, J. B.
CA BiGS Consortium
TI A genome-wide association study of attempted suicide
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE ACP1; LRRTM4; 2p25; Wnt; lithium
ID PROTEIN-TYROSINE-PHOSPHATASE; BIPOLAR DISORDER; MAJOR DEPRESSION;
   GENE-EXPRESSION; EARLY-ONSET; GENOTYPE IMPUTATION; PREFRONTAL CORTEX;
   FAMILIAL PATHWAYS; BEHAVIOR; LINKAGE
AB The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. Although attempted suicide linkage regions have been identified on 2p11-12 and 6q25-26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single-nucleotide polymorphism (SNP) genotypes of 1201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1497 BP subjects without a history of suicide attempts. In all, 2507 SNPs with evidence for association at P < 0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (P = 5.07 x 10(-8)). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. Molecular Psychiatry (2012) 17, 433-444; doi: 10.1038/mp.2011.4; published online 22 March 2011
C1 [Willour, V. L.; Seifuddin, F.; Mahon, P. B.; Jancic, D.; Pirooznia, M.; Schweizer, B.; Goes, F. S.; Mondimore, F. M.; MacKinnon, D. F.; DePaulo, J. R., Jr.; Zandi, P. P.; Potash, J. B.] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
   [Steele, J.; Schulze, T. G.; McMahon, F. J.] Natl Inst Mental Hlth Intramural Res Program, Genet Basis Mood & Anxiety Disorders Unit, NIH, US Dept HHS, Bethesda, MD USA.
   [Perlis, R. H.; Lee, P. H.; Huang, J.; Purcell, S.; Smoller, J. W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
   [Perlis, R. H.; Lee, P. H.; Huang, J.; Purcell, S.; Smoller, J. W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Kelsoe, J. R.; Shilling, P. D.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
   [Rietschel, M.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany.
   [Rietschel, M.] Univ Bonn, Dept Psychiat, Bonn, Germany.
   [Noethen, M.; Cichon, S.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
   [Noethen, M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
   [Cichon, S.] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany.
   [Gurling, H.] UCL, Dept Mental Hlth Sci, London, England.
   [Craddock, N.] Cardiff Univ, Sch Med, Dept Psychol, Cardiff, Wales.
   [Schulze, T. G.] Univ Gottingen, Dept Psychiat & Psychotherapy, Sect Psychiat Genet, Gottingen, Germany.
RP Willour, VL (reprint author), Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-132, Baltimore, MD 21287 USA.
EM willour@jhmi.edu
RI Smith, Erin/E-5933-2011; McInnis, Melvin/F-6963-2012; Schulze,
   Thomas/H-2157-2013; Gurling, Hugh/A-5029-2010; Cichon, Sven/H-8803-2013;
   Cichon, Sven/B-9618-2014; Zhang, Peng/N-2920-2014; 
OI McInnis, Melvin/0000-0002-0375-6247; Cichon, Sven/0000-0002-9475-086X;
   Cichon, Sven/0000-0002-9475-086X; Zhang, Peng/0000-0003-1182-1392;
   Nothen, Markus/0000-0002-8770-2464; McMahon, Francis/0000-0002-9469-305X
FU Concordant Rater Systems; Proteus Biomedical; RIDVentures; National
   Institute of Mental Health [MH079240]; American Foundation for Suicide
   Prevention; Margaret Price Investigatorships;  [R01 MH079799]
FX The authors declare no conflict of interest. Dr Perlis has received
   consulting fees from Concordant Rater Systems, Proteus Biomedical, and
   RIDVentures, and royalties/patent fees from Concordant Rater Systems.;
   This work was supported by grants from the National Institute of Mental
   Health (MH079240 to VLW) and the American Foundation for Suicide
   Prevention (VLW). It was also supported in part by R01 MH079799 (JWS).
   Drs Willour and Potash were also supported by Margaret Price
   Investigatorships. DNA samples were prepared and distributed by Rutgers
   University under a contract from the NIMH. We are grateful to the many
   interviewers and diagnosticians who contributed to this project, and to
   the families who devoted their time and effort to the study. Genome-wide
   SNP genotyping of the NIMH samples was performed through the Genetic
   Association Information Network under the direction of The Bipolar
   Genome Study (BiGS) Consortium. The Principal Investigators and
   Co-Investigators were: University of California San Diego, La Jolla, CA:
   John R Kelsoe (PI), Tiffany A Greenwood, Thomas B Barrett, Caroline M
   Nievergelt, Rebecca McKinney, Paul D Shilling; Scripps Research
   Institute, La Jolla, CA: Nicholas Schork (PI), Erin N Smith, Cinnamon S
   Bloss; Indiana University, Bloomington, IN: John I Nurnberger, Jr (PI),
   Howard J Edenberg, Tatiana Foroud, Daniel M Koller; University of
   Chicago, Chicago, IL: Elliot Gershon (PI), Chunyu Liu, Judith A Badner;
   Rush University Medical Center, Chicago, IL: William A Scheftner; Howard
   University, Washington, DC: William B Lawson (PI), Evaristus A Nwulia,
   Maria Hipolito; University of Iowa, Iowa City, IA: William Coryell (PI);
   Washington University, St Louis, MO: John Rice (PI); University of
   California San Francisco, San Francisco, CA: William Byerley (PI);
   National Institute of Mental Health, Bethesda, MD: Francis McMahon (PI),
   Thomas G Schulze; University of Pennsylvania, Philadelphia, PA: Wade
   Berrettini (PI); Johns Hopkins University, Baltimore, MD: James B Potash
   (PI), Peter P Zandi, Pamela B Mahon; University of Michigan, Ann Arbor,
   MI: Melvin G McInnis (PI), Sebastian Zollner, Peng Zhang; The
   Translational Genomics Research Institute, Phoenix, AZ: David Craig
   (PI), Szabolics Szelinger. Data and biomaterials were collected in four
   projects that participated in the National Institute of Mental Health
   (NIMH) Bipolar Disorder Genetics Initiative. From 1991 to 1998, the
   Principal Investigators and Co-Investigators were: Indiana University,
   Indianapolis, IN, U01 MH46282: John Nurnberger, Marvin Miller and
   Elizabeth Bowman; Washington University, St Louis, MO, U01 MH46280:
   Theodore Reich, Allison Goate and John Rice; Johns Hopkins University,
   Baltimore, MD U01 MH46274: J Raymond DePaulo, Jr, Sylvia Simpson and
   Colin Stine; NIMH Intramural Research Program, Clinical Neurogenetics
   Branch, Bethesda, MD: Elliot Gershon, Diane Kazuba and Elizabeth
   Maxwell. Data and biomaterials were collected as part of 10 projects
   that participated in the National Institute of Mental Health (NIMH)
   Bipolar Disorder Genetics Initiative.; From 1999 to 2003, the Principal
   Investigators and Co-Investigators were: Indiana University,
   Indianapolis, IN, R01 MH59545: John Nurnberger, Marvin J Miller,
   Elizabeth S Bowman, N Leela Rau, P Ryan Moe, Nalini Samavedy, Rif
   El-Mallakh (at the University of Louisville), Husseini Manji (at the
   Wayne State University), Debra A Glitz (at the Wayne State University),
   Eric T Meyer, Carrie Smiley, Tatiana Foroud, Leah Flury, Danielle M
   Dick, Howard Edenberg; Washington University, St Louis, MO, R01
   MH059534: John Rice, Theodore Reich, Allison Goate, Laura Bierut; Johns
   Hopkins University, Baltimore, MD, R01 MH59533: Melvin McInnis, J
   Raymond DePaulo, Jr, Dean F MacKinnon, Francis M Mondimore, James B
   Potash, Peter P Zandi, Dimitrios Avramopoulos and Jennifer Payne;
   University of Pennsylvania, PA, R01 MH59553: Wade Berrettini; University
   of California at Irvine, CA, R01 MH60068: William Byerley and Mark
   Vawter; University of Iowa, IA, R01 MH059548: William Coryell and
   Raymond Crowe; University of Chicago, IL, R01 MH59535: Elliot Gershon,
   Judith Badner, Francis McMahon, Chunyu Liu, Alan Sanders, Maria Caserta,
   Steven Dinwiddie, Tu Nguyen, Donna Harakal; University of California at
   San Diego, CA, R01 MH59567: John Kelsoe, Rebecca McKinney; Rush
   University, IL, R01 MH059556: William Scheftner, Howard M Kravitz, Diana
   Marta, Annette Vaughn-Brown and Laurie Bederow; NIMH Intramural Research
   Program, Bethesda, MD, 1Z01MH002810-01: Francis J Mc Mahon, Layla
   Kassem, Sevilla Detera-Wadleigh, Lisa Austin and Dennis L Murphy. Data
   and biomaterials were collected as part of 11 projects (Study 40) that
   participated in the National Institute of Mental Health (NIMH) Bipolar
   Disorder Genetics Initiative. From 2003 to 2007, the Principal
   Investigators and Co-Investigators were: Indiana University,
   Indianapolis, IN, R01 MH59545: John Nurnberger, Marvin J Miller,
   Elizabeth S Bowman, N Leela Rau, P Ryan Moe, Nalini Samavedy, Rif
   El-Mallakh (at the University of Louisville), Husseini Manji (at Johnson
   and Johnson), Debra A Glitz (at the Wayne State University), Eric T
   Meyer (at the Oxford University, UK), Carrie Smiley, Tatiana Foroud,
   Leah Flury, Danielle M Dick (at the Virginia Commonwealth University),
   Howard Edenberg; Washington University, St Louis, MO, R01 MH059534: John
   Rice, Theodore Reich, Allison Goate, Laura Bierut K02 DA21237; Johns
   Hopkins University, Baltimore, MD, R01 MH59533: Melvin McInnis, J
   Raymond DePaulo, Jr, Dean F MacKinnon, Francis M Mondimore, James B
   Potash, Peter P Zandi, Dimitrios Avramopoulos and Jennifer Payne;
   University of Pennsylvania, PA, R01 MH59553: Wade Berrettini; University
   of California at San Francisco, CA, R01 MH60068: William Byerley and
   Sophia Vinogradov; University of Iowa, IA, R01 MH059548: William
   Coryell, and Raymond Crowe; University of Chicago, IL, R01 MH59535:
   Elliot Gershon, Judith Badner, Francis McMahon, Chunyu Liu, Alan
   Sanders, Maria Caserta, Steven Dinwiddie, Tu Nguyen, Donna Harakal;
   University of California at San Diego, CA, R01 MH59567: John Kelsoe,
   Rebecca McKinney; Rush University, IL, R01 MH059556: William Scheftner,
   Howard M Kravitz, Diana Marta, Annette Vaughn-Brown, and Laurie Bederow;
   NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01: Francis
   J McMahon, Layla Kassem, Sevilla Detera-Wadleigh, Lisa Austin, Dennis L
   Murphy; Howard University: William B Lawson, Evarista Nwulia, and Maria
   Hipolito.
NR 47
TC 43
Z9 43
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD APR
PY 2012
VL 17
IS 4
BP 433
EP 444
DI 10.1038/mp.2011.4
PG 12
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 917KL
UT WOS:000302173900010
PM 21423239
ER

PT J
AU Zatorre, RJ
   Fields, RD
   Johansen-Berg, H
AF Zatorre, Robert J.
   Fields, R. Douglas
   Johansen-Berg, Heidi
TI Plasticity in gray and white: neuroimaging changes in brain structure
   during learning
SO NATURE NEUROSCIENCE
LA English
DT Review
ID VOXEL-BASED MORPHOMETRY; IN-VIVO MRI; ACTION-POTENTIALS;
   MULTIPLE-SCLEROSIS; VAL66MET POLYMORPHISM; CORTICAL THICKNESS; MATTER
   DEVELOPMENT; STRUCTURE PREDICTS; CORPUS-CALLOSUM; NERVOUS-SYSTEM
AB Human brain imaging has identified structural changes in gray and white matter that occur with learning. However, ascribing imaging measures to underlying cellular and molecular events is challenging. Here we review human neuroimaging findings of structural plasticity and then discuss cellular and molecular level changes that could underlie observed imaging effects. Greater dialog between researchers in these different fields would help to facilitate cross-talk between cellular and systems level explanations of how learning sculpts brain structure.
C1 [Johansen-Berg, Heidi] John Radcliffe Hosp, Oxford Ctr Funct MRI Brain FMRIB, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
   [Zatorre, Robert J.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
   [Fields, R. Douglas] NICHHD, Nervous Syst Dev, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Fields, R. Douglas] NICHHD, Plast Sect, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Johansen-Berg, H (reprint author), John Radcliffe Hosp, Oxford Ctr Funct MRI Brain FMRIB, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
EM heidi@fmrib.ox.ac.uk
OI Johansen-Berg, Heidi/0000-0002-4134-9730
FU Canadian Institutes of Health Research; Natural Sciences and Engineering
   Research Council of Canada; US National Institutes of Health; Wellcome
   Trust
FX R.J.Z. is supported by the Canadian Institutes of Health Research and
   the Natural Sciences and Engineering Research Council of Canada; R.D.F.
   is supported by funds for intramural research at the US National
   Institutes of Health; H.J.-B. is supported by the Wellcome Trust.
NR 101
TC 395
Z9 402
U1 14
U2 121
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD APR
PY 2012
VL 15
IS 4
BP 528
EP 536
DI 10.1038/nn.3045
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 916PA
UT WOS:000302114500010
PM 22426254
ER

PT J
AU Restifo, NP
   Dudley, ME
   Rosenberg, SA
AF Restifo, Nicholas P.
   Dudley, Mark E.
   Rosenberg, Steven A.
TI Adoptive immunotherapy for cancer: harnessing the T cell response
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID CHIMERIC ANTIGEN RECEPTOR; VERSUS-HOST-DISEASE; ESTABLISHED PULMONARY
   METASTASES; TUMOR-INFILTRATING LYMPHOCYTES; SUPERIOR ANTITUMOR IMMUNITY;
   HEMATOPOIETIC STEM-CELLS; IN-VIVO; GENE-THERAPY; MELANOMA PATIENTS;
   ENGINEERED LYMPHOCYTES
AB Immunotherapy based on the adoptive transfer of naturally occurring or gene-engineered T cells can mediate tumour regression in patients with metastatic cancer. Here, we discuss progress in the use of adoptively transferred T cells, focusing on how they can mediate tumour cell eradication. Recent advances include more accurate targeting of antigens expressed by tumours and the associated vasculature, and the successful use of gene engineering to re-target T cells before their transfer into the patient. We also describe how new research has helped to identify the particular T cell subsets that can most effectively promote tumour eradication.
C1 [Restifo, Nicholas P.; Dudley, Mark E.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
EM restifon@mail.nih.gov; sar@mail.nih.gov
RI Restifo, Nicholas/A-5713-2008; 
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Center for Cancer Research, US National Cancer Institute (NCI), National
   Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
   for Cancer Research, US National Cancer Institute (NCI), National
   Institutes of Health. The authors would like to thank C. Klebanoff, L.
   Gattinoni, C. Hinrichs and P. Muranski for discussions about T cell
   differentiation, M. Bachinski for editorial help, E. Tran for critically
   reading the manuscript, and all the members of the translational
   immunology team at the NCI, especially J. C. Yang, P. F. Robbins, R. A.
   Morgan, R. M. Sherry, S. Feldman, M. Parkhurst, M. Hughes, G. Phan and
   U. Kammula.
NR 166
TC 546
Z9 556
U1 30
U2 302
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD APR
PY 2012
VL 12
IS 4
BP 269
EP 281
DI 10.1038/nri3191
PG 13
WC Immunology
SC Immunology
GA 916WA
UT WOS:000302132700012
PM 22437939
ER

PT J
AU Weng, NP
   Araki, Y
   Subedi, K
AF Weng, Nan-ping
   Araki, Yasuto
   Subedi, Kalpana
TI The molecular basis of the memory T cell response: differential gene
   expression and its epigenetic regulation
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID HEMATOPOIETIC STEM-CELLS; IFN-GAMMA LOCI; HISTONE ACETYLATION; CUTTING
   EDGE; HUMAN GENOME; CPG ISLANDS; CHROMATIN-STRUCTURE; DNA METHYLATION;
   DYNAMIC CHANGES; B-CELLS
AB How the immune system remembers a previous encounter with a pathogen and responds more efficiently to a subsequent encounter has been one of the central enigmas for immunologists for over a century. The identification of pathogen-specific memory lymphocytes that arise after an infection provided a cellular basis for immunological memory. But the molecular mechanisms of immunological memory remain only partially understood. The emerging evidence suggests that epigenetic changes have a key role in controlling the distinct transcriptional profiles of memory lymphocytes and thus in shaping their function. In this Review, we summarize the recent progress that has been made in assessing the differential gene expression and chromatin modifications in memory CD4(+) and CD8(+) T cells, and we present our current understanding of the molecular basis of memory T cell function.
C1 [Weng, Nan-ping; Araki, Yasuto; Subedi, Kalpana] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Weng, NP (reprint author), NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM Wengn@mail.nih.gov
RI perumal, murugiah/D-1565-2012
FU US National Institute on Aging, National Institutes of Health
FX We thank R. Hodes, K. Zhao and the anonymous reviewers for critical
   reading of the manuscript and helpful suggestions. This research was
   supported by the Intramural Research Programs of the US National
   Institute on Aging, National Institutes of Health.
NR 67
TC 89
Z9 91
U1 2
U2 24
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 APR
PY 2012
VL 12
IS 4
BP 306
EP 315
DI 10.1038/nri3173
PG 10
WC Immunology
SC Immunology
GA 916WA
UT WOS:000302132700015
PM 22421787
ER

PT J
AU Crowley, RW
   Asthagiri, AR
   Starke, RM
   Zusman, EE
   Chiocca, EA
   Lonser, RR
AF Crowley, R. Webster
   Asthagiri, Ashok R.
   Starke, Robert M.
   Zusman, Edie E.
   Chiocca, E. Antonio
   Lonser, Russell R.
CA Res Comm Congress Neurological
TI In-training Factors Predictive of Choosing and Sustaining a Productive
   Academic Career Path in Neurological Surgery
SO NEUROSURGERY
LA English
DT Article
DE Academic career; Neurosurgery; Publications; Residency training
ID MEDICAL-SCHOOL PERFORMANCE; RESIDENT-SELECTION; CRITERIA; CHOICE
AB BACKGROUND: Factors during neurosurgical residency that are predictive of an academic career path and promotion have not been defined.
   OBJECTIVE: To determine factors associated with selecting and sustaining an academic career in neurosurgery by analyzing in-training factors for all graduates of American College of Graduate Medical Education (ACGME)-accredited programs between 1985 and 1990.
   METHODS: Neurological surgery residency graduates (between 1985 and 1990) from ACGME-approved training programs were analyzed to determine factors associated with choosing an academic career path and having academic success.
   RESULTS: Information was available for 717 of the 720 (99%) neurological surgery resident training graduates (678 male, 39 female). One hundred thirty-eight graduates (19.3%) held full-time academic positions. One hundred seven (14.9%) were professors and 35 (4.9%) were department chairs/chiefs. An academic career path/success was associated with more total (5.1 vs 1.9; P < .001) and first-author publications (3.0 vs 1.0; P < .001) during residency. Promotion to professor or chair/chief was associated with more publications during residency (P < .001). Total publications and first-author publications were independent predictors of holding a current academic position and becoming professor or chair/chief. Although male trainees published more than female trainees (2.6 vs 0.9 publications; P < .004) during training, no significant sex difference was observed regarding current academic position. Program size (>= 2 graduates a year; P = .02) was predictive of an academic career but not predictive of becoming professor or chair/chief (P > .05).
   CONCLUSION: Defined in-training factors including number of total publications, number of first-author publications, and program size are predictive of residents choosing and succeeding in an academic career path.
C1 [Crowley, R. Webster; Starke, Robert M.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA.
   [Asthagiri, Ashok R.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
   [Zusman, Edie E.] Sutter Neurosci Inst, Sacramento, CA USA.
   [Chiocca, E. Antonio] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA.
RP Crowley, RW (reprint author), Barrow Neurol Inst, 2910 N 3rd Ave, Phoenix, AZ 85013 USA.
EM Webster.crowley@bnaneuro.net
FU National Institutes of Health, National Institute of Neurological
   Disorders and Stroke
FX We would like to thank the American Board of Neurological Surgeons, in
   particular Mary Louise Sanderson and Maggie Hall. Their assistance was
   invaluable in accumulating and providing the list of neurosurgical
   residency graduates included in this study. This research was supported
   in part by the Intramural Research Program of the National Institutes of
   Health, National Institute of Neurological Disorders and Stroke. The
   Research Committee of the Congress of Neurological Surgeons comprises
   the following individuals: Russell R. Lonser, MD (chair), National
   Institutes of Health, Bethesda, Maryland; P. David Adelson, MD, Phoenix
   Children's Hospital, Phoenix, Arizona; Ashok R. Asthagiri, MD, National
   Institutes of Health, Bethesda, Maryland; Mitchel S. Berger, MD,
   University of California, San Francisco, San Francisco, California;
   Nicholas M. Boulis, MD, Emory University, Atlanta, Georgia; Thomas C.
   Chen, MD, PhD, University of Southern California, Los Angeles,
   California; E. Antonio Chiocca, MD, PhD, Ohio State University,
   Columbus, Ohio; E. Sander Connolly, MD, Columbia University, New York,
   New York; R. Webster Crowley, MD, University of Virginia,
   Charlottesville, Virginia; Ralph G. Dacey, MD, Washington University,
   St. Louis, Missouri; Zoher Ghogawala, MD, Greenwich Hospital, Greenwich,
   Connecticut; Rachel Groman, American Association of Neurological
   Surgeons/Congress of Neurological Surgeons Washington Office,
   Washington, DC; Robert E. Gross, MD, PhD, Emory University, Atlanta,
   Georgia; Murat Gunel, MD, Yale University, New Haven, Connecticut; David
   D. Limbrick, MD, PhD, Washington University, St. Louis, Missouri; Guy
   McKhann, MD, Columbia University, New York, New York; John K. Park, MD,
   PhD, National Institutes of Health, Bethesda, Maryland; Ganesh Rao, MD,
   MD Anderson Cancer Center, Houston, Texas; Jonas Sheehan, MD,
   Pennsylvania State University, Hershey, Pennsylvania; Michael P.
   Steinmetz, MD, Cleveland Clinic, Cleveland, Ohio; Michael A. Vogelbaum,
   MD, PhD, Cleveland Clinic, Cleveland, Ohio; Gregory J. Zipfel, MD,
   Washington University, St. Louis, Missouri; and Edie E. Zusman, MD,
   Sutter Neuroscience Institute, Sacramento, California.
NR 13
TC 8
Z9 8
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD APR
PY 2012
VL 70
IS 4
BP 1024
EP 1032
DI 10.1227/NEU.0b013e3182367143
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 914FF
UT WOS:000301934000079
PM 21946503
ER

PT J
AU Jackson, AB
   Nanda, PK
   Rold, TL
   Sieckman, GL
   Szczodroski, AF
   Hoffman, TJ
   Chen, XY
   Smith, CJ
AF Jackson, Andrew B.
   Nanda, Prasant K.
   Rold, Tammy L.
   Sieckman, Gary L.
   Szczodroski, Ashley F.
   Hoffman, Timothy J.
   Chen, Xiaoyuan
   Smith, Charles J.
TI Cu-64-NO2A-RGD-Glu-6-Ahx-BBN(7-14)NH2: a heterodimeric targeting vector
   for positron emission tomography imaging of prostate cancer
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Cu-64; RGD-BBN; Heterodimeric peptide; Gastrin-releasing peptide
   receptor (GRPr); Integrin alpha(v)beta(3) receptor; Positron emission
   tomography (PET)
ID PEPTIDE RADIOPHARMACEUTICALS; BREAST-CANCER; RGD PEPTIDES; IN-VIVO;
   BOMBESIN; EXPRESSION; TUMORS; PET; RADIOTRACERS; RECEPTORS
AB Introduction: The present study describes the design and development of a new heterodimeric RGD-bombesin (BBN) agonist peptide ligand for dual receptor targeting of the form Cu-64-NO2A-RGD-Glu-6-Ahx-BBN(7-14)NH2 in which Cu-64=a positron emitting radiometal; NO2A=1,4,7-triazacyclononane-1,4-diacetic acid; Glu=glutamic acid; 6-Ahx=6-aminohexanoic acid; RGD=the amino acid sequence [Arg-Gly-Asp], a nonregulatory peptide that has been used extensively to target alpha(v)beta(3) receptors up-regulated on tumor cells and neovasculature; and BBN(7-14)NH2=Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2, an agonist analogue of bombesin peptide for specific targeting of the gastrin-releasing peptide receptor (GRPr).
   Methods: RGD-Glu-6-Ahx-BBN(7-14)NH2 was manually coupled with NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and the resulting conjugate was labeled with Cu-64 to yield Cu-64-NO2A-RGD-Glu-6-Ahx-BBN(7-14)NH2. Purification was achieved via reversed-phase high-performance liquid chromatography and characterization confirmed by electrospray ionization mass spectrometry.
   Results: Competitive displacement binding assays displayed single-digit nanomolar IC50 values showing very high binding affinities toward the GRPr for the new heterodimeric peptide analogues. In vivo biodistribution studies showed high uptake and retention of tumor-associated radioactivity in PC-3 tumor-bearing rodent models with little accumulation and retention in nontarget tissues. The radiolabeled conjugate also exhibited rapid urinary excretion and high tumor-to-background ratios. Micro-positron emission tomography (microPET) molecular imaging investigations produced high-quality, high-contrast images in PC-3 tumor-bearing mice 15 h postinjection.
   Conclusions: Based on microPET imaging experiments that show high-quality, high-contrast images with virtually no residual gastrointestinal radioactivity, this new heterodimeric RGD-BBN conjugate can be considered as a promising PET tracer candidate for the diagnosis of GRPr-positive tumors in human patients. Published by Elsevier Inc.
C1 [Smith, Charles J.] Univ Missouri, Dept Radiol, MU Sch Med, Res Reactor Ctr, Columbia, MO 65211 USA.
   [Jackson, Andrew B.; Nanda, Prasant K.; Hoffman, Timothy J.; Smith, Charles J.] Univ Missouri, Sch Med, Dept Radiol, Columbia, MO 65211 USA.
   [Rold, Tammy L.; Sieckman, Gary L.; Szczodroski, Ashley F.; Hoffman, Timothy J.; Smith, Charles J.] Harry S Truman Mem Vet Hosp, Div Res, Columbia, MO 65201 USA.
   [Hoffman, Timothy J.; Smith, Charles J.] Univ Missouri, Sch Med, Dept Internal Med, Columbia, MO 65211 USA.
   [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Smith, CJ (reprint author), Univ Missouri, Dept Radiol, MU Sch Med, Res Reactor Ctr, 1 Hosp Dr, Columbia, MO 65211 USA.
EM smithcj@health.missouri.edu
FU United States Department of Veterans' Affairs VA
FX This material was the result of work supported with resources and the
   use of facilities at the Harry S. Truman Memorial Veterans' Hospital,
   Columbia, MO 65201, and the University of Missouri School of Medicine,
   Columbia, MO 65211, USA. This work was funded in part by The United
   States Department of Veterans' Affairs VA Merit Award.
NR 29
TC 22
Z9 23
U1 3
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD APR
PY 2012
VL 39
IS 3
BP 377
EP 387
DI 10.1016/j.nucmedbio.2011.10.004
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 914OV
UT WOS:000301961700007
PM 22226021
ER

PT J
AU Leventhal, A
   Chen, G
   Negro, A
   Boehm, M
AF Leventhal, A.
   Chen, G.
   Negro, A.
   Boehm, M.
TI The benefits and risks of stem cell technology
SO ORAL DISEASES
LA English
DT Review
DE medicine; stem cell; induced pluripotent stem cell; embryonic stem cell;
   regenerative therapy
ID UMBILICAL-CORD BLOOD; LONG-QT SYNDROME; BONE-MARROW;
   MYOCARDIAL-INFARCTION; PROGENITOR CELLS; MYELODYSPLASTIC SYNDROMES;
   DEFINED FACTORS; DENTAL-TISSUES; CARDIAC REPAIR; STROMAL CELLS
AB The potential impact of stem cell technology on medical and dental practice is vast. Stem cell research will not only provide the foundation for future therapies, but also reveal unique insights into basic disease mechanisms. Therefore, an understanding of stem cell technology will be necessary for clinicians in the future. Herein, we give a basic overview of stem cell biology and therapeutics for the practicing clinician. Oral Diseases ( 2012) 18, 217-222
C1 [Boehm, M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20817 USA.
RP Boehm, M (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10 CRC,Room 5-3132, Bethesda, MD 20817 USA.
EM boehmm@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL006079-03]
NR 62
TC 1
Z9 1
U1 1
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD APR
PY 2012
VL 18
IS 3
BP 217
EP 222
DI 10.1111/j.1601-0825.2011.01870.x
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 901RZ
UT WOS:000300985800001
PM 22093062
ER

PT J
AU Jarcho, JM
   Mayer, EA
   Jiang, ZK
   Feier, NA
   London, ED
AF Jarcho, Johanna M.
   Mayer, Emeran A.
   Jiang, Ziyue Karen
   Feier, Natasha A.
   London, Edythe D.
TI Pain, affective symptoms, and cognitive deficits in patients with
   cerebral dopamine dysfunction
SO PAIN
LA English
DT Review
DE Dopamine; Chronic pain; Depression; Anxiety; Parkinson disease; Drug
   abuse; Schizophrenia
ID CATECHOL-O-METHYLTRANSFERASE; RECEPTOR-BINDING CHARACTERISTICS; COMT
   VAL(158)MET POLYMORPHISM; BURNING MOUTH SYNDROME; LONG-TERM NOCICEPTION;
   RAT NUCLEUS-ACCUMBENS; DECISION-MAKING TASK; PARKINSONS-DISEASE; HUMAN
   BRAIN; TRANSPORTER AVAILABILITY
AB Converging preclinical, and human epidemiological, neuroimaging, and genetic evidence suggests a central role for dopamine neurotransmission in modulating pain perception and analgesia. Dysregulation in dopamine signaling may modulate the experience of pain both directly, by enhancing or diminishing the propagation of nociceptive signals, and indirectly, by influencing affective and cognitive processes, which affect the expectation, experience, and interpretation of nociceptive signals. Hypersensitivity to pain and high rates of comorbid chronic pain are common in disorders linked with deficits in dopamine system function, including disorders of mood and affect, substance abuse, and Parkinson disease. Hyposensitivity to pain, however, is common in patients with schizophrenia, which has been linked with excessive dopamine neurotransmission. Although patients are typically affected most by the primary symptoms of their disorders, alterations in pain perception may further increase the burden of their illness, compromising their quality of life. The present review focuses on this relationship, and discusses clinical and potential therapeutic implications for both patients with dopamine-related disorders and those with chronic pain syndromes. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Mayer, Emeran A.] Univ Calif Los Angeles, Ctr Neurobiol Stress, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
   [Jarcho, Johanna M.] NIMH, Bethesda, MD 20892 USA.
   [Jarcho, Johanna M.; Mayer, Emeran A.; Feier, Natasha A.; London, Edythe D.] Univ Calif Los Angeles, Oppenheimer Family Ctr Neurobiol Stress, Dept Med, Los Angeles, CA 90095 USA.
   [Jiang, Ziyue Karen; London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA.
RP Mayer, EA (reprint author), Univ Calif Los Angeles, Ctr Neurobiol Stress, Dept Mol & Med Pharmacol, CHS 42-210,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM emayer@ucla.edu
OI Jarcho, Johanna/0000-0001-9075-6968
FU National Institutes of Health [T32 MH017140, DK 64531, DK 48351, DK
   082370]; Thomas P. and Katherine K. Pike Chair in Addiction Studies;
   Margaret Greene Family Trust
FX This work was supported in part by National Institutes of Health Grants
   T32 MH017140 (JMJ), DK 64531, DK 48351, and DK 082370 (EM), and from the
   Thomas P. and Katherine K. Pike Chair in Addiction Studies, and the
   Margaret Greene Family Trust (EDL).
NR 175
TC 45
Z9 46
U1 2
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD APR
PY 2012
VL 153
IS 4
BP 744
EP 754
DI 10.1016/j.pain.2012.01.002
PG 11
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 913KS
UT WOS:000301877300006
PM 22386471
ER

PT J
AU Morton, CL
   Maris, JM
   Keir, ST
   Gorlick, R
   Kolb, EA
   Billups, CA
   Wu, JR
   Smith, MA
   Houghton, PJ
AF Morton, Christopher L.
   Maris, John M.
   Keir, Stephen T.
   Gorlick, Richard
   Kolb, E. Anders
   Billups, Catherine A.
   Wu, Jianrong
   Smith, Malcolm A.
   Houghton, Peter J.
TI Combination testing of cediranib (AZD2171) against childhood cancer
   models by the pediatric preclinical testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE AZD2171; cediranib; developmental therapeutics; preclinical testing
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; PHASE-I;
   COLORECTAL-CANCER; MAMMALIAN TARGET; MTOR INHIBITOR; RAPAMYCIN;
   ANGIOGENESIS; PATHWAY; POTENT
AB Background Cediranib (AZD2171) is a potent small molecule inhibitor of vascular endothelial growth factor (VEGF) receptors. Cediranib has demonstrated single agent activity in several adult cancers and is being studied in combination with standard cytotoxic agents in multiple disease settings. Procedures. Cediranib was tested in vivo against six childhood tumor xenograft models (four sarcomas, one glioblastoma, one neuroblastoma) alone or combined with cyclophosphamide (two models), vincristine (three models) or cisplatin (one model), each administered at its maximum tolerated dose, or rapamycin (six models). Results. The combination of cediranib with standard cytotoxic agents was superior to the cytotoxic agent used alone for a single xenograft (one of the three xenografts evaluated for the vincristine-cediranib combination). The cediranib-cyclophosphamide combination was inferior to single agent cyclophosphamide in time to event for both models studied and was significantly inferior for one of the models. Cediranib combined with rapamycin was superior to each of the agents used alone in two of the six models and was determined to be additive or supra-additive with rapamycin in four models, although the effects were not large. Conclusions. Cediranib combined with cytotoxic chemotherapy agents demonstrated little or no benefit (and in one case was significantly inferior) compared to chemotherapy alone for the six pediatric cancer xenografts studied. By contrast, the combination of cediranib with rapamycin was additive or supra-additive in four of the six models in terms of prolongation of time to event, though tumor regressions were not observed for this combination. Pediatr Blood Cancer 2012; 58: 566-571. (C) 2011 Wiley Periodicals, Inc.
C1 [Morton, Christopher L.; Billups, Catherine A.; Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA.
   [Houghton, Peter J.] Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc, Columbus, OH 43205 USA.
   [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
   [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
   [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
   [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc, 700 Childrens Dr, Columbus, OH 43205 USA.
EM peter.houghton@nationwidechildrens.org
FU National Cancer Institute [NO1-CM-42216, NO1-CM91001-03, CA21765,
   CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
   NO1-CM91001-03, CA21765, CA108786.
NR 39
TC 10
Z9 11
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD APR
PY 2012
VL 58
IS 4
BP 566
EP 571
DI 10.1002/pbc.23159
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 895NK
UT WOS:000300502800017
PM 21538824
ER

PT J
AU Houghton, PJ
   Kang, MH
   Reynolds, CP
   Morton, CL
   Kolb, EA
   Gorlick, R
   Keir, ST
   Carol, H
   Lock, R
   Maris, JM
   Billups, CA
   Smith, MA
AF Houghton, Peter J.
   Kang, Min H.
   Reynolds, C. Patrick
   Morton, Christopher L.
   Kolb, E. Anders
   Gorlick, Richard
   Keir, Stephen T.
   Carol, Hernan
   Lock, Richard
   Maris, John M.
   Billups, Catherine A.
   Smith, Malcolm A.
TI Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric
   preclinical testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; preclinical testing; SMAC mimetic
ID NF-KAPPA-B; APOPTOSIS PROTEINS; ACTIVATION; CANCER; XIAP; SMAC/DIABLO;
   INHIBITOR; THERAPIES; LEUKEMIA; CIAP1
AB LCL161, a SMAC mimetic, was tested against the PPTP in vitro panel (1.0?nM to 10.0?mu M) and the PPTP in vivo panels (30 or 75?mg/kg [solid tumors] or 100?mg/kg [ALL]) administered orally twice in a week. LCL161 showed a median relative IC50 value of >10?mu M, being more potent against several leukemia and lymphoma lines. In vivo LCL161 induced significant differences in EFS distribution in approximately one-third of solid tumor xenografts (osteosarcoma and glioblastoma), but not in ALL xenografts. No objective tumor responses were observed. In vivo LCL161 demonstrated limited single agent activity against the pediatric preclinical models studied. Pediatr Blood Cancer 2012; 58: 636639. (c) 2011 Wiley Periodicals, Inc.
C1 [Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, Columbus, OH 43205 USA.
   [Kang, Min H.; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
   [Morton, Christopher L.; Billups, Catherine A.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
   [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
   [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
   [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
   [Carol, Hernan; Lock, Richard] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
   [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
   [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
   [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, 700 Childrens Dr, Columbus, OH 43205 USA.
EM peter.houghton@nationwidechildrens.org
RI Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; 
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
   Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]; Novartis
   Pharmaceuticals [LCL161]
FX This work was supported by NO1-CM-42216, CA21765, and CA108786 from the
   National Cancer Institute, and LCL161 was provided by Novartis
   Pharmaceuticals. In addition to the authors represents work contributed
   by the following: Sherry Ansher, Joshua Courtright, Edward Favours,
   Henry S. Friedman, Debbie Payne-Turner, Charles Stopford, Chandra
   Tucker, Amy Wozniak, Joe Zeidner, Ellen Zhang, and Jian Zhang.
   Children's Cancer Institute Australia for Medical Research is affiliated
   with the University of New South Wales and Sydney Children's Hospital.
NR 23
TC 31
Z9 34
U1 0
U2 4
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD APR
PY 2012
VL 58
IS 4
BP 636
EP 639
DI 10.1002/pbc.23167
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 895NK
UT WOS:000300502800030
PM 21681929
ER

PT J
AU Wylie, L
   Philpott, A
AF Wylie, Luke
   Philpott, Anna
TI Neuroblastoma progress on many fronts: The neuroblastoma research
   symposium
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE molecular biology of neuroblastoma; neuroblastoma; neuroblastoma biology
ID GENE; CELL
AB Neuroblastoma (NBL) is a pediatric tumor of infancy derived from precursor cells of the sympathetic nervous system. Clinicians and researchers in developmental biology and genetics recently met to facilitate meaningful crosstalk and to discuss considerable progress made in the clinical treatment and basic biology of NBL. For instance, discoveries in familial NBL have identified genetic aberrations in Phox2b and Alk that predispose to NBL, while advances in epigenetics and MYCN regulation have also offered insight into NBL pathogenesis and future treatment. Moreover, novel therapeutic avenues are also being explored, including targeted immunotherapies, and innovative radiotherapeutic and chemotherapeutic approaches. This multi-disciplinary meeting was convened to aid the transfer of new biological findings into the clinic and to use clinical advances to inform the basic biological understanding of this devastating disease. Pediatr Blood Cancer 2012; 58: 649651. (C) 2011 Wiley Periodicals, Inc.
C1 [Wylie, Luke; Philpott, Anna] Univ Cambridge, Dept Oncol, Hutchison Med Res Council MRC Res Ctr, Cambridge CB2 0XZ, England.
   [Wylie, Luke] NCI, NIH, Bethesda, MD 20892 USA.
RP Philpott, A (reprint author), Univ Cambridge, Dept Oncol, Hutchison Med Res Council MRC Res Ctr, Cambridge CB2 0XZ, England.
EM ap113@cam.ac.uk
FU National Institutes of Health; Medical Research Council [G0700758]
FX Grant sponsor: National Institutes of Health Oxford-Cambridge Scholars
   Program; Grant sponsor: Medical Research Council; Grant number:
   G0700758.
NR 18
TC 1
Z9 1
U1 0
U2 4
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD APR
PY 2012
VL 58
IS 4
BP 649
EP 651
DI 10.1002/pbc.23329
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 895NK
UT WOS:000300502800036
PM 21922652
ER

PT J
AU Kim, HK
   Choi, IJ
   Kim, CG
   Kim, HS
   Oshima, A
   Yamada, Y
   Arao, T
   Nishio, K
   Michalowski, A
   Green, JE
AF Kim, H. K.
   Choi, I. J.
   Kim, C. G.
   Kim, H. S.
   Oshima, A.
   Yamada, Y.
   Arao, T.
   Nishio, K.
   Michalowski, A.
   Green, J. E.
TI Three-gene predictor of clinical outcome for gastric cancer patients
   treated with chemotherapy
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE gastric; cancer; chemotherapy; gene; expression
ID C-MYC; GENE-EXPRESSION; THYMIDYLATE SYNTHASE; DNA MICROARRAYS; TUMOR
   RESPONSE; PHASE-II; CISPLATIN; CARCINOMA; SURVIVAL; ADENOCARCINOMA
AB To identify transcriptional profiles predictive of the clinical benefit of cisplatin and fluorouracil (CF) chemotherapy to gastric cancer patients, endoscopic biopsy samples from 96 CF-treated metastatic gastric cancer patients were prospectively collected before therapy and analyzed using high-throughput transcriptional profiling and array comparative genomic hybridization. Transcriptional profiling identified 917 genes that are correlated with poor patient survival after CF at P<0.05 (poor prognosis signature), in which protein synthesis and DNA replication/recombination/repair functional categories are enriched. A survival risk predictor was then constructed using genes, which are included in the poor prognosis signature and are contained within identified genomic amplicons. The combined expression of three genes-MYC, EGFR and FGFR2-was an independent predictor for overall survival of 27 CF-treated patients in the validation set (adjusted P = 0.017), and also for survival of 40 chemotherapy-treated gastric cancer patients in a published data set (adjusted P = 0.026). Thus, combined expression of MYC, EGFR and FGFR2 is predictive of poor survival in CF-treated metastatic gastric cancer patients. The Pharmacogenomics Journal (2012) 12, 119-127; doi:10.1038/tpj.2010.87; published online 21 December 2010
C1 [Kim, H. K.; Oshima, A.; Michalowski, A.; Green, J. E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
   [Kim, H. K.; Choi, I. J.; Kim, C. G.; Kim, H. S.] Natl Canc Ctr, Goyang, Gyeonggi, South Korea.
   [Yamada, Y.] Natl Canc Ctr, Tokyo 104, Japan.
   [Arao, T.; Nishio, K.] Kinki Univ, Sch Med, Osaka 589, Japan.
RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, 37 Convent Dr, Bethesda, MD 20892 USA.
EM JEGreen@mail.nih.gov
FU National Institute of Health; Center for Cancer Research; National
   Cancer Institute; Korean National Cancer Center [0910570]; Ministry of
   Education, Science and Technology of Korea [2010K001121]
FX The work was supported in part by National Institute of Health
   Intramural Program, Center for Cancer Research, National Cancer
   Institute, Korean National Cancer Center Grant 0910570 and Converging
   Research Center Program through the Ministry of Education, Science and
   Technology of Korea (2010K001121). We thank Dr Richard Simon for
   valuable discussions and critical reading of the manuscript, Dr Lyuba
   Varticovski for critical review of the manuscript and Dr Chang-Hee Kim,
   Ms Susie Korolevich, Ms Eunbyul Lee, Ms Eugene Kim and Ms Ilji Jeon for
   technical help.
NR 37
TC 22
Z9 22
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD APR
PY 2012
VL 12
IS 2
BP 119
EP 127
DI 10.1038/tpj.2010.87
PG 9
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 916WK
UT WOS:000302133700005
PM 21173787
ER

PT J
AU Xu, K
   Hong, KA
   Zhou, ZF
   Hauger, RL
   Goldman, D
   Sinha, R
AF Xu, Ke
   Hong, Kwangik Adam
   Zhou, Zhifeng
   Hauger, Richard L.
   Goldman, David
   Sinha, Rajita
TI Genetic modulation of plasma NPY stress response is suppressed in
   substance abuse: Association with clinical outcomes
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE Neuropeptide Y; Functional haplotype; Stress; Substance use disorders
ID COCAINE-DEPENDENT INDIVIDUALS; PITUITARY-ADRENAL AXIS;
   HEART-RATE-VARIABILITY; NEUROPEPTIDE-Y; ALCOHOL DEPENDENCE;
   POPULATION-SAMPLE; DRUG-USE; ADDICTION; RATS; POLYMORPHISM
AB Background: Neuropeptide Y (NPY) is involved in stress regulation. Genetic variations predict plasma NPY and neural correlates of emotion and stress. We examined whether the functional NPY haplotype modulates stress-induced NPY and anxiety responses, and if plasma NPY stress responses are associated with substance dependence outcomes.
   Methods: Thirty-seven treatment-engaged, abstinent substance dependent (SD) patients and 28 healthy controls (HCs) characterized on NPY diplotypes (HH: high expression; HLLL: intermediate/low expression) were exposed to stress, alcohol/drug cues and neutral relaxing cues, using individualized guided imagery, in a 3-session laboratory experiment. Plasma NPY, heart rate and anxiety were assessed. Patients were prospectively followed for 90-days post-treatment to assess relapse outcomes.
   Results: HH individuals showed significantly lower stress-induced NPY with greater heart rate and anxiety ratings, while the HLLL group showed the reverse pattern of NPY, anxiety and heart rate responses. This differential genetic modulation of NPY stress response was suppressed in the SD group, who showed no stress-related increases in NPY and higher heart rate and greater anxiety, regardless of diplotype. Lower NPY predicted subsequent higher number of days and greater amounts of post-treatment drug use.
   Conclusion: These preliminary findings are the first to document chronic drug abuse influences on NPY diplotype expression where NPY diplotype modulation of stress-related plasma NPY, heart rate and anxiety responses was absent in the substance abuse sample. The finding that lower stress-related NPY is predictive of greater relapse severity provides support for therapeutic development of neuropeptide Y targets in the treatment of substance use disorders. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Xu, Ke; Hong, Kwangik Adam; Sinha, Rajita] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA.
   [Sinha, Rajita] Yale Child Study Ctr, New Haven, CT 06519 USA.
   [Zhou, Zhifeng; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Hauger, Richard L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
RP Sinha, R (reprint author), Yale Univ, Sch Med, Dept Psychiat, 2 Church St S,Suite 209, New Haven, CT 06519 USA.
EM Rajita.sinha@yale.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institutes of Health [R01-AA013892, R01-AG022982, R01-MH074697,
   T32-MH019961, R25-MH071584, UL1-DE019586, UL1-RR024139]; Department of
   Mental Health; Addiction Services of the State of Connecticut;
   Department of Veterans Affairs; VA Center of Excellence for Stress and
   Mental Health (CESAMH)
FX This research was supported by the National Institutes of Health grants
   R01-AA013892 (RS), R01-AG022982 (RLH), R01-MH074697 (RLH), T32-MH019961,
   R25-MH071584 and the NIH Roadmap Fund for Medical Research grants
   UL1-DE019586 (RS) and UL1-RR024139 (Yale CTSA) as well as the Department
   of Mental Health and Addiction Services of the State of Connecticut. Dr.
   Hauger was supported by a Merit Review grant from the Department of
   Veterans Affairs and the VISN22 VA Center of Excellence for Stress and
   Mental Health (CESAMH).
NR 65
TC 3
Z9 3
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD APR
PY 2012
VL 37
IS 4
BP 554
EP 564
DI 10.1016/j.psyneuen.2011.08.005
PG 11
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA 915RJ
UT WOS:000302044800011
PM 21917383
ER

PT J
AU Burke, JE
   Sashital, DG
   Zuo, XB
   Wang, YX
   Butcher, SE
AF Burke, Jordan E.
   Sashital, Dipali G.
   Zuo, Xiaobing
   Wang, Yun-Xing
   Butcher, Samuel E.
TI Structure of the yeast U2/U6 snRNA complex
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE NMR; RNA; SAXS; U6 snRNA; spliceosome
ID GROUP-II INTRON; INTRAMOLECULAR STEM-LOOP; LIQUID-CRYSTALLINE PHASE;
   METAL-ION COORDINATION; PROTEIN-FREE SNRNAS; SMALL NUCLEAR RNAS;
   MESSENGER-RNA; U6 SNRNA; WEB SERVER; CATALYTIC ACTIVATION
AB The U2/U6 snRNA complex is a conserved and essential component of the active spliceosome that interacts with the pre-mRNA substrate and essential protein splicing factors to promote splicing catalysis. Here we have elucidated the solution structure of a 111-nucleotide U2/U6 complex using an approach that integrates SAXS, NMR, and molecular modeling. The U2/U6 structure contains a three-helix junction that forms an extended "Y'' shape. The U6 internal stem-loop (ISL) forms a continuous stack with U2/U6 Helices Ib, Ia, and III. The coaxial stacking of Helix Ib on the U6 ISL is a configuration that is similar to the Domain V structure in group II introns. Interestingly, essential features of the complex-including the U80 metal binding site, AGC triad, and pre-mRNA recognition sites-localize to one face of the molecule. This observation suggests that the U2/U6 structure is well-suited for orienting substrate and cofactors during splicing catalysis.
C1 [Burke, Jordan E.; Sashital, Dipali G.; Butcher, Samuel E.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
   [Zuo, Xiaobing] Argonne Natl Lab, Adv Photon Source, Chicago, IL 60437 USA.
   [Wang, Yun-Xing] NCI, NIH, Frederick, MD 21702 USA.
RP Butcher, SE (reprint author), Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
EM butcher@biochem.wisc.edu
RI Zuo, Xiaobing/F-1469-2010; ID, BioCAT/D-2459-2012; 
OI Sashital, Dipali/0000-0001-7681-6987
FU NIH [P41RR02301 (BRTP/NCRR), P41GM66326 (NIGMS), RR02781, RR08438, T32
   GM07215-34, GM065166]; University of Wisconsin; NSF [DMB-8415048,
   OIA-9977486, BIR-9214394]; USDA; U.S. DOE [DE-AC02-06CH11357]
FX We thank Lawrence Clos II, Marco Tonelli, and the National Magnetic
   Resonance Facility at Madison (NMRFAM) staff as well as Soenke Seifert
   and the Advanced Photon Source (APS) staff for technical support. We
   also thank David Brow, Alex Grishaev, and all the members of the Butcher
   laboratory for helpful discussions. This study made use of the National
   Magnetic Resonance Facility at Madison, which is supported by NIH grants
   P41RR02301 (BRTP/NCRR) and P41GM66326 (NIGMS). Additional equipment was
   purchased with funds from the University of Wisconsin, the NIH (RR02781,
   RR08438), the NSF (DMB-8415048, OIA-9977486, BIR-9214394), and the USDA.
   Use of the Advanced Photon Source, an Office of Science User Facility
   operated for the U.S. Department of Energy (DOE) Office of Science by
   Argonne National Laboratory, was supported by the U.S. DOE under
   Contract No. DE-AC02-06CH11357. J.E.B. was supported by NIH Predoctoral
   training grant T32 GM07215-34. This work was supported by NIH grant
   GM065166 to S.E.B.
NR 72
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U1 2
U2 19
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 APR
PY 2012
VL 18
IS 4
BP 673
EP 683
DI 10.1261/rna.031138.111
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 914MQ
UT WOS:000301954600007
PM 22328579
ER

PT J
AU Baird, NJ
   Zhang, JW
   Hamma, T
   Ferre-D'Amare, AR
AF Baird, Nathan J.
   Zhang, Jinwei
   Hamma, Tomoko
   Ferre-D'Amare, Adrian R.
TI YbxF and YlxQ are bacterial homologs of L7Ae and bind K-turns but not
   K-loops
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE K-turn; K-loop; RNA-binding proteins; X-ray crystallography
ID RNA TERTIARY INTERACTIONS; LARGE RIBOSOMAL-SUBUNIT; CRYSTAL-STRUCTURE;
   BACILLUS-SUBTILIS; MESSENGER-RNA; X-RAY; ANGSTROM RESOLUTION; LYSINE
   RIBOSWITCH; PROTEIN NHP2P; I RIBOSWITCH
AB The archaeal protein L7Ae and eukaryotic homologs such as L30e and 15.5kD comprise the best characterized family of K-turn-binding proteins. K-turns are an RNA motif comprised of a bulge flanked by canonical and noncanonical helices. They are widespread in cellular RNAs, including bacterial gene-regulatory RNAs such as the c-di-GMP-II, lysine, and SAM-I riboswitches, and the T-box. The existence in bacteria of K-turn-binding proteins of the L7Ae family has not been proven, although two hypothetical proteins, YbxF and YlxQ, have been proposed to be L7Ae homologs based on sequence conservation. Using purified, recombinant proteins, we show that Bacillus subtilis YbxF and YlxQ bind K-turns (K-d similar to 270 nM and similar to 2300 nM, respectively). Crystallographic structure determination demonstrates that both YbxF and YlxQ adopt the same overall fold as L7Ae. Unlike the latter, neither bacterial protein recognizes K-loops, a structural motif that lacks the canonical helix of the K-turn. This property is shared between the bacterial and eukaryal family members. Comparison of our structure of YbxF in complex with the K-turn of the SAM-I riboswitch and previously determined structures of archaeal and eukaryal homologs bound to RNA indicates that L7Ae approaches the K-turn at a unique angle, which results in a considerably larger RNA-protein interface dominated by interactions with the noncanonical helix of the K-turn. Thus, the inability of the bacterial and eukaryal L7Ae homologs to bind K-loops probably results from their reliance on interactions with the canonical helix. The biological functions of YbxF and YlxQ remain to be determined.
C1 [Baird, Nathan J.; Zhang, Jinwei; Ferre-D'Amare, Adrian R.] NHLBI, Lab RNA Biophys & Cellular Physiol, Bethesda, MD 20892 USA.
   [Hamma, Tomoko] Pacific NW Univ Hlth Sci, Yakima, WA 98901 USA.
RP Ferre-D'Amare, AR (reprint author), NHLBI, Lab RNA Biophys & Cellular Physiol, Bethesda, MD 20892 USA.
EM adrian.ferre@nih.gov
RI Zhang, Jinwei/D-8953-2012
FU National Heart, Lung and Blood Institute, NIH
FX We thank the staff of Beamlines 5.0.1 and 5.0.2 of the ALS for data
   collection support, G. Piszczek for ITC support, D.-Y. Lee and R. Levine
   for generous help with mass spectrometry, and W. Winkler for
   discussions. This work was supported by the intramural program of the
   National Heart, Lung and Blood Institute, NIH.
NR 58
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U1 1
U2 4
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 APR
PY 2012
VL 18
IS 4
BP 759
EP 770
DI 10.1261/rna.031518.111
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 914MQ
UT WOS:000301954600015
PM 22355167
ER

PT J
AU Xin, HW
   Hari, DM
   Mullinax, JE
   Ambe, CM
   Koizumi, T
   Ray, S
   Anderson, AJ
   Wiegand, GW
   Garfield, SH
   Thorgeirsson, SS
   Avital, I
AF Xin, Hong-Wu
   Hari, Danielle M.
   Mullinax, John E.
   Ambe, Chenwi M.
   Koizumi, Tomotake
   Ray, Satyajit
   Anderson, Andrew J.
   Wiegand, Gordon W.
   Garfield, Susan H.
   Thorgeirsson, Snorri S.
   Avital, Itzhak
TI Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal
   Cancers Undergo Asymmetric Cell Division
SO STEM CELLS
LA English
DT Article
DE Adult stem cells; Cancer stem cells; Self-renewal; Asymmetric cell
   division; Cairns immortal strand hypothesis; Liver
ID TEMPLATE DNA STRANDS; HEMATOPOIETIC STEM-CELLS; HUMAN SOMATIC-CELLS;
   NEUTRAL ENDOPEPTIDASE; SISTER CHROMATIDS; TRANSGENIC MICE;
   MAMMARY-GLAND; IDENTIFICATION; SEGREGATION; GENE
AB Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. STEM CELLS 2012; 30:591598
C1 [Xin, Hong-Wu; Hari, Danielle M.; Mullinax, John E.; Ambe, Chenwi M.; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J.; Wiegand, Gordon W.; Avital, Itzhak] NCI, Gastrointestinal & Hepatobiliary Malignancies Sec, Surg Branch, NIH, Bethesda, MD 20892 USA.
   [Garfield, Susan H.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Avital, I (reprint author), NCI, Gastrointestinal & Hepatobiliary Malignancies Sec, Surg Branch, NIH, 10 Ctr Dr,CRC Room 4-3961, Bethesda, MD 20892 USA.
EM itzhak.avital@gmail.com
RI perumal, murugiah/D-1565-2012; Mullinax, John/L-2509-2014
FU NIH/National Cancer Institute
FX This study was supported by the intramural grant provided by the
   NIH/National Cancer Institute.
NR 54
TC 28
Z9 29
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD APR
PY 2012
VL 30
IS 4
BP 591
EP 598
DI 10.1002/stem.1061
PG 8
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 915DV
UT WOS:000302005000003
PM 22331764
ER

PT J
AU Rossouw, JE
   Johnson, KC
   Pettinger, M
   Cushman, M
   Sandset, PM
   Kuller, L
   Rosendaal, F
   Rosing, J
   Wasserthal-Smoller, S
   Martin, LW
   Manson, JE
   Lakshminarayan, K
   Merino, JG
   Lynch, J
AF Rossouw, Jacques E.
   Johnson, Karen C.
   Pettinger, Mary
   Cushman, Mary
   Sandset, Per Morten
   Kuller, Lewis
   Rosendaal, Frits
   Rosing, Jan
   Wasserthal-Smoller, Sylvia
   Martin, Lisa W.
   Manson, JoAnn E.
   Lakshminarayan, Kamakshi
   Merino, Jose G.
   Lynch, John
TI Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and
   Risk of Ischemic Stroke due to Postmenopausal Hormone Therapy
SO STROKE
LA English
DT Article
DE cerebrovascular accident; estrogen; hemostasis; menopause; randomized
   controlled trials
ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE
   ESTROGEN; VENOUS THROMBOSIS; ORAL-CONTRACEPTIVES; WOMEN
AB Background and Purpose-To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized activated protein C resistance ratio [nAPCsr]) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy.
   Methods-Nested case-control study of 455 cases of ischemic stroke and 565 matched control subjects in the Women's Health Initiative trials of postmenopausal hormone therapy.
   Results-Baseline free TFPI was associated with ischemic stroke risk (OR per SD increase, 1.17; 95% CI, 1.01-1.37; P=0.039), but baseline nAPCsr was not (OR per SD increase, 0.89; 95% CI, 0.75-1.05; P=0.15). Baseline TFPI levels and nAPCsr did not modify the effect of postmenopausal hormone therapy on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction P=0.452 and 0.971, respectively). In subgroup analyses, baseline nAPCsr was inversely associated with lacunar strokes (OR per SD increase, 0.74; 95% CI, 0.57-0.96; P=0.025) and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes (P=0.008).
   Conclusions-Procoagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to postmenopausal hormone therapy.
C1 [Rossouw, Jacques E.] NHLBI, Bethesda, MD 20892 USA.
   [Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
   [Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Cushman, Mary] Univ Vermont, Burlington, VT USA.
   [Sandset, Per Morten] Oslo Univ Hosp, Oslo, Norway.
   [Kuller, Lewis] Univ Pittsburgh, Pittsburgh, PA USA.
   [Rosendaal, Frits] Leiden Univ, Med Ctr, Leiden, Netherlands.
   [Rosing, Jan] Maastricht Univ, Maastricht, Netherlands.
   [Wasserthal-Smoller, Sylvia] Albert Einstein Coll Med, New York, NY USA.
   [Martin, Lisa W.] George Washington Univ, Washington, DC USA.
   [Manson, JoAnn E.] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Lakshminarayan, Kamakshi] Univ Minnesota, Minneapolis, MN USA.
   [Merino, Jose G.; Lynch, John] NINDS, Bethesda, MD 20892 USA.
RP Rossouw, JE (reprint author), NHLBI, 6701 Rockledge Dr,Room 9192, Bethesda, MD 20892 USA.
EM rossouwj@nih.gov
OI Merino, Jose/0000-0002-6676-0008; Martin, Lisa
   Warsinger/0000-0003-4352-0914
FU National Heart, Lung, and Blood Institute, National Institutes of
   Health, US Department of Health and Human Services [N01WH22110, 24152,
   32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
   42107-26, 42129-32, 44221]
FX The WHI program is funded by the National Heart, Lung, and Blood
   Institute, National Institutes of Health, US Department of Health and
   Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6,
   32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and
   44221. The study drugs were provided by Wyeth Research (St Davids, PA).
   The National Institutes of Health had input into the design and conduct
   of the study; collection, management, analysis, and interpretation of
   the data; and preparation of the article. Wyeth did not participate in
   any aspect of the aforementioned.
NR 27
TC 11
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD APR
PY 2012
VL 43
IS 4
BP 952
EP 957
DI 10.1161/STROKEAHA.111.643072
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 916ST
UT WOS:000302124200012
PM 22363056
ER

PT J
AU Berger, JS
   McGinn, AP
   Howard, BV
   Kuller, L
   Manson, JE
   Otvos, J
   Curb, JD
   Eaton, CB
   Kaplan, RC
   Lynch, JK
   Rosenbaum, DM
   Wassertheil-Smoller, S
AF Berger, Jeffrey S.
   McGinn, Aileen P.
   Howard, Barbara V.
   Kuller, Lewis
   Manson, JoAnn E.
   Otvos, Jim
   Curb, J. David
   Eaton, Charles B.
   Kaplan, Robert C.
   Lynch, John K.
   Rosenbaum, Daniel M.
   Wassertheil-Smoller, Sylvia
TI Lipid and Lipoprotein Biomarkers and the Risk of Ischemic Stroke in
   Postmenopausal Women
SO STROKE
LA English
DT Article
DE lipids; lipoproteins; ischemic stroke; women; triglycerides
ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; NONFASTING TRIGLYCERIDES;
   ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; CHOLESTEROL LEVELS;
   SERUM-CHOLESTEROL; ASSOCIATION; MEN; MORTALITY
AB Background-Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial.
   Methods-We conducted a prospective nested case-control study among postmenopausal women from the Women's Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), lipoproteins (LDL, HDL, and very low-density lipoprotein [VLDL] particle number and size, intermediate-density lipoprotein [IDL] particle number, and lipoprotein (a)), and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to control subjects, using a 1: 1 ratio.
   Results-In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, whereas levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides (odds ratio for the highest versus lowest quartile, 1.56; 95% confidence interval, 1.13-2.17; P for trend=0.02), VLDL size (odds ratio, 1.59; 95% confidence interval, 1.10-2.28; P for trend=0.03), and IDL particle number (odds ratio, 1.46; 95% confidence interval, 1.04-2.04; P for trend=0.02) were significantly associated with ischemic stroke.
   Conclusions-Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size, and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women. (Stroke. 2012;43:958-966.)
C1 [Berger, Jeffrey S.] NYU, Sch Med, Med Ctr, New York, NY 10016 USA.
   [McGinn, Aileen P.; Kaplan, Robert C.; Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Howard, Barbara V.] MedStar Res Inst, Washington, DC USA.
   [Howard, Barbara V.] Georgetown Univ, Sch Med, Washington, DC USA.
   [Kuller, Lewis] Univ Pittsburgh, Pittsburgh, PA USA.
   [Manson, JoAnn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
   [Otvos, Jim] Liposci Inc, Raleigh, NC USA.
   [Curb, J. David] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA.
   [Eaton, Charles B.] Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA.
   [Lynch, John K.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
   [Rosenbaum, Daniel M.] SUNY Downstate, Dept Neurol, Brooklyn, NY USA.
RP Berger, JS (reprint author), NYU, Sch Med, Med Ctr, 530 1st Ave,Skirball 9R, New York, NY 10016 USA.
EM jeffrey.berger@nyumc.org
FU National Heart, Lung, and Blood Institute, National Institutes of
   Health, US Department of Health and Human Services [N01WH22110, 24152,
   32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
   42107-26, 42129-32, 44221]; National Institutes of Neurological
   Disorders and Stroke [R01NS042618]; American Heart Association
   [0775074N]; Pfizer; Merck; Schering-Plough; Parexel; AstraZeneca;
   Auxilium; Forest Pharmaceuticals
FX The WHI program is funded by the National Heart, Lung, and Blood
   Institute, National Institutes of Health, US Department of Health and
   Human Services, through contracts N01WH22110, 24152, 32100-2, 32105-6,
   32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and
   44221. This study was supported by a grant from the National Institutes
   of Neurological Disorders and Stroke (R01NS042618). J.S.B. was partially
   funded by an American Heart Association Fellow to Faculty Award (No.
   0775074N).; The content is solely the responsibility of the authors and
   does not necessarily represent the official views of the NINDS or the
   NIH. B. V. H. is a consultant for Merck and Egg Nutrition Council and
   has received research support (donation of drugs) from Pfizer, Merck,
   and Schering-Plough and lectures for Schering-Plough. J.O. is an
   employee and stockholder of Liposcience, Inc. C. B. E. has received
   research support from Pfizer, Parexel, AstraZeneca, Auxilium, and Forest
   Pharmaceuticals; is on the Speakers Bureau for Pfizer and Merck-Shering
   Plough; and is a consultant for Pfizer, Merck-Shering Plough, Merck, and
   Johnson & Johnson.
NR 47
TC 22
Z9 26
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD APR
PY 2012
VL 43
IS 4
BP 958
EP U96
DI 10.1161/STROKEAHA.111.641324
PG 13
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 916ST
UT WOS:000302124200013
PM 22308251
ER

PT J
AU Saver, JL
   Warach, S
   Janis, S
   Odenkirchen, J
   Becker, K
   Benavente, O
   Broderick, J
   Dromerick, AW
   Duncan, P
   Elkind, MSV
   Johnston, K
   Kidwell, CS
   Meschia, JF
   Schwamm, L
AF Saver, Jeffrey L.
   Warach, Steven
   Janis, Scott
   Odenkirchen, Joanne
   Becker, Kyra
   Benavente, Oscar
   Broderick, Joseph
   Dromerick, Alexander W.
   Duncan, Pamela
   Elkind, Mitchell S. V.
   Johnston, Karen
   Kidwell, Chelsea S.
   Meschia, James F.
   Schwamm, Lee
CA Natl Inst Neurological Disorders
TI Standardizing the Structure of Stroke Clinical and Epidemiologic
   Research Data The National Institute of Neurological Disorders and
   Stroke (NINDS) Stroke Common Data Element (CDE) Project
SO STROKE
LA English
DT Article
DE database; education; educational campaigns
ID HEALTH; COLLECTION; NETWORK; BRAIN
AB Background and Purpose-The National Institute of Neurological Disorders and Stroke initiated development of stroke-specific Common Data Elements (CDEs) as part of a project to develop data standards for funded clinical research in all fields of neuroscience. Standardizing data elements in translational, clinical, and population research in cerebrovascular disease could decrease study start-up time, facilitate data sharing, and promote well-informed clinical practice guidelines.
   Methods-A working group of diverse experts in cerebrovascular clinical trials, epidemiology, and biostatistics met regularly to develop a set of stroke CDEs, selecting among, refining, and adding to existing, field-tested data elements from national registries and funded trials and studies. Candidate elements were revised on the basis of comments from leading national and international neurovascular research organizations and the public.
   Results-The first iteration of the National Institute of Neurological Disorders and Stroke (NINDS) stroke-specific CDEs comprises 980 data elements spanning 9 content areas: (1) biospecimens and biomarkers; (2) hospital course and acute therapies; (3) imaging; (4) laboratory tests and vital signs; (5) long-term therapies; (6) medical history and prior health status; (7) outcomes and end points; (8) stroke presentation; and (9) stroke types and subtypes. A CDE website provides uniform names and structures for each element, a data dictionary, and template case report forms, using the CDEs.
   Conclusions-Stroke-specific CDEs are now available as standardized, scientifically vetted, variable structures to facilitate data collection and data sharing in cerebrovascular patient-oriented research. The CDEs are an evolving resource that will be iteratively improved based on investigator use, new technologies, and emerging concepts and research findings. (Stroke. 2012;43:967-973.)
C1 [Warach, Steven; Janis, Scott; Odenkirchen, Joanne] NINDS, NIH, Bethesda, MD 20892 USA.
   [Becker, Kyra] Univ Washington, Sch Med, Seattle, WA USA.
   [Benavente, Oscar] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
   [Broderick, Joseph] Univ Cincinnati, Cincinnati, OH USA.
   [Dromerick, Alexander W.] Georgetown Univ, Sch Med, Washington, DC USA.
   [Duncan, Pamela] Duke Univ, Durham, NC USA.
   [Elkind, Mitchell S. V.] Columbia Univ, New York, NY USA.
   [Johnston, Karen] Univ Virginia, Charlottesville, VA USA.
   [Meschia, James F.] Mayo Clin, Coll Med, Jacksonville, FL 32224 USA.
   [Schwamm, Lee] Harvard Univ, Sch Med, Boston, MA USA.
RP Saver, JL (reprint author), Univ Calif Los Angeles, Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@ucla.edu
RI Lo, Warren/E-3531-2011; 
OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145
FU National Institute of Neurological Disorders and Stroke, National
   Institutes of Health [N01-NS-7-2372]; NIH; AGA; EV3; IMS III Trial; UC
   SPOTRIAS Center; FIA; C-32 Cerebrovascular Fellowship; Genetic and
   Environmental Risk Factors for Hemorrhagic Stroke; Comparison of
   Hemorrhagic and Ischemic Stroke Among Blacks; Whites; IRIS Trial; CREST;
   COSS; SWISS; Wake Forest Baptist Medical Center; BMS; diaDexus;
   NIH/NINDS [U01NS064498]; NINDS [U01NS069208];  [NS057401];  [NS069763]; 
   [NS044378]
FX The Common Data Element Project is funded by the National Institute of
   Neurological Disorders and Stroke, National Institutes of Health
   (contract No. N01-NS-7-2372).; J.L.S. reports the following: Research
   grants: NIH, AGA, EV3, and Concentric; consultant/advisory boards: ALA,
   EV3, Lunseck, Concentric, Talecris, and BrainsGate;
   institution/employer: UCLA. J.O. reports the following:
   Institution/employer: NIH employee. O.B. reports the following: Research
   grant. J.B. reports the following: Research grants: IMS III Trial, UC
   SPOTRIAS Center, FIA study, C-32 Cerebrovascular Fellowship Training,
   Genetic and Environmental Risk Factors for Hemorrhagic Stroke,
   Comparison of Hemorrhagic and Ischemic Stroke Among Blacks and Whites,
   IRIS Trial, CREST, COSS, and SWISS; honoraria: Genentech, PhotoThera,
   and Oakstone Medical Publishing. A. W. D. reports the following:
   Research grant. P. D. reports the following: Institution/employer: Wake
   Forest Baptist Medical Center. M. S. V. E. reports the following:
   Research grants: BMS Sanofi Partnership and diaDexus; other research
   support: NIH/NINDS; speakers bureau: BMS Sanofi Partnership and
   Genentech; expert witness: GlaxoSmithKline and Organon. K.J. reports the
   following: Research grant: NIH-NINDS U01NS064498. C. S. K. reports the
   following: Research grants: NS057401, NS069763, and NS044378. J.F.M.
   reports the following: Research grant: NINDS Sign U01NS069208.
NR 18
TC 50
Z9 53
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD APR
PY 2012
VL 43
IS 4
BP 967
EP U108
DI 10.1161/STROKEAHA.111.634352
PG 11
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 916ST
UT WOS:000302124200014
PM 22308239
ER

PT J
AU Cheng, YC
   Anderson, CD
   Bione, S
   Keene, K
   Maguire, JM
   Nalls, M
   Rasheed, A
   Zeginigg, M
   Attia, J
   Baker, R
   Barlera, S
   Biffi, A
   Bookman, E
   Brott, TG
   Brown, RD
   Chen, F
   Chen, WM
   Ciusani, E
   Cole, JW
   Cortellini, L
   Danesh, J
   Doheny, K
   Ferrucci, L
   Franzosi, MG
   Frossard, P
   Furie, KL
   Golledge, J
   Hankey, GJ
   Hernandez, D
   Holliday, EG
   Hsu, FC
   Jannes, J
   Kamal, A
   Khan, MS
   Kittner, SJ
   Koblar, SA
   Lewis, M
   Lincz, L
   Lisa, A
   Matarin, M
   Moscato, P
   Mychaleckyj, JC
   Parati, EA
   Parolo, S
   Pugh, E
   Rost, NS
   Schallert, M
   Schmidt, H
   Scott, RJ
   Sturm, JW
   Yadav, S
   Zaidi, M
   Boncoraglio, GB
   Levi, CR
   Meschia, JF
   Rosand, J
   Sale, M
   Saleheen, D
   Schmidt, R
   Sharma, P
   Worrall, B
   Mitchell, BD
AF Cheng, Yu-Ching
   Anderson, Christopher D.
   Bione, Silvia
   Keene, Keith
   Maguire, Jane M.
   Nalls, Michael
   Rasheed, Asif
   Zeginigg, Marion
   Attia, John
   Baker, Ross
   Barlera, Simona
   Biffi, Alessandro
   Bookman, Ebony
   Brott, Thomas G.
   Brown, Robert D., Jr.
   Chen, Fang
   Chen, Wei-Min
   Ciusani, Emilio
   Cole, John W.
   Cortellini, Lynelle
   Danesh, John
   Doheny, Kimberly
   Ferrucci, Luigi
   Franzosi, Maria Grazia
   Frossard, Philippe
   Furie, Karen L.
   Golledge, Jonathan
   Hankey, Graeme J.
   Hernandez, Dena
   Holliday, Elizabeth G.
   Hsu, Fang-Chi
   Jannes, Jim
   Kamal, Ayeesha
   Khan, Muhammad Saleem
   Kittner, Steven J.
   Koblar, Simon A.
   Lewis, Martin
   Lincz, Lisa
   Lisa, Antonella
   Matarin, Mar
   Moscato, Pablo
   Mychaleckyj, Josyf C.
   Parati, Eugenio A.
   Parolo, Silvia
   Pugh, Elizabeth
   Rost, Natalia S.
   Schallert, Michael
   Schmidt, Helena
   Scott, Rodney J.
   Sturm, Jonathan W.
   Yadav, Sunaina
   Zaidi, Moazzam
   Boncoraglio, Giorgio B.
   Levi, Christopher Royce
   Meschia, James F.
   Rosand, Jonathan
   Sale, Michele
   Saleheen, Danish
   Schmidt, Reinhold
   Sharma, Pankaj
   Worrall, Bradford
   Mitchell, Braxton D.
CA GARNET Collaborative Res Grp
   GENEVA Consortium
   Int Stroke Genetics Consortium
TI Are Myocardial Infarction-Associated Single-Nucleotide Polymorphisms
   Associated With Ischemic Stroke?
SO STROKE
LA English
DT Article
DE cerebral infarct; genetics; ischemia
ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION;
   AMERICAN-HEART-ASSOCIATION; VITAMIN INTERVENTION; CEREBRAL INFARCTION;
   SEQUENCE VARIANTS; FAMILY-HISTORY; PREVENTION; CLASSIFICATION; SUBTYPES
AB Methods-Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific beta s and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model.
   Results-Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons.
   Conclusions-Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events. (Stroke. 2012; 43:980-986.)
C1 [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
   [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Furie, Karen L.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
   [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
   [Bione, Silvia; Lisa, Antonella; Parolo, Silvia] CNR, Inst Mol Genet, Pavia, Italy.
   [Keene, Keith; Schallert, Michael] Univ Virginia, Dept Med, Charlottesville, VA USA.
   [Keene, Keith; Chen, Fang; Chen, Wei-Min; Mychaleckyj, Josyf C.; Schallert, Michael] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
   [Maguire, Jane M.; Attia, John; Holliday, Elizabeth G.; Lincz, Lisa; Scott, Rodney J.; Levi, Christopher Royce] Univ Newcastle, HMRI, Newcastle, NSW 2300, Australia.
   [Maguire, Jane M.] Univ Newcastle, Sch Nursing & Midwifery, Newcastle, NSW 2300, Australia.
   [Nalls, Michael; Hernandez, Dena] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Rasheed, Asif; Frossard, Philippe; Zaidi, Moazzam; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
   [Zeginigg, Marion; Schallert, Michael; Schmidt, Helena; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria.
   [Zeginigg, Marion; Schallert, Michael; Schmidt, Helena; Schmidt, Reinhold] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria.
   [Baker, Ross] Murdoch Univ, Ctr Thrombosis & Haemophilia, Perth, WA, Australia.
   [Baker, Ross] Royal Perth Hosp, Dept Haematol, Perth, WA, Australia.
   [Barlera, Simona; Franzosi, Maria Grazia] Ist Ric Farmacol Mario Negri, Milan, Italy.
   [Bookman, Ebony] NHGRI, NIH, Rockville, MD USA.
   [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
   [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA.
   [Chen, Wei-Min; Mychaleckyj, Josyf C.; Worrall, Bradford] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
   [Ciusani, Emilio; Parati, Eugenio A.; Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy.
   [Cole, John W.; Kittner, Steven J.] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA.
   [Cole, John W.; Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
   [Danesh, John; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Doheny, Kimberly; Pugh, Elizabeth] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA.
   [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA.
   [Golledge, Jonathan] James Cook Univ, Sch Med, Vasc Biol Unit, Townsville, Qld 4811, Australia.
   [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia.
   [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia.
   [Hsu, Fang-Chi] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
   [Hsu, Fang-Chi] Wake Forest Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
   [Jannes, Jim; Koblar, Simon A.; Lewis, Martin] Univ Adelaide, Stroke Res Programme, Sch Med, Adelaide, SA, Australia.
   [Jannes, Jim; Koblar, Simon A.; Lewis, Martin] Univ Adelaide, Stroke Res Programme, Sch Mol Biomed Sci, Adelaide, SA, Australia.
   [Kamal, Ayeesha] Aga Khan Univ, Neurol Sect, Karachi, Pakistan.
   [Khan, Muhammad Saleem; Yadav, Sunaina; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England.
   [Matarin, Mar] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London, England.
   [Moscato, Pablo] Univ Newcastle, Ctr Bioinformat, Newcastle, NSW 2300, Australia.
   [Sturm, Jonathan W.] Univ Newcastle, Gosford Hosp, Dept Neurosci, Newcastle, NSW 2300, Australia.
   [Schallert, Michael] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA.
   [Worrall, Bradford] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
   [Saleheen, Danish] Univ Penn, Philadelphia, PA 19104 USA.
RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Dept Med, 660 W Redwood St,Howard Hall,Room 492, Baltimore, MD 21201 USA.
EM bmitchel@medicine.umaryland.edu
RI MOSCATO, PABLO/G-7668-2013; golledge, jonathan/I-2371-2013; Attia,
   John/F-5376-2013; Hankey, Graeme /H-4968-2014; Lisa,
   Antonella/B-3117-2015; Boncoraglio, Giorgio/B-8647-2011; Matarin,
   Mar/F-1771-2016; 
OI Lewis, Martin/0000-0002-3332-3776; Attia, John/0000-0001-9800-1308;
   Hankey, Graeme /0000-0002-6044-7328; Lisa,
   Antonella/0000-0003-2458-5499; Matarin, Mar/0000-0002-4717-5735; Bione,
   Silvia/0000-0002-3924-4606; Parolo, Silvia/0000-0002-3671-5353;
   Anderson, Christopher/0000-0002-0053-2002; Koblar,
   Simon/0000-0002-8667-203X; Mitchell, Braxton/0000-0003-4920-4744
FU Australian National and Medical Health Research Council (NHMRC)
   [569257]; Australian National Heart Foundation (NHF) [G 04S 1623];
   University of Newcastle; Department of Health (United Kingdom); Henry
   Smith Charity; British Council (UKIERI); Italian Ministry of Health [RC
   2007/LR6, RC 2008/LR6, RC 2009/LR8, RC 2010/LR8]; Cariplo Foundation
   [2010-0253]; University of Pavia; European Community
   [LSHM-CT-2007-037273]; American Heart Association/Bugher Foundation
   Centers for Stroke Prevention Research [0775010N]; NIH-NINDS
   [K23NS064052, R01NS063925, P50NS051343]; Deane Institute for Integrative
   Study of Atrial Fibrillation and Stroke; Keane Stroke Genetics Research
   Fund; US National Institutes of Health; National Heart, Lung, and Blood
   Institute STAMPEED [R01 HL087676]; National Center for Research
   Resources; American Heart Association/Bugher Foundation Centers for
   Stroke Prevention Research; National Institutes of Health Genes,
   Environment and Health Initiative (GEI), GENEVA consortium under GEI
   [U01 HG004436]; National Institutes of Health [HHSN268200782096C];
   Office of Research and Development, Medical Research Service; Baltimore
   Geriatrics Research, Education, and Clinical Center of the Department of
   Veterans Affairs; National Institute of Neurological Disorders and
   Stroke (NINDS); NIH Office of Research on Women's Health [R01 NS45012,
   U01 NS069208-01]; Austrian Science Fund [P20545]; National Institute on
   Aging, National Institutes of Health, Department of Health and Human
   Services [Z01 AG000954-06, Z01 AG000015-50]; National Institute for
   Neurological Disorders and Stroke (United States) [R01 NS42733, R01
   NS39987]; National Institute of Neurological Disorders And Stroke
   [21NS064908]; National Human Genome Research Institute (NHGRI) [U01
   HG005160]; National Institutes of Health to the Johns Hopkins
   University; United States Public Health Service, National Institute of
   Neurological Disorders and Stroke of the National Institutes of Health,
   Bethesda, MD [R01 NS34447]
FX The ASGC was funded by grants from the Australian National and Medical
   Health Research Council (NHMRC Project Grant ID: 569257) and the
   Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623).
   Support was also received from the University of Newcastle. E. G. H. was
   supported by an NHMRC Training (Postdoctoral) Fellowship. BRAINS was
   supported by a Department of Health (United Kingdom) senior fellowship
   to P. S. and also by a grant from the Henry Smith Charity and the
   British Council (UKIERI). The Besta Cerebrovascular Diseases Registry
   (CEDIR) was supported by the Italian Ministry of Health, years 2007-2010
   (Annual Research Funding; Grant Numbers: RC 2007/LR6, RC 2008/LR6; RC
   2009/LR8; RC 2010/LR8). This study was supported also by Cariplo
   Foundation (grant No. 2010-0253). S. P. was supported by a PhD
   fellowship of the University of Pavia (PhD program in Genetic and
   Biomolecular Sciences). The PROCARDIS study was supported by the
   European Community Sixth Framework Program (LSHM-CT-2007-037273). GASROS
   was supported by the American Heart Association/Bugher Foundation
   Centers for Stroke Prevention Research (0775010N); NIH-NINDS grant Nos.
   K23NS064052 (N.S.R.), R01NS063925 (J.R.), and P50NS051343 (J.R and K. L.
   F.); the Deane Institute for Integrative Study of Atrial Fibrillation
   and Stroke; and the Keane Stroke Genetics Research Fund. The MIGen study
   was funded by the US National Institutes of Health and National Heart,
   Lung, and Blood Institute STAMPEED genomics research program (R01
   HL087676) and a grant from the National Center for Research Resources.
   A. B., N.S.R., and C. D. A. were supported in part by the American Heart
   Association/Bugher Foundation Centers for Stroke Prevention Research.
   The GEOS study was supported by the National Institutes of Health Genes,
   Environment and Health Initiative (GEI) Grant U01 HG004436, as part of
   the GENEVA consortium under GEI. Genotyping services were provided by
   the Johns Hopkins University Center for Inherited Disease Research
   (CIDR), which is fully funded through a federal contract from the
   National Institutes of Health to the Johns Hopkins University (contract
   No. HHSN268200782096C). Assistance with data cleaning was provided by
   the GENEVA Coordinating Center (U01 HG 004446; PI, Bruce S. Weir). Study
   recruitment and collection of datasets were supported by the Office of
   Research and Development, Medical Research Service, and the Baltimore
   Geriatrics Research, Education, and Clinical Center of the Department of
   Veterans Affairs and by grants from the National Institute of
   Neurological Disorders and Stroke (NINDS) and the NIH Office of Research
   on Women's Health (R01 NS45012, U01 NS069208-01). Genetic studies of the
   Austrian Stroke Prevention Study (GRAZ) are supported by the Austrian
   Science Fund (P20545). ISGS/SWISS: This work was supported in part by
   the Intramural Research Program of the National Institute on Aging,
   National Institutes of Health, Department of Health and Human Services;
   project No. Z01 AG000954-06. This work used samples and clinical data
   from the NINDS Human Genetics Resource Center DNA and Cell Line
   Repository (http://ccr.coriell.org/ninds), human subjects protocol Nos.
   2003-081 and 2004-147. The inclusion of Baltimore Longitudinal Study of
   Aging samples was supported in part by the Intramural Research Program
   of the National Institute on Aging, National Institutes of Health,
   Department of Health and Human Services; project No. Z01 AG000015-50,
   human subjects protocol number 2003-078.; The ISGS study was funded by a
   grant from the National Institute for Neurological Disorders and Stroke
   (United States), grant No. R01 NS42733 (PI, J. Meschia). The SWISS study
   was funded by a grant from the National Institute for Neurological
   Disorders and Stroke (United States), grant No. R01 NS39987 (PI, J.
   Meschia). This study used the high-performance computational
   capabilities of the Biowulf Linux cluster at the National Institutes of
   Health, Bethesda, MD (http://biowulf.nih.gov). The RACE study is
   supported by grants from the National Institute of Neurological
   Disorders And Stroke (Award No. 21NS064908) and educational awards to
   investigators at the Center for Noncommunicable Diseases, Pakistan. The
   GWAS component of the VISP study was supported by the National Human
   Genome Research Institute (NHGRI), Grant U01 HG005160 (PIs, Michele Sale
   and Bradford Worrall), as part of the Genomics and Randomized Trials
   Network (GARNET). Genotyping services were provided by the Johns Hopkins
   University Center for Inherited Disease Research (CIDR), which is fully
   funded through a federal contract from the National Institutes of Health
   to the Johns Hopkins University. Assistance with data cleaning was
   provided by the GARNET Coordinating Center (U01 HG005157; PI, Bruce S.
   Weir). Study recruitment and collection of datasets for the VISP
   clinical trial were supported by an investigator-initiated research
   grant (R01 NS34447; PI, James Toole) from the United States Public
   Health Service, National Institute of Neurological Disorders and Stroke
   of the National Institutes of Health, Bethesda, MD.
NR 36
TC 17
Z9 17
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD APR
PY 2012
VL 43
IS 4
BP 980
EP U143
DI 10.1161/STROKEAHA.111.632075
PG 26
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 916ST
UT WOS:000302124200016
PM 22363065
ER

PT J
AU Resnik, DB
AF Resnik, David B.
TI Limits on risks for healthy volunteers in biomedical research
SO THEORETICAL MEDICINE AND BIOETHICS
LA English
DT Article
DE Human participant research; Risk; Ethics; Regulations; Paternalism;
   Healthy volunteers
ID TRIALS
AB Healthy volunteers in biomedical research often face significant risks in studies that offer them no medical benefits. The U.S. federal research regulations and laws adopted by other countries place no limits on the risks that these participants face. In this essay, I argue that there should be some limits on the risks for biomedical research involving healthy volunteers. Limits on risk are necessary to protect human participants, institutions, and the scientific community from harm. With the exception of self-experimentation, limits on research risks faced by healthy volunteers constitute a type of soft, impure paternalism because participants usually do not fully understand the risks they are taking. I consider some approaches to limiting research risks and propose that healthy volunteers in biomedical research should not be exposed to greater than a 1% chance of serious harm, such as death, permanent disability, or severe illness or injury. While this guideline would restrict research risks, the limits would not be so low that they would prevent investigators from conducting valuable research. They would, however, set a clear upper boundary for investigators and signal to the scientific community and the public that there are limits on the risks that healthy participants may face in research. This standard provides guidance for decisions made by oversight bodies, but it is not an absolute rule. Investigators can enroll healthy volunteers in studies involving a greater than 1% chance of serious harm if they show that the research addresses a compelling public health or social problem and that the risk of serious harm is only slightly more than 1%. The committee reviewing the research should use outside experts to assess these risks.
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-03]
NR 46
TC 9
Z9 9
U1 0
U2 17
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-7415
J9 THEOR MED BIOETH
JI Theor. Med. Bioeth.
PD APR
PY 2012
VL 33
IS 2
BP 137
EP 149
DI 10.1007/s11017-011-9201-1
PG 13
WC Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Social Issues; Biomedical Social
   Sciences
GA 913MP
UT WOS:000301882400003
PM 22198413
ER

PT J
AU Lock, EF
   Abdo, N
   Huang, RL
   Xia, MH
   Kosyk, O
   O'Shea, SH
   Zhou, YH
   Sedykh, A
   Tropsha, A
   Austin, CP
   Tice, RR
   Wright, FA
   Rusyn, I
AF Lock, Eric F.
   Abdo, Nour
   Huang, Ruili
   Xia, Menghang
   Kosyk, Oksana
   O'Shea, Shannon H.
   Zhou, Yi-Hui
   Sedykh, Alexander
   Tropsha, Alexander
   Austin, Christopher P.
   Tice, Raymond R.
   Wright, Fred A.
   Rusyn, Ivan
TI Quantitative High-Throughput Screening for Chemical Toxicity in a
   Population-Based In Vitro Model
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE chemical cytotoxicity; apoptosis; HapMap; lymphoblasts; qHTS
ID HUMAN BREAST-CANCER; NF-KAPPA-B; GENE-EXPRESSION; ENVIRONMENTAL
   CHEMICALS; RISK-ASSESSMENT; HUMAN GENOME; CYTOTOXICITY; ASSOCIATION;
   CELLS; THIOREDOXIN
AB A shift in toxicity testing from in vivo to in vitro may efficiently prioritize compounds, reveal new mechanisms, and enable predictive modeling. Quantitative high-throughput screening (qHTS) is a major source of data for computational toxicology, and our goal in this study was to aid in the development of predictive in vitro models of chemical-induced toxicity, anchored on interindividual genetic variability. Eighty-one human lymphoblast cell lines from 27 Centre d'Etude du Polymorphisme Humain trios were exposed to 240 chemical substances (12 concentrations, 0.26nM-46.0 mu M) and evaluated for cytotoxicity and apoptosis. qHTS screening in the genetically defined population produced robust and reproducible results, which allowed for cross-compound, cross-assay, and cross-individual comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited interindividual differences in cytotoxicity. Specifically, the qHTS in a population-based human in vitro model system has several unique aspects that are of utility for toxicity testing, chemical prioritization, and high-throughput risk assessment. First, standardized and high-quality concentration-response profiling, with reproducibility confirmed by comparison with previous experiments, enables prioritization of chemicals for variability in interindividual range in cytotoxicity. Second, genome-wide association analysis of cytotoxicity phenotypes allows exploration of the potential genetic determinants of interindividual variability in toxicity. Furthermore, highly significant associations identified through the analysis of population-level correlations between basal gene expression variability and chemical-induced toxicity suggest plausible mode of action hypotheses for follow-up analyses. We conclude that as the improved resolution of genetic profiling can now be matched with high-quality in vitro screening data, the evaluation of the toxicity pathways and the effects of genetic diversity are now feasible through the use of human lymphoblast cell lines.
C1 [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
   [Huang, Ruili; Xia, Menghang; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
   [Tice, Raymond R.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27711 USA.
RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
EM iir@unc.edu
RI Tropsha, Alexander/G-6245-2014; Rusyn, Ivan/S-2426-2016
FU National Institute of Environmental Health Sciences interagency
   [Y2-ES-7020-01]; National Institutes of Health (NIH) [R01 ES015241];
   U.S. Environmental Protection Agency (U.S. EPA) [RD83382501]
FX This research was supported, in part, by the Intramural Research
   Programs of the National Toxicology Program, National Institute of
   Environmental Health Sciences interagency agreement Y2-ES-7020-01 and by
   grants from the National Institutes of Health (NIH) (R01 ES015241) and
   U.S. Environmental Protection Agency (U.S. EPA) (RD83382501).
NR 47
TC 21
Z9 22
U1 2
U2 19
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 APR
PY 2012
VL 126
IS 2
BP 578
EP 588
DI 10.1093/toxsci/kfs023
PG 11
WC Toxicology
SC Toxicology
GA 915FD
UT WOS:000302008600028
PM 22268004
ER

PT J
AU Zou, SM
   Stramer, SL
   Dodd, RY
AF Zou, Shimian
   Stramer, Susan L.
   Dodd, Roger Y.
TI Donor Testing and Risk: Current Prevalence, Incidence, and Residual Risk
   of Transfusion-Transmissible Agents in US Allogeneic Donations
SO TRANSFUSION MEDICINE REVIEWS
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; WEST-NILE-VIRUS; CROSS BLOOD SERVICES;
   TRANSMITTED VIRAL-INFECTIONS; NUCLEIC-ACID-AMPLIFICATION; UNSAFE
   INJECTION PRACTICES; UNITED-STATES; HEPATITIS-B; BORNE INFECTIONS;
   SEROLOGIC TEST
AB Over the past 20 years, there has been a major increase in the safety of the blood supply, as demonstrated by declining rates of posttransfusion infection and reductions in estimated residual risk for such infections. Reliable estimates of residual risk have been possible within the American Red Cross system because of the availability of a large amount of reliable and consistent data on donations and infectious disease testing results. Among allogeneic blood donations, the prevalence rates of infection markers for hepatitis C virus (HCV) and hepatitis B virus have decreased over time, although rates for markers of human immunodeficiency virus (HIV) and human T-cell lymphotropic virus did not. The incidence (/100 000 person-years) of HIV and HCV among repeat donors showed apparent increases from 1.55 and 1.89 in 2000 through 2001 to 2.16 and 2.98 in 2007 through 2008. These observed fluctuations confirm the need for continuous monitoring and evaluation. The residual risk of HIV. HCV, and human T-cell lymphotropic virus among all allogeneic donations is currently below 1 per 1 million donations, and that of hepatitis B surface antigen is close to 1 per 300 000 donations. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Zou, Shimian] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA.
   Amer Red Cross, Biomed Serv, Sci Support Off, Gaithersburg, MD USA.
   Amer Red Cross, Holland Lab, Gaithersburg, MD USA.
RP Zou, SM (reprint author), NHLBI, Natl Inst Hlth, Rockledge 2,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM shimian.zou@nih.gov
NR 63
TC 54
Z9 57
U1 3
U2 15
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0887-7963
J9 TRANSFUS MED REV
JI Transf. Med. Rev.
PD APR
PY 2012
VL 26
IS 2
BP 119
EP 128
DI 10.1016/j.tmrv.2011.07.007
PG 10
WC Hematology
SC Hematology
GA 916OI
UT WOS:000302112700002
PM 21871776
ER

PT J
AU Saslow, D
   Solomon, D
   Lawson, HW
   Killackey, M
   Kulasingam, SL
   Cain, J
   Garcia, FAR
   Moriarty, AT
   Waxman, AG
   Wilbur, DC
   Wentzensen, N
   Downs, LS
   Spitzer, M
   Moscicki, AB
   Franco, EL
   Stoler, MH
   Schiffman, M
   Castle, PE
   Myers, ER
AF Saslow, Debbie
   Solomon, Diane
   Lawson, Herschel W.
   Killackey, Maureen
   Kulasingam, Shalini L.
   Cain, Joanna
   Garcia, Francisco A. R.
   Moriarty, Ann T.
   Waxman, Alan G.
   Wilbur, David C.
   Wentzensen, Nicolas
   Downs, Levi S., Jr.
   Spitzer, Mark
   Moscicki, Anna-Barbara
   Franco, Eduardo L.
   Stoler, Mark H.
   Schiffman, Mark
   Castle, Philip E.
   Myers, Evan R.
TI American Cancer Society, American Society for Colposcopy and Cervical
   Pathology, and American Society for Clinical Pathology Screening
   Guidelines for the Prevention and Early Detection of Cervical Cancer
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; ATYPICAL
   SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL
   INCIDENCE RATES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY;
   LONG-TERM RISK; WOMEN 30 YEARS; COST-EFFECTIVENESS
AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HP V) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HP VI 6 and HPV18 infections.
C1 [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA.
   [Solomon, Diane] NCI, Canc Prevent Div, NIH, Rockville, MD USA.
   [Lawson, Herschel W.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA.
   [Killackey, Maureen] Mem Sloan Kettering Canc Ctr, Dept Surg, Mem Sloan Kettering Canc Ctr Reg Network, Gynecol Serv, New York, NY 10021 USA.
   [Kulasingam, Shalini L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
   [Cain, Joanna] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA.
   [Garcia, Francisco A. R.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Ctr Excellence Womens Hlth, Tucson, AZ USA.
   [Moriarty, Ann T.] AmeriPath Indiana, Dept Esoter Testing, Indianapolis, IN USA.
   [Waxman, Alan G.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA.
   [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA.
   [Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
   [Downs, Levi S., Jr.] Univ Minnesota, Sch Med, Dept Obstet Gynecol & Womens Hlth, Div Gynecol Oncol,Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Spitzer, Mark] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
   [Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
   [Franco, Eduardo L.] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
   [Franco, Eduardo L.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada.
   [Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA.
   [Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC USA.
   [Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St NW,Suite 600, Atlanta, GA 30303 USA.
EM debbie.saslow@cancer.org
RI perumal, murugiah/D-1565-2012; Colgan, Terence/J-2339-2016; 
OI Franco, Eduardo/0000-0002-4409-8084
FU Merck and Company; Roche Pharmaceutical/Roche Molecular; Hologic; Third
   Wave Technologies; MTM Laboratories; Qiagen; Becton, Dickson and Company
   (BD); MediSpectra/LUMA; Roche; Gen-Probe, Inc; Abbott Laboratories;
   Roche Molecular Systems; Merck, Inc; GlaxoSmithKline (GSK), Inc.; Merck
   Research Laboratories; Ventana Medical Systems, Inc; BD Diagnostics;
   National Institute of Allergy and Infectious Diseases
FX P. Castle receives payment for service on the Data Monitoring and Safety
   Board for Merck Sharp & Dohme and has received free or discounted human
   papillomavirus tests for research from Qiagen and Roche. C. Cohen serves
   as a speaker for Merck, Inc, and receives honoraria. M. Edelson's spouse
   is employed by and receives a salary from Merck and Company. F. Garcia
   is employed by the University of Arizona, which holds contracts for the
   performance of research with Roche Pharmaceutical/Roche Molecular;
   Hologic; Third Wave Technologies; MTM Laboratories; Qiagen; Becton,
   Dickson and Company (BD); and MediSpectra/LUMA. He also serves on the
   Speakers' Bureau for Qiagen and receives honoraria. J. Cuzick serves on
   advisory boards and as an ad hoc consultant for Qiagen; Roche;
   Gen-Probe, Inc; BD; and Abbott Laboratories, with research funds
   provided to his institution from Qiagen; Roche; Gen-Probe, Inc; BD; and
   Abbott Laboratories. P. Gravitt has acted as a member of the Women's
   Health Advisory Board for Qiagen Corporation and has received research
   funding from Roche Molecular Systems and Merck, Inc, within the last 5
   years. E. Myers received research support for investigations for
   Gen-Probe, Inc, and from GlaxoSmithKline (GSK), Inc. He served as a
   speaker for and received honoraria from Gen-Probe, Inc, and has served
   as a consultant for and received honoraria from Gen-Probe, Inc; Merck
   and Company; and GSK. M Schiffman holds a research agreement to serve as
   a medical monitor in the National Cancer Institute (NCI) vaccine trial
   through GSK; he also receives research support from Qiagen for careHPV
   research in Nigeria. D. Solomon serves as a medical monitor for the
   NCI's Costa Rica HPV Vaccine Trial; the trial receives vaccine from GSK.
   M Stoler received fees for serving as a consultant to Merck Research
   Laboratories; Roche; Ventana Medical Systems, Inc; BD; Hologic; MTM
   Laboratories; and Gen-Probe, Inc. D. Mody conducted lectures and
   workshops for the College of American Pathologists, American Society for
   Clinical Pathology, and the American Society of Cytopathology (ASC), for
   which she received honoraria and/or travel expenses. G. Birdsong 's
   employer receives funding for contracted research performed by him for
   BD Diagnostics. C. Wheeler is an employee of University of New Mexico,
   which is contracted by GSK for its vaccine trials and receives
   equipment/reagents from Roche Molecular Systems, Inc, for human
   papillomavirus genotyping. D. Wilbur serves on the scientific advisory
   board for Corista, LLC. T Darragh received ThinPrep supplies for
   research from Hologic. She also serves on an advisory board for
   OncoHealth Corporation and has received stock options as payment and
   serves on the advisory board of Arbor Vita Corporation. E. Mayeaux
   serves on the speakers' advisory board for both Merck, Inc, and
   PharmaDerm and receives honoraria from both companies for his service. M
   Spitzer serves as a speaker for both Merck, Inc, and Qiagen and receives
   honoraria. K. Ault received clinical research grants from the National
   Institute of Allergy and Infectious Diseases; Gen-Probe, Inc; Merck,
   Inc; and Roche and served as a site principal investigator for the
   research. All grants were provided to his employer, Emory University.
   E.; Franco received honorarium as a Study Steering Committee member for
   GSK; he also serves on the advisory boards of Merck, Inc; Roche; and
   Gen-Probe, Inc, from which he receives honoraria and has acted as an ad
   hoc consultant for Merck, Inc; Roche; Gen-Probe, Inc; and Qiagen, for
   which honoraria were paid to compensate for time away and work
   performed. M Gold received honorarium for serving as a speaker and
   consultant for Hologic. W. Huh serves as a consultant to Roche; Qiagen;
   Merck, Inc; and Inovio Pharmaceuticals, Inc, and receives honoraria from
   all 4 companies. A-B. Moscicki received honorarium for serving as a
   consultant to an advisory board for Merck, Inc. M Einstein has advised
   or participated in educational speaking activities, but does not receive
   an honorarium from any companies. His employer, Montefiore Medical
   Center, has received payment for his time spent on activities for Merck,
   Inc; GSK; Roche; Bristol-Myers Squibb; Hologic; Advaxis, Inc; Aura
   Biosciences, Inc; Inovio Pharmaceuticals, Inc; Photocure ASA;
   NeoDiagnostix, Inc; and PDS Biotechnology Corporation. Montefiore has
   received grant funding for research related to the costs of those Merck,
   GSK, Roche, Advaxis, and Hologic clinical trials for which Dr Einstein
   served as the Montefiore principal investigator. A. Moriarty received
   honorarium as a speaker for ASC. R. Guido has acted as the local
   principal investigator for a multicenter study (contracted research) for
   IKONOsys. A. Waxman receives honoraria and expenses for teaching related
   to the subject matter in this article from nonprofit professional
   organizations and governmental agencies and contractors. He is on the
   executive committee of the board of directors of the American Society
   for Colposcopy and Cervical Pathology; he lectures for them and
   codirects some of their courses and receives honoraria and expenses for
   these functions. He also lectures and directs courses for the American
   College/Congress of Obstetricians and Gynecologists on subjects related
   to this article and receives honoraria from them. Both organizations are
   nonprofit professional organizations. He has also received honoraria and
   expenses from the State of Alaska Department of Health and Social
   Services and several Alaska Native corporations (Southcentral
   Foundation, SouthEast Alaska Regional Health Corporation, Arctic Slope
   Regional Corporation, and Yukon-Kuskokwim Health Corporation) and the
   Breast Cancer Detection Center of Alaska for lecturing on material
   related to this article. He also received honoraria from the Center for
   Health Training, a contractor to Title X agencies for lecturing for the
   Texas Department of State Health Services. He also received a $200
   honorarium from Quadrant HealthCom, Inc, for writing an article related
   to cervical cancer screening for the journal OBG Management.
NR 159
TC 277
Z9 299
U1 5
U2 19
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD APR
PY 2012
VL 137
IS 4
BP 516
EP 542
DI 10.1309/AJCPTGD94EVRSJCG
PG 27
WC Pathology
SC Pathology
GA 912BJ
UT WOS:000301768400002
PM 22431528
ER

PT J
AU Khrutchinsky, A
   Drozdovitch, V
   Kutsen, S
   Minenko, V
   Khrouch, V
   Luckyanov, N
   Voilleque, P
   Bouville, A
AF Khrutchinsky, Arkady
   Drozdovitch, Vladimir
   Kutsen, Semion
   Minenko, Victor
   Khrouch, Valeri
   Luckyanov, Nickolas
   Voilleque, Paul
   Bouville, Andre
TI Mathematical modeling of a survey-meter used to measure radioactivity in
   human thyroids: Monte Carlo calculations of the device response and
   uncertainties
SO APPLIED RADIATION AND ISOTOPES
LA English
DT Article
DE Chernobyl; Thyroid; Measurement; Survey meter; Monte Carlo
ID CHERNOBYL ACCIDENT; I-131; BYELARUS; INHABITANTS; SIMULATION; PHANTOM;
   AREAS; MASS
AB This paper presents results of Monte Carlo modeling of the SRP-68-01 survey meter used to measure exposure rates near the thyroid glands of persons exposed to radioactivity following the Chernobyl accident. This device was not designed to measure radioactivity in humans. To estimate the uncertainty associated with the measurement results, a mathematical model of the SRP-68-01 survey meter was developed and verified. A Monte Carlo method of numerical simulation of radiation transport has been used to calculate the calibration factor for the device and evaluate its uncertainty. The SRP-68-01 survey meter scale coefficient, an important characteristic of the device, was also estimated in this study. The calibration factors of the survey meter were calculated for I-131, I-132, I-133, and I-135 content in the thyroid gland for six age groups of population: newborns; children aged 1 yr, 5 yr, 10 yr, 15 yr; and adults. A realistic scenario of direct thyroid measurements with an "extended" neck was used to calculate the calibration factors for newborns and one-year-olds. Uncertainties in the device calibration factors due to variability of the device scale coefficient, variability in thyroid mass and statistical uncertainty of Monte Carlo method were evaluated. Relative uncertainties in the calibration factor estimates were found to be from 0.06 for children aged 1 yr to 0.1 for 10-yr and 15-yr children. The positioning errors of the detector during measurements deviate mainly in one direction from the estimated calibration factors. Deviations of the device position from the proper geometry of measurements were found to lead to overestimation of the calibration factor by up to 24 percent for adults and up to 60 percent for 1-yr children. The results of this study improve the estimates of I-131 thyroidal content and, consequently, thyroid dose estimates that are derived from direct thyroid measurements performed in Belarus shortly after the Chernobyl accident. (c) 2012 Published by Elsevier Ltd.
C1 [Drozdovitch, Vladimir; Luckyanov, Nickolas; Bouville, Andre] NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Khrutchinsky, Arkady; Kutsen, Semion] Res Inst Nucl Problems, Minsk 220030, Byelarus.
   [Minenko, Victor] Belarusian Med Acad Postgrad Educ, Minsk 220714, Byelarus.
   [Khrouch, Valeri] Burnasyan Fed Med Biophys Ctr, Moscow 123182, Russia.
   [Voilleque, Paul] MJP Risk Assessment Inc, Denver, CO 80220 USA.
RP Drozdovitch, V (reprint author), NCI, DHHS, NIH, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7100, Bethesda, MD 20892 USA.
EM drozdovv@mail.nih.gov
RI Kuten, Semen/F-6699-2016
OI Kuten, Semen/0000-0003-0827-8421
FU National Institutes of Health, National Cancer Institute (USA)
   [N02-CP-45506]; ISTC [B-488P]; National Institute of Allergy and
   Infectious Diseases (USA); National Cancer Institute; NIAID
   [Y2-AI-5077]; NCI [Y3-CO-5117]
FX This work was supported by the National Institutes of Health, National
   Cancer Institute (USA) within the framework of Belarus-U.S. Study of
   Thyroid Cancer and Other Disease following the Chernobyl Accident
   [N02-CP-45506] and the ISTC Project B-488P; and by the Intra-Agency
   Agreement between the National Institute of Allergy and Infectious
   Diseases (USA) and the National Cancer Institute, NIAID agreement
   #Y2-AI-5077 and NCI agreement #Y3-CO-5117. The authors are grateful to
   Vladimir Guzov, Georgy Shulgovich (deceased), and Valeri Kozhemiakin
   (Atomtex, Minsk, Belarus) for performing measurements of the exposure
   rate and fruitful discussion of measurements results. Special thanks are
   to Nikolay Bakovets and Valeri Milevsky (Belstandard, Minsk, Belarus),
   who provided useful information on calibration of the SRP-68-01 device.
   The authors would like to thank the reviewer for constructive comments
   and suggestions that help improve the manuscript.
NR 18
TC 4
Z9 4
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0969-8043
J9 APPL RADIAT ISOTOPES
JI Appl. Radiat. Isot.
PD APR
PY 2012
VL 70
IS 4
BP 743
EP 751
DI 10.1016/j.apradiso.2011.12.032
PG 9
WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology,
   Nuclear Medicine & Medical Imaging
SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 913YW
UT WOS:000301914300030
PM 22245289
ER

PT J
AU Hasko, G
   Pacher, P
AF Hasko, Gyorgy
   Pacher, Pal
TI Regulation of Macrophage Function by Adenosine
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE cytokines; G proteins; immune system; immunosuppressive therapy;
   macrophages
ID ENDOTHELIAL GROWTH-FACTOR; A(2A) RECEPTOR AGONISTS;
   NECROSIS-FACTOR-ALPHA; ALTERNATIVELY ACTIVATED MACROPHAGES; SYNERGISTIC
   UP-REGULATION; TNF-ALPHA; MURINE MACROPHAGES; VASCULAR INJURY; HUMAN
   MONOCYTES; A2A RECEPTOR
AB Following its release into the extracellular space in response to metabolic disturbances, the endogenous nucleoside adenosine exerts a range of immunomodulatory effects and cells of the mononuclear phagocyte system are among its major targets. Adenosine governs mononuclear phagocyte functions via 4 G-protein-coupled cell membrane receptors, which are denoted A(1), A(2A), A(2B), and A(3) receptors. Adenosine promotes osteoclast differentiation via A(1) receptors and alters monocyte to dendritic cell differentiation through A(2B) receptors. Adenosine downregulates classical macrophage activation mainly through A(2A) receptors. In contrast A(2B) receptor activation upregulates alternative macrophage activation. Adenosine promotes angiogenesis, which is mediated by inducing the production of vascular endothelial growth factor by mononuclear phagocytes through A(2A), A(2B), and A(3) receptors. By regulating mononuclear phagocyte function adenosine dictates the course of inflammatory and vascular diseases and cancer. (Arterioscler Thromb Vasc Biol. 2012;32:865-869.)
C1 [Hasko, Gyorgy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
   [Hasko, Gyorgy] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA.
   [Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA.
EM haskoge@umdnj.edu
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU National Institutes of Health [R01GM66189]; USAMRMC [09065004,
   W81XWH-10-1-1015]; NIH/NIAAA
FX This work was supported by National Institutes of Health Grant
   R01GM66189 (to G.H.), USAMRMC grant log #09065004 (Contract
   W81XWH-10-1-1015) (to G.H.), and Intramural Research Program of
   NIH/NIAAA (to P.P.).
NR 59
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U1 0
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD APR
PY 2012
VL 32
IS 4
BP 865
EP 869
DI 10.1161/ATVBAHA.111.226852
PG 5
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 910VV
UT WOS:000301672300009
PM 22423038
ER

PT J
AU Kim, YC
   Hummer, G
AF Kim, Young C.
   Hummer, Gerhard
TI Proton-pumping mechanism of cytochrome c oxidase: A kinetic
   master-equation approach
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Review
DE Proton pumping; Cytochrome c oxidase; Respiratory chain; Energy
   transduction; Molecular machine; Kinetic master equation
ID HEME-COPPER OXIDASES; NONEQUILIBRIUM STEADY-STATE; ELECTRON-TRANSFER;
   PARACOCCUS-DENITRIFICANS; MOLECULAR MOTORS; CATALYTIC CYCLE;
   RHODOBACTER-SPHAEROIDES; OXYGEN ACTIVATION; TRANSLOCATION; WATER
AB Cytochrome c oxidase is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, cytochrome c oxidase translocates protons across the membrane against this potential. Based on a wealth of experiments and calculations, an increasingly detailed picture of the reaction intermediates in the redox cycle has emerged. However, the fundamental mechanism of proton pumping coupled to redox chemistry remains largely unresolved. Here we examine and extend a kinetic master-equation approach to gain insight into redox-coupled proton pumping in cytochrome c oxidase. Basic principles of the cytochrome c oxidase proton pump emerge from an analysis of the simplest kinetic models that retain essential elements of the experimentally determined structure, energetics, and kinetics, and that satisfy fundamental physical principles. The master-equation models allow us to address the question of how pumping can be achieved in a system in which all reaction steps are reversible. Whereas proton pumping does not require the direct modulation of microscopic reaction barriers, such kinetic gating greatly increases the pumping efficiency. Further efficiency gains can be achieved by partially decoupling the proton uptake pathway from the active-site region. Such a mechanism is consistent with the proposed Glu valve, in which the side chain of a key glutamic acid shuttles between the D channel and the active-site region. We also show that the models predict only small proton leaks even in the absence of turnover. The design principles identified here for cytochrome c oxidase provide a blueprint for novel biology-inspired fuel cells, and the master-equation formulation should prove useful also for other molecular machines. This article is part of a Special Issue entitled: Respiratory Oxidases. Published by Elsevier B.V.
C1 [Kim, Young C.] USN, Res Lab, Ctr Computat Mat Sci, Washington, DC 20375 USA.
   [Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, YC (reprint author), USN, Res Lab, Ctr Computat Mat Sci, Washington, DC 20375 USA.
EM youngchan.kim@nrl.navy.mil; gerhard.hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health
FX We thank Prof. Marten Wikstrom and Dr. Ville Kaila for many insightful
   and stimulating discussions. G.H. is supported by the Intramural
   Research Program of the National Institute of Diabetes and Digestive and
   Kidney Diseases, National Institutes of Health.
NR 80
TC 19
Z9 19
U1 2
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
EI 0006-3002
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD APR
PY 2012
VL 1817
IS 4
SI SI
BP 526
EP 536
DI 10.1016/j.bbabio.2011.09.004
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 913NV
UT WOS:000301885600008
PM 21946020
ER

PT J
AU Harlow, SD
   Gass, M
   Hall, JE
   Lobo, R
   Maki, P
   Rebar, RW
   Sherman, S
   Sluss, PM
   de Villiers, TJ
AF Harlow, Sioban D.
   Gass, Margery
   Hall, Janet E.
   Lobo, Roger
   Maki, Pauline
   Rebar, Robert W.
   Sherman, Sherry
   Sluss, Patrick M.
   de Villiers, Tobie J.
CA STRAW 10 Collaborative Grp
TI Executive summary of the Stages of Reproductive Aging Workshop+10:
   addressing the unfinished agenda of staging reproductive aging
SO CLIMACTERIC
LA English
DT Article
DE REPRODUCTIVE AGING; OVARIAN AGING; MENOPAUSE; FOLLICLE-STIMULATING
   HORMONE; ANTIMULLERIAN HORMONE; ANTRAL FOLLICLE COUNT; INHIBIN-B
ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; EARLY MENOPAUSAL
   TRANSITION; POLYCYSTIC-OVARY-SYNDROME; MIDDLE-AGED WOMEN; REGULAR
   MENSTRUAL CYCLES; INHIBIN-B; ANTIMULLERIAN HORMONE; LONGITUDINAL
   CHANGES; DEPRESSIVE SYMPTOMS
AB Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.
   Methods Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimullerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.
   Results STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.
   Conclusions STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.
C1 [Harlow, Sioban D.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Gass, Margery] N Amer Menopause Soc, Mayfield Hts, OH USA.
   [Hall, Janet E.] Harvard Univ, Sch Med, Dept Med, Endocrine Soc, Boston, MA USA.
   [Lobo, Roger] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
   [Maki, Pauline] Univ Illinois, Dept Psychiat & Psychol, Chicago, IL USA.
   [Rebar, Robert W.] Amer Soc Reprod Med, Birmingham, AL USA.
   [Sherman, Sherry] NIA, Bethesda, MD 20892 USA.
   [Sluss, Patrick M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [de Villiers, Tobie J.] Int Menopause Soc, Cape Town, South Africa.
RP Harlow, SD (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM harlow@umich.edu
FU North American Menopause Society (NAMS); National Institute on Aging
   (NIA); Eunice Kennedy Shriver National Institute of Child Health and
   Human Development (NICHD); Endocrine Society; National Institute on
   Mental Health (NIMH); National Institute of Allergy and Infectious
   Diseases (NIAID); National Institute on Drug Abuse (NIDA); Royal Ottawa
   Foundation for Mental Health; Mayo Clinic; Baycrest; Northwestern
   University; Society for Women's Health Research; International Menopause
   Society; Pfizer; Australasian Pacific Menopause Society; Virginia
   Commonwealth University Institute for Women's Health; ASRM; Adcock
   Ingram; Servier; Amgen; Bayer; National Institutes of Health (NIH),
   Department of Health and Human Services (DHHS), through the National
   Institute on Aging (NIA) [AG039961]; NIH Office of Research on Women's
   Health (ORWH); American Society for Reproductive Medicine (ASRM);
   International Menopause Society (IMS)
FX P.M.S. and S.S. declare no conflict of interest. M.G. receives salary
   support from The North American Menopause Society (NAMS). S.D.H. has
   grant support from the National Institute on Aging (NIA) and Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   (NICHD) and receives travel support from NAMS. J.E.H. has grant support
   from NIA and receives travel support from the Endocrine Society. R.L. is
   past president of the American Society for Reproductive Medicine (ASRM).
   P.M. receives grant support from the National Institute on Mental Health
   (NIMH), the NIA, the National Institute of Allergy and Infectious
   Diseases (NIAID), and the National Institute on Drug Abuse (NIDA); is on
   the Board of Trustees for NAMS; and has previously consulted for Noven
   Pharmaceuticals, received lecture fees from the Royal Ottawa Foundation
   for Mental Health, the Mayo Clinic, Baycrest, and Northwestern
   University and received travel support from the Society for Women's
   Health Research, the International Menopause Society, Pfizer, the
   Australasian Pacific Menopause Society, Virginia Commonwealth University
   Institute for Women's Health. R. W. R. receives salary support from
   ASRM. T.J.d.V. declares no direct conflict of interest as regards the
   submitted article but has in the past received consultancy fees from
   Adcock Ingram and Pfizer; speaker's fees from Servier; and travel
   support from Amgen, Pfizer, and Bayer.; The Stages of Reproductive Aging
   Workshop (STRAW) + 10 had grant support from the National Institutes of
   Health (NIH), Department of Health and Human Services (DHHS), through
   the National Institute on Aging (NIA) (AG039961), and the NIH Office of
   Research on Women's Health (ORWH) as well as from The North American
   Menopause Society (NAMS), the American Society for Reproductive Medicine
   (ASRM), the International Menopause Society (IMS), and the Endocrine
   Society.
NR 90
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U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1369-7137
J9 CLIMACTERIC
JI Climacteric
PD APR
PY 2012
VL 15
IS 2
BP 105
EP 114
DI 10.3109/13697137.2011.650656
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 908ZV
UT WOS:000301532500002
PM 22338612
ER

PT J
AU Truog, RD
   Miller, FG
AF Truog, Robert D.
   Miller, Franklin G.
TI "Brain death" is a useful fiction
SO CRITICAL CARE MEDICINE
LA English
DT Letter
C1 [Truog, Robert D.] Childrens Hosp, Boston, MA 02115 USA.
   [Miller, Franklin G.] NIH, Bethesda, MD 20892 USA.
RP Truog, RD (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
NR 6
TC 3
Z9 3
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD APR
PY 2012
VL 40
IS 4
BP 1393
EP 1394
DI 10.1097/CCM.0b013e3182451a08
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 912QC
UT WOS:000301813700080
PM 22425866
ER

PT J
AU Nance, JR
   Dowling, JJ
   Gibbs, EM
   Bonnemann, CG
AF Nance, Jessica R.
   Dowling, James J.
   Gibbs, Elizabeth M.
   Boennemann, Carsten G.
TI Congenital Myopathies: An Update
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE Congenital myopathy; Nemaline rod myopathy; Core myopathy; Central core
   disease; Multiminicore disease; Centronuclear myopathy; ACTA1; NEB;
   TMP2; TPM3; TNNT1; Cofilin 2; KTBDB13; RYR1; SEPN1; MTM1; DNM2; BIN1
ID CENTRAL-CORE DISEASE; LINKED MYOTUBULAR MYOPATHY; DNM2-RELATED
   CENTRONUCLEAR MYOPATHY; RYANODINE RECEPTOR GENE; THIN FILAMENT LENGTH;
   DYNAMIN 2 MUTATION; ALPHA-ACTIN GENE; NEMALINE MYOPATHY;
   SKELETAL-MUSCLE; RYR1 MUTATIONS
AB Congenital myopathy is a clinicopathological concept of characteristic histopathological findings on muscle biopsy in a patient with early-onset weakness. Three main categories are recognized within the classical congenital myopathies: nemaline myopathy, core myopathy, and centronuclear myopathy. Recent evidence of overlapping clinical and histological features between the classical forms and their different genetic entities suggests that there may be shared pathomechanisms between the congenital myopathies. Animal models, especially mouse and zebrafish, have been especially helpful in elucidating such pathomechanisms associated with the congenital myopathies and provide models in which future therapies can be investigated.
C1 [Boennemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
   [Nance, Jessica R.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
   [Dowling, James J.] Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA.
   [Dowling, James J.; Gibbs, Elizabeth M.] Univ Michigan, Med Ctr, Dept Neurol, Ann Arbor, MI 48109 USA.
   [Dowling, James J.; Gibbs, Elizabeth M.] Univ Michigan, Med Ctr, Dept Neurosci, Ann Arbor, MI 48109 USA.
RP Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Porter Neurosci Res Ctr, 35 Convent Dr,Bldg 35,Room 2A-116, Bethesda, MD 20892 USA.
EM carsten.bonnemann@nih.gov
FU National Institute of Neurological Disorders and Stroke, National
   Institutes of Health; NIH [NIH1K08AR054835]
FX CGB's research is supported by the Intramural Research Program of the
   National Institute of Neurological Disorders and Stroke, National
   Institutes of Health, JD is supported by an NIH K08 award
   (NIH1K08AR054835). We apologize to researchers whose work could not be
   cited due to this reviews restrictions in length and focus.
NR 105
TC 44
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U1 1
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD APR
PY 2012
VL 12
IS 2
BP 165
EP 174
DI 10.1007/s11910-012-0255-x
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 912KR
UT WOS:000301797400008
PM 22392505
ER

PT J
AU Vickers, KC
   Remaley, AT
AF Vickers, Kasey C.
   Remaley, Alan T.
TI Lipid-based carriers of microRNAs and intercellular communication
SO CURRENT OPINION IN LIPIDOLOGY
LA English
DT Review
DE intercellular communication; lipids; microRNAs
ID TUMOR-DERIVED EXOSOMES; CIRCULATING MICRORNAS; NEUTRAL
   SPHINGOMYELINASE-2; CHOLESTEROL HOMEOSTASIS; CARDIOVASCULAR-DISEASE;
   DIAGNOSTIC BIOMARKERS; SCAVENGER RECEPTOR; BREAST-CANCER; VIRAL MIRNAS;
   LUNG-CANCER
AB Purpose of review
   Extracellular microRNAs (miRNAs) are uniquely stable in plasma, and the levels of specific circulating miRNAs can differ with disease. Extracellular miRNAs are associated with lipid-based carriers and lipid-free proteins. miRNAs can be transferred from cell-to-cell by lipid-based carriers and affect gene expression. This review summarizes recent studies that demonstrate the transfer of miRNA between cells and their potential role in intercellular communication.
   Recent findings
   Microvesicles, exosomes, apoptotic bodies, lipoproteins, and large microparticles contain miRNAs. Recent studies have demonstrated that miRNAs are transferred between dendritic cells, hepatocellular carcinoma cells, and adipocytes in lipid-based carriers. miRNAs are also transferred from T cells to antigen-presenting cells, from stem cells to endothelial cells and fibroblasts, from macrophages to breast cancer cells, and from epithelial cells to hepatocytes in lipid-based carriers. The cellular export of miRNAs in lipid-based carriers is regulated by the ceramide pathway, and the delivery of lipid-associated miRNAs to recipient cells is achieved by various routes, including endocytotic uptake, membrane-fusion, and scavenger receptors.
   Summary
   Cellular miRNAs are exported in and to lipid-based carriers (vesicles and lipoprotein particles) and transferred to recipient cells with gene expression changes as intercellular communication.
C1 [Vickers, Kasey C.] NHLBI, Lipoprotein Metab Sect, Cardiovasc Pulm Sect, NIH, Bethesda, MD 20892 USA.
RP Vickers, KC (reprint author), NHLBI, Lipoprotein Metab Sect, Cardiovasc Pulm Sect, NIH, 10 Ctr Dr,Bldg 10,8N222 MSC-1765, Bethesda, MD 20892 USA.
EM vickerskc@nhlbi.nih.gov
FU NIH NHLBI
FX This work was funded by the NIH NHLBI Intramural Research Program.
NR 73
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U1 2
U2 59
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0957-9672
J9 CURR OPIN LIPIDOL
JI Curr. Opin. Lipidology
PD APR
PY 2012
VL 23
IS 2
BP 91
EP 97
DI 10.1097/MOL.0b013e328350a425
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral
   Vascular Disease
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
   Cardiovascular System & Cardiology
GA 910RL
UT WOS:000301658900003
PM 22418571
ER

PT J
AU Enoch, MA
AF Enoch, Mary-Anne
TI The Influence of Gene-Environment Interactions on the Development of
   Alcoholism and Drug Dependence
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Article
DE Childhood maltreatment; Sexual abuse; Physical abuse; Gene-environment
   interactions; Alcoholism; Drug dependence; Stressful life events;
   Crossover of risk; Differential susceptibility hypothesis; Alcohol
   dependence; Cocaine dependence; Adolescent problem drinking; HPA axis;
   Stress circuitry; Cortisol; Reward pathway; Dopamine; Corpus callosum;
   SLC6A4; 5-HTTLPR; MAOA-LPR; CRHBP; CRHR1; FKBP5; GABRA2; COMT; PER1;
   KCNJ6
ID CHILDHOOD SEXUAL-ABUSE; SUBSTANCE USE DISORDERS; STRESSFUL LIFE EVENTS;
   COMORBIDITY SURVEY REPLICATION; NATIONAL EPIDEMIOLOGIC SURVEY; ADULT
   PSYCHIATRIC-DISORDERS; SEROTONIN TRANSPORTER GENE; AGE-OF-ONSET;
   RISK-FACTORS; EXTERNALIZING BEHAVIOR
AB Alcoholism and drug dependence are common psychiatric disorders with a heritability of about 50%; therefore genetic and environmental influences are equally important. Early-life stress is a predictor of adolescent problem drinking/drug use and alcohol/drug dependence in adulthood, but moderating factors governing the availability of alcohol/drug are important. The risk-resilience balance for addiction may be due in part to the interaction between genetic variation and environment stressors (G x E); this has been confirmed by twin studies of inferred genetic risk. Measured genotype studies to detect G x E effects have used a range of alcohol consumption and diagnostic phenotypes and stressors ranging from early-life to adulthood past year life events. In this article, the current state of the field is critically reviewed and suggestions are put forth for future research.
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
FU Intramural NIH HHS [ZIA AA000306-04]
NR 94
TC 39
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U1 5
U2 44
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD APR
PY 2012
VL 14
IS 2
BP 150
EP 158
DI 10.1007/s11920-011-0252-9
PG 9
WC Psychiatry
SC Psychiatry
GA 907UG
UT WOS:000301443700008
PM 22367454
ER

PT J
AU Chen, GJ
   Ramos, E
   Adeyemo, A
   Shriner, D
   Zhou, J
   Doumatey, AP
   Huang, HX
   Erdos, MR
   Gerry, NP
   Herbert, A
   Bentley, AR
   Xu, HC
   Charles, BA
   Christman, MF
   Rotimi, CN
AF Chen, Guanjie
   Ramos, Edward
   Adeyemo, Adebowale
   Shriner, Daniel
   Zhou, Jie
   Doumatey, Ayo P.
   Huang, Hanxia
   Erdos, Michael R.
   Gerry, Norman P.
   Herbert, Alan
   Bentley, Amy R.
   Xu, Huichun
   Charles, Bashira A.
   Christman, Michael F.
   Rotimi, Charles N.
TI UGT1A1 is a major locus influencing bilirubin levels in African
   Americans
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE GWAS; replications; bilirubin; African Americans
ID GENOME-WIDE ASSOCIATION; HIGH SERUM BILIRUBIN; GENETIC-ANALYSIS;
   HEART-DISEASE; POPULATION; RISK; LINKAGE; NUMBER; FAMILY; ADULTS
AB Total serum bilirubin is associated with several clinical outcomes, including cardiovascular disease, diabetes and drug metabolism. We conducted a genome-wide association study in 619 healthy unrelated African Americans in an attempt to replicate reported findings in Europeans and Asians and to identify novel loci influencing total serum bilirubin levels. We analyzed a dense panel of over two million genotyped and imputed SNPs in additive genetic models adjusting for age, sex, and the first two significant principal components from the sample covariance matrix of genotypes. Thirty-nine SNPs spanning a 78 kb region within the UGT1A1 displayed P-values <5 x 10(-8). The lowest P-value was 1.7 x 10(-22) for SNP rs887829. None of SNPs in the UGT1A1 remained statistically significant in conditional association analyses that adjusted for rs887829. In addition, SNP rs10929302 located in phenobarbital response enhancer module was significantly associated with bilirubin level with a P-value of 1.37 x 10(-11); this enhancer module is believed to have a critical role in phenobarbital treatment of hyperbilirubinemia. Interestingly, the lead SNP, rs887829, is in strong linkage disequilibrium (LD) (r(2)>= 0.74) with rs10929302. Taking advantage of the lower LD and shorter haplotypes in African-ancestry populations, we identified rs887829 as a more refined proxy for the causative variant influencing bilirubin levels. Also, we replicated the reported association between variants in SEMA3C and bilirubin levels. In summary, UGT1A1 is a major locus influencing bilirubin levels and the results of this study promise to contribute to understanding of the etiology and treatment of hyperbilirubinaemia in African-ancestry populations. European Journal of Human Genetics (2012) 20, 463-468; doi: 10.1038/ejhg.2011.206; published online 16 November 2011
C1 [Chen, Guanjie; Ramos, Edward; Adeyemo, Adebowale; Shriner, Daniel; Zhou, Jie; Doumatey, Ayo P.; Huang, Hanxia; Bentley, Amy R.; Xu, Huichun; Charles, Bashira A.; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
   [Erdos, Michael R.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Gerry, Norman P.; Christman, Michael F.] Coriell Inst Med Res, Camden, NJ USA.
   [Herbert, Alan] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA.
RP Chen, GJ (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4047, Bethesda, MD 20892 USA.
EM chengu@mail.nih.gov; rotimic@mail.nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231
FU National Institute of General Medical Sciences MBRS/SCORE
   [S06GM008016-320107, S06GM008016-380111]; National Center for Research
   Resources at the National Institutes of Health (NIH) [2M01RR010284];
   National Human Genome Research Institute; National Institute of Diabetes
   and Digestive and Kidney Diseases; Center for Information Technology;
   Office of the Director at the NIH [Z01HG200362]
FX The study was supported by grants S06GM008016-320107 to CR and
   S06GM008016-380111 to AA, both from the National Institute of General
   Medical Sciences MBRS/SCORE Program. Participant enrollment was carried
   out at the Howard University General Clinical Research Center supported
   by National Center for Research Resources grant 2M01RR010284 at the
   National Institutes of Health (NIH). The contents of this publication
   are solely the responsibility of the authors and do not necessarily
   represent the official view of NIH or the Department of Health and Human
   Services. This research was supported in part by the Intramural Research
   Program of the Center for Research on Genomics and Global Health, which
   is supported by the National Human Genome Research Institute, the
   National Institute of Diabetes and Digestive and Kidney Diseases, the
   Center for Information Technology and the Office of the Director at the
   NIH (Z01HG200362). Genotyping support was provided by the Coriell
   Institute for Medical Research.
NR 35
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U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD APR
PY 2012
VL 20
IS 4
BP 463
EP 468
DI 10.1038/ejhg.2011.206
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 911RI
UT WOS:000301736600016
PM 22085899
ER

PT J
AU Pierson, TM
   Simeonov, DR
   Sincan, M
   Adams, DA
   Markello, T
   Golas, G
   Fuentes-Fajardo, K
   Hansen, NF
   Cherukuri, PF
   Cruz, P
   Mullikin, JC
   Blackstone, C
   Tifft, C
   Boerkoel, CF
   Gahl, WA
AF Pierson, Tyler Mark
   Simeonov, Dimitre R.
   Sincan, Murat
   Adams, David A.
   Markello, Thomas
   Golas, Gretchen
   Fuentes-Fajardo, Karin
   Hansen, Nancy F.
   Cherukuri, Praveen F.
   Cruz, Pedro
   Mullikin, James C.
   Blackstone, Craig
   Tifft, Cynthia
   Boerkoel, Cornelius F.
   Gahl, William A.
CA NISC Comparative Sequencing
TI Exome sequencing and SNP analysis detect novel compound heterozygosity
   in fatty acid hydroxylase-associated neurodegeneration
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE fatty acid 2-hydroxylase; fatty acid hydroxylase-associated
   neurodegeneration; exome sequencing; deletion analysis; neuropathy
ID SPASTIC PARAPLEGIA SPG35; GENE; FORM; 2-HYDROXYLASE; MODEL
AB Fatty acid hydroxylase-associated neurodegeneration due to fatty acid 2-hydroxylase deficiency presents with a wide range of phenotypes including spastic paraplegia, leukodystrophy, and/or brain iron deposition. All previously described families with this disorder were consanguineous, with homozygous mutations in the probands. We describe a 10-year-old male, from a non-consanguineous family, with progressive spastic paraplegia, dystonia, ataxia, and cognitive decline associated with a sural axonal neuropathy. The use of high-throughput sequencing techniques combined with SNP array analyses revealed a novel paternally derived missense mutation and an overlapping novel maternally derived similar to 28-kb genomic deletion in FA2H. This patient provides further insight into the consistent features of this disorder and expands our understanding of its phenotypic presentation. The presence of a sural nerve axonal neuropathy had not been previously associated with this disorder and so may extend the phenotype. European Journal of Human Genetics (2012) 20, 476-479; doi: 10.1038/ejhg.2011.222; published online 7 December 2011
C1 [Pierson, Tyler Mark; Blackstone, Craig] NINDS, Neurogenet Branch, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
   [Pierson, Tyler Mark; Adams, David A.; Markello, Thomas; Fuentes-Fajardo, Karin; Tifft, Cynthia; Boerkoel, Cornelius F.; Gahl, William A.] NIH Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA.
   [Simeonov, Dimitre R.; Sincan, Murat; Adams, David A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Markello, Thomas; Golas, Gretchen; Tifft, Cynthia; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   [Golas, Gretchen] NIH, Intramural Program, Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA.
   [Hansen, Nancy F.; Cherukuri, Praveen F.; Cruz, Pedro; Mullikin, James C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [NISC Comparative Sequencing] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
RP Pierson, TM (reprint author), NINDS, Neurogenet Branch, Porter Neurosci Res Ctr, Bldg 35,Room 2A-1000,35 Convent Dr,MSC 3705, Bethesda, MD 20892 USA.
EM piersonty@ninds.nih.gov
FU NIH; National Human Genome Research Institute, National Institutes of
   Health
FX We are grateful to the patients and the parents of the family for their
   cooperation. We thank Shannon McNeil, Ronald Austin, Jose Salas,
   Chevalia Robinson, Joy Bryant, and Cheryl Hipple, Eva Baker, Bryan
   Brooks, Barrington Burnett, Kenneth Fischbeck, Roxanne Fischer, Hiroko
   Hama, Tanya Lehky, Joseph Snow, Gilbert Vezina, Lynne Wolfe, and Sandra
   Yang, for administrative, clinical and technical assistance, and
   critical analysis. This work was supported by the NIH Undiagnosed
   Diseases Program and the Intramural Research Program of the National
   Human Genome Research Institute, National Institutes of Health.
NR 14
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD APR
PY 2012
VL 20
IS 4
BP 476
EP 479
DI 10.1038/ejhg.2011.222
PG 4
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 911RI
UT WOS:000301736600018
PM 22146942
ER

PT J
AU Kim, JW
   Gulley, JL
AF Kim, Joseph W.
   Gulley, James L.
TI Poxviral vectors for cancer immunotherapy
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE combination approach; immune-related response criteria; PANVAC-V/F;
   PROSTVAC-V/F; therapeutic cancer vaccine; tumor growth rate
ID RECOMBINANT VACCINIA VIRUS; HUMAN CARCINOEMBRYONIC ANTIGEN; RESISTANT
   PROSTATE-CANCER; COLONY-STIMULATING FACTOR; PHASE-I TRIAL; MULTIPLE
   COSTIMULATORY MOLECULES; CELL LUNG-CANCER; ANKARA MVA VIRUS; CD8(+)
   T-CELLS; IMMUNE-RESPONSES
AB Introduction: Poxviral vaccines have been given to over 1 billion people in the successful global eradication of smallpox. Recombinant poxviruses have been investigated extensively as a novel immunotherapy for cancer, undergoing several iterations to optimize their immunogenicity and efficacy. The current platform expressing multiple costimulatory molecules plus a tumor-associated antigen such as PSA, that is, PSA-TRICOM (PROSTVAC-V/F), is promising and is currently in a Phase III randomized, placebo-controlled clinical trial in metastatic castration-resistant prostate cancer.
   Areas covered: This review discusses the clinical development of poxviral-based cancer vaccines, with a particular focus on the rationale for combining vaccines with other treatment modalities, including radiotherapy, chemotherapy, hormonal therapy, other immune-based therapies and molecularly targeted therapy. We also discuss the importance of appropriate patient selection in clinical trial design.
   Expert opinion: Preclinical and early clinical studies employing poxviral-vector vaccines have shown promising results with this novel immunologic approach, both alone and combined with other therapies. The challenges of translating the science of immunotherapy to clinical practice include clinical trial design that includes appropriate patient selection, appropriate end points and identification of meaningful surrogate biomarkers.
C1 [Gulley, James L.] NCI, NIH, Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA.
   [Gulley, James L.] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, NIH, Ctr Canc Res, Lab Tumor Immunol & Biol, 10 Ctr Dr,Rm 13N208,MSC-1750, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU NIH
FX The authors state no conflict of interest and have received no payment
   in preparation of this manuscript. The authors have received general
   funding from the NIH.
NR 102
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U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1471-2598
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD APR
PY 2012
VL 12
IS 4
BP 463
EP 478
DI 10.1517/14712598.2012.668516
PG 16
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 907YR
UT WOS:000301457100007
PM 22413824
ER

PT J
AU Fairfield, KM
   Murray, KM
   Wierman, HR
   Han, PKJ
   Hallen, S
   Miesfeldt, S
   Trimble, EL
   Warren, JL
   Earle, CC
AF Fairfield, Kathleen M.
   Murray, Kimberly M.
   Wierman, Heidi R.
   Han, Paul K. J.
   Hallen, Sarah
   Miesfeldt, Susan
   Trimble, Edward L.
   Warren, Joan L.
   Earle, Craig C.
TI Disparities in hospice care among older women dying with ovarian cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Hospice; End-of-life; Ovarian cancer
ID OF-LIFE CARE; MEDICARE MANAGED CARE; END; POPULATION; INDICATORS;
   INTENSITY; QUALITY
AB Background. Timely hospice referral is an essential component of quality end-of-life care, although a growing body of research suggests that for patients with various types of cancer, hospice referrals often occur very late in the course of care, and are marked by sociodemographic disparities. However, little is known about the ovarian cancer patient population specifically. We examined the extent and timing of hospice referrals in ovarian cancer patients over age 65, and the factors associated with these outcomes.
   Methods. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 8211 women aged 66+ with ovarian cancer who were diagnosed between 2001 and 2005 and died by December 31, 2007. We excluded women who were not eligible for Medicare A continuously during the 6 months prior to death. Outcomes studied included overall hospice use in the last 6 months of life and late hospice enrollment, defined as within 3 days of death. We examined variations in these two measures based on year of diagnosis and sociodemographic characteristics (age, race, marital status, rural residence, income, education) and type of Medicare received (fee-for-service vs. managed care).
   Results. Among 8211 women in the cohort who died from ovarian cancer, 39.7% never received hospice care (3257/8211). Overall hospice care increased over the period of observation, from 49.7% in 2001 to 74.9% in 2005, but the proportion of women receiving hospice care within 3 days of death did not improve. Among those who received hospice care, 11.2% (556/4954) and 26.2% (1299/4954) received such care within 3 and 7 days of death, respectively. A higher proportion of black women (46.5% vs. 38.4% among whites), women in the lowest income group (42.8% vs. 37.0% in the highest income group), and those receiving fee-for-service Medicare (41.3% vs.33.5% for women in managed care) never received hospice care. In multi-variable models, factors associated with lack of hospice care included age younger than 80 years (OR 1.27, 95% CI 1.15-1.40), non-white race (OR 1.44, 95% CI 1.26-1.65), low income (OR 1.17, 95% CI 1.04-1.32) and enrollment in fee-for-service Medicare compared with managed care (OR 1.39, 95% CI 1.24-1.56).
   Conclusion. More older women with ovarian cancer are receiving hospice care over time, however, a substantial proportion receive such care very near death, and sociodemographic disparities in hospice care exist. Our data also support the need to target lower-income and minority women in efforts to increase optimally timed hospice referrals in this population. Our finding that ovarian cancer patients enrolled in managed care plans were more likely to receive hospice care suggests the importance of health care system factors in the utilization of hospice services. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Fairfield, Kathleen M.; Murray, Kimberly M.; Han, Paul K. J.; Miesfeldt, Susan] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Portland, ME 04102 USA.
   [Fairfield, Kathleen M.] Maine Med Ctr, Dept Med, Portland, ME 04102 USA.
   [Wierman, Heidi R.; Hallen, Sarah] Maine Med Ctr, Dept Geriatr, Portland, ME 04102 USA.
   [Trimble, Edward L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   [Warren, Joan L.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
   [Earle, Craig C.] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada.
RP Fairfield, KM (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, Res Inst, 22 Bramhall St, Portland, ME 04102 USA.
EM fairfk@mmc.org; wiermh@mmc.org; halles@mmc.org;
   trimblet@ctep.nci.nih.gov; joan_warren@nih.gov; craig.earle@ices.on.ca
OI Han, Paul/0000-0003-0165-1940
FU Maine Medical Center
FX Supported by Research funding from Maine Medical Center's RSP Grant
   Program (to Dr. Fairfield). The funder had no role in the conduct of
   this research or preparation of the article.
NR 23
TC 21
Z9 22
U1 0
U2 7
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 APR
PY 2012
VL 125
IS 1
BP 14
EP 18
DI 10.1016/j.ygyno.2011.11.041
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 913LO
UT WOS:000301879600003
PM 22138230
ER

PT J
AU Xu, JL
   Commins, J
   Partridge, E
   Riley, TL
   Prorok, PC
   Johnson, CC
   Buys, SS
AF Xu, Jian-Lun
   Commins, John
   Partridge, Edward
   Riley, Thomas L.
   Prorok, Philip C.
   Johnson, Christine C.
   Buys, Saundra S.
TI Longitudinal evaluation of CA-125 velocity and prediction of ovarian
   cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE CA-125; Ovarian cancer; Screening; Velocity
ID LOGISTIC-REGRESSION ANALYSIS; PROGNOSTIC MODELS; SCREENING TRIAL; SERUM
   CA-125; PROSTATE; LUNG; VALIDATION; MARKERS; STAGE
AB Objective. To determine whether CA-125 velocity is a statistically significant predictor of ovarian cancer and develop a classification rule to screen for ovarian cancer.
   Methods. In the ovarian component of the PLCO cancer screening trial, 28,038 women aged 55-74 had at least two CA-125 screening tests. Ovarian cancer was diagnosed in 72 (0.26%) women. A multiple logistic regression model was developed to evaluate CA-125 velocity and other related covariates as predictors of ovarian cancer. Predictive accuracy was assessed by the concordance index and measures of discrimination and calibration while the fit of the model was assessed by the Hosmer and Lemeshow's goodness-of-fit chi(2) test.
   Results. CA-125 velocity decreased as the number of CA-125 measurements increased but was unaffected by age at baseline screen and family history of ovarian cancer. The average velocity (19.749 U/ml per month) of the cancer group was more than 500 times the average velocity (0.035 U/ml per month) of the non-cancer group.
   Conclusion. Among six covariates used in the model, CA-125 velocity and time intervals between baseline and second to last screening test and between last two screening tests were statistically significant predictors of ovarian cancer. The chance of having ovarian cancer increased as velocity increased, and the chance decreased when the time intervals between baseline and the second to last screening test and between last two screening tests of an individual increased. Published by Elsevier Inc.
C1 [Xu, Jian-Lun; Prorok, Philip C.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
   [Commins, John; Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA.
   [Partridge, Edward] Univ Alabama, Sch Med, Birmingham, AL USA.
   [Johnson, Christine C.] Henry Ford Hlth Syst, Detroit, MI USA.
   [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
RP Xu, JL (reprint author), NCI, Biometry Res Grp, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA.
EM jx2b@nih.gov
OI Johnson, Christine Cole/0000-0002-6864-6604
FU Intramural NIH HHS [Z99 CA999999]
NR 25
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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 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD APR
PY 2012
VL 125
IS 1
BP 70
EP 74
DI 10.1016/j.ygyno.2011.12.440
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 913LO
UT WOS:000301879600013
PM 22198243
ER

PT J
AU Linkov, F
   Maxwell, GL
   Felix, AS
   Lin, Y
   Lenzner, D
   Bovbjerg, DH
   Lokshin, A
   Hennon, M
   Jakicic, JM
   Goodpaster, BH
   DeLany, JP
AF Linkov, Faina
   Maxwell, G. Larry
   Felix, Ashley S.
   Lin, Yan
   Lenzner, Diana
   Bovbjerg, Dana H.
   Lokshin, Anna
   Hennon, Meredith
   Jakicic, John M.
   Goodpaster, Bret H.
   DeLany, James P.
TI Longitudinal evaluation of cancer-associated biomarkers before and after
   weight loss in RENEW study participants: Implications for cancer risk
   reduction
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Obesity; Weight loss; Cancer biomarkers; Interleukins; Endometrial
   cancer
ID BODY-MASS-INDEX; ENDOMETRIAL CANCER; BARIATRIC SURGERY; EPIDEMIOLOGIC
   EVIDENCE; ADIPONECTIN LEVELS; OVARIAN-CANCER; SERUM-LEVELS; OBESITY;
   WOMEN; MORTALITY
AB Introduction. Obesity is a major risk factor for the development of endometrial cancer (EC). An improved understanding of biologic mechanisms associated with weight loss, including alteration in inflammation, hormonal balance, and cancer antigens expression may lead to the development of effective cancer prevention strategies. The goal of this study was to explore longitudinal biomarker changes in obese women who underwent weight loss intervention, testing the hypothesis biomarker levels can be altered through intentional weight loss.
   Methods. Serum samples from 89 participants with Class II and Class III obesity and 43 non morbidly obese comparisons were obtained in Re-Energize with Nutrition. Exercise and Weight Loss (RENEW) study as previously reported. Twenty-one bead-based xMAP immunoassays were utilized, including cancer-associated antigens, cytokines, chemokines, and hormones. One-way repeated measures ANOVA was used to examine the association between changes in biomarker expression levels over time (baseline, 6 months and 12 months). Linear mixed effects models were used to examine longitudinal relationships between biomarker expression levels.
   Results. Mean levels of VEGF, soluble E-selectin. GH, adiponectin, IL-6, IL-7, CA-125, and IGFBP-1 significantly differed between time periods. In adjusted mixed linear models, decreasing BMI was significantly associated with lower levels of soluble E-selectin and IL-6 and increases in GH, adiponectin, and IGFBP-1.
   Conclusions. This is one of the first efforts to explore changes in cancer-associated biomarkers in a cohort of weight loss research participants at high risk for EC development. Our findings demonstrate that changes in the expression of markers can be achieved with weight loss intervention. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Linkov, Faina; Lokshin, Anna] Univ Pittsburgh, Magee Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
   [Linkov, Faina; Hennon, Meredith] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
   [Maxwell, G. Larry] Walter Reed Army Med Ctr, Gynecol Canc Ctr, Washington, DC 20307 USA.
   [Felix, Ashley S.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD USA.
   [Bovbjerg, Dana H.] Univ Pittsburgh, Inst Canc, Biobehav Med Oncol Program, Pittsburgh, PA USA.
   [Lin, Yan; Lenzner, Diana] Univ Pittsburgh, Inst Canc, Dept Biostat Facil, Pittsburgh, PA USA.
   [Jakicic, John M.; Goodpaster, Bret H.; DeLany, James P.] Univ Pittsburgh, Phys Act & Weight Management Res Ctr, Dept Hlth & Phys Act, Pittsburgh, PA USA.
RP Linkov, F (reprint author), Magee Womens Res Inst, Dept OBGYN & Reprod Sci, 3380 Blvd Allies,Room 323 Isalys, Pittsburgh, PA 15232 USA.
EM Faina.Linkov@gmail.com
FU Commonwealth of Pennsylvania Department of Health, Henry M Jackson
   Foundation, ACS [MRSG-10-079-01-CPPB]; Bodymedia, Inc.
FX Research support: Commonwealth of Pennsylvania Department of Health,
   Henry M Jackson Foundation, ACS Mentored Research Award
   (MRSG-10-079-01-CPPB). Funding sources did not participate in project
   design and data analysis.; Author John M. Jakicic is a member of the
   Scientific Advisory Board of Alere Wellbeing (formerly Free 8, Clear).
   He also receives a Research Funding from Bodymedia, Inc. and a speaking
   honorarium from Jenny Craig. The rest of the authors declared no
   conflict of interest.
NR 46
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Z9 9
U1 0
U2 7
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 APR
PY 2012
VL 125
IS 1
BP 114
EP 119
DI 10.1016/j.ygyno.2011.12.439
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 913LO
UT WOS:000301879600021
PM 22198242
ER

PT J
AU Zachariah, JP
   Xanthakis, V
   Larson, MG
   Vita, JA
   Sullivan, LM
   Smith, HM
   Safa, R
   Peng, XY
   Hamburg, N
   Levy, D
   Sawyer, DB
   Mitchell, GF
   Vasan, RS
AF Zachariah, Justin P.
   Xanthakis, Vanessa
   Larson, Martin G.
   Vita, Joseph A.
   Sullivan, Lisa M.
   Smith, Holly M.
   Safa, Radwan
   Peng, Xuyang
   Hamburg, Naomi
   Levy, Daniel
   Sawyer, Douglas B.
   Mitchell, Gary F.
   Vasan, Ramachandran S.
TI Circulating Vascular Growth Factors and Central Hemodynamic Load in the
   Community
SO HYPERTENSION
LA English
DT Article
DE vasculature; growth substances; angiogenesis; arteriosclerosis;
   elasticity
ID PULSE-WAVE VELOCITY; ATTENUATES INTIMAL HYPERPLASIA; CROSS-SECTIONAL
   RELATIONS; CONGESTIVE-HEART-FAILURE; SMOOTH-MUSCLE CELLS; FACTOR-I;
   ARTERIAL STIFFNESS; AORTIC STIFFNESS; NITRIC-OXIDE; HYPERTENSIVE
   PATIENTS
AB Mean and pulsatile components of hemodynamic load are related to cardiovascular disease. Vascular growth factors play a fundamental role in vascular remodeling. The links between growth factors and hemodynamic load components are not well described. In 3496 participants from the Framingham Heart Study third generation cohort (mean age: 40+/-9 years; 52% women), we related 4 tonometry-derived measures of central arterial load (carotid femoral pulse wave velocity and forward pressure wave, mean arterial pressure, and the global reflection coefficient) to circulating concentrations of angiopoietin 2, its soluble receptor; vascular endothelial growth factor, its soluble receptor; hepatocyte growth factor; insulin-like growth factor 1; and its binding protein 3. Using multivariable linear regression models, adjusted for standard cardiovascular risk factors, serum insulin-like growth factor 1 concentrations were negatively associated with carotid femoral pulse wave velocity, mean arterial pressure, and reflection coefficient (P <= 0.01 for all), whereas serum vascular endothelial growth factor levels were positively associated with carotid femoral pulse wave velocity and mean arterial pressure (P<0.04). Serum insulin-like growth factor binding protein 3 and soluble angiopoietin 2 receptor levels were positively related to mean arterial pressure and to forward pressure wave, respectively (P<0.05). In our cross-sectional study of a large community-based sample, circulating vascular growth factor levels were related to measures of mean and pulsatile hemodynamic load in a pattern consistent with the known physiological effects of insulin-like growth factor 1 and vascular endothelial growth factor. (Hypertension. 2012;59:773-779.). Online Data Supplement
C1 [Zachariah, Justin P.; Xanthakis, Vanessa; Larson, Martin G.; Levy, Daniel; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
   [Zachariah, Justin P.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
   [Zachariah, Justin P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   [Mitchell, Gary F.] Cardiovascular Engn Inc, Norwood, MA USA.
   [Xanthakis, Vanessa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
   [Larson, Martin G.] Boston Univ, Sch Med, Dept Math, Boston, MA 02118 USA.
   [Xanthakis, Vanessa; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA.
   [Levy, Daniel] Natl Heart Lung & Blood Inst, Ctr Populat Studies, Bethesda, MD USA.
   [Smith, Holly M.; Sawyer, Douglas B.] Vanderbilt Univ, Nashville, TN USA.
RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM vasan@bu.edu
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
FU National Institutes of Health/National Heart, Lung, and Blood Institute
   [NO1-HC 25195, R01-HL-70100, RO1-HL-077447, T32 HL-007572]
FX This work was supported through National Institutes of Health/National
   Heart, Lung, and Blood Institute contract NO1-HC 25195, R01-HL-70100,
   RO1-HL-077447 (to R.S.V.), and T32 HL-007572 (to J.P.Z.).
NR 56
TC 17
Z9 18
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD APR
PY 2012
VL 59
IS 4
BP 773
EP U68
DI 10.1161/HYPERTENSIONAHA.111.179242
PG 14
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 911KQ
UT WOS:000301716100017
PM 22371357
ER

PT J
AU Shah, NS
   Vidal, JS
   Masaki, K
   Petrovitch, H
   Ross, GW
   Tilley, C
   DeMattos, RB
   Tracy, RP
   White, LR
   Launer, LJ
AF Shah, Nilay S.
   Vidal, Jean-Sebastien
   Masaki, Kamal
   Petrovitch, Helen
   Ross, G. Webster
   Tilley, Cathy
   DeMattos, Ronald B.
   Tracy, Russell P.
   White, Lon R.
   Launer, Lenore J.
TI Midlife Blood Pressure, Plasma beta-Amyloid, and the Risk for Alzheimer
   Disease The Honolulu Asia Aging Study
SO HYPERTENSION
LA English
DT Article
DE amyloid; blood pressure; brain; aging; dementia
ID CORONARY HEART-DISEASE; PLAQUE CORE PROTEIN; DEMENTIA; BRAIN; DIAGNOSIS;
   ASSOCIATION; BIOMARKERS; CALIFORNIA; STROKE; HEALTH
AB beta-Amyloid (A beta), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer disease (AD) and possibly vascular dementia. We investigated the joint association of midlife BP and A beta peptide levels with the risk for late-life AD and vascular dementia. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Program/Honolulu Asia Aging Study (1965-2000). Midlife BP was measured starting in 1971 in participants with a mean age of 58 years; A beta was measured in specimens collected in 1980-1982, and assessment of dementia and autopsy collection started in 1991-1993. The outcome measures were prevalent (present in 1991-1993) and incident AD (n=53, including 38 with no contributing cardiovascular disease) and vascular dementia (n=24). Cerebral amyloid angiopathy, beta-amyloid neuritic plaques, and neurofibrillary tangles were evaluated in postmortem tissue. The risk for AD significantly increased with lower levels of plasma A beta (A beta 1-40 hazard ratio: 2.1 [95% CI: 1.4 to 3.1]; A beta 1-42 hazard ratio: 1.6 [95% CI: 1.1 to 2.3]). Evidence of interaction between diastolic BP and plasma A beta (1-40 P-interaction <0.05; 1-42 P-interaction <0.07) levels indicated that the A beta-related risk for AD was higher when BP was higher. Low plasma A beta was associated with the presence of cerebral amyloid angiopathy (P-trend<0.05) but not the other neuropathologies. A beta plasma levels start decreasing >15 years before AD is diagnosed, and the association of A beta to AD is modulated by midlife diastolic BP. Elevated BP may compromise vascular integrity leading to cerebral amyloid angiopathy and impaired A beta clearance from the brain. (Hypertension. 2012;59:780-786.). Online Data Supplement
C1 [Shah, Nilay S.; Vidal, Jean-Sebastien; Launer, Lenore J.] NIH, Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Masaki, Kamal; Petrovitch, Helen; Ross, G. Webster; White, Lon R.] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA.
   [Masaki, Kamal; Petrovitch, Helen; Ross, G. Webster; White, Lon R.] Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA.
   [Petrovitch, Helen; Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
   [Tilley, Cathy; Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Colchester, Essex, England.
   [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Colchester, Essex, England.
   [DeMattos, Ronald B.] Lilly Res Labs, Div Neurosci, Indianapolis, IN USA.
RP Launer, LJ (reprint author), NIH, Natl Inst Aging, Lab Epidemiol Demog & Biometry, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA.
EM Launerl@mail.nih.gov
RI Vidal, Jean-Sebastien/D-1941-2016
OI Vidal, Jean-Sebastien/0000-0001-6770-0720
FU National Institutes of Health (National Institute on Aging)
   [NO1-AG-4-2149, 5U01AG017155-09, 5U01AG019349-08]
FX This work was supported by the National Institutes of Health (National
   Institute on Aging contract NO1-AG-4-2149, Cooperative Agreements
   5U01AG017155-09 and 5U01AG019349-08, and the Intramural Research Program
   of the National Institutes of Health and with resources at the Veterans
   Affairs Pacific Islands Health Care System). The information contained
   in this article does not necessarily reflect the position or the policy
   of the US government, and no official endorsement should be inferred.
NR 40
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Z9 65
U1 1
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD APR
PY 2012
VL 59
IS 4
BP 780
EP U82
DI 10.1161/HYPERTENSIONAHA.111.178962
PG 13
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 911KQ
UT WOS:000301716100018
PM 22392902
ER

PT J
AU Ponti, G
   Luppi, G
   Losi, L
   Cesinaro, AM
   Sartori, G
   Maiorana, A
   Pellacani, G
   Longo, C
   Boni, E
   Pepe, P
   Giannetti, A
   Seidenari, S
   Landi, MT
AF Ponti, Giovanni
   Luppi, Gabriele
   Losi, Lorena
   Cesinaro, Anna Maria
   Sartori, Giuliana
   Maiorana, Antonio
   Pellacani, Giovanni
   Longo, Caterina
   Boni, Elisa
   Pepe, Patrizia
   Giannetti, Alberto
   Seidenari, Stefania
   Landi, Maria Teresa
TI p16 immunohistochemistry of multiple primary melanomas as screening to
   identify Familial Melanoma Syndrome
SO INTERNATIONAL JOURNAL OF DERMATOLOGY
LA English
DT Letter
ID CUTANEOUS MALIGNANT-MELANOMA; PROTEIN EXPRESSION; CDKN2A; TUMORS;
   LOCALIZATION; P16(INK4A); CARCINOMAS; MUTATIONS
C1 [Ponti, Giovanni; Luppi, Gabriele] Univ Modena & Reggio Emilia, Dept Haematol & Oncol, I-41100 Modena, Italy.
   [Losi, Lorena; Cesinaro, Anna Maria; Sartori, Giuliana; Maiorana, Antonio] Univ Modena & Reggio Emilia, Dept Pathol, I-41100 Modena, Italy.
   [Pellacani, Giovanni; Longo, Caterina; Boni, Elisa; Pepe, Patrizia; Giannetti, Alberto; Seidenari, Stefania] Univ Modena & Reggio Emilia, Div Dermatol, Dept Internal Med, I-41100 Modena, Italy.
   [Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
RP Ponti, G (reprint author), Univ Modena & Reggio Emilia, Dept Haematol & Oncol, Via Pozzo 7, I-41100 Modena, Italy.
EM giovanni.ponti@unimo.it
RI Ponti, Giovanni/A-5565-2012; Maiorana, Antonino/H-6209-2014; Losi,
   Lorena/B-2583-2012; Longo, Caterina/A-8046-2012; pellacani,
   giovanni/E-8573-2011
OI Ponti, Giovanni/0000-0002-1971-7306; Maiorana,
   Antonino/0000-0001-9634-2520; Losi, Lorena/0000-0002-8483-3936; Longo,
   Caterina/0000-0002-8218-3896; pellacani, giovanni/0000-0002-7222-2951
NR 12
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0011-9059
J9 INT J DERMATOL
JI Int. J. Dermatol.
PD APR
PY 2012
VL 51
IS 4
BP 488
EP 492
DI 10.1111/j.1365-4632.2010.04496.x
PG 5
WC Dermatology
SC Dermatology
GA 912GZ
UT WOS:000301785100026
PM 21671908
ER

PT J
AU Hudson, TS
   Perkins, SN
   Hursting, SD
   Young, HA
   Kim, YS
   Wang, TC
   Wang, TTY
AF Hudson, Tamaro S.
   Perkins, Susan N.
   Hursting, Stephen D.
   Young, Heather A.
   Kim, Young S.
   Wang, Tien-Chung
   Wang, Thomas T. Y.
TI Inhibition of androgen-responsive LNCaP prostate cancer cell tumor
   xenograft growth by dietary phenethyl isothiocyanate correlates with
   decreased angiogenesis and inhibition of cell attachment
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE angiogenesis; phenethyl isothiocyanate; prevention; prostate cancer;
   xenograft
ID IN-VITRO; PHENYLETHYL ISOTHIOCYANATE; UNITED-STATES; CYCLE ARREST; PC-3
   CELLS; EXPRESSION; APOPTOSIS; INVASION; PHYTOCHEMICALS; ADENOCARCINOMA
AB Phenethyl isothiocyanate (PEITC) is a candidate anticancer compound found in certain cruciferous vegetables. In our tumor cell xenograft model, dietary administration of PEITC (100-150 mg/kg body weight/d) inhibited androgen-responsive LNCaP human prostate cancer cell tumor growth. We found that dietary treatment with PEITC significantly inhibited tumor platelet/endothelial cell adhesion molecule (PECAM-1/CD31) expression, a marker of angiogenesis. By contrast, we did not find the inhibitory effects of PEITC on tumor growth to be associated with alteration of specific markers for apoptosis, cell proliferation or androgen receptor-mediated pathways. Consistent with in vivo results, PEITC exerted little effects on cell proliferation, cell cycle and androgen-dependent pathways. Interestingly, PEITC significantly attenuated LNCaP cell plating efficiency that correlated with inhibition of integrin family proteins integrin beta 1, alpha 2 and alpha 6 mRNA expression. Thus, PEITC may be a dietary factor that inhibits androgen-responsive prostate tumor growth indirectly by selectively targeting factors involved in the tumor microenvironment.
C1 [Wang, Thomas T. Y.] ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA.
   [Hudson, Tamaro S.] NCI, Lab Cellular Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA.
   [Perkins, Susan N.; Hursting, Stephen D.] Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA.
   [Hursting, Stephen D.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA.
   [Young, Heather A.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Div Epidemiol & Biostat, Washington, DC 20037 USA.
   [Kim, Young S.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
   [Wang, Tien-Chung] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
RP Wang, TTY (reprint author), ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, 1300 Baltimore Ave,Bldg 307C,Room 132, Beltsville, MD 20705 USA.
EM tom.wang@ars.usda.gov
FU US [1235-51530-052-00]; National Cancer Institute; National Institute of
   Environmental Health Sciences [P30ES007784]; Howard-Hopkins partnership
   [U54CA091431]
FX This work was supported by US appropriated funding to USDA, project no.
   1235-51530-052-00 (T.T.Y.W., T.-C.W.) and the National Cancer Institute
   (T.S.H., S.D.H., S.N.P.), Grant no. P30ES007784 from the National
   Institute of Environmental Health Sciences (SDH, SNP) and by U54
   Howard-Hopkins partnership grant (U54CA091431, TSH). T.S.H. was
   supported by a National Cancer Institute Cancer Prevention Fellowship
   when the work was performed. The authors would like to thank Dr Diana
   Haines, Maureen Kennedy, and Scott Lawrence of the
   Pathology/Histotechnology Laboratory, SAIC-Frederick, for their
   assistance in immunohistochemical analysis.
NR 39
TC 13
Z9 14
U1 0
U2 3
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD APR
PY 2012
VL 40
IS 4
BP 1113
EP 1121
DI 10.3892/ijo.2012.1335
PG 9
WC Oncology
SC Oncology
GA 910LI
UT WOS:000301637800026
PM 22266918
ER

PT J
AU Pardini, M
   Elia, M
   Garaci, FG
   Guida, S
   Coniglione, F
   Krueger, F
   Benassi, F
   Gialloreti, LE
AF Pardini, Matteo
   Elia, Maurizio
   Garaci, Francesco G.
   Guida, Silvia
   Coniglione, Filadelfo
   Krueger, Frank
   Benassi, Francesca
   Gialloreti, Leonardo Emberti
TI Long-term Cognitive and Behavioral Therapies, Combined with Augmentative
   Communication, are Related to Uncinate Fasciculus Integrity in Autism
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Diffusion Tensor Imaging; Autism; Uncinate fasciculus; Cognitive
   therapy; Long-term rehabilitation
ID CEREBRAL WHITE-MATTER; DIFFUSION TENSOR; SPECTRUM DISORDER; BRAIN;
   CONNECTIVITY; CHILDREN
AB Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive and behavioral therapy. Uncinate fasciculus structural properties correlated significantly with therapy length and early onset, as well as to clinical outcome, independently from IQ, age or symptoms severity at therapy onset. Moreover, adherence to therapy was linked with better clinical outcome and uncinate fasciculus structural integrity. The results point to the capability of a long-term rehabilitation of subjects with low-functioning autism to produce white-matter structural modifications, which could thus play a role in the rehabilitative outcome.
C1 [Gialloreti, Leonardo Emberti] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy.
   [Pardini, Matteo; Guida, Silvia] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy.
   [Pardini, Matteo] Univ Genoa, Magnet Resonance Res Ctr Nervous Syst Dis, Genoa, Italy.
   [Pardini, Matteo; Benassi, Francesca; Gialloreti, Leonardo Emberti] Ctr Commun & Neurorehabil Res CNAPP, Rome, Italy.
   [Elia, Maurizio] Hospitalizat & Hlth Care IRCCS Oasi Maria SS, Unit Neurol & Clin Neurophysiopathol, Sci Inst Res, Troina, EN, Italy.
   [Garaci, Francesco G.] Univ Roma Tor Vergata, Dept Diagnost Imaging & Intervent Radiol, Rome, Italy.
   [Coniglione, Filadelfo] Univ Roma Tor Vergata, Dept Anaesthesiol & Intens Care Med, Rome, Italy.
   [Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA.
   [Krueger, Frank] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD USA.
RP Gialloreti, LE (reprint author), Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy.
EM leonardo.emberti.gialloreti@uniroma2.it
RI Emberti Gialloreti, Leonardo/H-4702-2012; Pardini, Matteo/F-8414-2010;
   Elia, Maurizio/K-3285-2016
OI Pardini, Matteo/0000-0002-4740-1982; Elia, Maurizio/0000-0002-0414-1359
NR 31
TC 15
Z9 16
U1 1
U2 14
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD APR
PY 2012
VL 42
IS 4
BP 585
EP 592
DI 10.1007/s10803-011-1281-2
PG 8
WC Psychology, Developmental
SC Psychology
GA 909NL
UT WOS:000301571300012
PM 21573693
ER

PT J
AU Farlow, DW
   Xu, X
   Veenstra, TD
AF Farlow, D. W.
   Xu, X.
   Veenstra, T. D.
TI Comparison of estrone and 17 beta-estradiol levels in commercial goat
   and cow milk
SO JOURNAL OF DAIRY SCIENCE
LA English
DT Article
DE goat milk; cow milk; estrone; 17 beta-estradiol
ID CHROMATOGRAPHY-MASS SPECTROMETRY; BREAST-CANCER; QUANTITATIVE
   MEASUREMENT; ENDOGENOUS ESTROGENS; PROSTATE-CANCER; RISK-FACTORS;
   METABOLITES; HORMONES; ESTRADIOL; THERAPY
AB Increased levels of estrogen metabolites are believed to be associated with cancers of the reproductive system. One potential dietary source of these metabolites that is commonly consumed worldwide is milk. In North America, dairy cows are the most common source of milk; however, goats are the primary source of milk worldwide. In this study, the absolute concentrations of unconjugated and total (unconjugated plus conjugated) estrone (E-1) and 17 beta-estradiol (E-2) were compared in a variety of commercial cow milks (regular and organic) and goat milk. A lower combined concentration of E-1 and E-2 was found in goat milk than in any of the cow milk products tested. The differences in E-1 and E-2 levels between regular and organic cow milks were not as significant as the differences between goat milk and any of the cow milk products. Goat milk represents a better dietary choice for individuals concerned with limiting their estrogen intake.
C1 [Farlow, D. W.; Xu, X.; Veenstra, T. D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA.
RP Veenstra, TD (reprint author), SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA.
EM veenstra@ncifcrf.gov
FU National Cancer Institute, National Institutes of Health (Bethesda, MD)
   [HHSN261200800001E]
FX This project has been funded in whole or in part with Federal funds from
   the National Cancer Institute, National Institutes of Health (Bethesda,
   MD), under Contract HHSN261200800001E.
NR 23
TC 5
Z9 5
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-0302
J9 J DAIRY SCI
JI J. Dairy Sci.
PD APR
PY 2012
VL 95
IS 4
BP 1699
EP 1708
DI 10.3168/jds.2011-5072
PG 10
WC Agriculture, Dairy & Animal Science; Food Science & Technology
SC Agriculture; Food Science & Technology
GA 913NW
UT WOS:000301885700012
PM 22459818
ER

PT J
AU Richardson, A
   He, JP
   Curry, L
   Merikangas, K
AF Richardson, Amanda
   He, Jian-Ping
   Curry, Laurel
   Merikangas, Kathleen
TI Cigarette smoking and mood disorders in US adolescents: Sex-specific
   associations with symptoms, diagnoses, impairment and health services
   use
SO JOURNAL OF PSYCHOSOMATIC RESEARCH
LA English
DT Article
DE Adolescents; Anxiety; Depression; Impairment; Services; Smoking
ID MAJOR DEPRESSIVE DISORDER; SUBSTANCE USE DISORDERS;
   PSYCHIATRIC-DISORDERS; NICOTINE DEPENDENCE; TOBACCO USE;
   MENTAL-DISORDERS; ANXIETY DISORDERS; UNITED-STATES; YOUNG-ADULTS;
   INTERVIEW SCHEDULE
AB Objective: To report sex-specific associations between cigarette smoking and DSM-IV disorders, symptoms, and mental health services use related to depression and anxiety in a nationally representative sample of U.S. adolescents.
   Methods: Data on two samples were drawn from the 1999-2004 National Health and Nutrition Examination Surveys to examine the association of ever smoking (versus never smoking) with depression (n = 1884 12-15 year-olds) and anxiety (n = 6336 12-19 year-olds). Sex-specific associations between smoking and DSM-IV diagnoses, subthreshold and severe disorder, symptoms, impairment and mental health services use were assessed using logistic regression modeling.
   Results: Rates of DSM-IV depression and anxiety were increased in adolescent female ever smokers as compared to never smokers (OR=3.9,95% CI: 1.3-11.3 and OR=10.6,95% CI: 3.1-37.0, respectively). Females also showed statistically significant increases in severe disorder; subthreshold disorder, all symptoms of major depressive disorder, most symptoms of panic disorder, and increases in severe impairment, especially those related to schoolwork and teachers. Male adolescents showed smaller variations in depression and anxiety by smoking status, but were more likely to seek mental health services.
   Conclusions: Smoking prevention efforts may benefit from specifically targeting female youth who show signs of depression or anxiety diagnoses through a school-based program, while greater benefits with males may be evident through programs integrated into mental health services. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Richardson, Amanda; Curry, Laurel] Legacy, Washington, DC USA.
   [He, Jian-Ping; Merikangas, Kathleen] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
RP Richardson, A (reprint author), 1724 Massachusetts Ave NW, Washington, DC 20036 USA.
EM arichardson@legacyforhealth.org
FU Intramural NIH HHS [Z99 MH999999]
NR 102
TC 8
Z9 8
U1 11
U2 23
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3999
J9 J PSYCHOSOM RES
JI J. Psychosomat. Res.
PD APR
PY 2012
VL 72
IS 4
BP 269
EP 275
DI 10.1016/j.jpsychores.2012.01.013
PG 7
WC Psychiatry
SC Psychiatry
GA 910FG
UT WOS:000301622000005
PM 22405220
ER

PT J
AU Shaikh, Q
   Kamal, AK
AF Shaikh, Quratulain
   Kamal, Ayeesha Kamran
TI My patient has a lot of variability in his blood pressure measurements?
   Should I be worried? What can I do which may be better?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ARM ASCOT-BPLA; TRIAL; OUTCOMES; HYPERTENSION
C1 [Shaikh, Quratulain] Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
   Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Natl Inst Neurol Disorders & Stroke, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
RP Shaikh, Q (reprint author), Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
OI Shaikh, Quratulain/0000-0001-6106-2713
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 6
TC 0
Z9 0
U1 0
U2 0
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD APR
PY 2012
VL 62
IS 4
BP 407
EP 408
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 912SS
UT WOS:000301820800026
PM 22755294
ER

PT J
AU Petrini, I
   French, CA
   Rajan, A
   Cameron, MJ
   Jaffe, ES
   Zucali, PA
   Xie, JW
   Wang, YS
   Giaccone, G
AF Petrini, Iacopo
   French, Christopher A.
   Rajan, Arun
   Cameron, Michael J.
   Jaffe, Elaine S.
   Zucali, Paolo A.
   Xie, Jianwu
   Wang, Yisong
   Giaccone, Giuseppe
TI NUT Rearrangement is Uncommon in Human Thymic Epithelial Tumors
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE t(15;19) translocation; BRD4-NUT; Thymoma; Thymic carcinoma
ID T(15-19)(Q15-P13) CHROMOSOME ABNORMALITY; BROMODOMAIN PROTEIN BRD4;
   MIDLINE CARCINOMA; AGGRESSIVE CARCINOMA; P-TEFB; EXPRESSION;
   DIFFERENTIATION; TRANSCRIPTION; THYMOMAS; FAMILY
AB Introduction: Thymic carcinomas represent the most aggressive histotype of thymic epithelial tumors (TETs). The 2004 World Health Organization classification has assigned a subgroup of thymic carcinomas as t(15; 19) carcinomas based on the presence of t(15; 19), a translocation found in poorly differentiated and highly aggressive NUT midline carcinomas. These tumors are characterized by rearrangement of the NUT (nuclear protein in testis) gene on chromosome 15q14, which in most cases fuses to the bromodomain containing 4 (BRD4) gene on chromosome 19p13.1 through reciprocal t(15; 19) translocation, resulting in constitutive BRD4-NUT fusion protein expression. To our knowledge, NUT translocation has been reported only in four thymic carcinomas. Due to the rarity of TETs, the prevalence of NUT rearrangement in TETs has however never been systematically explored.
   Methods: Formalin-fixed paraffin-embedded samples of histologically confirmed TETs were evaluated for NUT expression and rearrangement by immunohistochemistry and fluorescence in situ hybridization, respectively.
   Results: A series of 148 TETs (37 carcinomas and 111 thymomas) were examined for NUT expression and rearrangement. Only one thymic carcinoma (2.7% of thymic carcinomas or 0.68% of TETs) was found positive for NUT expression and rearrangement.
   Conclusions: Rearrangement of NUT is infrequent in TETs. We propose that caution should be taken to distinguish t(15; 19) thymic carcinoma from other mediastinal carcinomas, as NUT midline carcinomas are often associated with dreadful prognosis or overt lethality.
C1 [Petrini, Iacopo; Rajan, Arun; Xie, Jianwu; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [French, Christopher A.; Cameron, Michael J.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Jaffe, Elaine S.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   [Zucali, Paolo A.] IRCCS, Dept Med Oncol, Humanitas Canc Ctr, Milan, Italy.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wangyi1@mail.nih.gov; giacconeg@mail.nih.gov
RI Petrini, Iacopo/K-7316-2016; Giaccone, Giuseppe/E-8297-2017; 
OI Petrini, Iacopo/0000-0002-7752-6866; Giaccone,
   Giuseppe/0000-0002-5023-7562; Jaffe, Elaine/0000-0003-4632-0301
FU National Cancer Institute
FX Supported by National Cancer Institute intramural fund.
NR 27
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD APR
PY 2012
VL 7
IS 4
BP 744
EP 750
DI 10.1097/JTO.0b013e3182460f8f
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 913HA
UT WOS:000301866500016
ER

PT J
AU Schwandt, A
   Mekhail, T
   Halmos, B
   O'Brien, T
   Ma, PC
   Fu, PF
   Ivy, P
   Dowlati, A
AF Schwandt, Anita
   Mekhail, Tarek
   Halmos, Balazs
   O'Brien, Timothy
   Ma, Patrick C.
   Fu, Pingfu
   Ivy, Percy
   Dowlati, Afshin
TI Phase-II Trial of Rebeccamycin Analog, a Dual Topoisomerase-I and -II
   Inhibitor, in Relapsed "Sensitive" Small Cell Lung Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
ID NSC-655649; TOPOTECAN; DNA; METAANALYSIS; DERIVATIVES; ETOPOSIDE
AB Relapsed small cell lung cancer (SCLC) carries a poor prognosis. Topoisomerase I and II inhibitors and DNA-damaging agents are considered among the most active agents against SCLC. Rebeccamycin analog (RA, Becatecarin) is an antitumor antibiotic with inhibitory activity against both topoisomerase I and II, and DNA-intercalating properties. We performed a phase-II trial of RA in relapsed, sensitive SCLC with the primary end point of response rate. Patients with previously treated SCLC who relapsed more than 60 days after the completion of first-line chemotherapy were treated with RA-administered intravenously at a dose of 140 mg/m(2) on days 1 to 5 of 21-day cycles for a maximum of six cycles. Eligibility included Eastern Cooperative Oncology Group performance status 0 to 2 and adequate organ function. A two-stage design was employed. Twenty evaluable patients were enrolled. Median age was 61 years. Two patients (10%) had a partial response and six had stable disease. The clinical benefit rate was 40% (95% confidence interval [CI], 23-64%). The median progression-free survival was 2 months (95% CI, 1.2-5.2 months). The median survival was 6.7 months (95% CI, 3.3-8.0 months). No treatment-related deaths occurred. Grade-4 neutropenia and thrombocytopenia occurred in 23% and 14% of the patients, respectively. In conclusion, RA has single-agent activity in relapsed, sensitive SCLC with manageable toxicities but is unlikely to provide any superiority compared to existing agents for this disease.
C1 [Schwandt, Anita; Halmos, Balazs; Ma, Patrick C.; Dowlati, Afshin] Univ Hosp Seidman Canc Ctr, Div Hematol & Oncol, Cleveland, OH USA.
   [Schwandt, Anita; Halmos, Balazs; Ma, Patrick C.; Dowlati, Afshin] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Mekhail, Tarek] Cleveland Clin Taussig Canc Inst, Cleveland, OH USA.
   [O'Brien, Timothy] Metrohlth Med Ctr, Cleveland, OH USA.
   [Mekhail, Tarek; Halmos, Balazs; Ma, Patrick C.; Fu, Pingfu; Dowlati, Afshin] Case Comprehens Canc Ctr, Cleveland, OH USA.
   [Mekhail, Tarek; Halmos, Balazs; Ma, Patrick C.; Fu, Pingfu; Dowlati, Afshin] NCI, Canc Therapy & Evaluat Program, Bethesda, MB, Canada.
RP Dowlati, A (reprint author), Univ Hosp Case Med Ctr, 11000 Euclid Ave, Cleveland, OH USA.
EM afshin.dowlati@case.edu
FU National Institutes of Health [U01-CA62502, K23 CA109348]
FX Supported by grant U01-CA62502 (PI: A. Dowlati) and K23 CA109348 (PI: A.
   Dowlati) from the National Institutes of Health.
NR 14
TC 12
Z9 14
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD APR
PY 2012
VL 7
IS 4
BP 751
EP 754
DI 10.1097/JTO.0b013e31824abca2
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 913HA
UT WOS:000301866500017
PM 22425925
ER

PT J
AU Histed, SN
   Lindenberg, ML
   Mena, E
   Turkbey, B
   Choyke, PL
   Kurdziel, KA
AF Histed, Stephanie N.
   Lindenberg, Maria L.
   Mena, Esther
   Turkbey, Baris
   Choyke, Peter L.
   Kurdziel, Karen A.
TI Review of functional/anatomical imaging in oncology
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Review
DE magnetic resonance/positron emission tomography; multimodality imaging;
   positron emission tomography/computed tomography; single-photon emission
   tomography/computed tomography
ID POSITRON-EMISSION-TOMOGRAPHY; PLANAR BONE-SCINTIGRAPHY; COMBINED PET/CT
   SCANNER; PROLIFERATION IN-VIVO; TUMOR ANGIOGENESIS; ALPHA-V-BETA-3
   EXPRESSION; NEUROENDOCRINE TUMORS; COMPUTED-TOMOGRAPHY;
   PANCREATIC-CANCER; NUCLEAR-MEDICINE
AB Patient management in oncology increasingly relies on imaging for diagnosis, response assessment, and follow-up. The clinical availability of combined functional/anatomical imaging modalities, which integrate the benefits of visualizing tumor biology with those of high-resolution structural imaging, revolutionized clinical management of oncologic patients. Conventional high-resolution anatomical imaging modalities such as computed tomography (CT) and MRI excel at providing details on lesion location, size, morphology, and structural changes to adjacent tissues; however, these modalities provide little insight into tumor physiology. With the increasing focus on molecularly targeted therapies, imaging radiolabeled compounds with PET and single-photon emission tomography (SPECT) is often carried out to provide insight into a tumor's biological functions and its surrounding microenvironment. Despite their high sensitivity and specificity, PET and SPECT alone are substantially limited by low spatial resolution and inability to provide anatomical detail. Integrating SPECT or PET with a modality capable of providing these (i.e. CT or MR) maximizes their separate strengths and provides anatomical localization of physiological processes with detailed visualization of a tumor's structure. The availability of multimodality (hybrid) imaging with PET/CT, SPEC/CT, and PET/MR improves our ability to characterize lesions and affect treatment decisions and patient management. We have just begun to exploit the truly synergistic capabilities of multimodality imaging. Continued advances in the development of instrumentation and imaging agents will improve our ability to noninvasively characterize disease processes. This review will discuss the evolution of hybrid imaging technology and provide examples of its current and potential future clinical uses. Nucl Med Commun 33:349-361 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Histed, Stephanie N.; Lindenberg, Maria L.; Mena, Esther; Turkbey, Baris; Choyke, Peter L.; Kurdziel, Karen A.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Kurdziel, KA (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,Blg 10 Rm B3B403, Bethesda, MD 20892 USA.
EM karen.kurdziel@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 105
TC 57
Z9 60
U1 4
U2 25
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0143-3636
EI 1473-5628
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD APR
PY 2012
VL 33
IS 4
BP 349
EP 361
DI 10.1097/MNM.0b013e32834ec8a5
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 912BC
UT WOS:000301767400002
PM 22314804
ER

PT J
AU Charkoudian, LD
   Ying, GS
   Pujari, SS
   Gangaputra, S
   Thorne, JE
   Foster, CS
   Jabs, DA
   Levy-Clarke, GA
   Nussenblatt, RB
   Rosenbaum, JT
   Suhler, EB
   Kempen, JH
AF Charkoudian, Leon D.
   Ying, Gui-shuang
   Pujari, Siddharth S.
   Gangaputra, Sapna
   Thorne, Jennifer E.
   Foster, C. Stephen
   Jabs, Douglas A.
   Levy-Clarke, Grace A.
   Nussenblatt, Robert B.
   Rosenbaum, James T.
   Suhler, Eric B.
   Kempen, John H.
TI High-dose Intravenous Corticosteroids for Ocular Inflammatory Diseases
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE corticosteroids; inflammation; intravenous; noninfectious; uveitis
ID PULSE METHYLPREDNISOLONE THERAPY; UVEITIS; GLUCOCORTICOIDS; MECHANISMS;
   DISORDERS; DRUGS
AB Purpose: To evaluate the effectiveness and risk of complications of high-dose intravenous pulsed corticosteroids for noninfectious ocular inflammatory diseases.
   Methods: Retrospective cohort study in which 104 eyes of 70 patients who received high-dose intravenous corticosteroids for treatment of active ocular inflammation were identified from five centers. The main outcome measures were control of inflammation and occurrence of ocular or systemic complications within 1 month after treatment.
   Results: Within <= 1 month of starting treatment, 57% of eyes achieved complete control of inflammation (95% confidence interval (CI): 33-83%), improving to 82% when near-complete control was included (95% CI: 61-96%). Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in anterior chamber inflammation. One patient developed a colon perforation during treatment. No other major complications were recorded.
   Conclusions: Treatment of ocular inflammation with high-dose intravenous corticosteroids resulted in substantial clinical improvement for most cases within 1 month. Complications of therapy were infrequent.
C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
   [Charkoudian, Leon D.; Ying, Gui-shuang; Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Charkoudian, Leon D.] Emory Univ, Atlanta, GA 30322 USA.
   [Ying, Gui-shuang; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Pujari, Siddharth S.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
   [Pujari, Siddharth S.] LIONS NAB Eye Hosp, Miraj, Maharastra, India.
   [Gangaputra, Sapna; Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Gangaputra, Sapna] Univ Wisconsin, Sch Med, Fundus Photograph Reading Ctr, Madison, WI USA.
   [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
   [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
   [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
   [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA.
   [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
   [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
   [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
   [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
FU National Eye Institute (Bethesda, MD) [EY014943]; Research to Prevent
   Blindness (New York, NY); Paul and Evanina Mackall Foundation (New York,
   NY); Research to Prevent Blindness; National Eye Institute; Unites
   States Veterans' Administration
FX This study was supported primarily by the National Eye Institute
   (Bethesda, MD) Grant EY014943 (Dr. Kempen). Additional support was
   provided by Research to Prevent Blindness (New York, NY) and the Paul
   and Evanina Mackall Foundation (New York, NY). Dr. Kempen is a Research
   to Prevent Blindness James S. Adams Special Scholar Award recipient. Dr.
   Jabs and Dr. Rosenbaum were Research to Prevent Blindness Senior
   Scientific Investigator Award recipients during the conduct of the
   study. Dr. Thorne is a Research to Prevent Blindness Harrington Special
   Scholar Award recipient. Dr. Levy-Clarke was previously supported by and
   Dr. Nussenblatt continues to be supported by intramural funds of the
   National Eye Institute. Dr. Suhler also received support from the Unites
   States Veterans' Administration. None of the sponsors had any role in
   the design and conduct of the report; collection, management, analysis,
   and interpretation of the data; nor in the preparation, review, and
   approval of this paper.
NR 25
TC 7
Z9 7
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD APR
PY 2012
VL 20
IS 2
BP 91
EP 99
DI 10.3109/09273948.2011.646382
PG 9
WC Ophthalmology
SC Ophthalmology
GA 908FL
UT WOS:000301476200005
PM 22409561
ER

PT J
AU Sen, HN
   Drye, LT
   Goldstein, DA
   Larson, TA
   Merrill, PT
   Pavan, PR
   Sheppard, JD
   Burke, A
   Srivastava, SK
   Jabs, DA
AF Sen, H. Nida
   Drye, Lea T.
   Goldstein, Debra A.
   Larson, Theresa A.
   Merrill, Pauline T.
   Pavan, Peter R.
   Sheppard, John D.
   Burke, Alyce
   Srivastava, Sunil K.
   Jabs, Douglas A.
CA Multictr Uveitis Steroid Treatment
TI Hypotony in Patients with Uveitis: The Multicenter Uveitis Steroid
   Treatment (MUST) Trial
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE hypotony; multicenter uveitis steroid treatment trial; uveitis; visual
   impairment; visual loss
ID ARTHRITIS-ASSOCIATED UVEITIS; CHRONIC OCULAR HYPOTONY; VISUAL-ACUITY;
   SURGERY; COMPLICATIONS; SARCOIDOSIS; MANAGEMENT; DISEASE; INFLAMMATION;
   CHILDHOOD
AB Purpose: To assess the prevalence of hypotony in patients with severe forms of uveitis.
   Methods: The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified.
   Results: Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis >= 5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. < 51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01).
   Conclusions: Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment.
C1 [Sen, H. Nida; Larson, Theresa A.] NEI, NIH, Bethesda, MD 20892 USA.
   [Drye, Lea T.; Burke, Alyce; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Goldstein, Debra A.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA.
   [Merrill, Pauline T.] Rush Univ, Med Ctr, Dept Ophthalmol, Chicago, IL 60612 USA.
   [Pavan, Peter R.] Univ S Florida, Coll Med, Dept Ophthalmol, Tampa, FL USA.
   [Sheppard, John D.] Virginia Eye Consultants, Dept Ophthalmol, Norfolk, VA USA.
   [Sheppard, John D.] Thomas R Lee Ctr Ocular Pharmacol, Norfolk, VA USA.
   [Srivastava, Sunil K.] Emory Univ, Ctr Eye, Dept Ophthalmol, Atlanta, GA 30322 USA.
   [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
   [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,10-10N112, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
RI Pavan, Peter/B-6473-2013; Taylor, Simon/C-1496-2008; 
OI Taylor, Simon/0000-0002-1228-881X; Drye, Lea/0000-0002-2964-1878
FU National Eye Institute [U10 EY 014655]; Johns Hopkins University
   Bloomberg School of Public Health [U10 EY 014660]; University of
   Wisconsin, Madison, School of Medicine [U10 EY 014656]; Roche
   Laboratories, Inc.
FX Supported by cooperative agreements from the National Eye Institute to
   Mount Sinai School of Medicine (U10 EY 014655), the Johns Hopkins
   University Bloomberg School of Public Health (U10 EY 014660), and the
   University of Wisconsin, Madison, School of Medicine (U10 EY 014656). Dr
   Sen's work is supported by the National Eye Institute Intramural
   Research Program.; Bausch & Lomb provided support to the study in the
   form of donationof a limited number of fluocinolone acetonide implants
   for patients randomized to implant therapy who were uninsured or
   otherwise unable to pay for implants, but did not otherwise support the
   study. Dr. Goldstein has served as a consultant to Bausch & Lomb. Dr.
   Drye reports no conflict of interest. Dr. Larson reports no conflict of
   interest. Dr. Sen reports no conflict of interest. Dr. Merrill has
   served as a consultant for Bausch & Lomb and Allergan Pharmaceutical
   Corporation. Dr. Pavan reports no conflict of interest. Dr. Sheppard has
   served as a consultant or Bausch & Lomb, Alcon Laboratories, Allergan
   Pharmaceutical Corporation, Lux Biosciences, and EyeGate
   Pharmaceuticals, and Inspire Pharmaceuticals. Ms. Burke reports no
   conflict of interest. Dr. Srivastava has served as a consultant for
   Bausch & Lomb, Alimera, Novartis Pharmaceuticals Corporation, and
   Allergan Pharmaceutical Corporation. Douglas A. Jabs, MD, MBA has acted
   as a consultant for Ciba Vision, Bayer Corporation, Novartis
   Pharmaceutical Corporation, Centocor, Inc., and SmithKline Beecham.
   Currently, Dr. Jabs is a consultant for Abbott Laboratories, Alcon
   Laboratories, Allergan Pharmaceutical Corporation, Corcept Therapeutics,
   GenenTech, Genzyme Corporation, GlaxoSmithKline, Novartis
   Pharmaceuticals Corporation, and Roche Pharmaceuticals. Research support
   has been provided from Roche Laboratories, Inc. in the past. Dr. Jabs
   currently acts as a Data and Safety Monitoring Board (DSMB) member for
   Applied Genetic Technologies Corporation (AGTC).
NR 30
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PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD APR
PY 2012
VL 20
IS 2
BP 104
EP 112
DI 10.3109/09273948.2011.647228
PG 9
WC Ophthalmology
SC Ophthalmology
GA 908FL
UT WOS:000301476200007
PM 22409563
ER

PT J
AU Wagner, PD
   Srivastava, S
AF Wagner, Paul D.
   Srivastava, Sudhir
TI New paradigms in translational science research in cancer biomarkers
SO TRANSLATIONAL RESEARCH
LA English
DT Article
ID MOLECULAR MARKERS; OVARIAN-CANCER; VALIDATION; SPECIMENS; FRAMEWORK;
   DESIGN; PHASES
AB Despite significant investments in basic science by the US National Institutes of Health, there is a concern that the return on this investment has been limited in terms of clinical utility. In the field of biomarkers, translational research is used to bridge the gap between the results of basic research that identify biomolecules involved in or the consequence of carcinogenesis and their incorporation into medical application. The cultural separation between different scientific disciplines often makes it difficult to establish the multidisciplinary and multi-skilled teams that are necessary for successful translational research. The field of biomarker research requires extensive interactions between academic researchers and industrial developers, and clinicians are needed to help shape the research direction that can be addressed only by a multidisciplinary, multi-institutional approach. In this article, we provide our perspective on the relatively slow pace of cancer biomarker translation, especially those for early detection and screening. (Translational Research 2012;159:343-353)
C1 [Wagner, Paul D.; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Rockville, MD 20852 USA.
RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3142,MSC 7362, Rockville, MD 20852 USA.
EM srivasts@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 18
TC 20
Z9 22
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1931-5244
J9 TRANSL RES
JI Transl. Res.
PD APR
PY 2012
VL 159
IS 4
BP 343
EP 353
DI 10.1016/j.trsl.2012.01.015
PG 11
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
   Research & Experimental
SC Medical Laboratory Technology; General & Internal Medicine; Research &
   Experimental Medicine
GA 913YG
UT WOS:000301912700013
PM 22424436
ER

PT J
AU Moraski, GC
   Markley, LD
   Chang, M
   Cho, S
   Franzblau, SG
   Hwang, CH
   Boshoff, H
   Miller, MJ
AF Moraski, Garrett C.
   Markley, Lowell D.
   Chang, Mayland
   Cho, Sanghyun
   Franzblau, Scott G.
   Hwang, Chang Hwa
   Boshoff, Helena
   Miller, Marvin J.
TI Generation and exploration of new classes of antitubercular agents: The
   optimization of oxazolines, oxazoles, thiazolines, thiazoles to
   imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Mycobacterium tuberculosis; MDR-TB; XDR-TB; 5,6-Fused heteroaromatics;
   Imidazo[1,2-a]pyridine
ID MYCOBACTERIUM-TUBERCULOSIS; GROWTH; HYDROXAMATE; RESISTANCE; INHIBITORS;
   ESTERS; POTENT; ASSAY
AB Tuberculosis (TB) is a devastating disease resulting in a death every 20 s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds-oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole,imidazo[1,2-a] pyridine, imidazo[1,2-a] pyrimidine and imidazo[1,2-c] pyrimidine-which have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's as low as < 0.195 mu M (9 and 11). Overall, the imidazo[1,2-a] pyridine class was determined to be most promising, with potency similar to isoniazid and PA-824 against replicating Mtb H(37)Rv, clinically relevant drug sensitive, multi-and extensively resistant Mtb strains as well as having good in vitro metabolic stability. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Moraski, Garrett C.; Markley, Lowell D.; Chang, Mayland; Miller, Marvin J.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46656 USA.
   [Cho, Sanghyun; Franzblau, Scott G.; Hwang, Chang Hwa] Univ Illinois, Inst TB Res, Coll Pharm, Chicago, IL 60612 USA.
   [Boshoff, Helena] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Miller, MJ (reprint author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46656 USA.
EM mmiller1@nd.edu
OI Franzblau, Scott/0000-0002-8698-0243; Moraski,
   Garrett/0000-0002-6992-5584
FU NIH, NIAID; National Institutes of Health (NIH) [2R01AI054193,
   CHE-0741793]
FX This research was supported in part by the Intramural Research Program
   of the NIH, NIAID and by Grant 2R01AI054193 from the National Institutes
   of Health ( NIH) and in part by intermediates provided from DAS. We
   would like to thank the University of Notre Dame, especially the Mass
   Spectrometry and Proteomics Facility (Bill Boggess, Michelle Joyce,
   Nonka Sevova), which is supported by the grant CHE-0741793 from the NIH.
   We thank Prof. Jennifer DuBois for regular and lasting scientific
   discussions. The excellent technical assistance of Baojie Wan and
   Yuehong Wang with antitubercular assays at UIC is greatly appreciated.
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD APR 1
PY 2012
VL 20
IS 7
BP 2214
EP 2220
DI 10.1016/j.bmc.2012.02.025
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
   Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 906WH
UT WOS:000301379300003
PM 22391032
ER

PT J
AU Van Poecke, S
   Barrett, MO
   Kumar, TS
   Sinnaeve, D
   Martins, JC
   Jacobson, KA
   Harden, TK
   Van Calenbergh, S
AF Van Poecke, Sara
   Barrett, Matthew O.
   Kumar, T. Santhosh
   Sinnaeve, Davy
   Martins, Jose C.
   Jacobson, Kenneth A.
   Harden, T. Kendall
   Van Calenbergh, Serge
TI Synthesis and P2Y(2) receptor agonist activities of uridine 5
   '-phosphonate analogues
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE P2Y(2) receptor; G protein-coupled receptor; Uracil nucleotides;
   Nucleoside phosphonates; Partial agonists
ID CONFORMATIONAL-ANALYSIS; PHOSPHONATE ANALOGS; MAGNETIC-RESONANCE; P2
   RECEPTORS; SUGAR RING; NUCLEOTIDES; NUCLEOSIDES; ATP; EXPRESSION;
   CLONING
AB We explored the influence of modifications of uridine 5'-methylenephosphonate on biological activity at the human P2Y(2) receptor. Key steps in the synthesis of a series of 5-substituted uridine 5'-methylenephosphonates were the reaction of a suitably protected uridine 5'-aldehyde with [(diethoxyphosphinyl) methylidene] triphenylphosphorane, C-5 bromination and a Suzuki-Miyaura coupling. These analogues behaved as selective agonists at the P2Y(2) receptor, with three analogues exhibiting potencies in the submicromolar range. Although maximal activities observed with the phosphonate analogues were much less than observed with UTP, high concentrations of the phosphonates had no effect on the stimulatory effect of UTP. These results suggest that these phosphonates bind to an allosteric site of the P2Y(2) receptor. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Van Poecke, Sara; Van Calenbergh, Serge] Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, B-9000 Ghent, Belgium.
   [Barrett, Matthew O.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Kumar, T. Santhosh; Harden, T. Kendall] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Sinnaeve, Davy; Martins, Jose C.] Univ Ghent, Dept Organ Chem, NMR & Struct Anal Unit, B-9000 Ghent, Belgium.
RP Van Calenbergh, S (reprint author), Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, Harelbekestr 72, B-9000 Ghent, Belgium.
EM serge.vancalenbergh@ugent.be
RI Jacobson, Kenneth/A-1530-2009; Van Calenbergh, Serge/A-3167-2008;
   Sinnaeve, Davy/F-2293-2013
OI Jacobson, Kenneth/0000-0001-8104-1493; Van Calenbergh,
   Serge/0000-0002-4201-1264; Sinnaeve, Davy/0000-0003-2556-5895
FU NIDDK; National Institutes of General Medical Sciences [GM38213];
   Institute for the Promotion of Innovation by Science and Technology in
   Flanders (IWT)
FX We highly appreciate the technical assistance of Izet Karalic. This
   research was supported in part by the Intramural Research Programs of
   NIDDK and by the National Institutes of General Medical Sciences
   (GM38213). We thank the Institute for the Promotion of Innovation by
   Science and Technology in Flanders (IWT) for providing a scholarship to
   S.V.P.
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U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD APR 1
PY 2012
VL 20
IS 7
BP 2304
EP 2315
DI 10.1016/j.bmc.2012.02.012
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
   Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 906WH
UT WOS:000301379300013
PM 22386981
ER

PT J
AU Justice, AC
   Freiberg, MS
   Tracy, R
   Kuller, L
   Tate, JP
   Goetz, MB
   Fiellin, DA
   Vanasse, GJ
   Butt, AA
   Rodriguez-Barradas, MC
   Gibert, C
   Oursler, KA
   Deeks, SG
   Bryant, K
AF Justice, Amy C.
   Freiberg, Matthew S.
   Tracy, Russ
   Kuller, Lew
   Tate, Janet P.
   Goetz, Matthew Bidwell
   Fiellin, David A.
   Vanasse, Gary J.
   Butt, Adeel A.
   Rodriguez-Barradas, Maria C.
   Gibert, Cynthia
   Oursler, Kris Ann
   Deeks, Steven G.
   Bryant, Kendall
CA VACS Project Team
TI Does an Index Composed of Clinical Data Reflect Effects of Inflammation,
   Coagulation, and Monocyte Activation on Mortality Among Those Aging With
   HIV?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; COLLABORATIVE ANALYSIS; INFECTION; COHORT;
   FIBROSIS; COINFECTION; POPULATION; CLEARANCE; ANEMIA; MARKER
AB Background. When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality.
   Methods. Samples from 1302 HIV-infected veterans on antiretroviral therapy were analyzed. Indices were calculated closest to date of collection. We calculated Spearman correlations stratified by HIV-1 RNA and HCV status and measured association with mortality using C statistics and net reclassification improvement (NRI).
   Results. Of 1302 subjects, 915 had HIV-1 RNA < 500 copies/mL and 154 died. The VACS Index was more correlated with IL-6, D-dimer, and sCD14 than the Restricted Index (P < .001). It was also more predictive of mortality (C statistic, 0.76; 95% confidence interval [CI],.72-.80) than any biomarker (C statistic, 0.66-0.70) or the Restricted Index (C statistic, 0.71; 95% CI,.67-.75). Compared to the Restricted Index alone, NRI resulted from incremental addition of VACS Index components (10%), D-dimer (7%), and sCD14 (4%), but not from IL-6 (0%).
   Conclusions. Among HIV-infected individuals, independent of CD4, HIV-1 RNA, and age, hemoglobin and markers of liver and renal injury are associated with inflammation. Addition of D-dimer and sCD14, but not IL-6, improves the predictive accuracy of the VACS Index for mortality.
C1 [Justice, Amy C.; Tate, Janet P.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA.
   [Fiellin, David A.] Yale Univ, Dept Med, New Haven, CT 06520 USA.
   [Justice, Amy C.; Tate, Janet P.] Yale Univ, Gen Internal Med Sect, New Haven, CT USA.
   [Freiberg, Matthew S.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
   [Freiberg, Matthew S.; Kuller, Lew] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA.
   [Tracy, Russ] Univ Vermont, Coll Med, Burlington, VT 05405 USA.
   [Goetz, Matthew Bidwell] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
   [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Vanasse, Gary J.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA.
   [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
   [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA.
   [Gibert, Cynthia] Washington DC Vet Affairs Med Ctr, Washington, DC USA.
   [Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA.
   [Oursler, Kris Ann] Baltimore Vet Affairs Hlth Care Syst, Baltimore, MD USA.
   [Oursler, Kris Ann] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
   [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
   [Bryant, Kendall] NIAAA, Bethesda, MD USA.
RP Justice, AC (reprint author), VA CT Healthcare Syst 11ACSLG, Bldg 35A,Rm 2-212,950 Campbell Ave, West Haven, CT 06516 USA.
EM amy.justice2@va.gov
OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X
FU National Institutes of Health; National Institute on Alcohol Abuse and
   Alcoholism [U10-AA13566]; National Heart, Lung, and Blood Institute
   [R01-HL095136, R01-HL090342, RCI-HL100347]; National Institute on Aging
   [R01-AG029154, K23 AG024896]; Training Program in Environmental
   Epidemiology [T32 ES07069]
FX This work was supported by the National Institutes of Health: National
   Institute on Alcohol Abuse and Alcoholism (U10-AA13566), National Heart,
   Lung, and Blood Institute (R01-HL095136; R01-HL090342; RCI-HL100347),
   and National Institute on Aging (R01-AG029154; K23 AG024896). J. P. T.
   was supported by the Training Program in Environmental Epidemiology (T32
   ES07069).
NR 34
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 1
PY 2012
VL 54
IS 7
BP 984
EP 994
DI 10.1093/cid/cir989
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 905TB
UT WOS:000301296200023
PM 22337823
ER

PT J
AU Havens, PL
   Stephensen, CB
   Hazra, R
   Flynn, PM
   Wilson, CM
   Rutledge, B
   Bethel, J
   Pan, CG
   Woodhouse, LR
   Van Loan, MD
   Liu, N
   Lujan-Zilbermann, J
   Baker, A
   Kapogiannis, BG
   Mulligan, K
AF Havens, Peter L.
   Stephensen, Charles B.
   Hazra, Rohan
   Flynn, Patricia M.
   Wilson, Craig M.
   Rutledge, Brandy
   Bethel, James
   Pan, Cynthia G.
   Woodhouse, Leslie R.
   Van Loan, Marta D.
   Liu, Nancy
   Lujan-Zilbermann, Jorge
   Baker, Alyne
   Kapogiannis, Bill G.
   Mulligan, Kathleen
CA Adolescent Med Trials Network ATN
TI Vitamin D3 Decreases Parathyroid Hormone in HIV-Infected Youth Being
   Treated With Tenofovir: A Randomized, Placebo-Controlled Trial
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID OPTIMIZED BACKGROUND REGIMEN; BONE-MINERAL DENSITY; DISOPROXIL FUMARATE;
   ANTIRETROVIRAL THERAPY; ALKALINE-PHOSPHATASE; TUBULAR DYSFUNCTION;
   SALVAGE THERAPY; YOUNG-ADULTS; D DEFICIENCY; ADOLESCENTS
AB Background. The study goal was to determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C-telopeptide (CTX) in youth infected with human immunodeficiency virus (HIV) receiving and not receiving combination antiretroviral therapy (cART) containing tenofovir disoproxil fumarate (TDF).
   Methods. This randomized, double-blind, placebo-controlled multicenter trial enrolled HIV-infected youth 18-25 years based on stable treatment with cART containing TDF (n = 118) or no TDF (noTDF; n = 85), and randomized within those groups to vitamin D3, 50 000 IU (n = 102) or placebo (n = 101), administered at 0, 4, and 8 weeks. Outcomes included change in TRP, PTH, BAP, and CTX from baseline to week 12 by TDF/noTDF; and VITD/placebo.
   Results. At baseline, VITD and placebo groups were similar except those on TDF had lower TRP and higher PTH and CTX. At week 12, 95% in the VITD group had sufficient serum 25-hydroxy vitamin D (25-OHD; >= 20 ng/mL), increased from 48% at baseline, without change in placebo (P < .001). PTH decreased in the TDF group receiving VITD (P = .031) but not in the noTDF group receiving VITD, or either placebo group. The decrease in PTH with VITD in those on TDF occurred with insufficient and sufficient baseline 25-OHD (mean PTH change, -7.9 and -6.2 pg/mL; P = .031 and .053, respectively).
   Conclusions. In youth on TDF, vitamin D3 supplementation decreased PTH, regardless of baseline 25-OHD concentration. Clinical Trials Registration. NCT00490412.
C1 [Havens, Peter L.; Pan, Cynthia G.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Pediat, Childrens Res Inst, Milwaukee, WI 53201 USA.
   [Stephensen, Charles B.; Woodhouse, Leslie R.; Van Loan, Marta D.] Agr Res Serv, Western Human Nutr Res Ctr, USDA, Davis, CA USA.
   [Hazra, Rohan; Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
   [Flynn, Patricia M.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
   [Wilson, Craig M.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
   [Rutledge, Brandy; Bethel, James; Liu, Nancy] WESTAT Corp, Rockville, MD 20850 USA.
   [Lujan-Zilbermann, Jorge] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA.
   [Baker, Alyne] Tulane Univ, Dept Pediat Adolescent Med, New Orleans, LA 70118 USA.
   [Mulligan, Kathleen] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Havens, PL (reprint author), Med Coll Wisconsin, Dept Pediat Infect Dis, Suite C450,POB 1997, Milwaukee, WI 53201 USA.
EM phavens@mcw.edu
FU GCRC of the National Center for Research Resources; National Institutes
   of Health; Department of Health and Human Services; Children's National
   Medical Center [M01RR020359]; University of Pennsylvania/Children's
   Hospital of Philadelphia [NCRRUL1-RR-024134]; University of California,
   San Francisco [UL1 RR024131]; Seattle Children's Hospital
   [UL1-RR025014]; Texas Children's Hospital and Baylor College of Medicine
   [M01-RR00188]; Boston University Medical Center [UL1-RR02517]; SUNY
   Stony Brook [M01-RR10710]; Louisiana Board of Regents RC/EEP
   [RC/EEP-06]; ATN from the National Institutes of Health through Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   (NICHD) [U01 HD 040533, U01 HD 040474]; National Institute on Drug
   Abuse; National Institute of Mental Health (NIMH); National Institute of
   Allergy and Infectious Diseases; NICHD; NIMH [U01 A1068632]
FX Eight of these sites used their General Clinical Research Center
   (GCRC)/Pediatric Clinical Research Center (PCRC) for the study; the
   centers were supported by grants from the GCRC Program of the National
   Center for Research Resources, National Institutes of Health, Department
   of Health and Human Services, as follows: Children's National Medical
   Center, M01RR020359; University of Pennsylvania/Children's Hospital of
   Philadelphia, NCRRUL1-RR-024134; University of California, San
   Francisco, UL1 RR024131; Seattle Children's Hospital, UL1-RR025014;
   Texas Children's Hospital and Baylor College of Medicine, M01-RR00188;
   Boston University Medical Center, UL1-RR02517; and SUNY Stony Brook,
   M01-RR10710. The Tulane University Health Sciences Center used its
   Clinical and Translational Research Center (CTRC) for the study; the
   center was supported in whole or in part by funds provided through the
   Louisiana Board of Regents RC/EEP (RC/EEP-06). This work was supported
   by the ATN from the National Institutes of Health (U01 HD 040533 and U01
   HD 040474) through the Eunice Kennedy Shriver National Institute of
   Child Health and Human Development (NICHD) (B. Kapogiannis), with
   supplemental funding from the National Institute on Drug Abuse (N.
   Borek) and the National Institute of Mental Health (NIMH) (P. Brouwers,
   S. Allison). The protocol was coendorsed by the IMPAACT Group. Support
   for IMPAACT was provided by the National Institute of Allergy and
   Infectious Diseases, NICHD, and NIMH (U01 A1068632). The study was
   scientifically reviewed by the ATN's Therapeutic Leadership Group.
   Network, scientific and logistical support was provided by the ATN
   Coordinating Center (C. Wilson, C. Partlow) at the University of Alabama
   at Birmingham. Network operations and analytic support was provided by
   the ATN Data and Operations Center at Westat, Inc (J. Korelitz, B.
   Driver). We thank the ATN Community Advisory Board and the youth who
   participated in the study.
NR 39
TC 28
Z9 30
U1 1
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 1
PY 2012
VL 54
IS 7
BP 1013
EP 1025
DI 10.1093/cid/cir968
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 905TB
UT WOS:000301296200027
PM 22267714
ER

PT J
AU Silverberg, MJ
   Lau, B
   Justice, AC
   Engels, E
   Gill, MJ
   Goedert, JJ
   Kirk, GD
   D'Souza, G
   Bosch, RJ
   Brooks, JT
   Napravnik, S
   Hessol, NA
   Jacobson, LP
   Kitahata, MM
   Klein, MB
   Moore, RD
   Rodriguez, B
   Rourke, SB
   Saag, MS
   Sterling, TR
   Gebo, KA
   Press, N
   Martin, JN
   Dubrow, R
AF Silverberg, Michael J.
   Lau, Bryan
   Justice, Amy C.
   Engels, Eric
   Gill, M. John
   Goedert, James J.
   Kirk, Gregory D.
   D'Souza, Gypsyamber
   Bosch, Ronald J.
   Brooks, John T.
   Napravnik, Sonia
   Hessol, Nancy A.
   Jacobson, Lisa P.
   Kitahata, Mari M.
   Klein, Marina B.
   Moore, Richard D.
   Rodriguez, Benigno
   Rourke, Sean B.
   Saag, Michael S.
   Sterling, Timothy R.
   Gebo, Kelly A.
   Press, Natasha
   Martin, Jeffrey N.
   Dubrow, Robert
CA N Amer AIDS Cohort Collaboration
TI Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in
   North America
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS INFECTION; ACTIVE ANTIRETROVIRAL THERAPY;
   HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; COST-EFFECTIVENESS; HAART
   ERA; DEFINING MALIGNANCIES; AIDS COHORT; MEN; PREVALENCE
AB Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends.
   Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men).
   Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7-151.1) for HIV-infected MSM and 26.7 ( 95% CI, 11.5-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8-6.0), but no difference was observed comparing women with other men ( RR, 1.0; 95% CI, 0.5-2.2). In comparison with the period 2000-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI,.3-.9) in 1996-1999 and 0.9 (95% CI,.6-1.2) in 2004-2007.
   Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
C1 [Silverberg, Michael J.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA.
   [Lau, Bryan; Kirk, Gregory D.; D'Souza, Gypsyamber; Jacobson, Lisa P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Justice, Amy C.; Dubrow, Robert] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
   [Justice, Amy C.; Dubrow, Robert] Yale Univ, Sch Med, New Haven, CT USA.
   [Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA.
   [Engels, Eric; Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
   [Gill, M. John] Univ Calgary, Calgary, AB T2N 1N4, Canada.
   [Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Brooks, John T.] Ctr Dis Control & Prevent, Atlanta, GA USA.
   [Napravnik, Sonia] Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27515 USA.
   [Hessol, Nancy A.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Kitahata, Mari M.] Univ Washington, Seattle, WA 98195 USA.
   [Klein, Marina B.] McGill Univ, Montreal, PQ, Canada.
   [Moore, Richard D.; Gebo, Kelly A.] Johns Hopkins Sch Med, Baltimore, MD USA.
   [Rodriguez, Benigno] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Rourke, Sean B.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
   [Saag, Michael S.] Univ Alabama Birmingham, Birmingham, AL USA.
   [Sterling, Timothy R.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
   [Press, Natasha] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
RP Silverberg, MJ (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA.
EM michael.j.silverberg@kp.org
RI Rodriguez, Benigno/C-3365-2009; Gill, John/G-7083-2016
OI Rodriguez, Benigno/0000-0001-9736-7957; Gill, John/0000-0002-8546-8790
FU National Institutes of Health (General Clinical Research Centers [GCRC])
   [U01-AI069918, U01-AA013566, U01-AI-35042, U01-AI-35043, U01-AI-35039,
   5-M01-RR-00052, U01-AI-35040, U01-AI-35041, U01-AI38855]; AIDS Clinical
   Trials Group Longitudinal Linked Randomized Trials (ALLRT) [U01-AI38858,
   U01-AI68634, U01-AI68636, AI-69432, AI-69434, U01-AI-35004,
   U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, U01-AI-42590,
   U01-HD-32632, UL1-RR024131, P30-AI27757, K23-AI-61-0320, P30-AI27767,
   P30-AI50410, RR025747, P30-AI54999, R01-DA04334, R01-DA12568,
   R01-MH54907, R24-AI067039, N02-CP55504, Z01 CP010176, AHQ290-01-0012,
   K01-AI071754, K24-00432, R01-DA11602, K01-AI071725, R01 AG026250, P30
   AI027763]; Canadian Institutes for Health Research (CIHR) [TGF-96118,
   HCP-97105, CBR-86906, CBR-94036, KRS-86251, 169621]; Canadian Trials
   Network [242]; Centers for Disease Control [CDC200-2006-18797]; Pfizer;
   Merck; Abbott; Gilead; Tibotec; Bristol-Myers Squibb; GlaxoSmithKline;
   Schering Plough Canada
FX This work was supported by grants from the National Institutes of
   Health: U01-AI069918, U01-AA013566, U01-AI-35042, 5-M01-RR-00052
   (General Clinical Research Centers [GCRC]), U01-AI-35043, U01-AI-35039,
   U01-AI-35040, U01-AI-35041, U01-AI38855: AIDS Clinical Trials Group
   Longitudinal Linked Randomized Trials (ALLRT); U01-AI38858; U01-AI68634;
   U01-AI68636; AI-69432; AI-69434, U01-AI-35004, U01-AI-31834,
   U01-AI-34994, U01-AI-34989, U01-AI-34993, and U01-AI-42590,
   U01-HD-32632, UL1-RR024131, P30-AI27757; K23-AI-61-0320, P30-AI27767,
   P30-AI50410; RR025747, P30-AI54999, R01-DA04334; R01-DA12568,
   R01-MH54907, R24-AI067039, N02-CP55504; Z01 CP010176, AHQ290-01-0012,
   K01-AI071754, K24-00432; R01-DA11602, K01-AI071725, R01 AG026250, and
   P30 AI027763. This work was also supported by the Canadian Institutes
   for Health Research (CIHR: TGF-96118; HCP-97105; CBR-86906; CBR-94036;
   KRS-86251; 169621) and the Canadian Trials Network (project 242).
   Finally, support was also provided by the Centers for Disease Control
   (CDC200-2006-18797); the findings and conclusions in this report are
   those of the authors and do not necessarily represent the views of the
   Centers for Disease Control and Prevention.; M. J. S. received research
   grant support from Pfizer and Merck. G. D. K. has been a consultant to
   GlaxoSmithKline and Merck. G. D. has been a consultant to and received
   research grant support from Merck. M. B. K. has been a consultant to
   GlaxoSmithKline, Abbott, Pfizer, and Boehringer-Ingelheim, has received
   lecture fees from Abbott, Gilead, Tibotec, Bristol-Myers Squibb, and
   GlaxoSmithKline, and received research support from Schering Plough
   Canada. R. D. M. has been a consultant to Bristol-Myers Squibb and
   Merck. T. R. S. received research grant support from Pfizer and
   Bristol-Myers Squibb. All other authors report no potential conflicts.
NR 39
TC 174
Z9 177
U1 1
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 1
PY 2012
VL 54
IS 7
BP 1026
EP 1034
DI 10.1093/cid/cir1012
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 905TB
UT WOS:000301296200028
PM 22291097
ER

PT J
AU Semba, RD
   Cappola, AR
   Sun, K
   Bandinelli, S
   Dalal, M
   Crasto, C
   Guralnik, JM
   Ferrucci, L
AF Semba, Richard D.
   Cappola, Anne R.
   Sun, Kai
   Bandinelli, Stefania
   Dalal, Mansi
   Crasto, Candace
   Guralnik, Jack M.
   Ferrucci, Luigi
TI Relationship of low plasma klotho with poor grip strength in older
   community-dwelling adults: the InCHIANTI study
SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE Aging; Klotho; Muscle strength; Sarcopenia
ID ENDOTHELIAL DYSFUNCTION; HANDGRIP STRENGTH; PROTEIN; MUSCLE; DISABILITY;
   SARCOPENIA; AUTOPHAGY; MEMBRANE; PATHWAYS; GENE
AB Handgrip strength is a strong indicator of total body muscle strength and is a predictor of poor outcomes in older adults. The aging suppressor gene klotho encodes a single-pass transmembrane protein that is secreted as a circulating hormone. In mice, disruption of klotho expression results in a syndrome that includes sarcopenia, atherosclerosis, osteoporosis, and shortened lifespan, and conversely, overexpression of klotho leads to a greater longevity. The objective was to determine whether plasma klotho levels are related to skeletal muscle strength in humans. We measured plasma klotho in 804 adults, a parts per thousand yen65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. Grip strength was positively correlated with plasma klotho at threshold < 681 pg/mL. After adjusting for age, sex, education, smoking, physical activity, cognition, and chronic diseases, plasma klotho (per 1 standard deviation increase) was associated with grip strength (beta = 1.20, standard error = 0.35, P = 0.0009) in adults with plasma klotho < 681 pg/mL. These results suggest that older adults with lower plasma klotho have poor skeletal muscle strength.
C1 [Semba, Richard D.; Sun, Kai; Dalal, Mansi; Crasto, Candace] Johns Hopkins Univ Hosp, Dept Ophthalmol, Sch Med, Baltimore, MD 21287 USA.
   [Cappola, Anne R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
   [Bandinelli, Stefania] Azienda Sanit, Florence, Italy.
   [Guralnik, Jack M.] NIA, Epidemiol & Demog Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Semba, RD (reprint author), Johns Hopkins Univ Hosp, Dept Ophthalmol, Sch Med, Smith Bldg,M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
FU National Institute on Aging (NIA) [R01 AG027012, R01 HL094507, 263 MD
   9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Italian
   Ministry of Health [ICS110.1/RF97.71]; NIA, National Institutes of
   Health, Baltimore, Maryland
FX This work was supported by National Institute on Aging (NIA) Grant R01
   AG027012, R01 HL094507, the Italian Ministry of Health
   (ICS110.1/RF97.71), NIA contracts 263 MD 9164, 263 MD 821336,
   N.1-AG-1-1, N.1-AG-1-2111, and N01-AG-5-0002, the Intramural Research
   Program of NIA, National Institutes of Health, Baltimore, Maryland.
NR 34
TC 21
Z9 22
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1439-6319
J9 EUR J APPL PHYSIOL
JI Eur. J. Appl. Physiol.
PD APR
PY 2012
VL 112
IS 4
BP 1215
EP 1220
DI 10.1007/s00421-011-2072-3
PG 6
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 909LV
UT WOS:000301566900003
PM 21769735
ER

PT J
AU Barentsz, JO
   Richenberg, J
   Clements, R
   Choyke, P
   Verma, S
   Villeirs, G
   Rouviere, O
   Logager, V
   Futterer, JJ
AF Barentsz, Jelle O.
   Richenberg, Jonathan
   Clements, Richard
   Choyke, Peter
   Verma, Sadhna
   Villeirs, Geert
   Rouviere, Olivier
   Logager, Vibeke
   Futterer, Jurgen J.
TI ESUR prostate MR guidelines 2012
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Prostate cancer; MRI; Guidelines; Oncology; ESUR
ID CONTRAST-ENHANCED MRI; EXTERNAL-BEAM RADIOTHERAPY; DIFFUSION-WEIGHTED
   MRI; ACTIVE SURVEILLANCE; RADICAL PROSTATECTOMY; RADIATION-THERAPY;
   LOCAL RECURRENCE; CANCER LOCALIZATION; PERIPHERAL ZONE; ANTIGEN LEVELS
AB The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated, but a compromise, reflected by "minimal" and "optimal" requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines for the optimal technique and three protocols for "detection", "staging" and "node and bone" are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented.
   Key Points
   aEuro cent This report provides guidelines for magnetic resonance imaging (MRI) in prostate cancer.
   aEuro cent Clinical indications, and minimal and optimal imaging acquisition protocols are provided.
   aEuro cent A structured reporting system (PI-RADS) is described.
C1 [Barentsz, Jelle O.; Futterer, Jurgen J.] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6525 ED Nijmegen, Netherlands.
   [Richenberg, Jonathan] Brighton & Sussex Univ Hosp Trust, Brighton, E Sussex, England.
   [Clements, Richard] Royal Gwent Hosp, Dept Clin Radiol, Newport, Gwent, Wales.
   [Choyke, Peter] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
   [Verma, Sadhna] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA.
   [Villeirs, Geert] Ghent Univ Hosp, Div Genitourinary Radiol, Ghent, Belgium.
   [Rouviere, Olivier] Hop Edouard Herriot, Hosp Civils Lyon, Dept Urinary & Vasc Imaging, Lyon, France.
   [Rouviere, Olivier] Univ Lyon, Lyon, France.
   [Rouviere, Olivier] Univ Lyon 1, Fac Med Lyon Est, F-69365 Lyon, France.
   [Logager, Vibeke] Univ Copenhagen, Herlev Hosp, DK-2730 Herlev, Denmark.
RP Barentsz, JO (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6525 ED Nijmegen, Netherlands.
EM j.barentsz@rad.umcn.nl
RI Barentsz, Jelle/D-3515-2009; futterer, jurgen/A-1455-2014; 
OI Logager, Vibeke Berg/0000-0001-5343-6869; Rouviere,
   Olivier/0000-0002-0030-478X
NR 76
TC 743
Z9 779
U1 11
U2 41
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
J9 EUR RADIOL
JI Eur. Radiol.
PD APR
PY 2012
VL 22
IS 4
BP 746
EP 757
DI 10.1007/s00330-011-2377-y
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 908NK
UT WOS:000301496900004
PM 22322308
ER

PT J
AU Thavavel, V
   Basha, JJ
   Krishna, MC
   Murugesan, R
AF Thavavel, V.
   Basha, J. Jaffer
   Krishna, M. C.
   Murugesan, R.
TI Heuristic wavelet approach for low-dose EPR tomographic reconstruction:
   An applicability analysis with phantom and in vivo imaging
SO EXPERT SYSTEMS WITH APPLICATIONS
LA English
DT Article
DE Electron magnetic resonance imaging; Low-dose tomographic
   reconstruction; Filtered backprojection; Wavelet thresholding; Threshold
   optimization; Genetic algorithm and Multiobjective function
ID GENETIC ALGORITHM; TRANSFORM; SHRINKAGE; DESIGN; DOMAIN
AB Electron paramagnetic resonance imaging (EPRI) is a new functional imaging modality that can provide valuable in vivo physiological information and aids as a complimentary imaging technique to MRI and PET of tissues especially with respect to in vivo pO2, redox status and pharmacology. EPRI deals with the measurement of distribution and in vivo dynamics, using exogenous paramagnetic spin probes injected into the scan subject. The bio-clearance and dosage of these spin probes are issues of concern in EPRI. As a consequence, tomographic reconstruction from 'noisy' and 'sparse' number of projections is highly desirable in EPRI for the purpose of dose reduction and fast acquisition time respectively. The aim of research is to address the incompleteness of such projection data by developing a software which requires no change in acquisition hardware and/or no a priori knowledge of imaging process. The new software approach integrates soft computing and multiresolution within tomographic reconstruction to "intelligently" extract the details of importance at several levels of resolution. The new multiresolution reconstruction algorithm is based on wavelet transform with computational complexity same as the clinically used, filtered backprojection (FBP) method, except that the filters are now angle dependent. Gain in intelligence is achieved employing multiobjective genetic algorithm (GA) to find values for wavelet denoising threshold with optimum performance in terms of signal to noise ratio (SNR) and resolution of the reconstructed image. Feasibility of the approach for fast and low dose tomographic reconstruction is demonstrated with simulated SheppLogan head phantom. Subsequently, the experimental results with phantom and in vivo EPRI proves that the developed method can reduce the dose level and number of projections by 60-75% in tomographic reconstruction. In particular the quantitative analysis, using RMSE, PSNR and Liu's error factor, shows that our approach outperforms the widely used, FBP and state-of-art wavelet-based tomographic reconstruction method in achieving image quality with acceptable diagnostic accuracy. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Thavavel, V.] Karunya Univ, Dept Comp Applicat, Coimbatore, Tamil Nadu, India.
   [Basha, J. Jaffer] Sree Sowdambika Coll Engn, Dept Comp Sci & Engn, Aruppukottai, Tamil Nadu, India.
   [Krishna, M. C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Murugesan, R.] Madurai Kamaraj Univ, Networking Resource Ctr Biol Sci, Madurai 625021, Tamil Nadu, India.
RP Thavavel, V (reprint author), Karunya Univ, Dept Comp Applicat, Coimbatore, Tamil Nadu, India.
EM thavavelmurugesanv@gmail.com; jafferbasha@gmail.com; rammku@eth.net
FU Department of Science and Technology; UGC, New Delhi, India; Office of
   International Affairs, National Cancer Institute, NIH, DHHS, USA
FX This work was supported in part by Department of Science and Technology
   and UGC sponsored Center for Potential in Genomic Sciences Programme,
   New Delhi, India, and in part by the Scientist Exchange Program of the
   Office of International Affairs, National Cancer Institute, NIH, DHHS,
   USA.
NR 33
TC 4
Z9 4
U1 1
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0957-4174
EI 1873-6793
J9 EXPERT SYST APPL
JI Expert Syst. Appl.
PD APR
PY 2012
VL 39
IS 5
BP 5717
EP 5726
DI 10.1016/j.eswa.2011.11.098
PG 10
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
   Electronic; Operations Research & Management Science
SC Computer Science; Engineering; Operations Research & Management Science
GA 903XF
UT WOS:000301155300110
ER

PT J
AU Lee, JC
   Hasnain-Wynia, R
   Lau, DT
AF Lee, Jae Chul
   Hasnain-Wynia, Romana
   Lau, Denys T.
TI Delay in Seeing a Doctor Due to Cost: Disparity between Older Adults
   with and without Disabilities in the United States
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Elderly; disability; disparities; delaying doctor visits; BRFSS
ID QUALITY-OF-LIFE; FACTOR SURVEILLANCE SYSTEM; SECONDARY HEALTH
   CONDITIONS; MEDICARE BENEFICIARIES; PREVENTIVE SERVICES; RISK-FACTORS;
   CARE ACCESS; POPULATION; INSURANCE; CANCER
AB Objective. To examine the disparity in delaying seeing a doctor due to cost between older adults with and without disabilities, and whether the disparity could be explained by health and financial variables.
   Data Sources. Nationally representative sample of community-dwelling adults aged >= 65 who have health insurance and a usual source of care from the 2006 Behavioral Risk Factor Surveillance System (n = 85,015).
   Study Design. This cross-sectional study used sequential logistic regression models to examine the associations of delaying seeing a doctor due to cost with disability status, including demographic, health, and financial variables.
   Principal Findings. Older adults with disabilities had significantly higher odds of delaying seeing a doctor due to cost compared to older adults without disabilities after controlling for demographic, health, and financial factors. Although health and financial variables collectively attenuated the disparity, they did not fully explain the disparity.
   Conclusions. Despite having health insurance and a usual source of care, older adults with disabilities encountered greater economic difficulties in seeing a doctor than their counterparts without disabilities. Policy makers should continue addressing the economic burden to improve timely visits to health care providers.
C1 [Hasnain-Wynia, Romana] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Equ, Inst Healthcare Studies, Chicago, IL 60611 USA.
   [Lau, Denys T.] Univ Illinois, Coll Pharm, Dept Pharm Adm, Chicago, IL USA.
   [Lee, Jae Chul] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Lee, JC (reprint author), NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, CRC, Bldg 10,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA.
EM leej31@cc.nih.gov
FU National Institute on Disability and Rehabilitation [H133P080006];
   National Institute on Aging [K01AG027295]
FX All authors do not have any interests that may be interpreted as
   affecting this study. During this study, Dr. Lee was supported in part
   by an Advanced Rehabilitation Research Training Fellowship under a grant
   from the National Institute on Disability and Rehabilitation (grant no.
   H133P080006; PI: Allen Heinemann, Ph.D.). However, the content presented
   in the study does not represent the policy of the NIDRR, and no
   endorsement by the Federal Government should be assumed. During this
   study, Dr. Denys Lau was supported in part by Award Number K01AG027295
   (PI: D. T. Lau) from the National Institute on Aging.
NR 66
TC 12
Z9 12
U1 4
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0017-9124
J9 HEALTH SERV RES
JI Health Serv. Res.
PD APR
PY 2012
VL 47
IS 2
BP 698
EP 720
DI 10.1111/j.1475-6773.2011.01346.x
PG 23
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 904WJ
UT WOS:000301229300009
PM 22092264
ER

PT J
AU Steer, CD
   Hibbeln, JR
   Golding, J
   Smith, GD
AF Steer, Colin D.
   Hibbeln, Joseph R.
   Golding, Jean
   Smith, George Davey
TI Polyunsaturated fatty acid levels in blood during pregnancy, at birth
   and at 7 years: their associations with two common FADS2 polymorphisms
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ALPHA-LINOLENIC ACID; FADS1-FADS2 GENE-CLUSTER; ERYTHROCYTE
   PHOSPHOLIPIDS; VARIANTS; COHORT; POPULATION; METABOLISM; DISEASE;
   PLASMA; N-6
AB Minor alleles of polymorphisms in the fatty acid desaturase (FADS) gene cluster have been associated with reduced desaturation of the precursor polyunsaturated fatty acids (FAs) in small studies. The effects of these polymorphisms during progressive developmental stages have not previously been reported. Data from blood samples for 4342 pregnant women, 3343 umbilical cords reflecting the newborns blood supply and 5240 children aged 7 years were analysed to investigate the associations of polyunsaturated FAs with rs1535 and rs174575two polymorphisms in the FADS2 gene. Strong positive associations were observed between the minor G allele for these two markers, especially rs1535, and the substrates linoleic (18:2n-6) and -linolenic (18:3n-3) acid. Negative associations were observed for the more highly unsaturated FAs such as arachidonic acid (20:4n-6), timnodonic acid (EPA, 20:5n-3) and cervonic acid (DHA, 22:6n-3). Bivariable genetic associations using the mother and child genotypes suggested that the newborn metabolism had a greater capacity to synthesize the more highly unsaturated omega-6 FAs than the more highly unsaturated omega-3 FAs. Nevertheless, despite the immaturity of the neonate, there was evidence that synthesis of DHA was occurring. However, by 7 years, no associations were observed with the maternal genotype. This suggested that the childrens FA levels were related only to their own metabolism with no apparent lasting influences of the in utero environment.
C1 [Steer, Colin D.; Golding, Jean] Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Bristol BS8 2BN, Avon, England.
   [Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD USA.
   [Smith, George Davey] Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England.
RP Steer, CD (reprint author), Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Barley House, Bristol BS8 2BN, Avon, England.
EM colin.steer@bristol.ac.uk
OI Golding, Jean/0000-0003-2826-3307; Davey Smith,
   George/0000-0002-1407-8314
FU UK Medical Research Council [74882]; Wellcome Trust [076467]; University
   of Bristol; National Oceanic and Atmospheric Administration, USA;
   Waterloo Foundation, UK
FX We are extremely grateful to all the families who took part in this
   study, the midwives for their help in recruiting them and the whole
   ALSPAC team, which includes interviewers, computer and laboratory
   technicians, clerical workers, research scientists, volunteers,
   managers, receptionists and nurses. The UK Medical Research Council
   (Grant ref: 74882), the Wellcome Trust (Grant ref: 076467) and the
   University of Bristol currently provide core support for ALSPAC. This
   publication is the work of the authors and C.D.S. will serve as
   guarantor for the contents of this paper.; This work was supported by
   the National Oceanic and Atmospheric Administration, USA and the
   Waterloo Foundation, UK.
NR 42
TC 17
Z9 17
U1 0
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD APR 1
PY 2012
VL 21
IS 7
BP 1504
EP 1512
DI 10.1093/hmg/ddr588
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 905UC
UT WOS:000301299700005
PM 22194195
ER

PT J
AU Tan, AH
   Sun, JL
   Xia, N
   Qin, X
   Hu, YL
   Zhang, SJ
   Tao, S
   Gao, Y
   Yang, XB
   Zhang, HY
   Kim, ST
   Peng, T
   Lin, XL
   Li, L
   Mo, LJ
   Liang, ZJ
   Shi, DY
   Huang, Z
   Huang, XH
   Liu, M
   Ding, Q
   Trent, JM
   Zheng, SL
   Mo, ZN
   Xu, JF
AF Tan, Aihua
   Sun, Jielin
   Xia, Ning
   Qin, Xue
   Hu, Yanling
   Zhang, Shijun
   Tao, Sha
   Gao, Yong
   Yang, Xiaobo
   Zhang, Haiying
   Kim, Seong-Tae
   Peng, Tao
   Lin, Xiaoling
   Li, Li
   Mo, Linjian
   Liang, Zhengjia
   Shi, Deyi
   Huang, Zhang
   Huang, Xianghua
   Liu, Ming
   Ding, Qiang
   Trent, Jeffrey M.
   Zheng, S. Lilly
   Mo, Zengnan
   Xu, Jianfeng
TI A genome-wide association and gene-environment interaction study for
   serum triglycerides levels in a healthy Chinese male population
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ALDEHYDE DEHYDROGENASE 2; CARDIOVASCULAR-DISEASE; PLASMA TRIGLYCERIDE;
   ALCOHOL-CONSUMPTION; METABOLIC SYNDROME; RISK; LOCI; POLYMORPHISM;
   DRINKING; TRAITS
AB Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Geneenvironment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 10(26) and 1.41 10(9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P 3.34 10(5)). Rs671 was significantly associated with serum TG levels in drinkers (P 1.90 10(10)), while no association was observed in non-drinkers (P 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P 1.28 10(8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.
C1 [Tan, Aihua; Qin, Xue; Hu, Yanling; Zhang, Shijun; Gao, Yong; Yang, Xiaobo; Zhang, Haiying; Mo, Zengnan] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning 530021, Guangxi, Peoples R China.
   [Hu, Yanling; Li, Li] Guangxi Med Univ, Med Sci Res Ctr, Nanning 530021, Guangxi, Peoples R China.
   [Yang, Xiaobo; Zhang, Haiying] Guangxi Med Univ, Dept Occupat Hlth & Environm Hlth, Sch Publ Hlth, Nanning 530021, Guangxi, Peoples R China.
   [Sun, Jielin; Kim, Seong-Tae; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC 27157 USA.
   [Xia, Ning] Guangxi Med Univ, Affiliated Hosp 1, Ctr Metab Dis & Diabet, Nanning 530021, Guangxi, Peoples R China.
   [Qin, Xue] Guangxi Med Univ, Affiliated Hosp 1, Dept Clin Lab, Nanning 530021, Guangxi, Peoples R China.
   [Peng, Tao] Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Nanning 530021, Guangxi, Peoples R China.
   [Mo, Linjian; Mo, Zengnan] Guangxi Med Univ, Affiliated Hosp 1, Inst Urol & Nephrol, Nanning 530021, Guangxi, Peoples R China.
   [Tao, Sha; Trent, Jeffrey M.; Xu, Jianfeng] Van Andel Res Inst, Ctr Genet Epidemiol, Grand Rapids, MI 49503 USA.
   [Gao, Yong; Lin, Xiaoling; Xu, Jianfeng] Fudan Univ, Sch Life Sci, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China.
   [Peng, Tao] NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA.
   [Liang, Zhengjia; Shi, Deyi; Huang, Zhang] Fangchenggang First Peoples Hosp, Med Examinat Ctr, Fangchenggang 538021, Guangxi, Peoples R China.
   [Huang, Xianghua] Guigang Peoples Hosp, Med Examinat Ctr, Guigang 537100, Guangxi, Peoples R China.
   [Liu, Ming] Yulin First Peoples Hosp, Med Examinat Ctr, Yulin 537000, Guangxi, Peoples R China.
   [Ding, Qiang; Xu, Jianfeng] Fudan Univ, Huashan Hosp, Fudan Univ Inst Urol, Shanghai 200040, Peoples R China.
RP Mo, ZN (reprint author), Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning 530021, Guangxi, Peoples R China.
EM zengnanmo@hotmail.com
RI tao, sha/B-7750-2012; Yang, Xiaobo/G-3854-2016; Kim,
   Seong-Tae/E-4474-2017
OI Kim, Seong-Tae/0000-0001-7436-1405
FU National Natural Science Foundation of China [30945204, 30360124,
   30260110, 81060029]; Provincial Natural Science Foundation of Guangxi
   [2010GXNSFA013174]; Guangxi Provincial Department of Finance and
   Education [2009GJCJ150, 200911MS42]; Fudan-VARI Center for genetic
   Epidemiology; Fudan University Institute of Urology
FX This work was partially supported by the General Program of National
   Natural Science Foundation of China (30945204, 30360124, 30260110,
   81060029), Provincial Natural Science Foundation of Guangxi
   (2010GXNSFA013174), the Guangxi Provincial Department of Finance and
   Education (2009GJCJ150, 200911MS42) and intramural funding from
   Fudan-VARI Center for genetic Epidemiology and intramural funding from
   Fudan University Institute of Urology.
NR 23
TC 32
Z9 34
U1 2
U2 22
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 APR 1
PY 2012
VL 21
IS 7
BP 1658
EP 1664
DI 10.1093/hmg/ddr587
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 905UC
UT WOS:000301299700019
PM 22171074
ER

PT J
AU Jin, JJ
   Sabatino, M
   Somerville, R
   Wilson, JR
   Dudley, ME
   Stroncek, DF
   Rosenberg, SA
AF Jin, Jianjian
   Sabatino, Marianna
   Somerville, Robert
   Wilson, John R.
   Dudley, Mark E.
   Stroncek, David F.
   Rosenberg, Steven A.
TI Simplified Method of the Growth of Human Tumor Infiltrating Lymphocytes
   in Gas-permeable Flasks to Numbers Needed for Patient Treatment
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE adoptive cell therapy; cancer; tumor infiltrating lymphocytes; G-Rex
   flasks; melanoma
ID ADOPTIVE CELL THERAPY; HOLLOW-FIBER BIOREACTORS; METASTATIC MELANOMA;
   T-CELLS; RAPID EXPANSION; IMMUNOTHERAPY; REGRESSION; INTERLEUKIN-2;
   PERSISTENCE; CULTURES
AB Adoptive cell therapy of metastatic melanoma with autologous tumor infiltrating lymphocytes (TIL) is clinically effective, but TIL production can be challenging. Here we describe a simplified method for initial TIL culture and rapid expansion in gas-permeable flasks. TIL were initially cultured from tumor digests and fragments in 40 mL capacity flasks with a 10 cm(2) gas-permeable silicone bottom, G-Rex10. A TIL rapid expansion protocol (REP) was developed using 500 mL capacity flasks with a 100 cm(2) gas-permeable silicone bottom, G-Rex100. TIL growth was successfully initiated in G-Rex10 flasks from tumor digests from 13 of 14 patients and from tumor fragments in all 11 tumor samples tested. TIL could then be expanded to 8-10 x 10(9) cells in a 2-step REP that began by seeding 5 x 10(6) TIL into a G-Rex100 flask, followed by expansion at day 7 into 3 G-Rex100 flasks. To obtain the 30-60 x 10(9) cells used for patient treatment, we seeded 6 G-Rex100 flasks with 5 x 10(6) cells and expanded into 18 G-Rex100 flasks. Large-scale TIL REP in gas-permeable flasks requires approximately 9-10 L of media, about 3-4 times less than other methods. In conclusion, TIL initiation and REP in gas-permeable G-Rex flasks require fewer total vessels, less media, less incubator space, and less labor than initiation and REP in 24-well plates, tissue culture flasks, and bags. TIL culture in G-Rex flasks will facilitate the production of TIL at the numbers required for patient treatment at most cell processing laboratories.
C1 [Jin, Jianjian; Sabatino, Marianna; Stroncek, David F.] NCI, Cell Proc Sect, Dept Transfus Med, Ctr Clin,NIH, Bethesda, MD 20892 USA.
   [Somerville, Robert; Dudley, Mark E.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
   [Wilson, John R.] Wilson Wolf Mfg, New Brighton, MN USA.
RP Stroncek, DF (reprint author), NCI, Cell Proc Sect, Dept Transfus Med, Ctr Clin,NIH, Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
FU TIL Laboratory, Surgery Branch, NCI; Cell Processing Laboratory,
   Department of Transfusion Medicine, Clinical Center; Surgery Branch,
   NCI, NIH; Department of Transfusion Medicine, Clinical Center, NIH
FX The authors thank the staff of TIL Laboratory, Surgery Branch, NCI and
   Cell Processing Laboratory, Department of Transfusion Medicine, Clinical
   Center for their support and help with these studies. The authors are
   especially grateful to Jiaqiang Ren for helping prepare the figures.;
   Supported by the Surgery Branch, NCI, NIH, and the Department of
   Transfusion Medicine, Clinical Center, NIH.
NR 19
TC 26
Z9 26
U1 1
U2 5
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 APR
PY 2012
VL 35
IS 3
BP 283
EP 292
DI 10.1097/CJI.0b013e31824e801f
PG 10
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 910QT
UT WOS:000301656800009
PM 22421946
ER

PT J
AU Limou, S
   Delaneau, O
   van Manen, D
   An, P
   Sezgin, E
   Le Clerc, S
   Coulonges, C
   Troyer, JL
   Veldink, JH
   van den Berg, LH
   Spadoni, JL
   Taing, L
   Labib, T
   Montes, M
   Delfraissy, JF
   Schachter, F
   O'Brien, SJ
   Buchbinder, S
   van Natta, ML
   Jabs, DA
   Froguel, P
   Schuitemaker, H
   Winkler, CA
   Zagury, JF
AF Limou, Sophie
   Delaneau, Olivier
   van Manen, Danielle
   An, Ping
   Sezgin, Efe
   Le Clerc, Sigrid
   Coulonges, Cedric
   Troyer, Jennifer L.
   Veldink, Jan H.
   van den Berg, Leonard H.
   Spadoni, Jean-Louis
   Taing, Lieng
   Labib, Taoufik
   Montes, Matthieu
   Delfraissy, Jean-Francois
   Schachter, Francois
   O'Brien, Stephen J.
   Buchbinder, Susan
   van Natta, Mark L.
   Jabs, Douglas A.
   Froguel, Philippe
   Schuitemaker, Hanneke
   Winkler, Cheryl A.
   Zagury, Jean-Francois
TI Multicohort Genomewide Association Study Reveals a New Signal of
   Protection Against HIV-1 Acquisition
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID WIDE ASSOCIATION; OCULAR COMPLICATIONS; AIDS; INFECTION; DETERMINANTS;
   APOPTOSIS; LOCI; GENE; NONPROGRESSION; RESTRICTION
AB Background. To date, onlymutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility.
   Methods. We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10(-5) in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent.
   Results. After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: P-combined = 7.76 x 10(-8).
   Conclusions. We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.
C1 [Limou, Sophie; Delaneau, Olivier; Le Clerc, Sigrid; Coulonges, Cedric; Spadoni, Jean-Louis; Taing, Lieng; Labib, Taoufik; Montes, Matthieu; Schachter, Francois; Zagury, Jean-Francois] Conservatoire Natl Arts & Metiers, Lab Genom Bioinformat & Applicat, Chaire Bioinformat, EA4627, F-75003 Paris, France.
   [Limou, Sophie; Le Clerc, Sigrid; Coulonges, Cedric; Delfraissy, Jean-Francois; Zagury, Jean-Francois] French Agcy Res AIDS & Hepatitis, ANRS Genom Grp, Paris, France.
   [Froguel, Philippe] CNRS, Inst Pasteur Lille, UMR 8090, F-75700 Paris, France.
   [Limou, Sophie; An, Ping; Winkler, Cheryl A.] NCI, Basic Res Lab, Basic Sci Program SAIC Frederick Inc, Frederick, MD 21701 USA.
   [Sezgin, Efe; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
   [Troyer, Jennifer L.] NCI, Lab Genom Divers, SAIC Frederick Inc, SAIC Frederick, Frederick, MD 21701 USA.
   [van Manen, Danielle; Schuitemaker, Hanneke] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Landsteiner Lab,Ctr Infect Dis & Immun Amsterdam, NL-1012 WX Amsterdam, Netherlands.
   [Veldink, Jan H.; van den Berg, Leonard H.] Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands.
   [Buchbinder, Susan] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA.
   [van Natta, Mark L.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
   [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
   [Froguel, Philippe] Imperial Coll London, Hammersmith Hosp, Genom Med, London, England.
RP Zagury, JF (reprint author), Conservatoire Natl Arts & Metiers, Lab Genom Bioinformat & Applicat, Chaire Bioinformat, EA4627, 29E Rue St Martin, F-75003 Paris, France.
EM zagury@cnam.fr
RI Ghartouchent, malek/B-9088-2012; Sezgin, Efe/B-8418-2012; 
OI Sezgin, Efe/0000-0002-8000-7485; Montes, Matthieu/0000-0001-5921-460X
FU Agence Nationale de Recherche sur le SIDA; Netherlands Organization for
   Scientific Research (TOP) [9120.6046]; Netherlands National Institute
   for Public Health and the Environment; National Cancer Institute (NCI);
   National Institutes of Health (NIH) [HHSN26120080001E]; Center for
   Cancer Research; National Eye Institute; Mount Sinai School of Medicine
   [U10 EY 08052]; Johns Hopkins University Bloomberg School of Public
   Health [U10 EY 08057]; University of Wisconsin; Madison School of
   Medicine [U10 EY 08067]; Sidaction; Conservatoire National des Arts et
   Metiers; Neovacs SA; Vaxconsulting
FX This work was supported by Agence Nationale de Recherche sur le SIDA:
   Sidaction: the Conservatoire National des Arts et Metiers: Neovacs SA:
   and Vaxconsulting.; The authors acknowledge funding from the Netherlands
   Organization for Scientific Research (TOP; registration number
   9120.6046). The Amsterdam Cohort Studies on HIVI infection and AIDS, a
   collaboration between the Amsterdam Health Service, the Academic Medical
   Center of the University of Amsterdam, Sanquin Research, and the
   University Medical Center Utrecht, are part of the Netherlands HIV
   Monitoring Foundation and are financially supported by the Netherlands
   National Institute for Public Health and the Environment.; This project
   has been funded in part by federal funds from the National Cancer
   Institute (NCI), National Institutes of Health (NIH) (contract
   HHSN26120080001E) and by the Intramural Research Program of the NIH,
   NCI, Center for Cancer Research. 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.; The
   LSOCA is supported by cooperative agreements from the National Eye
   Institute, NIH, to The Mount Sinai School of Medicine (U10 EY 08052),
   The Johns Hopkins University Bloomberg School of Public Health (U10 EY
   08057), and the University of Wisconsin, Madison School of Medicine (U10
   EY 08067).
NR 41
TC 13
Z9 13
U1 1
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 1
PY 2012
VL 205
IS 7
BP 1155
EP 1162
DI 10.1093/infdis/jis028
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 906OQ
UT WOS:000301356200017
PM 22362864
ER

PT J
AU Traynor, BJ
AF Traynor, Bryan J.
TI Road to the chromosome 9p-linked ALS/FTD locus
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Editorial Material
ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL DEMENTIA; HEXANUCLEOTIDE
   REPEAT; ALS; SUSCEPTIBILITY; C9ORF72; FTD
C1 NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
RI Traynor, Bryan/G-5690-2010
FU Intramural NIH HHS [ZIA AG000933-05]; NIA NIH HHS [Z01 AG000949]
NR 8
TC 6
Z9 6
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD APR
PY 2012
VL 83
IS 4
BP 356
EP 357
DI 10.1136/jnnp-2012-302429
PG 2
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 905TE
UT WOS:000301296600002
PM 22399792
ER

PT J
AU Rothman, RB
   Partilla, JS
   Baumann, MH
   Lightfoot-Siordia, C
   Blough, BE
AF Rothman, Richard B.
   Partilla, John S.
   Baumann, Michael H.
   Lightfoot-Siordia, Catrissa
   Blough, Bruce E.
TI Studies of the Biogenic Amine Transporters. 14. Identification of
   Low-Efficacy "Partial" Substrates for the Biogenic Amine Transporters
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID COUPLED NEUROTRANSMITTER TRANSPORTERS; HUMAN DOPAMINE TRANSPORTER;
   IN-VITRO; MONOAMINE TRANSPORTERS; SEROTONIN TRANSPORTER; UPTAKE
   INHIBITORS; BINDING-SITES; RAT-BRAIN; RELEASE; AMPHETAMINE
AB Several compounds have been identified that display low-efficacy, "partial substrate" activity. Here, we tested the hypothesis that the mechanism of this effect is a slower rate of induced neurotransmitter efflux than that produced by full substrates. Biogenic amine transporter release assays were carried out in rat brain synaptosomes and followed published procedures. [H-3] 1-methyl-4-phenylpyridinium (MPP+) was used to assess release from dopamine (DA) and norepinephrine nerve terminals, whereas [H-3] 5-hydroxytryptamine (5-HT) was used to assess release from 5-HT nerve terminals. A detailed time-course evaluation of DA transporter (DAT)-mediated efflux was conducted by measuring the efflux of [H-3] MPP+ after the addition of various test compounds. In vivo microdialysis experiments compared the effects of the full substrates [(+/-)-1-(2-naphthyl) propan-2-amine (PAL-287) and (S)-N-methyl-1-(2-naphthyl) propan-2-amine (PAL-1046)], to that of a partial DAT/5-HT transporter substrate [(S)-N-ethyl-1-(2-naphthyl) propan-2-amine (PAL-1045)] on extracellular DA and 5-HT in the nucleus accumbens of the rat. The in vitro release assays demonstrated that partial substrate activity occurs at all three transporters. In the DAT efflux experiments, D-amphetamine (full substrate) promoted a fast efflux (K1 = 0.24 min(-1)) and a slow efflux (K2 = 0.008 min(-1)). For the partial DAT substrates, K1 = similar to 0.04 min(-1), and K2 approximated zero. The in vivo microdialysis experiments showed that the partial substrate (PAL-1045) was much less effective in elevating extracellular DA and 5-HT than the comparator full substrates. We conclude that low-efficacy partial DAT substrates promote efflux at a slower rate than full substrates, and "partiality" reflects the ultra-slow K2 constant, which functionally limits the ability of these compounds to increase extracellular DA. We speculate that partial biogenic amine transporter substrates bind to the transporter but are less effective in inducing conformational changes required for reverse transport activity.
C1 [Rothman, Richard B.; Partilla, John S.; Baumann, Michael H.; Lightfoot-Siordia, Catrissa] NIDA, Translat Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Blough, Bruce E.] Res Triangle Inst Int, Life Sci Grp, Res Triangle Pk, NC USA.
RP Rothman, RB (reprint author), NIDA, Translat Pharmacol Sect, Intramural Res Program, NIH, 333 Cassell Dr,Suite 4500, Baltimore, MD 21224 USA.
EM rrothman@mail.nih.gov
NR 31
TC 7
Z9 8
U1 0
U2 0
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 APR
PY 2012
VL 341
IS 1
BP 251
EP 262
DI 10.1124/jpet.111.188946
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 908YX
UT WOS:000301530100026
PM 22271821
ER

PT J
AU Hymes, SR
   Alousi, AM
   Cowen, EW
AF Hymes, Sharon R.
   Alousi, Amin M.
   Cowen, Edward W.
TI Graft-versus-host disease Part I. Pathogenesis and clinical
   manifestations of graft-versus-host disease
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE fasciitis; fibrosis; graft-versus-host disease; hematopoietic cell
   transplantation
ID BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; CONSENSUS DEVELOPMENT
   PROJECT; WORKING GROUP-REPORT; ANTIGEN-PRESENTING CELLS; MINOR
   HISTOCOMPATIBILITY ANTIGENS; TREATMENT-RELATED MORTALITY; TERM
   FOLLOW-UP; B-CELLS; CHRONIC GVHD
AB Approximately 25,000 allogeneic hematopoietic cell transplants are performed worldwide each year for a variety of malignant and non-malignant conditions. Graft-versus-host disease represents one of the most frequent complications and is a major source of long-term morbidity and mortality. Whereas acute graft-versus-host disease is induced by recognition of host tissues as foreign by immunocompetent donor cells, the pathogenesis of chronic graft-versus-host disease is not as well understood, and continues to be a major treatment challenge. Part I of this two-part series reviews the epidemiologic factors, classification, pathogenesis, and clinical manifestations of acute and chronic graft-versus-host disease. Part II discusses the topical, physical, and systemic treatment options available to patients with graft-versus-host disease. (J Am Acad Dermatol 2012;66:515.e1-18.)
C1 [Hymes, Sharon R.] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA.
   [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
   [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hymes, SR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Dermatol, 1515 Holcombe Blvd 434, Houston, TX 77030 USA.
EM srhymes@mdanderson.org
FU National Cancer Institute, Center for Cancer Research
FX Supported in part by the Intramural Research Program of the National
   Cancer Institute, Center for Cancer Research.
NR 117
TC 15
Z9 15
U1 1
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2012
VL 66
IS 4
BP 515
EP 534
DI 10.1016/j.jaad.2011.11.960
PG 20
WC Dermatology
SC Dermatology
GA 907UP
UT WOS:000301444600007
ER

PT J
AU Hymes, SR
   Alousi, AM
   Cowen, EW
AF Hymes, Sharon R.
   Alousi, Amin M.
   Cowen, Edward W.
TI Graft-versus-host disease Part II. Management of cutaneous
   graft-versus-host disease
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE cyclosporine; extracorporeal photopheresis; graft-versus-host disease;
   hematopoietic cell transplantation; imatinib mesylate; mycophenolate
   mofetil; phototherapy; tacrolimus; rituximab
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; REFRACTORY
   CHRONIC GVHD; CONSENSUS DEVELOPMENT PROJECT; RECEPTOR FUSION PROTEIN;
   WORKING GROUP-REPORT; REGULATORY T-CELLS; QUALITY-OF-LIFE;
   CLINICAL-TRIALS; EXTRACORPOREAL PHOTOCHEMOTHERAPY
AB Dermatologists are ideally suited to manage the various cutaneous sequelae of graft-versus-host disease (GVHD) outlined in part I of this review. However, the complexity of the patient with GVHD, including comorbidities, potential drug interactions related to polypharmacy, and the lack of evidence-based treatment guidelines, are significant challenges to optimizing patient care. In this section, we will provide an outline for the role of the dermatologist in a multispecialty approach to caring for patients with GVHD. (J Am Acad Dermatol 2012;66:535.e1-16.)
C1 [Hymes, Sharon R.] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA.
   [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
   [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hymes, SR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Dermatol, 1515 Holcombe Blvd 434, Houston, TX 77030 USA.
EM srhymes@mdanderson.org
FU National Cancer Institute, Center for Cancer Research
FX Supported in part by the Intramural Research Program of the National
   Cancer Institute, Center for Cancer Research.
NR 133
TC 8
Z9 8
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2012
VL 66
IS 4
BP 535
EP 552
DI 10.1016/j.jaad.2011.11.961
PG 18
WC Dermatology
SC Dermatology
GA 907UP
UT WOS:000301444600008
ER

PT J
AU Brubaker, L
   Richter, HE
   Norton, PA
   Albo, M
   Zyczynski, HM
   Chai, TC
   Zimmern, P
   Kraus, S
   Sirls, L
   Kusek, JW
   Stoddard, A
   Tennstedt, S
   Gormley, EA
AF Brubaker, L.
   Richter, H. E.
   Norton, P. A.
   Albo, M.
   Zyczynski, H. M.
   Chai, T. C.
   Zimmern, P.
   Kraus, S.
   Sirls, L.
   Kusek, J. W.
   Stoddard, A.
   Tennstedt, S.
   Gormley, E. Ann
CA Urinary Incontinence Treatment Net
TI 5-Year Continence Rates, Satisfaction and Adverse Events of Burch
   Urethropexy and Fascial Sling Surgery for Urinary Incontinence
SO JOURNAL OF UROLOGY
LA English
DT Article
DE treatment outcome; urinary incontinence, stress; longitudinal studies
ID FREE VAGINAL TAPE; QUALITY-OF-LIFE; STRESS-INCONTINENCE;
   RANDOMIZED-TRIAL; FOLLOW-UP; COLPOSUSPENSION; WOMEN
AB Purpose: We characterized continence, satisfaction and adverse events in women at least 5 years after Burch urethropexy or fascial sling with longitudinal followup of randomized clinical trial participants.
   Materials and Methods: Of 655 women who participated in a randomized surgical trial comparing the efficacy of the Burch and sling treatments 482 (73.6%) enrolled in this long-term observational study. Urinary continence status was assessed yearly for a minimum of 5 years postoperatively. Continence was defined as no urinary leakage on a 3-day voiding diary, and no self-reported stress incontinence symptoms and no stress incontinence surgical re-treatment.
   Results: Incontinent participants were more likely to enroll in the followup study than continent patients (85.5% vs 52.2%) regardless of surgical group (p <0.0001). Overall the continence rates were lower in the Burch urethropexy group than in the fascial sling group (p = 0.002). The continence rates at 5 years were 24.1% (95% CI 18.5 to 29.7) vs 30.8% (95% CI 24.7 to 36.9), respectively. Satisfaction at 5 years was related to continence status and was higher in women undergoing sling surgery (83% vs 73%, p = 0.04). Satisfaction decreased with time (p = 0.001) and remained higher in the sling group (p = 0.03). The 2 groups had similar adverse event rates (Burch 10% vs sling 9%) and similar numbers of participants with adverse events (Burch 23 vs sling 22).
   Conclusions: Continence rates in both groups decreased substantially during 5 years, yet most women reported satisfaction with their continence status. Satisfaction was higher in continent women and in those who underwent fascial sling surgery, despite the voiding dysfunction associated with this procedure.
C1 [Brubaker, L.] Loyola Univ Chicago, Dept Obstet & Gynecol, Stritch Sch Med, Maywood, IL 60153 USA.
   [Brubaker, L.] Loyola Univ Chicago, Dept Urol, Stritch Sch Med, Maywood, IL 60153 USA.
   [Richter, H. E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
   [Norton, P. A.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
   [Albo, M.] Univ Calif San Diego, Div Urol, San Diego, CA 92103 USA.
   [Zyczynski, H. M.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
   [Chai, T. C.] Univ Maryland, Sch Med, Div Urol, Baltimore, MD 21201 USA.
   [Kusek, J. W.] NIDDK, NIH, Bethesda, MD USA.
   [Zimmern, P.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
   [Kraus, S.] Univ Texas San Antonio, Dept Urol, San Antonio, TX USA.
   [Sirls, L.] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA.
   [Stoddard, A.; Tennstedt, S.] New England Res Inst, Watertown, MA 02172 USA.
   [Gormley, E. Ann] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
RP Brubaker, L (reprint author), Loyola Univ Chicago, Dept Obstet & Gynecol, Stritch Sch Med, 2160 S 1st Ave,Bldg 103,Room 1004, Maywood, IL 60153 USA.
EM LBrubaker@lumc.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
   DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01
   DK60380, U01 DK60393, U01 DK60395, U01 DK60397, 60401]; National
   Institute of Child Health and Human Development; Office of Research in
   Women's Health, National Institutes of Health
FX Supported by cooperative agreements from the National Institute of
   Diabetes and Digestive and Kidney Diseases U01 DK58225, U01 DK58229, U01
   DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01
   DK60395, U01 DK60397 and 60401, in conjunction with additional support
   provided by the National Institute of Child Health and Human Development
   and Office of Research in Women's Health, National Institutes of Health
   for all aspects of study including design and conduct of the study, data
   collection, management, analysis and interpretation, as well as
   manuscript preparation, review and approval.
NR 13
TC 24
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 0022-5347
J9 J UROLOGY
JI J. Urol.
PD APR
PY 2012
VL 187
IS 4
BP 1324
EP 1330
DI 10.1016/j.juro.2011.11.087
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 914AY
UT WOS:000301922300059
PM 22341290
ER

PT J
AU Lin, TY
   Dowd, KA
   Manhart, CJ
   Nelson, S
   Whitehead, SS
   Pierson, TC
AF Lin, Tsai-Yu
   Dowd, Kimberly A.
   Manhart, Carolyn J.
   Nelson, Steevenson
   Whitehead, Stephen S.
   Pierson, Theodore C.
TI A Novel Approach for the Rapid Mutagenesis and Directed Evolution of the
   Structural Genes of West Nile Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ANTIBODY-MEDIATED NEUTRALIZATION; FLAVIVIRUS RNA REPLICATION; BORNE
   ENCEPHALITIS-VIRUS; PROTEIN DOMAIN-III; HUMANIZED MONOCLONAL-ANTIBODY;
   ENVELOPE PROTEIN; DENGUE VIRUS; PRM PROTEIN; JAPANESE ENCEPHALITIS;
   REACTIVE EPITOPES
AB Molecular clone technology has proven to be a powerful tool for investigating the life cycle of flaviviruses, their interactions with the host, and vaccine development. Despite the demonstrated utility of existing molecular clone strategies, the feasibility of employing these existing approaches in large-scale mutagenesis studies is limited by the technical challenges of manipulating relatively large molecular clone plasmids that can be quite unstable when propagated in bacteria. We have developed a novel strategy that provides an extremely rapid approach for the introduction of mutations into the structural genes of West Nile virus (WNV). The backbone of this technology is a truncated form of the genome into which DNA fragments harboring the structural genes are ligated and transfected directly into mammalian cells, bypassing entirely the requirement for cloning in bacteria. The transfection of cells with this system results in the rapid release of WNV that achieves a high titer (similar to 10(7) infectious units/ml in 48 h). The suitability of this approach for large-scale mutagenesis efforts was established in two ways. First, we constructed and characterized a library of variants encoding single defined amino acid substitutions at the 92 residues of the "pr" portion of the precursor-to-membrane (prM) protein. Analysis of a subset of these variants identified a mutation that conferred resistance to neutralization by an envelope protein-specific antibody. Second, we employed this approach to accelerate the identification of mutations that allow escape from neutralizing antibodies. Populations of WNV encoding random changes in the E protein were produced in the presence of a potent monoclonal antibody, E16. Viruses resistant to neutralization were identified in a single passage. Together, we have developed a simple and rapid approach to produce infectious WNV that accelerates the process of manipulating the genome to study the structure and function of the structural genes of this important human pathogen.
C1 [Lin, Tsai-Yu; Dowd, Kimberly A.; Manhart, Carolyn J.; Nelson, Steevenson; Pierson, Theodore C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA.
   [Whitehead, Stephen S.] NIH, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Pierson, TC (reprint author), NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bldg 10, Bethesda, MD 20892 USA.
EM piersontc@mail.nih.gov
RI perumal, murugiah/D-1565-2012; Lin, Tsai-Yu/B-8873-2016
OI Lin, Tsai-Yu/0000-0002-8076-1584
FU National Institute of Allergy and Infectious Diseases, NIH
FX This work was funded by the intramural research program of the National
   Institute of Allergy and Infectious Diseases, NIH.
NR 80
TC 11
Z9 11
U1 2
U2 8
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 APR
PY 2012
VL 86
IS 7
BP 3501
EP 3512
DI 10.1128/JVI.06435-11
PG 12
WC Virology
SC Virology
GA 906TV
UT WOS:000301371500010
PM 22258236
ER

PT J
AU Hansman, GS
   Taylor, DW
   McLellan, JS
   Smith, TJ
   Georgiev, I
   Tame, JRH
   Park, SY
   Yamazaki, M
   Gondaira, F
   Miki, M
   Katayama, K
   Murata, K
   Kwong, PD
AF Hansman, Grant S.
   Taylor, David W.
   McLellan, Jason S.
   Smith, Thomas J.
   Georgiev, Ivelin
   Tame, Jeremy R. H.
   Park, Sam-Yong
   Yamazaki, Makoto
   Gondaira, Fumio
   Miki, Motohiro
   Katayama, Kazuhiko
   Murata, Kazuyoshi
   Kwong, Peter D.
TI Structural Basis for Broad Detection of Genogroup II Noroviruses by a
   Monoclonal Antibody That Binds to a Site Occluded in the Viral Particle
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRUS-LIKE PARTICLES; BLOOD GROUP ANTIGENS; NORWALK VIRUS;
   CONFORMATIONAL-CHANGES; CAPSID PROTEIN; MURINE NOROVIRUS; DENGUE VIRUS;
   COMMERCIAL ELISA; MEMBRANE-FUSION; LOW PH
AB Human noroviruses are genetically and antigenically highly divergent. Monoclonal antibodies raised in mice against one kind of norovirus virus-like particle (VLP), however, were found to have broad recognition. In this study, we present the crystal structure of the antigen-binding fragment (Fab) for one of these broadly reactive monoclonal antibodies, 5B18, in complex with the capsid-protruding domain from a genogroup II genotype 10 (GII.10) norovirus at 3.3-angstrom resolution and, also, the cryo-electron microscopy structure of the GII. 10 VLP at similar to 10-angstrom resolution. The GII. 10 VLP structure was more similar in overall architecture to the GV.1 murine norovirus virion than to the prototype GI.1 human norovirus VLP, with the GII. 10 protruding domain raised similar to 15 angstrom off the shell domain and rotated similar to 40 degrees relative to the GI.1 protruding domain. In the crystal structure, the 5B18 Fab bound to a highly conserved region of the protruding domain. Based on the VLP structure, this region is involved in interactions with other regions of the capsid and is buried in the virus particle. Despite the occluded nature of the recognized epitope in the VLP structure, enzyme-linked immunosorbent assay (ELISA) binding suggested that the 5B18 antibody was able to capture intact VLPs. Together, the results provide evidence that the norovirus particle is capable of extreme conformational flexibility, which may allow for antibody recognition of conserved surfaces that would otherwise be buried on intact particles.
C1 [Hansman, Grant S.; McLellan, Jason S.; Georgiev, Ivelin; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Hansman, Grant S.; Miki, Motohiro; Katayama, Kazuhiko] Natl Inst Infect Dis, Dept Virol 2, Tokyo, Japan.
   [Taylor, David W.] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA.
   [Taylor, David W.; Murata, Kazuyoshi] Natl Inst Physiol Sci, Okazaki, Aichi 444, Japan.
   [Smith, Thomas J.] Donald Danforth Plant Sci Ctr, St Louis, MO USA.
   [Tame, Jeremy R. H.; Park, Sam-Yong] Yokohama City Univ, Prot Design Lab, Yokohama, Kanagawa 232, Japan.
   [Yamazaki, Makoto; Gondaira, Fumio; Miki, Motohiro] Denka Seiken Co Ltd, Niigata, Japan.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kazum@nips.ac.jp; pdkwong@nih.gov
RI Hansman, Grant/K-7983-2013; Smith, Thomas/K-9086-2013; 
OI Smith, Thomas/0000-0003-3528-6793; Hansman, Grant/0000-0001-8735-4618;
   Taylor, David/0000-0002-6198-1194
FU National Institutes of Health (NIAID, USA; Ministry of Health, Labor,
   and Welfare of Japan; National Institute of Natural Sciences (NINS),
   Japan; U.S. Department of Energy, Basic Energy Sciences, Office of
   Science [W-31-109-Eng-38]
FX Support for this work was provided by the Intramural Research Program of
   the National Institutes of Health (NIAID [P.D.K.]), USA, and by a
   Grant-in-Aid for Scientific Research, grants from the Ministry of
   Health, Labor, and Welfare of Japan, and a grant from the National
   Institute of Natural Sciences (NINS), Japan (K.M.). D.W.T is an NSF
   Graduate Research Fellow and performed this work in Japan as a JSPS/NSF
   East Asia and Pacific Summer Institute Fellow. Use of Sector 22
   (Southeast Region Collaborative Access team) at the Advanced Photon
   Source was supported by the U.S. Department of Energy, Basic Energy
   Sciences, Office of Science, under contract no. W-31-109-Eng-38.
NR 72
TC 30
Z9 31
U1 0
U2 14
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD APR
PY 2012
VL 86
IS 7
BP 3635
EP 3646
DI 10.1128/JVI.06868-11
PG 12
WC Virology
SC Virology
GA 906TV
UT WOS:000301371500022
PM 22278249
ER

PT J
AU Ferrando-Martinez, S
   Casazza, JP
   Leal, M
   Machmach, K
   Munoz-Fernandez, MA
   Viciana, P
   Koup, RA
   Ruiz-Mateos, E
AF Ferrando-Martinez, Sara
   Casazza, Joseph P.
   Leal, Manuel
   Machmach, Kawthar
   Angeles Munoz-Fernandez, Ma
   Viciana, Pompeyo
   Koup, Richard A.
   Ruiz-Mateos, Ezequiel
TI Differential Gag-Specific Polyfunctional T Cell Maturation Patterns in
   HIV-1 Elite Controllers
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; REPLICATION; INFECTION; MEMORY;
   NONPROGRESSORS; LYMPHOCYTES; PHENOTYPE
AB A small fraction of HIV-infected individuals (<1%), referred to as elite controllers (EC), are able to maintain undetectable viral loads indefinitely without treatment. The role of the maturational phenotype of T cells in the control of HIV infection in these individuals is not well described. We compared the maturational and functional phenotypes of Gag-specific CD4 and CD8 T cells from EC, who maintain undetectable viral loads without treatment; relative controllers (RC), who maintain viral loads of <1,000 copies/ml without treatment; and noncontrollers (NC), who fail to control viral replication. EC maintained higher frequencies of HIV-specific CD4 T cells, less mature polyfunctional Gag-specific CD4 T cells (CD27(+) CD57(-) CD45RO(+)), and Gag-specific polyfunctional CD4 T cells than those observed in NC. In EC, the frequency of polyfunctional Gag-specific CD8 T cells was higher than that observed in RC and NC. RC had a similar functional phenotype to that observed in NC, despite consistently lower viral loads. Finally, we found a direct correlation between the frequency of Gag-specific CD27(+) CD57(+) CD45RO(+) CD4(+) T cells and the frequency of mature HIV-specific CD8 T cells. Altogether, our data suggest that immature Gag-specific interleukin-2 (IL-2)-producing CD4(+) T cells may play an important role in spontaneous control of HIV viremia by effectively supporting HIV-specific CD8 T lymphocytes. This difference appears to differentiate EC from RC.
C1 [Ferrando-Martinez, Sara; Leal, Manuel; Machmach, Kawthar; Ruiz-Mateos, Ezequiel] Hosp Univ Virgen del Rocio, Lab Immunovirol, Infect Dis Serv, Inst Biomed Sevilla IBiS, Seville, Spain.
   [Ferrando-Martinez, Sara; Angeles Munoz-Fernandez, Ma] Hosp Gen Univ Gregorio Maranon, Lab Mol Immunobiol, Madrid, Spain.
   [Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Ruiz-Mateos, E (reprint author), Hosp Univ Virgen del Rocio, Lab Immunovirol, Infect Dis Serv, Inst Biomed Sevilla IBiS, Seville, Spain.
EM ezequiel.ruizmateos@gmail.com
RI Ghartouchent, malek/B-9088-2012; Leal, Manuel/C-8458-2015; Ruiz-Mateos,
   Ezequiel/F-2937-2015; IBIS, INFECCIOSAS/O-1940-2015; IBIS,
   VIH/O-8856-2015; IBIS, INMUNOVIROLOGI/O-9246-2015
OI Ruiz-Mateos, Ezequiel/0000-0001-6747-7813; 
FU Fondo de Investigaciones Sanitarias [CD10/00382, CP08/00172]; Redes
   Tematicas de Investigacion en SIDA [ISCIII RETIC RD06/0006/0035,
   RD06/0006/0021]; CICE [P10-CTS-6313]; Proyecto de Excelencia; Consejeria
   de Salud, SAS [PI-0270, PI-0066, PI0278]; Fondo de Investigacion
   Sanitaria [PS09-00120]; Vaccine Research Center, National Institute of
   Allergy and Infectious Diseases, National Institutes of Health
FX S.F.-M. and E.R.-M. received grants from the Fondo de Investigaciones
   Sanitarias (CD10/00382 and CP08/00172, respectively). This study was
   supported by Redes Tematicas de Investigacion en SIDA (ISCIII RETIC
   RD06/0006/0035 and RD06/0006/0021), Proyecto de Excelencia, CICE
   (P10-CTS-6313), Consejeria de Salud, SAS (PI-0270, PI-0066, and PI0278),
   and Fondo de Investigacion Sanitaria (PS09-00120). This work was funded
   in part by the Intramural Research Program of the Vaccine Research
   Center, National Institute of Allergy and Infectious Diseases, National
   Institutes of Health.
NR 24
TC 18
Z9 19
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2012
VL 86
IS 7
BP 3667
EP 3674
DI 10.1128/JVI.07034-11
PG 8
WC Virology
SC Virology
GA 906TV
UT WOS:000301371500025
PM 22278254
ER

PT J
AU Xiao, S
   Khattar, SK
   Subbiah, M
   Collins, PL
   Samal, SK
AF Xiao, Sa
   Khattar, Sunil K.
   Subbiah, Madhuri
   Collins, Peter L.
   Samal, Siba K.
TI Mutation of the F-Protein Cleavage Site of Avian Paramyxovirus Type 7
   Results in Furin Cleavage, Fusion Promotion, and Increased Replication
   In Vitro but Not Increased Replication, Tissue Tropism, or Virulence in
   Chickens
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NEWCASTLE-DISEASE-VIRUS; COMPLETE GENOME SEQUENCE;
   HEMAGGLUTININ-NEURAMINIDASE PROTEIN; CLONED CDNA; AMINO-ACID; STRAIN;
   EXPRESSION; SEROTYPE; CLEAVABILITY; ACTIVATION
AB We constructed a reverse genetics system for avian paramyxovirus serotype 7 (APMV-7) to investigate the role of the fusion F glycoprotein in tissue tropism and virulence. The AMPV-7 F protein has a single basic residue arginine (R) at position -1 in the F cleavage site sequence and also is unusual in having alanine at position +2 (LPSS (R) under bar down arrow FA) (underlining indicates the basic amino acids at the F protein cleavage site, and the arrow indicates the site of cleavage.). APMV-7 does not form syncytia or plaques in cell culture, but its replication in vitro does not depend on, and is not increased by, added protease. Two mutants were successfully recovered in which the cleavage site was modified to mimic sites that are found in virulent Newcastle disease virus isolates and to contain 4 or 5 basic residues as well as isoleucine in the +2 position: ((RR) under barQ (KR) under bar down arrow FI) or ((RRKKR) under bar down arrow FI), named Fcs-4B or Fcs-5B, respectively. In cell culture, one of the mutants, Fcs-5B, formed protease-independent syncytia and grew to 10-fold-higher titers compared to the parent and Fcs-4B viruses. This indicated the importance of the single additional basic residue (K) at position -3. Syncytium formation and virus yield of the Fcs-5B virus was impaired by the furin inhibitor decanoyl-RVKR-CMK, whereas parental APMV-7 was not affected. APMV-7 is avirulent in chickens and is limited in tropism to the upper respiratory tract of 1-day-old and 2-week-old chickens, and these characteristics were unchanged for the two mutant viruses. Thus, the acquisition of furin cleavability by APMV-7 resulted in syncytium formation and increased virus yield in vitro but did not alter virus yield, tropism, or virulence in chickens.
C1 [Xiao, Sa; Khattar, Sunil K.; Subbiah, Madhuri; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
   [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, 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 for his technical assistance. We thank Flavia
   Dias and Sachin Kumar for his help with handling of chickens during the
   animal experiments. The pTM-1 vector and MVA/T7 vaccinia virus
   recombinant were kindly provided by Bernard Moss, NIAID. This research
   was supported by NIAID contract no. N01A060009 (85% support) and NIAID,
   NIH Intramural Research Program (15% support).
NR 42
TC 8
Z9 8
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2012
VL 86
IS 7
BP 3828
EP 3838
DI 10.1128/JVI.06765-11
PG 11
WC Virology
SC Virology
GA 906TV
UT WOS:000301371500040
PM 22258248
ER

PT J
AU Lee, K
   Mulky, A
   Yuen, W
   Martin, TD
   Meyerson, NR
   Choi, L
   Yu, H
   Sawyer, SL
   KewalRamani, VN
AF Lee, KyeongEun
   Mulky, Alok
   Yuen, Wendy
   Martin, Thomas D.
   Meyerson, Nicholas R.
   Choi, Laura
   Yu, Hyun
   Sawyer, Sara L.
   KewalRamani, Vineet N.
TI HIV-1 Capsid-Targeting Domain of Cleavage and Polyadenylation
   Specificity Factor 6
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA VIRUSES; FACTOR-I-M;
   REVERSE TRANSCRIPTION; RETROVIRUS RESTRICTION; POSITIVE SELECTION;
   NUCLEAR IMPORT; INFECTION; PROTEIN; CELLS
AB The antiviral factor CPSF6-358 restricts human immunodeficiency virus type 1 (HIV-1) infection through an interaction with capsid (CA), preventing virus nuclear entry and integration. HIV-1 acquires resistance to CPSF6-358 through an N74D mutation of CA that impairs binding of the antiviral factor. Here we examined the determinants within CPSF6-358 that are necessary for CA-specific interaction. Residues 314 to 322 include amino acids that are essential for CPSF6-358 restriction of HIV-1. Fusion of CPSF6 residues 301 to 358 to rhesus TRIM5 alpha is also sufficient to restrict wild-type but not N74D HIV-1. Restriction is lost if CPSF6 residues in the amino acid 314 to 322 interaction motif are mutated. Examination of the CA targeting motif in CPSF6-358 did not reveal evidence of positive selection. Given the sensitivity of different primate lentiviruses to CPSF6-358 and apparent conservation of this interaction, our data suggest that CPSF6-358-mediated targeting of HIV-1 could provide a broadly effective antiviral strategy.
C1 [Lee, KyeongEun; Mulky, Alok; Yuen, Wendy; Martin, Thomas D.; Choi, Laura; Yu, Hyun; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
   [Yuen, Wendy] SAIC Frederick, Basic Sci Program, Frederick, MD USA.
   [Meyerson, Nicholas R.; Sawyer, Sara L.] Univ Texas Austin, Sect Mol Genet & Microbiol, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
RP KewalRamani, VN (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM vineet@mail.nih.gov
RI Ghartouchent, malek/B-9088-2012
FU National Cancer Institute's intramural Center for Cancer Research;
   National Science Foundation
FX This work was supported by the National Cancer Institute's intramural
   Center for Cancer Research, which supports the HIV Drug Resistance
   Program (V.N.K.). N.R.M. is supported by a National Science Foundation
   graduate research fellowship.
NR 41
TC 31
Z9 31
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 APR
PY 2012
VL 86
IS 7
BP 3851
EP 3860
DI 10.1128/JVI.06607-11
PG 10
WC Virology
SC Virology
GA 906TV
UT WOS:000301371500042
PM 22301135
ER

PT J
AU Iijima, S
   Lee, YJ
   Ode, H
   Arold, ST
   Kimura, N
   Yokoyama, M
   Sato, H
   Tanaka, Y
   Strebel, K
   Akari, H
AF Iijima, Sayuki
   Lee, Young-Jung
   Ode, Hirotaka
   Arold, Stefan T.
   Kimura, Nobuyuki
   Yokoyama, Masaru
   Sato, Hironori
   Tanaka, Yasuhito
   Strebel, Klaus
   Akari, Hirofumi
TI A Noncanonical mu-1A-Binding Motif in the N Terminus of HIV-1 Nef
   Determines Its Ability To Downregulate Major Histocompatibility Complex
   Class I in T Lymphocytes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MU-SUBUNIT; VIRION INCORPORATION;
   MOLECULAR-MECHANICS; VIRAL INFECTIVITY; CYTOPLASMIC TAIL; PROTEIN BINDS;
   FREE-ENERGY; AP-1; MHC
AB Downregulation of major histocompatibility complex class I (MHC-I) by HIV-1 Nef protein is indispensable for evasion of protective immunity by HIV-1. Though it has been suggested that the N-terminal region of Nef contributes to the function by associating with a mu-1A subunit of adaptor protein 1, the structural basis of the interaction between Nef and mu-1A remains elusive. We found that a tripartite hydrophobic motif (Trp13/Val16/Met20) in the N terminus of Nef was required for the MHC-I downregulation. Importantly, the motif functioned as a noncanonical mu-1A-binding motif for the interaction with the tyrosine motif-binding site of the mu-1A subunit. Our findings will help understanding of how HIV-1 evades the antiviral immune response by selectively redirecting the cellular protein trafficking system.
C1 [Iijima, Sayuki; Lee, Young-Jung; Kimura, Nobuyuki; Akari, Hirofumi] Natl Inst Biomed Innovat, Tsukuba Primate Res Ctr, Lab Dis Control, Tsukuba, Ibaraki, Japan.
   [Iijima, Sayuki; Tanaka, Yasuhito] Nagoya City Univ, Grad Sch Med Sci, Dept Virol, Liver Unit,Mizuho Ku, Nagoya, Aichi, Japan.
   [Arold, Stefan T.] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Ode, Hirotaka; Yokoyama, Masaru; Sato, Hironori] Natl Inst Infect Dis, Pathogen Genom Ctr, Tokyo, Japan.
   [Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
   [Akari, Hirofumi] Kyoto Univ, Primate Res Inst, Inuyama, Aichi 484, Japan.
RP Akari, H (reprint author), Natl Inst Biomed Innovat, Tsukuba Primate Res Ctr, Lab Dis Control, Tsukuba, Ibaraki, Japan.
EM akari@pri.kyoto-u.ac.jp
RI Ghartouchent, malek/B-9088-2012; 
OI Arold, Stefan T/0000-0001-5278-0668
FU Ministry of Health, Labor and Welfare; Japan Health Sciences Foundation
FX This work was supported by grants-in-aid from the Ministry of Health,
   Labor and Welfare. S.I. was supported by a postdoctoral fellowship from
   the Japan Health Sciences Foundation.
NR 52
TC 6
Z9 6
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 APR
PY 2012
VL 86
IS 7
BP 3944
EP 3951
DI 10.1128/JVI.06257-11
PG 8
WC Virology
SC Virology
GA 906TV
UT WOS:000301371500050
PM 22301137
ER

PT J
AU Mendoza, D
   Royce, C
   Ruff, LE
   Ambrozak, DR
   Quigley, MF
   Dang, T
   Venturi, V
   Price, DA
   Douek, DC
   Migueles, SA
   Connors, M
AF Mendoza, Daniel
   Royce, Cassandra
   Ruff, Laura E.
   Ambrozak, David R.
   Quigley, Maire F.
   Dang, Thurston
   Venturi, Vanessa
   Price, David A.
   Douek, Daniel C.
   Migueles, Stephen A.
   Connors, Mark
TI HLA B(star)5701-Positive Long-Term Nonprogressors/Elite Controllers Are
   Not Distinguished from Progressors by the Clonal Composition of
   HIV-Specific CD8(+) T Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ELITE SUPPRESSORS; TCR REPERTOIRE; IMMUNE
   CONTROL; GENE USAGE; INFECTION; REPLICATION; RESPONSES; ESCAPE;
   RECOGNITION
AB To better understand the qualitative features of effective human immunodeficiency virus (HIV)-specific immunity, we examined the TCR clonal composition of CD8(+) T cells recognizing conserved HIV p24-derived epitopes in HLA-B(star)5701-positive long-term nonprogressors/elite controllers (LTNP/EC) and HLA-matched progressors. Both groups displayed oligoclonal HLA-B5701-restricted p24-specific CD8(+) T-cell responses with similar levels of diversity and few public clonotypes. Thus, HIV-specific CD8(+)T-cell responses in LTNP/EC are not differentiated from those of progressors on the basis of clonal diversity or TCR sharing.
C1 [Mendoza, Daniel; Royce, Cassandra; Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Ruff, Laura E.; Ambrozak, David R.; Quigley, Maire F.; Price, David A.; Douek, Daniel C.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Quigley, Maire F.; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff, S Glam, Wales.
   [Dang, Thurston; Venturi, Vanessa] Univ New S Wales, Computat Biol Grp, Ctr Vasc Res, Kensington, NSW 2033, Australia.
RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
RI Ghartouchent, malek/B-9088-2012; Price, David/C-7876-2013; 
OI Price, David/0000-0001-9416-2737; Mendoza, Daniel/0000-0002-6362-0771
FU National Institute of Allergy and Infectious Disease, NIH
FX This research was supported by the Intramural Research Program of the
   National Institute of Allergy and Infectious Disease, NIH.
NR 44
TC 17
Z9 17
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2012
VL 86
IS 7
BP 4014
EP 4018
DI 10.1128/JVI.06982-11
PG 5
WC Virology
SC Virology
GA 906TV
UT WOS:000301371500057
PM 22278241
ER

PT J
AU Amlin-Van Schaick, J
   Kim, S
   Broman, KW
   Reilly, KM
AF Amlin-Van Schaick, Jessica
   Kim, Sungjin
   Broman, Karl W.
   Reilly, Karlyne M.
TI Scram1 is a modifier of spinal cord resistance for astrocytoma on mouse
   Chr 5
SO MAMMALIAN GENOME
LA English
DT Article
ID CANCER; GLIOMA; ERYTHROPOIETIN; SUSCEPTIBILITY; INVASIVENESS; RECEPTOR;
   GROWTH; MUTANT; TUMORS; LOCUS
AB Tumor location can profoundly affect morbidity and patient prognosis, even for the same tumor type. Very little is known about whether tumor location is determined stochastically or whether genetic risk factors can affect where tumors arise within an organ system. We have taken advantage of the Nf1-/+;Trp53-/+cis mouse model of astrocytoma/glioblastoma to map genetic loci affecting whether astrocytomas are found in the spinal cord. We identify a locus on distal Chr 5, termed Scram1 for spinal cord resistance to astrocytoma modifier 1, with a LOD score of 5.0 and a genome-wide significance of P < 0.004. Mice heterozygous for C57BL/6Jx129S4/SvJae at this locus show less astrocytoma in the spinal cord compared to 129S4/SvJae homozygous mice, although we have shown previously that 129S4/SvJae mice are more resistant to astrocytoma than C57BL/6J. Furthermore, the astrocytomas that are found in the spinal cord of Scram1 heterozygous mice arise in older mice. Because spinal cord astrocytomas are very rare and difficult to treat, a better understanding of the genetic factors that govern astrocytoma in the spine may lead to new targets of therapy or prevention.
C1 [Amlin-Van Schaick, Jessica; Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
   [Amlin-Van Schaick, Jessica] George Washington Univ, Inst Biomed Sci, Washington, DC 20037 USA.
   [Kim, Sungjin; Broman, Karl W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53706 USA.
RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, W 7th St,Ft Detrick,POB B, Frederick, MD 21702 USA.
EM ReillyK@mail.nih.gov
OI Broman, Karl/0000-0002-4914-6671
FU National Institutes of Health, National Cancer Institute [ZIA BC
   010539]; National Cancer Institute [N01-CO-12400]; National Institutes
   of Health [HHSN268200782096C, R01 GM074244]
FX We thank M. Anvers, R. Tuskan, K. Smith, K. Fox, and E. Truffer for
   technical assistance and D. Louis and G. Jallo for helpful discussions.
   JCAVS is a predoctoral student in the Graduate Partnership Program of
   the NIH and the Institute for Biomedical Sciences at George Washington
   University. This work is from a dissertation to be prepared in partial
   fulfillment of the requirements for the PhD degree. 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 endorsements by the
   US Government. This work was funded by the Intramural Research Program
   of the National Institutes of Health, National Cancer Institute (ZIA BC
   010539 to KMR), federal funds from the National Cancer Institute to SAIC
   Frederick (contract N01-CO-12400), federal contract from the National
   Institutes of Health to The Johns Hopkins University (contract
   HHSN268200782096C), and extramural funding from the National Institutes
   of Health (R01 GM074244 to KWB).
NR 31
TC 7
Z9 7
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
J9 MAMM GENOME
JI Mamm. Genome
PD APR
PY 2012
VL 23
IS 3-4
BP 277
EP 285
DI 10.1007/s00335-011-9380-0
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
GA 905VP
UT WOS:000301304600006
PM 22160242
ER

PT J
AU Gredilla, R
   Weissman, L
   Yang, JL
   Bohr, VA
   Stevnsner, T
AF Gredilla, Ricardo
   Weissman, Lior
   Yang, Jenq-Lin
   Bohr, Vilhelm A.
   Stevnsner, Tinna
TI Mitochondrial base excision repair in mouse synaptosomes during normal
   aging and in a model of Alzheimer's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE DNA repair; Mitochondria; Synaptic dysfunction; Neurodegeneration
ID DNA-POLYMERASE-GAMMA; TRIPLE-TRANSGENIC MODEL; RAT-BRAIN; SYNAPTIC
   MITOCHONDRIA; AXONAL-TRANSPORT; OXIDATIVE STRESS; CALORIC RESTRICTION;
   AGED BRAIN; DAMAGE; NEURONS
AB Brain aging is associated with synaptic decline and synaptic function is highly dependent on mitochondria. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of several neurodegenerative diseases. Here we have investigated the repair of oxidative base damage, in synaptosomes of mouse brain during normal aging and in an AD model. During normal aging, a reduction in the base excision repair (BER) capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of presymptomatic and symptomatic AD mice harboring mutated amyolid precursor protein (APP), Tau, and presinilin-1 (PS1) (3xTgAD). Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Gredilla, Ricardo; Stevnsner, Tinna] Univ Aarhus, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark.
   [Gredilla, Ricardo; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark.
   [Weissman, Lior; Yang, Jenq-Lin; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
   [Yang, Jenq-Lin] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
RP Stevnsner, T (reprint author), Univ Aarhus, Danish Ctr Mol Gerontol, CF Moellers Alle 3,Bldg 1130, DK-8000 Aarhus C, Denmark.
EM tvs@mb.au.dk
OI Yang, Jenq-Lin/0000-0002-9897-8087
FU European Commission [LSHM-CT-2004-512020]; Lundbeck Foundation
   [4-55951-95094019]; Danish Research Council [271-08-0697]; Danish Aging
   Research Center; National Institute on Aging, NIH
FX This research was supported by grants from the European Commission
   (LSHM-CT-2004-512020), Lundbeck Foundation (4-55951-95094019), The
   Danish Research Council (271-08-0697), and The Danish Aging Research
   Center to TS. This research was also supported by funds from the
   intramural program of the National Institute on Aging, NIH.
NR 64
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 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD APR
PY 2012
VL 33
IS 4
BP 694
EP 707
DI 10.1016/j.neurobiolaging.2010.06.019
PG 14
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 908RC
UT WOS:000301506800007
PM 20708822
ER

PT J
AU Beydoun, MA
   Boueiz, A
   Abougergi, MS
   Kitner-Triolo, MH
   Beydoun, HA
   Resnick, SM
   O'Brien, R
   Zonderman, AB
AF Beydoun, May A.
   Boueiz, Adel
   Abougergi, Marwan S.
   Kitner-Triolo, Melissa H.
   Beydoun, Hind A.
   Resnick, Susan M.
   O'Brien, Richard
   Zonderman, Alan B.
TI Sex differences in the association of the apolipoprotein E epsilon 4
   allele with incidence of dementia, cognitive impairment, and decline
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Apolipoprotein E genotype; Dementia; Cognitive decline; Cognitive
   impairment; Aging
ID DWELLING ELDERLY INDIVIDUALS; ALZHEIMERS-DISEASE; E GENOTYPE; APOE
   GENOTYPE; OLDER-ADULTS; POPULATION-SAMPLE; EPISODIC MEMORY; HEALTH; AGE;
   APOE-EPSILON-4
AB We examined longitudinal associations between the apolipoprotein E epsilon 4 allele (ApoE4(+) status) and several cognitive outcomes and tested effect modification by sex. Data on 644 non-Hispanic Caucasian adults, from the Baltimore Longitudinal Study of Aging (BLSA) were used. Dementia onset, cognitive impairment and decline were assessed longitudinally. After 27.5 years median follow-up, 113 participants developed dementia. ApoE4(+) predicted dementia significantly (hazard ratio [HR] = 2.89; 95% confidence interval [CI], 1.93-4.33), with nonsignificant sex differences. Taking all time points for predicting cognition, women had significantly stronger positive associations than men between ApoE4(+) status and impairment or decline on the California Verbal Learning Test (CVLT; delayed recall and List A total recall) and on Verbal Fluency Test-Categories. This ApoE4 x sex interaction remained significant with Bonferroni correction only for CVLT-delayed recall. Taking time points prior to dementia for cognitive predictions, the positive association between impairment in CVLT-delayed recall and ApoE4(+) status remained stronger among women, though only before Bonferroni correction. While ApoE4+ status appears to be a sex neutral risk factor for dementia, its association with verbal memory and learning decline and impairment was stronger among women. Published by Elsevier Inc.
C1 [Beydoun, May A.] NIA, NIH, Biomed Res Ctr, IRP, Baltimore, MD 21224 USA.
   [Boueiz, Adel; Abougergi, Marwan S.] Johns Hopkins Univ, Sch Med, Dept Internal Med, Baltimore, MD USA.
   [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
   [O'Brien, Richard] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
RP Beydoun, MA (reprint author), NIA, NIH, Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU NIH; National Institute on Aging
FX We thank Larry Brant and Vonetta Dotson (Laboratory of Personality and
   Cognition, NIA/NIH/IRP) for internally reviewing our manuscript. We also
   thank Bethrand Ugwu (Eastern Virginia Medical School, Norfolk, VA) for
   his assistance with literature search and review. This research was
   supported entirely by the Intramural Research Program of the NIH,
   National Institute on Aging.
NR 70
TC 18
Z9 18
U1 0
U2 4
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 APR
PY 2012
VL 33
IS 4
AR 720
DI 10.1016/j.neurobiolaging.2010.05.017
PG 16
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 908RC
UT WOS:000301506800009
PM 20619505
ER

PT J
AU Hafsteinsdottir, SH
   Eiriksdottir, G
   Sigurdsson, S
   Aspelund, T
   Harris, TB
   Launer, LJ
   Gudnason, V
AF Hafsteinsdottir, Sigridur Harpa
   Eiriksdottir, Gudny
   Sigurdsson, Sigurdur
   Aspelund, Thor
   Harris, Tamara B.
   Launer, Lenore J.
   Gudnason, Vilmundur
TI Brain tissue volumes by APOE genotype and leisure activity-the
   AGES-Reykjavik Study
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE APOE; Leisure activities; Brain volumes; MRI; AGES-Reykjavik study
ID APOLIPOPROTEIN-E EPSILON-4; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME;
   COGNITIVE FUNCTION; LIFE-SPAN; DEMENTIA; ATROPHY; ALLELE; DECLINE; RISK
AB This study investigates the association of the APOE epsilon 4 allele and leisure activity with brain tissue volumes, including white matter hyperintensities (WMH), in a population- based cohort of 4303 nondemented individuals, aged 66-96 years. APOE epsilon 4 carriers were shown to have greater WMH and cerebrospinal fluid (CSF) volumes than noncarriers but smaller gray matter (GM) volumes. There was no significant difference in white matter (WM) and total brain parenchymal (TBP) volumes between APOE epsilon 4 carriers and noncarriers. Tests for linear trend showed that individuals with lower leisure activity levels had greater WMH and CSF volumes, smaller TBP, WM and GM volumes than those with the highest levels of participation. The significant positive trend of the leisure activity with the brain tissue volumes was observed in the APOE epsilon 4 carriers as well as in noncarriers after adjustment for demographic and health factors. These cross-sectional data suggest leisure activity is associated with tissue volumes in the brain irrespective of the APOE epsilon 4 risk allele status. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Hafsteinsdottir, Sigridur Harpa; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
   [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
   [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Hafsteinsdottir, SH (reprint author), Hjartavernd Iceland Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland.
EM sigridur@hjarta.is
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
   Vilmundur/0000-0001-5696-0084
FU NIH [N01-AG-12100]; NIA; Icelandic Heart Association; Icelandic
   Parliament
FX The Age, Gene/Environment Susceptibility-Reykjavik Study is funded by
   NIH contract N01-AG-12100, the NIA Intramural Research Program,
   Hjartavernd (the Icelandic Heart Association), and Althingi (the
   Icelandic Parliament).
NR 44
TC 1
Z9 1
U1 4
U2 10
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 APR
PY 2012
VL 33
IS 4
AR 829.e1
DI 10.1016/j.neurobiolaging.2011.06.028
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 908RC
UT WOS:000301506800031
PM 21856047
ER

PT J
AU Langbaum, JBS
   Chen, KW
   Launer, LJ
   Fleisher, AS
   Lee, W
   Liu, XF
   Protas, HD
   Reeder, SA
   Bandy, D
   Yu, MX
   Caselli, RJ
   Reiman, EM
AF Langbaum, Jessica B. S.
   Chen, Kewei
   Launer, Lenore J.
   Fleisher, Adam S.
   Lee, Wendy
   Liu, Xiaofen
   Protas, Hillary D.
   Reeder, Stephanie A.
   Bandy, Daniel
   Yu, Meixiang
   Caselli, Richard J.
   Reiman, Eric M.
TI Blood pressure is associated with higher brain amyloid burden and lower
   glucose metabolism in healthy late middle-age persons
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE APOE; Blood pressure; Arterial stiffness; Brain imaging; PET;
   Alzheimer's disease; Amyloid; PiB; Pittsburgh Compound-B
ID ANTIHYPERTENSIVE-MEDICATION-USE; NEUROFIBRILLARY TANGLES NFT; INCIDENT
   ALZHEIMER-DISEASE; APOLIPOPROTEIN-E; NONDEMENTED INDIVIDUALS; COGNITIVE
   IMPAIRMENT; COMMUNITY POPULATION; KUNGSHOLMEN PROJECT; HIPPOCAMPAL
   ATROPHY; PROSPECTIVE COHORT
AB Epidemiological studies suggest that elevated blood pressure (BP) in midlife is associated with increased risk of Alzheimer's disease (AD) in late life. In this preliminary study, we investigated the extent to which BP measurements are related to positron emission tomography (PET) measurements of fibrillar amyloid-beta burden using Pittsburgh Compound-B (PiB) and fluorodeoxyglucose (FDG) PET measures of cerebral metabolic rate for glucose metabolism (CMRgl) in cognitively normal, late middle-aged to older adult apolipoprotein E (APOE) epsilon 4 homozygotes, heterozygotes and noncarriers. PiB PET results revealed that systolic BP (SBP) and pulse pressure (PP) were each positively correlated with cerebral-to-cerebellar PiB distribution volume ratio (DVR) in frontal, temporal, and posterior-cingulate/precuneus regions, whereas no significant positive correlations were found between PiB distribution volume ratios and diastolic BP (DBP). FDG PET results revealed significant inverse correlations between each of the BP measures and lower glucose metabolism in frontal and temporal brain regions. These preliminary findings provide additional evidence that higher BP, likely a reflection of arterial stiffness, during late midlife may be associated with increased risk of presymptomatic AD. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Langbaum, Jessica B. S.; Chen, Kewei; Fleisher, Adam S.; Lee, Wendy; Liu, Xiaofen; Protas, Hillary D.; Reeder, Stephanie A.; Bandy, Daniel; Yu, Meixiang; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ 85006 USA.
   [Langbaum, Jessica B. S.; Chen, Kewei; Fleisher, Adam S.; Lee, Wendy; Liu, Xiaofen; Protas, Hillary D.; Reeder, Stephanie A.; Bandy, Daniel; Caselli, Richard J.; Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA.
   [Chen, Kewei] Arizona State Univ, Sch Math & Stat Sci, Tempe, AZ USA.
   [Launer, Lenore J.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA.
   [Fleisher, Adam S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Caselli, Richard J.] Mayo Clin Arizona, Dept Neurol, Scottsdale, AZ USA.
   [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Tucson, AZ USA.
   [Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA.
RP Langbaum, JBS (reprint author), Banner Alzheimers Inst, 901 E Willetta St, Phoenix, AZ 85006 USA.
EM jessica.langbaum@bannerhealth.com
RI Chen, kewei/P-6304-2015
OI Chen, kewei/0000-0001-8497-3069
FU National Institute of Mental Health [R01MH57899]; National Institute on
   Aging [R01AG031581, P30AG19610]; state of Arizona; NIH, National
   Institute on Aging
FX This work was supported by the National Institute of Mental Health
   (R01MH57899 [EMR]), the National Institute on Aging (R01AG031581 and
   P30AG19610 [EMR]), the state of Arizona (EMR, RJC, KC), and
   contributions from the Banner Alzheimer's Foundation and Mayo Clinic
   Foundation. This research was supported in part by the Intramural
   Research Program of the NIH, National Institute on Aging. We thank Cole
   Reschke, Jennifer Keppler, and Anita Prouty for their assistance.
NR 62
TC 3
Z9 4
U1 1
U2 6
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 APR
PY 2012
VL 33
IS 4
AR 827.e11
DI 10.1016/j.neurobiolaging.2011.06.020
PG 9
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 908RC
UT WOS:000301506800027
PM 21821316
ER

PT J
AU Rothman, SM
   Herdener, N
   Camandola, S
   Texel, SJ
   Mughal, MR
   Cong, WN
   Martin, B
   Mattson, MP
AF Rothman, Sarah M.
   Herdener, Nathan
   Camandola, Simonetta
   Texel, Sarah J.
   Mughal, Mohamed R.
   Cong, Wei-Na
   Martin, Bronwen
   Mattson, Mark P.
TI 3xTgAD mice exhibit altered behavior and elevated A beta after chronic
   mild social stress
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; Amyloid oligomers; Psychosocial stress;
   Corticosterone; Hippocampus; BDNF
ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENOCORTICAL AXIS; CHRONIC
   PSYCHOSOCIAL STRESS; AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL;
   HIGH-FAT DIET; ALZHEIMERS-DISEASE; GLUCOCORTICOID-RECEPTOR; NEUROTROPHIC
   FACTOR; PREFRONTAL CORTEX
AB Chronic stress may be a risk factor for developing Alzheimer's disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety, and hippocampal amyloid beta-particle (A beta), phosphorylated tau (ptau), and brain-derived neurotrophic factor (BDNF) levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6-week stress period 3xTgAD mice displayed increased anxiety, elevated levels of A beta oligomers and intraneuronal A beta, and decreased brain-derived neurotrophic factor levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates A beta accumulation and impairs neurotrophic signaling. Published by Elsevier Inc.
C1 [Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Cong, Wei-Na; Martin, Bronwen] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Lab Neurosci, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging
FX The authors thank Dr. Henriette van Praag for the use of imaging
   equipment and Catherine Crews for assistance with maintenance for the in
   vivo portion of the study. This research was supported by the Intramural
   Research Program of the National Institute on Aging.
NR 94
TC 8
Z9 9
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD APR
PY 2012
VL 33
IS 4
AR 830.e1
DI 10.1016/j.neurobiolaging.2011.07.005
PG 12
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 908RC
UT WOS:000301506800034
PM 21855175
ER

PT J
AU Baumann, MH
   Ayestas, MA
   Partilla, JS
   Sink, JR
   Shulgin, AT
   Daley, PF
   Brandt, SD
   Rothman, RB
   Ruoho, AE
   Cozzi, NV
AF Baumann, Michael H.
   Ayestas, Mario A., Jr.
   Partilla, John S.
   Sink, Jacqueline R.
   Shulgin, Alexander T.
   Daley, Paul F.
   Brandt, Simon D.
   Rothman, Richard B.
   Ruoho, Arnold E.
   Cozzi, Nicholas V.
TI The Designer Methcathinone Analogs, Mephedrone and Methylone, are
   Substrates for Monoamine Transporters in Brain Tissue
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE dopamine; MDMA; mesolimbic; microdialysis; serotonin (5-HT);
   transporters
ID RAT-BRAIN; 4-METHYLMETHCATHINONE MEPHEDRONE; MDMA; SEROTONIN; DOPAMINE;
   ABUSE; DRUG; CATHINONE; TOXICITY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE
AB The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study. Neuropsychopharmacology (2012) 37, 1192-1203; doi:10.1038/npp.2011.304; published online 14 December 2011
C1 [Baumann, Michael H.; Ayestas, Mario A., Jr.; Partilla, John S.; Sink, Jacqueline R.; Rothman, Richard B.] Natl Inst Drug Abuse, Translat Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Shulgin, Alexander T.; Daley, Paul F.] Alexander Shulgin Res Inst, Lafayette, CA USA.
   [Brandt, Simon D.] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 5UX, Merseyside, England.
   [Ruoho, Arnold E.] Univ Wisconsin, Dept Neurosci, Sch Med & Publ Hlth, Madison, WI USA.
   [Ruoho, Arnold E.] Univ Wisconsin, UW Eye Res Inst, Sch Med & Publ Hlth, Madison, WI USA.
   [Cozzi, Nicholas V.] Univ Wisconsin, Dept Cell & Regenerat Biol, Sch Med & Publ Hlth, Neuropharmacol Lab, Madison, WI USA.
RP Baumann, MH (reprint author), Natl Inst Drug Abuse, Translat Pharmacol Sect, Intramural Res Program, NIH, 333 Cassell Dr,Suite 4500, Baltimore, MD 21224 USA.
EM mbaumann@mail.nih.gov
OI Brandt, Simon/0000-0001-8632-5372
FU National Institute on Drug Abuse (NIDA) [DA017675, DA027191]; Retina
   Research Foundation/UW Eye Research Institute
FX This work was generously supported by the National Institute on Drug
   Abuse (NIDA), Intramural Research Program (MHB, MAA, JSP, JRS and RBR),
   NIDA Grants DA017675 (NVC) and DA027191 (AER), and the Retina Research
   Foundation/UW Eye Research Institute Edwin and Dorothy Gamewell
   Professorship (AER). We thank Ava Cozzi and Lisa Ehrlicher for helpful
   discussions.
NR 44
TC 158
Z9 161
U1 5
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD APR
PY 2012
VL 37
IS 5
BP 1192
EP 1203
DI 10.1038/npp.2011.304
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 909YD
UT WOS:000301602400013
PM 22169943
ER

PT J
AU Tuncbag, N
   Keskin, O
   Nussinov, R
   Gursoy, A
AF Tuncbag, Nurcan
   Keskin, Ozlem
   Nussinov, Ruth
   Gursoy, Attila
TI Fast and accurate modeling of protein-protein interactions by combining
   template-interface-based docking with flexible refinement
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE template-based docking; flexible refinement; 3D modeling; protein
   interaction prediction
ID INTERACTION NETWORKS; STRUCTURAL MOTIFS; PREDICTION; DATABASE;
   PRINCIPLES; COMPLEXES; SEQUENCE; IDENTIFICATION; ARCHITECTURES;
   SIMILARITIES
AB The similarity between folding and binding led us to posit the concept that the number of proteinprotein interface motifs in nature is limited, and interacting protein pairs can use similar interface architectures repeatedly, even if their global folds completely vary. Thus, known proteinprotein interface architectures can be used to model the complexes between two target proteins on the proteome scale, even if their global structures differ. This powerful concept is combined with a flexible refinement and global energy assessment tool. The accuracy of the method is highly dependent on the structural diversity of the interface architectures in the template dataset. Here, we validate this knowledge-based combinatorial method on the Docking Benchmark and show that it efficiently finds high-quality models for benchmark complexes and their binding regions even in the absence of template interfaces having sequence similarity to the targets. Compared to classical docking, it is computationally faster; as the number of target proteins increases, the difference becomes more dramatic. Further, it is able to distinguish binders from nonbinders. These features allow performing large-scale network modeling. The results on an independent target set (proteins in the p53 molecular interaction map) show that current method can be used to predict whether a given protein pair interacts. Overall, while constrained by the diversity of the template set, this approach efficiently produces high-quality models of proteinprotein complexes. We expect that with the growing number of known interface architectures, this type of knowledge-based methods will be increasingly used by the broad proteomics community. Proteins 2012; (c) 2011 Wiley Periodicals, Inc.
C1 [Tuncbag, Nurcan; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Coll Engn, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey.
   [Nussinov, Ruth] SAIC Frederick Inc, NCI Frederick, Basic Sci Program,Nanobiol Program, Ctr Canc Res, Frederick, MD 21702 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Keskin, O (reprint author), Koc Univ, Coll Engn, Ctr Computat Biol & Bioinformat, Rumelifeneri Yolu, TR-34450 Istanbul, Turkey.
EM okeskin@ku.edu.tr; agursoy@ku.edu.tr
RI Tuncbag, Nurcan/D-3383-2011; Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU TUBITAK [109T343, 109E207]; Turkish Academy of Sciences; NIH, National
   Cancer Institute, Center for Cancer Research; National Cancer Institute,
   National Institutes of Health [HHSN261200800001E]
FX Grant sponsor: TUBITAK; Grant numbers: 109T343 and 109E207; Grant
   sponsor: Turkish Academy of Sciences; Grant sponsors: Intramural
   Research Program of the NIH, National Cancer Institute, Center for
   Cancer Research, Federal Funds from National Cancer Institute, National
   Institutes of Health; Grant number: HHSN261200800001E.
NR 49
TC 23
Z9 23
U1 1
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD APR
PY 2012
VL 80
IS 4
BP 1239
EP 1249
DI 10.1002/prot.24022
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 901RO
UT WOS:000300984700021
PM 22275112
ER

PT J
AU Quist, EM
   Tanabe, M
   Mansell, JEKL
   Edwards, JL
AF Quist, Erin M.
   Tanabe, Mika
   Mansell, Joanne E. K. L.
   Edwards, Jeffrey L.
TI A case series of thermal scald injuries in dogs exposed to hot water
   from garden hoses (garden hose scalding syndrome)
SO VETERINARY DERMATOLOGY
LA English
DT Article
ID BURNS; SKIN; CATS
AB In this report, we present a series of cases of thermal burns (scalds) in dogs resulting from exposure to hot water from a garden hose that had been lying in the sun. These dogs typically inhabited the southern and western regions of the USA, where the recorded high temperatures often exceed 32 degrees C (90 degrees F) during the warm summer months. Dogs with thermal scald injury in these cases presented with linear thermal burns along the dorsum, in addition to a variety of other macroscopic lesions that were dependent upon the degree of burn exposure and ranged from local erythema to ulcerated, necrotic and sloughing skin. Chronic, healed wounds were often alopecic, with markedly thickened skin and characteristically smooth and glassy scar tissue formation. Histologically, the lesions of thermal scald injury in these dogs were indistinguishable from any other second or third degree burn, and consisted of full-thickness dermal and epidermal necrosis with occasional fibrinoid necrosis of vessel walls, vasculitis and intravascular thrombosis. Here, we closely examine 10 cases of dogs with dorsal thermal burns collected from Texas, Arizona, California, Utah, Nevada, Indiana, Michigan and North Carolina and propose the term garden hose scalding syndrome (GHS) to describe this unique type of scald injury.
C1 [Quist, Erin M.; Mansell, Joanne E. K. L.] Texas A&M Univ, Dept Vet Pathol, College Stn, TX 77843 USA.
   [Tanabe, Mika; Edwards, Jeffrey L.] Antech Diagnost, Irvine, CA 92614 USA.
RP Quist, EM (reprint author), Natl Inst Environm Hlth Sci, NTP Pathol Grp, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
EM quiste@niehs.nih.gov
OI mansell, joanne/0000-0001-6426-9867
FU Antech Diagnostics; Department of Veterinary Pathobiology at Texas A M
   University
FX This study was funded by Antech Diagnostics and the Department of
   Veterinary Pathobiology at Texas A & M University.
NR 11
TC 3
Z9 3
U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0959-4493
J9 VET DERMATOL
JI Vet. Dermatol.
PD APR
PY 2012
VL 23
IS 2
DI 10.1111/j.1365-3164.2011.01015.x
PG 6
WC Dermatology; Veterinary Sciences
SC Dermatology; Veterinary Sciences
GA 906MJ
UT WOS:000301349000014
PM 22132799
ER

PT J
AU Sharma, N
   Cohen, LG
AF Sharma, Nikhil
   Cohen, Leonardo G.
TI Recovery of motor function after stroke
SO DEVELOPMENTAL PSYCHOBIOLOGY
LA English
DT Article
DE rehabilitation; motor recovery; stroke
ID TRANSCRANIAL MAGNETIC STIMULATION; NONINVASIVE CORTICAL STIMULATION;
   SUBCORTICAL STROKE; PREMOTOR CORTEX; SOMATOSENSORY STIMULATION; HAND
   FUNCTION; INTERHEMISPHERIC INTERACTIONS; BRAIN POLARIZATION; DORSAL
   PREMOTOR; HEMISPHERE
AB The human brain possesses a remarkable ability to adapt in response to changing anatomical (e.g., aging) or environmental modifications. This form of neuroplasticity is important at all stages of life but is critical in neurological disorders such as amblyopia and stroke. This review focuses upon our new understanding of possible mechanisms underlying functional deficits evidenced after adult-onset stroke. We review the functional interactions between different brain regions that may contribute to motor disability after stroke and, based on this information, possible interventional approaches to motor stroke disability. New information now points to the involvement of non-primary motor areas and their interaction with the primary motor cortex as areas of interest. The emergence of this new information is likely to impact new efforts to develop more effective neurorehabilitative interventions using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) that may be relevant to other neurological disorders such as amblyopia. (C) 2010 Wiley Periodicals, Inc. Dev Psychobiol 54:254-262, 2012.
C1 [Sharma, Nikhil; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
RP Sharma, N (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM sharmanik@ninds.nih.gov; cohenL@ninds.nih.gov
OI Sharma, Nikhil/0000-0001-8903-2938
FU NINDS, NIH
FX Contract grant sponsor: Intramural Research Program of the NINDS, NIH
NR 73
TC 26
Z9 26
U1 3
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1630
J9 DEV PSYCHOBIOL
JI Dev. Psychobiol.
PD APR
PY 2012
VL 54
IS 3
SI SI
BP 254
EP 262
DI 10.1002/dev.20508
PG 9
WC Developmental Biology; Psychology
SC Developmental Biology; Psychology
GA 907RP
UT WOS:000301435600004
PM 22415914
ER

PT J
AU Song, G
   Riemer, C
   Dickins, B
   Kim, HL
   Zhang, L
   Zhang, Y
   Hsu, CH
   Hardison, RC
   Green, ED
   Miller, W
AF Song, Giltae
   Riemer, Cathy
   Dickins, Benjamin
   Kim, Hie Lim
   Zhang, Louxin
   Zhang, Yu
   Hsu, Chih-Hao
   Hardison, Ross C.
   Green, Eric D.
   Miller, Webb
CA Program, NCS
TI Revealing Mammalian Evolutionary Relationships by Comparative Analysis
   of Gene Clusters
SO GENOME BIOLOGY AND EVOLUTION
LA English
DT Article
DE gene clusters; orthology; conversion; evolutionary inference; KIR
AB Many software tools for comparative analysis of genomic sequence data have been released in recent decades. Despite this, it remains challenging to determine evolutionary relationships in gene clusters due to their complex histories involving duplications, deletions, inversions, and conversions. One concept describing these relationships is orthology. Orthologs derive from a common ancestor by speciation, in contrast to paralogs, which derive from duplication. Discriminating orthologs from paralogs is a necessary step in most multispecies sequence analyses, but doing so accurately is impeded by the occurrence of gene conversion events. We propose a refined method of orthology assignment based on two paradigms for interpreting its definition: by genomic context or by sequence content. X-orthology (based on context) traces orthology resulting from speciation and duplication only, while N-orthology (based on content) includes the influence of conversion events. We developed a computational method for automatically mapping both types of orthology on a per-nucleotide basis in gene cluster regions studied by comparative sequencing, and we make this mapping accessible by visualizing the output. All of these steps are incorporated into our newly extended CHAP 2 package. We evaluate our method using both simulated data and real gene clusters (including the well-characterized alpha-globin and beta-globin clusters). We also illustrate use of CHAP 2 by analyzing four more loci: CCL (chemokine ligand), IFN (interferon), CYP2abf (part of cytochrome P450 family 2), and KIR (killer cell immunoglobulin-like receptors). These new methods facilitate and extend our understanding of evolution at these and other loci by adding automated accurate evolutionary inference to the biologist's toolkit. The CHAP 2 package is freely available from http://www.bx.psu.edu/miller_lab.
C1 [Song, Giltae; Riemer, Cathy; Dickins, Benjamin; Kim, Hie Lim; Zhang, Yu; Hardison, Ross C.; Miller, Webb] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Zhang, Louxin] Natl Univ Singapore, Dept Math, Singapore, Singapore.
   [Hsu, Chih-Hao] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
   [Green, Eric D.] NIH, Intramural Sequencing Ctr, Bldg 10, Bethesda, MD 20892 USA.
   [Green, Eric D.; Program, NCS] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Song, G (reprint author), Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
EM gsong@bx.psu.edu
RI Kim, Hie Lim/E-7393-2017; Hardison, Ross/G-1142-2010
OI Kim, Hie Lim/0000-0003-3080-9524; Song, Giltae/0000-0001-8796-4678;
   Dickins, Benjamin/0000-0002-0866-6232; Hardison,
   Ross/0000-0003-4084-7516
FU National Human Genome Research Institute [HG02238]; National Science
   Foundation [DEB 0733029]
FX We thank Federico Hoffmann for helpful discussion. This work was
   supported by grant HG02238 to W.M. from the National Human Genome
   Research Institute and National Science Foundation award DEB 0733029.
NR 79
TC 5
Z9 5
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1759-6653
J9 GENOME BIOL EVOL
JI Genome Biol. Evol.
PD APR
PY 2012
VL 4
IS 4
BP 586
EP 601
DI 10.1093/gbe/evs032
PG 16
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA V45OR
UT WOS:000209826400001
PM 22454131
ER

PT J
AU Arthos, J
   Nawaz, F
   Wei, D
   Van Ryk, D
   Jelicic, K
   Pascuccio, M
   Cicala, C
   Fauci, AS
AF Arthos, J.
   Nawaz, F.
   Wei, D.
   Van Ryk, D.
   Jelicic, K.
   Pascuccio, M.
   Cicala, C.
   Fauci, A. S.
TI HIV-1 gp120 Interactions With the Gut Homing Receptor Integrin alpha 4
   beta 7 on CD4+T Cells
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Arthos, J.; Nawaz, F.; Wei, D.; Van Ryk, D.; Jelicic, K.; Pascuccio, M.; Cicala, C.; Fauci, A. S.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 103
BP 41
EP 41
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100014
ER

PT J
AU Lusso, P
AF Lusso, Paolo
TI Interleukin-7 As an Immune Reconstitution Agent in HIV-1 Infection: Ex
   Vivo and in Vivo Protective Effects on CD4+T Cells
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Lusso, Paolo] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 107
BP 43
EP 43
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100018
ER

PT J
AU Margolis, L
AF Margolis, Leonid
TI HIV-1 Transmission From Semen to the Female Genital Tract and its
   Prevention, as Seen in an ex vivo Tissue Model
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 109
BP 44
EP 44
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100020
ER

PT J
AU Pavlakis, GN
   Jalah, R
   Patel, V
   Kulkarni, V
   Valentin, A
   Alicea, C
   Rosati, M
   von Gegerfelt, A
   Sardesai, NY
AF Pavlakis, G. N.
   Jalah, Rashmi
   Patel, V.
   Kulkarni, V.
   Valentin, A.
   Alicea, C.
   Rosati, M.
   von Gegerfelt, A.
   Sardesai, N. Y.
TI DNA and Protein Vaccination via Electroporation Confers Protection Upon
   Mucosal Challenge with Heterologous SIVsmE660
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Pavlakis, G. N.; Jalah, Rashmi; Patel, V.; Kulkarni, V.; Valentin, A.; Alicea, C.; Rosati, M.; von Gegerfelt, A.; Sardesai, N. Y.] NCI, Human Retrovirus Sect, Vaccine Branch, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 115
BP 47
EP 47
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100026
ER

PT J
AU Fauci, AS
AF Fauci, Anthony S.
TI Ending the HIV/AIDS Pandemic: A Realistic Goal
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 117
BP 48
EP 48
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100028
ER

PT J
AU Kwong, PD
AF Kwong, Peter D.
TI Structural Immunology and Vaccine Development
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Kwong, Peter D.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 120
BP 49
EP 49
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100030
ER

PT J
AU Xiao, P
   Patterson, LJ
   Kuate, S
   Brocca-Cofano, E
   Venzon, D
   Daltabuit-Test, M
   Mckinnon, K
   Dipasquale, J
   Lee, EM
   Pal, R
   Keele, B
   Robert-Guroff, M
AF Xiao, Peng
   Patterson, L. Jean
   Kuate, Seraphin
   Brocca-Cofano, Egidio
   Venzon, David
   Daltabuit-Test, Mara
   Mckinnon, Katherine
   Dipasquale, Janet
   Lee, Eun Mi
   Pal, Ranajit
   Keele, Brandon
   Robert-Guroff, Marjorie
TI Vaccine-Elicited Antibodies Contribute to Protective Efficacy, Including
   Mucosal Antibodies, Correlated with Delayed SIV Acquisition
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Xiao, Peng; Patterson, L. Jean; Kuate, Seraphin; Brocca-Cofano, Egidio; Venzon, David; Daltabuit-Test, Mara; Mckinnon, Katherine; Dipasquale, Janet; Robert-Guroff, Marjorie] NCI, Bethesda, MD 20892 USA.
   [Lee, Eun Mi; Pal, Ranajit] Adv BioSci Labs Inc, Gaithersburg, MD USA.
   [Keele, Brandon] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 123
BP 50
EP 50
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100033
ER

PT J
AU Robinson, HL
   Amara, RR
   Moss, B
AF Robinson, Harriet L.
   Amara, Rama Rao
   Moss, Bernard
TI GeoVax HIV/AIDS Vaccine Program, Preclinical and Clinical Studies
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Robinson, Harriet L.] GeoVax Labs Inc, Smyrna, GA USA.
   [Amara, Rama Rao] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Amara, Rama Rao] Emory Univ, Yerkes Primate Res Ctr, Atlanta, GA 30322 USA.
   [Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 124
BP 51
EP 51
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100034
ER

PT J
AU Nabel, GJ
   Wu, X
   Yang, ZY
   Li, Y
   Hogerkorp, CM
   Schief, WR
   Seaman, MS
   Zhou, T
   Schmidt, SD
   Wu, L
   Xu, L
   Longo, NS
   Mckee, K
   O'Dell, S
   Louder, MK
   Wycuff, DL
   Feng, Y
   Nason, M
   Doria-Rose, N
   Connors, M
   Roederer, M
   Kwong, PD
   Mascola, JR
AF Nabel, G. J.
   Wu, X.
   Yang, Z. Y.
   Li, Y.
   Hogerkorp, C. M.
   Schief, W. R.
   Seaman, M. S.
   Zhou, T.
   Schmidt, S. D.
   Wu, L.
   Xu, L.
   Longo, N. S.
   McKee, K.
   O'Dell, S.
   Louder, M. K.
   Wycuff, D. L.
   Feng, Y.
   Nason, M.
   Doria-Rose, N.
   Connors, M.
   Roederer, M.
   Kwong, P. D.
   Mascola, J. R.
TI Broadly Neutralizing HIV Abs: Gains and Losses in Translation
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Nabel, G. J.; Wu, X.; Yang, Z. Y.; Li, Y.; Zhou, T.; Schmidt, S. D.; Wu, L.; Xu, L.; Longo, N. S.; McKee, K.; O'Dell, S.; Louder, M. K.; Wycuff, D. L.; Feng, Y.; Roederer, M.; Kwong, P. D.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Nason, M.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
   [Doria-Rose, N.; Connors, M.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
   [Schief, W. R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Seaman, M. S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA.
   [Hogerkorp, C. M.] Novo Nordisk AS, Dept Mol Genet, Malov, Denmark.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 126
BP 52
EP 52
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100036
ER

PT J
AU Liu, L
   Cimbro, R
   Lusso, P
   Berger, EA
AF Liu, L.
   Cimbro, R.
   Lusso, P.
   Berger, E. A.
TI Epitope Masking Mechanism Within the HIV-1 Env Trimer Analyzed by
   Functional Subunit Complementation
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Liu, L.; Berger, E. A.] NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA.
   [Cimbro, R.; Lusso, P.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 139
BP 58
EP 58
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100048
ER

PT J
AU Lugli, DE
   Gattinoni, L
   Restifo, NP
   Roederer, M
AF Lugli, D. Enrico
   Gattinoni, Luca
   Restifo, Nicholas P.
   Roederer, Mario
TI The Role of T Memory Stem Cells: Pathogenesis and Vaccines
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Lugli, D. Enrico; Roederer, Mario] NIAID, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA.
   [Gattinoni, Luca; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 141
BP 59
EP 59
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100050
ER

PT J
AU Yarchoan, R
   Uldrick, T
   Polizzotto, M
   Little, RF
   Aleman, KA
   Wyvill, KM
   Whitby, D
   Tosato, G
   Davis, DA
   Wang, V
AF Yarchoan, Robert
   Uldrick, Thomas
   Polizzotto, Mark
   Little, Richard F.
   Aleman, Karen A.
   Wyvill, Kathleen M.
   Whitby, Denise
   Tosato, Giovanna
   Davis, David A.
   Wang, Victoria
TI Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Related Multicentric
   Castleman's Disease (MCD) and Inflammatory Cytokine Syndrome (KICS):
   Pathogenesis and Treatment
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Yarchoan, Robert; Uldrick, Thomas; Polizzotto, Mark; Little, Richard F.; Aleman, Karen A.; Wyvill, Kathleen M.; Whitby, Denise; Tosato, Giovanna; Davis, David A.; Wang, Victoria] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 148
BP 62
EP 62
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100057
ER

PT J
AU Goedert, J
AF Goedert, James
TI Update on Malignancies Among People with HIV/AIDS
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Goedert, James] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 150
BP 63
EP 63
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100059
ER

PT J
AU Mbulaiteye, SM
AF Mbulaiteye, Sam M.
TI Virally Associated Malignancies in the HIV Era
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 151
BP 64
EP 64
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100060
ER

PT J
AU Franchini, G
AF Franchini, Genoveffa
TI Retooling the Macaque Model to Evaluate the Relative Efficacy of HIV
   Vaccine Candidates
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Franchini, Genoveffa] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 154
BP 65
EP 65
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100063
ER

PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI Transformation of Human Cells by HTLV-1 Tax
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Jeang, Kuan-Teh] NIAID, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 153
BP 65
EP 65
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100062
ER

PT J
AU Berzofsky, JA
AF Berzofsky, Jay A.
TI Strategies for Anti-Cancer Immunotherapy Using Vaccines and Blockade of
   Negative Regulation
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Berzofsky, Jay A.] NCI, Vaccine Branch, CCR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA 157
BP 67
EP 67
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100066
ER

PT J
AU Farci, P
   Wollenberg, K
   Alter, HJ
AF Farci, Patrizia
   Wollenberg, Kurt
   Alter, Harvey J.
TI Molecular Evolution of Hepatitis C Virus (HCV) and Clinical Outcome in
   Patients with Hepatitis C
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Farci, Patrizia] NIAID, LID, Bethesda, MD 20892 USA.
   [Wollenberg, Kurt] NIAID, BCBB, Bethesda, MD 20892 USA.
   [Alter, Harvey J.] NIH, DTM, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA A2
BP 68
EP 68
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100068
ER

PT J
AU Saba, E
   Ferrari, D
   Origoni, M
   Taccagni, G
   Doglioni, C
   Lisco, A
   Margolis, L
   Poli, G
AF Saba, Elisa
   Ferrari, Davide
   Origoni, Massimo
   Taccagni, Gianluca
   Doglioni, Claudio
   Lisco, Andrea
   Margolis, Leonid
   Poli, Guido
TI Productive HIV-1 Infection of Cervical Tissue Ex Vivo
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Saba, Elisa; Poli, Guido] Ist Sci San Raffaele, AIDS Immunopathogenesis Unit, Milan, Italy.
   [Saba, Elisa; Origoni, Massimo; Doglioni, Claudio; Poli, Guido] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy.
   [Ferrari, Davide; Origoni, Massimo] Ist Sci San Raffaele, Dept Obsetr & Gynecol, Milan, Italy.
   [Taccagni, Gianluca; Doglioni, Claudio] Ist Sci San Raffaele, Dept Pathol, Milan, Italy.
   [Lisco, Andrea; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA B5
BP 75
EP 75
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100081
ER

PT J
AU Tosi, G
   Forlani, G
   Andresen, V
   Turci, M
   Bertazzoni, U
   Franchini, G
   Poli, G
   Accolla, RS
AF Tosi, Giovanna
   Forlani, Greta
   Andresen, Vibeke
   Turci, Marco
   Bertazzoni, Umberto
   Franchini, Genoveffa
   Poli, Guido
   Accolla, Roberto S.
TI The MHC-II Transactivator CIITA, a Viral Restriction Factor Targeting
   Human T-Cell Lymphotropic Virus Type 1 Tax-1 Function and Inhibiting
   Viral Replication
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Tosi, Giovanna; Forlani, Greta; Accolla, Roberto S.] Univ Insubria, Dept Expt Med, Varese, Italy.
   [Andresen, Vibeke; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
   [Turci, Marco; Bertazzoni, Umberto] Univ Verona, Sect Biol & Genet, Dept Life & Reprod Sci, Verona, Italy.
   [Poli, Guido] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, AIDS Immunopathogenesis Unit, Milan, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA E2
BP 82
EP 82
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100094
ER

PT J
AU Tang, MZ
   Lautenberger, JA
   Gao, XJ
   Sezgin, E
   Hendrickson, SL
   Troyer, JL
   David, VA
   Guan, L
   Mcintosh, CE
   Raymond, M
   Guo, XC
   Zheng, YM
   Liao, J
   Deng, H
   Malasky, M
   Pontius, J
   Kessing, B
   Carrington, M
   de The, G
   Zeng, Y
   O'Brien, SJ
AF Tang Minzhong
   Lautenberger, James A.
   Gao, Xiaojiang
   Sezgin, Efe
   Hendrickson, Sher L.
   Troyer, Jennifer L.
   David, Victor A.
   Guan, Li
   Mcintosh, Carl E.
   Raymond, Marilyn
   Guo, Xiuchan
   Zheng, Yuming
   Liao, Jian
   Deng, Hong
   Malasky, Michael
   Pontius, Joan
   Kessing, Bailey
   Carrington, Mary
   de The, Guy
   Zeng, Yi
   O'Brien, Stephen J.
TI The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China
   Involve HLA Class I Antigen Recognition Groove
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Meeting Abstract
CT 13th Annual International Meeting of the Institute of Human Virology
CY OCT 30-NOV 03, 2011
CL Baltimore, MD
C1 [Zeng, Yi] Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing, Peoples R China.
   [Zheng, Yuming; Deng, Hong] Wuzhou Red Cross Hosp, Ctr Canc, Guangxi, Peoples R China.
   [Sezgin, Efe; Hendrickson, Sher L.; David, Victor A.; Raymond, Marilyn; Pontius, Joan; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
   [Lautenberger, James A.; Guan, Li; Mcintosh, Carl E.; Guo, Xiuchan; Malasky, Michael; Kessing, Bailey] NCI, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21701 USA.
   [Gao, Xiaojiang; Carrington, Mary] NCI, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.
   [Guo, Xiuchan; Zeng, Yi] Chinese Ctr Dis Control & Prevent, Inst Viral Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China.
   [Liao, Jian] Cangwu Inst Nasopharyngeal Carcinoma Control & Pr, Dept Epidemiol, Guangxi, Peoples R China.
   [de The, Guy] Inst Pasteur, Oncogen Virus Epidemiol & Pathophysiol, Paris, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2012
VL 59
SU 1
MA F5
BP 88
EP 88
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA V45YE
UT WOS:000209851100103
ER

PT J
AU Musunuru, K
   Roden, DM
   Boineau, R
   Bristow, MR
   McCaffrey, TA
   Newton-Cheh, C
   Paltoo, DN
   Rosenberg, Y
   Wohlgemuth, JG
   Zineh, I
   Hasan, AAK
AF Musunuru, Kiran
   Roden, Dan M.
   Boineau, Robin
   Bristow, Michael R.
   McCaffrey, Timothy A.
   Newton-Cheh, Christopher
   Paltoo, Dina N.
   Rosenberg, Yves
   Wohlgemuth, Jay G.
   Zineh, Issam
   Hasan, Ahmed A. K.
TI Cardiovascular Pharmacogenomics: Current Status and Future
   Directions-Report of a National Heart, Lung, and Blood Institute Working
   Group
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE genetic polymorphisms; genetics; pharmacogenetics; pharmacogenetics
   anticoagulants; pharmacogenetics cholesterol
ID ACUTE CORONARY SYNDROMES; GENOME-WIDE ASSOCIATION; TRP719ARG
   POLYMORPHISM; MYOCARDIAL-INFARCTION; CYP2C19 GENOTYPE; WARFARIN;
   CLOPIDOGREL; ANTICOAGULATION; EFFICACY; OUTCOMES
C1 [Musunuru, Kiran] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Musunuru, Kiran] Harvard Univ, Cambridge, MA 02138 USA.
   [Roden, Dan M.] Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA.
   [Boineau, Robin; Paltoo, Dina N.; Rosenberg, Yves; Hasan, Ahmed A. K.] NHLBI, Bethesda, MD 20892 USA.
   [Bristow, Michael R.] Univ Colorado, Cardiovasc Inst, Aurora, CO USA.
   [McCaffrey, Timothy A.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
   [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
   [Wohlgemuth, Jay G.] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA.
   [Zineh, Issam] US FDA, Silver Spring, MD USA.
RP Musunuru, K (reprint author), Harvard Univ, 7 Divin Ave, Cambridge, MA 02138 USA.
EM kiranmusunuru@gmail.com
FU National Heart, Lung, and Blood Institute; Personalized Medicine
   Coalition; American College of Cardiology; American Medical Association;
   Cheney Cardiovascular Institute at George Washington University
FX The Working Group meeting was underwritten by the National Heart, Lung,
   and Blood Institute at the National Institutes of Health, Bethesda, MD.
   The New Frontiers in Personalized Medicine: Cardiovascular Research and
   Clinical Care was supported and/or cosponsored by the National Heart,
   Lung, and Blood Institute; Personalized Medicine Coalition; American
   College of Cardiology; American Medical Association; and the Cheney
   Cardiovascular Institute at George Washington University.
NR 37
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD APR
PY 2012
VL 1
IS 2
AR UNSP e000554
DI 10.1161/JAHA.111.000554
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 243QY
UT WOS:000326333200009
PM 23130127
ER

PT J
AU Blivis, D
   O'Donovan, MJ
AF Blivis, Dvir
   O'Donovan, Michael J.
TI Retrograde Loading of Nerves, Tracts, and Spinal Roots with Fluorescent
   Dyes
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neuroscience; Issue 62; Retrograde labeling; Fluorescent dyes; Spinal
   cord; Nerves; Spinal tracts; Optical imaging; Electrophysiology;
   Calcium-sensitive dyes
AB Retrograde labeling of neurons is a standard anatomical method(1,2) that has also been used to load calcium and voltage-sensitive dyes into neurons(3-6). Generally, the dyes are applied as solid crystals or by local pressure injection using glass pipettes. However, this can result in dilution of the dye and reduced labeling intensity, particularly when several hours are required for dye diffusion. Here we demonstrate a simple and low-cost technique for introducing fluorescent and ion-sensitive dyes into neurons using a polyethylene suction pipette filled with the dye solution. This method offers a reliable way for maintaining a high concentration of the dye in contact with axons throughout the loading procedure.
C1 [Blivis, Dvir; O'Donovan, Michael J.] NINDS, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Blivis, D (reprint author), NINDS, Dev Neurobiol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM blivisd@ninds.nih.gov
OI Blivis, Dvir/0000-0001-6203-7325
FU National Institutes of Neurological Disorders and Stroke at the National
   Institutes of Health
FX This work was supported by the intramural program of the National
   Institutes of Neurological Disorders and Stroke at the National
   Institutes of Health. We would also like to thank Dr. George Mentis for
   his earlier contributions to the method and to the data in Figure 3.
NR 15
TC 0
Z9 0
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 APR
PY 2012
IS 62
AR UNSP e4008
DI 10.3791/4008
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36PG
UT WOS:000209222900056
ER

PT J
AU Lindsey, JW
   Scott, TF
   Lynch, SG
   Cofield, SS
   Nelson, F
   Conwit, R
   Gustafson, T
   Cutter, GR
   Wolinsky, JS
   Lublin, FD
AF Lindsey, J. W.
   Scott, T. F.
   Lynch, S. G.
   Cofield, S. S.
   Nelson, F.
   Conwit, R.
   Gustafson, T.
   Cutter, G. R.
   Wolinsky, J. S.
   Lublin, F. D.
CA CombiRx Investigators Grp
TI The CombiRx trial of combined therapy with interferon and glatiramer
   acetate in relapsing remitting MS: Design and baseline characteristics
SO MULTIPLE SCLEROSIS AND RELATED DISORDERS
LA English
DT Article
DE Interferon beta-1a; Glatiramer acetate; Combination therapy; Clinical
   trial; Multiple sclerosis; Randomized
AB Background: Interferon-beta 1a (IFNB) and glatiramer acetate (GA) are distinct therapies which are both partially effective for relapsing MS. It is not known if combining the two treatments would be more effective.
   Objective: To review the rationale, design, and baseline characteristics of the CombiRx study of combined treatment with IFNB and GA. Methods: The key inclusion criteria included a diagnosis of relapsing MS, at least 2 episodes of MS activity in the previous 3 years, expanded disability status scale of 0-5.5, and no prior treatment with either IFNB or GA. Subjects were randomized to IFNB+GA, IFNB monotherapy, or GA monotherapy in a 2:1:1 ratio.
   Results: From 2005 to 2009, we enrolled 1008 subjects. The participants were 72.4% female and 87.6% Caucasian with a mean age of 37.7 years. The median duration of symptoms was 2 years at entry into the study, and the mean EDSS was 2.1. On the baseline MRI, the mean total lesion load was 12.2 ml, and 40% of the participants had enhancing lesions.
   Conclusion: We have recruited a population of patients with clinical and MRI characteristics typical for early MS. The study results will aid in deciding on the optimum early treatment. This trial should serve as a model for future studies of combination therapy. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Nelson, F.; Wolinsky, J. S.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA.
   [Scott, T. F.] Drexel Coll Med, Dept Neurol, Pittsburgh, PA USA.
   [Lynch, S. G.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
   [Cofield, S. S.; Cutter, G. R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
   [Conwit, R.] NINDS, NIH, Bethesda, MD 20892 USA.
   [Gustafson, T.; Lublin, F. D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Corinne Goldsmith Dickinson Ctr Multiple Sclerosi, New York, NY 10029 USA.
RP Lindsey, JW (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Neurol, 6431 Fannin St,Suite 7-044, Houston, TX 77030 USA.
EM John.w.lindsey@uth.tmc.edu
FU National Institutes of Health; National Institute of Neurological
   Disorders and Stroke [UO1 NS045719, R21 NS41986]; National Multiple
   Sclerosis Society
FX The study is funded by The National Institutes of Health, The National
   Institute of Neurological Disorders and Stroke (Phase III study: UO1
   NS045719, Planning Grant: R21 NS41986) and is listed on
   www.clinicaltrials.gov NCT00211887. Materials were provided to the study
   by Biogen Idec and Teva Pharmaceutical. Contrast Letter Acuity funding
   provided by the National Multiple Sclerosis Society. We would like to
   thank Theresa McVie, MS, for assistance with preparation of tables and
   data analysis; CCC, SDMC, and MRI-AC staff; the following site
   investigators and staff who have enrolled participants: M. Agius,
   Sacramento, CA; K. Bashir, Birmingham, AL; R. Baumhefner, Los Angeles,
   CA; G. Birnbaum, Golden Valley, MN; G. Blevins, Edmonton, AB Canada; R.
   Bomprezzi, Phoenix, AZ; A. Boster, Columbus, OH; T. Brown, Kirkland, WA;
   J. Burkholder, Canton, OH; A. Camac, Lexington, MA; D. Campagnolo,
   Phoenix, AZ; J. Carter, Scottsdale, AZ; B. Cohen, Chicago, IL; J.
   Cooper, Berkeley, CA; J. Corboy, Aurora, CO; A. Cross, Saint Louis, MO;
   L. Dewitt, Salt Lake City, UT; J. Dunn, Kirkland, WA; K. Edwards,
   Latham, NY; E. Eggenberger, East Lansing, MI; J. English, Atlanta, GA;
   W. Felton, Richmond, VA; P. Fodor, Colorado Springs, CO; C. Ford,
   Albuquerque, NM; M. Freedman, Ottawa, Ontario, Canada; S. Galetta,
   Philadelphia, PA; G. Garmany, Boulder, CO; A. Goodman, Rochester, NY; M.
   Gottesman, Mineola, NY; C. Gottschalk, New Haven CT; M. Gruental,
   Albany, NY; M. Gudesblatt, Patchogue, NY; R. Hamill, Burlington, VT; J.
   Herbert, New York, NY; R. Holub, Albany, NY; W. Honeycutt, Maitland, FL;
   B. Hughes, Des Moines, IA; G. Hutton, Houston, TX; D. Jacobs,
   Philadelphia, PA; K. Johnson, Baltimore, MD; L. Kasper, Lebanon, NH; J.
   Kattah, Peoria, IL; M. Kaufman, Charlotte, NC; M. Keegan, Rochester, NY;
   O. Khan, Detroit, MI; B. Khatri, Milwaukee, WI; M. Kita, Seattle, WA; B.
   Koffman, Toledo, OH; E. Lallana, Lebanon, NH; N. Lava, Albany, NY; J.
   Lindsey, Houston, TX; P. Loge, Billings, MT; S. Lynch, Kansas City, KS;
   F. McGee, Richmond, VA; L. Mejico, Syracuse, NY; L. Metz, Calgary, AB
   Canada; P. O'Connor, Toronto, ON, Canada; K. Pandey, Albany, NY; H.
   Panitch, Burlington, VT; J. Preiningerova, New Haven, CT; K. Rammohan,
   Columbus, OH; C. Riley, New Haven, CT; P. Riskind, Worcester, MA; L.
   Rolak, Marshfield, WI; W. Royal, Baltimore, MD; S. Scarberry, Fargo, ND;
   A. Schulman, Richmond, VA; T. Scott, Pittsburgh, PA; C. Sheppard,
   Uniontown, OH; W. Sheremata, Miami, FL; L. Stone, Cleveland, OH; W.
   Stuart, Atlanta, GA; S. Subramaniam, Nashville, TN; V. Thadani, Lebanon,
   NH; F. Thomas, Saint Louis, MO; B. Thrower, Atlanta, GA; M. Tullman, New
   York, NY; A. Turel, Danville, PA; T. Vollmer, Phoenix, AZ; S. Waldman,
   La Habra, CA; B. Weinstock-Guttman, Buffalo, NY; J. Wendt, Tucson, AZ;
   R. Williams, Billings, MT; D. Wynn, Northbrook, IL; M. Yeung, Calgary,
   AB Canada.
NR 25
TC 16
Z9 17
U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2211-0348
EI 2211-0356
J9 MULT SCLER RELAT DIS
JI Mult. Scler. Relat. Disord.
PD APR
PY 2012
VL 1
IS 2
BP 81
EP 86
DI 10.1016/j.msard.2012.01.006
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA V37KY
UT WOS:000209275900007
PM 22754793
ER

PT J
AU Averbeck, B
AF Averbeck, Bruno
TI OXYTOCIN IMPROVES EMOTION RECOGNITION IN PATIENTSWITH SCHIZOPHRENIA
SO SCHIZOPHRENIA RESEARCH
LA English
DT Meeting Abstract
C1 [Averbeck, Bruno] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD APR
PY 2012
VL 136
SU 1
BP S69
EP S69
PG 1
WC Psychiatry
SC Psychiatry
GA V45US
UT WOS:000209842100248
ER

PT J
AU Lee, M
AF Lee, Mary
TI ADJUNCTIVE INTRANASAL OXYTOCINTO IMPROVE SOCIAL COGNITION AND
   FUNCTIONING IN SCHIZOPHRENIA
SO SCHIZOPHRENIA RESEARCH
LA English
DT Meeting Abstract
C1 [Lee, Mary] NIDA, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD APR
PY 2012
VL 136
SU 1
BP S70
EP S71
PG 2
WC Psychiatry
SC Psychiatry
GA V45US
UT WOS:000209842100252
ER

PT J
AU Miller, R
   Richards, T
   Gochman, P
   Greenstein, DK
   Gogtay, N
   Rapoport, JL
AF Miller, Rachel
   Richards, Tasia
   Gochman, Peter
   Greenstein, Deanna K.
   Gogtay, Nitin
   Rapoport, Judith L.
TI A LONGITUDINAL FOLLOW-UP OF DIAGNOSTIC OUTCOMES OF CHILDHOOD-ONSET
   SCHIZOPHRENIA AFTER INPATIENT EVALUATION AND MEDICATION WASHOUT
SO SCHIZOPHRENIA RESEARCH
LA English
DT Meeting Abstract
C1 [Miller, Rachel; Richards, Tasia; Gochman, Peter; Greenstein, Deanna K.; Gogtay, Nitin; Rapoport, Judith L.] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD APR
PY 2012
VL 136
SU 1
MA 69
BP S210
EP S210
PG 1
WC Psychiatry
SC Psychiatry
GA V45US
UT WOS:000209842101351
ER

PT J
AU Papaleo, F
   Burdick, M
   Callicott, J
   Weinberger, D
AF Papaleo, Francesco
   Burdick, Madeline
   Callicott, Joseph
   Weinberger, Daniel
TI EPISTATIC INTERACTION OF COMT AND DTNBP1 MODULATES WORKING MEMORY
   PERFORMANCE IN MICE AND RELATED PREFRONTAL PHYSIOLOGY IN HUMANS
SO SCHIZOPHRENIA RESEARCH
LA English
DT Meeting Abstract
C1 [Papaleo, Francesco] Ist Italiano Tecnol, Genoa, Italy.
   [Papaleo, Francesco; Burdick, Madeline; Callicott, Joseph; Weinberger, Daniel] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD APR
PY 2012
VL 136
SU 1
MA 111
BP S132
EP S132
PG 1
WC Psychiatry
SC Psychiatry
GA V45US
UT WOS:000209842101136
ER

PT J
AU Scheggia, D
   Bebensee, A
   Benfenati, F
   Weinberger, DR
   Papaleo, F
AF Scheggia, Diego
   Bebensee, Audrey
   Benfenati, Fabio
   Weinberger, Daniel R.
   Papaleo, Francesco
TI A NOVEL SEMI-AUTOMATED ATTENTIONAL SET SHIFTING TASK FOR MICE
SO SCHIZOPHRENIA RESEARCH
LA English
DT Meeting Abstract
C1 [Scheggia, Diego; Benfenati, Fabio; Papaleo, Francesco] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, Genoa, Italy.
   [Bebensee, Audrey; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD APR
PY 2012
VL 136
SU 1
MA 13
BP S285
EP S285
PG 1
WC Psychiatry
SC Psychiatry
GA V45US
UT WOS:000209842101556
ER

PT J
AU Vyas, NS
   Rubinstein, DY
   Carver, FW
   Mattai, AA
   Stidd, R
   Holroyd, T
   Weisinger, BM
   David, CN
   Turner, C
   Clasen, L
   Miller, R
   Tossell, JW
   Coppola, R
   Rapoport, JL
   Gogtay, N
AF Vyas, Nora S.
   Rubinstein, Daniel Y.
   Carver, Frederick W.
   Mattai, Anand A.
   Stidd, Reva
   Holroyd, Tom
   Weisinger, Brian M.
   David, Christopher N.
   Turner, Cheryl
   Clasen, Liv
   Miller, Rachel
   Tossell, Julia W.
   Coppola, Richard
   Rapoport, Judith L.
   Gogtay, Nitin
TI ALTERATIONS IN MAGNETOENCEPHALOGRAPHIC GAMMA OSCILLATORY PATTERNS DURING
   RESTING-STATE IN PATIENTS WITH CHILDHOOD-ONSET SCHIZOPHRENIA,
   NON-PSYCHOTIC SIBLINGS AND HEALTHY CONTROLS
SO SCHIZOPHRENIA RESEARCH
LA English
DT Meeting Abstract
C1 [Vyas, Nora S.; Mattai, Anand A.; Stidd, Reva; Weisinger, Brian M.; David, Christopher N.; Turner, Cheryl; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
   [Rubinstein, Daniel Y.; Carver, Frederick W.; Holroyd, Tom; Coppola, Richard] NIH, MEG Core Facil, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD APR
PY 2012
VL 136
SU 1
MA 15:30
BP S90
EP S90
PG 1
WC Psychiatry
SC Psychiatry
GA V45US
UT WOS:000209842101025
ER

PT J
AU Wehring, HJ
   Lee, MR
   McMahon, RP
   Bellack, A
   Linthicum, J
   Feldman, S
   Vyas, G
   Richardson, C
   Buchanan, RW
   Contoreggi, C
   Kearns, AM
   Kelly, DL
AF Wehring, Heidi J.
   Lee, Mary R.
   McMahon, Robert P.
   Bellack, Alan
   Linthicum, Jared
   Feldman, Stephanie
   Vyas, Gopal
   Richardson, Charles
   Buchanan, Robert W.
   Contoreggi, Carlo
   Kearns, Ann Marie
   Kelly, Deanna L.
TI INTRANASAL OXYTOCIN EFFECTS ON SOCIAL ANXIETY AND DEPRESSION IN
   SCHIZOPHRENIA: RESULTS FROM A DOUBLE BLIND PLACEBO CONTROLLED TRIAL
SO SCHIZOPHRENIA RESEARCH
LA English
DT Meeting Abstract
C1 [Wehring, Heidi J.; McMahon, Robert P.; Linthicum, Jared; Feldman, Stephanie; Vyas, Gopal; Richardson, Charles; Buchanan, Robert W.; Kearns, Ann Marie; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA.
   [Lee, Mary R.; Contoreggi, Carlo] NIDA, NIH, Baltimore, MD USA.
   [Bellack, Alan] Baltimore Vet Adm Med Ctr, VA Capital Hlth Care Network Mental Illness Res E, Baltimore, MD USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD APR
PY 2012
VL 136
SU 1
MA 220
BP S360
EP S360
PG 1
WC Psychiatry
SC Psychiatry
GA V45US
UT WOS:000209842102082
ER

PT J
AU Morris, BA
   Shakespeare-Finch, J
   Scott, JL
AF Morris, Bronwyn A.
   Shakespeare-Finch, Jane
   Scott, Jennifer L.
TI Posttraumatic growth after cancer: the importance of health-related
   benefits and newfound compassion for others
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Posttraumatic growth; Cancer; Oncology; Qualitative; Mixed method
ID BREAST-CANCER; INVENTORY; STRESS; TRAUMA; WOMEN
AB There is growing evidence in psycho-oncology that people can experience posttraumatic growth (PTG), or positive life change, in addition to the distress that may occur after a cancer diagnosis. Many studies utilise existing PTG measures that were designed for general trauma experiences, such as the Posttraumatic Growth Inventory. However, such inventories may not take into account life changes associated with a crisis specifically in a health-related context.
   The current study presents a mixed method exploration of the post-diagnosis experience of cancer survivors (N = 209) approximately 3 years after diagnosis.
   Quantitative and qualitative assessment of PTG showed that appreciating life was the most salient area of positive life change for cancer survivors. The results also revealed that in addition to several PTG domains captured by existing quantitative PTG measures, further positive life changes were reported, including compassion for others and health-related life changes.
   These domains of PTG highlight the unique context of a cancer diagnosis and the potential underestimation of positive life change by existing inventories. Further research is warranted that is directed towards designing a context-specific PTG measure for cancer survivors.
C1 [Morris, Bronwyn A.; Scott, Jennifer L.] Univ Tasmania, Sch Psychol, Sandy Bay, Tas, Australia.
   [Shakespeare-Finch, Jane] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Sch Psychol & Counselling, Brisbane, Qld 4001, Australia.
RP Morris, BA (reprint author), NHGRI, NIH, 31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA.
EM bronwyn.morris@nih.gov
OI Shakespeare-Finch, Jane/0000-0003-4237-1320
NR 28
TC 17
Z9 19
U1 2
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD APR
PY 2012
VL 20
IS 4
BP 749
EP 756
DI 10.1007/s00520-011-1143-7
PG 8
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 908XF
UT WOS:000301525700010
PM 21494782
ER

PT J
AU Chen, K
   Yap, LP
   Park, R
   Hui, XL
   Wu, KC
   Fan, DM
   Chen, XY
   Conti, PS
AF Chen, Kai
   Yap, Li-Peng
   Park, Ryan
   Hui, Xiaoli
   Wu, Kaichun
   Fan, Daiming
   Chen, Xiaoyuan
   Conti, Peter S.
TI A Cy5.5-labeled phage-displayed peptide probe for near-infrared
   fluorescence imaging of tumor vasculature in living mice
SO AMINO ACIDS
LA English
DT Article
DE Molecular imaging probe; Phage-displayed peptide; Fluorescence imaging;
   Tumor vasculature
ID GASTRIC-CANCER; INTEGRIN ALPHA(V)BETA(3); ANGIOGENIC SWITCH; CONTRAST
   AGENTS; RGD PEPTIDES; VIVO; RECEPTOR; TUMORIGENESIS; XENOGRAFTS; THERAPY
AB Near-infrared (NIR) fluorescence optical imaging is an emerging imaging technique for studying diseases at the molecular level. Optical imaging with a NIR emitting fluorophore for targeting tumor vasculature offers a noninvasive method for early detection of tumor angiogenesis and efficient monitoring of response to anti-tumor vasculature therapy. The previous in vitro results demonstrated that the GX1 peptide, identified by phage-display technology, is a tumor vasculature endothelium-specific ligand. In this report, Cy5.5-conjugated GX1 peptide was evaluated in a subcutaneous U87MG glioblastoma xenograft model to investigate tumor-targeting efficacy. The in vitro flow cytometry results revealed dose-dependent binding of Cy5.5-GX1 peptide to U87MG glioma cells. In vivo optical imaging with the Cy5.5-GX1 probe exhibited rapid U87MG tumor targeting at 0.5 h p.i., and high tumor-to-background contrast at 4 h p.i. Tumor specificity of Cy5.5-GX1 was confirmed by effective blocking of tumor uptake in the presence of unlabeled GX1 peptide (20 mg/kg). Ex vivo imaging further confirmed in vivo imaging findings, and demonstrated that Cy5.5-GX1 has a tumor-to-muscle ratio (15.21 +/- A 0.84) at 24 h p.i. for the non-blocked group and significantly decreased ratio (6.95 +/- A 0.75) for the blocked group. In conclusion, our studies suggest that Cy5.5-GX1 is a promising molecular probe for optical imaging of tumor vasculature.
C1 [Chen, Kai; Yap, Li-Peng; Park, Ryan; Conti, Peter S.] Univ So Calif, Keck Sch Med, Dept Radiol, Mol Imaging Ctr, Los Angeles, CA 90033 USA.
   [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
   [Hui, Xiaoli; Wu, Kaichun; Fan, Daiming] Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian 710032, Shanxi, Peoples R China.
   [Hui, Xiaoli; Wu, Kaichun; Fan, Daiming] Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, Xian 710032, Shanxi, Peoples R China.
RP Chen, K (reprint author), Univ So Calif, Keck Sch Med, Dept Radiol, Mol Imaging Ctr, 2250 Alcazar St,CSC 103, Los Angeles, CA 90033 USA.
EM chenkai@usc.edu; pconti@usc.edu
FU Molecular Imaging Center, the USC Department of Radiology, and the
   Provost's Biomedical Imaging Science Initiative
FX This study was supported by Molecular Imaging Center, the USC Department
   of Radiology, and the Provost's Biomedical Imaging Science Initiative.
NR 40
TC 21
Z9 25
U1 3
U2 36
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD APR
PY 2012
VL 42
IS 4
BP 1329
EP 1337
DI 10.1007/s00726-010-0827-5
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 904GD
UT WOS:000301181400024
PM 21212998
ER

PT J
AU Gabay, O
   Oppenheimer, H
   Meir, H
   Zaal, K
   Sanchez, C
   Dvir-Ginzberg, M
AF Gabay, Odile
   Oppenheimer, Hanna
   Meir, Hadar
   Zaal, Kristien
   Sanchez, Christelle
   Dvir-Ginzberg, Mona
TI Increased apoptotic chondrocytes in articular cartilage from adult
   heterozygous SirT1 mice
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID CATHEPSIN-B; OSTEOARTHRITIS; PATHOLOGY; DISEASES; PROTEIN; PATHWAY
AB Objective A growing body of evidence indicates that the protein deacetylase, SirT1, affects chondrocyte biology and survival. This report aims to evaluate in vivo attributes of SirT1 in cartilage biology of 129/J murine strains.
   Methods Heterozygous haploinsufficient (SirT1(+/-)) and wild-type (WT; SirT1(+/+)) 129/J mice aged 1 or 9 months were systematically compared for musculoskeletal features, scored for osteoarthritis (OA) severity, and monitored for chondrocyte apoptosis in articular cartilage. Sections of femorotibial joints were stained for type II collagen and aggrecan. Protein extracts from articular chondrocytes were isolated and immunoblotted for SirT1 and active caspase 3.
   Results Phenotypic observations show that, at 1 month of age, SirT1(+/-) mice were smaller than WT and showed a significant decrease in full-length SirT1 (FLSirT1; 110 kDa) protein levels. Levels of FLSirT1 were further decreased in both strains at 9 months. Immunoblot assays for 9-month-old strains revealed the presence of the inactive cleaved SirT1 variant (75 SirT1; 75 kDa) in WT mice, which was undetected in age-matched SirT1(+/-) mice. Nine-month-old SirT1(+/-) mice also showed increased OA and increased levels of apoptosis compared with age-matched WT mice.
   Conclusion The data suggest that the presence of 75 SirT1 may prolong viability of articular chondrocytes in adult (9-month-old) mice.
C1 [Oppenheimer, Hanna; Meir, Hadar; Dvir-Ginzberg, Mona] Hebrew Univ Hadassah Ein Kerem, Lab Cartilage Biol, Inst Dent Sci, Jerusalem, Israel.
   [Gabay, Odile] NIAMSD, Cartilage Mol Genet Grp, Cartilage Biol & Orthoped Branch, Bethesda, MD 20892 USA.
   [Zaal, Kristien] NIAMSD, NIAMS Light Imaging Sect, Bethesda, MD 20892 USA.
   [Sanchez, Christelle] Univ Liege, Bone & Cartilage Res Unit, Liege, Belgium.
RP Dvir-Ginzberg, M (reprint author), Hebrew Univ Hadassah Ein Kerem, Lab Cartilage Biol, Inst Dent Sci, Room 503,4th Floor,POB 12272, Jerusalem, Israel.
EM monad@ekmd.huji.ac.il
FU Marie Curie European IRG; National Institute of Arthritis and
   Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of
   Health; NIH; EU
FX This work was supported by the Marie Curie European IRG reintegration
   grant and Intramural Research Program of the National Institute of
   Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National
   Institutes of Health. We thank Professor Michael W McBurney (Ottawa
   Hospital Research Institute) for his contribution of 129/J mice strains
   and for critically reviewing the manuscript. The retroviral expression
   plasmid, pHanPuro-mSirT1, was a gift from Dr Vittorio Sartorelli, NIAMS,
   NIH.; NIH and EU.
NR 15
TC 43
Z9 45
U1 0
U2 3
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD APR
PY 2012
VL 71
IS 4
BP 613
EP 616
DI 10.1136/annrheumdis-2011-200504
PG 4
WC Rheumatology
SC Rheumatology
GA 902UG
UT WOS:000301066500026
PM 22258484
ER

PT J
AU Narkis, G
   Tzchori, I
   Cohen, T
   Holtz, A
   Wier, E
   Westphal, H
AF Narkis, Ginat
   Tzchori, Itai
   Cohen, Tsadok
   Holtz, Alex
   Wier, Eric
   Westphal, Heiner
TI Isl1 and Ldb Co-regulators of transcription are essential early
   determinants of mouse limb development
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE mouse limb development; Isl1 and Ldb co-regulators of transcription;
   limb bud initiation
ID VERTEBRATE LIMB; FGF8; INITIATION; OUTGROWTH; BUD; DROSOPHILA; GENES;
   SPECIFICATION; INACTIVATION; EXPRESSION
AB Background: The developing limb has served as an excellent model for studying pattern formation and signal transduction in mammalians. Many of the crucial genes that regulate growth and patterning of the limb following limb bud formation are now well known. However, details regarding the control of limb initiation and early stages of outgrowth remain to be defined. This report is focused on genetic events that pave the way for the establishment of a hindlimb bud. Results: Fgf10 and Tbx are crucial for early phases of limb bud initiation. Here we show that in the absence of Isl1 or of Ldb1/2, there is no hindlimb bud development. Fgf10 expression in the bud mesenchyme is dependent on Isl1 and its Ldb co-regulators. Conclusions: Thus, Isl1 and the Ldb co-regulators of transcription are essential early determinants of mouse limb development. Isl1/Ldb complexes regulate Fgf10 to orchestrate the earliest stages of hindlimb formation. Developmental Dynamics 241:787791, 2012. Published 2012 Wiley Periodicals, Inc.
C1 [Narkis, Ginat; Tzchori, Itai; Cohen, Tsadok; Holtz, Alex; Wier, Eric; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Program Genom Dev, NIH, Bethesda, MD 20892 USA.
RP Narkis, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Program Genom Dev, NIH, Bethesda, MD 20892 USA.
EM ginatnarkis@gmail.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development
FX Grant sponsor: Intramural Research Program of the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development.
NR 27
TC 11
Z9 12
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD APR
PY 2012
VL 241
IS 4
BP 787
EP 791
DI 10.1002/dvdy.23761
PG 5
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 906LP
UT WOS:000301347000012
PM 22411555
ER

PT J
AU Cooper, JD
   Howson, JMM
   Smyth, D
   Walker, NM
   Stevens, H
   Yang, JHM
   She, JX
   Eisenbarth, GS
   Rewers, M
   Todd, JA
   Akolkar, B
   Concannon, P
   Erlich, HA
   Julier, C
   Morahan, G
   Nerup, J
   Nierras, C
   Pociot, F
   Rich, SS
AF Cooper, J. D.
   Howson, J. M. M.
   Smyth, D.
   Walker, N. M.
   Stevens, H.
   Yang, J. H. M.
   She, J. -X.
   Eisenbarth, G. S.
   Rewers, M.
   Todd, J. A.
   Akolkar, B.
   Concannon, P.
   Erlich, H. A.
   Julier, C.
   Morahan, G.
   Nerup, J.
   Nierras, C.
   Pociot, F.
   Rich, S. S.
CA Type 1 Diabet Genetics Consortium
TI Confirmation of novel type 1 diabetes risk loci in families
SO DIABETOLOGIA
LA English
DT Article
DE Families; Population stratification bias; Power; Replication;
   Susceptibility; Type 1 diabetes
ID GENOME-WIDE ASSOCIATION
AB Over 50 regions of the genome have been associated with type 1 diabetes risk, mainly using large case/control collections. In a recent genome-wide association (GWA) study, 18 novel susceptibility loci were identified and replicated, including replication evidence from 2,319 families. Here, we, the Type 1 Diabetes Genetics Consortium (T1DGC), aimed to exclude the possibility that any of the 18 loci were false-positives due to population stratification by significantly increasing the statistical power of our family study.
   We genotyped the most disease-predicting single-nucleotide polymorphisms at the 18 susceptibility loci in 3,108 families and used existing genotype data for 2,319 families from the original study, providing 7,013 parent-child trios for analysis. We tested for association using the transmission disequilibrium test.
   Seventeen of the 18 susceptibility loci reached nominal levels of significance (p < 0.05) in the expanded family collection, with 14q24.1 just falling short (p = 0.055). When we allowed for multiple testing, ten of the 17 nominally significant loci reached the required level of significance (p < 2.8 x 10(-3)). All susceptibility loci had consistent direction of effects with the original study.
   The results for the novel GWA study-identified loci are genuine and not due to population stratification. The next step, namely correlation of the most disease-associated genotypes with phenotypes, such as RNA and protein expression analyses for the candidate genes within or near each of the susceptibility regions, can now proceed.
C1 [Cooper, J. D.; Howson, J. M. M.; Smyth, D.; Walker, N. M.; Stevens, H.; Yang, J. H. M.; Todd, J. A.] Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn,Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab,Dept Med Ge, Cambridge CB2 0YX, England.
   [She, J. -X.] Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA.
   [Eisenbarth, G. S.; Rewers, M.] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA.
   [Akolkar, B.] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA.
   [Concannon, P.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA.
   [Concannon, P.; Rich, S. S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
   [Erlich, H. A.] Roche Mol Syst, Pleasanton, CA USA.
   [Julier, C.] Ctr Natl Genotypage, Evry, France.
   [Julier, C.] Fac Med Denis Diderot, INSERM, UMR S958, Paris, France.
   [Julier, C.] Univ Paris 07, Paris, France.
   [Morahan, G.] Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia.
   [Morahan, G.] Univ Western Australia, Ctr Diabet Res, Western Australian Inst Med Res, Perth, WA 6009, Australia.
   [Nerup, J.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
   [Nerup, J.] Hagedorn Res Inst, Gentofte, Denmark.
   [Nierras, C.] Juvenile Diabet Res Fdn, New York, NY USA.
   [Pociot, F.] Glostrup Cty Hosp, Glostrup Res Inst, Glostrup, Denmark.
   [Rich, S. S.] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA.
RP Cooper, JD (reprint author), Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn,Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab,Dept Med Ge, Cambridge CB2 0YX, England.
EM jason.cooper@cimr.cam.ac.uk
RI Todd, John/A-3542-2010; 
OI Walker, Neil/0000-0001-9796-7688; Concannon,
   Patrick/0000-0002-5801-1859; Pociot, Flemming/0000-0003-3274-5448
FU National Institute of Diabetes and Digestive and Kidney Diseases
   (NIDDK); 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
   (JDRF); Juvenile Diabetes Research Foundation International; Wellcome
   Trust; National Institute for Health Research Cambridge Biomedical
   Centre; Wellcome Trust [079895];  [U01 DK062418]
FX We gratefully acknowledge the participation of all the patients and
   family members. We acknowledge use of DNA from the Human Biological Data
   Interchange and Diabetes UK for the USA and UK multiplex families,
   respectively, D. Savage of the Belfast Health and Social Care Trust, C.
   Patterson and D. Carson of Queen's University Belfast and P. Maxwell of
   Belfast City Hospital for the Northern Irish families, the Genetics of
   Type 1 Diabetes in Finland (GET1FIN; J. Tuomilehto, L. Kinnunen, E.
   Tuomilehto-Wolf, V. Harjutsalo and T. Valle of the National Public
   Health Institute, Helsinki) for the Finnish families, and C. Guja and C.
   Ionescu-Tirgoviste of the Institute of Diabetes 'N Paulescu', Romania
   for the Romanian families. This research uses resources provided by the
   T1DGC, a collaborative clinical study sponsored by the National
   Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
   National Institute of Allergy and Infectious Diseases, National Human
   Genome Research Institute, National Institute of Child Health and Human
   Development, and Juvenile Diabetes Research Foundation International
   (JDRF) and supported by U01 DK062418. We also thank H. Stevens, P.
   Clarke, G. Coleman, S. Duley, D. Harrison, S. Hawkins, M. Maisuria, T.
   Mistry and N. Taylor from the JDRF/Wellcome Trust Diabetes and
   Inflammation Laboratory for preparation of DNA samples and David Clayton
   from the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory for
   useful discussions.; This work was funded by the Juvenile Diabetes
   Research Foundation International, the Wellcome Trust and the National
   Institute for Health Research Cambridge Biomedical Centre. The Cambridge
   Institute for Medical Research is in receipt of a Wellcome Trust
   Strategic Award (079895).
NR 10
TC 21
Z9 22
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD APR
PY 2012
VL 55
IS 4
BP 996
EP 1000
DI 10.1007/s00125-012-2450-3
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 904GJ
UT WOS:000301182000016
PM 22278338
ER

PT J
AU Ammary-Risch, NJ
   Aguilar, M
   Goodman, LS
   Quiroz, L
AF Ammary-Risch, Neyal J.
   Aguilar, Marcela
   Goodman, Laura Saunders
   Quiroz, Leslie
TI Diabetes and Healthy Eyes Toolkit A Community Health Worker Program to
   Prevent Vision Loss and Blindness Among People With Diabetes
SO FAMILY & COMMUNITY HEALTH
LA English
DT Article
DE blindness prevention; diabetes; diabetic eye disease; Hispanics/Latinos;
   vision loss; promotores
ID INTERVENTION; RETINOPATHY; PREVALENCE; ADULTS; TRIAL; CARE
AB Diabetic eye disease is a leading cause of vision loss and blindness in the United States and disproportionately affects Hispanics/Latinos. This article provides an overview of the Diabetes and Healthy Eyes Toolkit, a culturally and linguistically appropriate resource designed for community health workers to educate people with diabetes about eye health complications. The toolkit provides science-based, easy-to-understand information that can be used to conduct interactive, educational sessions about diabetes and eye health, the importance of comprehensive dilated eye examinations at least once a year for people with diabetes, and other ways to prevent vision loss and blindness.
C1 [Ammary-Risch, Neyal J.] NEI, Natl Eye Hlth Educ Program, NIH, Bethesda, MD 20892 USA.
   [Aguilar, Marcela; Goodman, Laura Saunders; Quiroz, Leslie] ICF Int, Rockville, MD USA.
RP Ammary-Risch, NJ (reprint author), NEI, Natl Eye Hlth Educ Program, NIH, 2020 Vis Pl, Bethesda, MD 20892 USA.
EM ammaryn@nei.nih.gov
NR 21
TC 4
Z9 4
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0160-6379
J9 FAM COMMUNITY HEALTH
JI Fam. Community Health
PD APR-JUN
PY 2012
VL 35
IS 2
BP 103
EP 110
DI 10.1097/FCH.0b013e3182464fc0
PG 8
WC Family Studies; Public, Environmental & Occupational Health
SC Family Studies; Public, Environmental & Occupational Health
GA 899DQ
UT WOS:000300795700004
PM 22367257
ER

PT J
AU Spinner, JR
   Alvarado, M
AF Spinner, Jovonni R.
   Alvarado, Matilde
TI Salud Para Su Carozon-A Latino Promotora-Led Cardiovascular Health
   Education Program
SO FAMILY & COMMUNITY HEALTH
LA English
DT Article
DE education; heart disease; health disparities; Latino; promotora
ID AFRICAN-AMERICAN; WORKERS; DISEASE; DESIGN; ADULTS; RISK
AB Salud Para Su Carozon is a culturally sensitive, community-based program to increase heart healthy knowledge and behaviors among Latinos. Promotoras were trained using a 10-session manual to teach participants from 7 communities about heart disease risk factors and skills to achieve heart healthy behaviors. In 435 participants with pre-to-post self-reported data, there were increases in physical activity outside of work (57%-78%), heart health knowledge (49%-76%), and confidence in preparing heart healthy meals (66%-81%) (all Ps < .001). Results suggest that promotoras can provide effective health education to improve heart health risk behaviors in select Latino communities.
C1 [Spinner, Jovonni R.; Alvarado, Matilde] NHLBI, Div Applicat Res Discoveries, NIH, Bethesda, MD 20892 USA.
RP Spinner, JR (reprint author), NHLBI, Div Applicat Res Discoveries, NIH, 31 Ctr Dr,MSC 2480, Bethesda, MD 20892 USA.
EM Jovonni.spinner@nih.gov
NR 25
TC 7
Z9 8
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0160-6379
J9 FAM COMMUNITY HEALTH
JI Fam. Community Health
PD APR-JUN
PY 2012
VL 35
IS 2
BP 111
EP 119
DI 10.1097/FCH.0b013e3182465058
PG 9
WC Family Studies; Public, Environmental & Occupational Health
SC Family Studies; Public, Environmental & Occupational Health
GA 899DQ
UT WOS:000300795700005
PM 22367258
ER

PT J
AU Tomasi, D
   Volkow, ND
AF Tomasi, Dardo
   Volkow, Nora D.
TI Gender differences in brain functional connectivity density
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE fMRI; scale-free networks; default mode networks; consciousness;
   resting-state; functional connectomes; local functional connectivity
   density; lFCD
ID INDEPENDENT COMPONENT ANALYSIS; RESTING-STATE DATA; ALZHEIMERS-DISEASE;
   SEX-DIFFERENCES; WORKING-MEMORY; DEFAULT MODE; SMALL-WORLD; FMRI;
   ACTIVATION; NETWORK
AB The neural bases of gender differences in emotional, cognitive, and socials behaviors are largely unknown. Here, magnetic resonance imaging data from 336 women and 225 men revealed a gender dimorphism in the functional organization of the brain. Consistently across five research sites, women had 14% higher local functional connectivity density (lFCD) and up to 5% higher gray matter density than men in cortical and subcortical regions. The negative power scaling of the lFCD was steeper for men than for women, suggesting that the balance between strongly and weakly connected nodes in the brain is different across genders. The more distributed organization of the male brain than that of the female brain could help explain the gender differences in cognitive style and behaviors and in the prevalence of neuropsychiatric diseases (i.e., autism spectrum disorder). Hum Brain Mapp, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Lab Neuroimaging, 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 Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481]
FX Contract grant sponsor: National Institutes of Alcohol Abuse and
   Alcoholism; Contract grant number: 2RO1AA09481.
NR 36
TC 54
Z9 55
U1 4
U2 42
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD APR
PY 2012
VL 33
IS 4
BP 849
EP 860
DI 10.1002/hbm.21252
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 906JI
UT WOS:000301341000008
PM 21425398
ER

PT J
AU Jin, SH
   Lin, P
   Hallett, M
AF Jin, Seung-Hyun
   Lin, Peter
   Hallett, Mark
TI Reorganization of brain functional small-world networks during finger
   movements
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE functional small-world networks; economical reorganization; EEG; simple
   sequential finger-tapping task
ID SCIENTIFIC HYPOTHESIS GENERATION; GRAPH-THEORETICAL ANALYSIS; NEURONAL
   SYNCHRONY; MUTUAL INFORMATION; OSCILLATORY SYNCHRONY; BIMANUAL
   MOVEMENTS; COMPLEX NETWORKS; CORTICAL AREAS; BETA RHYTHMS; MOTOR
AB A functional measure of brain organization is the efficiency of functional connectivity. The degree of functional connectivity can differ during a task compared to the rest, and to study this issue, we investigated the functional connectivity networks in healthy subjects during a simple, right-handed, sequential finger-tapping task using graph theoretic measures. EEGs were recorded from 58 channels in 15 healthy subjects at rest and during a motor task. We estimated mutual information values of wavelet coefficients to create an association matrix between EEG electrodes and produced a series of adjacency matrices or graphs, A, by thresholding with network cost. These graphs are called small-world networks, and we assessed their efficiency measures. We found economical small-world properties in brain functional connectivity networks in the alpha and beta band networks. The efficiency of the brain networks was enhanced during the task in the beta band networks, but not in the alpha band networks. A regional efficiency analysis during the task showed that the bilateral primary motor and left sensory areas showed increased nodal efficiency, Enodal, whereas decreased Enodal was found over the posterior parietal areas. The present study provides evidence for the reorganization of brain functional connectivity networks in a motor task with the greatest increase in Enodal in motor executive areas. Hum Brain Mapp, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Jin, Seung-Hyun; Lin, Peter; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
EM hallettm@mail.nih.gov
FU NINDS, NIH
FX Contract grant sponsor: Intramural Research Program of the NINDS, NIH.
NR 63
TC 28
Z9 29
U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD APR
PY 2012
VL 33
IS 4
BP 861
EP 872
DI 10.1002/hbm.21253
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 906JI
UT WOS:000301341000009
PM 21484955
ER

PT J
AU Liu, YL
   Keil, A
   Ding, MZ
AF Liu, Yuelu
   Keil, Andreas
   Ding, Mingzhou
TI Effects of emotional conditioning on early visual processing: Temporal
   dynamics revealed by ERP single-trial analysis
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE conditioning; emotional learning; single-trial analysis; ASEO;
   event-related potential
ID GENERALIZED ANXIETY DISORDER; EVENT-RELATED POTENTIALS; FACIAL
   EXPRESSIONS; AUDITORY-CORTEX; HUMAN AMYGDALA; GRANGER CAUSALITY;
   REPETITION SUPPRESSION; INFEROTEMPORAL CORTEX; UNCONDITIONED STIMULI;
   AFFECTIVE PERCEPTION
AB Studies using event-related potentials (ERPs) have shown that affectively arousing stimuli enhance attention and perception. In addition, simple neutral stimuli, when paired with emotionally engaging unconditioned stimuli (i.e., the CS+) in classical conditioning paradigms, were found to evoke increased sensory responses as learning progresses, compared to responses elicited by the same stimuli not paired with a noxious stimulus (CS-). To date the detailed trial-to-trial temporal dynamics of this sensory facilitation process is not known. Signal averaging required for the ERP analysis eliminates trial-to-trial information of temporal cortical dynamics. In the current study, a novel single-trial analysis method called Analysis of Single-trial ERP and Ongoing activity (ASEO) was adopted to study the detailed electrocortical dynamics of sensory processing during classical aversive conditioning. Focusing on the P1 component of the ERP evoked by simple grating patterns serving as CS+ and CS-, we found that over a session of conditioning trials, there were three phases of P1 amplitude changes for both CS+ and CS-: (1) an initial decrease phase, (2) a subsequent increase phase, and (3) a final habituating phase. Tests on the rates of P1 amplitude changes in each of the three phases between CS+ and CS- conditions revealed differential effects of CS+ and CS- for all three phases. No such effects were found for a session of control trials where the same grating patterns were paired with checkerboards. We interpret these results as providing evidence supporting the view that emotional experience can modulate early visual processing and dynamics of perceptual learning. Hum Brain Mapp, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Liu, Yuelu; Ding, Mingzhou] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
   [Keil, Andreas] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA.
   [Keil, Andreas] Univ Florida, NIMH Ctr Emot & Attent, Gainesville, FL 32611 USA.
RP Ding, MZ (reprint author), Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, J-285 Biomed Sci Bldg,POB 116131, Gainesville, FL 32611 USA.
EM MDing@bme.ufl.edu
RI Liu, Yuelu/C-8434-2013; Keil, Andreas/F-9427-2011; Liu,
   Yuelu/I-3542-2015
OI Keil, Andreas/0000-0002-4064-1924; 
NR 66
TC 7
Z9 7
U1 4
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD APR
PY 2012
VL 33
IS 4
BP 909
EP 919
DI 10.1002/hbm.21259
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 906JI
UT WOS:000301341000013
PM 21500315
ER

PT J
AU Lockenhoff, CE
   Terracciano, A
   Ferrucci, L
   Costa, PT
AF Loeckenhoff, Corinna E.
   Terracciano, Antonio
   Ferrucci, Luigi
   Costa, Paul T., Jr.
TI Five-Factor Personality Traits and Age Trajectories of Self-Rated
   Health: The Role of Question Framing
SO JOURNAL OF PERSONALITY
LA English
DT Article
ID ALL-CAUSE MORTALITY; QUALITY-OF-LIFE; NEO-PI-R; OLD-AGE; SUBJECTIVE
   HEALTH; BIG 5; FUNCTIONAL ABILITY; PRIMARY-CARE; ADULTS; WOMEN
AB We examined the influence of personality traits on mean levels and age trends in 4 single-item measures of self-rated health: general rating, comparison to age peers, comparison to past health, and expectations for future health. Community-dwelling participants (N?=?1,683) completed 7,474 self-rated health assessments over a period of up to 19 years. In hierarchical linear modeling analyses, age-associated declines differed across the 4 health items. Across age groups, high Neuroticism and low Conscientiousness, low Extraversion, and low Openness were associated with worse health ratings, with notable differences across the 4 health items. Furthermore, high Neuroticism predicted steeper declines in health ratings involving temporal comparisons. We consider theoretical implications regarding the mechanisms behind associations among personality traits and self-rated health.
C1 [Loeckenhoff, Corinna E.] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA.
   [Terracciano, Antonio; Ferrucci, Luigi; Costa, Paul T., Jr.] NIA, Bethesda, MD 20892 USA.
RP Lockenhoff, CE (reprint author), Cornell Univ, Dept Human Dev, Martha Van Rensselaer Hall, Ithaca, NY 14853 USA.
EM CEL72@cornell.edu
RI terracciano, antonio/B-1884-2008; 
OI Costa, Paul/0000-0003-4375-1712; Loeckenhoff,
   Corinna/0000-0003-1605-1323
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000183-22, ZIA AG000184-22, ZIA
   AG000197-03]
NR 82
TC 16
Z9 16
U1 0
U2 18
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3506
J9 J PERS
JI J. Pers.
PD APR
PY 2012
VL 80
IS 2
BP 375
EP 401
DI 10.1111/j.1467-6494.2011.00724.x
PG 27
WC Psychology, Social
SC Psychology
GA 903JQ
UT WOS:000301113000005
PM 21299558
ER

PT J
AU Purushotham, A
   Xu, Q
   Lu, J
   Foley, JF
   Yan, XJ
   Kim, DH
   Kemper, JK
   Li, XL
AF Purushotham, Aparna
   Xu, Qing
   Lu, Jing
   Foley, Julie F.
   Yan, Xingjian
   Kim, Dong-Hyun
   Kemper, Jongsook Kim
   Li, Xiaoling
TI Hepatic Deletion of SIRT1 Decreases Hepatocyte Nuclear Factor 1
   alpha/Farnesoid X Receptor Signaling and Induces Formation of
   Cholesterol Gallstones in Mice
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NEGATIVE FEEDBACK-REGULATION; PANCREATIC BETA-CELLS; BILE-ACID;
   INSULIN-SECRETION; TRANSCRIPTION FACTORS; DEACETYLASE SIRT1; METABOLIC
   DISEASE; GENE-EXPRESSION; FXR; HOMEOSTASIS
AB SIRT1, a highly conserved NAD(+)-dependent protein deacetylase, is a key metabolic sensor that directly links nutrient signals to animal metabolic homeostasis. Although SIRT1 has been implicated in a number of hepatic metabolic processes, the mechanisms by which hepatic SIRT1 modulates bile acid metabolism are still not well understood. Here we report that deletion of hepatic SIRT1 reduces the expression of farnesoid X receptor (FXR), a nuclear receptor that regulates bile acid homeostasis. We provide evidence that SIRT1 regulates the expression of FXR through hepatocyte nuclear factor 1 alpha (HNF1 alpha). SIRT1 deficiency in hepatocytes leads to decreased binding of HNF1 alpha to the FXR promoter. Furthermore, we show that hepatocyte-specific deletion of SIRT1 leads to derangements in bile acid metabolism, predisposing the mice to development of cholesterol gallstones on a lithogenic diet. Taken together, our findings indicate that SIRT1 plays a vital role in the regulation of hepatic bile acid homeostasis through the HNF1 alpha/FXR signaling pathway.
C1 [Purushotham, Aparna; Xu, Qing; Lu, Jing; Li, Xiaoling] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA.
   [Foley, Julie F.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA.
   [Yan, Xingjian] Univ N Carolina, Undergrad Program Biol, Chapel Hill, NC USA.
   [Yan, Xingjian] Univ N Carolina, Undergrad Program Biostat, Chapel Hill, NC USA.
   [Kim, Dong-Hyun; Kemper, Jongsook Kim] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA.
RP Li, XL (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA.
EM lix3@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01 ES102205]
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute of Environmental Health Sciences, to X. L. (Z01
   ES102205).
NR 61
TC 27
Z9 29
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD APR
PY 2012
VL 32
IS 7
BP 1226
EP 1236
DI 10.1128/MCB.05988-11
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 906QC
UT WOS:000301360700003
PM 22290433
ER

PT J
AU Donovan, DM
   Bigelow, GE
   Brigham, GS
   Carroll, KM
   Cohen, AJ
   Gardin, JG
   Hamilton, JA
   Huestis, MA
   Hughes, JR
   Lindblad, R
   Marlatt, GA
   Preston, KL
   Selzer, JA
   Somoza, EC
   Wakim, PG
   Wells, EA
AF Donovan, Dennis M.
   Bigelow, George E.
   Brigham, Gregory S.
   Carroll, Kathleen M.
   Cohen, Allan J.
   Gardin, John G.
   Hamilton, John A.
   Huestis, Marilyn A.
   Hughes, John R.
   Lindblad, Robert
   Marlatt, G. Alan
   Preston, Kenzie L.
   Selzer, Jeffrey A.
   Somoza, Eugene C.
   Wakim, Paul G.
   Wells, Elizabeth A.
TI Primary outcome indices in illicit drug dependence treatment research:
   systematic approach to selection and measurement of drug use end-points
   in clinical trials
SO ADDICTION
LA English
DT Article
DE Clinical trials; drug dependence; end-points; primary outcome;
   self-report; toxicology; treatment research
ID MAUDSLEY ADDICTION PROFILE; ALCOHOL TREATMENT RESEARCH;
   SMOKING-CESSATION TRIALS; ABUSE-TREATMENT PATIENTS; LINE FOLLOW-BACK;
   SELF-REPORT; COCAINE-USE; SUBSTANCE USE; FORM 90; PROLONGED ABSTINENCE
AB Aims Clinical trials test the safety and efficacy of behavioral and pharmacological interventions in drug-dependent individuals. However, there is no consensus about the most appropriate outcome(s) to consider in determining treatment efficacy or on the most appropriate methods for assessing selected outcome(s). We summarize the discussion and recommendations of treatment and research experts, convened by the US National Institute on Drug Abuse, to select appropriate primary outcomes for drug dependence treatment clinical trials, and in particular the feasibility of selecting a common outcome to be included in all or most trials. Methods A brief history of outcomes employed in prior drug dependence treatment research, incorporating perspectives from tobacco and alcohol research, is included. The relative merits and limitations of focusing on drug-taking behavior, as measured by self-report and qualitative or quantitative biological markers, are evaluated. Results Drug-taking behavior, measured ideally by a combination of self-report and biological indicators, is seen as the most appropriate proximal primary outcome in drug dependence treatment clinical trials. Conclusions We conclude that the most appropriate outcome will vary as a function of salient variables inherent in the clinical trial, such as the type of intervention, its target, treatment goals (e. g. abstinence or reduction of use) and the perspective being taken (e. g. researcher, clinical program, patient, society). It is recommended that a decision process, based on such trial variables, be developed to guide the selection of primary and secondary outcomes as well as the methods to assess them.
C1 [Donovan, Dennis M.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98105 USA.
   [Donovan, Dennis M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA.
   [Bigelow, George E.] Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, Baltimore, MD USA.
   [Brigham, Gregory S.] Maryhaven, Columbus, OH USA.
   [Carroll, Kathleen M.] Yale Univ, Sch Med, Dept Psychiat, Div Addict, West Haven, CT 06516 USA.
   [Cohen, Allan J.] Bay Area Addict Res & Treatment, Sherman Oaks, CA USA.
   [Gardin, John G.] ADAPT Inc, Roseburg, OR USA.
   [Hamilton, John A.] Reg Network Programs Inc, Shelton, CT USA.
   [Huestis, Marilyn A.; Preston, Kenzie L.] NIDA, Intramural Res Program, Baltimore, MD USA.
   [Hughes, John R.] Univ Vermont, Dept Psychiat, Burlington, VT USA.
   [Lindblad, Robert] EMMES Corp, Rockville, MD USA.
   [Marlatt, G. Alan] Univ Washington, Dept Psychol, Addict Behav Res Ctr, Seattle, WA 98105 USA.
   [Selzer, Jeffrey A.] Comm Phys Hlth, Albany, NY USA.
   [Somoza, Eugene C.] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA.
   [Wakim, Paul G.] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
   [Wells, Elizabeth A.] Univ Washington, Sch Social Work, Seattle, WA 98105 USA.
RP Donovan, DM (reprint author), Univ Washington, Alcohol & Drug Abuse Inst, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA.
EM ddonovan@u.washington.edu
RI Preston, Kenzie/J-5830-2013; 
OI Preston, Kenzie/0000-0003-0603-2479; Brigham,
   Gregory/0000-0003-1150-4493; Carroll, Kathleen/0000-0003-3263-3374
FU NIDA NIH HHS [U10 DA013038, U10 DA013714, R01 DA015969, P50 DA009241]
NR 100
TC 55
Z9 55
U1 4
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD APR
PY 2012
VL 107
IS 4
BP 694
EP 708
DI 10.1111/j.1360-0443.2011.03473.x
PG 15
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 899QV
UT WOS:000300832100003
PM 21781202
ER

PT J
AU Zou, S
   Carey, JR
   Liedo, P
   Ingram, DK
   Yu, BB
AF Zou, Sige
   Carey, James R.
   Liedo, Pablo
   Ingram, Donald K.
   Yu, Binbing
TI Prolongevity effects of a botanical with oregano and cranberry extracts
   in Mexican fruit flies: examining interactions of diet restriction and
   age
SO AGE
LA English
DT Article
DE Lifespan; Cranberry; Oregano; Dietary restriction; Reproduction; Aging
   intervention; Dietary nutrient; Anastrepha ludens Loew
ID LIFE-SPAN; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; CALORIC
   RESTRICTION; ANASTREPHA-LUDENS; RESVERATROL; DISEASE; EXTENSION; MICE;
   REPRODUCTION
AB Botanicals rich with phytochemicals have numerous health benefits. Dietary restriction (DR) extends lifespan in diverse species. We previously demonstrated that an oregano-cranberry (OC) mixture can promote longevity in the Mexican Fruit fly (Mexfly, Anastrepha ludens Loew). However, little is known about the interaction between botanicals and DR, and the age-dependent effect of botanicals on lifespan and reproduction. Here we investigated these issues by feeding Mexflies a full or DR diet supplemented with or without 2% OC. Lifespan and daily egg production of individual flies were recorded. The effect of short-term OC supplementation was evaluated by implementing the supplementation at three age intervals-young, middle, and old age. We found that OC increased lifespan of Mexflies on the full or DR diet when compared to their respective controls. OC increased reproduction of females on the full diet and, to a lesser extent, on the DR diet. Short-term OC supplementation was not sufficient to extend lifespan for males at all three age intervals nor for females at young and old age intervals. However, OC supplementation at the middle age interval was sufficient to extend lifespan in females, while only OC supplementation at the young age interval increased reproduction in females. Our findings suggest that OC extends lifespan and promotes reproduction partly through DR-independent pathways, and short-term supplementation have varied impact on longevity and reproduction. This also suggests a positive interaction between non-genetic interventions in promoting longevity and provides guidance for using botanicals as aging interventions in humans.
C1 [Zou, Sige] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
   [Carey, James R.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
   [Liedo, Pablo] Colegio Frontera Sur, Tapachula, Chiapas, Mexico.
   [Ingram, Donald K.] Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA.
   [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA.
RP Zou, S (reprint author), NIA, Lab Expt Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM zous@grc.nia.nih.gov
RI Liedo, Pablo/E-9313-2010
OI Liedo, Pablo/0000-0002-0004-1721
FU NIA, NIH [P01-AG022500-01, P01-AG08761-10]; Cranberry Institute
FX We would like to thank A. Oropeza, R. Bustamente, E. de Leon, S.
   Salgado, S. Rodriguez, R. Rincon, and G. Rodas for excellent technical
   support; Edward Spangler and Anne White-Olson for editing the
   manuscript; and the Moscamed-Moscafrut facility in Metapa, Chiapas,
   Mexico, for Mexflies and lab space. This project was supported by grants
   from the NIA, NIH to JRC (P01-AG022500-01; P01-AG08761-10), and the
   Cranberry Institute to SZ, and the Intramural Research Program at the
   NIA, NIH to SZ.
NR 41
TC 7
Z9 7
U1 1
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD APR
PY 2012
VL 34
IS 2
BP 269
EP 279
DI 10.1007/s11357-011-9230-8
PG 11
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 899YT
UT WOS:000300853300001
PM 21455602
ER

PT J
AU Hyun, DH
   Kim, J
   Moon, C
   Lim, CJ
   de Cabo, R
   Mattson, MP
AF Hyun, Dong-Hoon
   Kim, Jiyeong
   Moon, Chanil
   Lim, Chang-Jin
   de Cabo, Rafael
   Mattson, Mark P.
TI The plasma membrane redox enzyme NQO1 sustains cellular energetics and
   protects human neuroblastoma cells against metabolic and proteotoxic
   stress
SO AGE
LA English
DT Article
DE Aging; NAD(+)/NADH; Neuroprotection; NQO1; PMRS; Proteotoxicity
ID FACTOR-KAPPA-B; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; NAD(P)H-QUINONE
   OXIDOREDUCTASE-1; PARKINSONS-DISEASE; CEREBRAL-ISCHEMIA; IN-VITRO;
   INDUCED DIFFERENTIATION; GLUCOSE DEPRIVATION; NAD(+) DEPLETION
AB The plasma membrane redox system (PMRS) of nicotinamide adenine dinucleotide (NADH)-related enzymes plays a key role in the maintenance of cellular energetics. During the aging process, neural cells are particularly sensitive to impaired energy metabolism and oxidative damage, but the involvement of the PMRS in these processes is unknown. Here, we used human neuroblastoma cells with either elevated or reduced levels of the PMRS enzyme NADH-quinone oxidoreductase 1 (NQO1) to investigate how the PMRS regulates neuronal stress responses. Cells with elevated NQO1 levels were more resistant to death induced by 2-deoxyglucose, potassium cyanide (energetic stress), and lactacystin (proteotoxic stress), but were not protected from being killed by H2O2 and serum withdrawal. The NAD(+)(an oxidized form of NADH)/NADH ratio was maintained at a significantly higher level in cells overexpressing NQO1, consistent with enhanced levels of NQO1 activity. Levels of the neuroprotective transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and nuclear factor (erythroid-derived 2)-like 2, and the protein chaperone HSP70 were elevated in cells overexpressing NQO1. Cells in which NQO1 levels were decreased by RNA interference exhibited increased vulnerability to death induced by 2-deoxyglucose and lactacystin. Thus, a higher NAD(+)/NADH ratio and activation of adaptive stress response pathways are enhanced by the PMRS in neuroblastoma cells, enabling them to maintain redox homeostasis under conditions of energetic and proteotoxic stress. These findings have implications for the development of therapeutic interventions for neural tumors and neurodegenerative conditions.
C1 [Hyun, Dong-Hoon; Kim, Jiyeong] Ewha Womans Univ, Div Life & Pharmaceut Sci, Dept Life Sci, Seoul 120750, South Korea.
   [Moon, Chanil] Hanyang Univ, Seoul Hosp, Cell Therapy Ctr, Seoul 133792, South Korea.
   [Lim, Chang-Jin] Kangwon Natl Univ, Div Life Sci, Chunchon 200701, South Korea.
   [de Cabo, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Hyun, DH (reprint author), Ewha Womans Univ, Div Life & Pharmaceut Sci, Dept Life Sci, Seoul 120750, South Korea.
EM hyundh@ewha.ac.kr
RI Mattson, Mark/F-6038-2012; de Cabo, Rafael/J-5230-2016; 
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU National Research Foundation of Korea (NRF); Ministry of Education,
   Science and Technology, South Korea [20100003064]
FX We thank Alan Sartorelli (Yale University School of Medicine, USA) and
   David Ross (University of Colorado at Denver, USA) for providing pBE8
   and antibodies against NQO1, respectively. This study was supported, in
   whole and in part, by the Basic Science Research Program through the
   National Research Foundation of Korea (NRF) funded by the Ministry of
   Education, Science and Technology (20100003064), South Korea.
NR 68
TC 6
Z9 6
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD APR
PY 2012
VL 34
IS 2
BP 359
EP 370
DI 10.1007/s11357-011-9245-1
PG 12
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 899YT
UT WOS:000300853300008
PM 21487704
ER

PT J
AU Abbatecola, AM
   Chiodini, P
   Gallo, C
   Lakatta, E
   Sutton-Tyrrell, K
   Tylavsky, FA
   Goodpaster, B
   de Rekeneire, N
   Schwartz, AV
   Paolisso, G
   Harris, T
AF Abbatecola, Angela Marie
   Chiodini, Paolo
   Gallo, Ciro
   Lakatta, Edward
   Sutton-Tyrrell, Kim
   Tylavsky, Frances A.
   Goodpaster, Bret
   de Rekeneire, Natalie
   Schwartz, Ann V.
   Paolisso, Giuseppe
   Harris, Tamara
CA Hlth ABC Study
TI Pulse wave velocity is associated with muscle mass decline: Health ABC
   study
SO AGE
LA English
DT Article
DE Aging; Sarcopenia; Pulse wave velocity; Vascular stiffness
ID X-RAY ABSORPTIOMETRY; BODY-COMPOSITION; ARTERIAL STIFFNESS; AORTIC
   STIFFNESS; CARDIOVASCULAR MORTALITY; SKELETAL-MUSCLE; OLDER-ADULTS;
   ALL-CAUSE; STRENGTH; SARCOPENIA
AB Age-related mechanisms that lead to sarcopenia are not entirely understood. Basal leg blood flow declines with aging by augmented sympathetic vasoconstriction and arterial stiffening, thus a dysfunction in blood vessel dynamics may have an independent role on sarcopenia. We determined whether pulse wave velocity (PWV), marker of arterial stiffness, was associated with skeletal muscle decline. Observational cohort study of older adults(70-79 years) living in Pittsburgh, PA, USA or Memphis, TN, USA. Analyses included 2,405 participants. Correlations among muscle parameters including skeletal muscle density and intermuscular adipose tissue using mid-thigh CT scans were assessed. Linear mixed models tested the association between the change in the sarcopenic index (SI) (assessed by dual energy X-ray absorptiometry) over time and baseline PWV independently of multiple confounders. SI was defined: appendicular lean mass/squared height and calculated at every follow-up (n = 6). Baseline PWV was significantly higher in black women compared to white women (930 +/- 431 vs. 843 +/- 366; p = 0.0001), while there were no significant differences between black and white men (943 +/- 402 vs. 911 +/- 375; p = 0.1786). Baseline analyses showed an independent negative association between PWV and muscle parameters after adjusting for confounders in both genders. The PWV-by-race interaction was significant in women and analyses are reported separately by race. Prospective mixed models showed that PWV was an independent determinant of the SI in all men (beta = -0.1043; p = 0.0065) and in white women (beta = -0.1091; p = 0.0192). In analyses examining the effect of arterial stiffness on limb lean mass over time, PWV correlated with lower leg (beta = -0.2196; p = 0.0002)and arm mass (beta = -0.0985; p = 0.0011) in all men and lower leg mass(beta = -0.1608; p = 0.0027)in white women. In older persons, arterial stiffening is associated with skeletal muscle mass decline differently for race and gender.
C1 [Paolisso, Giuseppe] Univ Naples 2, Dept Geriatr Med & Metab Dis, Div Med Interna 6, I-80138 Naples, Italy.
   [Abbatecola, Angela Marie] INRCA, Ancona, Italy.
   [Chiodini, Paolo; Gallo, Ciro] Univ Naples 2, Dept Med & Publ Hlth, I-80138 Naples, Italy.
   [Lakatta, Edward] NIA, Cardiovasc Sci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
   [Sutton-Tyrrell, Kim] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
   [Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
   [Goodpaster, Bret] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
   [de Rekeneire, Natalie] Yale Univ, Sch Med, Ctr Disabil & Disabling Disorders, New Haven, CT USA.
   [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Paolisso, G (reprint author), Univ Naples 2, Dept Geriatr Med & Metab Dis, Div Med Interna 6, Piazza Miraglia 2, I-80138 Naples, Italy.
EM giuseppe.paolisso@unina2.it
RI Chiodini, Paolo/E-7290-2014; 
OI Chiodini, Paolo/0000-0003-0139-2264; Paolisso,
   Giuseppe/0000-0002-2137-455X
FU National Institute on Aging at the National Institute of Health
   [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of
   Health, National Institute on Aging
FX This study was by the following contracts: National Institute on Aging
   at the National Institute of Health with the following contract numbers:
   N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106. This research was supported
   in part by the Intramural Research Program of the National Institute of
   Health, National Institute on Aging
NR 27
TC 24
Z9 25
U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD APR
PY 2012
VL 34
IS 2
BP 469
EP 478
DI 10.1007/s11357-011-9238-0
PG 10
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 899YT
UT WOS:000300853300017
PM 21479573
ER

PT J
AU White, CD
   Erdemir, HH
   Sacks, DB
AF White, Colin D.
   Erdemir, Huseyin H.
   Sacks, David B.
TI IQGAP1 and its binding proteins control diverse biological functions
SO CELLULAR SIGNALLING
LA English
DT Review
DE Cell signalling; IQGAP; IQGAP1; Scaffold protein
ID GROWTH-FACTOR; CELL-MIGRATION; TRANSCRIPTION FACTOR; SCAFFOLD PROTEINS;
   INTEGRATES CA2+/CALMODULIN; SUSCEPTIBILITY LOCI; NEURITE OUTGROWTH;
   ACTIN-FILAMENTS; EXOCYST COMPLEX; ERBB RECEPTORS
AB IQGAP proteins have been identified in a wide spectrum of organisms, ranging from yeast to humans. The most extensively studied family member is the ubiquitously expressed scaffold protein IQGAP1, which participates in multiple essential aspects of mammalian biology. IQGAP1 mediates these effects by binding to and regulating the function of numerous interacting proteins. Over ninety proteins have been reported to associate with IQGAP1, either directly or as part of a larger complex. In this review, we summarise those IQGAP1 binding partners that have been identified in the last five years. The molecular mechanisms by which these interactions contribute to the functions of receptors and their signalling cascades, small GTPase function, cytoskeletal dynamics, neuronal regulation and intracellular trafficking are evaluated. The evidence that has accumulated recently validates the role of IQGAP1 as a scaffold protein and expands the repertoire of cellular activities in which it participates. Published by Elsevier Inc.
C1 [Erdemir, Huseyin H.; Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
   [White, Colin D.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA.
   [White, Colin D.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Sacks, DB (reprint author), NIH, Dept Lab Med, Room 2C306,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sacksdb@mail.nih.gov
OI Sacks, David/0000-0003-3100-0735
FU Department of Defense; US National Institutes of Health
FX The authors apologise to all whose primary work could not be cited owing
   to space restrictions. This work was supported in part by the Department
   of Defense Breast Cancer Research Programme (to C.D.W.) and by the
   Intramural Research Programme of the US National Institutes of Health.
NR 121
TC 85
Z9 90
U1 4
U2 27
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
EI 1873-3913
J9 CELL SIGNAL
JI Cell. Signal.
PD APR
PY 2012
VL 24
IS 4
BP 826
EP 834
DI 10.1016/j.cellsig.2011.12.005
PG 9
WC Cell Biology
SC Cell Biology
GA 900WL
UT WOS:000300922300002
PM 22182509
ER

PT J
AU Kwon, O
   Soung, NK
   Thimmegowda, NR
   Jeong, SJ
   Jang, JH
   Moon, DO
   Chung, JK
   Lee, KS
   Kwon, YT
   Erikson, RL
   Ahn, JS
   Kim, BY
AF Kwon, Osong
   Soung, Nak Kyun
   Thimmegowda, N. R.
   Jeong, Sook Jung
   Jang, Jae Hyuk
   Moon, Dong-Oh
   Chung, Jong Kyeong
   Lee, Kyung Sang
   Kwon, Yong Tae
   Erikson, Raymond Leo
   Ahn, Jong Seog
   Kim, Bo Yeon
TI Patulin induces colorectal cancer cells apoptosis through EGR-1
   dependent ATF3 up-regulation
SO CELLULAR SIGNALLING
LA English
DT Article
DE ATF3; EGR-1; ROS; Patulin
ID ACTIVATING TRANSCRIPTION FACTOR-3; ENDOPLASMIC-RETICULUM STRESS; OXYGEN
   SPECIES ROS; NF-KAPPA-B; E-CADHERIN; PENICILLIUM-EXPANSUM; MYCOTOXIN
   PATULIN; MAMMALIAN-CELLS; IN-VITRO; GENE
AB Patulin is a fungal mycotoxin of Aspergilus and Penicillium that is commonly found in rotting fruits and exerts its potential toxic effect mainly by reactive oxygen species (ROS) generation. However, the effect of patulin on cancer cells as well as its intracellular mechanism has been controversial and not clearly defined yet In this study, patulin was found to induce G1/S accumulation and cell growth arrest accompanied by caspase-3 activation, PARP cleavage and ATF3 expression in human colon cancer cell line HCT116. Ser/Thr phosphorylation of a transcription factor. EGR-1, was increased while its expression did not change upon patulin treatment to the cells. Knockdown of ATF3 and EGR-1 using their respective siRNAs showed EGR-1 dependent ATF3 expression. Moreover, treatment of the cells with antioxidants N-acetylcysteine (NAC) and glutathione (GSH) revealed that patulin induced ATF3 expression and apoptosis were dependent on ROS generation. ATF3 expression was also increased by patulin in other colorectal cancer cell types, Caco2 and SW620. Collectively, our data present a new anti-cancer molecular mechanism of patulin, suggesting EGR-1 and ATF3 as critical targets for the development of anti-cancer chemotherapeutics. In this regard, patulin could be a candidate for the treatment of colorectal cancers. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Kwon, Osong; Soung, Nak Kyun; Thimmegowda, N. R.; Jeong, Sook Jung; Jang, Jae Hyuk; Ahn, Jong Seog; Kim, Bo Yeon] KRIBB, Cheongwon Gun 363883, South Korea.
   [Moon, Dong-Oh] Daegu Univ, Dept Nat Sci, Kyungsan, South Korea.
   [Chung, Jong Kyeong] Seoul Natl Univ, Natl Creat Res Initiat Ctr, Seoul, South Korea.
   [Chung, Jong Kyeong] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea.
   [Lee, Kyung Sang] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
   [Kwon, Yong Tae] Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA.
   [Kwon, Yong Tae] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
   [Erikson, Raymond Leo] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Ahn, JS (reprint author), KRIBB, 685-2 Ochang Eup, Cheongwon Gun 363883, South Korea.
EM jsahn@kribb.re.kr; bykim@kribb.re.kr
FU National Research Foundation of Korea (NRF); Ministry of Education,
   Science and Technology (MEST); KRIBB Research Initiative
FX This work was supported by the World Class Institute (WCI) Program,
   Global R&D Center (GRDC) Program of the National Research Foundation of
   Korea (NRF) funded by the Ministry of Education, Science and Technology
   (MEST), and also supported by KRIBB Research Initiative Program.
NR 53
TC 29
Z9 30
U1 2
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD APR
PY 2012
VL 24
IS 4
BP 943
EP 950
DI 10.1016/j.cellsig.2011.12.017
PG 8
WC Cell Biology
SC Cell Biology
GA 900WL
UT WOS:000300922300016
PM 22230687
ER

PT J
AU Hicks, JD
   Donsante, A
   Pierson, TM
   Gillespie, MJ
   Chou, DE
   Kaler, SG
AF Hicks, Julia D.
   Donsante, Anthony
   Pierson, Tyler M.
   Gillespie, Matthew J.
   Chou, Denise E.
   Kaler, Stephen G.
TI Increased frequency of congenital heart defects in Menkes disease
SO CLINICAL DYSMORPHOLOGY
LA English
DT Article
DE ATP7A; congenital heart disease; lysyl oxidase; Menkes disease;
   occipital horn syndrome
ID DISEASE/OCCIPITAL HORN SYNDROME; LYSYL OXIDASE; DOWN-REGULATION; COPPER;
   MOUSE; GENE; DYSFUNCTION; ANEURYSMS; EMBRYOS; ATP7A
AB ATP7A is a copper-transporting ATPase critical for central and peripheral nervous system function. Mutations in ATP7A cause Menkes disease and occipital horn syndrome (OHS), allelic X-linked recessive conditions that feature vascular abnormalities ascribed to low activity of lysyl oxidase, a copper-dependent enzyme. From a recently created Menkes disease/OHS patient registry, we identified four of 95 patients with major congenital heart defects (4.2%), a proportion exceeding the general population prevalence (approximate to 1%). In conjunction with mouse models of Menkes disease, OHS, and lysyl oxidase deficiency (which feature aortic aneurysms, irregular attachment between vascular endothelium and mesoderm, and other defects of embryological development) our observation suggests an important role of copper metabolism in cardiac development. Congenital heart disease may be an under-appreciated abnormality in Menkes disease, and should be considered in a broad differential diagnosis of cardiac defects found prenatally in male fetuses. Conversely, newborn infants with suspected or confirmed Menkes disease should be evaluated for heart disease by careful clinical examination and echocardiography, if indicated. Clin Dysmorphol 21: 59-63 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Hicks, Julia D.; Donsante, Anthony; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA.
   [Pierson, Tyler M.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
   [Gillespie, Matthew J.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Pediat Cardiol, Philadelphia, PA 19104 USA.
   [Chou, Denise E.] New York Presbyterian Hosp Cornell, Dept Neurol, New York, NY USA.
RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bldg 10,Room 10N313,10 Ctr Dr,MSC 1853, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
FU National Institutes of Health, Division of Intramural Research
   [HD008768]
FX This work was supported by the National Institutes of Health, Division
   of Intramural Research, Grant HD008768 (NICHD).
NR 33
TC 7
Z9 8
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0962-8827
J9 CLIN DYSMORPHOL
JI Clin. Dysmorphol.
PD APR
PY 2012
VL 21
IS 2
BP 59
EP 63
DI 10.1097/MCD.0b013e32834ea52b
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 902RP
UT WOS:000301056800001
PM 22134099
ER

PT J
AU Ji, ZY
   Weldon, RH
   Marchetti, F
   Chen, H
   Li, GL
   Xing, CH
   Kurtovich, E
   Young, S
   Schmid, TE
   Waidyanatha, S
   Rappaport, S
   Zhang, LP
   Eskenazi, B
AF Ji, Zhiying
   Weldon, Rosana H.
   Marchetti, Francesco
   Chen, Howard
   Li, Guilan
   Xing, Caihong
   Kurtovich, Elaine
   Young, Suzanne
   Schmid, Thomas E.
   Waidyanatha, Suramya
   Rappaport, Stephen
   Zhang, Luoping
   Eskenazi, Brenda
TI Comparison of aneuploidies of chromosomes 21, X, and Y in the blood
   lymphocytes and sperm of workers exposed to benzene
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE occupational exposure; chromosome 21; sex chromosomes
ID IN-SITU HYBRIDIZATION; CHINESE WORKERS; LEUKEMIA; ABERRATIONS; HUMANS;
   HEMATOTOXICITY; METABOLISM; INTERPHASE; BIOMARKERS; ANEUSOMY
AB Benzene is a primary industrial chemical and a ubiquitous environmental pollutant that causes human leukemia and maybe other malignancies. Occupational exposure to benzene has been associated with increased chromosomal aneuploidies in blood lymphocytes and, in separate studies, in sperm. However, aneuploidy detection in somatic and germ cells within the same benzene-exposed individuals has never been reported. To compare aneuploidies in blood lymphocytes and sperm within the same individuals exposed to benzene, a cross-sectional study was conducted in 33 benzene-exposed male workers and 33 unexposed workers from Chinese factories. Air benzene concentrations in the exposed workers ranged from below the detection limit to 24 ppm (median, 2.9 ppm) and were undetectable in the unexposed subjects. Aneuploidies of chromosomes 21, X, and Y in blood lymphocytes were examined by multicolor fluorescence in situ hybridization and were compared to the previously reported aneuploidies in sperm. The results showed that benzene exposure was positively associated with the gain of chromosome 21 but not sex chromosomes in blood lymphocytes. This was in contrast to analysis of sperm, where the gain of sex chromosomes, but not chromosome 21, was significantly increased in the exposed workers. Furthermore, a significant correlation in the gain of sex chromosomes between blood lymphocytes and sperm was observed among the unexposed subjects, but not among the exposed workers. The findings suggest that benzene exposure induces aneuploidies in both blood cells and sperm within the same individuals, but selectively affects chromosome 21 in blood lymphocytes and the sex chromosomes in sperm. Environ. Mol. Mutagen. 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Weldon, Rosana H.; Kurtovich, Elaine; Young, Suzanne; Eskenazi, Brenda] Univ Calif Berkeley, CERCH, Sch Publ Hlth, Berkeley, CA 94704 USA.
   [Marchetti, Francesco; Xing, Caihong; Schmid, Thomas E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
   [Xing, Caihong] Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Dept Toxicol, Beijing, Peoples R China.
   [Waidyanatha, Suramya] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
   [Ji, Zhiying; Chen, Howard; Li, Guilan; Rappaport, Stephen; Zhang, Luoping] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
RP Eskenazi, B (reprint author), Univ Calif Berkeley, CERCH, Sch Publ Hlth, 1995 Univ Ave,Suite 265, Berkeley, CA 94704 USA.
EM luoping@berkeley.edu; eskenazi@berkeley.edu
OI Marchetti, Francesco/0000-0002-9435-4867
FU American Petroleum Institute; American Chemistry Council; National
   Institute of Environmental Health Sciences [R03 ES015340-02,
   P42ES004705]; Lawrence Livermore National Laboratory [W-7405-END-48];
   Lawrence Berkeley National Laboratory [DE-AC02-05CH11231]; National
   Institutes of Health; Jennifer and Brian Maxwell Chair
FX S.R. has received consulting and expert testimony fees from law firms
   representing plaintiffs' cases involving exposure to benzene and has
   received research support from the American Petroleum Institute and the
   American Chemistry Council. All other authors declare that they have no
   actual or potential competing financial interests.; Grant sponsor:
   National Institute of Environmental Health Sciences; Grant numbers: R03
   ES015340-02; P42ES004705; Grant sponsor: Lawrence Livermore National
   Laboratory; Grant number: W-7405-END-48; Grant sponsor: Lawrence
   Berkeley National Laboratory; Grant number: DE-AC02-05CH11231; Grant
   sponsors: National Institutes of Health; Jennifer and Brian Maxwell
   Chair.
NR 35
TC 6
Z9 7
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD APR
PY 2012
VL 53
IS 3
BP 218
EP 226
DI 10.1002/em.21683
PG 9
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 901PT
UT WOS:000300980000007
PM 22351378
ER

PT J
AU Hobbs, CA
   Chhabra, RS
   Recio, L
   Streicker, M
   Witt, KL
AF Hobbs, Cheryl A.
   Chhabra, Rajendra S.
   Recio, Leslie
   Streicker, Michael
   Witt, Kristine L.
TI Genotoxicity of styrene-acrylonitrile trimer in brain, liver, and blood
   cells of weanling F344 rats
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE chromosomal damage; DNA damage; Comet assay; micronuclei; superfund;
   childhood cancer
ID ZERO DOSE CONTROL; COMET ASSAY; MICRONUCLEUS ASSAY; DNA-DAMAGE;
   CHEMICALS; FREQUENCY; SENSITIVITY; GUIDELINES; EXPOSURE; MUTANTS
AB Styreneacrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P < 0.0001) in MN-RET were measured in both male and female rats administered SAN Trimer. The RET population was reduced in high dose male rats, suggesting chemical-related bone marrow toxicity. Results of the Comet assay showed significant, dose-related increases in DNA damage in brain cells of male (P < 0.0074) and female (P < 0.0001) rats; increased levels of DNA damage were also measured in liver cells and leukocytes of treated rats. Chemical-related cytotoxicity was not indicated in any of the tissues examined for DNA damage. The results of this subacute MN/Comet assay indicate induction of significant genetic damage in multiple tissues of weanling F344 male and female rats after oral exposure to SAN Trimer. Environ. Mol. Mutagen. 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Hobbs, Cheryl A.; Recio, Leslie] Dept Genet & Mol Toxicol, Res Triangle Pk, NC USA.
   [Chhabra, Rajendra S.; Witt, Kristine L.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
   [Streicker, Michael] ILS Inc, Invest Toxicol Div, Res Triangle Pk, NC 27709 USA.
RP Hobbs, CA (reprint author), ILS Inc, Genet & Mol Toxicol Div, POB 13501, Res Triangle Pk, NC 27709 USA.
EM chobbs@ils-inc.com
FU National Institute of Environmental Health Sciences (NIEHS)
   [N01-ES-35514]
FX Contract grant sponsor: National Institute of Environmental Health
   Sciences (NIEHS)/National Toxicology Program (NTP); Contract grant
   number: N01-ES-35514.
NR 40
TC 3
Z9 3
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD APR
PY 2012
VL 53
IS 3
BP 227
EP 238
DI 10.1002/em.21680
PG 12
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 901PT
UT WOS:000300980000008
PM 22351108
ER

PT J
AU Sonpavde, G
   Di Lorenzo, G
   Higano, CS
   Kantoff, PW
   Madan, R
   Shore, ND
AF Sonpavde, Guru
   Di Lorenzo, Giuseppe
   Higano, Celestia S.
   Kantoff, Philip W.
   Madan, Ravi
   Shore, Neal D.
TI The Role of Sipuleucel-T in Therapy for Castration-Resistant Prostate
   Cancer: A Critical Analysis of the Literature
SO EUROPEAN UROLOGY
LA English
DT Article
DE Immunotherapy; Prostate cancer; Sipuleucel-T; CTLA-4; PD-1; Prostvac VF
   Tricom; Ipilimumab
ID COLONY-STIMULATING FACTOR; PHASE-I TRIAL; CELLULAR IMMUNOTHERAPY;
   RECEPTOR ACTIVATOR; ACID-PHOSPHATASE; DENDRITIC CELLS; WORKING GROUP;
   END-POINTS; ANTIGEN; SURVIVAL
AB Context: Sipuleucel-T, an autologous antigen-presenting cell vaccine loaded with prostate acid phosphatase conjugated with granulocyte-macrophage colony-stimulating factor (GM-CSF), yielded a survival advantage in men with metastatic castration-resistant prostate cancer (mCRPC).
   Objective: Critically analyze the role of sipuleucel-T in therapy for mCRPC.
   Evidence acquisition: A systematic review of the literature was performed in June 2011 using Medline and an abstract search of major cancer conferences. The search strategy included the terms sipuleucel-T, APC-8015, castration-resistant, prostate cancer, and immunotherapy.
   Evidence synthesis: The era of targeted immunotherapy was initiated with the regulatory approval in 2010 of sipuleucel-T for asymptomatic and minimally symptomatic mCRPC. The median survival was prolonged by 4.1 mo (25.8 vs 21.7 mo; hazard ratio: 0.78; 95% confidence interval, 0.61-0.98; p = 0.03), coupled with an improvement in 3-yr survival (31.7% vs 23.0%). Outcomes were characterized by the lack of tumor regression or delay in progression. Further development is proceeding in earlier stages of prostate cancer and in the context of a host of emerging agents.
   Conclusions: The addition of sipuleucel-T, an immunotherapeutic agent, to the armamentarium represents a paradigm shift in therapy for mCRPC. The rational combination and proper sequencing of sipuleucel-T with other newly approved agents (abiraterone acetate, cabazitaxel) and emerging agents (MDV3100, TAK-700, ipilimumab) will be important to evaluate. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Sonpavde, Guru] Texas Oncol, Houston, TX USA.
   [Sonpavde, Guru] Vet Affairs Med Ctr, Houston, TX 77030 USA.
   [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA.
   [Di Lorenzo, Giuseppe] Univ Naples Federico 2, Naples, Italy.
   [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA.
   [Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA.
   [Madan, Ravi] NCI, Bethesda, MD 20892 USA.
   [Shore, Neal D.] Grand Strand Urol, Myrtle Beach, SC USA.
RP Sonpavde, G (reprint author), 501 Med Ctr Blvd, Webster, TX 77598 USA.
EM guru.sonpavde@usoncology.com
FU Bellicum Pharmaceuticals; Dendreon; Medivation; Cougar Biotech; Dendreon
   Corporation
FX I certify that all conflicts of interest, including specific financial
   interests and relationships and affiliations relevant to the subject
   matter or materials discussed in the manuscript (eg,
   employment/affiliation, grants or funding, consultancies, honoraria,
   stock ownership or options, expert testimony, royalties, or patents
   filed, received, or pending), are the following: Guru Sonpavde receives
   research support for his institution from Bellicum Pharmaceuticals and
   is on the speakers' bureau or advisory boards for Dendreon, Centocor
   Biotech, Amgen, Novartis, and Sanofi-Aventis. Giuseppe Di Lorenzo
   receives research support from, and is on the advisory board for,
   Dendreon. Celestia S. Higano receives research support for her
   institution from Dendreon, Medivation, and Cougar Biotech and is on the
   advisory board for Dendreon, Medivation, and Amgen. Philip W. Kantoff is
   a consultant to Dendreon, Bellicum Pharmaceuticals, and BN-IT. Neal D.
   Shore receives research support from, and is on the advisory board for,
   Dendreon.; Dendreon Corporation sponsored the trials that are discussed
   in this review.
NR 51
TC 12
Z9 12
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2012
VL 61
IS 4
BP 639
EP 647
DI 10.1016/j.eururo.2011.10.027
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 899TB
UT WOS:000300838000013
PM 22036643
ER

PT J
AU Sonpavde, G
   Di Lorenzo, G
   Higano, CS
   Kantoff, PW
   Madan, RA
   Shore, ND
AF Sonpavde, Guru
   Di Lorenzo, Giuseppe
   Higano, Celestia S.
   Kantoff, Philip W.
   Madan, Ravi A.
   Shore, Neal D.
TI Reply form Authors re: Bertrand Tombal. Continuous Improvement Versus
   Innovation: The Case for Sipuleucel-T. Eur Urol 2012;61:648-9
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID RESISTANT PROSTATE-CANCER; IMMUNOTHERAPY; TRIAL
C1 [Sonpavde, Guru] Texas Oncol, Houston, TX USA.
   [Sonpavde, Guru] Vet Affairs Med Ctr, Houston, TX 77030 USA.
   [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA.
   [Di Lorenzo, Giuseppe] Univ Naples Federico II, Naples, Italy.
   [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA.
   [Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA.
   [Madan, Ravi A.] NCI, Bethesda, MD 20892 USA.
   [Shore, Neal D.] Grand Strand Urol, Myrtle Beach, SC USA.
RP Sonpavde, G (reprint author), 501 Med Ctr Blvd, Webster, TX 77598 USA.
EM guru.sonpavde@usoncology.com
NR 10
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2012
VL 61
IS 4
BP 650
EP 651
DI 10.1016/j.eururo.2011.12.007
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 899TB
UT WOS:000300838000015
ER

PT J
AU Stek, AM
   Best, BM
   Luo, W
   Capparelli, E
   Burchett, S
   Hu, C
   Li, H
   Read, JS
   Jennings, A
   Barr, E
   Smith, E
   Rossi, SS
   Mirochnick, M
AF Stek, A. M.
   Best, B. M.
   Luo, W.
   Capparelli, E.
   Burchett, S.
   Hu, C.
   Li, H.
   Read, J. S.
   Jennings, A.
   Barr, E.
   Smith, E.
   Rossi, S. S.
   Mirochnick, M.
TI Effect of pregnancy on emtricitabine pharmacokinetics
SO HIV MEDICINE
LA English
DT Article
DE emtricitabine; HIV; pregnancy; pharmacokinetics
ID HUMAN-IMMUNODEFICIENCY-VIRUS; STEADY-STATE PHARMACOKINETICS;
   HEALTHY-VOLUNTEERS; WOMEN; ZIDOVUDINE; INFANTS; SAFETY; COMBINATION;
   NEVIRAPINE; LAMIVUDINE
AB Objectives
   The aim of the study was to describe emtricitabine pharmacokinetics during pregnancy and postpartum.
   Methods
   The International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT), formerly Pediatric AIDS Clinical Trials Group (PACTG), study P1026s is a prospective pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including a cohort taking emtricitabine 200 mg once daily. Intensive steady-state 24-hour emtricitabine pharmacokinetic profiles were performed during the third trimester and 6-12 weeks postpartum, and on maternal and umbilical cord blood samples collected at delivery. Emtricitabine was measured by liquid chromatography-mass spectrometry with a quantification limit of 0.0118 mg/L. The target emtricitabine area under the concentration versus time curve, from time 0 to 24 hours post dose (AUC(0-24)), was >= 7 mg h/L (<= 30% reduction from the typical AUC of 10 mg h/L in nonpregnant historical controls). Third-trimester and postpartum pharmacokinetics were compared within subjects.
   Results
   Twenty-six women had pharmacokinetics assessed during the third trimester (median 35 weeks of gestation) and 22 postpartum (median 8 weeks postpartum). Mean [90% confidence interval (CI)] emtricitabine pharmacokinetic parameters during the third trimester vs. postpartum were, respectively: AUC: 8.0 (7.1-8.9) vs. 9.7 (8.6-10.9) mg h/L (P = 0.072); apparent clearance (CL/F): 25.0 (22.6-28.3) vs. 20.6 (18.4-23.2) L/h (P = 0.025); 24 hour post dose concentration (C-24): 0.058 (0.037-0.063) vs. 0.085 (0.070-0.010) mg/L (P = 0.006). The mean cord: maternal ratio was 1.2 (90% CI 1.0-1.5). The viral load was < 400 HIV-1 RNA copies/mL in 24 of 26 women in the third trimester, in 24 of 26 at delivery, and in 15 of 19 postpartum. Within-subject comparisons demonstrated significantly higher CL/F and significantly lower C24 during pregnancy; however, the C24 was well above the inhibitory concentration 50%, or drug concentration that suppresses viral replication by half (IC50) in all subjects.
   Conclusions
   While we found higher emtricitabine CL/F and lower C24 and AUC during pregnancy compared with postpartum, these changes were not sufficiently large to warrant dose adjustment during pregnancy. Umbilical cord blood concentrations were similar to maternal concentrations.
C1 [Stek, A. M.] Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
   [Best, B. M.; Luo, W.; Capparelli, E.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
   [Best, B. M.; Capparelli, E.; Rossi, S. S.] Univ Calif San Diego, Dept Pediat, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA.
   [Burchett, S.] Childrens Hosp, Boston, MA 02115 USA.
   [Hu, C.; Li, H.] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
   [Read, J. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
   [Jennings, A.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
   [Barr, E.] Childrens Hosp, Aurora, CO USA.
   [Smith, E.] NIAID, Bethesda, MD 20892 USA.
   [Mirochnick, M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Stek, AM (reprint author), LAC USC, Maternal Child & Adolescent HIV Program, 1640 Marengo St,3rd Floor, Los Angeles, CA 90033 USA.
EM stek@usc.edu
RI Ghartouchent, malek/B-9088-2012; Hu, Chengcheng/A-8391-2017
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
   AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
   Human Development (NICHD); National Institute of Mental Health (NIMH)
   [AI068632]; Statistical and Data Analysis Center at Harvard School of
   Public Health, under the National Institute of Allergy and Infectious
   Diseases [U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG) [1
   U01 AI068616]; IMPAACT Group; National Institute of Allergy and
   Infectious Diseases (NIAID); NICHD International and Domestic Pediatric
   and Maternal HIV Clinical Trials Network; 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 AI068632), 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) and the NICHD International and
   Domestic Pediatric and Maternal HIV Clinical Trials Network funded by
   NICHD (contract number N01-DK-9-001/HHSN267200800001C).
NR 25
TC 17
Z9 17
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-2662
J9 HIV MED
JI HIV Med.
PD APR
PY 2012
VL 13
IS 4
BP 226
EP 235
DI 10.1111/j.1468-1293.2011.00965.x
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 902PZ
UT WOS:000301051700005
PM 22129166
ER

PT J
AU Kim, H
   Lee, Y
   Yoo, H
   Kim, J
   Kong, H
   Yoon, JH
   Jung, Y
   Kim, YM
AF Kim, Hyunjeong
   Lee, Yonghyun
   Yoo, Hansun
   Kim, Jihye
   Kong, Hyesik
   Yoon, Jeong-Hyun
   Jung, Yunjin
   Kim, Young Mi
TI Synthesis and evaluation of sulfate conjugated metronidazole as a
   colon-specific prodrug of metronidazole
SO JOURNAL OF DRUG TARGETING
LA English
DT Article
DE Controlled drug delivery; drug delivery; drug targeting; oral drug
   delivery
ID INFLAMMATORY-BOWEL-DISEASE; DRUG-DELIVERY SYSTEMS; POTENTIAL PRODRUGS;
   21-SULFATE SODIUM; PHARMACOKINETICS; AMEBIASIS; THERAPY; RATS
AB For an effort to improve therapeutic property of metronidazole (MTZ) which is a drug of choice for protozoal infections such as luminal amoebiasis, sulfate conjugated metronidazole (MTZS) was prepared and evaluated as a colon-specific prodrug of MTZ. The apparent partition coefficient of MTZ was greatly reduced by the sulfate conjugation. While (bio) chemically stable in the contents of the upper intestine, MTZS was rapidly cleaved to liberate MTZ on incubation with the cecal contents of rats. MTZ liberated from MTZS metabolized quickly at least partly by a microbial nitroreductase, suggesting the relevance of the metabolism to bioactivation of MTZ for antimicrobial action. Consistent with the hypothesis, MTZS elicited antibacterial activity in the cecal contents, which was as potent as free MTZ. The systemic absorption of MTZS was very low after oral administration of MTZS. In parallel with this, whereas MTZ disappeared mostly during the transit of the proximal small intestine, a substantial amount of MTZS remained in the small intestine, moving down to the large intestine where it metabolized rapidly. In addition to the efficient colonic delivery of MTZS, MTZS markedly reduced the systemic absorption of MTZ. Taken together, MTZS may be a potential colon-specific prodrug of MTZ which possesses improved therapeutic and toxicological properties.
C1 [Kim, Hyunjeong; Lee, Yonghyun; Yoo, Hansun; Kim, Jihye; Yoon, Jeong-Hyun; Jung, Yunjin; Kim, Young Mi] Pusan Natl Univ, Coll Pharm, Lab Biomed Med Chem, Pusan 609735, South Korea.
   [Kong, Hyesik] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Kim, YM (reprint author), Pusan Natl Univ, Coll Pharm, Lab Biomed Med Chem, Pusan 609735, South Korea.
EM jungy@pusan.ac.kr; ymikim@pusan.ac.kr
FU Korea Research Foundation (KRF); Korea government (MEST)
   [KRF-2008-314-E00315, KRF-2007-314-E00245]
FX This work was supported by the Korea Research Foundation (KRF) grant
   funded by the Korea government (MEST) (KRF-2008-314-E00315 and
   KRF-2007-314-E00245).
NR 28
TC 4
Z9 5
U1 4
U2 12
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1061-186X
J9 J DRUG TARGET
JI J. Drug Target.
PD APR
PY 2012
VL 20
IS 3
BP 255
EP 263
DI 10.3109/1061186X.2011.639024
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 900HV
UT WOS:000300878500006
PM 22118327
ER

PT J
AU Massad, LS
   Weber, KM
   Wilson, TE
   Goderre, JL
   Hessol, NA
   Henry, D
   Colie, C
   Strickler, HD
   Levine, AM
   Watts, DH
   Evans, CT
AF Massad, L. Stewart
   Weber, Kathleen M.
   Wilson, Tracey E.
   Goderre, Johanna L.
   Hessol, Nancy A.
   Henry, Donna
   Colie, Christine
   Strickler, Howard D.
   Levine, Alexandra M.
   Watts, D. Heather
   Evans, Charlesnika T.
TI Correlating Knowledge of Cervical Cancer Prevention and Human
   Papillomavirus With Compliance After Colposcopy Referral
SO JOURNAL OF LOWER GENITAL TRACT DISEASE
LA English
DT Article
DE cervical cancer prevention; Pap test; health education; perceived
   stress; HIV in women
ID HUMAN-IMMUNODEFICIENCY-VIRUS; WOMENS INTERAGENCY HIV; INFORMATION
   LEAFLETS; PAPANICOLAOU SMEARS; FOLLOW-UP; ABNORMALITIES; PREVALENCE;
   INFECTION; ADHERENCE; STRESS
AB Objective. This study aimed to assess the impact of knowledge of cervical cancer biology and prevention as well as noncognitive measures on compliance with colposcopy referral in a high-risk population.
   Methods. Participants in a US cohort of women with human immunodeficiency virus (HIV) infection and at-risk comparison women completed behavior questionnaires and instruments measuring knowledge of cervical cancer prevention, depressive symptoms, trust in physicians, and perceived stress. Examinations including Pap tests also were conducted. Associations with compliance with resulting indicated colposcopy were assessed in multivariable models.
   Results. Of 326 women with indicated colposcopy, 222 (68%) were compliant with colposcopy referral and 104 (32%) were noncompliant. In multivariable analysis, better colposcopy compliance was associated with less education (odds ratio [OR] for compliance = 2.24, 95% confidence interval = 1.12-4.51 vs more than high school), previous abnormal Pap result (OR per previous abnormal Pap result = 1.08, 95% CI = 1.01-1.15), study site (OR for site with best vs worst compliance = 16.1, 95% CI = 2.91-88.6), and higher stress (OR for perceived stress scale 10 score >16 vs lower 3.25, 95% CI = 1.45-7.26).
   Conclusions. Noncognitive factors and how sites manage abnormal Pap testing affect colposcopy compliance. Educational interventions alone are unlikely to improve colposcopy compliance in similar high-risk populations.
C1 [Massad, L. Stewart] Washington Univ, Sch Med, Div Gyn Oncol, St Louis, MO 63110 USA.
   [Weber, Kathleen M.] John H Stroger Hosp Cook Cty, Hektoen Inst Med, Chicago, IL USA.
   [Weber, Kathleen M.] John H Stroger Hosp Cook Cty, CORE Ctr, Chicago, IL USA.
   [Wilson, Tracey E.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
   [Goderre, Johanna L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Hessol, Nancy A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Henry, Donna] Montefiore Med Ctr, Bronx, NY 10467 USA.
   [Colie, Christine] Georgetown Univ, Sch Med, Washington, DC USA.
   [Strickler, Howard D.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Levine, Alexandra M.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
   [Levine, Alexandra M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
   [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Evans, Charlesnika T.] Dept Vet Affairs Hines Vet Adm Med Ctr, Chicago, IL USA.
   [Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Massad, LS (reprint author), Washington Univ, Sch Med, Div Gyn Oncol, 4911 Barnes Jewish Hosp Plaza, St Louis, MO 63110 USA.
EM massadl@wudosis.wustl.edu
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
   UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [UO1-HD-32632]; National Cancer Institute; National
   Institute on Drug Abuse; National Institute on Deafness and Other
   Communication Disorders; National Center for Research Resources
   (UCSF-CTSI) [UL1 RR024131]
FX The WIHS is funded by the National Institute of Allergy and Infectious
   Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989,
   UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development (UO1-HD-32632).
   The study is cofunded by the National Cancer Institute, the National
   Institute on Drug Abuse, and the National Institute on Deafness and
   Other Communication Disorders. Funding is also provided by the National
   Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The
   contents of this publication are solely the responsibility of the
   authors and do not necessarily represent the official views of the
   National Institutes of Health.
NR 32
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U1 3
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1089-2591
J9 J LOW GENIT TRACT DI
JI J. Low. Genit. Tract. Dis.
PD APR
PY 2012
VL 16
IS 2
BP 98
EP 105
DI 10.1097/LGT.0b013e318238e83d
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 899YS
UT WOS:000300853200005
PM 22227841
ER

PT J
AU Yuan, A
   Xu, JF
   Zheng, G
AF Yuan, Ao
   Xu, Jinfeng
   Zheng, Gang
TI Root-n estimability of some missing data models
SO JOURNAL OF MULTIVARIATE ANALYSIS
LA English
DT Article
DE Information operator; Missing data model; Root-n estimability; Score
   operator
ID DOUBLY CENSORED-DATA; NONPARAMETRIC-ESTIMATION; SEMIPARAMETRIC MODELS;
   EMPIRICAL LIKELIHOOD; ASYMPTOTIC NORMALITY; SURVIVAL FUNCTION; LARGE
   SAMPLE; ESTIMATOR; INFORMATION; CONSISTENCY
AB It is known that in many missing data models, for example, survival data models, some parameters are root-n estimable while the others are not. When they are, their limiting distributions are often. Gaussian and easy to use. When they are not, their limiting distributions, if exists, are often non-Gaussian and difficult to evaluate. Thus it is important to have some preliminary assessments of the root-n estimability in these models. In this article, we study this problem for four missing data models: two-point interval censoring, double censoring, interval truncation, and a case-control genetic association model. For the first three models, we identify some parameters which are not root-n estimable. For some root-n estimable parameters, we derive the corresponding information bounds when they exist. Also, as the Cox regression model is commonly used for such data, we give asymptotic efficient information for these regression parameters. For the case-control genetic association model, we compute the asymptotic efficient information and relative efficiency, in relation to that of the full data, when only the case-control status data are available, as is often the case in practice. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Yuan, Ao] Howard Univ, Washington, DC 20059 USA.
   [Xu, Jinfeng] Natl Univ Singapore, Singapore 117546, Singapore.
   [Zheng, Gang] NIH, Bethesda, MD 20892 USA.
RP Yuan, A (reprint author), Howard Univ, Washington, DC 20059 USA.
EM yuanao@hotmail.com
OI Xu, Jinfeng/0000-0002-3165-2015
FU National Center for Research Resources at NIH [2G12RR003048]; National
   University of Singapore [R-155-000-112-112]
FX This work is supported in part by the National Center for Research
   Resources at NIH grant 2G12RR003048 (Yuan), and National University of
   Singapore, Grant R-155-000-112-112 (Xu).
NR 35
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U1 0
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0047-259X
J9 J MULTIVARIATE ANAL
JI J. Multivar. Anal.
PD APR
PY 2012
VL 106
BP 147
EP 166
DI 10.1016/j.jmva.2011.11.007
PG 20
WC Statistics & Probability
SC Mathematics
GA 900TP
UT WOS:000300913400010
PM 22505783
ER

PT J
AU Leopoldino, AM
   Squarize, CH
   Garcia, CB
   Almeida, LO
   Pestana, CR
   Polizello, ACM
   Uyemura, SA
   Tajara, EH
   Gutkind, JS
   Curti, C
AF Leopoldino, Andreia M.
   Squarize, Cristiane H.
   Garcia, Cristiana B.
   Almeida, Luciana O.
   Pestana, Cezar R.
   Polizello, Ana C. M.
   Uyemura, Sergio A.
   Tajara, Eloiza H.
   Gutkind, J. Silvio
   Curti, Carlos
TI Accumulation of the SET protein in HEK293T cells and mild oxidative
   stress: cell survival or death signaling
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE SET; I2PP2A; Oxidative stress; Cell death; Akt phosphorylation; PTEN
   phosphorylation
ID UNCOUPLING PROTEIN-3; PHOSPHATASE-ACTIVITY; ALZHEIMERS-DISEASE; NUCLEAR
   PTEN; CANCER-CELLS; MUSCLE-CELLS; PHOSPHORYLATION; EXPRESSION; TUMOR;
   APOPTOSIS
AB SET protein (I2PP2A) is an inhibitor of PP2A, which regulates the phosphorylated Akt (protein kinase B) levels. We assessed the effects of SET overexpression in HEK293T cells, both in the presence and the absence of mild oxidative stress induced by 50 mu M tert-butyl hydroperoxide. Immunoblotting assays demonstrated that SET accumulated in HEK293T cells and increased the levels of phosphorylated Akt and PTEN; in addition, SET decreased glutathione antioxidant defense of cell and increased expression of genes encoding antioxidant defense proteins. Immunofluorescence analysis demonstrated that accumulated SET was equally distributed in cytoplasm and nucleus; however, in cells that had been exposed to oxidative stress, SET was found in large aggregates in the cytoplasm. SET accumulation in HEK293T cells correlated with inhibition of basal apoptosis as evidenced by a decrease in annexin V staining and activity of caspases; under mild oxidative stress, SET accumulation correlated with caspase-independent cell death, as evidenced by increased PI and annexin V/PI double staining. The results suggest that accumulated SET could act via Akt/PTEN either as cell survival signal or as oxidative stress sensor for cell death.
C1 [Leopoldino, Andreia M.; Garcia, Cristiana B.; Almeida, Luciana O.; Uyemura, Sergio A.] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
   [Squarize, Cristiane H.] Univ Michigan, Sch Dent, Div Oral Pathol Med Radiol, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA.
   [Pestana, Cezar R.; Polizello, Ana C. M.; Curti, Carlos] Univ Sao Paulo, Dept Quim & Fis, Fac Ciencias Farmaceut Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
   [Tajara, Eloiza H.] Fac Med Sao Jose do Rio Preto, Dept Biol Mol, Sao Jose Do Rio Preto, SP, Brazil.
   [Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Leopoldino, AM (reprint author), Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
EM andreiaml@usp.br
RI Uyemura, Sergio/B-4656-2011; Leopoldino, Andreia/E-9926-2012; Curti,
   Carlos/H-6982-2016; Garcia, Cristiana/G-7601-2012; Pestana,
   Cezar/K-6250-2012; Inov Farmaceutica, Inct/K-2313-2013
OI Uyemura, Sergio/0000-0001-5505-9817; Leopoldino,
   Andreia/0000-0002-8313-4754; Curti, Carlos/0000-0001-8154-5595; Oliveira
   de Almeida, Luciana/0000-0002-5342-0434; 
FU FAPESP [2005/03380-2, 2006/06334-4, 2009/52228-0]; CNPq; CAPES; NIH,
   National Institute of Dental and Craniofacial Research
FX Research supported by FAPESP (Fellowship 2005/03380-2, Young research
   project 2006/06334-4, Grant 2009/52228-0), CNPq, CAPES and the
   Intramural Research Program of NIH, National Institute of Dental and
   Craniofacial Research. The authors thank Fabiana R. Morais for technical
   support with the FACS analysis.
NR 51
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Z9 10
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD APR
PY 2012
VL 363
IS 1-2
BP 65
EP 74
DI 10.1007/s11010-011-1158-x
PG 10
WC Cell Biology
SC Cell Biology
GA 900LP
UT WOS:000300888900007
PM 22143534
ER

PT J
AU Cornwell, BR
   Mueller, SC
   Kaplan, R
   Grillon, C
   Ernst, M
AF Cornwell, Brian R.
   Mueller, Sven C.
   Kaplan, Raphael
   Grillon, Christian
   Ernst, Monique
TI Anxiety, a benefit and detriment to cognition: Behavioral and
   magnetoencephalographic evidence from a mixed-saccade task
SO BRAIN AND COGNITION
LA English
DT Article
DE Anxiety; Beta oscillation; Magnetoencephalography; Saccadic eye
   movement; Stimulus-driven attention; Theta oscillation
ID MONKEY SUPERIOR COLLICULUS; ATTENTIONAL CONTROL-THEORY; STIMULUS-DRIVEN
   ATTENTION; INFERIOR FRONTAL GYRUS; ANTISACCADE TASK; EYE-MOVEMENTS;
   PREPULSE INHIBITION; RESPONSE-INHIBITION; WORKING-MEMORY; HUMAN BRAIN
AB Anxiety is typically considered an impediment to cognition. We propose anxiety-related impairments in cognitive-behavioral performance are the consequences of enhanced stimulus-driven attention. Accordingly, reflexive, habitual behaviors that rely on stimulus-driven mechanisms should be facilitated in an anxious state, while novel, flexible behaviors that compete with the former should be impaired. To test these predictions, healthy adults (N = 17) performed a mixed-saccade task, which pits habitual actions (pro-saccades) against atypical ones (anti-saccades), under anxiety-inducing threat of shock and safe conditions. Whole-head magnetoencephalography (MEG) captured oscillatory responses in the preparatory interval preceding target onset and saccade execution. Results showed threat-induced anxiety differentially impacted response times based on the type of saccade initiated, slowing anti-saccades but facilitating erroneous pro-saccades on anti-saccade trials. MEG source analyses revealed that successful suppression of reflexive pro-saccades and correct initiation of anti-saccades during threat was marked by increased theta power in right ventrolateral prefrontal cortical and midbrain regions (superior colliculi) implicated in stimulus-driven attention. Theta activity may delay stimulus-driven processes to enable generation of an anti-saccade. Moreover, compared to safety, threat reduced beta desynchronization in inferior parietal cortices during anti-saccade preparation but increased it during pro-saccade preparation. Differential effects in inferior parietal cortices indicate a greater readiness to execute anti-saccades during safety and to execute pro-saccades during threat. These findings suggest that, in an anxiety state, reduced cognitive-behavioral flexibility may stem from enhanced stimulus-driven attention, which may serve the adaptive function of optimizing threat detection. Published by Elsevier Inc.
C1 [Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
   [Cornwell, Brian R.; Kaplan, Raphael; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
   [Mueller, Sven C.] Univ Ghent, Dept Expt Clin & Hlth Psychol, Ghent, Belgium.
RP Ernst, M (reprint author), NIMH, Sect Dev & Affect Neurosci, NIH, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
OI Kaplan, Raphael/0000-0002-5023-1566
FU National Institute of Mental Health (NIMH) at the National Institutes of
   Health (NIH)
FX This work was supported by the Intramural Research Program of the
   National Institute of Mental Health (NIMH) at the National Institutes of
   Health (NIH).
NR 76
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Z9 12
U1 6
U2 26
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0278-2626
J9 BRAIN COGNITION
JI Brain Cogn.
PD APR
PY 2012
VL 78
IS 3
BP 257
EP 267
DI 10.1016/j.bandc.2012.01.002
PG 11
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 899HL
UT WOS:000300806900009
PM 22289426
ER

PT J
AU Chung, CC
   Boland, J
   Yeager, M
   Jacobs, KB
   Zhang, XJ
   Deng, ZM
   Matthews, C
   Berndt, SI
   Chanock, SJ
AF Chung, Charles C.
   Boland, Joseph
   Yeager, Meredith
   Jacobs, Kevin B.
   Zhang, Xijun
   Deng, Zuoming
   Matthews, Casey
   Berndt, Sonja I.
   Chanock, Stephen J.
TI Comprehensive resequence analysis of a 123-kb region of chromosome 11q13
   associated with prostate cancer
SO PROSTATE
LA English
DT Article
DE resequence; 11q13; prostate cancer; SNP
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; BREAST-CANCER; MULTIPLE
   LOCI; IDENTIFIES 5; RISK; VARIANTS; GENE; 8Q24; MYEOV
AB BACKGROUND Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 11q13.3 in men of European decent. A fine-mapping analysis with tag SNPs in the cancer genetic markers of susceptibility study identified three independent loci, marked by rs10896438, rs12793759, and rs10896449. This study further annotates common and uncommon variation across this region.
   METHODS. A next generation resequence analysis of a 122.9-kb region of 11q13.3 (68,642,755-68,765,690) was conducted in 78 unrelated individuals of European background, 1 CEPH trio, and 1 YRI trio.
   RESULTS. In total, 644 polymorphic loci were identified by our sequence analysis. Of these, 166 variants-118 SNPs and 48 insertion-deletion polymorphisms (indels)-were novel, namely not present in the 1000 Genomes or International HapMap Projects. We identified 22, 25, 6, and 4 variants strongly correlated (r(2) >= 0.8) with rs10896438, rs10896449, rs12793759, and rs11228565, respectively. HapMap SNPs were in linkage disequilibrium (r(2) >= 0.8) with 48%, 69%, 14%, and 60% of SNPs marking bins by rs10896438, rs10896449, rs12793759, and rs11228565, respectively.
   CONCLUSIONS. Our next generation resequence analysis compliments publicly available datasets of European descent (HapMap, build 28 and 1000 Genome, Pilot 1, October 2010), underscoring the value of targeted resequence analysis prior to initiating functional studies based on public databases alone. Increasing the number of common variants enables investigators to better prioritize variants for functional studies designed to uncover the biological basis of the direct association(s) in the region. Prostate 72: 476-486, 2012. Published 2011. This article is a U. S. Government work and is in the public domain in the USA.
C1 [Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Ctr,Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
   [Boland, Joseph; Yeager, Meredith; Jacobs, Kevin B.; Zhang, Xijun; Deng, Zuoming; Matthews, Casey] NCI, SAIC Frederick Inc, Adv Technol Program, Core Genotyping Facil, Frederick, MD 21701 USA.
RP Chanock, SJ (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Ctr,Dept Hlth & Human Serv,NIH, NCI 8717, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
   National Institutes of Health (NIH)
FX Grant sponsor: Intramural Research Program of the Division of Cancer
   Epidemiology and Genetics, National Cancer Institute, National
   Institutes of Health (NIH).; This study was supported by the Intramural
   Research Program of the Division of Cancer Epidemiology and Genetics,
   National Cancer Institute, National Institutes of Health (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 organization indicate
   endorsement by the US Government. The authors thank Drs. Christine Berg
   and Philip Prorok, Division of Cancer Prevention, NCI, the screening
   center investigators and staff of the PLCO Cancer Screening Trial, Mr.
   Thomas Riley and staff at Information Management Services, Inc., and Ms.
   Barbara O'Brien and staff at Westat, Inc. for their contributions to the
   PLCO Cancer Screening Trial. We thank Marie-Josephe Horner for editorial
   support. Finally, we acknowledge the study participants for donating
   their time and making this study possible.
NR 30
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U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD APR
PY 2012
VL 72
IS 5
BP 476
EP 486
DI 10.1002/pros.21450
PG 11
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 897ZN
UT WOS:000300703000002
PM 22468268
ER

PT J
AU Zheng, J
   Liu, F
   Lin, XL
   Wang, X
   Ding, Q
   Jiang, HW
   Chen, HY
   Lu, DR
   Jin, GF
   Hsing, AW
   Shao, Q
   Qi, J
   Ye, Y
   Wang, Z
   Gao, X
   Wang, GZ
   Chu, LW
   OuYang, J
   Huang, YC
   Chen, YB
   Gao, YT
   Shi, R
   Wu, QJ
   Wang, ML
   Zhang, ZD
   Hu, YL
   Sun, JL
   Zheng, SL
   Gao, X
   Xu, CL
   Mo, ZN
   Sun, YH
   Xu, JF
AF Zheng, Jie
   Liu, Fang
   Lin, Xiaoling
   Wang, Xiang
   Ding, Qiang
   Jiang, Haowen
   Chen, Hongyan
   Lu, Daru
   Jin, Guangfu
   Hsing, Ann W.
   Shao, Qiang
   Qi, Jun
   Ye, Yu
   Wang, Zhong
   Gao, Xin
   Wang, Guozeng
   Chu, Lisa W.
   OuYang, Jun
   Huang, Yichen
   Chen, Yanbo
   Gao, Yutang
   Shi, Rong
   Wu, Qijun
   Wang, Meilin
   Zhang, Zhengdong
   Hu, Yanlin
   Sun, Jielin
   Zheng, S. Lilly
   Gao, Xu
   Xu, Chuanliang
   Mo, Zengnan
   Sun, Yinghao
   Xu, Jianfeng
TI Predictive Performance of prostate cancer risk in Chinese men using 33
   reported prostate cancer risk-associated SNPs
SO PROSTATE
LA English
DT Article
DE genetic score; cumulative risk; prostate cancer; AUC; risk prediction;
   susceptibility; Chinese
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; VARIANTS; IDENTIFICATION;
   8Q24
AB BACKGROUND Genome-wide association studies (GWAS) have identified more than 30 single nucleotide polymorphisms (SNPs) that were reproducibly associated with prostate cancer (PCa) risk in populations of European descent. In aggregate, these variants have shown potential to predict risk for PCa in European men. However, their utility for PCa risk prediction in Chinese men is unknown.
   METHODS. We selected 33 PCa risk-related SNPs that were originally identified in populations of European descent. Genetic scores were estimated for subjects in a Chinese casecontrol study (1,108 cases and 1,525 controls) based on these SNPs. To assess the performance of the genetic score on its ability to predict risk for PCa, we calculated area under the curve (AUC) of the receiver operating characteristic (ROC) in combination with 10-fold crossvalidation.
   RESULTS. The genetic score was significantly higher for cases than controls (P = 5.91 x 10(-20)), and was significantly associated with risk of PCa in a dose-dependent manner (P for trend: 4.78 x 10(-18)). The AUC of the genetic score was 0.604 for risk prediction of PCa in Chinese men. When ORs derived from this Chinese study population were used to calculate genetic score, the AUCs were 0.631 for all 33 SNPs and 0.617 when using only the 11 significant SNPs.
   CONCLUSION. Our results indicate that genetic variants related to PCa risk may be useful for risk prediction in Chinese men. Prospective studies are warranted to further evaluate these findings. Prostate 72: 577-583, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Gao, Xu; Xu, Chuanliang; Sun, Yinghao] Second Mil Med Univ, Changhai Hosp, Dept Urol, Shanghai 200433, Peoples R China.
   [Zheng, Jie; Wang, Xiang; Ding, Qiang; Jiang, Haowen; Xu, Jianfeng] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai 200433, Peoples R China.
   [Liu, Fang; Lin, Xiaoling; Chen, Hongyan; Lu, Daru; Sun, Jielin; Zheng, S. Lilly; Xu, Jianfeng] Fudan Univ, Sch Life Sci, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China.
   [Chen, Hongyan; Lu, Daru; Xu, Jianfeng] Fudan Univ, Sch Life Sci, Key Lab Contemporary Anthropol, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
   [Jin, Guangfu; Sun, Jielin; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
   [Hsing, Ann W.; Chu, Lisa W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Shao, Qiang] Suzhou Municipal Hosp, Dept Urol, Suzhou, Peoples R China.
   [Qi, Jun; Huang, Yichen] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Urol, Shanghai, Peoples R China.
   [Ye, Yu; Hu, Yanlin; Mo, Zengnan] Guangxi Med Univ, Affiliated Hosp 1, Dept Urol, Guangxi, Peoples R China.
   [Wang, Zhong; Chen, Yanbo] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Urol, Shanghai, Peoples R China.
   [Gao, Xin] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Urol, Guangzhou 510275, Guangdong, Peoples R China.
   [Wang, Guozeng] Pudong Gongli Hosp, Dept Urol, Shanghai, Peoples R China.
   [OuYang, Jun] Suzhou Univ, Peoples Hosp 1, Dept Urol, Suzhou 215006, Peoples R China.
   [Gao, Yutang] Shanghai Canc Inst, Shanghai, Peoples R China.
   [Shi, Rong; Wu, Qijun] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai, Peoples R China.
   [Wang, Meilin; Zhang, Zhengdong] Nanjing Med Univ, Ctr Canc, Sch Publ Hlth, Dept Mol & Genet Toxicol, Nanjing, Jiangsu, Peoples R China.
   [Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Dept Urol, Winston Salem, NC 27103 USA.
   [Xu, Jianfeng] Van Andel Res Inst, Grand Rapids, MI USA.
RP Sun, YH (reprint author), Second Mil Med Univ, Changhai Hosp, Dept Urol, 168 Changhai Rd, Shanghai 200433, Peoples R China.
EM sunyh@medmail.com.cn; jxu@wfubmc.edu
FU National Cancer Institute [1R01CA129684-01]
FX Grant sponsor: National Cancer Institute; Grant number: 1R01CA129684-01.
NR 20
TC 16
Z9 18
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD APR
PY 2012
VL 72
IS 5
BP 577
EP 583
DI 10.1002/pros.21462
PG 7
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 897ZN
UT WOS:000300703000013
PM 21796652
ER

PT J
AU Padilla-Nash, HM
   Hathcock, K
   McNeil, NE
   Mack, D
   Hoeppner, D
   Ravin, R
   Knutsen, T
   Yonescu, R
   Wangsa, D
   Dorritie, K
   Barenboim, L
   Hu, Y
   Ried, T
AF Padilla-Nash, Hesed M.
   Hathcock, Karen
   McNeil, Nicole E.
   Mack, David
   Hoeppner, Daniel
   Ravin, Rea
   Knutsen, Turid
   Yonescu, Raluca
   Wangsa, Danny
   Dorritie, Kathleen
   Barenboim, Linda
   Hu, Yue
   Ried, Thomas
TI Spontaneous transformation of murine epithelial cells requires the early
   acquisition of specific chromosomal aneuploidies and genomic imbalances
SO GENES CHROMOSOMES & CANCER
LA English
DT Review
ID ATM-DEFICIENT MICE; SPONTANEOUS MALIGNANT TRANSFORMATION;
   GENETICALLY-ENGINEERED MICE; TELOMERASE GENE TERC; IN-VITRO;
   COLORECTAL-CANCER; BREAST-CANCER; COPY-NUMBER; TRANSCRIPTIONAL
   DEREGULATION; CENTROSOME AMPLIFICATION
AB Human carcinomas are defined by recurrent chromosomal aneuploidies, which result in a tissue-specific distribution of genomic imbalances. In order to develop models for these genome mutations and to determine their role in tumorigenesis, we generated 45 spontaneously transformed murine cell lines from normal epithelial cells derived from bladder, cervix, colon, kidney, lung, and mammary gland. Phenotypic changes, chromosomal aberrations, centrosome number, and telomerase activity were assayed in control uncultured cells and in three subsequent stages of transformation. Supernumerary centrosomes, binucleate cells, and tetraploidy were observed as early as 48 hr after explantation. In addition, telomerase activity increased throughout progression. Live-cell imaging revealed that failure of cytokinesis, not cell fusion, promoted genome duplication. Spectral karyotyping demonstrated that aneuploidy preceded immortalization, consisting predominantly of whole chromosome losses (4, 9, 12, 13, 16, and Y) and gains (1, 10, 15, and 19). After transformation, focal amplifications of the oncogenes Myc and Mdm2 were frequently detected. Fifty percent of the transformed lines resulted in tumors on injection into immunocompromised mice. The phenotypic and genomic alterations observed in spontaneously transformed murine epithelial cells recapitulated the aberration pattern observed during human carcinogenesis. The dominant aberration of these cell lines was the presence of specific chromosomal aneuploidies. We propose that our newly derived cancer models will be useful tools to dissect the sequential steps of genome mutations during malignant transformation, and also to identify cancer-specific genes, signaling pathways, and the role of chromosomal instability in this process. (c) 2011 Wiley Periodicals, Inc.
C1 [Padilla-Nash, Hesed M.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Hathcock, Karen] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA.
   [Mack, David] NCI, Stem Cell Biol Sect, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA.
   [Hoeppner, Daniel; Ravin, Rea] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Padilla-Nash, HM (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
EM nashh@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX Supported by: The Intramural Research Program of the NIH, National
   Cancer Institute, Center for Cancer Research.
NR 104
TC 11
Z9 12
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD APR
PY 2012
VL 51
IS 4
BP 353
EP 374
DI 10.1002/gcc.21921
PG 22
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 889CL
UT WOS:000300051000005
PM 22161874
ER

PT J
AU Kim, A
   McCully, C
   Cruz, R
   Cole, DE
   Fox, E
   Balis, FM
   Widemann, BC
AF Kim, AeRang
   McCully, Cindy
   Cruz, Rafael
   Cole, Diane E.
   Fox, Elizabeth
   Balis, Frank M.
   Widemann, Brigitte C.
TI The plasma and cerebrospinal fluid pharmacokinetics of sorafenib after
   intravenous administration in non-human primates
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Sorafenib; Pharmacokinetics; Cerebrospinal fluid; Non-human primate
   model
ID REFRACTORY SOLID TUMORS; FACTOR RECEPTOR INHIBITOR; DAYS ON/7 DAYS;
   PHASE-I; BRAIN-TUMORS; RAF KINASE; ANTITUMOR-ACTIVITY; RHESUS-MONKEY;
   BAY-43-9006; PATHWAY
AB Purpose Sorafenib is a small molecule inhibitor of multiple signaling kinases thought to contribute to the pathogenesis of many tumors including brain tumors. Clinical trials with sorafenib in primary and metastatic brain tumors are ongoing. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of sorafenib after an intravenous (IV) dose in a non-human primate (NHP) model. Methods 7.3 mg/kg of sorafenib free base equivalent solubilized in 20% cyclodextrin was administered IV over 1 h to three adult rhesus monkeys. Serial paired plasma and CSF samples were collected over 24 h. Sorafenib was quantified with a validated HPLC/tandem mass spectrometry assay. PK parameters were estimated using non-compartmental methods. CSF penetration was calculated from the AUC(CSF) : AUC(plasma). Results Peak plasma concentrations after IV dosing ranged from 3.4 to 7.6 mu g/mL. The mean +/- standard deviation (SD) area under the plasma concentration from 0 to 24 h was 28 +/- 4.3 mu gaEuro cent h/mL, which is comparable to the exposure observed in humans at recommended doses. The mean +/- SD clearance was 1.7 +/- 0.5 mL/min/kg. The peak CSF concentrations ranged from 0.00045 to 0.00058 mu g/mL. The mean +/- SD area under the CSF concentration from 0 to 24h was 0.0048 +/- 0.0016 mu gaEuro cent h/mL. The mean CSF penetration of sorafenib was 0.02% and 3.4% after correcting for plasma protein binding. Conclusion Sorafenib is well tolerated in NHP and measurable in CSF after an IV dose. The CSF penetration of sorafenib is limited relative to total and free drug exposure in plasma.
C1 [Kim, AeRang] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA.
   [Kim, AeRang; McCully, Cindy; Cruz, Rafael; Cole, Diane E.; Fox, Elizabeth; Balis, Frank M.; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Pharmacol & Expt Therapeut Sect, Bethesda, MD 20892 USA.
RP Kim, A (reprint author), Childrens Natl Med Ctr, Dept Hematol Oncol, 111 Michigan Ave,NW, Washington, DC 20010 USA.
EM aekim@cnmc.org
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
   NIH, National Cancer Institute, Center for Cancer Research. The views
   expressed do not necessarily represent the views of the National
   Institutes of Health or the US government.
NR 30
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U1 1
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2012
VL 30
IS 2
BP 524
EP 528
DI 10.1007/s10637-010-9585-1
PG 5
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 890QX
UT WOS:000300160800010
PM 21072558
ER

PT J
AU Ramaswamy, B
   Phelps, MA
   Baiocchi, R
   Bekaii-Saab, T
   Ni, WJ
   Lai, JP
   Wolfson, A
   Lustberg, ME
   Wei, L
   Wilkins, D
   Campbell, A
   Arbogast, D
   Doyle, A
   Byrd, JC
   Grever, MR
   Shah, MH
AF Ramaswamy, Bhuvaneswari
   Phelps, Mitch A.
   Baiocchi, Robert
   Bekaii-Saab, Tanios
   Ni, Wenjun
   Lai, Ju-Ping
   Wolfson, Anna
   Lustberg, Mark E.
   Wei, Lai
   Wilkins, Deidre
   Campbell, Angela
   Arbogast, Daria
   Doyle, Austin
   Byrd, John C.
   Grever, Michael R.
   Shah, Manisha H.
TI A dose-finding, pharmacokinetic and pharmacodynamic study of a novel
   schedule of flavopiridol in patients with advanced solid tumors
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Flavopiridol; CDK inhibitor; Phase I trial; Solid tumors
ID DEPENDENT KINASE INHIBITOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; 72-HOUR
   CONTINUOUS-INFUSION; MANTLE CELL LYMPHOMA; BREAST-CANCER CELLS; PHASE-II
   TRIAL; CARCINOMA-CELLS; TRANSCRIPTIONAL REPRESSION; DOWN-REGULATION;
   IN-VITRO
AB Purpose: Based on the promising activity and tolerability of flavopiridol administered with a pharmacokinetically-derived dosing schedule in chronic lymphocytic leukemia (CLL), we conducted a phase I study using this schedule in patients with advanced solid tumors. Experimental Design: Flavopiridol was given IV as a 30-min loading dose followed by a 4-hr infusion weekly for 4 weeks repeated every 6 weeks. Dose-escalation was in cohorts of three patients using the standard 3+3 phase I study design. Blood samples were obtained for pharmacokinetic and pharmacodynamic studies. Results: Thirty-four eligible patients with advanced solid tumors received a total of 208 doses (median 7, range 1-24). Total doses ranged from 40 to 105 mg/m(2). The primary dose limiting toxicity was cytokine release syndrome (CKRS). No antitumor responses were observed. The mean peak plasma concentration across all doses was 1.65+/-0.86 mu M. Area under the concentration-versus-time curve (AUC(0-infinity)) ranged from 4.31 to 32.2 mu M.hr with an overall mean of 13.6+/-7.0 mu M.hr. Plasma flavopiridol concentrations and AUC increased proportionally with dose. There was no correlation between cytokine levels and clinical outcomes. Conclusions: The maximum-tolerated dose of flavopiridol is 20 mg/m(2) bolus followed by 20 mg/m(2) infusion over 4 h given weekly for 4 weeks on a 6-week cycle in patients with advanced solid tumors. Flavopiridol PK was notably different, and there was a higher frequency of CKRS, despite prophylactic steroids, seen in this patient group compared to previous studies with CLL using a similar dosing schedule.
C1 [Ramaswamy, Bhuvaneswari; Baiocchi, Robert; Bekaii-Saab, Tanios; Wolfson, Anna; Lustberg, Mark E.; Wilkins, Deidre; Campbell, Angela; Arbogast, Daria; Byrd, John C.; Grever, Michael R.; Shah, Manisha H.] Ohio State Univ, Coll Med, Dept Internal Med, Columbus, OH 43210 USA.
   [Phelps, Mitch A.; Ni, Wenjun; Lai, Ju-Ping] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA.
   [Wei, Lai] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
   [Doyle, Austin] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Shah, MH (reprint author), A438 Starling Loving Hall,320W 10th Ave, Columbus, OH 43210 USA.
EM manisha.shah@osumc.edu
RI Phelps, Mitch/H-3941-2013; Ramaswamy, Bhuvaneswari/E-3919-2011;
   Bekaii-Saab, Tanios/E-2733-2011
OI Phelps, Mitch/0000-0002-1615-5280; 
FU National Cancer Institute [U01 CA76576]
FX This work was supported by Grant No. U01 CA76576 from the National
   Cancer Institute.
NR 41
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U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2012
VL 30
IS 2
BP 629
EP 638
DI 10.1007/s10637-010-9563-7
PG 10
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 890QX
UT WOS:000300160800021
PM 20938713
ER

PT J
AU Alva, A
   Slovin, S
   Daignault, S
   Carducci, M
   DiPaola, R
   Pienta, K
   Agus, D
   Cooney, K
   Chen, A
   Smith, DC
   Hussain, M
AF Alva, Ajjai
   Slovin, Susan
   Daignault, Stephanie
   Carducci, Michael
   DiPaola, Robert
   Pienta, Ken
   Agus, David
   Cooney, Kathleen
   Chen, Alice
   Smith, David C.
   Hussain, Maha
TI Phase II study of Cilengitide (EMD 121974, NSC 707544) in patients with
   non-metastatic castration resistant prostate cancer, NCI-6735. A study
   by the DOD/PCF prostate cancer clinical trials consortium
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE EMD 121974; Cilengitide; Non-metastatic castration resistant prostate
   cancer
ID CIRCULATING TUMOR-CELLS; ADVANCED SOLID TUMORS; BONE METASTASES;
   ENDOTHELIAL-CELLS; INTEGRIN ALPHA(V)BETA(3); RECEPTOR ANTAGONIST;
   WORKING GROUP; END-POINTS; ALPHA-V-BETA-3; SURVIVAL
AB Background: Integrins mediate invasion and angiogenesis in prostate cancer bone metastases. We conducted a phase II study of Cilengitide, a selective antagonist of alpha(v)beta(3) and alpha(v)beta(5) integrins, in non-metastatic castration resistant prostate cancer with rising PSA. Methods: Patients were observed for 4 weeks with PSA monitoring, and then treated with 2,000 mg IV of cilengitide twice weekly until toxicity/progression. PSA, circulating tumor cells (CTCs) and circulating endothelial cells (CECs) were monitored each cycle with imaging performed every three cycles. Primary end point was PSA decline by a parts per thousand yen50%. Secondary endpoints were safety, PSA slope, time to progression (TTP), overall survival (OS), CTCs, CECs and gene expression. Results: 16 pts were enrolled; 13 were eligible with median age 65.5 years, baseline PSA 8.4 ng/mL and median Gleason sum 7. Median of three cycles was administered. Treatment was well tolerated with two grade three toxicities and no grade four toxicities. There were no PSA responses; 11 patients progressed by PSA after three cycles. Median TTP was 1.8 months and median OS has not been reached. Median pre- and on-treatment PSA slopes were 1.1 and 1.8 ng/mL/month. Baseline CTCs were detected in 1/9 patients. CTC increased (0 to 1; 2 pts), remained at 0 (2 pts) or decreased (23 to 0; 1 patient) at progression. Baseline median CEC was 26 (0-61) and at progression, 47 (15-148). Low cell counts precluded gene expression studies. Conclusions: Cilengitide was well tolerated but had no detectable clinical activity. CTCs are of questionable utility in non-metastatic prostate cancer.
C1 [Alva, Ajjai; Daignault, Stephanie; Pienta, Ken; Cooney, Kathleen; Smith, David C.; Hussain, Maha] Univ Michigan, Ctr Comprehens Canc, Canc Ctr 7314, Ann Arbor, MI 48109 USA.
   [Slovin, Susan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
   [Carducci, Michael] Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Sch Med, Baltimore, MD USA.
   [DiPaola, Robert] Canc Inst New Jersey, New Brunswick, NJ USA.
   [Agus, David] Univ So Calif, Los Angeles, CA USA.
   [Chen, Alice] NCI, Bethesda, MD 20892 USA.
RP Hussain, M (reprint author), Univ Michigan, Ctr Comprehens Canc, Canc Ctr 7314, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM mahahuss@med.umich.edu
RI Pienta, Kenneth/E-7679-2015
OI Pienta, Kenneth/0000-0002-4138-2186
FU NCI NIH HHS [N01 CM062206, PC051375, PC051382]
NR 49
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U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2012
VL 30
IS 2
BP 749
EP 757
DI 10.1007/s10637-010-9573-5
PG 9
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 890QX
UT WOS:000300160800036
PM 21049281
ER

PT J
AU Bobe, G
   Murphy, G
   Albert, PS
   Sansbury, LB
   Lanza, E
   Schatzkin, A
   Cross, AJ
AF Bobe, Gerd
   Murphy, Gwen
   Albert, Paul S.
   Sansbury, Leah B.
   Lanza, Elaine
   Schatzkin, Arthur
   Cross, Amanda J.
TI Dietary lignan and proanthocyanidin consumption and colorectal adenoma
   recurrence in the Polyp Prevention Trial
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cancer prevention; colorectal adenoma; colorectal cancer; lignans;
   proanthocyanidins
ID CANCER RISK; PHYTOESTROGEN INTAKE; IN-VITRO; INCLUDING ISOFLAVONES;
   POSTMENOPAUSAL WOMEN; FLAVONOID INTAKE; FOOD SOURCES; HIGH-FIBER;
   LOW-FAT; ENTEROLACTONE
AB Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to prospectively evaluate the association between lignan and proanthocyanidin intake, estimated from databases linked to a food frequency questionnaire, and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial. Overall, individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence. However, in sex-specific analyses, total lignan intake was positively associated with any adenoma recurrence in women (highest vs. lowest lignan intake quartile OR = 2.07, 95% CI: 1.223.52, p trend = 0.004) but not in men (p interaction = 0.04). To conclude, dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence; however, high lignan intake may increase the risk of adenoma recurrence in women.
C1 [Bobe, Gerd] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA.
   [Bobe, Gerd] Oregon State Univ, Dept Anim Sci, Corvallis, OR 97331 USA.
   [Bobe, Gerd; Lanza, Elaine] NCI, Lab Canc Prevent, Ctr Canc Res, NIH,DHHS, Frederick, MD 21701 USA.
   [Murphy, Gwen; Schatzkin, Arthur; Cross, Amanda J.] NCI, Nutr Epidemiol Branch, DCEG, NIH, Rockville, MD USA.
   [Albert, Paul S.] NICHHD, Biostat & Bioinformat Branch, NIH, Rockville, MD USA.
   [Sansbury, Leah B.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
RP Bobe, G (reprint author), Oregon State Univ, Linus Pauling Inst, 112 Withycombe Hall, Corvallis, OR 97331 USA.
EM gerd.bobe@oregonstate.edu
FU National Cancer Institute, NIH, DHHS (Bethesda, MD)
FX Grant sponsor: Intramural Research Program, National Cancer Institute,
   NIH, DHHS (Bethesda, MD)
NR 47
TC 3
Z9 3
U1 2
U2 7
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 APR 1
PY 2012
VL 130
IS 7
BP 1649
EP 1659
DI 10.1002/ijc.26184
PG 11
WC Oncology
SC Oncology
GA 883KQ
UT WOS:000299633300019
PM 21618513
ER

PT J
AU Wang, QH
   Dinse, GE
   Liu, CL
AF Wang, Qihua
   Dinse, Gregg E.
   Liu, Chunling
TI Hazard function estimation with cause-of-death data missing at random
SO ANNALS OF THE INSTITUTE OF STATISTICAL MATHEMATICS
LA English
DT Article
DE Imputation estimator; Inverse probability weighted estimator; Kernel
   estimator; Regression surrogate estimator
ID CENSORED-DATA; COMPETING RISKS; KERNEL DENSITY;
   NONPARAMETRIC-ESTIMATION; REGRESSION-COEFFICIENTS; EFFICIENT ESTIMATION;
   MULTIPLE IMPUTATION; SMOOTHING PARAMETER; SURVIVAL FUNCTION; FAILURE
   DATA
AB Hazard function estimation is an important part of survival analysis. Interest often centers on estimating the hazard function associated with a particular cause of death. We propose three nonparametric kernel estimators for the hazard function, all of which are appropriate when death times are subject to random censorship and censoring indicators can be missing at random. Specifically, we present a regression surrogate estimator, an imputation estimator, and an inverse probability weighted estimator. All three estimators are uniformly strongly consistent and asymptotically normal. We derive asymptotic representations of the mean squared error and the mean integrated squared error for these estimators and we discuss a data-driven bandwidth selection method. A simulation study, conducted to assess finite sample behavior, demonstrates that the proposed hazard estimators perform relatively well. We illustrate our methods with an analysis of some vascular disease data.
C1 [Wang, Qihua] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China.
   [Wang, Qihua] Yunnan Univ, Dept Math & Stat, Kunming 650091, Peoples R China.
   [Wang, Qihua] Univ Hong Kong, Dept Stat & Actuarial Sci, Pokfulam, Hong Kong, Peoples R China.
   [Dinse, Gregg E.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
   [Liu, Chunling] Hong Kong Polytech Univ, Dept Appl Math, Hong Hum, Hong Kong, Peoples R China.
RP Wang, QH (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China.
EM qhwang@amss.ac.cn
RI Liu, Chunling/A-4827-2015
OI Liu, Chunling/0000-0003-3410-445X
FU National Science Fund for Distinguished Young Scholars; National Natural
   Science Foundation of China [10671198]; National Science Fund for
   Creative Research Groups; Research Grants Council of the Hong Kong,
   China [HKU 7050/06P]; Key Lab of Random Complex Structures and Data
   Science, CAS; NIH; National Institute of Environmental Health Sciences
   [Z01-ES-102685]; Eunice Kennedy Shriver National Institute of Child
   Health and Human Development (NICHD)
FX This research was supported by National Science Fund for Distinguished
   Young Scholars, National Natural Science Foundation of China (10671198),
   National Science Fund for Creative Research Groups, a grant from the
   Research Grants Council of the Hong Kong, China (HKU 7050/06P), a grant
   from Key Lab of Random Complex Structures and Data Science, CAS (Qihua
   Wang), the Intramural Research Program of the NIH, National Institute of
   Environmental Health Sciences (Z01-ES-102685) (Gregg Dinse), and the
   Intramural Research Traineeship Award (IRTA) program of the Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
   (NICHD), the National Institutes of Health (NIH) (Chunling Liu). The
   authors thank Dr. Shyamal Peddada and Dr. Norman Kaplan for their
   comments and suggestions.
NR 43
TC 3
Z9 3
U1 1
U2 8
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0020-3157
J9 ANN I STAT MATH
JI Ann. Inst. Stat. Math.
PD APR
PY 2012
VL 64
IS 2
BP 415
EP 438
DI 10.1007/s10463-010-0317-2
PG 24
WC Statistics & Probability
SC Mathematics
GA 877IL
UT WOS:000299171000010
PM 22267874
ER

PT J
AU Sarwar, N
   Butterworth, AS
   Freitag, DF
   Gregson, J
   Willeit, P
   Gorman, DN
   Gao, P
   Saleheen, D
   Rendon, A
   Nelson, CP
   Braund, PS
   Hall, AS
   Chasman, DI
   Tybjaerg-Hansen, A
   Chambers, JC
   Benjamin, EJ
   Franks, PW
   Clarke, R
   Wilde, AAM
   Trip, MD
   Steri, M
   Witteman, JCM
   Qi, L
   van der Schoot, CE
   de Faire, U
   Erdmann, J
   Stringham, HM
   Koenig, W
   Rader, DJ
   Melzer, D
   Reich, D
   Psaty, BM
   Kleber, ME
   Panagiotakos, DB
   Willeit, J
   Wennberg, P
   Woodward, M
   Adamovic, S
   Rimm, EB
   Meade, TW
   Gillum, RF
   Shaffer, JA
   Hofman, A
   Onat, A
   Sundstrom, J
   Wassertheil-Smoller, S
   Mellstrom, D
   Gallacher, J
   Cushman, M
   Tracy, RP
   Kauhanen, J
   Karlsson, M
   Salonen, JT
   Wilhelmsen, L
   Amouyel, P
   Cantin, B
   Best, LG
   Ben-Shlomo, Y
   Manson, JE
   Davey-Smith, G
   de Bakker, PIW
   O'Donnell, CJ
   Wilson, JF
   Wilson, AG
   Assimes, TL
   Jansson, JO
   Ohlsson, C
   Tivesten, A
   Ljunggren, O
   Reilly, MP
   Hamsten, A
   Ingelsson, E
   Cambien, F
   Hung, J
   Thomas, GN
   Boehnke, M
   Schunkert, H
   Asselbergs, FW
   Kastelein, JJP
   Gudnason, V
   Salomaa, V
   Harris, TB
   Kooner, JS
   Allin, KH
   Nordestgaard, BG
   Hopewell, JC
   Goodall, AH
   Ridker, PM
   Holm, H
   Watkins, H
   Ouwehand, WH
   Samani, NJ
   Kaptoge, S
   Di Angelantonio, E
   Harari, O
   Danesh, J
AF Sarwar, Nadeem
   Butterworth, Adam S.
   Freitag, Daniel F.
   Gregson, John
   Willeit, Peter
   Gorman, Donal N.
   Gao, Pei
   Saleheen, Danish
   Rendon, Augusto
   Nelson, Christopher P.
   Braund, Peter S.
   Hall, Alistair S.
   Chasman, Daniel I.
   Tybjaerg-Hansen, Anne
   Chambers, John C.
   Benjamin, Emelia J.
   Franks, Paul W.
   Clarke, Robert
   Wilde, Arthur A. M.
   Trip, Mieke D.
   Steri, Maristella
   Witteman, Jacqueline C. M.
   Qi, Lu
   van der Schoot, C. Ellen
   de Faire, Ulf
   Erdmann, Jeanette
   Stringham, Heather M.
   Koenig, Wolfgang
   Rader, Daniel J.
   Melzer, David
   Reich, David
   Psaty, Bruce M.
   Kleber, Marcus E.
   Panagiotakos, Demosthenes B.
   Willeit, Johann
   Wennberg, Patrik
   Woodward, Mark
   Adamovic, Svetlana
   Rimm, Eric B.
   Meade, Tom W.
   Gillum, Richard F.
   Shaffer, Jonathan A.
   Hofman, Albert
   Onat, Altan
   Sundstrom, Johan
   Wassertheil-Smoller, Sylvia
   Mellstrom, Dan
   Gallacher, John
   Cushman, Mary
   Tracy, Russell P.
   Kauhanen, Jussi
   Karlsson, Magnus
   Salonen, Jukka T.
   Wilhelmsen, Lars
   Amouyel, Philippe
   Cantin, Bernard
   Best, Lyle G.
   Ben-Shlomo, Yoav
   Manson, JoAnn E.
   Davey-Smith, George
   de Bakker, Paul I. W.
   O'Donnell, Christopher J.
   Wilson, James F.
   Wilson, Anthony G.
   Assimes, Themistocles L.
   Jansson, John-Olov
   Ohlsson, Claes
   Tivesten, Asa
   Ljunggren, Osten
   Reilly, Muredach P.
   Hamsten, Anders
   Ingelsson, Erik
   Cambien, Francois
   Hung, Joseph
   Thomas, G. Neil
   Boehnke, Michael
   Schunkert, Heribert
   Asselbergs, Folkert W.
   Kastelein, John J. P.
   Gudnason, Vilmundur
   Salomaa, Veikko
   Harris, Tamara B.
   Kooner, Jaspal S.
   Allin, Kristine H.
   Nordestgaard, Borge G.
   Hopewell, Jemma C.
   Goodall, Alison H.
   Ridker, Paul M.
   Holm, Hilma
   Watkins, Hugh
   Ouwehand, Willem H.
   Samani, Nilesh J.
   Kaptoge, Stephen
   Di Angelantonio, Emanuele
   Harari, Olivier
   Danesh, John
CA IL6R Genetics Consortium Emerging
TI Interleukin-6 receptor pathways in coronary heart disease: a
   collaborative meta-analysis of 82 studies
SO LANCET
LA English
DT Article
ID C-REACTIVE PROTEIN; INDIVIDUAL PARTICIPANT METAANALYSIS; WOMENS GENOME
   HEALTH; RHEUMATOID-ARTHRITIS; MENDELIAN RANDOMIZATION; GENE-EXPRESSION;
   ARTERY-DISEASE; RISK; LOCI; ATHEROSCLEROSIS
AB Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling.
   Methods In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6.
   Findings The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes.
   Interpretation Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
C1 [Sarwar, Nadeem] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England.
   [Nelson, Christopher P.; Braund, Peter S.; Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Leicester LE1 7RH, Leics, England.
   [Hall, Alistair S.] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England.
   [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Chasman, Daniel I.; Reich, David; Manson, JoAnn E.; O'Donnell, Christopher J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
   [Tybjaerg-Hansen, Anne; Allin, Kristine H.; Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Univ Hosp, DK-1168 Copenhagen, Denmark.
   [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England.
   [Benjamin, Emelia J.] Boston Univ, Sch Med & Publ Hlth, Boston, MA 02215 USA.
   [Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
   [Franks, Paul W.] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
   [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
   [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Med Sect, Umea, Sweden.
   [Clarke, Robert; Hopewell, Jemma C.; Watkins, Hugh] Univ Oxford, Oxford OX1 2JD, England.
   [Wilde, Arthur A. M.; Trip, Mieke D.; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands.
   [Steri, Maristella] CNR, IRGB, I-00185 Rome, Italy.
   [Witteman, Jacqueline C. M.; Hofman, Albert] Erasmus MC, Rotterdam, Netherlands.
   [Qi, Lu] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Cambridge, MA 02138 USA.
   [de Faire, Ulf] Karolinska Inst, S-10401 Stockholm, Sweden.
   [Erdmann, Jeanette; Schunkert, Heribert] Univ Lubeck, Lubeck, Germany.
   [Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Koenig, Wolfgang] Univ Ulm, D-89069 Ulm, Germany.
   [Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Philadelphia, PA 19104 USA.
   [Melzer, David] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX4 4QJ, Devon, England.
   [Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA.
   [Kleber, Marcus E.] LURIC Study Nonprofit LLC, Freiburg, Germany.
   [Panagiotakos, Demosthenes B.] Harokopio Univ Athens, Athens, Greece.
   [Willeit, Johann] Med Univ Innsbruck, Innsbruck, Austria.
   [Woodward, Mark] Univ Sydney, Sydney, NSW 2006, Australia.
   [Adamovic, Svetlana; Mellstrom, Dan; Ohlsson, Claes; Tivesten, Asa] Sahlgrens Univ Hosp, Gothenburg, Sweden.
   [Meade, Tom W.] London Sch Hyg & Trop Med, London, England.
   [Gillum, Richard F.] Ctr Dis Control & Prevent, Atlanta, GA USA.
   [Shaffer, Jonathan A.] Columbia Univ, Med Ctr, New York, NY 10027 USA.
   [Onat, Altan] Istanbul Univ, Istanbul, Turkey.
   [Sundstrom, Johan] Uppsala Univ, Uppsala, Sweden.
   [Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Bronx, NY USA.
   [Gallacher, John] Cardiff Univ, Cardiff, Wales.
   [Cushman, Mary; Tracy, Russell P.] Univ Vermont, Burlington, VT 05405 USA.
   [Kauhanen, Jussi] Univ Eastern Finland, Kuopio, Finland.
   [Karlsson, Magnus] Lund Univ, S-22100 Lund, Sweden.
   [Wilhelmsen, Lars] Univ Gothenburg, Gothenburg, Sweden.
   [Amouyel, Philippe] Inst Pasteur, Lille, France.
   [Cantin, Bernard] Hop Laval, Laval, PQ, Canada.
   [Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, MO USA.
   [Ben-Shlomo, Yoav; Davey-Smith, George] Univ Bristol, Bristol BS8 1TH, Avon, England.
   [Wilson, James F.] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
   [Wilson, Anthony G.] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England.
   [Assimes, Themistocles L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [Jansson, John-Olov] Gothenburg Univ, S-41124 Gothenburg, Sweden.
   [Ljunggren, Osten] Uppsala Univ, S-75105 Uppsala, Sweden.
   [Hamsten, Anders; Ingelsson, Erik] Karolinska Inst, Stockholm, Sweden.
   [Cambien, Francois] INSERM, F-75654 Paris 13, France.
   [Hung, Joseph] Univ Western Australia, Nedlands, WA 6009, Australia.
   [Thomas, G. Neil] Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
   [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
   [Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland.
   [Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland.
   [Holm, Hilma] deCODE Genet, Reykjavik, Iceland.
RP Sarwar, N (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England.
EM erfc@phpc.cam.ac.uk
RI Smith, Albert Vernon/K-5150-2015; Willenborg, Christina/D-2668-2012;
   Singleton, Andrew/C-3010-2009; Thomas, G. Neil/A-1879-2013; Shaffer,
   Jonathan/B-2783-2013; Sabater-Lleal, Maria/I-5832-2013; de Bakker,
   Paul/B-8730-2009; Sundstrom, Johan/A-6286-2009; McQuillan,
   Brendan/B-8271-2013; Woodward, Mark/D-8492-2015; Gudnason,
   Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Davey Smith,
   George/A-7407-2013; 
OI Watkins, Hugh/0000-0002-5287-9016; Ouwehand, Willem/0000-0002-7744-1790;
   Kleber, Marcus/0000-0003-0663-7275; Sabater Lleal,
   Maria/0000-0002-0128-379X; Di Angelantonio,
   Emanuele/0000-0001-8776-6719; Fraser, Ross/0000-0003-0488-2592; Smith,
   Albert Vernon/0000-0003-1942-5845; Steri, Anna
   Maristella/0000-0001-5869-3872; Mannisto, Satu/0000-0002-8668-3046;
   Willeit, Peter/0000-0002-1866-7159; Benjamin,
   Emelia/0000-0003-4076-2336; Franks, Paul/0000-0002-0520-7604; Melzer,
   David/0000-0002-0170-3838; Willenborg, Christina/0000-0001-5217-6882;
   Thomas, G. Neil/0000-0002-2777-1847; de Bakker,
   Paul/0000-0001-7735-7858; Sundstrom, Johan/0000-0003-2247-8454;
   McQuillan, Brendan/0000-0002-2130-8114; Gudnason,
   Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178;
   Davey Smith, George/0000-0002-1407-8314; Shungin,
   Dmitry/0000-0001-7900-5856
FU British Heart Foundation [RG/08/014)]; UK Medical Research Council; UK
   National Institute of Health Research, Cambridge Biomedical Research
   Centre; BUPA Foundation; Zoll
FX Since April, 2011, Nadeem Sarwar has been a full-time employee of Pfizer
   Inc. Olivier Harari is an employee of Roche Products. Hilma Holm is an
   employee of deCODE genetics. Bruce Psaty serves on a data safety and
   monitoring board for a clinical trial of a device funded by the
   manufacturer Zoll. JoAnn Manson is listed as a co-inventor on a pending
   patent held by Brigham and Women's Hospital, Harvard Medical School,
   that relates to inflammatory markers in diabetes prediction. Paul M
   Ridker is listed as a co-inventor on patents held by Brigham and Women's
   Hospital that relate to the use of inflammatory markers in
   cardiovascular disease, and that have been licensed to AstraZeneca and
   Siemens. John Danesh has received research funding from the British
   Heart Foundation, BUPA Foundation, Denka, diaDexus, European Union,
   European Research Council, Evelyn Trust, Fogarty International Centre,
   GlaxoSmithKline, Medical Research Council, Merck Sharp and Dohme,
   National Heart, Lung and Blood Institute, National Institute of
   Neurological Disorders and Stroke, National Institute for Health
   Research, Novartis, Pfizer, Roche, Wellcome Trust, and UK Biobank, and
   has served on advisory boards for Merck, Pfizer, and Novartis, for which
   he has received compensation. All other members of the writing committee
   declare that they have no conflicts of interest.; The coordinating
   centre was supported by the British Heart Foundation (RG/08/014), the UK
   Medical Research Council, the UK National Institute of Health Research,
   Cambridge Biomedical Research Centre, and a specific grant from the BUPA
   Foundation. Various sources have supported recruitment, follow-up, and
   laboratory measurements in the studies contributing to this report.
   Investigators of several of these studies have contributed to a list
   naming some of these funding sources. Sekar Kathiresan, Kenneth G C
   Smith, and John Todd commented helpfully on an earlier version of this
   report.
NR 49
TC 204
Z9 212
U1 4
U2 60
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAR 31
PY 2012
VL 379
IS 9822
BP 1205
EP 1213
DI 10.1016/S0140-6736(11)61931-4
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 918DV
UT WOS:000302230400033
ER

PT J
AU de Joussineau, C
   Sahut-Barnola, I
   Levy, I
   Saloustros, E
   Val, P
   Stratakis, CA
   Martinez, A
AF de Joussineau, Cyrille
   Sahut-Barnola, Isabelle
   Levy, Isaac
   Saloustros, Emmanouil
   Val, Pierre
   Stratakis, Constantine A.
   Martinez, Antoine
TI The cAMP pathway and the control of adrenocortical development and
   growth
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE cAMP; PKA; Adrenal; Pathology
ID HUMAN ADRENAL-CORTEX; SUBUNIT TYPE 1A; KINASE-A PKA; CARNEY COMPLEX;
   REGULATORY SUBUNIT; BETA-CATENIN; X-ZONE; CYTOCHROME B5;
   GLUCOCORTICOID-RECEPTOR; MICRORNA SIGNATURE
AB In the last 10 years, extensive studies showed that the cAMP pathway is deregulated in patients suffering from adrenocortical tumours, and particularly in primary pigmented nodular adrenocortical disease (PPNAD). Here we describe how evidence arising from the analysis of patients' data, mouse models and in vitro experiments, have shed light on the cAMP pathway as a central player in adrenal physiopathology. We also show how novel data generated from mouse models may point to new targets for potential therapies. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [de Joussineau, Cyrille; Sahut-Barnola, Isabelle; Val, Pierre; Martinez, Antoine] Clermont Univ, CNRS, INSERM, UMR6247,U931, F-63171 Aubiere, France.
   [Levy, Isaac; Saloustros, Emmanouil; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Martinez, A (reprint author), Clermont Univ, CNRS, INSERM, UMR6247,U931, BP 80026,24 Ave Landais, F-63171 Aubiere, France.
EM antoine.martinez@univ-bpclermont.fr
OI Saloustros, Emmanouil /0000-0002-0485-0120
FU Intramural NIH HHS [ZIA HD008920-01]
NR 66
TC 26
Z9 26
U1 1
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD MAR 31
PY 2012
VL 351
IS 1
SI SI
BP 28
EP 36
DI 10.1016/j.mce.2011.10.006
PG 9
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 911ZE
UT WOS:000301762400005
PM 22019902
ER

PT J
AU Ananworanich, J
   Schuetz, A
   Vandergeeten, C
   Sereti, I
   de Souza, M
   Rerknimitr, R
   Dewar, R
   Marovich, M
   van Griensven, F
   Sekaly, R
   Pinyakorn, S
   Phanuphak, N
   Trichavaroj, R
   Rutvisuttinunt, W
   Chomchey, N
   Paris, R
   Peel, S
   Valcour, V
   Maldarelli, F
   Chomont, N
   Michael, N
   Phanuphak, P
   Kim, JH
AF Ananworanich, Jintanat
   Schuetz, Alexandra
   Vandergeeten, Claire
   Sereti, Irini
   de Souza, Mark
   Rerknimitr, Rungsun
   Dewar, Robin
   Marovich, Mary
   van Griensven, Frits
   Sekaly, Rafick
   Pinyakorn, Suteeraporn
   Phanuphak, Nittaya
   Trichavaroj, Rapee
   Rutvisuttinunt, Wiriya
   Chomchey, Nitiya
   Paris, Robert
   Peel, Sheila
   Valcour, Victor
   Maldarelli, Frank
   Chomont, Nicolas
   Michael, Nelson
   Phanuphak, Praphan
   Kim, Jerome H.
CA RV
TI Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell
   Depletion and HIV Reservoir Seeding during Acute HIV Infection
SO PLOS ONE
LA English
DT Article
ID IMMUNE ACTIVATION; THERAPY; RALTEGRAVIR; PERSISTENCE; DYNAMICS; RISK;
   INTENSIFICATION; INTERRUPTION; RESTORATION; REPLICATION
AB Background: Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.
   Methods and Findings: We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm(3). HIV RNA was 5.5 log(10) copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/10(6) PBMC) vs. Fiebig I (8 copy/10(6) PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of,50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).
   Conclusions: Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.
C1 [Ananworanich, Jintanat; Pinyakorn, Suteeraporn; Phanuphak, Nittaya; Chomchey, Nitiya; Valcour, Victor; Phanuphak, Praphan; Kim, Jerome H.] SE Asia Res Collaborat Hawaii, Bangkok, Thailand.
   [Ananworanich, Jintanat; Pinyakorn, Suteeraporn; Phanuphak, Nittaya; Chomchey, Nitiya; Phanuphak, Praphan] Thai Red Cross AIDS Res Ctr, Bangkok, Thailand.
   [Ananworanich, Jintanat; Pinyakorn, Suteeraporn] HIV NAT, Bangkok, Thailand.
   [Ananworanich, Jintanat; Rerknimitr, Rungsun; Phanuphak, Praphan] Chulalongkorn Univ, Fac Med, Dept Med, Bangkok 10330, Thailand.
   [Ananworanich, Jintanat; Schuetz, Alexandra; de Souza, Mark; Trichavaroj, Rapee; Rutvisuttinunt, Wiriya; Paris, Robert; Kim, Jerome H.] Armed Forces Res Inst Med Sci US Component, Dept Retrovirol, Bangkok, Thailand.
   [Schuetz, Alexandra; de Souza, Mark; Marovich, Mary; Paris, Robert; Peel, Sheila; Michael, Nelson; Kim, Jerome H.] US Mil HIV Res Program, Rockville, MD USA.
   [Vandergeeten, Claire; Sekaly, Rafick; Chomont, Nicolas] Vaccine & Gene Therapy Inst, Port St Lucie, FL USA.
   [Sereti, Irini] NIAID, Immunoregulat Lab, Clin & Mol Retrovirol Sect, Bethesda, MD 20892 USA.
   [Dewar, Robin] NCI, Virus Isolat & Serol Lab, Appl & Dev Res Directorate, Sci Applicat Int Corp,Frederick Inc,Frederick Can, Frederick, MD 21701 USA.
   [van Griensven, Frits] Minist Publ Hlth, Dept Dis Control, Thailand Minist Publ Hlth, US Ctr Dis Control & Prevent Collaborat, Amphur Muang, Nonthaburi, Thailand.
   [Valcour, Victor] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA.
   [Maldarelli, Frank] NIH, In Vivo Biol Grp, Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Ananworanich, J (reprint author), SE Asia Res Collaborat Hawaii, Bangkok, Thailand.
EM jintanat.a@searchthailand.org
FU UCLA CFAR [5P30 AI028697]; United States Military HIV Research Program,
   Walter Reed Army Institute of Research, Rockville, Maryland
   [W81XWH-07-2-0067]; federal funds from the National Cancer Institute
   [HHSN261200800001E]; National Institute of Allergy and Infectious
   Diseases; National Institute of Mental Health [NH-R21MH089341]; Vaccine
   and Gene Therapy Institute; Gilead (Truvada(R), Atripla(R)); Merck
   (Sustiva(R), Isentress(R)); Pfizer (Selzentry(R)); Monogram Biosciences;
   Abbott; Gilead; ViiV
FX We thank our study participants and staff from the Thai Red Cross AIDS
   Research Centre and the Silom Community Clinic in Bangkok for their
   valuable contributions to this study. We thank Ms. Piraporn June Ohata
   and Ms. Varaporn Pothipala for their help in preparing this manuscript.
   SEARCH is a research collaboration between the Thai Red Cross AIDS
   Research Centre (TRCARC), the University of Hawaii and the Department of
   Retrovirology, U.S. Army Medical Component, Armed Forces Research
   Institute of Medical Sciences (AFRIMS). We also thank the UCLA CFAR
   Mucosal Immunology Core Laboratory, funded by UCLA CFAR grant 5P30
   AI028697 for their support and guidance regarding the isolation of MMC.;
   The United States Military HIV Research Program, Walter Reed Army
   Institute of Research, Rockville, Maryland funded the study under a
   cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson
   Foundation for the Advancement of Military Medicine, Inc., and the
   United States Department of Defense. This project has been funded in
   whole or in part with federal funds from the National Cancer Institute
   (Contract No. HHSN261200800001E), the National Institute of Allergy and
   Infectious Diseases and the National Institute of Mental Health
   (NH-R21MH089341). The study was also funded in part by the Vaccine and
   Gene Therapy Institute. Antiretroviral therapy was supported by Gilead
   (Truvada (R), Atripla (R)), Merck (Sustiva (R), Isentress (R)) and
   Pfizer (Selzentry (R)). Monogram Biosciences supported the Trofile (R)
   test. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.; JA has
   received speaker's fee and/or honorarium from Abbott, Gilead and ViiV.
   There are no patents, products in development or marketed products to
   declare. This does not alter the authors' adherence to all the PLoS ONE
   policies on sharing data and materials, as detailed online in the guide
   for authors.
NR 39
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 30
PY 2012
VL 7
IS 3
AR e33948
DI 10.1371/journal.pone.0033948
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UC
UT WOS:000305339100089
PM 22479485
ER

PT J
AU Li, JZ
   Brumme, CJ
   Lederman, MM
   Brumme, ZL
   Wang, HY
   Spritzler, J
   Carrington, M
   Medvik, K
   Walker, BD
   Schooley, RT
   Kuritzkes, DR
AF Li, Jonathan Z.
   Brumme, Chanson J.
   Lederman, Michael M.
   Brumme, Zabrina L.
   Wang, Hongying
   Spritzler, John
   Carrington, Mary
   Medvik, Kathleen
   Walker, Bruce D.
   Schooley, Robert T.
   Kuritzkes, Daniel R.
CA AIDS Clin Trials Grp A5197 Study
TI Characteristics and Outcomes of Initial Virologic Suppressors during
   Analytic Treatment Interruption in a Therapeutic HIV-1 gag Vaccine Trial
SO PLOS ONE
LA English
DT Article
ID REVERSE-TRANSCRIPTASE INHIBITOR; IMMUNODEFICIENCY-VIRUS TYPE-1;
   PLACEBO-CONTROLLED TRIAL; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY;
   DISEASE PROGRESSION; PROTEASE INHIBITOR; HIV-1-INFECTED PERSONS; VIRAL
   LOAD; INFECTION
AB Background: In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 gag vaccine.
   Objective: To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 log(10) copies/ml) during the analytic treatment interruption (ATI) and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution.
   Methods: HIV-1 gag and pol RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher's exact tests.
   Results: Eleven out of 104 participants (10.6%) were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04). However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log10 copies/ml. HIV-1 Gag-specific CD4+ interferon-c responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-alpha+ cells expressing either CTLA-4 or PD-1.
   Conclusions: Among individuals participating in a rAd5 therapeutic HIV-1 gag vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other therapeutic vaccines in development.
C1 [Li, Jonathan Z.; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
   [Li, Jonathan Z.; Walker, Bruce D.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA.
   [Brumme, Chanson J.; Brumme, Zabrina L.; Carrington, Mary; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA.
   [Brumme, Chanson J.; Brumme, Zabrina L.; Carrington, Mary; Walker, Bruce D.] Harvard Univ, Cambridge, MA 02138 USA.
   [Lederman, Michael M.; Medvik, Kathleen] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA.
   [Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
   [Wang, Hongying; Spritzler, John] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
   [Carrington, Mary] NCI Frederick, SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA.
   [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
   [Schooley, Robert T.] Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA.
RP Li, JZ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
EM Jli22@partners.org
OI Brumme, Chanson/0000-0003-2722-5288
FU National Institutes of Health (NIH) [T32 AI07387, U01 AI068636, U01
   AI068634, P30 AI60354, K24 RR016482]; Clinical Investigator Training
   Program Fellowship: Harvard/MIT Health Sciences and Technology - Beth
   Israel Deaconess Medical Center; Pfizer Inc.; Merck Co.; New
   Investigator Award from the Canadian Institutes of Health Research
   (CIHR); National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; Intramural Research Program of the NIH, National
   Cancer Institute, Center for Cancer Research; Merck
FX This work was supported in part by National Institutes of Health (NIH)
   grants T32 AI07387 (to Dr. Li), U01 AI068636 (AIDS Clinical Trials
   Group), U01 AI068634 (ACTG Statistical and Data Management Center), P30
   AI60354 (Harvard University Center for AIDS Research), K24 RR016482 (to
   Dr. Kuritzkes), and subcontracts from U01 AI068636 to the Harvard
   Virology Support Laboratory and the Case Immunology Support Laboratory.
   The Harvard Virologic Support Laboratory is affiliated with Harvard
   Medical School and the Case Immunology Support Laboratory is affiliated
   with Case Western Reserve University. Dr. Li is the recipient of a
   Clinical Investigator Training Program Fellowship: Harvard/MIT Health
   Sciences and Technology - Beth Israel Deaconess Medical Center, in
   collaboration with Pfizer Inc. and Merck & Co. Dr. Brumme is supported
   by a New Investigator Award from the Canadian Institutes of Health
   Research (CIHR). This project has been funded in part with federal funds
   from the National Cancer Institute, National Institutes of Health, under
   Contract No. HHSN261200800001E, and by the Intramural Research Program
   of the NIH, National Cancer Institute, Center for Cancer Research. 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. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.; The authors have the following competing
   interests: Drs. Kuritzkes, Lederman, and Schooley are consultants to
   Merck; Dr. Kuritzkes has received research support from Merck. Mary
   Carrington is an employee of SAIC-Frederick, Inc. Dr. Li is the
   recipient of a Clinical Investigator Training Program Fellowship:
   Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess
   Medical Center, in collaboration with Pfizer Inc. and Merck & Co. The
   authors appreciate Dr. Michael Robertson's (Merck Research Laboratories)
   input in the design of the study and review of the manuscript. There are
   no patents, products in development or marketed products to declare.
   This does not alter the authors' adherence to all the PLoS ONE policies
   on sharing data and materials.
NR 34
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U2 3
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 MAR 30
PY 2012
VL 7
IS 3
AR e34134
DI 10.1371/journal.pone.0034134
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UC
UT WOS:000305339100121
PM 22479542
ER

PT J
AU Mariotti, M
   Ridge, PG
   Zhang, Y
   Lobanov, AV
   Pringle, TH
   Guigo, R
   Hatfield, DL
   Gladyshev, VN
AF Mariotti, Marco
   Ridge, Perry G.
   Zhang, Yan
   Lobanov, Alexei V.
   Pringle, Thomas H.
   Guigo, Roderic
   Hatfield, Dolph L.
   Gladyshev, Vadim N.
TI Composition and Evolution of the Vertebrate and Mammalian
   Selenoproteomes
SO PLOS ONE
LA English
DT Article
ID MITOCHONDRIAL THIOREDOXIN REDUCTASE; MULTIPLE SEQUENCE ALIGNMENT; 21ST
   AMINO-ACID; GLUTATHIONE-PEROXIDASE; SELENOCYSTEINE INCORPORATION;
   FUNCTIONAL-CHARACTERIZATION; SECIS ELEMENT; EXPRESSION; GENE;
   IDENTIFICATION
AB Background: Selenium is an essential trace element in mammals due to its presence in proteins in the form of selenocysteine (Sec). Human genome codes for 25 Sec-containing protein genes, and mouse and rat genomes for 24.
   Methodology/Principal Findings: We characterized the selenoproteomes of 44 sequenced vertebrates by applying gene prediction and phylogenetic reconstruction methods, supplemented with the analyses of gene structures, alternative splicing isoforms, untranslated regions, SECIS elements, and pseudogenes. In total, we detected 45 selenoprotein subfamilies. 28 of them were found in mammals, and 41 in bony fishes. We define the ancestral vertebrate (28 proteins) and mammalian (25 proteins) selenoproteomes, and describe how they evolved along lineages through gene duplication (20 events), gene loss (10 events) and replacement of Sec with cysteine (12 events). We show that an intronless selenophosphate synthetase 2 gene evolved in early mammals and replaced functionally the original multiexon gene in placental mammals, whereas both genes remain in marsupials. Mammalian thioredoxin reductase 1 and thioredoxin-glutathione reductase evolved from an ancestral glutaredoxin-domain containing enzyme, still present in fish. Selenoprotein V and GPx6 evolved specifically in placental mammals from duplications of SelW and GPx3, respectively, and GPx6 lost Sec several times independently. Bony fishes were characterized by duplications of several selenoprotein families (GPx1, GPx3, GPx4, Dio3, MsrB1, SelJ, SelO, SelT, SelU1, and SelW2). Finally, we report identification of new isoforms for several selenoproteins and describe unusually conserved selenoprotein pseudogenes.
   Conclusions/Significance: This analysis represents the first comprehensive survey of the vertebrate and mammal selenoproteomes, and depicts their evolution along lineages. It also provides a wealth of information on these selenoproteins and their forms.
C1 [Mariotti, Marco; Zhang, Yan; Lobanov, Alexei V.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Mariotti, Marco; Zhang, Yan; Lobanov, Alexei V.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA.
   [Mariotti, Marco; Guigo, Roderic] Ctr Genom Regulat, Barcelona, Spain.
   [Mariotti, Marco; Guigo, Roderic] Univ Pompeu Fabra, Barcelona, Spain.
   [Ridge, Perry G.] Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA.
   [Ridge, Perry G.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68583 USA.
   [Zhang, Yan] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Syst Biol, Shanghai, Peoples R China.
   [Pringle, Thomas H.] Sperling Fdn, Eugene, OR USA.
   [Hatfield, Dolph L.] NCI, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
RP Mariotti, M (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM vgladyshev@rics.bwh.harvard.edu
RI Gladyshev, Vadim/A-9894-2013; Guigo, Roderic/D-1303-2010
OI Guigo, Roderic/0000-0002-5738-4477
FU NIH [GM061603, GM065204]
FX Supported by NIH GM061603 and GM065204. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 88
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U1 1
U2 25
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 MAR 30
PY 2012
VL 7
IS 3
AR e33066
DI 10.1371/journal.pone.0033066
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UC
UT WOS:000305339100031
PM 22479358
ER

PT J
AU Tsai-Morris, CH
   Sato, H
   Gutti, R
   Dufau, ML
AF Tsai-Morris, Chon-Hwa
   Sato, Hisashi
   Gutti, Ravi
   Dufau, Maria L.
TI Role of Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) on
   Polysomal Associated mRNAs in Mouse Testis
SO PLOS ONE
LA English
DT Article
ID HEAT-SHOCK PROTEINS; GENE-EXPRESSION; HUMAN SPERM; HISTONE
   UBIQUITINATION; HAPLOID SPERMATIDS; CHROMATOID BODY; LEYDIG-CELLS; RAT
   TESTIS; ZETA 1; SPERMATOGENESIS
AB Gonadotropin Regulated Testicular RNA Helicase (GRTH/Ddx25) is a testis-specific multifunctional RNA helicase and an essential post-transcriptional regulator of spermatogenesis. GRTH transports relevant mRNAs from nucleus to cytoplasmic sites of meiotic and haploid germ cells and associates with actively translating polyribosomes. It is also a negative regulator of steroidogenesis in Leydig cells. To obtain a genome-wide perspective of GRTH regulated genes, in particularly those associated with polyribosomes, microarray differential gene expression analysis was performed using polysome-bound RNA isolated from testes of wild type (WT) and GRTH KO mice. 792 genes among the entire mouse genome were found to be polysomal GRTH-linked in WT. Among these 186 were down-regulated and 7 up-regulated genes in GRTH null mice. A similar analysis was performed using total RNA extracted from purified germ cell populations to address GRTH action in individual target cells. The down-regulation of known genes concerned with spermatogenesis at polysomal sites in GRTH KO and their association with GRTH in WT coupled with early findings of minor or unchanged total mRNAs and abolition of their protein expression in KO underscore the relevance of GRTH in translation. Ingenuity pathway analysis predicted association of GRTH bound polysome genes with the ubiquitin-proteasome-heat shock protein signaling network pathway and NF kappa B/TP53/TGFB1 signaling networks were derived from the differentially expressed gene analysis. This study has revealed known and unexplored factors in the genome and regulatory pathways underlying GRTH action in male reproduction.
C1 [Tsai-Morris, Chon-Hwa; Sato, Hisashi; Gutti, Ravi; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20814 USA.
RP Tsai-Morris, CH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20814 USA.
EM morrisch@mail.nih.gov
OI Gutti, Ravi/0000-0002-0912-5796
FU National Institutes of Health Intramural Program through the Eunice
   Kennedy Shriver National Institutes of Child Health and Human
   Development
FX This work was supported by the National Institutes of Health Intramural
   Program through the Eunice Kennedy Shriver National Institutes of Child
   Health and Human Development. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 67
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U1 3
U2 5
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 MAR 30
PY 2012
VL 7
IS 3
AR e32470
DI 10.1371/journal.pone.0032470
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UC
UT WOS:000305339100011
PM 22479328
ER

PT J
AU Furey, ML
   Nugent, AC
   Speer, AM
   Luckenbaugh, DA
   Hoffman, EM
   Frankel, E
   Drevets, WC
   Zarate, CA
AF Furey, Maura L.
   Nugent, Allison C.
   Speer, Andrew M.
   Luckenbaugh, David A.
   Hoffman, Elana M.
   Frankel, Erica
   Drevets, Wayne C.
   Zarate, Carlos A., Jr.
TI Baseline mood-state measures as predictors of antidepressant response to
   scopolamine
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Mood-disorders; Response prediction; Scopolamine; Major depressive
   disorder; Bipolar disorder
ID HIPPOCAMPAL VOLUME; RATING-SCALE; ASTERISK-D; DEPRESSION; METAANALYSIS;
   SENSITIVITY; KETAMINE; PLACEBO; TRIAL; MANIA
AB Identifying predictors of antidepressant response will facilitate the successful treatment of patients suffering from depression. Scopolamine produces robust antidepressant responses in unipolar and bipolar depression. Here we evaluate the potential for baseline self-ratings to predict treatment response to scopolamine. Fifty-one unipolar and bipolar patients participated in a double-blind, placebo-controlled crossover trial. Following a single-blind placebo session, participants randomly received P/S or S/P (P = 3 placebo; S = 3 scopolamine (4 mu g/kg) sessions). Mood-state self-ratings (Profile of Mood State (POMS) and Visual Analog Scales (VAS)) and depression severity (Montgomery-Asberg Depression Rating Scale (MADRS)) were obtained before each infusion. Day 1 (baseline/placebo) self-ratings were used in a discriminant function analysis to identify linear combinations of individual items that predict response. The discriminant analysis significantly separated responders from non-responders in both the unipolar and bipolar diagnostic subgroups. The discriminant functions accurately classified over 85% of patients as responders/non-responders. The POMS depression sub-scale significantly correlated with clinical response, as did the VAS restlessness, sad, and irritated scales. These results indicate that self-report mood-ratings obtained before treatment can predict response outcome to scopolamine, and suggest that a constellation of mood-state features may be related to clinical response. Published by Elsevier Ireland Ltd.
C1 [Furey, Maura L.; Nugent, Allison C.; Luckenbaugh, David A.; Hoffman, Elana M.; Frankel, Erica; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
   [Speer, Andrew M.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
   [Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
   [Drevets, Wayne C.] Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK 74136 USA.
RP Furey, ML (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 15K North Dr,Bldg 15K,Rm 115B, Bethesda, MD 20892 USA.
EM mfurey@mail.nih.gov
RI Furey, Maura/H-5273-2013; 
OI Nugent, Allison/0000-0003-2569-2480
FU NIH NIMH-DIRP
FX We thank Ashish Khanna, Mark Opal and Summer Peck for technical support,
   Michele Drevets and Joan Williams for patient recruitment and
   evaluation, and Paul Carlson, Alan Mallinger, and the 5SW Day Hospital
   nursing staff for medical support. This research was supported by the
   NIH NIMH-DIRP.
NR 34
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U1 4
U2 9
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 MAR 30
PY 2012
VL 196
IS 1
BP 62
EP 67
DI 10.1016/j.psychres.2012.01.003
PG 6
WC Psychiatry
SC Psychiatry
GA 955SL
UT WOS:000305041100011
PM 22349648
ER

PT J
AU Park, S
   Hong, JP
   Lee, HB
   Samuels, J
   Bienvenu, OJ
   Chung, HY
   Eaton, WW
   Costa, PT
   Nestadt, G
AF Park, Subin
   Hong, Jin Pyo
   Lee, Hochang B.
   Samuels, Jack
   Bienvenu, O. Joseph
   Chung, Hye Yoon
   Eaton, William W.
   Costa, Paul T., Jr.
   Nestadt, Gerald
TI Relationship between personality disorder dimensions and verbal memory
   functioning in a community population
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Memory complaints; Verbal memory; Personality traits; Personality
   disorders
ID DIAGNOSTIC INTERVIEW SCHEDULE; OBSESSIVE-COMPULSIVE DISORDER;
   WORKING-MEMORY; NEUROPSYCHOLOGICAL PERFORMANCE; 5-FACTOR MODEL;
   FOLLOW-UP; BORDERLINE; SCHIZOPHRENIA; COMPLAINTS; TRAITS
AB Based on the Baltimore Epidemiologic Catchment Area (ECA) follow-up survey, we examined relationships between dimensions of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) personality disorders and both subjective and objective memory functioning in a community population. Our study subjects consisted of 736 individuals from the ECA follow-up study of the original Baltimore ECA cohort, conducted between 1993 and 1996 and available for assessment in the Hopkins Epidemiology Study of Personality Disorders from 1997 to 1999. Subjects were assessed for DSM-IV personality disorders using a semi-structured instrument, the International Personality Disorder Examination, and were asked about a subjective appraisal of memory. Verbal memory function, including immediate recall, delayed recall, and recognition, were also evaluated. Multiple linear regression analyses were used to determine associations between personality dimensions of DSM-IV Axis II traits and subjective and objective memory functioning. Scores on schizoid and schizotypal personality dimensions were associated with subjective and objective memory dysfunction, both with and without adjustment for Axis I disorders. Borderline, antisocial, avoidant, and dependent personality disorder scores were associated with subjective memory impairment only, both with and without adjustment for Axis I disorders. This study suggests that subjective feelings of memory impairment and/or objective memory dysfunction are associated with specific personality disorder dimensions. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Park, Subin; Hong, Jin Pyo; Chung, Hye Yoon] Univ Ulsan, Sch Med, Asan Med Ctr, Dept Psychiat, Seoul, South Korea.
   [Lee, Hochang B.; Samuels, Jack; Bienvenu, O. Joseph; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
   [Eaton, William W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
   [Costa, Paul T., Jr.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
RP Nestadt, G (reprint author), Meyer 131,600 N Wolfe St, Baltimore, MD 21287 USA.
EM gnestadt@jhmi.edu
OI Samuels, Jack/0000-0002-6715-7905; Costa, Paul/0000-0003-4375-1712
FU NIMH NIH HHS [R01 MH050616, R01 MH050616-09, R01 MH047447, R01
   MH047447-15]
NR 56
TC 5
Z9 6
U1 6
U2 16
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 MAR 30
PY 2012
VL 196
IS 1
BP 109
EP 114
DI 10.1016/j.psychres.2011.08.012
PG 6
WC Psychiatry
SC Psychiatry
GA 955SL
UT WOS:000305041100019
PM 22342178
ER

PT J
AU Xu, XQ
   Francischetti, IMB
   Lai, R
   Ribeiro, JMC
   Andersen, JF
AF Xu, Xueqing
   Francischetti, Ivo M. B.
   Lai, Ren
   Ribeiro, Jose M. C.
   Andersen, John F.
TI Structure of Protein Having Inhibitory Disintegrin and Leukotriene
   Scavenging Functions Contained in Single Domain
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMINE-BINDING PROTEIN; CRYSTAL-STRUCTURE; SNAKE-VENOM; INTEGRIN
   ALPHA-V-BETA-3; EXTRACELLULAR SEGMENT; RHODNIUS-PROLIXUS; IIB-IIIA;
   RECOGNITION; FIBRINOGEN; SALIVA
AB The antihemostatic/antiangiogenic protein tablysin-15 is a member of the CAP (cysteine-rich secretory, antigen 5, and pathogenesis-related 1 protein) superfamily and has been shown to bind the integrins alpha(IIb)beta(3) and alpha(V)beta(3) by means of an Arg-Gly-Asp (RGD) tripeptide sequence. Here we describe the x-ray crystal structure of tablysin-15 and show that the RGD motif is located in a novel structural context. The motif itself is contained in a type II beta-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin alpha V beta 3. The CAP domain also contains a hydrophobic channel that appears to bind a fatty acid molecule in the crystal structure after purification from Escherichia coli. After delipidation of the protein, tablysin-15 was found to bind proinflammatory cysteinyl leukotrienes with sub-micromolar affinities. The structure of the leukotriene E-4-tablysin-15 complex shows that the ligand binds with the nonfunctionalized end of the fatty acid chain buried in the hydrophobic pocket, whereas the carboxylate end of the ligand binds forms hydrogen bond/salt bridge interactions with polar side chains at the channel entrance. Therefore, tablysin-15 functions as an inhibitor of integrin function and as an anti-inflammatory scavenger of eicosanoids.
C1 [Lai, Ren] Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China.
   [Xu, Xueqing; Francischetti, Ivo M. B.; Ribeiro, Jose M. C.; Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Lai, R (reprint author), Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming 6550223, Yunnan, Peoples R China.
EM lairen72@yahoo.com.cn; jandersen@niaid.nih.gov
RI Ribeiro, Jose/J-7011-2015; 
OI Ribeiro, Jose/0000-0002-9107-0818
FU National Institutes of Health of NIAID; U.S. Department of Energy,
   Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
FX This work was supported, in whole or in part, by the National Institutes
   of Health intramural research program of NIAID. This work was also
   supported in part by the U.S. Department of Energy, Office of Science,
   Office of Basic Energy Sciences under Contract W-31-109-Eng-38.
NR 42
TC 11
Z9 11
U1 0
U2 7
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 MAR 30
PY 2012
VL 287
IS 14
BP 10967
EP 10976
DI 10.1074/jbc.M112.340471
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 925RY
UT WOS:000302780100025
PM 22311975
ER

PT J
AU Teijido, O
   Ujwal, R
   Hillerdal, CO
   Kullman, L
   Rostovtseva, TK
   Abramson, J
AF Teijido, Oscar
   Ujwal, Rachna
   Hillerdal, Carl-Olof
   Kullman, Lisen
   Rostovtseva, Tatiana K.
   Abramson, Jeff
TI Affixing N-terminal alpha-Helix to the Wall of the Voltage-dependent
   Anion Channel Does Not Prevent Its Voltage Gating
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MITOCHONDRIAL OUTER-MEMBRANE; NEUROSPORA-CRASSA; CRYSTAL-STRUCTURE; VDAC
   CHANNELS; BCL-2 FAMILY; CELL-DEATH; LOOP 3; PROTEIN; PORIN;
   OLIGOMERIZATION
AB The voltage-dependent anion channel (VDAC) governs the free exchange of ions and metabolites between the mitochondria and the rest of the cell. The three-dimensional structure of VDAC1 reveals a channel formed by 19 beta-strands and an N-terminal alpha-helix located near the midpoint of the pore. The position of this alpha-helix causes a narrowing of the cavity, but ample space for metabolite passage remains. The participation of the N-terminus of VDAC1 in the voltage-gating process has been well established, but the molecular mechanism continues to be debated; however, the majority of models entail large conformational changes of this N-terminal segment. Here we report that the pore-lining N-terminal alpha-helix does not undergo independent structural rearrangements during channel gating. We engineered a double Cys mutant in murine VDAC1 that cross-links the alpha-helix to the wall of the beta-barrel pore and reconstituted the modified protein into planar lipid bilayers. The modified murine VDAC1 exhibited typical voltage gating. These results suggest that the N-terminal alpha-helix is located inside the pore of VDAC in the open state and remains associated with beta-strand 11 of the pore wall during voltage gating.
C1 [Teijido, Oscar; Rostovtseva, Tatiana K.] Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
   [Ujwal, Rachna; Abramson, Jeff] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
   [Hillerdal, Carl-Olof; Kullman, Lisen] Uppsala Univ, Dept Med Cell Biol, S-75123 Uppsala, Sweden.
RP Rostovtseva, TK (reprint author), Eunice Kennedy Shriver NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
EM rostovtt@mail.nih.gov; jabramson@mednet.ucla.edu
FU Eunice Kennedy Shriver NICHD, National Institutes of Health; National
   Institutes of Health [RO1 GM078844]
FX This work was supported, in whole or in part, by the Intramural Research
   Program of the Eunice Kennedy Shriver NICHD, National Institutes of
   Health (to O. T. and T. K. R.) and National Institutes of Health Grant
   RO1 GM078844 (to J. A.).
NR 48
TC 31
Z9 31
U1 0
U2 9
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 MAR 30
PY 2012
VL 287
IS 14
BP 11437
EP 11445
DI 10.1074/jbc.M111.314229
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 925RY
UT WOS:000302780100072
PM 22275367
ER

PT J
AU Nakashiba, T
   Cushman, JD
   Pelkey, KA
   Renaudineau, S
   Buhl, DL
   McHugh, TJ
   Barrera, VR
   Chittajallu, R
   Iwamoto, KS
   McBain, CJ
   Fanselow, MS
   Tonegawa, S
AF Nakashiba, Toshiaki
   Cushman, Jesse D.
   Pelkey, Kenneth A.
   Renaudineau, Sophie
   Buhl, Derek L.
   McHugh, Thomas J.
   Barrera, Vanessa Rodriguez
   Chittajallu, Ramesh
   Iwamoto, Keisuke S.
   McBain, Chris J.
   Fanselow, Michael S.
   Tonegawa, Susumu
TI Young Dentate Granule Cells Mediate Pattern Separation, whereas Old
   Granule Cells Facilitate Pattern Completion
SO CELL
LA English
DT Article
ID ADULT HIPPOCAMPAL NEUROGENESIS; ENHANCED SYNAPTIC PLASTICITY; DOUBLE
   DISSOCIATION; DORSAL HIPPOCAMPUS; CRITICAL PERIOD; NMDA RECEPTORS;
   SPATIAL MEMORY; GYRUS; CA3; NEURONS
AB Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally. To ascertain whether young and old GCs perform distinct memory functions, we created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts, which was reduced following ablation of young GCs. Furthermore, these mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation requires adult-born young GCs but not old GCs, and older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion.
C1 [Nakashiba, Toshiaki; Renaudineau, Sophie; Buhl, Derek L.; McHugh, Thomas J.; Tonegawa, Susumu] MIT, Picower Inst Learning & Memory, RIKEN MIT Ctr Neural Circuit Genet, Dept Biol, Cambridge, MA 02139 USA.
   [Nakashiba, Toshiaki; Renaudineau, Sophie; Buhl, Derek L.; McHugh, Thomas J.; Tonegawa, Susumu] MIT, Picower Inst Learning & Memory, RIKEN MIT Ctr Neural Circuit Genet, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Cushman, Jesse D.; Barrera, Vanessa Rodriguez; Fanselow, Michael S.] Univ Calif Los Angeles, Dept Psychol, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
   [Pelkey, Kenneth A.; Chittajallu, Ramesh; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Cellular & Synapt Neurophysiol, Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Iwamoto, Keisuke S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA.
RP Tonegawa, S (reprint author), MIT, Picower Inst Learning & Memory, RIKEN MIT Ctr Neural Circuit Genet, Dept Biol, Cambridge, MA 02139 USA.
EM tonegawa@mit.edu
RI McHugh, Thomas/A-6693-2010
OI McHugh, Thomas/0000-0002-1243-5189
FU Howard Hughes Medical Institute; Otsuka Maryland Research Institute;
   Picower Foundation; NIH [R01-MH078821, P50-MH58880, R01-MH62122]; NICHD
FX We wish to thank F. Bushard, A. Ogawa, J. Derwin, C. Lovett, D. Rooney,
   C. Twiss, M. Pfau, and M. Serock for excellent technical assistance,
   Tonegawa lab members including J. Biedenkapp, J. Young, and G. Dragoi
   for comments on earlier versions of the manuscript, N. Arzoumanian for
   help with manuscript preparation, C. Lois for plasmids, I. Wickersham
   and H.S. Seung for the rabies virus, and S. Lee for help with
   preliminary irradiation experiments. This work was supported by the
   Howard Hughes Medical Institute, the Otsuka Maryland Research Institute,
   the Picower Foundation, and NIH grants R01-MH078821 and P50-MH58880 to
   S.T.; NIH grant R01-MH62122 to M.S.F.; and NICHD intramural funding to
   C.J.M.
NR 50
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U2 82
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 30
PY 2012
VL 149
IS 1
BP 188
EP 201
DI 10.1016/j.cell.2012.01.046
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 918FT
UT WOS:000302235400020
PM 22365813
ER

PT J
AU Vertino, PM
   Wade, PA
AF Vertino, Paula M.
   Wade, Paul A.
TI R Loops: Lassoing DNA Methylation at CpGi
SO MOLECULAR CELL
LA English
DT Editorial Material
AB In this issue of Molecular Cell, Ginno et al. (2012) describe unusual sequence features at promoter CpG islands that can lead to formation of persistent RNA-DNA hybrids (R loops), which are proposed to prevent genomic DNA methylation.
C1 [Vertino, Paula M.] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30307 USA.
   [Vertino, Paula M.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30307 USA.
   [Wade, Paul A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Vertino, PM (reprint author), Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30307 USA.
EM pvertin@emory.edu; wadep2@niehs.nih.gov
FU NCI NIH HHS [R01 CA132065]
NR 10
TC 1
Z9 1
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD MAR 30
PY 2012
VL 45
IS 6
BP 708
EP 709
DI 10.1016/j.molcel.2012.03.014
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 920ES
UT WOS:000302386100003
PM 22464440
ER

PT J
AU Lee, EK
   Kim, W
   Tominaga, K
   Martindale, JL
   Yang, XL
   Subaran, SS
   Carlson, OD
   Mercken, EM
   Kulkarni, RN
   Akamatsu, W
   Okano, H
   Perrone-Bizzozero, NI
   de Cabo, R
   Egan, JM
   Gorospe, M
AF Lee, Eun Kyung
   Kim, Wook
   Tominaga, Kumiko
   Martindale, Jennifer L.
   Yang, Xiaoling
   Subaran, Sarah S.
   Carlson, Olga D.
   Mercken, Evi M.
   Kulkarni, Rohit N.
   Akamatsu, Wado
   Okano, Hideyuki
   Perrone-Bizzozero, Nora I.
   de Cabo, Rafael
   Egan, Josephine M.
   Gorospe, Myriam
TI RNA-Binding Protein HuD Controls Insulin Translation
SO MOLECULAR CELL
LA English
DT Article
ID MESSENGER-RNA; BETA-CELL; POSTTRANSCRIPTIONAL REGULATION; GLUCOSE;
   ELEMENT; BIOSYNTHESIS; INCREASE; RECEPTOR; REGION; ELAV
AB Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic (3 cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic beta cells.
C1 [Lee, Eun Kyung; Tominaga, Kumiko; Martindale, Jennifer L.; Yang, Xiaoling; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Kim, Wook; Subaran, Sarah S.; Carlson, Olga D.; Egan, Josephine M.] NIA, Clin Invest Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Mercken, Evi M.; de Cabo, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Lee, Eun Kyung] Catholic Univ Korea, Dept Biochem, Coll Med, Seoul 137701, South Korea.
   [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Islet Cell Biol & Regenerat Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
   [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
   [Akamatsu, Wado; Okano, Hideyuki] Keio Univ, Dept Physiol, Grad Sch Med, Shinjuku Ku, Tokyo 1608582, Japan.
   [Perrone-Bizzozero, Nora I.] Univ New Mexico, Dept Neurosci, Sch Med, Albuquerque, NM 87131 USA.
RP Gorospe, M (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
RI Akamatsu, Wado/L-1214-2013; Hidokano, Hideyuki/J-5973-2013; de Cabo,
   Rafael/J-5230-2016; 
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU National Institute on Aging-Intramural Research Program, National
   Institutes of Health (NIH); NIH [RO1 DK 67536, 68721]; Japanese Ministry
   of Education, Science, Sports, Culture and Technology; Korean Ministry
   of Education, Science and Technology [5-2011-A0154-00046]
FX We thank H.J. Okano, M. Igarashi, R. Selimyan, D. Nines, and D. Boyer
   for assistance and H. Huang for reagents. This work was supported in
   part by the National Institute on Aging-Intramural Research Program,
   National Institutes of Health (NIH). R.N.K. is supported by NIH grants
   RO1 DK 67536 and 68721. H.O. and W.A. are funded by the Japanese
   Ministry of Education, Science, Sports, Culture and Technology. E.K.L.
   is funded by the Korean Ministry of Education, Science and Technology
   (5-2011-A0154-00046).
NR 22
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U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD MAR 30
PY 2012
VL 45
IS 6
BP 826
EP 835
DI 10.1016/j.molcel.2012.01.016
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 920ES
UT WOS:000302386100014
PM 22387028
ER

PT J
AU Zhou, XH
   Johnson, LL
AF Zhou, Xiao-Hua
   Johnson, Laura Lee
TI Preface
SO STATISTICS IN MEDICINE
LA English
DT Article
C1 [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, VA Puget Sound Hlth Care Syst, HSB, Seattle, WA 98195 USA.
   [Johnson, Laura Lee] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, VA Puget Sound Hlth Care Syst, HSB, 1705 Pacific St NE,F600, Seattle, WA 98195 USA.
EM azhou@u.washington.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD MAR 30
PY 2012
VL 31
IS 7
SI SI
BP 601
EP 601
DI 10.1002/sim.4442
PG 1
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 903MY
UT WOS:000301121900001
PM 22392624
ER

PT J
AU Scott, JD
   Carlson, DE
AF Scott, Jane D.
   Carlson, Drew E.
TI K08 and K99 Cardiovascular Training Comparisons and Trends Among Current
   Awardees
SO CIRCULATION RESEARCH
LA English
DT Editorial Material
C1 [Scott, Jane D.] NHLBI, Off Res Training & Career Dev, Div Cardiovasc Sci, NIH,DCVS, Bethesda, MD 20892 USA.
RP Scott, JD (reprint author), NHLBI, Off Res Training & Career Dev, Div Cardiovasc Sci, NIH,DCVS, RKL2 Room 8138,MSC 7940,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM scottj2@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 2
TC 5
Z9 5
U1 1
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 MAR 30
PY 2012
VL 110
IS 7
BP 910
EP 914
DI 10.1161/RES.0b013e3182533291
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
   Disease
SC Cardiovascular System & Cardiology; Hematology
GA 917ZZ
UT WOS:000302219900006
PM 22461361
ER

PT J
AU Carey, HV
   Martin, SL
   Horwitz, BA
   Yan, L
   Bailey, SM
   Podrabsky, J
   Storz, JF
   Ortiz, RM
   Wong, RP
   Lathrop, DA
AF Carey, Hannah V.
   Martin, Sandra L.
   Horwitz, Barbara A.
   Yan, Lin
   Bailey, Shannon M.
   Podrabsky, Jason
   Storz, Jay F.
   Ortiz, Rudy M.
   Wong, Renee P.
   Lathrop, David A.
TI Elucidating Nature's Solutions to Heart, Lung, and Blood Diseases and
   Sleep Disorders
SO CIRCULATION RESEARCH
LA English
DT Article
DE animal models; deep-diving; diapause; human disease; hibernation;
   hypoxia; high-altitude
ID ISCHEMIA-REPERFUSION INJURY; CHRONIC MOUNTAIN-SICKNESS; NORTHERN
   ELEPHANT SEAL; KILLIFISH AUSTROFUNDULUS-LIMNAEUS; SQUIRREL
   CITELLUS-CITELLUS; EXTREME ANOXIA TOLERANCE; HIGH-ALTITUDE;
   GROUND-SQUIRREL; HETEROSYNAPTIC FACILITATION; ACETYLCHOLINE-RECEPTORS
AB Evolution has provided a number of animal species with extraordinary phenotypes. Several of these phenotypes allow species to survive and thrive in environmental conditions that mimic disease states in humans. The study of evolved mechanisms responsible for these phenotypes may provide insights into the basis of human disease and guide the design of new therapeutic approaches. Examples include species that tolerate acute or chronic hypoxemia like deep-diving mammals and high-altitude inhabitants, as well as those that hibernate and interrupt their development when exposed to adverse environments. The evolved traits exhibited by these animal species involve modifications of common biological pathways that affect metabolic regulation, organ function, antioxidant defenses, and oxygen transport. In 2006, the National Heart, Lung, and Blood Institute released a funding opportunity announcement to support studies that were designed to elucidate the natural molecular and cellular mechanisms of adaptation in species that tolerate extreme environmental conditions. The rationale for this funding opportunity is detailed in this article, and the specific evolved mechanisms examined in the supported research are described. Also highlighted are past medical advances achieved through the study of animal species that have evolved extraordinary phenotypes as well as the expectations for new understanding of nature's solutions to heart, lung, blood, and sleep disorders through future research in this area. (Circ Res. 2012; 110:915-921.)
C1 [Carey, Hannah V.] Univ Wisconsin, Dept Comparat Biosci, Sch Vet Med, Madison, WI 53706 USA.
   [Martin, Sandra L.] Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO USA.
   [Horwitz, Barbara A.] Univ Calif Davis, Dept Neurobiol, Davis, CA 95616 USA.
   [Yan, Lin] Univ Med & Dent New Jersey, Dept Cell Biol & Mol Med, Newark, NJ 07103 USA.
   [Bailey, Shannon M.] Univ Alabama Birmingham, Dept Environm Hlth Sci, Birmingham, AL USA.
   [Podrabsky, Jason] Portland State Univ, Dept Biol, Portland, OR 97207 USA.
   [Storz, Jay F.] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA.
   [Ortiz, Rudy M.] Univ Calif Merced, Sch Nat Sci, Merced, CA USA.
   [Wong, Renee P.; Lathrop, David A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Carey, HV (reprint author), Univ Wisconsin, Dept Comparat Biosci, Sch Vet Med, 2015 Linden Dr, Madison, WI 53706 USA.
EM careyh@vetmed.wisc.edu
OI Podrabsky, Jason/0000-0003-1411-8547
FU NSF
FX H.V.C. was supported by the NSF while working at the Foundation. Any
   views expressed are those of the authors and do not necessarily reflect
   those of the National Science Foundation. R. P. W. and D. A. L. are
   employees of National Heart, Lung, and Blood Institute at National
   Institutes of Health, and although their participation in the
   development of this manuscript was performed as an official duty
   activity, the views expressed do not necessarily represent those of the
   Institutes.
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U1 0
U2 12
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 MAR 30
PY 2012
VL 110
IS 7
BP 915
EP 921
DI 10.1161/CIRCRESAHA.111.255398
PG 7
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
   Disease
SC Cardiovascular System & Cardiology; Hematology
GA 917ZZ
UT WOS:000302219900007
PM 22461362
ER

PT J
AU Bosnjakovic, A
   Mishra, MK
   Han, HJ
   Romero, R
   Kannan, RM
AF Bosnjakovic, Admira
   Mishra, Manoj K.
   Han, Hye Jung
   Romero, Roberto
   Kannan, Rangaramanujam M.
TI A dendrimer-based immunosensor for improved capture and detection of
   tumor necrosis factor-alpha cytokine
SO ANALYTICA CHIMICA ACTA
LA English
DT Article
DE PAMAM dendrimer; TNF-alpha; ELISA; Dendrimer biosensor
ID AMNIOTIC-FLUID; INTRAAMNIOTIC INFECTION; METAL NANOPARTICLES; PAMAM
   DENDRIMERS; SOLID SUPPORTS; PRETERM LABOR; PROTEIN; ASSAY; DELIVERY;
   SURFACE
AB A dendrimer-based sandwich type enzyme-linked immunosorbent assay (ELISA) was developed for the improved detection of recombinant human tumor necrosis factor-alpha (TNF-alpha) for early diagnosis of perinatal diseases. Hydroxyl-terminated generation four poly(amidoamine) dendrimer (G4-OH) was used for the development of a solid phase bio-sensing platform. The surface of the ELISA plate was modified with polyethylene-glycol (PEG) and thiol-functionalized G4-OH was immobilized on the PEG-functionalized plate. A capture antibody was oxidized and covalently immobilized onto the dendrimer-modified ELISA plate, which provides favorable orientation for the antigen binding sites toward the analyte. The dendrimer-modified plate showed enhanced sensitivity, and the detection limit for TNF-alpha was found to be 0.48 pg mL(-1), which is significantly better than the commercially available ELISA kit. The selectivity of the dendrimer-modified ELISA plate was further evaluated with a mixture of cytokines, which showed results for similar to that of TNF-alpha alone. The modified plate provides a greater opportunity for the detection of a wide range of cytokines and biomarkers. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Bosnjakovic, Admira; Mishra, Manoj K.; Han, Hye Jung; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA.
   [Han, Hye Jung; Romero, Roberto; Kannan, Rangaramanujam M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI 48201 USA.
RP Kannan, RM (reprint author), Johns Hopkins Sch Med, Ctr Nanomed Ophthalmol, Wilmer Eye Inst, Baltimore, MD 21287 USA.
EM krangar1@jhmi.edu
FU Division of Intramural Research; Eunice Kennedy Shriver National
   Institute of Child Health and Human Development, National Institutes of
   Health, Department of Health and Human Services (NICHD/NIH/DHHS); Ralph
   C. Wilson Foundation for Biomedical Research; WSU Nanotechnology effort
FX This research was supported by the Division of Intramural Research,
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health, Department of Health and
   Human Services (NICHD/NIH/DHHS), and the Ralph C. Wilson Foundation for
   Biomedical Research, and WSU Nanotechnology effort.
NR 62
TC 17
Z9 17
U1 5
U2 31
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0003-2670
J9 ANAL CHIM ACTA
JI Anal. Chim. Acta
PD MAR 30
PY 2012
VL 720
BP 118
EP 125
DI 10.1016/j.aca.2012.01.017
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 911AG
UT WOS:000301689100017
PM 22365129
ER

PT J
AU Pletnev, S
   Subach, FV
   Dauter, Z
   Wlodawer, A
   Verkhusha, VV
AF Pletnev, Sergei
   Subach, Fedor V.
   Dauter, Zbigniew
   Wlodawer, Alexander
   Verkhusha, Vladislav V.
TI A Structural Basis for Reversible Photoswitching of Absorbance Spectra
   in Red Fluorescent Protein rsTagRFP
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE KFP; Dronpa; TagRFP; PAmCherry; FRET
ID STATE STRUCTURE; DRONPA MUTANTS; MICROSCOPY; GENERATION; RESOLUTION;
   MECHANISM; NANOSCOPY; HOMOLOG; FRET
AB rsTagRFP is the first monomeric red fluorescent protein (FP) with reversibly photoswitchable absorbance spectra. The switching is realized by irradiation of rsTagRFP with blue (440 nm) and yellow (567 nm) light, turning the protein fluorescence ON and OFF, respectively. It is perhaps the most useful probe in this color class that has yet been reported. Because of the photoswitchable absorbance, rsTagRFP can be used as an acceptor in photochromic Forster resonance energy transfer. Yellow FPs, YPet and mVenus, are demonstrated to be excellent photochromic Forster resonance energy transfer donors for the rsTagRFP acceptor in its fusion constructs. Analysis of X-ray structures has shown that photoswitching of rsTagRFP is accompanied by cis-trans isomerization and protonation/deprotonation of the chromophore, with the deprotonated cis- and protonated trans-isomers corresponding to its ON and OFF states, respectively. Unlike in other photoswitchable FPs, both conformers of rsTagRFP chromophore are essentially coplanar. Two other peculiarities of the rsTagRFP chromophore are an essentially hydrophobic environment of its p-hydroxyphenyl site and the absence of direct hydrogen bonding between this moiety and the protein scaffold. The influence of the immediate environment on rsTagRFP chromophore was probed by site-directed mutagenesis. Residues Glu145 and His197 were found to participate in protonation/deprotonation of the chromophore accompanying the photoswitching of rsTagRFP fluorescence, whereas residues Met160 and Leu174 were shown to spatially restrict chromophore isomerization, favoring its radiative decay. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Pletnev, Sergei; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
   [Pletnev, Sergei] SAIC Frederick, Basic Res Program, Argonne, IL 60439 USA.
   [Subach, Fedor V.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
   [Subach, Fedor V.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Gruss Lipper Biophoton Ctr, Bronx, NY 10461 USA.
   [Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Pletnev, S (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM pletnevs@gmail.nih.gov; vladislav.verkhusha@einstein.yu.edu
RI Subach, Fedor/K-7080-2014
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
   Sciences [W-31-109-Eng-38]; National Cancer Institute, National
   Institutes of Health (NIH) [HHSN261200800001E]; NIH [GM073913,
   CA164468]; NIH, National Cancer Institute, Center for Cancer Research
FX We thank K. D. Piatkevich for discussions. We acknowledge the use of
   beamline 22-BM of the Southeast Regional Collaborative Access Team,
   located at the Advanced Photon Source, Argonne National Laboratory. Use
   of the Advanced Photon Source was supported by the U.S. Department of
   Energy, Office of Science, Office of Basic Energy Sciences, under
   Contract No. W-31-109-Eng-38. This project was supported in part by
   Federal funds from the National Cancer Institute, National Institutes of
   Health (NIH) contract No. HHSN261200800001E; the Intramural Research
   Program of the NIH, National Cancer Institute, Center for Cancer
   Research; and NIH grants GM073913 and CA164468 to V.V.V.
NR 31
TC 21
Z9 22
U1 2
U2 20
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 MAR 30
PY 2012
VL 417
IS 3
BP 144
EP 151
DI 10.1016/j.jmb.2012.01.044
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 912NB
UT WOS:000301805800002
PM 22310052
ER

PT J
AU Posner, M
   Kiss, AJ
   Skiba, J
   Drossman, A
   Dolinska, MB
   Hejtmancik, JF
   Sergeev, YV
AF Posner, Mason
   Kiss, Andor J.
   Skiba, Jackie
   Drossman, Amy
   Dolinska, Monika B.
   Hejtmancik, J. Fielding
   Sergeev, Yuri V.
TI Functional Validation of Hydrophobic Adaptation to Physiological
   Temperature in the Small Heat Shock Protein alpha A-crystallin
SO PLOS ONE
LA English
DT Article
ID CHAPERONE-LIKE ACTIVITY; ZEBRAFISH DANIO-RERIO; TOOTHFISH
   DISSOSTICHUS-MAWSONI; DIFFERENT THERMAL ENVIRONMENTS; EYE LENS
   CRYSTALLINS; B-CRYSTALLIN; PHYLOGENETIC ANALYSIS; MOLECULAR CHAPERONE;
   MAXIMUM-LIKELIHOOD; SUBUNIT EXCHANGE
AB Small heat shock proteins (sHsps) maintain cellular homeostasis by preventing stress and disease-induced protein aggregation. While it is known that hydrophobicity impacts the ability of sHsps to bind aggregation-prone denaturing proteins, the complex quaternary structure of globular sHsps has made understanding the significance of specific changes in hydrophobicity difficult. Here we used recombinant protein of the lenticular sHsp alpha A-crystallin from six teleost fishes environmentally adapted to temperatures ranging from -2 degrees C to 40 degrees C to identify correlations between physiological temperature, protein stability and chaperone-like activity. Using sequence and structural modeling analysis we identified specific amino acid differences between the warm adapted zebrafish and cold adapted Antarctic toothfish that could contribute to these correlations and validated the functional consequences of three specific hydrophobicity-altering amino acid substitutions in alpha A-crystallin. Site directed mutagenesis of three residues in the zebrafish (V62T, C143S, T147V) confirmed that each impacts either protein stability or chaperone-like activity or both, with the V62T substitution having the greatest impact. Our results indicate a role for changing hydrophobicity in the thermal adaptation of alpha A-crystallin and suggest ways to produce sHsp variants with altered chaperone-like activity. These data also demonstrate that a comparative approach can provide new information about sHsp function and evolution.
C1 [Posner, Mason; Skiba, Jackie; Drossman, Amy] Ashland Univ, Dept Biol, Ashland, OH USA.
   [Kiss, Andor J.] Miami Univ, Dept Zool, Oxford, OH 45056 USA.
   [Dolinska, Monika B.; Hejtmancik, J. Fielding; Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Posner, M (reprint author), Ashland Univ, Dept Biol, Ashland, OH USA.
EM mposner@ashland.edu
FU National Eye Institute at the National Institutes of Health [R15
   EY13535]
FX This research was funded by grant R15 EY13535 from the National Eye
   Institute at the National Institutes of Health.
   http://grants.nih.gov/grants/funding/area.htm. The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 71
TC 8
Z9 9
U1 5
U2 13
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 MAR 29
PY 2012
VL 7
IS 3
AR e34438
DI 10.1371/journal.pone.0034438
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 948SR
UT WOS:000304523400084
PM 22479631
ER

PT J
AU Veleri, S
   Bishop, K
   Nogare, DED
   English, MA
   Foskett, TJ
   Chitnis, A
   Sood, R
   Liu, P
   Swaroop, A
AF Veleri, Shobi
   Bishop, Kevin
   Nogare, Damian E. Dalle
   English, Milton A.
   Foskett, Trevor J.
   Chitnis, Ajay
   Sood, Raman
   Liu, Paul
   Swaroop, Anand
TI Knockdown of Bardet-Biedl Syndrome Gene BBS9/PTHB1 Leads to Cilia
   Defects
SO PLOS ONE
LA English
DT Article
ID PLANAR CELL POLARITY; RESPONSIVE B1 GENE; WPK RAT; DISEASE; PROTEIN;
   DISSECTION; GENOMICS; COMPLEX; FAMILY; MODEL
AB Bardet-Biedl Syndrome (BBS, MIM#209900) is a genetically heterogeneous disorder with pleiotropic phenotypes that include retinopathy, mental retardation, obesity and renal abnormalities. Of the 15 genes identified so far, seven encode core proteins that form a stable complex called BBSome, which is implicated in trafficking of proteins to cilia. Though BBS9 (also known as PTHB1) is reportedly a component of BBSome, its direct function has not yet been elucidated. Using zebrafish as a model, we show that knockdown of bbs9 with specific antisense morpholinos leads to developmental abnormalities in retina and brain including hydrocephaly that are consistent with the core phenotypes observed in syndromic ciliopathies. Knockdown of bbs9 also causes reduced number and length of cilia in Kupffer's vesicle. We also demonstrate that an orthologous human BBS9 mRNA, but not one carrying a missense mutation identified in BBS patients, can rescue the bbs9 morphant phenotype. Consistent with these findings, knockdown of Bbs9 in mouse IMCD3 cells results in the absence of cilia. Our studies suggest a key conserved role of BBS9 in biogenesis and/or function of cilia in zebrafish and mammals.
C1 [Veleri, Shobi; English, Milton A.; Foskett, Trevor J.; Swaroop, Anand] NEI, N NRL, NIH, Bethesda, MD 20892 USA.
   [Bishop, Kevin; English, Milton A.; Sood, Raman; Liu, Paul] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Nogare, Damian E. Dalle; Chitnis, Ajay] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Veleri, S (reprint author), NEI, N NRL, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI Liu, Paul/A-7976-2012; 
OI Liu, Paul/0000-0002-6779-025X; Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute, National Human Genome Research Institute;
   National Institute of Child Health and Development, National Institutes
   of Health
FX The study was supported by intramural funds of the National Eye
   Institute, National Human Genome Research Institute and National
   Institute of Child Health and Development, 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 41
TC 17
Z9 18
U1 0
U2 5
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 MAR 29
PY 2012
VL 7
IS 3
AR e34389
DI 10.1371/journal.pone.0034389
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 948SR
UT WOS:000304523400080
PM 22479622
ER

PT J
AU Yutin, N
   Koonin, EV
AF Yutin, Natalya
   Koonin, Eugene V.
TI Archaeal origin of tubulin
SO BIOLOGY DIRECT
LA English
DT Article
ID CELL-DIVISION; PHYLOGENETIC TREES; DATABASE SEARCHES; CYTOSKELETON;
   EVOLUTION; SEQUENCE; FTSZ; EUKARYOTES; INSIGHTS; PROSTHECOBACTER
AB Tubulins are a family of GTPases that are key components of the cytoskeleton in all eukaryotes and are distantly related to the FtsZ GTPase that is involved in cell division in most bacteria and many archaea. Among prokaryotes, bona fide tubulins have been identified only in bacteria of the genus Prosthecobacter. These bacterial tubulin genes appear to have been horizontally transferred from eukaryotes. Here we describe tubulins encoded in the genomes of thaumarchaeota of the genus Nitrosoarchaeum that we denote artubulins Phylogenetic analysis results are compatible with the origin of eukaryotic tubulins from artubulins. These findings expand the emerging picture of the origin of key components of eukaryotic functional systems from ancestral forms that are scattered among the extant archaea.
C1 [Yutin, Natalya; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health; Human Services
FX The authors' research is supported by the US Department of Health and
   Human Services intramural funds (to National Library of Medicine).
NR 48
TC 29
Z9 29
U1 2
U2 14
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 MAR 29
PY 2012
VL 7
AR 10
DI 10.1186/1745-6150-7-10
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 941QP
UT WOS:000303978000001
PM 22458654
ER

PT J
AU Ippolito, G
   Feldmann, H
   Lanini, S
   Vairo, F
   Di Caro, A
   Capobianchi, MR
   Nicastri, E
AF Ippolito, Giuseppe
   Feldmann, Heinz
   Lanini, Simone
   Vairo, Francesco
   Di Caro, Antonino
   Capobianchi, Maria Rosaria
   Nicastri, Emanuele
TI Viral hemorrhagic fevers: advancing the level of treatment
SO BMC MEDICINE
LA English
DT Article
DE clinical management; innovative therapeutics; viral hemorrhagic fever
ID HANTAVIRUS CARDIOPULMONARY SYNDROME; POLYMERASE-CHAIN-REACTION; PUUMALA
   VIRUS-INFECTION; EBOLA-VIRUS; DENGUE VIRUS; POSTEXPOSURE PROTECTION;
   NONHUMAN-PRIMATES; RNA INTERFERENCE; EUROPEAN NETWORK; RENAL SYNDROME
AB The management of viral hemorrhagic fevers (VHFs) has mainly focused on strict infection control measures, while standard clinical interventions that are provided to patients with other life-threatening conditions are rarely offered to patients with VHFs. Despite its complexity, a proper clinical case management of VHFs is neither futile nor is it lacking in scientific rationale. Given that patient outcomes improve when treatment is started as soon as possible, development and implementation of protocols to promptly identify and treat patients in the earliest phases of diseases are urgently needed. Different pharmacological options have been proposed to manage patients and, as for other life-threatening conditions, advanced life support has been proved effective to address multiorgan failure. In addition, high throughput screening of small molecular libraries has emerged as a novel promising way to find new candidates drugs for VHFs therapy and a relevant number of new molecules are currently under investigation. Here we discuss the current knowledge about VHF clinical management to propose a way to step up the approach to VHFs beyond the mere application of infection control measures.
C1 [Ippolito, Giuseppe; Lanini, Simone; Vairo, Francesco; Di Caro, Antonino; Capobianchi, Maria Rosaria; Nicastri, Emanuele] Natl Inst Infect Dis Lazzaro Spallanzani, I-00149 Rome, Italy.
   [Feldmann, Heinz] NIAID, Rocky Mt Labs, Virol Lab, Div Intramural Res,NIH, Hamilton, MT 59840 USA.
   [Vairo, Francesco] Italian Hlth Cooperat, I-00135 Rome, Italy.
RP Ippolito, G (reprint author), Natl Inst Infect Dis Lazzaro Spallanzani, Via Portuense 292, I-00149 Rome, Italy.
EM giuseppe.ippolito@inmi.it; simone.lanini@inmi.it
RI Di Caro, Antonino/K-6854-2016; 
OI Di Caro, Antonino/0000-0001-6027-3009; Ippolito,
   Giuseppe/0000-0002-1076-2979; Vairo, Francesco/0000-0002-8375-7468;
   nicastri, emanuele/0000-0002-5606-8712; Capobianchi, Maria
   Rosaria/0000-0003-3465-0071
FU European Commission [2003207, 2003214, 2005202, 2006205, 200620]
FX This work has been partly supported by grants from Italian Ministry of
   Health (Ricerca Corrente and Ricerca Finalizzata), and is part of the
   activities supported by European Commission in the projects 'European
   Network of Infectious Diseases Phisicians (EUNID)' contract 2003207,
   'European Network of P4 Laboratories (EURONET-P4)' contract 2003214,
   'European Training for Infectious Disease Emergencies (ETIDE)' contract
   2005202, 'European Network for Highly Infectious Diseases (EuroNHID)'
   contract 2006205, 'European Network of P4 Laboratories (ENP4Lab)'
   contract 200620.
NR 63
TC 8
Z9 9
U1 0
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD MAR 29
PY 2012
VL 10
AR 31
DI 10.1186/1741-7015-10-31
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 926VM
UT WOS:000302860000001
PM 22458265
ER

PT J
AU Ludwig, H
   Durie, BGM
   McCarthy, P
   Palumbo, A
   Miguel, JS
   Barlogie, B
   Morgan, G
   Sonneveld, P
   Spencer, A
   Andersen, KC
   Facon, T
   Stewart, KA
   Einsele, H
   Mateos, MV
   Wijermans, P
   Waage, A
   Beksac, M
   Richardson, PG
   Hulin, C
   Niesvizky, R
   Lokhorst, H
   Landgren, O
   Bergsagel, PL
   Orlowski, R
   Hinke, A
   Cavo, M
   Attal, M
AF Ludwig, Heinz
   Durie, Brian G. M.
   McCarthy, Philip
   Palumbo, Antonio
   San Miguel, Jesus
   Barlogie, Bart
   Morgan, Gareth
   Sonneveld, Pieter
   Spencer, Andrew
   Andersen, Kenneth C.
   Facon, Thierry
   Stewart, Keith A.
   Einsele, Hermann
   Mateos, Maria-Victoria
   Wijermans, Pierre
   Waage, Anders
   Beksac, Meral
   Richardson, Paul G.
   Hulin, Cyrille
   Niesvizky, Ruben
   Lokhorst, Henk
   Landgren, Ola
   Bergsagel, P. Leif
   Orlowski, Robert
   Hinke, Axel
   Cavo, Michele
   Attal, Michel
CA Int Myeloma Working Grp
TI IMWG consensus on maintenance therapy in multiple myeloma
SO BLOOD
LA English
DT Review
ID PREDNISONE PLUS THALIDOMIDE; RANDOMIZED CONTROLLED-TRIAL; STEM-CELL
   TRANSPLANTATION; ELDERLY-PATIENTS; INDUCTION THERAPY; IMPROVES SURVIVAL;
   ORAL MELPHALAN; DEXAMETHASONE; INTERFERON; LENALIDOMIDE
AB Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established. (Blood. 2012; 119(13):3003-3015)
C1 [Ludwig, Heinz] Wilhelminenspital Stadt Wien, Ctr Oncol & Hematol, Dept Med 1, A-1160 Vienna, Austria.
   [Durie, Brian G. M.] Int Myeloma Fdn, SW Oncol Grp, Los Angeles, CA USA.
   [Durie, Brian G. M.] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA.
   [McCarthy, Philip] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
   [Palumbo, Antonio] Univ Turin, Div Hematol, Azienda Osped Univ S Giovanni Battista, Myeloma Unit, Turin, Italy.
   [San Miguel, Jesus; Mateos, Maria-Victoria] Univ Hosp Salamanca, Salamanca, Spain.
   [Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
   [Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands.
   [Morgan, Gareth] Royal Marsden Hosp, Haematooncol Unit, London SW3 6JJ, England.
   [Spencer, Andrew] Alfred Hosp, Clin Haematol Bone Marrow Transplant Dept, Melbourne, Vic, Australia.
   [Andersen, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Facon, Thierry] Hosp Claude Huriez, Dept Hematol, Lille, France.
   [Stewart, Keith A.; Bergsagel, P. Leif] Mayo Clin, Div Hematol Oncol, Scottsdale, AZ USA.
   [Einsele, Hermann] Univ Hosp, Dept Internal Med 2, Wurzburg, Germany.
   [Wijermans, Pierre] Haga Hosp, The Hague, Netherlands.
   [Waage, Anders] Norwegian Univ Sci & Technol, St Olavs Hosp, Dept Hematol, N-7034 Trondheim, Norway.
   [Beksac, Meral] Ankara Univ, Sch Med, Dept Microbiol & Clin Microbiol, Ibn I Sina Hosp, TR-06100 Ankara, Turkey.
   [Hulin, Cyrille] Univ Hosp, Dept Hematol, Nancy, France.
   [Niesvizky, Ruben] Weill Cornell Med Coll, New York, NY USA.
   [Lokhorst, Henk] Univ Med Ctr, Utrecht, Netherlands.
   [Landgren, Ola] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
   [Orlowski, Robert] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Lymphoma Myeloma, Houston, TX 77030 USA.
   [Hinke, Axel] WISP Res Inst, Langenfeld, Germany.
   [Cavo, Michele] S Orsolas Univ Hosp, Bologna Sch Med, Seragnoli Inst Haematol, Bologna, Italy.
   [Attal, Michel] Hosp Purpan, Serv Hematol, Toulouse, France.
RP Ludwig, H (reprint author), Wilhelminenspital Stadt Wien, Ctr Oncol & Hematol, Dept Med 1, Montleartstr 37, A-1160 Vienna, Austria.
EM heinz.ludwig@wienkav.at
RI Beksac, Meral/D-6411-2013; Waage, Anders/D-7705-2013; FACON,
   THIERRY/M-9736-2014; 
OI FACON, THIERRY/0000-0001-7705-8460; SAN MIGUEL,
   JESUS/0000-0002-9183-4857; CAVO, MICHELE/0000-0003-4514-3227
FU International Myeloma Foundation; Austrian Forum against Cancer;
   Celgene; Novartis; NCI; Millennium; Johnson Johnson; Centocor; Onyx;
   Icon; Janssen-Cilag; Mundipharma
FX The experts' meetings on maintenance therapy were supported by the
   International Myeloma Foundation. This study was supported in part by
   the Austrian Forum against Cancer.; K.C.A. received honoraria from ONYX,
   Millennium, Celgene, Novartis, BMS, and Merck and was the cofounder for
   Acetylon. B.B. received honoraria from Celgene, IMF, MMRF, Millennium,
   and Genzyme and research funding from Celgene, Novartis, NCI,
   Millennium, Johnson & Johnson, Centocor, Onyx, and Icon. M.B. received
   honoraria from Celgene and Janssen-Cilag. P.L.B. received honoraria from
   Celgene. M.C. received honoraria from Celgene and Janssen-Cilag.
   B.G.M.D. received honoraria from Celgene and Millennium. H.E. received
   honoraria from Celgene and Janssen-Cilag. T.F. received honoraria from
   Celgene, Merck, Onyx, BMS, and Janssen-Cilag. H. Lokhorst received
   honoraria from Celgene. H. Ludwig received honoraria from Celgene,
   Janssen-Cilag, and Mundipharma and research funding from Celgene,
   Janssen-Cilag, and Mundipharma. M.-V.M. received honoraria from
   Janssen-Cilag, Celgene, and Millennium. P.M. received honoraria from
   Celgene and Onyx. R.N. received honoraria from Celgene and Millennium
   and research funding from Celgene, Onyx, and Millennium. A.P. received
   honoraria from Celgene, Janssen-Cilag, Merck, and AMGEN. P.G.R. received
   honoraria from Celgene, Millennium, and Johnson & Johnson. J.S.M.
   received honoraria from Celgene, Millennium, and Janssen-Cilag. K.A.S.
   received honoraria from Celgene, Millennium, and ONYX and research
   funding from Millenium. A.W. received honoraria from Janssen-Cilag,
   Celgene, and Mundipharma. The remaining authors declare no competing
   financial interests.
NR 48
TC 83
Z9 90
U1 0
U2 8
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 MAR 29
PY 2012
VL 119
IS 13
BP 3003
EP 3015
DI 10.1182/blood-2011-11-374249
PG 13
WC Hematology
SC Hematology
GA 916ZH
UT WOS:000302141200013
PM 22271445
ER

PT J
AU Aalbers, AM
   Kajigaya, S
   van den Heuvel-Eibrink, MM
   van der Velden, VHJ
   Calado, RT
   Young, NS
AF Aalbers, Anna M.
   Kajigaya, Sachiko
   van den Heuvel-Eibrink, Marry M.
   van der Velden, Vincent H. J.
   Calado, Rodrigo T.
   Young, Neal S.
TI Human telomere disease due to disruption of the CCAAT box of the TERC
   promoter
SO BLOOD
LA English
DT Article
ID GAMMA-GLOBIN GENE; MARROW FAILURE SYNDROMES; NF-Y; FETAL-HEMOGLOBIN; RNA
   GENE; MUTATIONS; BINDING; IDENTIFICATION; PERSISTENCE; MOTIF
AB Mutations in the coding region of telomerase complex genes can result in accelerated telomere attrition and human disease. Manifestations of telomere disease include the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia, acute myeloid leukemia, liver cirrhosis, and pulmonary fibrosis. Here, we describe a mutation in the CCAAT box (GCAAT) of the TERC gene promoter in a family in which multiple members had typical features of telomeropathy. The genetic alteration in this critical regulatory sequence resulted in reduced reporter gene activity and absent binding of transcription factor NF-Y, likely responsible for reduced TERC levels, decreased telomerase activity, and short telomeres. This is the first description of a pathogenic mutation in the highly con-served CCAAT box and the first instance of a mutation in the promoter region of TERC producing a telomeropathy. We propose that current mutation-screening strategies should include gene promoter regions for the diagnosis of telomere diseases. This clinical trial was registered at www.clinicaltrials.gov as #NCT00071045. (Blood. 2012;119(13):3060-3063)
C1 [Aalbers, Anna M.; Kajigaya, Sachiko; Calado, Rodrigo T.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   [Aalbers, Anna M.; van den Heuvel-Eibrink, Marry M.] Sophia Childrens Univ Hosp, Dept Pediat Oncol Hematol, Erasmus MC, Rotterdam, Netherlands.
   [Aalbers, Anna M.; van der Velden, Vincent H. J.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands.
   [Calado, Rodrigo T.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Sao Paulo, Brazil.
RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10,CRC Room 3-5140, Bethesda, MD 20892 USA.
EM youngns@mail.nih.gov
RI Calado, Rodrigo/G-2619-2011
FU National Institutes of Health (National Heart, Lung, and Blood
   Institute); KiKa Foundation, Amstelveen, The Netherlands; Rene Vogels
   Foundation, Oirschot, The Netherlands
FX This research was supported in part by the National Institutes of Health
   (National Heart, Lung, and Blood Institute) Intramural Research Program.
   A.M.A. was supported by the KiKa Foundation, Amstelveen, The
   Netherlands, and the Rene Vogels Foundation, Oirschot, The Netherlands.
NR 18
TC 14
Z9 14
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 MAR 29
PY 2012
VL 119
IS 13
BP 3060
EP 3063
DI 10.1182/blood-2011-10-383182
PG 4
WC Hematology
SC Hematology
GA 916ZH
UT WOS:000302141200020
PM 22323451
ER

PT J
AU Tietze, JK
   Wilkins, DEC
   Sckisel, GD
   Bouchlaka, MN
   Alderson, KL
   Weiss, JM
   Ames, E
   Bruhn, KW
   Craft, N
   Wiltrout, RH
   Longo, DL
   Lanier, LL
   Blazar, BR
   Redelman, D
   Murphy, WJ
AF Tietze, Julia K.
   Wilkins, Danice E. C.
   Sckisel, Gail D.
   Bouchlaka, Myriam N.
   Alderson, Kory L.
   Weiss, Jonathan M.
   Ames, Erik
   Bruhn, Kevin W.
   Craft, Noah
   Wiltrout, Robert H.
   Longo, Dan L.
   Lanier, Lewis L.
   Blazar, Bruce R.
   Redelman, Doug
   Murphy, William J.
TI Delineation of antigen-specific and antigen-nonspecific CD8(+) memory
   T-cell responses after cytokine-based cancer immunotherapy
SO BLOOD
LA English
DT Article
ID IN-VIVO; BYSTANDER ACTIVATION; VIRAL-INFECTION; NKG2D RECEPTOR; NK
   CELLS; ANTITUMOR RESPONSES; TUMOR-IMMUNITY; IFN-GAMMA; PROLIFERATION;
   PD-1
AB Memory T cells exhibit tremendous antigen specificity within the immune system and accumulate with age. Our studies reveal an antigen-independent expansion of memory, but not naive, CD8(+) T cells after several immunotherapeutic regimens for cancer resulting in a distinctive phenotype. Signaling through T-cell receptors (TCRs) or CD3 in both mouse and human memory CD8(+) T cells markedly up-regulated programmed death-1 (PD-1) and CD25 (IL-2 receptor alpha chain), and led to antigen-specific tumor cell killing. In contrast, exposure to cytokine alone in vitro or with immunotherapy in vivo did not up-regulate these markers but resulted in expanded memory CD8(+) T cells expressing NKG2D, granzyme B, and possessing broadly lytic capabilities. Blockade of NKG2D in mice also resulted in significantly diminished antitumor effects after immunotherapy. Treatment of TCR-transgenic mice bearing nonantigen expressing tumors with immunotherapy still resulted in significant antitumor effects. Human melanoma tissue biopsies obtained from patients after topically applied immunodulatory treatment resulted in increased numbers of these CD8(+) CD25(-) cells within the tumor site. These findings demonstrate that memory CD8(+) T cells can express differential phenotypes indicative of adaptive or innate effectors based on the nature of the stimuli in a process conserved across species. (Blood. 2012;119(13):3073-3083)
C1 [Murphy, William J.] Univ Calif Davis, Sch Med, Dept Dermatol, Sacramento, CA 95817 USA.
   [Tietze, Julia K.; Sckisel, Gail D.; Ames, Erik; Murphy, William J.] Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA.
   [Wilkins, Danice E. C.; Bouchlaka, Myriam N.; Alderson, Kory L.] Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA.
   [Weiss, Jonathan M.; Wiltrout, Robert H.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
   [Bruhn, Kevin W.; Craft, Noah] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Div Dermatol, Torrance, CA USA.
   [Longo, Dan L.] NIA, Immunol Lab, Baltimore, MD 21224 USA.
   [Lanier, Lewis L.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Lanier, Lewis L.] Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA.
   [Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
   [Blazar, Bruce R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Redelman, Doug] Univ Nevada, Dept Physiol & Cell Biol, Reno, NV 89557 USA.
RP Murphy, WJ (reprint author), Univ Calif Davis, Sch Med, Dept Dermatol, 2921 Stockton Blvd, Sacramento, CA 95817 USA.
EM wmjmurphy@ucdavis.edu
OI Bouchlaka, Myriam/0000-0003-2865-0817
FU National Institutes of Health (NIH) [CA095572, AI068129, CA72669]
FX This work was supported by National Institutes of Health (NIH) grant
   CA095572. L.L.L. is an American Cancer Society Professor and supported
   by NIH grants AI068129 and CA72669.
NR 47
TC 22
Z9 22
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 MAR 29
PY 2012
VL 119
IS 13
BP 3073
EP 3083
DI 10.1182/blood-2011-07-369736
PG 11
WC Hematology
SC Hematology
GA 916ZH
UT WOS:000302141200022
PM 22251483
ER

PT J
AU Mahnke, YD
   Greenwald, JH
   DerSimonian, R
   Roby, G
   Antonelli, LRV
   Sher, A
   Roederer, M
   Sereti, I
AF Mahnke, Yolanda D.
   Greenwald, Jamieson H.
   DerSimonian, Rebecca
   Roby, Gregg
   Antonelli, Lis R. V.
   Sher, Alan
   Roederer, Mario
   Sereti, Irini
TI Selective expansion of polyfunctional pathogen-specific CD4(+) T cells
   in HIV-1-infected patients with immune reconstitution inflammatory
   syndrome
SO BLOOD
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACTIVE ANTIRETROVIRAL
   THERAPY; RESTORATION DISEASE; GRAVES-DISEASE; RISK-FACTORS;
   MYCOBACTERIUM-TUBERCULOSIS; STRONGYLOIDES-STERCORALIS; CRYPTOCOCCAL
   MENINGITIS; INFECTED PATIENTS; CASE DEFINITIONS
AB Since the introduction of highly active antiretroviral therapies (ART), the prognosis for HIV-1 patients has improved immensely. However, approximately 25% of patients can experience a variety of inflammatory symptoms that are collectively known as immune reconstitution inflammatory syndrome (IRIS). Studying the etiology and immunopathology of IRIS has been hampered by the fact that the symptoms and associated opportunistic infections are highly varied. We hypothesized that there is a common mechanism underlying IRIS pathogenesis and investigated a patient group with IRIS related to different pathogens. Functional and phenotypic characterization of PBMC samples was performed by polychromatic flow cytometry after in vitro stimulation with relevant antigenic preparations. In most patients, IRIS events were characterized by the robust increase of preexisting polyfunctional, highly differentiated effector CD4(+) T-cell responses that specifically targeted the antigens of the underlying co-infection. T-cell responses to HIV-1 or other underlying infections were not affected and did not differ between IRIS and non-IRIS patients. These data suggest that patients with IRIS do not have a generalized T-cell dysfunction; instead, IRIS represents a dysregulated CD4(+) T-cell response against residual opportunistic infection antigen. These studies were registered at www.clinical-trials.gov as NCT00557570 and NCT00286767. (Blood. 2012;119(13):3105-3112)
C1 [Sereti, Irini] NIAID, Magnuson Clin Ctr, Clin & Mol Retrovirol Sect, Lab Immunoregulat,NIH, Bethesda, MD 20892 USA.
   [Mahnke, Yolanda D.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [DerSimonian, Rebecca; Roby, Gregg] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
   [Antonelli, Lis R. V.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), NIAID, Magnuson Clin Ctr, Clin & Mol Retrovirol Sect, Lab Immunoregulat,NIH, Bldg 10,Rm11B07A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
RI Vacinas, Inct/J-9431-2013; Antonelli, Lis/G-2907-2012
FU National Institute of Allergy and Infectious Diseases, National
   Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Allergy and Infectious Diseases, National
   Institutes of Health.
NR 45
TC 41
Z9 41
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 MAR 29
PY 2012
VL 119
IS 13
BP 3105
EP 3112
DI 10.1182/blood-2011-09-380840
PG 8
WC Hematology
SC Hematology
GA 916ZH
UT WOS:000302141200025
PM 22219223
ER

PT J
AU Hou, WQ
   Gibbs, JS
   Lu, XJ
   Brooke, CB
   Roy, D
   Modlin, RL
   Bennink, JR
   Yewdell, JW
AF Hou, Wanqiu
   Gibbs, James S.
   Lu, Xiuju
   Brooke, Christopher B.
   Roy, Devika
   Modlin, Robert L.
   Bennink, Jack R.
   Yewdell, Jonathan W.
TI Viral infection triggers rapid differentiation of human blood monocytes
   into dendritic cells
SO BLOOD
LA English
DT Article
ID CHEMOKINE RECEPTOR; MACROPHAGES; INFLUENZA; ALPHA
AB Surprisingly little is known about the interaction of human blood mononuclear cells with viruses. Here, we show that monocytes are the predominant cell type infected when peripheral blood mononuclear cells are exposed to viruses ex vivo. Remarkably, infection with vesicular stomatitis virus, vaccinia virus, and a variety of influenza A viruses (including circulating swine-origin virus) induces monocytes to differentiate within 18 hours into CD16(-)CD83(+) mature dendritic cells with enhanced capacity to activate T cells. Differentiation into dendritic cells does not require cell division and occurs despite the synthesis of viral proteins, which demonstrates that monocytes counteract the capacity of these highly lytic viruses to hijack host cell biosynthetic capacity. Indeed, differentiation requires infectious virus and viral protein synthesis. These findings demonstrate that monocytes are uniquely susceptible to viral infection among blood mononuclear cells, with the likely purpose of generating cells with enhanced capacity to activate innate and acquired antiviral immunity. (Blood. 2012;119(13):3128-3131)
C1 [Hou, Wanqiu; Gibbs, James S.; Lu, Xiuju; Brooke, Christopher B.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Hou, Wanqiu; Roy, Devika; Modlin, Robert L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med, Los Angeles, CA 90095 USA.
   [Modlin, Robert L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33,Rm 2E13C,33 North Dr, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI Modlin, Robert/M-7941-2014
OI Modlin, Robert/0000-0003-4720-031X
FU Division of Intramural Research; National Institute of Allergy and
   Infectious Diseases; National Institutes of Health
FX This work was generously supported by the Division of Intramural
   Research, National Institute of Allergy and Infectious Diseases (J.R.B.
   and J.W.Y.) and the National Institutes of Health (R.L.M.).
NR 15
TC 23
Z9 24
U1 1
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 MAR 29
PY 2012
VL 119
IS 13
BP 3128
EP 3131
DI 10.1182/blood-2011-09-379479
PG 4
WC Hematology
SC Hematology
GA 916ZH
UT WOS:000302141200028
PM 22310910
ER

PT J
AU Xiao, J
   Kannan, G
   Jones-Brando, L
   Brannock, C
   Krasnova, IN
   Cadet, JL
   Pletnikov, M
   Yolken, RH
AF Xiao, J.
   Kannan, G.
   Jones-Brando, L.
   Brannock, C.
   Krasnova, I. N.
   Cadet, J. L.
   Pletnikov, M.
   Yolken, R. H.
TI SEX-SPECIFIC CHANGES IN GENE EXPRESSION AND BEHAVIOR INDUCED BY CHRONIC
   TOXOPLASMA INFECTION IN MICE
SO NEUROSCIENCE
LA English
DT Article
DE Toxoplasma; sex-dependent; mice; gene expression; behavior
ID CAT ODOR; LATENT TOXOPLASMOSIS; FATAL ATTRACTION; GONDII; DOPAMINE;
   GENDER; MOUSE; CLOZAPINE; LESIONS; STRAIN
AB There is growing evidence that Toxoplasma gondii modifies the behavior of its intermediate hosts. We investigated the molecular basis of these infection-induced behavioral changes, followed by five related behavioral tests to assess the extent of biological relevance. Gene expression signatures were generated in the frontal cortex of male and female mice during the latent stage of infection. We found marked sex-dependent expression differences in mice. In female mice, Toxoplasma infection altered the expression of genes involved in the development of the forebrain, neurogenesis, and sensory and motor coordination (i.e. downregulation of fatty acid-binding protein 7 and eyes absent homolog 1, upregulation of semaphorin 7A). In male mice, infection led mainly to modulation of genes associated with olfactory function (i.e. downregulation of a number of olfactory receptors and dopamine receptor 04, upregulation of slit homolog 1). Although infection appears to affect the olfactory function in male mice, it is the female but not male mice that exhibited attraction to cat odor. In contrast, infected male mice showed a deficit in social transmission of food preference. In contrast to males, infected females displayed locomotor hyperactivity in open field. General olfaction and sensorimotor gating were normal in both male and female infection. Our results indicate that the sex of the host plays a major role in determining variable brain and behavior changes following Toxoplasma infection. These observations are consistent with heterogeneity of neuropsychiatric outcomes of the infection in humans. (C) 2012 Published by Elsevier Ltd on behalf of IBRO.
C1 [Xiao, J.; Jones-Brando, L.; Yolken, R. H.] Johns Hopkins Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21287 USA.
   [Kannan, G.; Pletnikov, M.] Johns Hopkins Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21287 USA.
   [Brannock, C.; Krasnova, I. N.; Cadet, J. L.] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,Dept Hlth & Humam Serv, Baltimore, MD 21224 USA.
RP Yolken, RH (reprint author), Johns Hopkins Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21287 USA.
EM yolken@mail.jhmi.edu
FU Stanley Medical Research Institute
FX This work was supported by Stanley Medical Research Institute. The
   authors are grateful to Chunxia Yang for her technical assistance.
NR 39
TC 34
Z9 37
U1 6
U2 30
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 MAR 29
PY 2012
VL 206
BP 39
EP 48
DI 10.1016/j.neuroscience.2011.12.051
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 917UA
UT WOS:000302202900005
PM 22240252
ER

PT J
AU Ayele, FT
   Adeyemo, A
   Finan, C
   Hailu, E
   Sinnott, P
   Burlinson, ND
   Aseffa, A
   Rotimi, CN
   Newport, MJ
   Davey, G
AF Ayele, Fasil Tekola
   Adeyemo, Adebowale
   Finan, Chris
   Hailu, Elena
   Sinnott, Paul
   Burlinson, Natalia Diaz
   Aseffa, Abraham
   Rotimi, Charles N.
   Newport, Melanie J.
   Davey, Gail
TI HLA Class II Locus and Susceptibility to Podoconiosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID NON-FILARIAL ELEPHANTIASIS; ENDEMIC ELEPHANTIASIS; SOUTHERN ETHIOPIA;
   GENETIC-ANALYSIS; COMPLEX DISEASE; LOWER LEGS; ASSOCIATION; SILICOSIS;
   CONSENT; STIGMA
AB BACKGROUND
   Podoconiosis is a tropical lymphedema resulting from long-term barefoot exposure to red-clay soil derived from volcanic rock. The World Health Organization recently designated it as a neglected tropical disease. Podoconiosis develops in only a subgroup of exposed people, and studies have shown familial clustering with high heritability (63%).
   METHODS
   We conducted a genomewide association study of 194 case patients and 203 controls from southern Ethiopia. Findings were validated by means of family-based association testing in 202 family trios and HLA typing in 94 case patients and 94 controls.
   RESULTS
   We found a genomewide significant association of podoconiosis with the single-nucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the HLA-DQA1 locus (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to 3.26; P = 1.42x10(-9); and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to 2.90; P = 3.44x10(-8)), and suggestive associations (P<1.0x10(-5)) with seven other SNPs in or near HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations using family-based association testing. HLA typing showed the alleles HLA-DRB1*0701 (odds ratio, 2.00), DQA1*0201 (odds ratio, 1.91), and DQB1*0202 (odds ratio, 1.79) and the HLA-DRB1*0701-DQB1*0202 haplotype (odds ratio, 1.92) were risk variants for podoconiosis.
   CONCLUSIONS
   Association between variants in HLA class II loci with podoconiosis (a noncommunicable disease) suggests that the condition may be a T-cell-mediated inflammatory disease and is a model for gene-environment interactions that may be relevant to other complex genetic disorders. (Funded by the Wellcome Trust and others.)
C1 [Ayele, Fasil Tekola; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
   [Ayele, Fasil Tekola; Finan, Chris; Newport, Melanie J.; Davey, Gail] Brighton & Sussex Med Sch, Brighton, E Sussex, England.
   [Ayele, Fasil Tekola; Hailu, Elena; Aseffa, Abraham] Armauer Hansen Res Inst, Addis Ababa, Ethiopia.
   [Sinnott, Paul; Burlinson, Natalia Diaz] Royal London Hosp, Clin Transplantat Lab, London E1 1BB, England.
RP Ayele, FT (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Rm 4044,12 South Dr,MSC 5635, Bethesda, MD 20892 USA.
EM ayeleft@mail.nih.gov
RI Aseffa, Abraham/J-3248-2016; 
OI Aseffa, Abraham/0000-0002-8028-1150; Davey, Gail/0000-0003-2796-7468;
   Tekola-Ayele, Fasil/0000-0003-4194-9370
FU Wellcome Trust [079791]; Association of Physicians of Great Britain and
   Ireland; Center for Research on Genomics and Global Health (CRGGH);
   National Human Genome Research Institute; National Institute of Diabetes
   and Digestive and Kidney Diseases; Center for Information Technology;
   Office of the Director at the National Institutes of Health
   [Z01HG200362]
FX Funded by the Wellcome Trust and others.; Supported in part by grants
   from the Wellcome Trust (079791) and the Association of Physicians of
   Great Britain and Ireland's Links with Developing Country Scheme, as
   well as the Intramural Research Program of the Center for Research on
   Genomics and Global Health (CRGGH). The CRGGH is supported by a grant
   from the National Human Genome Research Institute, the National
   Institute of Diabetes and Digestive and Kidney Diseases, the Center for
   Information Technology, and the Office of the Director at the National
   Institutes of Health (Z01HG200362).
NR 28
TC 27
Z9 27
U1 1
U2 8
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 MAR 29
PY 2012
VL 366
IS 13
BP 1200
EP 1208
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 915DW
UT WOS:000302005100008
ER

PT J
AU Korn, EL
   Freidlin, B
   Abrams, JS
AF Korn, Edward L.
   Freidlin, Boris
   Abrams, Jeffrey S.
TI Bevacizumab in Ovarian Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID CLINICAL-TRIALS
C1 [Korn, Edward L.; Freidlin, Boris; Abrams, Jeffrey S.] NCI, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 6
TC 2
Z9 2
U1 0
U2 4
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 MAR 29
PY 2012
VL 366
IS 13
BP 1256
EP 1256
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 915DW
UT WOS:000302005100022
PM 22455428
ER

PT J
AU Kwee, LC
   Liu, YT
   Haynes, C
   Gibson, JR
   Stone, A
   Schichman, SA
   Kamel, F
   Nelson, LM
   Topol, B
   Van Den Eeden, SK
   Tanner, CM
   Cudkowicz, ME
   Grasso, DL
   Lawson, R
   Muralidhar, S
   Oddone, EZ
   Schmidt, S
   Hauser, MA
AF Kwee, Lydia Coulter
   Liu, Yutao
   Haynes, Carol
   Gibson, Jason R.
   Stone, Annjanette
   Schichman, Steven A.
   Kamel, Freya
   Nelson, Lorene M.
   Topol, Barbara
   Van Den Eeden, Stephen K.
   Tanner, Caroline M.
   Cudkowicz, Merit E.
   Grasso, Daniela L.
   Lawson, Robert
   Muralidhar, Sumitra
   Oddone, Eugene Z.
   Schmidt, Silke
   Hauser, Michael A.
TI A High-Density Genome-Wide Association Screen of Sporadic ALS in US
   Veterans
SO PLOS ONE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; GULF-WAR VETERANS; HEXANUCLEOTIDE REPEAT;
   RISK; GENE; POPULATION; SUSCEPTIBILITY; EXPOSURE; SURVIVAL; DIAGNOSIS
AB Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U. S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U. S. veterans. We tested,1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4x10(-4)) and rs6985069 near ELP3 (p = 4.8x10(-4)). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder.
C1 [Kwee, Lydia Coulter; Liu, Yutao; Gibson, Jason R.; Oddone, Eugene Z.; Schmidt, Silke; Hauser, Michael A.] Durham Vet Affairs Med Ctr, Epidemiol Res & Informat Ctr, Durham, NC 27705 USA.
   [Kwee, Lydia Coulter; Liu, Yutao; Haynes, Carol; Gibson, Jason R.; Schmidt, Silke; Hauser, Michael A.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA.
   [Kwee, Lydia Coulter; Liu, Yutao; Haynes, Carol; Gibson, Jason R.; Oddone, Eugene Z.; Schmidt, Silke; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Stone, Annjanette; Schichman, Steven A.] Cent Arkansas Vet Healthcare Syst, Pathol & Lab Med Serv, Little Rock, AR USA.
   [Stone, Annjanette; Schichman, Steven A.] Cent Arkansas Vet Healthcare Syst, Res Serv, Little Rock, AR USA.
   [Schichman, Steven A.] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA.
   [Kamel, Freya] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
   [Nelson, Lorene M.; Topol, Barbara] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA.
   [Van Den Eeden, Stephen K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
   [Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA USA.
   [Cudkowicz, Merit E.; Grasso, Daniela L.; Lawson, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Unit, Boston, MA USA.
   [Muralidhar, Sumitra] Dept Vet Affairs, Off Res & Dev, Washington, DC USA.
RP Kwee, LC (reprint author), Durham Vet Affairs Med Ctr, Epidemiol Res & Informat Ctr, Durham, NC 27705 USA.
EM mike.hauser@duke.edu
OI Kamel, Freya/0000-0001-5052-6615
FU Office of Research and Development, Cooperative Studies Program,
   Department of Veterans Affairs [CSP] [500B, 500A, 478]; National
   Institute of Environmental Health Sciences/National Institutes of Health
   [R01 ES 013244]; ALS Association [ALSA 1230]; National Institutes of
   Health; National Institute of Environmental Health Sciences
   [Z01-ES049005, R01-ES08150]; National Institute of Neurological
   Disorders and Stroke/National Institutes of Health [R01 NS 031964]; ALS
   Therapy Alliance; Wellcome Trust [076113, 085475]
FX The authors gratefully acknowledge support for this work from the Office
   of Research and Development, Cooperative Studies Program, Department of
   Veterans Affairs [CSP #500B]. The GENEVA study was supported by National
   Institute of Environmental Health Sciences/National Institutes of Health
   [R01 ES 013244] and the ALS Association [ALSA 1230]. The National
   Registry of Veterans with ALS and its DNA bank were supported by the
   Office of Research and Development, Cooperative Studies Program,
   Department of Veterans Affairs [CSP #500A, CSP #478]. The study was
   supported in part by the intramural research program of the National
   Institutes of Health, by National Institute of Environmental Health
   Sciences [Z01-ES049005]. The GEM study was supported by the National
   Institute of Environmental Health Sciences [R01-ES08150] and the
   National Institute of Neurological Disorders and Stroke/National
   Institutes of Health [R01 NS 031964]. The NEALS consortium was supported
   by the ALS Association and the ALS Therapy Alliance. This study makes
   use of data generated by the Wellcome Trust Case-Control Consortium. A
   full list of the investigators who contributed to the generation of the
   data is available from www.wtccc.org.uk. Funding for the project was
   provided by the Wellcome Trust under award 076113 and 085475. This study
   was overseen by an Executive Committee appointed by the Veterns Affairs
   (VA): Mary Brophy, MD, MPH; MAH, PhD; Donald Humphries, PhD; LCK, PhD;
   EZO, MD, MHSc; SAS, MD, PhD; SS, PhD. The VA Cooperative Studies Program
   provided policies and requirements for conducting the research,
   contributed to study design, and provided administrative review of the
   paper but did not alter the contents. All other 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 0
U2 4
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 MAR 28
PY 2012
VL 7
IS 3
AR e32768
DI 10.1371/journal.pone.0032768
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 948FM
UT WOS:000304489000008
PM 22470424
ER

PT J
AU Martin, TA
   Jayanthi, S
   McCoy, MT
   Brannock, C
   Ladenheim, B
   Garrett, T
   Lehrmann, E
   Becker, KG
   Cadet, JL
AF Martin, Tracey A.
   Jayanthi, Subramaniam
   McCoy, Michael T.
   Brannock, Christie
   Ladenheim, Bruce
   Garrett, Tiffany
   Lehrmann, Elin
   Becker, Kevin G.
   Cadet, Jean Lud
TI Methamphetamine Causes Differential Alterations in Gene Expression and
   Patterns of Histone Acetylation/Hypoacetylation in the Rat Nucleus
   Accumbens
SO PLOS ONE
LA English
DT Article
ID CORTICOTROPIN-RELEASING-FACTOR; DOPAMINE-MEDIATED BEHAVIORS; INDUCED
   NEURONAL APOPTOSIS; INDUCED LOCOMOTOR-ACTIVITY; TRANSCRIPTIONAL
   REPRESSION; C-JUN; INDUCED REINSTATEMENT; CHOLECYSTOKININ-LIKE; FACTOR
   RECEPTORS; NUCLEOSOMAL DNA
AB Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might play in METH-induced gene expression needs to be investigated further.
C1 [Martin, Tracey A.; Jayanthi, Subramaniam; McCoy, Michael T.; Brannock, Christie; Ladenheim, Bruce; Garrett, Tiffany; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, Baltimore, MD 21224 USA.
   [Lehrmann, Elin; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Martin, TA (reprint author), NIDA, Mol Neuropsychiat Res Branch, NIH, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656
FU National Institutes of Health (NIDA); National Institutes of Health
   (NIA)
FX This work is supported by the National Institutes of Health (Intramural
   Research Programs of NIDA and NIA). The funders had no role in the study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 91
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U1 1
U2 11
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 MAR 28
PY 2012
VL 7
IS 3
AR e34236
DI 10.1371/journal.pone.0034236
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 948FM
UT WOS:000304489000080
PM 22470541
ER

PT J
AU Rodondi, N
   Locatelli, I
   Aujesky, D
   Butler, J
   Vittinghoff, E
   Simonsick, E
   Satterfield, S
   Newman, AB
   Wilson, PWF
   Pletcher, MJ
   Bauer, DC
AF Rodondi, Nicolas
   Locatelli, Isabella
   Aujesky, Drahomir
   Butler, Javed
   Vittinghoff, Eric
   Simonsick, Eleanor
   Satterfield, Suzanne
   Newman, Anne B.
   Wilson, Peter W. F.
   Pletcher, Mark J.
   Bauer, Douglas C.
CA Hlth ABC Study
TI Framingham Risk Score and Alternatives for Prediction of Coronary Heart
   Disease in Older Adults
SO PLOS ONE
LA English
DT Article
ID ARTERY CALCIUM SCORE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION;
   EVENTS; MORTALITY; ASSOCIATION; MODELS; HEALTH; WOMEN; INFLAMMATION
AB Background: Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS.
   Methods: Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization.
   Results: During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS.
   Conclusions: The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.
C1 [Rodondi, Nicolas; Aujesky, Drahomir] Univ Bern, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland.
   [Locatelli, Isabella] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland.
   [Locatelli, Isabella] Univ Lausanne, Univ Inst Social & Prevent Med, Lausanne, Switzerland.
   [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA.
   [Vittinghoff, Eric; Pletcher, Mark J.; Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Simonsick, Eleanor] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Satterfield, Suzanne] Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA.
   [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
   [Wilson, Peter W. F.] Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
   [Pletcher, Mark J.; Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA.
RP Rodondi, N (reprint author), Univ Bern, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland.
EM Nicolas.Rodondi@insel.ch
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU NIAMS NIH HHS [K24 AR051895]
NR 34
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U1 1
U2 10
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 MAR 28
PY 2012
VL 7
IS 3
AR e34287
DI 10.1371/journal.pone.0034287
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 948FM
UT WOS:000304489000090
PM 22470551
ER

PT J
AU Ranjan, A
   Jacobs, GC
   Woods, DL
   Negussie, AH
   Partanen, A
   Yarmolenko, PS
   Gacchina, CE
   Sharma, KV
   Frenkel, V
   Wood, BJ
   Dreher, MR
AF Ranjan, Ashish
   Jacobs, Genevieve C.
   Woods, David L.
   Negussie, Ayele H.
   Partanen, Ari
   Yarmolenko, Pavel S.
   Gacchina, Carmen E.
   Sharma, Karun V.
   Frenkel, Victor
   Wood, Bradford J.
   Dreher, Matthew R.
TI Image-guided drug delivery with magnetic resonance guided high intensity
   focused ultrasound and temperature sensitive liposomes in a rabbit Vx2
   tumor model
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Drug delivery; Liposome; MR-HIFU; Vx2 tumor model
ID SOLID TUMORS; THERMOSENSITIVE LIPOSOME; MILD HYPERTHERMIA; TARGETED
   DELIVERY; XENOGRAFT MODEL; BREAST-CANCER; MURINE TUMORS; DOXORUBICIN;
   PHARMACOKINETICS; RELEASE
AB Clinical-grade doxorubicin encapsulated low temperature sensitive liposomes (LTSLs) were combined with a clinical magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) platform to investigate in vivo image-guided drug delivery. Plasma pharmacokinetics were determined in 3 rabbits. Fifteen rabbits with Vx2 tumors within superficial thigh muscle were randomly assigned into three treatment groups: 1) free doxorubicin, 2) LTSL and 3) LTSL+ MR-HIFU. For the LTSL+ MR-HIFU group, mild hyperthermia (40-41 degrees C) was applied to the tumors using an MR-HIFU system. Image-guided non-invasive hyperthermia was applied for a total of 30 min, completed within 1 h after LTSL infusion. High-pressure liquid chromatography (HPLC) analysis of the harvested tumor and organ/tissue homogenates was performed to determine doxorubicin concentration. Fluorescence microscopy was performed to determine doxorubicin spatial distribution in the tumors. Sonication of Vx2 tumors resulted in accurate (mean= 40.5 +/- 0.1 degrees C) and spatially homogenous (SD= 1.0 degrees C) temperature control in the target region. LTSL+ MR-HIFU resulted in significantly higher tumor doxorubicin concentrations (7.6- and 3.4-fold greater compared to free doxorubicin and LTSL respectively, pb0.05, Newman-Keuls). This improved tumor concentration was achieved despite heating b25% of the tumor volume. Free doxorubicin and LTSL treatments appeared to deliver more drug in the tumor periphery as compared to the tumor core. In contrast, LTSL+ MR-HIFU treatment suggested an improved distribution with doxorubicin found in both the tumor periphery and core. Doxorubicin bio-distribution in non-tumor organs/ tissues was fairly similar between treatment groups. This technique has potential for clinical translation as an image-guided method to deliver drug to a solid tumor. Published by Elsevier B. V.
C1 [Dreher, Matthew R.] Natl Radiol & Imaging Sci, NIH, Ctr Intervent Oncol, Clin Ctr, Bethesda, MD 20892 USA.
   [Ranjan, Ashish; Jacobs, Genevieve C.; Woods, David L.; Negussie, Ayele H.; Partanen, Ari; Yarmolenko, Pavel S.; Gacchina, Carmen E.; Sharma, Karun V.; Wood, Bradford J.; Dreher, Matthew R.] NCI, NIH, Bethesda, MD 20892 USA.
   [Yarmolenko, Pavel S.] Duke Univ, Durham, NC USA.
   [Partanen, Ari] Philips Healthcare, Cleveland, OH USA.
   [Partanen, Ari] Univ Helsinki, Dept Phys, Helsinki, Finland.
   [Frenkel, Victor] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA.
RP Dreher, MR (reprint author), Natl Radiol & Imaging Sci, NIH, Ctr Intervent Oncol, Clin Ctr, Room 2N212,Bldg 10,MSC 1182,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dreherm@cc.nih.gov
OI Partanen, Ari/0000-0003-1985-149X
FU Center for Interventional Oncology of the National Institutes of Health
   (NIH)
FX This research was supported by the Center for Interventional Oncology in
   the Intramural Research Program of the National Institutes of Health
   (NIH). NIH and Celsion Corp. have a Cooperative Research and Development
   Agreement. NIH and Philips Healthcare have a Cooperative Research and
   Development Agreement. We thank Dr. Mark Dewhirst, Dr. Ivan Spasojevic
   and Dr. Sham Sokka for their advice and useful discussions. We also
   thank Dr. Max Kohler, Julia Enholm, and Jaakko Tolo of Philips
   Healthcare for their support and technical expertise. We would also like
   to thank Dr. James Coad for providing us with a viability staining
   protocol.
NR 45
TC 110
Z9 113
U1 5
U2 76
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 MAR 28
PY 2012
VL 158
IS 3
BP 487
EP 494
DI 10.1016/j.jconrel.2011.12.011
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 931QL
UT WOS:000303234300018
PM 22210162
ER

PT J
AU Berezhkovskii, AM
   Dagdug, L
AF Berezhkovskii, Alexander M.
   Dagdug, Leonardo
TI Effect of binding on escape from cavity through narrow tunnel
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
DE diffusion; molecular biophysics; proteins
ID MEMBRANE
AB When a diffusing particle escapes from a spherical cavity through a narrow, not too long tunnel, the escape kinetics is essentially single-exponential. The presence of reversible binding sites on the cavity wall leads to retention of the particle in the system and converts the single-exponential kinetics into bi-exponential. We develop a theory that describes these effects. The theory shows how the delay time and the average number of binding events depend on the geometric and kinetic parameters of the system. To study the effect of the cavity shape, we also analyze the kinetics when the particle escapes from a cylindrical cavity with reversible binding sites. [http://dx.doi.org/10.1063/1.3697972]
C1 [Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
   [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
FU National Institutes of Health (NIH), Center for Information Technology
FX This study was supported by the Intramural Research Program of the
   National Institutes of Health (NIH), Center for Information Technology.
NR 13
TC 1
Z9 1
U1 0
U2 5
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 MAR 28
PY 2012
VL 136
IS 12
AR 124110
DI 10.1063/1.3697972
PG 3
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 917YU
UT WOS:000302216200014
PM 22462838
ER

PT J
AU Chen, ZY
   Kim, L
   Subbarao, K
   Jin, H
AF Chen, Zhongying
   Kim, Lomi
   Subbarao, Kanta
   Jin, Hong
TI The 2009 pandemic H1N1 virus induces anti-neuraminidase (NA) antibodies
   that cross-react with the NA of H5N1 viruses in ferrets
SO VACCINE
LA English
DT Article
DE Influenza virus; Live-attenuated influenza vaccine; Ferret;
   Anti-neuraminidase antibody response; Neuraminidase inhibition assay;
   Cross-reactivity
ID INFLUENZA-A VIRUS; LIVE ATTENUATED INFLUENZA; LETHAL INFLUENZA;
   IMMUNE-RESPONSE; VACCINE; HEMAGGLUTININ; MICE; PROTECTION; INFECTION;
   IMMUNIZATION
AB A miniaturized neuraminidase inhibition (NI) assay using HA-mismatched H6 reassortant viruses was performed to examine the neuraminidase (NA)-specific antibody response in ferrets immunized with live-attenuated influenza vaccine (LAIV) strains. The strains tested possessed different NAs derived from seasonal H1N1 and H3N2, 2009 pandemic H1N1, and the highly pathogenic influenza H5N1 virus. The anti-NA antibodies from the 2009 pandemic strain (A/California/7/2009) immunized ferrets cross-reacted with the NA of H5N1 but not with the NA of seasonal H1N1 viruses. The plaque size reduction assay confirmed the cross-reactivity between the NAs of A/California/7/2009 and the H5N1 virus. Sequence and structural analyses of these N1 NA proteins showed that the NA of the 2009 pandemic H1N1 strain shared at least 22 more amino acids in the head domain with the NAs of the avian H5N1 strains than with the NAs of seasonal human H1N1 viruses. Our data demonstrated LAIV-induced NA antibody responses in ferrets and cross-reactive NA antibodies induced by 2009 pandemic H1N1 and H5N1 LAIV viruses. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Chen, Zhongying; Kim, Lomi; Jin, Hong] MedImmune LLC, Mountain View, CA 94043 USA.
   [Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, ZY (reprint author), MedImmune LLC, Mountain View, CA 94043 USA.
EM chenz@medimmune.com
FU NIAID, NIH
FX We thank Dr. Maryna C. Eichelberger from CBER/FDA for providing the NI
   assay protocol. The H5N1 and H6N1 vaccine viruses and plasmids were
   produced under the Cooperative Research and Development Agreement
   (CRADA) between MedImmune and NIAID/NIH. This research was supported in
   part by the Intramural Research Program of NIAID, NIH. We thank
   MedImmune's animal care facility for the ferret studies; cell culture
   group for providing tissue culture cells; lab service group for
   preparing reagents; Chinfen Yang for helping with sequence analysis;
   Drs. Gary Van Nest, Amorsolo Suguitan Jr and Xing Cheng for reviewing
   the manuscript.
NR 41
TC 20
Z9 20
U1 0
U2 3
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 MAR 28
PY 2012
VL 30
IS 15
BP 2516
EP 2522
DI 10.1016/j.vaccine.2012.01.090
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 926HT
UT WOS:000302822600003
PM 22330124
ER

PT J
AU Rosenberg, SA
AF Rosenberg, Steven A.
TI Raising the Bar: The Curative Potential of Human Cancer Immunotherapy
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID RENAL-CELL CARCINOMA; HIGH-DOSE INTERLEUKIN-2; PHASE-III TRIAL;
   METASTATIC MELANOMA; RECOMBINANT INTERLEUKIN-2; COMPLETE RESPONSES;
   GENE-THERAPY; LYMPHOCYTES; EXPRESSION; REGRESSION
AB Immunotherapy with interleukin-2 can cure 5 to 10% of patients with metastatic melanoma and renal cancer. Recent adoptive cell transfer (ACT) immunotherapies have improved cure rates in metastatic melanoma to 20 to 40%. Genetic engineering of T cells to express conventional alpha/beta T cell receptors or antibody-based chimeric antigen receptors provides an opportunity to extend ACT to patients with common epithelial cancers.
C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sar@nih.gov
NR 41
TC 76
Z9 80
U1 3
U2 17
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 MAR 28
PY 2012
VL 4
IS 127
AR 127ps8
DI 10.1126/scitranslmed.3003634
PG 5
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 917XZ
UT WOS:000302213400003
PM 22461638
ER

PT J
AU Klabunde, CN
   Brown, M
   Ballard-Barbash, R
   White, MC
   Thompson, T
   Plescia, M
   King, SC
AF Klabunde, Carrie N.
   Brown, Martin
   Ballard-Barbash, Rachel
   White, Mary C.
   Thompson, Trevor
   Plescia, Marcus
   King, Sallyann Coleman
TI Cancer Screening-United States, 2010 (Reprinted from MMWR, vol 61, pg
   41-45, 2012)
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Reprint
C1 [King, Sallyann Coleman] CDC, EIS, Atlanta, GA 30333 USA.
   [Klabunde, Carrie N.; Brown, Martin; Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA.
   [White, Mary C.; Thompson, Trevor; Plescia, Marcus] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
RP King, SC (reprint author), CDC, EIS, Atlanta, GA 30333 USA.
EM scolemanking@cdc.gov
RI White, Mary /C-9242-2012
OI White, Mary /0000-0002-9826-3962
NR 1
TC 0
Z9 0
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 28
PY 2012
VL 307
IS 12
BP 1248
EP 1250
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 914UP
UT WOS:000301978400010
ER

PT J
AU Mehari, A
   Gladwin, MT
   Tian, X
   Machado, RF
   Kato, GJ
AF Mehari, Alem
   Gladwin, Mark T.
   Tian, Xin
   Machado, Roberto F.
   Kato, Gregory J.
TI Mortality in Adults With Sickle Cell Disease and Pulmonary Hypertension
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Mehari, Alem] Howard Univ, Coll Med, Washington, DC 20059 USA.
   [Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
   [Tian, Xin; Kato, Gregory J.] NHLBI, Bethesda, MD 20892 USA.
   [Machado, Roberto F.] Univ Illinois, Sect Pulm Crit Care Med Sleep & Allergy, Chicago, IL USA.
RP Mehari, A (reprint author), Howard Univ, Coll Med, Washington, DC 20059 USA.
EM gkato@mail.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [ZIA HL006011-04, ZIA HL006012-02, ZIA HL006015-04];
   NHLBI NIH HHS [ZIA HL006012, K23 HL098454, K23HL098454, P01 HL103455,
   P01HL103455, R01 HL096973, R01 HL098032, R01HL096973, R01HL098032, ZIA
   HL006011, ZIA HL006015]; NIDDK NIH HHS [RC1 DK085852, RC1DK085852]
NR 5
TC 71
Z9 74
U1 1
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 28
PY 2012
VL 307
IS 12
BP 1254
EP 1256
DI 10.1001/jama.2012.358
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 914UP
UT WOS:000301978400017
PM 22453563
ER

PT J
AU Ecke, LE
   Elmer, GI
   Suto, N
AF Ecke, Laurel E.
   Elmer, Greg I.
   Suto, Nobuyoshi
TI Cocaine self-administration is not dependent upon mesocortical alpha 1
   noradrenergic signaling
SO NEUROREPORT
LA English
DT Article
DE alpha 1 receptors; cocaine self-administration; D1 receptors; dopamine;
   medial prefrontal cortex; norepinephrine; ventral tegmental area
ID D-AMPHETAMINE; ALPHA-1B-ADRENERGIC RECEPTORS; ALPHA-1-ADRENERGIC
   RECEPTORS; PREFRONTAL CORTEX; DOPAMINE RELEASE; RHESUS-MONKEYS; RATS;
   LOCOMOTOR; BLOCKADE; REWARD
AB The rewarding properties of psychomotor stimulants are traditionally thought to be independent of norepinephrine. Recent findings, however, suggest that local noradrenergic signaling through alpha 1 receptors in the medial prefrontal cortex and the ventral tegmental area - brain regions critically important in natural and drug rewards - is in a position to influence stimulant reward. Despite this controversy, the contribution of this targeted signaling to stimulant self-administration has not been directly assessed. We have thus examined whether pharmacological blockade of alpha 1 receptors in the medial prefrontal cortex and ventral tegmental area alters cocaine self-administration. Rats were trained to lever-press for cocaine (1.0 mg/kg/infusion) under a fixed ratio 1 schedule of reinforcement for 10 days. After training, the rats received a bilateral microinjection of an alpha 1 noradrenergic antagonist (terazosin: 1.0, 5.0, or 10 mM/side), a D1 dopaminergic antagonist (SCH23390: 12.3 mM/side), or saline into either the medial prefrontal cortex or ventral tegmental area immediately before a cocaine self-administration session. Although SCH23390 significantly increased cocaine self-administration when injected into either brain region, terazosin, at all doses and sites tested, failed to alter this behavior. Thus, the maintenance of cocaine self-administration appears to be under the influence of D1 dopaminergic, rather than alpha 1 noradrenergic, signaling at these mesocortical sites. NeuroReport 23:325-330 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Ecke, Laurel E.; Suto, Nobuyoshi] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH DHHS, Baltimore, MD USA.
   [Elmer, Greg I.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
RP Suto, N (reprint author), Scripps Res Inst, Mol & Integrat Neurosci Dept, 10550 N Torrey Pines Rd,SP30-2120, La Jolla, CA 92037 USA.
EM nsuto@scripps.edu
FU National Institute on Drug Abuse (NIDA), National Institutes of Health,
   Department of Health and Human Services; NIDA Residual Research Services
   [N01DA-5-9909]
FX This study is supported by funding from the Intramural Research Program,
   National Institute on Drug Abuse (NIDA), National Institutes of Health,
   Department of Health and Human Services as well as NIDA Residual
   Research Services (N01DA-5-9909). The authors thank Dr Roy A. Wise for
   critical input to the study. They also thank Eric Thorndike for
   technical assistance with acquisition of self-administration data.
NR 26
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD MAR 28
PY 2012
VL 23
IS 5
BP 325
EP 330
DI 10.1097/WNR.0b013e3283517628
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 905RE
UT WOS:000301289300012
PM 22336873
ER

PT J
AU Tuo, JS
   Cao, XG
   Shen, DF
   Wang, YJ
   Zhang, J
   Oh, JY
   Prockop, DJ
   Chan, CC
AF Tuo, Jingsheng
   Cao, Xiaoguang
   Shen, Defen
   Wang, Yujuan
   Zhang, Jun
   Oh, Joo Youn
   Prockop, Darwin J.
   Chan, Chi-Chao
TI Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal
   retinal degeneration in a murine model
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
DE Age-related macular degeneration; Animal model; IL-17a; TNF-alpha;
   TSG-6; Treatment
ID PIGMENT EPITHELIAL-CELLS; INTER-ALPHA-INHIBITOR; MACULAR DEGENERATION;
   PROTEIN TSG-6; DEFICIENT MICE; EXPRESSION; MOUSE; LESIONS; AUTOIMMUNITY;
   INFLAMMATION
AB Background: Inflammatory responses are detected in the retina of patients with age-related macular degeneration and Ccl2(-/-)/Cx3cr1(-/-) mice on rd8 background,(Ccl2(-/-)/Cx3cr1(-/-) mice) a model that develops progressive age-related macular degeneration-like retinal lesions including focal photoreceptor degeneration, abnormal retinal pigment epithelium and A2E accumulation. Tumor necrosis factor-inducible gene 6 protein is an anti-inflammatory protein and has been shown to improve myocardial infarction outcome and chemically injured cornea in mice by suppressing inflammation. In this study, we evaluated the effect of an intravitreous injection of recombinant TSG-6 on the retinal lesions of Ccl2(-/-)/Cx3cr1(-/-) mice.
   Methods: Recombinant TSG-6 (400 ng) was administered by intravitreous injection into the right eye of six-week-old Ccl2(-/-)/Cx3cr1(-/-) mice. Their left eye was injected with phosphate-buffered saline as a control. Funduscopic pictures were taken before injection and sequentially once a month after injection. The mice were killed two months after injection and the ocular histology examined. Retinal A2E, a major component of lipofuscin, was measured by high performance liquid chromatography. The microarray of ocular mRNA of 92 immunological genes was performed. The genes showing differentiated expression in microarray were further compared between the injected right eye and the contralateral (control) eye by [real-time quantitative reverse transcription polymerase chain reaction] qRT-PCR.
   Results: The continuous monitoring of the fundus for two months showed a slower progression or alleviation of retinal lesions in the treated right eyes as compared with the untreated left eyes. Among 23 pairs of eyes, the lesion levels improved in 78.3%, stayed the same in 8.7% and progressed in 13.0%. Histology confirmed the clinical observation. Even though there was no difference in the level of A2E between the treated and the untreated eyes, microarray analysis of 92 immune genes showed that IL-17a was substantially decreased after the treatment. Expression of TNF-alpha showed a similar pattern to IL-17a. The results were consistent in duplicated arrays and confirmed by qRT-PCR.
   Conclusions: We concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice on rd8 background. Modulation of ocular immunological gene expressions, especially IL-17a, could be one of the mechanisms.
C1 [Tuo, Jingsheng; Cao, Xiaoguang; Shen, Defen; Wang, Yujuan; Zhang, Jun; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Oh, Joo Youn; Prockop, Darwin J.] Scott & White Mem Hosp & Clin, Inst Regenerat Med, Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA.
RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
RI Zhang, Jun/K-2424-2012; wang, yujuan/C-8428-2016; 
OI Tuo, Jingsheng/0000-0002-1372-7810
FU National Eye Institute, National Institutes of Health
FX This work was carried out in the National Eye Institute, National
   Institutes of Health, Bethesda, MD, USA and supported by the Intramural
   Research Program of National Eye Institute, National Institutes of
   Health.
NR 42
TC 12
Z9 14
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD MAR 27
PY 2012
VL 9
AR 59
DI 10.1186/1742-2094-9-59
PG 8
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 949EM
UT WOS:000304559100001
PM 22452753
ER

PT J
AU Bushel, PR
   McGovern, R
   Liu, LW
   Hofmann, O
   Huda, A
   Lu, J
   Hide, W
   Lin, XH
AF Bushel, Pierre R.
   McGovern, Ray
   Liu, Liwen
   Hofmann, Oliver
   Huda, Ahsan
   Lu, Jun
   Hide, Winston
   Lin, Xihong
TI Population Differences in Transcript-Regulator Expression Quantitative
   Trait Loci
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SET ENRICHMENT ANALYSIS; HUMAN GENE-EXPRESSION;
   BREAST-CANCER; SIGNAL-TRANSDUCTION; FALSE DISCOVERY; RNA-SEQ;
   IDENTIFICATION; GENOTYPE; SNP
AB Gene expression quantitative trait loci (eQTL) are useful for identifying single nucleotide polymorphisms (SNPs) associated with diseases. At times, a genetic variant may be associated with a master regulator involved in the manifestation of a disease. The downstream target genes of the master regulator are typically co-expressed and share biological function. Therefore, it is practical to screen for eQTLs by identifying SNPs associated with the targets of a transcript-regulator (TR). We used a multivariate regression with the gene expression of known targets of TRs and SNPs to identify TReQTLs in European (CEU) and African (YRI) HapMap populations. A nominal p-value of <1 x 10(-6) revealed 234 SNPs in CEU and 154 in YRI as TReQTLs. These represent 36 independent (tag) SNPs in CEU and 39 in YRI affecting the downstream targets of 25 and 36 TRs respectively. At a false discovery rate (FDR) = 45%, one cis-acting tag SNP (within 1 kb of a gene) in each population was identified as a TReQTL. In CEU, the SNP (rs16858621) in Pcnxl2 was found to be associated with the genes regulated by CREM whereas in YRI, the SNP (rs16909324) was linked to the targets of miRNA hsa-miR-125a. To infer the pathways that regulate expression, we ranked TReQTLs by connectivity within the structure of biological process subtrees. One TReQTL SNP (rs3790904) in CEU maps to Lphn2 and is associated (nominal p-value = 8.1 x 10(-7)) with the targets of the X-linked breast cancer suppressor Foxp3. The structure of the biological process subtree and a gene interaction network of the TReQTL revealed that tumor necrosis factor, NF-kappaB and variants in G-protein coupled receptors signaling may play a central role as communicators in Foxp3 functional regulation. The potential pleiotropic effect of the Foxp3 TReQTLs was gleaned from integrating mRNA-Seq data and SNP-set enrichment into the analysis.
C1 [Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
   [Liu, Liwen] Natl Inst Environm Hlth Sci, Microarray Core, Res Triangle Pk, NC USA.
   [McGovern, Ray; Hofmann, Oliver; Hide, Winston] Harvard Univ, Sch Publ Hlth, Bioinformat Core, Boston, MA 02115 USA.
   [Hofmann, Oliver; Hide, Winston; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Huda, Ahsan; Lu, Jun] SRA Int Inc, Res Triangle Pk, NC USA.
RP Bushel, PR (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
EM bushel@niehs.nih.gov
RI Hofmann, Oliver/F-1800-2013; 
OI Hofmann, Oliver/0000-0002-7738-1513; Hide, Winston/0000-0002-8621-3271
FU National Institutes of Health (NIH); National Institute of Environmental
   Health Sciences (NIEHS) [Z01 ES102345-04]; National Cancer Institute
   [R37CA76404, P01CA134294]
FX This research was supported in part by the Intramural Research Program
   of the National Institutes of Health (NIH) and National Institute of
   Environmental Health Sciences (NIEHS) [Z01 ES102345-04] and in part by
   the National Cancer Institute Grants R37CA76404 and P01CA134294. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 73
TC 5
Z9 5
U1 0
U2 8
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 MAR 27
PY 2012
VL 7
IS 3
AR e34286
DI 10.1371/journal.pone.0034286
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 940MY
UT WOS:000303894900078
PM 22479588
ER

PT J
AU Ngamskulrungroj, P
   Chang, Y
   Roh, J
   Kwon-Chung, KJ
AF Ngamskulrungroj, Popchai
   Chang, Yun
   Roh, Jamin
   Kwon-Chung, Kyung J.
TI Differences in Nitrogen Metabolism between Cryptococcus neoformans and
   C. gattii, the Two Etiologic Agents of Cryptococcosis
SO PLOS ONE
LA English
DT Article
ID D-PROLINE ASSIMILATION; SACCHAROMYCES-CEREVISIAE; VANCOUVER-ISLAND;
   MOLECULAR CHARACTERIZATION; RAPID IDENTIFICATION; VAR. GRUBII;
   EPIDEMIOLOGIC DIFFERENCES; ASPERGILLUS-FUMIGATUS; THREONINE ALDOLASE;
   CANDIDA-ALBICANS
AB Two members of the Cryptococcus neoformans-gattii species complex, the etiologic agents of cryptococcosis, can be differentiated by biological, biochemical, serological and molecular typing techniques. Based on their differences in carbon and nitrogen utilization patterns, cost effective and very specific diagnostic tests using D-proline and canvanine-glycine-bromthymol blue (CGB) media have been formulated and are widely used for identification of the two species. However, these methods have yet to be tested for strains with confirmed molecular types to assess the degree of specificity for each molecular type in the two species. We collected global isolates of every major molecular type available and tested their patterns of nitrogen utilization. We confirmed specificity of the CGB test to be 100% regardless of molecular type while the D-proline test yielded 8-38% false negative results in three of the four C. gattii molecular types, VGI-VGIII. The utilization pattern of a new set of amino acids: D-alanine, L-tryptophan and L-phenylalanine, showed species specificity comparable to that of D-proline. We discovered that the transcription factor Gat1 (Are1) regulates the utilization of nitrogen differently between C. neoformans and C. gattii strains. Unlike in C. neoformans, expression of the genes encoding glycine decarboxylase complex in C. gatti was only partially suppressed by nitrogen catabolite repression in the presence of ammonium. GAT1 in C. neoformans controlled the induction of three of the four genes encoding the glycine decarboxylase complex when glycine was used as the sole nitrogen source while in C. gattii its regulation of these genes was less stringent. Moreover, while virulence of C. neoformans strains in mice was not affected by Gat1, the transcription factor positively influenced the virulence of C. gattii strain.
C1 [Ngamskulrungroj, Popchai; Chang, Yun; Roh, Jamin; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Ngamskulrungroj, Popchai] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Microbiol, Bangkok 10700, Thailand.
RP Ngamskulrungroj, P (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM june_kwon-chung@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
   Institutes of Health
FX This study was supported by funds from the intramural program of 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 72
TC 10
Z9 10
U1 1
U2 2
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 MAR 27
PY 2012
VL 7
IS 3
AR e34258
DI 10.1371/journal.pone.0034258
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 940MY
UT WOS:000303894900075
PM 22479580
ER

PT J
AU Sucheston, LE
   Bensen, JT
   Xu, ZL
   Singh, PK
   Preus, L
   Mohler, JL
   Su, LJ
   Fontham, ETH
   Ruiz, B
   Smith, GJ
   Taylor, JA
AF Sucheston, Lara E.
   Bensen, Jeannette T.
   Xu, Zongli
   Singh, Prashant K.
   Preus, Leah
   Mohler, James L.
   Su, L. Joseph
   Fontham, Elizabeth T. H.
   Ruiz, Bernardo
   Smith, Gary J.
   Taylor, Jack A.
TI Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans
   and European Americans in the PCaP Cohort
SO PLOS ONE
LA English
DT Article
ID HUMAN-POPULATION STRUCTURE; PROSTATE-CANCER; ASSOCIATION;
   STRATIFICATION; TWINS; RISK; MUTATIONS; ADMIXTURE
AB Background: Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.
   Methods: Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.
   Results: Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.
   Conclusions: Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.
C1 [Sucheston, Lara E.; Preus, Leah] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
   [Bensen, Jeannette T.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
   [Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Xu, Zongli; Taylor, Jack A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
   [Xu, Zongli; Taylor, Jack A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA.
   [Singh, Prashant K.] Roswell Pk Canc Inst, Dept Genet & Pharmacol, Buffalo, NY 14263 USA.
   [Mohler, James L.; Smith, Gary J.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA.
   [Mohler, James L.; Smith, Gary J.] SUNY Buffalo, Dept Urol, Buffalo, NY 14260 USA.
   [Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, Dept Epidemiol, Sch Publ Hlth, New Orleans, LA USA.
   [Ruiz, Bernardo] Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, New Orleans, LA USA.
RP Sucheston, LE (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
EM lara.sucheston@roswellpark.org
OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398
FU National Institutes of Health (NIH), National Institute of Environmental
   Health Sciences; NIH National Center on Minority Health and Health
   Disparities; Department of Defense [DAMD 17-03-2-0052]
FX This research was supported in part by the Intramural Research Program
   of the National Institutes of Health (NIH), National Institute of
   Environmental Health Sciences and the NIH National Center on Minority
   Health and Health Disparities. The North Carolina Louisiana Prostate
   Cancer Project (PCaP) is carried out as a collaborative study supported
   by the Department of Defense contract DAMD 17-03-2-0052. No additional
   external funding received for this study. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 33
TC 11
Z9 12
U1 1
U2 5
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 MAR 27
PY 2012
VL 7
IS 3
AR e30950
DI 10.1371/journal.pone.0030950
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 940MY
UT WOS:000303894900001
PM 22479307
ER

EF